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Impact of body composition on very-low-density lipoprotein-triglycerides kinetics - PubMed This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content An official website of the United States government Here's how you know The .gov means it’s official. Federal government websites often end in .gov or .mil. Before

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Log in Show account info Close Account Logged in as: username Dashboard Publications Account settings Log out Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Advanced Clipboard User Guide Save Email Send to Clipboard My Bibliography Collections Citation manager Display options Display options Format Abstract PubMed PMID Save citation to file Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel Email citation Subject: 1 selected item: 18984851 - PubMed To: From: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Add to My Bibliography My Bibliography Unable to load your delegates due to an error Please try again Add Cancel Your saved search Name of saved search: Search terms: Test search terms Would you like email updates of new search results? 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Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel Create a file for external citation management software Create file Cancel Your RSS Feed Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy Full text links Atypon Full text links Actions Cite Collections Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Display options Display options Format Abstract PubMed PMID Share Permalink Copy Page navigation Title & authors Abstract Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Title & authors Abstract Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Am J Physiol Endocrinol Metab Actions Search in PubMed Search in NLM Catalog Add to Search . 2009 Jan;296(1):E165-73. doi: 10.1152/ajpendo.90675.2008. Epub 2008 Nov 4. Impact of body composition on very-low-density lipoprotein-triglycerides kinetics Lars C Gormsen 1 , Birgitte Nellemann , Lars P Sørensen , Michael D Jensen , Jens S Christiansen , Søren Nielsen Affiliations Expand Affiliation 1 Dept. of Nuclear Medicine, Aarhus Univ. Hospital, DK-8000 Aarhus C, Denmark. [email protected] PMID: 18984851 DOI: 10.1152/ajpendo.90675.2008 Free article Item in Clipboard Impact of body composition on very-low-density lipoprotein-triglycerides kinetics Lars C Gormsen et al. Am J Physiol Endocrinol Metab . 2009 Jan . Free article Show details Display options Display options Format Abstract PubMed PMID Am J Physiol Endocrinol Metab Actions Search in PubMed Search in NLM Catalog Add to Search . 2009 Jan;296(1):E165-73. doi: 10.1152/ajpendo.90675.2008. Epub 2008 Nov 4. Authors Lars C Gormsen 1 , Birgitte Nellemann , Lars P Sørensen , Michael D Jensen , Jens S Christiansen , Søren Nielsen Affiliation 1 Dept. of Nuclear Medicine, Aarhus Univ. Hospital, DK-8000 Aarhus C, Denmark. [email protected] PMID: 18984851 DOI: 10.1152/ajpendo.90675.2008 Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Abstract Upper body obese (UBO) subjects have greater cardiovascular disease risk than lower body obese (LBO) or lean subjects. Obesity is also associated with hypertriglyceridemia that may involve greater production and impaired removal of very-low-density lipoprotein (VLDL)-triglycerides (TG). In these studies, we assessed the impact of body composition on basal VLDL-TG production, VLDL-TG oxidation, and VLDL-TG storage. VLDL-TG kinetics were assessed in 10 UBO, 10 LBO, and 10 lean women using a bolus injection of [1-(14)C]VLDL-TG. VLDL-TG oxidation was measured by (14)CO(2) production (hyamine trapping) and VLDL-TG adipose tissue storage by fat biopsies. Insulin sensititvity was assessed by the hyperinsulinemic-euglycemic clamp technique and body composition by dual X-ray absorptiometry in combination with computed tomography. Hepatic VLDL-TG production was significantly greater in UBO than in lean women [(mumol/min) UBO: 64.8 (SD 40.0) vs. LBO: 42.5 (SD 25.6) vs. lean: 31.8 (SD 13.3), P = 0.04], whereas VLDL-TG oxidation was similar in the three groups and averaged 20% of resting energy expenditure [(mumol/min) UBO: 38.3 (SD 26.5) vs. LBO: 23.5 (SD 13.5) vs. lean: 21.1 (SD 9.7), P = 0.09]. In UBO women, more VLDL-TG was deposited in upper body subcutaneous fat [VLDL-TG redeposition in abdominal adipose tissue (mumol/min): UBO: 5.0 (SD 2.9) vs. LBO: 4.0 (SD 3.2) vs. lean: 1.3 (SD 1.0), ANOVA P = 0.01]; in LBO women, more VLDL-TG was deposited in femoral fat [VLDL-TG redeposition in femoral adipose tissue (mumol/min): UBO: 5.1 (SD 3.1) vs. LBO: 5.8 (SD 4.3) vs. lean: 2.3 (SD 1.5), ANOVA P = 0.04]. Only a small proportion of VLDL-TG (8-16%) was partitioned into redeposition in either group. We found that elevated VLDL-TG production without concomitant increased clearance via oxidation and adipose tissue redeposition contributes to hypertriglyceridemia in UBO women. PubMed Disclaimer Similar articles Impaired insulin-mediated antilipolysis and lactate release in adipose tissue of upper-body obese women. Nellemann B, Gormsen LC, Sørensen LP, Christiansen JS, Nielsen S. Nellemann B, et al. Obesity (Silver Spring). 2012 Jan;20(1):57-64. doi: 10.1038/oby.2011.290. Epub 2011 Sep 29. Obesity (Silver Spring). 2012. PMID: 21959346 Body composition determines direct FFA storage pattern in overweight women. Søndergaard E, Gormsen LC, Nellemann B, Jensen MD, Nielsen S. Søndergaard E, et al. Am J Physiol Endocrinol Metab. 2012 Jun 15;302(12):E1599-604. doi: 10.1152/ajpendo.00015.2012. Epub 2012 Apr 17. Am J Physiol Endocrinol Metab. 2012. PMID: 22510710 VLDL-triglyceride kinetics during hyperglycemia-hyperinsulinemia: effects of sex and obesity. Mittendorfer B, Patterson BW, Klein S, Sidossis LS. Mittendorfer B, et al. Am J Physiol Endocrinol Metab. 2003 Apr;284(4):E708-15. doi: 10.1152/ajpendo.00411.2002. Epub 2002 Dec 10. Am J Physiol Endocrinol Metab. 2003. PMID: 12475756 Determinants of VLDL-triglycerides production. Nielsen S, Karpe F. Nielsen S, et al. Curr Opin Lipidol. 2012 Aug;23(4):321-6. doi: 10.1097/MOL.0b013e3283544956. Curr Opin Lipidol. 2012. PMID: 22617755 Review. Removal of triacylglycerols from chylomicrons and VLDL by capillary beds: the basis of lipoprotein remnant formation. Karpe F, Bickerton AS, Hodson L, Fielding BA, Tan GD, Frayn KN. Karpe F, et al. Biochem Soc Trans. 2007 Jun;35(Pt 3):472-6. doi: 10.1042/BST0350472. Biochem Soc Trans. 2007. PMID: 17511631 Review. See all similar articles Cited by TG/HDL Ratio Is an Independent Predictor for Estimating Resting Energy Expenditure in Adults with Normal Weight, Overweight, and Obesity. Widmer A, Mercante MG, Silver HJ. Widmer A, et al. Nutrients. 2022 Dec 1;14(23):5106. doi: 10.3390/nu14235106. Nutrients. 2022. PMID: 36501139 Free PMC article. Emerging Evidence of Pathological Roles of Very-Low-Density Lipoprotein (VLDL). Huang JK, Lee HC. Huang JK, et al. Int J Mol Sci. 2022 Apr 13;23(8):4300. doi: 10.3390/ijms23084300. Int J Mol Sci. 2022. PMID: 35457118 Free PMC article. Review. Adipocyte Proteins and Storage of Endogenous Fatty Acids in Visceral and Subcutaneous Adipose Tissue in Severe Obesity. Lytle KA, Bush NC, Triay JM, Kellogg TA, Kendrick ML, Swain JM, Gathaiya NW, Hames KC, Jensen MD. Lytle KA, et al. Obesity (Silver Spring). 2021 Jun;29(6):1014-1021. doi: 10.1002/oby.23149. Epub 2021 Apr 24. Obesity (Silver Spring). 2021. PMID: 33893721 Free PMC article. Clinical Trial. Metabolic communication during exercise. Murphy RM, Watt MJ, Febbraio MA. Murphy RM, et al. Nat Metab. 2020 Sep;2(9):805-816. doi: 10.1038/s42255-020-0258-x. Epub 2020 Aug 3. Nat Metab. 2020. PMID: 32747791 Review. Visceral fat does not contribute to metabolic disease in lipodystrophy. Malandrino N, Reynolds JC, Brychta RJ, Chen KY, Auh S, Gharib AM, Startzell M, Cochran EK, Brown RJ. Malandrino N, et al. Obes Sci Pract. 2019 Jan 24;5(1):75-82. doi: 10.1002/osp4.319. eCollection 2019 Feb. Obes Sci Pract. 2019. PMID: 30847226 Free PMC article. See all "Cited by" articles Publication types Research Support, Non-U.S. Gov't Actions Search in PubMed Search in MeSH Add to Search MeSH terms Absorptiometry, Photon Actions Search in PubMed Search in MeSH Add to Search Adipose Tissue / metabolism* Actions Search in PubMed Search in MeSH Add to Search Adult Actions Search in PubMed Search in MeSH Add to Search Blood Glucose / metabolism Actions Search in PubMed Search in MeSH Add to Search Body Composition / physiology* Actions Search in PubMed Search in MeSH Add to Search Calorimetry, Indirect Actions Search in PubMed Search in MeSH Add to Search Female Actions Search in PubMed Search in MeSH Add to Search Humans Actions Search in PubMed Search in MeSH Add to Search Insulin / blood Actions Search in PubMed Search in MeSH Add to Search Insulin / metabolism Actions Search in PubMed Search in MeSH Add to Search Kinetics Actions Search in PubMed Search in MeSH Add to Search Lipoproteins, VLDL / metabolism* Actions Search in PubMed Search in MeSH Add to Search Middle Aged Actions Search in PubMed Search in MeSH Add to Search Obesity / metabolism* Actions Search in PubMed Search in MeSH Add to Search Triglycerides / metabolism* Actions Search in PubMed Search in MeSH Add to Search Young Adult Actions Search in PubMed Search in MeSH Add to Search Substances Blood Glucose Actions Search in PubMed Search in MeSH Add to Search Insulin Actions Search in PubMed Search in MeSH Add to Search Lipoproteins, VLDL Actions Search in PubMed Search in MeSH Add to Search Triglycerides Actions Search in PubMed Search in MeSH Add to Search very low density lipoprotein triglyceride Actions Search in PubMed Search in MeSH Add to Search Related information MedGen PubChem Compound PubChem Compound (MeSH Keyword) PubChem Substance LinkOut - more resources Full Text Sources Atypon Medical MedlinePlus Health Information Miscellaneous NCI CPTAC Assay Portal Full text links [x] Atypon [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Send To Clipboard Email Save My Bibliography Collections Citation Manager [x] NCBI Literature Resources MeSH PMC Bookshelf Disclaimer The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). 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Bilirubin; a diagnostic marker for appendicitis - PubMed This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content An official website of the United States government Here's how you know The .gov means it’s official. Federal government websites often end in .gov or .mil. Before

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Log in Show account info Close Account Logged in as: username Dashboard Publications Account settings Log out Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Advanced Clipboard User Guide Save Email Send to Clipboard My Bibliography Collections Citation manager Display options Display options Format Abstract PubMed PMID Save citation to file Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel Email citation Subject: 1 selected item: 24080115 - PubMed To: From: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Add to My Bibliography My Bibliography Unable to load your delegates due to an error Please try again Add Cancel Your saved search Name of saved search: Search terms: Test search terms Would you like email updates of new search results? Saved Search Alert Radio Buttons Yes No Email: ( change ) Frequency: Monthly Weekly Daily Which day? The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday Which day? Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel Create a file for external citation management software Create file Cancel Your RSS Feed Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy Full text links Elsevier Science Full text links Actions Cite Collections Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Display options Display options Format Abstract PubMed PMID Share Permalink Copy Page navigation Title & authors Abstract Comment in Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Title & authors Abstract Comment in Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Observational Study Int J Surg Actions Search in PubMed Search in NLM Catalog Add to Search . 2013;11(10):1114-7. doi: 10.1016/j.ijsu.2013.09.006. Epub 2013 Sep 27. Bilirubin; a diagnostic marker for appendicitis N D'Souza 1 , D Karim , R Sunthareswaran Affiliations Expand Affiliation 1 Poole Hospital, UK. Electronic address: [email protected]. PMID: 24080115 DOI: 10.1016/j.ijsu.2013.09.006 Free article Item in Clipboard Observational Study Bilirubin; a diagnostic marker for appendicitis N D'Souza et al. Int J Surg . 2013 . Free article Show details Display options Display options Format Abstract PubMed PMID Int J Surg Actions Search in PubMed Search in NLM Catalog Add to Search . 2013;11(10):1114-7. doi: 10.1016/j.ijsu.2013.09.006. Epub 2013 Sep 27. Authors N D'Souza 1 , D Karim , R Sunthareswaran Affiliation 1 Poole Hospital, UK. Electronic address: [email protected]. PMID: 24080115 DOI: 10.1016/j.ijsu.2013.09.006 Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Abstract Introduction: Every investigation that can contribute towards a diagnosis of appendicitis is valuable to the emergency general surgeon. Previous research has suggested that hyperbilirubinaemia is a more specific marker for both simple and perforated appendicitis than WBC (white blood count) and CRP (C-reactive protein), but this investigation is not commonly used to help diagnose appendicitis. Aims: This study investigated whether there is an association between hyperbilirubinaemia and appendicitis. We also reviewed the diagnostic value of bilirubin in perforated vs simple appendicitis, and compared it with the serum C-reactive protein (CRP) and white blood cell count (WBC). Methods: This single centre, prospective observational study included all patients admitted with right iliac fossa (RIF) pain who had liver function tests performed. Statistical analysis was performed using Fisher's exact test to compare bilirubin, WBC and CRP levels for normal appendices, simple appendicitis, and perforated appendicitis. Results: 242 patients were included in this study, of whom 143 were managed operatively for RIF pain. Hyperbilirubinaemia was significantly associated with appendicitis vs RIF pain of other aetiologies (p < 0.0001). Bilirubin had a higher specificity (0.96), than WBC (0.71) and CRP (0.62), but a lower sensitivity (0.27 vs 0.68 and 0.82 respectively). Hyperbilirubinaemia was associated with perforated appendicitis vs simple appendicitis with statistical significance (p < 0.0001). Bilirubin had a higher specificity (0.82) than both WBC (0.34) and CRP (0.21), but a lower sensitivity (0.70 vs 0.80 and 0.95 respectively). Conclusion: Our findings confirm that hyperbilirubinaemia has a high specificity for distinguishing acute appendicitis, especially when perforated, from other causes of RIF pain, particularly those not requiring surgery. Keywords: Appendicitis; Diagnostic techniques and procedures; Hyperbilirubinaemia; Sensitivity and specificity. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. PubMed Disclaimer Comment in Correspondence to: Bilirubin; a diagnostic marker for appendicitis. Dholakia S, Khalid U. Dholakia S, et al. Int J Surg. 2014;12(2):188. doi: 10.1016/j.ijsu.2013.11.015. Epub 2013 Dec 1. Int J Surg. 2014. PMID: 24296156 No abstract available. Similar articles The value of biochemical markers in predicting a perforation in acute appendicitis. McGowan DR, Sims HM, Zia K, Uheba M, Shaikh IA. McGowan DR, et al. ANZ J Surg. 2013 Jan;83(1-2):79-83. doi: 10.1111/ans.12032. Epub 2012 Dec 12. ANZ J Surg. 2013. PMID: 23231057 Hyperbilirubinaemia: its utility in non-perforated appendicitis. Sandstrom A, Grieve DA. Sandstrom A, et al. ANZ J Surg. 2017 Jul;87(7-8):587-590. doi: 10.1111/ans.13373. Epub 2015 Nov 17. ANZ J Surg. 2017. PMID: 26573997 Hyperbilirubinaemia in appendicitis: the diagnostic value for prediction of appendicitis and appendiceal perforation. Adams HL, Jaunoo SS. Adams HL, et al. Eur J Trauma Emerg Surg. 2016 Apr;42(2):249-52. doi: 10.1007/s00068-015-0540-x. Epub 2015 May 22. Eur J Trauma Emerg Surg. 2016. PMID: 26038057 Elevated serum bilirubin in assessing the likelihood of perforation in acute appendicitis: a diagnostic meta-analysis. Giordano S, Pääkkönen M, Salminen P, Grönroos JM. Giordano S, et al. Int J Surg. 2013;11(9):795-800. doi: 10.1016/j.ijsu.2013.05.029. Epub 2013 May 31. Int J Surg. 2013. PMID: 23732757 Review. Hyperbilirubinemia as a predictor for appendiceal perforation: a systematic review. Burcharth J, Pommergaard HC, Rosenberg J, Gögenur I. Burcharth J, et al. Scand J Surg. 2013;102(2):55-60. doi: 10.1177/1457496913482248. Scand J Surg. 2013. PMID: 23820677 Review. See all similar articles Cited by Elevated total and direct bilirubin are associated with acute complicated appendicitis: a single-center based study in Saudi Arabia. Alfehaid MS, Babiker AM, Alkharraz AH, Alsaeed HY, Alzunaydi AA, Aldubaiyan AA, Sinyan HA, Alkhalaf BK, Alshuwaykan R, Khalil R, Al-Wutayd O. Alfehaid MS, et al. BMC Surg. 2023 Nov 10;23(1):342. doi: 10.1186/s12893-023-02258-2. BMC Surg. 2023. PMID: 37950198 Free PMC article. The Diagnostic Accuracy of Hyperbilirubinemia in Predicting Appendicitis and Appendiceal Perforation. Khalid SY, Elamin A. Khalid SY, et al. Cureus. 2023 Nov 3;15(11):e48203. doi: 10.7759/cureus.48203. eCollection 2023 Nov. Cureus. 2023. PMID: 37929270 Free PMC article. Bilirubin as a Predictor of Complicated Appendicitis in a District General Hospital: A Retrospective Analysis. Halaseh SA, Kostalas M, Kopec C, Nimer A. Halaseh SA, et al. Cureus. 2022 Sep 11;14(9):e29036. doi: 10.7759/cureus.29036. eCollection 2022 Sep. Cureus. 2022. PMID: 36237793 Free PMC article. The predictive value of ischemia-modified albumin in the diagnosis of acute appendicitis: A prospective case-control study. Ünsal A, Turhan VB, Öztürk D, Buluş H, Türkeş GF, Erel Ö. Ünsal A, et al. Ulus Travma Acil Cerrahi Derg. 2022 Apr;28(4):523-528. doi: 10.14744/tjtes.2020.58675. Ulus Travma Acil Cerrahi Derg. 2022. PMID: 35485513 Free PMC article. Magnetic resonance imaging (MRI) for diagnosis of acute appendicitis. D'Souza N, Hicks G, Beable R, Higginson A, Rud B. D'Souza N, et al. Cochrane Database Syst Rev. 2021 Dec 14;12(12):CD012028. doi: 10.1002/14651858.CD012028.pub2. Cochrane Database Syst Rev. 2021. PMID: 34905621 Free PMC article. Review. See all "Cited by" articles Publication types Observational Study Actions Search in PubMed Search in MeSH Add to Search MeSH terms Abdominal Pain / blood Actions Search in PubMed Search in MeSH Add to Search Abdominal Pain / etiology Actions Search in PubMed Search in MeSH Add to Search Adolescent Actions Search in PubMed Search in MeSH Add to Search Adult Actions Search in PubMed Search in MeSH Add to Search Aged Actions Search in PubMed Search in MeSH Add to Search Aged, 80 and over Actions Search in PubMed Search in MeSH Add to Search Appendicitis / blood* Actions Search in PubMed Search in MeSH Add to Search Appendicitis / diagnosis Actions Search in PubMed Search in MeSH Add to Search Bilirubin / blood* Actions Search in PubMed Search in MeSH Add to Search Biomarkers / blood Actions Search in PubMed Search in MeSH Add to Search Child Actions Search in PubMed Search in MeSH Add to Search Child, Preschool Actions Search in PubMed Search in MeSH Add to Search Humans Actions Search in PubMed Search in MeSH Add to Search Hyperbilirubinemia / blood Actions Search in PubMed Search in MeSH Add to Search Male Actions Search in PubMed Search in MeSH Add to Search Middle Aged Actions Search in PubMed Search in MeSH Add to Search Prospective Studies Actions Search in PubMed Search in MeSH Add to Search Young Adult Actions Search in PubMed Search in MeSH Add to Search Substances Biomarkers Actions Search in PubMed Search in MeSH Add to Search Bilirubin Actions Search in PubMed Search in MeSH Add to Search Related information Cited in Books MedGen PubChem Compound (MeSH Keyword) LinkOut - more resources Full Text Sources Elsevier Science Ovid Technologies, Inc. Other Literature Sources The Lens - Patent Citations scite Smart Citations Medical MedlinePlus Health Information Research Materials NCI CPTC Antibody Characterization Program Miscellaneous NCI CPTAC Assay Portal Full text links [x] Elsevier Science [x] Cite Copy Download .nbib .nbib Format: AMA APA MLA NLM Send To Clipboard Email Save My Bibliography Collections Citation Manager [x] NCBI Literature Resources MeSH PMC Bookshelf Disclaimer The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited. Follow NCBI Twitter Facebook LinkedIn GitHub Connect with NLM Twitter SM-Facebook SM-Youtube National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers NLM NIH HHS USA.gov

Coffee for Cardioprotection and Longevity - PubMed This site needs JavaScript to work properly. Please enable it to take advantage of the complete set of features! Clipboard, Search History, and several other advanced features are temporarily unavailable. Skip to main page content An official website of the United States government Here's how you know The .gov means it’s official. Federal government websites often end in .gov or .mil. Before

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Log in Show account info Close Account Logged in as: username Dashboard Publications Account settings Log out Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation Search: Search Advanced Clipboard User Guide Save Email Send to Clipboard My Bibliography Collections Citation manager Display options Display options Format Abstract PubMed PMID Save citation to file Format: Summary (text) PubMed PMID Abstract (text) CSV Create file Cancel Email citation Subject: 1 selected item: 29474816 - PubMed To: From: Format: Summary Summary (text) Abstract Abstract (text) MeSH and other data Send email Cancel Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Add to My Bibliography My Bibliography Unable to load your delegates due to an error Please try again Add Cancel Your saved search Name of saved search: Search terms: Test search terms Would you like email updates of new search results? Saved Search Alert Radio Buttons Yes No Email: ( change ) Frequency: Monthly Weekly Daily Which day? The first Sunday The first Monday The first Tuesday The first Wednesday The first Thursday The first Friday The first Saturday The first day The first weekday Which day? Sunday Monday Tuesday Wednesday Thursday Friday Saturday Report format: Summary Summary (text) Abstract Abstract (text) PubMed Send at most: 1 item 5 items 10 items 20 items 50 items 100 items 200 items Send even when there aren't any new results Optional text in email: Save Cancel Create a file for external citation management software Create file Cancel Your RSS Feed Name of RSS Feed: Number of items displayed: 5 10 15 20 50 100 Create RSS Cancel RSS Link Copy Full text links Elsevier Science Full text links Actions Cite Collections Add to Collections Create a new collection Add to an existing collection Name your collection: Name must be less than 100 characters Choose a collection: Unable to load your collection due to an error Please try again Add Cancel Display options Display options Format Abstract PubMed PMID Share Permalink Copy Page navigation Title & authors Abstract Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Title & authors Abstract Similar articles Cited by Publication types MeSH terms Substances Related information LinkOut - more resources Review Prog Cardiovasc Dis Actions Search in PubMed Search in NLM Catalog Add to Search . 2018 May-Jun;61(1):38-42. doi: 10.1016/j.pcad.2018.02.002. Epub 2018 Feb 21. Coffee for Cardioprotection and Longevity James H O'Keefe 1 , James J DiNicolantonio 2 , Carl J Lavie 3 Affiliations Expand Affiliations 1 Saint Luke's Mid America Heart Institute, Kansas City, MO, United States. Electronic address: [email protected]. 2 Saint Luke's Mid America Heart Institute, Kansas City, MO, United States. 3 Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, United States. PMID: 29474816 DOI: 10.1016/j.pcad.2018.02.002 Item in Clipboard Review Coffee for Cardioprotection and Longevity James H O'Keefe et al. Prog Cardiovasc Dis . 2018 May-Jun . Show details Display options Display options Format Abstract PubMed PMID Prog Cardiovasc Dis Actions Search in PubMed Search in NLM Catalog Add to Search . 2018 May-Jun;61(1):38-42. doi: 10.1016/j.pcad.2018.02.002. Epub 2018 Feb 21. Authors James H O'Keefe 1 , James J DiNicolantonio 2 , Carl J Lavie 3 Affiliations 1 Saint Luke's Mid America Heart Institute, Kansas City, MO, United States. Electronic address: [email protected]. 2 Saint Luke's Mid America Heart Institute, Kansas City, MO, United States. 3 Department of Cardiovascular Diseases, John Ochsner Heart and Vascular Institute, Ochsner Clinical School, The University of Queensland School of Medicine, New Orleans, LA, United States. PMID: 29474816 DOI: 10.1016/j.pcad.2018.02.002 Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Abstract Coffee, a complex brew containing hundreds of biologically active compounds, exerts potent effects on long-term human health. Recently, a plethora of studies have been published focusing on health outcomes associated with coffee intake. An inverse association between coffee consumption and all-cause mortality has been seen consistently in large prospective studies. Habitual coffee consumption is also associated with lower risks for cardiovascular (CV) death and a variety of adverse CV outcomes, including coronary heart disease (CHD), congestive heart failure (HF), and stroke; coffee's effects on arrhythmias and hypertension are neutral. Coffee consumption is associated with improvements in some CV risk factors, including type 2 diabetes (T2D), depression, and obesity. Chronic coffee consumption also appears to protect against some neurodegenerative diseases, and is associated with improved asthma control, and lower risks for liver disease and cancer. Habitual intake of 3 to 4 cups of coffee appears to be safe and is associated with the most robust beneficial effects. However, most of the studies regarding coffee's health effects are based on observational data, with very few randomized controlled trials. Furthermore, the possible benefits of coffee drinking must be weighed against potential risks, which are generally due to its high caffeine content, including anxiety, insomnia, headaches, tremulousness, and palpitations. Coffee may also increase risk of fracture in women, and when consumed in pregnancy coffee increases risk for low birth weight and preterm labor. Keywords: Cancer; Cardiovascular disease; Coffee; Coronary heart disease; Diabetes; Heart failure; Stroke. Copyright © 2018. Published by Elsevier Inc. PubMed Disclaimer Similar articles Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality. O'Keefe JH, Bhatti SK, Patil HR, DiNicolantonio JJ, Lucan SC, Lavie CJ. O'Keefe JH, et al. J Am Coll Cardiol. 2013 Sep 17;62(12):1043-1051. doi: 10.1016/j.jacc.2013.06.035. Epub 2013 Jul 17. J Am Coll Cardiol. 2013. PMID: 23871889 Review. Coffee and tea: perks for health and longevity? Bhatti SK, O'Keefe JH, Lavie CJ. Bhatti SK, et al. Curr Opin Clin Nutr Metab Care. 2013 Nov;16(6):688-97. doi: 10.1097/MCO.0b013e328365b9a0. Curr Opin Clin Nutr Metab Care. 2013. PMID: 24071782 Review. Coffee consumption and health: umbrella review of meta-analyses of multiple health outcomes. Poole R, Kennedy OJ, Roderick P, Fallowfield JA, Hayes PC, Parkes J. Poole R, et al. BMJ. 2017 Nov 22;359:j5024. doi: 10.1136/bmj.j5024. BMJ. 2017. PMID: 29167102 Free PMC article. Review. Coffee: A Selected Overview of Beneficial or Harmful Effects on the Cardiovascular System? Whayne TF Jr. Whayne TF Jr. Curr Vasc Pharmacol. 2015;13(5):637-48. Curr Vasc Pharmacol. 2015. PMID: 25277696 Review. Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of cohort studies. Shahinfar H, Jayedi A, Khan TA, Shab-Bidar S. Shahinfar H, et al. Nutr Metab Cardiovasc Dis. 2021 Aug 26;31(9):2526-2538. doi: 10.1016/j.numecd.2021.05.014. Epub 2021 May 24. Nutr Metab Cardiovasc Dis. 2021. PMID: 34112583 See all similar articles Cited by Association of daily sitting time and coffee consumption with the risk of all-cause and cardiovascular disease mortality among US adults. Zhou H, Nie J, Cao Y, Diao L, Zhang X, Li J, Chen S, Zhang X, Chen G, Zhang Z, Li B. Zhou H, et al. BMC Public Health. 2024 Apr 17;24(1):1069. doi: 10.1186/s12889-024-18515-9. BMC Public Health. 2024. PMID: 38632571 Free PMC article. Acute Effects of Coffee Consumption on Blood Pressure and Endothelial Function in Individuals with Hypertension on Antihypertensive Drug Treatment: A Randomized Crossover Trial. Lima de Castro FBA, Castro FG, da Cunha MR, Pacheco S, Freitas-Silva O, Neves MF, Klein MRST. Lima de Castro FBA, et al. High Blood Press Cardiovasc Prev. 2024 Jan;31(1):65-76. doi: 10.1007/s40292-024-00622-8. Epub 2024 Feb 3. High Blood Press Cardiovasc Prev. 2024. PMID: 38308805 Clinical Trial. Exploring the connection between caffeine intake and constipation: a cross-sectional study using national health and nutrition examination survey data. Kang Y, Yan J. Kang Y, et al. BMC Public Health. 2024 Jan 2;24(1):3. doi: 10.1186/s12889-023-17502-w. BMC Public Health. 2024. PMID: 38167025 Free PMC article. Plants of the Rubiaceae Family with Effect on Metabolic Syndrome: Constituents, Pharmacology, and Molecular Targets. González-Castelazo F, Soria-Jasso LE, Torre-Villalvazo I, Cariño-Cortés R, Muñoz-Pérez VM, Ortiz MI, Fernández-Martínez E. González-Castelazo F, et al. Plants (Basel). 2023 Oct 15;12(20):3583. doi: 10.3390/plants12203583. Plants (Basel). 2023. PMID: 37896046 Free PMC article. Review. Caffeine causes cell cycle arrest at G0/G1 and increases of ubiquitinated proteins, ATP and mitochondrial membrane potential in renal cells. Kanlaya R, Subkod C, Nanthawuttiphan S, Thongboonkerd V. Kanlaya R, et al. Comput Struct Biotechnol J. 2023 Sep 21;21:4552-4566. doi: 10.1016/j.csbj.2023.09.023. eCollection 2023. Comput Struct Biotechnol J. 2023. PMID: 37799542 Free PMC article. 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Familial hypercholesterolemia: A review - PMC Back to Top Skip to main content An official website of the United States government Here's how you know The .gov means it’s official. Federal government websites often end in .gov or .mil. Before

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the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Ann Pediatr Cardiol. 2014 May-Aug; 7(2): 107–117. doi: 10.4103/0974-2069.132478 PMCID: PMC4070199 PMID: 24987256 Familial hypercholesterolemia: A review Mithun J Varghese Mithun J Varghese Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India Find articles by Mithun J Varghese Author information Copyright and License information PMC Disclaimer Department of Cardiology, Christian Medical College, Vellore, Tamil Nadu, India Address for correspondence: Dr. Mithun J Varghese, Department of Cardiology, Christian Medical College, Vellore - 632 004, Tamil Nadu, India. E-mail: moc.liamg@vjnuhtimrd Copyright : © Annals of Pediatric Cardiology This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL) cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs). The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH. Keywords: Familial hypercholesterolemia, heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, low-density lipoprotein receptor mutation INTRODUCTION Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism characterized by highly elevated plasma total-cholesterol levels with detrimental cardiovascular consequences that commence in childhood. Although atherosclerosis due to FH manifests primarily in adulthood, it has a precocious inception as early as the 1 st decade of life.[ 1 ] That early treatment of risk factors can reverse the atherosclerotic changes in the arterial system[ 2 ] underscores the need for prompt detection and treatment of children with this condition. Fagge identified this disorder more than a century ago as a skin ailment,[ 3 ] but its correlation with atherosclerosis was first recognized in 1939 by Norwegian physician Carl Muller.[ 4 ] The past decade saw a flurry of research in this disease with respect to its genetic basis and therapy. However, FH remains underdiagnosed till late due to the lack of awareness among pediatricians and the general public and the diagnosis is often arrived at only after the irreversible consequences of atherosclerosis have been established. This review describes the current status of the diagnosis, screening, and management of this malady. GENETICS OF FH ’Familial hypercholesterolemia’ represents the phenotypic manifestation of abnormal lipoprotein metabolism caused by a variety of genetic abnormalities. After the seminal discovery by Brown and Goldstein that mutations in the low-density lipoprotein receptor (LDLR) was the cause of monogenetic FH, over 1,500 mutations of this gene have been detected[ 5 , 6 ] and these account for more than 80% of cases of monogenetic FH.[ 7 ] Heterozygous FH (HeFH) is not an uncommon disorder in children, with an estimated prevalence of 1 in 500 in the western world.[ 8 ] Homozygous FH (HoFH), although uncommon (prevalence is less than one per million in the general population), is a critical condition which commences in the first few years of life.[ 9 ] It is principally noted in countries such as Lebanon, Canada, and South Africa possibly because of the founder mutations and isolation of population.[ 10 ] In addition to the LDLR defect, two other sets of autosomal dominant mutations play a central role in the pathogenesis of FH; one, a defective apo-B100 component of LDL, known as familial defective apoB-100 (clinically indistinguishable from heterozygous LDLR mutations).[ 11 , 12 , 13 ] Secondly, a gain of function mutation affecting proprotein convertase subtilisin/kexin 9 (PCSK9) encoded by chromosome 1 has also been shown to trigger FH by negatively modulating LDL receptor expression.[ 14 ] Although the rare autosomal recessive form of FH called autosomal recessive hypercholesterolemia has been described in a few families,[ 15 , 16 ] in clinical practice, monogenetic hypercholesterolemia is primarily an autosomal dominant disorder with greater than 90% penetrance. Though single gene disorders play a crucial role in the etiology of FH, linkage studies have exposed that the majority of cases of FH are caused by numerous unexceptional genetic variations.[ 11 ] An interplay of these polygenic variations together with environmental factors remains the leading cause for hypercholesterolemia in the general population.[ 17 , 18 ] However, a monogenetic etiology is usually the reason for more severe forms of LDL elevation and also for phenotypic expression of FH in the 1 st decade of life. SCREENING FOR FH The ideal strategy to screen for FH is currently a controversial issue. Former lipid guidelines advocated ‘targeted screening’, which comprised a fasting lipid profile test in children with risk factors for FH such as a family history of premature cardiovascular diseases (CVDs), dyslipidemia, or obesity.[ 19 ] However, despite its cost effectiveness, this approach entailed the risk of missing 30-60% of affected patients.[ 20 ] An alternative approach to screening is termed ‘cascade screening’,[ 21 , 22 ] wherein health workers actively screen for disease among the first and second degree relatives of patients diagnosed by targeted screening. Although this method is associated with improved detection rates, there remains a considerable risk of missing affected individuals. This shortcoming has prompted some of the recent guidelines to recommend a strategy of universal lipid screening.[ 23 , 24 ] However, the cost effectiveness or utility of universal screening as well as the psychological impact on the children and the parents are not well-studied. Furthermore, a minority of patients of FH (7%) may have a normal lipid profile at the time of screening,[ 25 ] thus, facing the risk of missing the diagnosis in some despite screening of the entire population. An equally important question is what to screen — lipids or genes? Genetic screening strategy involves searching for the common genes causing FH among suspected children and their close relatives. Recent National Institute for Health and Care Excellence (NICE) guidelines recommend a DNA testing on all patients diagnosed with FH and a subsequent genetic screening among their close relatives in order to augment case detection rates.[ 26 ] Although intuitively attractive, a significant number of patients clinically diagnosed with FH are negative for mutations conventionally tested for by genetic screening, probably due to polygenic inheritance.[ 27 ] In such patients, genetic cascade testing is expected to have a very low yield and is unlikely to be cost effective.[ 17 ] Hence, genetic cascade screening is likely to benefit only probands where a definite mutation is identified; in others, a strategy of lipid profile-based cascade screening is preferable. The ideal age of lipid screening among children is also a keenly debated issue. The normal cord blood levels of LDL-cholesterol ranges from 35 to 70 mg/dl.[ 28 ] Although cord blood LDL levels for screening for FH is an appealing concept, studies have shown significant overlap in these levels between neonates with and without HeFH,[ 29 ] thus precluding this as a screening strategy. The Lipid Research Clinics prevalence studies demonstrated that by the age of 2 years, the serum lipid level reached that of young adults,[ 30 ] while the National Health and Nutrition Examination Surveys (NHANESs)[ 31 ], reported that the peak lipid levels are reached by the age of 9-11 years. Therefore, universal screening is best performed between 9 and 11 years of age, whereas a screening at any time after the age of 2 years is preferred in those who are candidates of targeted screening.[ 11 , 32 , 33 ] Table 1 summarizes national lipid association guidelines for screening children for FH. Table 1 National lipid association key screening recommendations for FH Open in a separate window Clinical features and diagnosis Patients with HeFH are, by and large, asymptomatic in childhood and adolescence and typically diagnosed by screening methods. Their total and LDL-cholesterol levels are characteristically over the 95 th centile of the recommended levels and a strong family history corroborates the diagnosis. Some involved persons may bear peripheral markers of fat deposition such as tendon xanthoma or arcus lipoides. Homozygous or compound HeFH, on the other hand, presents in the 1 st decade of life with a distinctive and severe clinical phenotype. The age at presentation depends on the degree of LDL receptor activity,[ 16 ] those with the null phenotype (<2% LDL receptor activity) tend to present earlier, resulting even in intrauterine death. These patients have primarily dermatological and ocular manifestations — tendon xanthomas and interdigital xanthomas are pathognomic of HoFH [ Figure 1 ]. Tendon xanthomas are frequently missed on visual inspection alone and necessitate careful palpation in the Achilles, biceps and triceps tendons for early detection. Although tuberous xanthomas, xanthelasma, and corneal arcus appear in conditions other than FH,[ 34 ] their occurrence at a younger age should prompt evaluation for FH. Severe atherosclerosis involving multiple vascular beds, including coronary, cerebral, and peripheral vascular system, manifest in a myriad ways. Though coronary atherosclerosis is frequently the cause of premature death, calcific aortic valve stenosis and aortic root disease, including supravalvular aortic stenosis due to cholesterol and inflammatory cell infiltration, may result in significant morbidity in these patients, often requiring aortic valve and root replacement.[ 35 ] Open in a separate window Figure 1 Dermatological manifestations: (a) Eruptive xanthoma, (b) tendon xanthoma, and (c) tuberous xanthoma in a 12-year-old girl with homozygous familial hypercholesterolemia (FH). (d) Her father who was diagnosed to have heterozygous FH with coronary artery disease had xanthelasma When FH is suspected based on elevated lipid levels and clinical features, secondary dyslipidemias such as diabetes, endocrine disorders including hypothyroidism, renal disorders, obesity, and incriminating drugs must be ruled out before arriving at the diagnosis. A detailed family history should be taken not only to assess the mode of transmission but also to identify other affected individuals for early commencement of treatment. A comprehensive CVD risk assessment is required in all diagnosed patients and correction of modifiable risk factors must be pursued. The value of CVD risk assessment tools used in adults such as Framingham Risk Score have not been validated in the pediatric and adolescent populations with FH and are liable to underestimate the risk.[ 11 ] Ancillary investigations such as carotid intima medial thickness and ankle brachial index, which are usually used in research settings, may be helpful in monitoring the progression of disease in selected cases. The diagnosis of FH is typically based on elevation of total-, LDL-, and non-HDL-cholesterol above the 95 th centile recommended for the age and sex of the patient together with positive family history or identification of a causative mutation. The MEDPED criteria from the United States,[ 36 ] the Dutch Lipid Clinic criteria,[ 37 ] and the British Simon Broome Registry criteria[ 38 ] [ Table 2 ] are validated diagnostic systems in this regard. The first relies solely on the age and the blood lipid levels of the patient, while the latter two require family history and clinical findings as well. These criteria are credited with simplicity and ease of use; however, they may be relatively ineffective at diagnosing index cases. Moreover, these criteria may not be clinically sensitive when applied to mild phenotypes and children in whom phenotypic expression is not yet completed. Table 2 Criteria for diagnosis of familial hypercholesterolemia Open in a separate window Management Lipid targets Recommendations differ with respect to target lipid levels in pediatric and adolescent patients. National Lipid Association guidelines recommend a target LDL level of <130 mg/dl or >50% reduction from baseline values.[ 24 ] More rigorous targets are proposed in patients with additional risk factors such as diabetes, obesity, and a family history of CVD. Belgian multisocietal guidelines, on the other hand, recommend age-specific targets.[ 33 ] In children aged 10-14 years, an LDL level of <160 mg/dl or >30% reduction from baseline levels is targeted. A rigorous target lipid level of <130 mg/dl is recommended in children between the ages of 14 and 18 years. In patients older than 18 years, a lipid target of <100 mg/dl is deemed appropriate. It should be noted that, a recent cross-sectional study in the Netherlands showed that no more than 21% of HeFH patients realized their lipid goals despite the recent advances in therapy.[ 39 ] Among patients who failed to achieve LDL-cholesterol goal, only 21% were on maximal dose of approved drugs, suggesting shortcomings in adequate monitoring and implementation of therapy.[ 39 ] Lifestyle changes Therapeutic lifestyle adjustments forman important part in the management of FH. This encompasses specific dietary manipulations, physical activity, limitation of alcohol intake, and total avoidance of tobacco products. Recent guidelines recommend a low calorie diet with a total fat intake of ≤3% of the total dietary intake including <8% of saturated fat and <75 mg/1,000 kcal cholesterol for these patients.[ 33 ] However, dietary restrictions are noted to have a modest effect in lowering lipid levels,[ 40 ] with unproven long-term clinical benefits.[ 41 ] Consequently, a concurrent drug therapy is indicated in patients with severe hypercholesterolemia. Dietary supplementation of phytosterol esters and stanol esters is controversial: Although a few recent studies have demonstrated a reduction of LDL levels in children with FH,[ 42 ] there are concerns regarding their accumulation in atheromas[ 43 ] and lowering of serum levels of lipid soluble vitamins.[ 44 ] Similarly, dietary supplementation of soy proteins and polyunsaturated fatty acids in this population is not substantiated by clinical evidence and is, hence, not currently recommended.[ 33 ] Drug therapy-when to start? The former guidelines issued by National Heart, Lung, and Blood Institute (NHLBI) advised treatment with bile acid sequestrants, the lowest age recommended for initiation being 10 years.[ 19 ] This was based on the excellent long-term safety profile of this group of drugs owing to lack of their systemic absorption. However, modest efficacy[ 45 ] and poor tolerability of these drugs resulted in alterations in the recent expert opinions and consensus papers.[ 23 , 24 , 33 ] In a recent statement by the American Heart Association,[ 46 ] later endorsed by the American Academy of Pediatrics,[ 20 ] statins were proposed as first-line drugs and the age of initiation of therapy was lowered to 8 years. Bile acid Sequestrants Formerly, this class of drugs was deemed the first-line of therapy of FH in children owing to their lack of systemic uptake. They bind to bile acids in the intestine, thereby, preventing their systemic absorption; this results in a greater conversion of cholesterol to bile acids and an enhanced production of LDL receptors by the liver. Cholestyramine and colestipol were the most frequently used drugs in this class; however, they fell out of favor due to their modest efficacy (10-20% LDL reduction) and gastrointestinal intolerance. Of late, a novel drug in this class, colesevelam hydrochloride, has been studied in HeFH patients. A short-term, randomized trial showed good tolerability and efficacy of colesevelam alone and in combination with statins leading to a renewed interest in this class of drugs.[ 47 ] Statins Statins (3-hydroxy-3methyl-glutaryl-CoA reductase inhibitors) are currently the first line of drugs in the treatment of FH in children and adolescents. They inhibit the rate-limiting step in cholesterol synthesis, thus, increasing the expression of LDL receptors, resulting in the rapid clearance of LDL from the blood. However, they have a restricted role in patients of HoFH with null phenotype in view of the need for receptor production for their action. Among the various generic statins available, the Food and Drug Administration (FDA) has approved of pravastatin in children over 8 years of age and lovastatin, atorvastatin, and simvastatin above the age of 10 years.[ 48 ] The prepubertal commencement of statin therapy remains controversial,[ 49 ] as this can potentially hamper the production of steroid hormones in the body. Moreover, their effects on muscles and the liver are still an issue of grave concern. A recent Cochrane review[ 50 ] and two meta-analysis[ 51 , 52 ] of placebo-controlled trials on statins in children and adolescents with FH showed no major side effects with regard to growth, sexual development, muscle, and liver toxicity. Concurrently, they showed excellent efficacy in lipid lowering with a 26.5% mean relative reduction in LDL-cholesterol levels. The apprehension regarding growth disruption by statins at puberty was allayed, in part, by the paradoxical finding of increased growth in the children treated with the drug.[ 51 , 52 ] However, it is noteworthy that all the trials included in these meta-analyses studied only short-term outcomes; the long-term safety of statins in this population is unknown. The longest follow-up data on the effects of statin therapy in pediatric population is a retrospective study over a 7-year period in 185 children with FH treated with pravastatin, which revealed minor side effects in 13% of patients and myopathy in four patients.[ 53 ] Modern trends of drug usage among children indicate that the utilization of statins in the pediatric population is in the upswing,[ 54 ] despite the aforementioned concerns in relation to long-term safety. There are specific recommendations on the subject of monitoring of patients commencing statin therapy. Creatine phosphokinase (CK) to assess muscle toxicity and aspartate amino transferase (AST), and alanine amino transferase (ALT) to monitor liver toxicity are mandatory prior to initiation of statins. Follow-up measurements must be done 1-3 months after starting the drug and yearly thereafter. Drug therapy should be interrupted when CK levels reach five times and AST and ALT three times over the upper limit of normal; the same drug at a lower dose or a different statin may be introduced after a drug-free interval of 3 months. Other drugs may be tried if the patient does not tolerate statins despite these measures.[ 33 ] Ezetimibe Ezetimibe is a new class of cholesterol absorption inhibitors that acts on the brush border of the small intestinal epithelium. The specific site of its action is believed to be the epithelial cell Niemann — Pick C1-like protein.[ 55 ] As their mechanism of action is not based on the expression of LDL receptors, they are especially beneficial in the management of HoFH. Clinical trials have displayed their efficacy in reducing LDL levels when used alone[ 56 ] or in combination with statins.[ 57 , 58 ] However, the initial fervor over their use was dampened by the largest prospective trial (ENHANCE trial) on cholesterol absorption inhibitors until this time, which demonstrated that ezetimibe added to high dose simvastatin failed to lessen carotid intima medial thickness in spite of a significant diminution in LDL levels.[ 59 ] Lastly, the discovery of a small but significant rise in the incidence of cancer in patients treated with ezetimibe patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial[ 60 ] is a cause for concern in view of the need for lifelong therapy required in patients with FH. Therefore, additional data is required on clinically significant outcomes as well as safety endpoints before their widespread adoption in pediatric practice. Although US Food and Drug Administration (FDA) has approved of ezetemibe therapy in children over the age of 10years, current guidelines recommend drug initiation before 18 years of age only in patients intolerant to statins and in patients who fail to realize lipid goals with statin monotherapy.[ 11 , 33 ] Therapeutic options in patients who failed to attain lipid targets despite maximal medical therapy Newer drugs Mipomirsen, an antisense oligonucleotide that targets apoB-100 mRNA in the liver, is presently under investigation in the therapy of FH. This drug significantly lowered LDL and lipoprotein (a) levels in adults with heterozygous[ 61 ] and homozygous[ 62 ] hypercholesterolemia in recent phase 3 trials. Although the mean LDL reduction with 200 mg of subcutaneous mipomirsen administered weekly was significant in patients with HoFH (-24.7% in treatment group and -3.3% in the placebo group, P = 0.0003), the response to therapy was inconsistent and compounded by a significant number of nonresponders.[ 62 ] The most frequent side effects of mipomirsen include reactions at the site of injection and flu-like symptoms, but apprehension regarding their hepatic toxicity, especially steatosis, still remains. Moreover, as they have not been studied in the pediatric population in a prospective clinical trial, their safety profile in this group of patients is not defined. Serum PCSK9 are proteins which bind to LDL receptors and promote their degradation, thus, raising LDL levels in the blood. A variety of molecular techniques based on terminating the effect of PCSK9 in order to lower LDL-cholesterol levels is under investigation, including the development of monoclonal antibodies that bind to PCSK9,[ 63 ] antisense nucleotide-based therapy,[ 64 ] and small interfering RNAs.[ 65 ] In a randomized control trial experimenting on monoclonal antibodies in adults with various forms of hypercholesterolemia, the combination of this drug with 10 and 80 mg of atorvastatin was more efficacious than80mg of atorvastatin alone in reducing LDL levels.[ 66 ] However, as this antibody requires some residual LDL receptor function to fulfill its function, it is useful only in patients with HeFH and non-null phenotype HoFH. Lomitapide is a new lipid-lowering agent with a novel method of action: It inhibits the microsomal triglyceride transfer protein(MTP). The role of MTP in the production of LDL involves assisting inthe transfer of triglycerides to apolipoprotein B.[ 67 ] The US FDA has approved of its use as an orphan drug in the treatment of HoFH.[ 68 ] In a recently published phase 3 dose escalation trial, lomitapide reduced LDL-cholesterol by 50% in HoFH patients with poorly controlled LDL levels.[ 69 ] Although this small study showed a satisfactory safety profile of the drug, there are still lingering doubts regarding the hepatic side effects like steatosis and transaminitis owing to their distinctive mechanism of action. In addition to the aforementioned drugs, other classes of drugs like thyroid mimetics (e.g., eprotirome and sobetirome),[ 70 ] HDL-bound enzyme cholesterol ester transfer protein (CETP) inhibitors (e.g., torcetrapib, anacetrapib, and evacetrapib) and reconstituted high-density lipoprotein (rHDL)[ 71 ] are currently under research in the treatment of elevated LDL-cholesterol and shows variable efficacy and safety. All the ongoing trials on modern drug therapy of dyslipidemia focuses on adult patients and excludes the pediatric population. Given that a majority of these novel therapies are yet unproven with regard to clinical efficacy and safety endpoints, their role is presently confined to that of a lipid apheresis-sparing therapy in patients with HoFH who have fallen short of their lipid goals. Additional studies in the pediatric population are required prior to their clinical adoption in the treatment of heterozygous patients. LDL apheresis Patients with homozygous and compound HeFH frequently have elevated lipid levels in spite of optimal medical therapy. These are fitting candidates for LDL apheresis, which has proved to be a very beneficial treatment option to reducing LDL levels. Numerous studies have affirmed its capability to lower LDL-cholesterol levels by 55-75%.[ 72 ] Commonly used techniques of LDL apheresis include heparin-induced extracorporeal LDL-cholesterol precipitation (HELP), dextran sulfate cellulose adsorption (DSA), double filtration plasmapheresis (DFPP), polyacrylate full blood adsorption (PFBA also known as DALI), and immune adsorption. Details on the techniques are beyond the scope of this update and interested readers may consult excellent reviews available on the subject.[ 73 , 74 , 75 ] The decline in LDL-cholesterol levels by apheresis is a transitory event and is associated with a rebound escalation of lipid levels after the procedure. This rebound is expeditious in patients without FH, slower in those with HeFH and delayed in patients in HoFH.[ 76 ] Weekly to fortnightly sessions are advocated for patients with HoFH, as such episodic sittings have been shown to reduce the degree of rebound and retard the progression of atherosclerosis.[ 77 , 78 ] Regular apheresis therapy along with medications in patients of HoFH has improved the average life expectancy to over 50 years of age compared to the formerly bleak prognosis of death in the2 nd or 3 rd decade.[ 79 ] Despite its established efficacy, lipid apheresis has not yet been widely embraced in clinical practice due to lack of accessibility for the majority of patients, the prohibitive cost involved, the invasive nature of the procedure, and the lack of motivation among patients. Gene therapy HoFH was among the first disorders wherein gene therapy was experimented. Contrary to other treatment alternatives, the possibility of a definitive cure by a one-time procedure for a disease that lasts a lifetime renders this an appealing choice. However, due to the problems related to appropriate gene vector, lack of persistent gene expression as well as due to safety concerns,[ 80 ] this modality failed to demonstrate substantial clinical efficacy in preliminary trials. Upcoming research should focus on improving gene vectors and transfer techniques, while concurrently reducing their oncogenic dangers before it can be relevant to clinical practice.[ 81 ] Surgical options In addition to the therapies enumerated prior, surgical options including ileal bypass and portocaval shunt have been tried earlier in refractory cases. Owing to the significant comorbidities involved and the need for treatment before the onset of clinical effects of atherosclerosis, these never became a popular choice of treatment. Recent case reports of successful pediatric liver transplant done for the treatment of HoFH suggest excellent efficacy and good safety profile of this option.[ 82 , 83 ] However, in view of the scarcity of donor liver available and complexities of the transplant and post-transplant management, such a decision should be taken only after carefully assessing the risk benefit ratio. Natural and modified natural history of FH The natural history of FH depends primarily on the degree of functional LDL receptor activity present, and in turn, on LDL-cholesterol levels, resulting in widely varying prognosis even among homozygous individuals.[ 84 ] Symptom onset is age-dependent and typically occurs in the 2 nd decade in homozygous patients. The extent of atherosclerosis is primarily determined by the degree of LDL elevation and its duration, calculated by the cholesterol year score.[ 85 ] Precocious onset of clinically significant atherosclerotic changes are very common and involve multiple vascular beds including coronary, cerebral, and peripheral systems.[ 85 ] Studies in the pre-statin era indicated poor outcomes in the majority of patients with HoFH, cardiovascular events being the chief cause of morbidity and mortality.[ 86 ] Aortic root disease was reported to be the commonest cardiac manifestation followed by coronary artery disease.[ 86 ] While some studies in this interval purported a mean survival of 18 years among patients with HoFH,[ 87 ] others observed an average survival of 40 years;[ 86 ] this variation may be ascribed to the differences in the proportion of receptor-negative patients included in these studies. It was conventionally believed that modern day drug therapy for HoFH does not alter prognosis owing to the lack of significant reduction in LDL. However, this assumption was challenged by a recent retrospective analysis by Raal et al ., involving 149 patients, wherein patients treated with statins had hazard ratios for mortality and cardiovascular events of 0.34 and 0.49, respectively when compared with patients in the pre-statin era, despite achieving only a modest 26% reduction in LDL levels. 87 Although this result may be partly influenced by the beneficial effects of cardiovascular preventive drugs such as antiplatelet agents and beta blockers, this study underscores the benefit of statin therapy even in FH homozygous individuals. Among patients with untreated HeFH, coronary artery disease (CAD) develops in about 50% of males by the age of 50 years and 30% of females by 60 years. Although CAD appears 10years later in females compared to males, an accelerated development of CAD is observed after menopause.[ 88 , 89 ] Simon Broome registry data from England in the pre-statin era showed that mortality associated with CAD was increased a 100-fold in the age group of 20-40 years and four-fold in the 40-59 year age group.[ 38 ] Among those surviving to the age of 60 years, however, the risk seems akin to that in the general population.[ 38 ] The benefits of present day therapeutic advances in this population is confirmed by a large prospective study from the UK, which reveals a 37% relative reduction in standardized mortality rate from 3.4 in the pre-statin era to 2.1 after widespread use of statins.[ 90 ] Despite strong association of FH with coronary and peripheral vascular disease, its relation with stroke risk is more controversial. A large prospective registry data from United Kingdom showed that ischemic stroke mortality among treated HeFH patients not to be different from general population.[ 91 ] The reason for this difference is presently unknown. CONCLUSION FH is a grave ailment with its genesis in early childhood resulting in damaging consequences in later life. Although the need for a screening strategy to detect this disease early is widely accepted, there is no consensus regarding whom and when to screen. Early initiation of lipid-lowering therapy and lifestyle measures might improve the clinical outcome. While such treatment initiatives have notably improved the prognosis of HeFH, the outcomes of familial homozygous hypercholesterolemia remain disappointing. Although most cases may be treated with a combination of statins and cholesterol absorption inhibitors, some will have need of more invasive therapies such as LDL apheresis. 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Epub 2010 Jan 20. Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals S Torabian 1 , E Haddad , Z Cordero-MacIntyre , J Tanzman , M L Fernandez , J Sabate Affiliations Expand Affiliation 1 Department of Nutrition, School of Public Health, Loma Linda University, Loma Linda, CA, USA. [email protected] PMID: 20087377 DOI: 10.1038/ejcn.2009.152 Item in Clipboard Randomized Controlled Trial Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals S Torabian et al. Eur J Clin Nutr . 2010 Mar . Show details Display options Display options Format Abstract PubMed PMID Eur J Clin Nutr Actions Search in PubMed Search in NLM Catalog Add to Search . 2010 Mar;64(3):274-9. doi: 10.1038/ejcn.2009.152. Epub 2010 Jan 20. Authors S Torabian 1 , E Haddad , Z Cordero-MacIntyre , J Tanzman , M L Fernandez , J Sabate Affiliation 1 Department of Nutrition, School of Public Health, Loma Linda University, Loma Linda, CA, USA. [email protected] PMID: 20087377 DOI: 10.1038/ejcn.2009.152 Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID Abstract Background/objectives: Walnuts have been shown to reduce serum lipids in short-term well-controlled feeding trials. Little information exists on the effect and sustainability of walnut consumption for longer duration in a free-living situation. Subjects/methods: A randomized crossover design in which 87 subjects with normal to moderate high plasma total cholesterol were initially assigned to a walnut-supplemented diet or habitual (control) diet for a 6-month period, then switched to the alternate dietary intervention for a second 6-month period. Each subject attended seven clinics 2 months apart. At each clinic, body weight was measured, and in five clinics (months 0, 4, 6, 10 and 12), a blood sample was collected. Results: Our study showed that supplementing a habitual diet with walnuts (12% of total daily energy intake equivalent) improves the plasma lipid profile. This beneficial effect was more significant in subjects with high plasma total cholesterol at baseline. Significant changes in serum concentrations of total cholesterol (P=0.02) and triglycerides (P=0.03) were seen and nearly significant changes in low-density lipoprotein cholesterol (LDL-C) (P=0.06) were found. No significant change was detected in either high-density lipoprotein (HDL) cholesterol LDL to HDL ratio. Conclusions: Including walnuts as part of a habitual diet favorably altered the plasma lipid profile. The lipid-lowering effects of walnuts were more evident among subjects with higher lipid baseline values, precisely those people with greater need of reducing plasma total and LDL-C. PubMed Disclaimer Comment in Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals. Um CY, He K. Um CY, et al. Eur J Clin Nutr. 2011 Mar;65(3):421; author reply 422. doi: 10.1038/ejcn.2010.246. Epub 2010 Nov 10. Eur J Clin Nutr. 2011. PMID: 21063430 No abstract available. Similar articles Long-term walnut supplementation without dietary advice induces favorable serum lipid changes in free-living individuals. Um CY, He K. Um CY, et al. Eur J Clin Nutr. 2011 Mar;65(3):421; author reply 422. doi: 10.1038/ejcn.2010.246. Epub 2010 Nov 10. Eur J Clin Nutr. 2011. PMID: 21063430 No abstract available. Influence of body mass index and serum lipids on the cholesterol-lowering effects of almonds in free-living individuals. Jaceldo-Siegl K, Sabaté J, Batech M, Fraser GE. Jaceldo-Siegl K, et al. Nutr Metab Cardiovasc Dis. 2011 Jun;21 Suppl 1:S7-13. doi: 10.1016/j.numecd.2011.03.007. Epub 2011 May 12. Nutr Metab Cardiovasc Dis. 2011. PMID: 21570268 Serum lipid profiles in Japanese women and men during consumption of walnuts. Iwamoto M, Imaizumi K, Sato M, Hirooka Y, Sakai K, Takeshita A, Kono M. Iwamoto M, et al. Eur J Clin Nutr. 2002 Jul;56(7):629-37. doi: 10.1038/sj.ejcn.1601400. Eur J Clin Nutr. 2002. PMID: 12080402 Clinical Trial. Almonds have a neutral effect on serum lipid profiles: a meta-analysis of randomized trials. Phung OJ, Makanji SS, White CM, Coleman CI. Phung OJ, et al. J Am Diet Assoc. 2009 May;109(5):865-73. doi: 10.1016/j.jada.2009.02.014. J Am Diet Assoc. 2009. PMID: 19394473 Review. Walnuts decrease risk of cardiovascular disease: a summary of efficacy and biologic mechanisms. Kris-Etherton PM. Kris-Etherton PM. J Nutr. 2014 Apr;144(4 Suppl):547S-554S. doi: 10.3945/jn.113.182907. Epub 2014 Feb 5. J Nutr. 2014. PMID: 24500935 Review. See all similar articles Cited by In Vitro Assessment of the Bioaccessibility of Zn, Ca, Mg, and Se from Various Types of Nuts. Moskwa J, Naliwajko SK, Puścion-Jakubik A, Soroczyńska J, Socha K, Koch W, Markiewicz-Żukowska R. Moskwa J, et al. Foods. 2023 Dec 12;12(24):4453. doi: 10.3390/foods12244453. Foods. 2023. PMID: 38137257 Free PMC article. Tree Nut and Peanut Consumption and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Houston L, Probst YC, Chandra Singh M, Neale EP. Houston L, et al. Adv Nutr. 2023 Sep;14(5):1029-1049. doi: 10.1016/j.advnut.2023.05.004. Epub 2023 May 5. Adv Nutr. 2023. PMID: 37149262 Free PMC article. Review. Nuts and seeds consumption and risk of cardiovascular disease, type 2 diabetes and their risk factors: a systematic review and meta-analysis. Arnesen EK, Thorisdottir B, Bärebring L, Söderlund F, Nwaru BI, Spielau U, Dierkes J, Ramel A, Lamberg-Allardt C, Åkesson A. Arnesen EK, et al. Food Nutr Res. 2023 Feb 14;67. doi: 10.29219/fnr.v67.8961. eCollection 2023. Food Nutr Res. 2023. PMID: 36816545 Free PMC article. Review. The Effect of Walnut Intake on Lipids: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Alshahrani SM, Mashat RM, Almutairi D, Mathkour A, Alqahtani SS, Alasmari A, Alzahrani AH, Ayed R, Asiri MY, Elsherif A, Alsabaani A. Alshahrani SM, et al. Nutrients. 2022 Oct 23;14(21):4460. doi: 10.3390/nu14214460. Nutrients. 2022. PMID: 36364723 Free PMC article. Review. Association of nut consumption with CVD risk factors in young to middle-aged adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study. Yi SY, Steffen LM, Zhou X, Shikany JM, Jacobs DR Jr. Yi SY, et al. Nutr Metab Cardiovasc Dis. 2022 Oct;32(10):2321-2329. doi: 10.1016/j.numecd.2022.07.013. Epub 2022 Jul 31. Nutr Metab Cardiovasc Dis. 2022. PMID: 35970686 Free PMC article. 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Walnut consumption in a weight reduction intervention: effects on body weight, biological measures, blood pressure and satiety - PMC Back to Top Skip to main content An official website of the United States government Here's how you know The .gov means it’s official. Federal government websites often end in .gov or .mil. Before

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the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice Nutr J. 2017; 16: 76. Published online 2017 Dec 4. doi: 10.1186/s12937-017-0304-z PMCID: PMC5715655 PMID: 29202751 Walnut consumption in a weight reduction intervention: effects on body weight, biological measures, blood pressure and satiety Cheryl L. Rock , Shirley W. Flatt , Hava-Shoshana Barkai , Bilge Pakiz , and Dennis D. Heath Cheryl L. Rock Department of Family Medicine and Public Health, School of Medicine, University of California, 3855 Health Sciences Drive, Room 3077, La Jolla, CA 92093-0901 USA Find articles by Cheryl L. Rock Shirley W. Flatt Department of Family Medicine and Public Health, School of Medicine, University of California, 3855 Health Sciences Drive, Room 3077, La Jolla, CA 92093-0901 USA Find articles by Shirley W. Flatt Hava-Shoshana Barkai Department of Family Medicine and Public Health, School of Medicine, University of California, 3855 Health Sciences Drive, Room 3077, La Jolla, CA 92093-0901 USA Find articles by Hava-Shoshana Barkai Bilge Pakiz Department of Family Medicine and Public Health, School of Medicine, University of California, 3855 Health Sciences Drive, Room 3077, La Jolla, CA 92093-0901 USA Find articles by Bilge Pakiz Dennis D. Heath Department of Family Medicine and Public Health, School of Medicine, University of California, 3855 Health Sciences Drive, Room 3077, La Jolla, CA 92093-0901 USA Find articles by Dennis D. Heath Author information Article notes Copyright and License information PMC Disclaimer Department of Family Medicine and Public Health, School of Medicine, University of California, 3855 Health Sciences Drive, Room 3077, La Jolla, CA 92093-0901 USA Cheryl L. Rock, Phone: 858-822-1126, Email: ude.dscu@kcorlc . Corresponding author. Received 2017 Sep 21; Accepted 2017 Nov 27. Copyright © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Associated Data Data Availability Statement The datasets generated and/or analyzed during the current study are not publicly available due to the private (and not public) sponsorship but are available from the corresponding author on reasonable request. Abstract Background Dietary strategies that help patients adhere to a weight reduction diet may increase the likelihood of weight loss maintenance and improved long-term health outcomes. Regular nut consumption has been associated with better weight management and less adiposity. The objective of this study was to compare the effects of a walnut-enriched reduced-energy diet to a standard reduced-energy-density diet on weight, cardiovascular disease risk factors, and satiety. Methods Overweight and obese men and women ( n = 100) were randomly assigned to a standard reduced-energy-density diet or a walnut-enriched (15% of energy) reduced-energy diet in the context of a behavioral weight loss intervention. Measurements were obtained at baseline and 3- and 6-month clinic visits. Participants rated hunger, fullness and anticipated prospective consumption at 3 time points during the intervention. Body measurements, blood pressure, physical activity, lipids, tocopherols and fatty acids were analyzed using repeated measures mixed models. Results Both study groups reduced body weight, body mass index and waist circumference (time effect p < 0.001 for each). Change in weight was −9.4 (0.9)% vs. -8.9 (0.7)% (mean [SE]), for the standard vs. walnut-enriched diet groups, respectively. Systolic blood pressure decreased in both groups at 3 months, but only the walnut-enriched diet group maintained a lower systolic blood pressure at 6 months. The walnut-enriched diet group, but not the standard reduced-energy-density diet group, reduced total cholesterol and low-density lipoprotein cholesterol (LDL-C) at 6 months, from 203 to 194 mg/dL and 121 to 112 mg/dL, respectively ( p < 0.05). Self-reported satiety was similar in the groups. Conclusions These findings provide further evidence that a walnut-enriched reduced-energy diet can promote weight loss that is comparable to a standard reduced-energy-density diet in the context of a behavioral weight loss intervention. Although weight loss in response to both dietary strategies was associated with improvements in cardiovascular disease risk factors, the walnut-enriched diet promoted more favorable effects on LDL-C and systolic blood pressure. Trial registration The trial is registered at ( {"type":"clinical-trial","attrs":{"text":"NCT02501889","term_id":"NCT02501889"}} NCT02501889 ). Keywords: Weight loss, Nuts, Satiety, Cardiovascular disease risk factors, Blood pressure Introduction Current guidelines for the management of overweight and obesity recommend prescribing a reduced-energy diet as a primary treatment intervention to promote weight loss, as part of a comprehensive lifestyle intervention, and conclude that a variety of dietary approaches can produce weight loss [ 1 ]. However, dietary patterns, specific foods, and macronutrient composition may differentially affect metabolic factors, satiety, and the postprandial gastrointestinal peptide response that could affect hunger and appetite [ 2 , 3 ]. Dietary strategies that help patients reduce energy intake and adhere to a reduced-energy diet may increase the likelihood of improved long-term health outcomes and reduced risk for obesity-related conditions and diseases. In several large cohorts and a few clinical trials, a dietary pattern that includes regular nut consumption has been associated with less weight gain in adulthood and a lower degree of adiposity [ 4 – 11 ]. In a few previous studies, the effects of consuming almonds, pistachios, walnuts and peanuts on weight change and cardiovascular disease risk factors in the context of a weight loss intervention have been examined, with mixed results [ 12 – 18 ]. A proposed mechanism for the favorable effect of nuts on weight control is that they promote increased satiety, resulting in a compensatory reduction in total energy intake [ 4 , 5 ]. Feelings of satiety, fullness, and hunger following walnut consumption has been examined in only a few previous studies. In those studies, acute postprandial peptide response and early phase satiety was observed to be similar following a meal with or without walnuts, although increased satiety and fullness were found on days 3 and 4 following a walnut-containing meal [ 19 , 20 ]. Measuring responses over the long-term would better model the observational studies that have linked regular nut consumption with lower adiposity and better weight control. In the present study, we compared the effects of a walnut-enriched reduced-energy diet to a reduced-energy-density diet, which has been suggested to be a useful dietary strategy to promote reduced energy intake without compromising meal satiety [ 21 ]. The primary objective of this study was to compare the effects of a walnut-enriched reduced-energy diet to a standard reduced-energy-density diet on body weight and cardiovascular disease risk factors in a sample of overweight and obese adults in an intensive 6-month weight loss intervention. A secondary objective was to examine whether there is a differential response in satiety- and appetite-related ratings scales in association with a walnut-enriched reduced-energy diet and a reduced-energy-density diet among the participants in this weight-loss study. Methods Subjects One hundred non-diabetic overweight and obese men and women were randomized from a screened sample of 647 (Fig. 1 ). To be included in the study, participants had to meet the following criteria: Aged 21 years and older, body mass index (BMI) between 27 and 40 kg/m 2 ; willing and able to participate in clinic visits, group sessions, and telephone and internet communications; able to provide data through questionnaires and telephone; willing to maintain contact with investigators for 6 months; willing to allow blood collections; no known allergy to tree nuts; and capable of performing a simple test for assessing cardiopulmonary fitness. Exclusion criteria were any of the following: Inability to participate in physical activity due to severe disability; history or presence of a comorbid diseases where diet modification and increased physical activity may be contraindicated; self-reported pregnancy or breastfeeding or planning a pregnancy within the next year; currently involved in another diet intervention study or weight loss program; and having a history or presence of a significant psychiatric disorder or any condition that would interfere with participation in the trial. The University of California, San Diego (UCSD), institutional review board approved the study protocol, and all participants provided written informed consent. Open in a separate window Fig. 1 Flow chart for study participants Prior to enrollment, potential participants were screened for diabetes and considered ineligible with a fasting blood glucose ≥125 mg/dL. At screening and recruitment, the ability to participate in moderate intensity physical activity was assessed by questionnaire, a standard procedure for screening participants for community-based weight loss programs of this nature. Participants were additionally asked to report all prescription medications and were asked if they had ever been told by a doctor that they had high blood cholesterol. Once enrolled, participants were randomly assigned to one of the two study arms using a sequence stratified by age (≤52 vs. >52 years) and BMI (≤33 vs. >33 kg/m 2 ). Intervention All participants were provided a detailed diet prescription in an individual counseling session with a dietitian, in which a caloric deficit was set based on the participant’s goals, and a sample meal plan was developed according to study arm and participant food preferences. The overall goal of the dietary guidance was to promote a reduction in energy intake, aiming for a 500- to 1000-kcal/day deficit relative to expenditure. All participants had follow-up contact with the dietitian by telephone or email a minimum of every 1–2 weeks for additional support and to reinforce adherence throughout the intervention. Participants assigned to the standard reduced-energy-density diet arm were provided diet plans that emphasized lower energy density food choices such as vegetables, fruit and whole grains, as well as lean protein sources and reduced-fat dairy foods, with macronutrient composition within current guidelines ( https://www.choosemyplate.gov/MyPlate ). Participants assigned to this study group were asked to refrain from eating any nuts (and products containing them) for the duration of the study. Participants assigned to the walnut-enriched reduced-energy study group were instructed to consume an average of 42 g (1.5 oz) of walnuts/day for diet prescriptions that were ≥1500 kcal/day, or 28 g (1 oz) of walnuts/ for diet prescriptions <1500 kcal/day, all within their energy-reduced diet plan (thus, walnuts provided approximately 15% of total energy intake). Participants were provided meal and snack suggestions and recipes to facilitate adherence, and the nuts were distributed to participants assigned to that group on a weekly basis for 12 weeks and then biweekly for the remainder of the study. Also, participants were queried about walnut consumption for the previous week when the walnuts were distributed, and adherence was recorded. Use of a Web-based planning and tracking program that enabled tracking kilocalories was encouraged. All participants were provided a scale and were asked to weigh themselves daily and to record their progress. An activity tracker was provided and participants were asked to gradually build up to a minimum of 10,000 steps per day within the first month and then to maintain or increase that level of lifestyle activity. An additional daily exercise goal was an average of at least 60 min/day of purposeful aerobic activity at a moderate level of intensity. Strength training 2–3 times/week also was encouraged. Tools such as measuring cups, small exercise equipment, and videos were provided to encourage adherence. In addition to individualized diet prescription and counseling, all participants were assigned to a series of closed group sessions (weekly for 12 weeks, then biweekly), based on a semi-structured cognitive-behavioral weight loss intervention. Briefly, strategies discussed included: Planning and tracking meals and exercise; environmental control; realistic goal-setting; triggers to eating and ways to deal with them; problem-solving; dealing with negative thoughts; promoting self-efficacy through goal accomplishments and other strategies; self-nurturing; dealing with lapses; and addressing body image concerns. Measurements Study data were collected and managed using a Research Electronic Data Capture (REDcap) database hosted at UCSD [ 22 ]. At baseline and 3- and 6-month follow-up data collection clinic visits, weight, height (baseline only), waist circumference, and blood pressure were measured, and a fasting (≥6 h) blood sample and questionnaires were collected. Systolic and diastolic blood pressure was averaged from two sitting blood pressure measurements. The 3-min step test, which measures heart rate during the first 30 s of recovery from stepping, was used to assess cardiopulmonary fitness. This test has high reliability and is sensitive to change [ 23 ]. Physical activity was estimated using the Godin Leisure-Time Exercise Questionnaire, a validated self-report measure of physical activity that has been widely used in previous research [ 24 ]. This questionnaire assesses weekly hours of moderate and strenuous physical activity. These data were compared with current recommendations for physical activity in adults, which are 150 min weekly of moderate physical activity, or 75 min weekly of strenuous physical activity, or a combination of these [ 25 ]. Participants were asked to rate general (rather than meal-specific) satiation by using a visual analog scale (VAS), an approach which has been shown to have validity, reliability, and reproducibility [ 26 ]. Similar to other studies in which satiety and satiation over time (rather than meal-specific) have been assessed [ 19 ], participants were asked to complete these scales before lunch and dinner meals at three time points during the 6 months of active participation (weeks 1, 6, and 13). Specifically, subjects were asked to rate their satiety by answering three questions. Each of the questions was completed by the participant and transferred by staff (blinded to study arm assignment) to a REDCap (Vanderbilt University, Nashville, TN, USA) file database, with a 100 mm horizontal line anchored at either end, so that answers can be quantified on a continuous scale. The questions are: “How hungry do you feel?” with anchor values ranging from “I have never been more hungry” (scored as 0) to “I am not hungry at all” (scored as 100); “How full do you feel?”, with anchor values ranging from “Not at all full” (scored as 0) to “Totally full” (scored as 100); and “How much do you think you could eat now?” with anchor values ranging from “Nothing at all” (scored as 0) to “A lot” (scored as 100). Laboratory measures Laboratory measurements were conducted with plasma samples that had been frozen at -80 ο C after blood collection and processing. Total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were measured by Arup Laboratories (Salt Lake City, UT, USA) using enzymatic methods. The coefficient of variation (CV) for human serum for cholesterol at 76.2 mg/dL and 276 mg/dL is 1.6% and 1.4%, respectively; for triglycerides at 104 mg/dL and 261 mg/dL is 1.9% and 1.8%, respectively; and for HDL-C at 46.4 mg/dL and 80.4 mg/dL is 0.6% and 0.7%, respectively. Low-density lipoprotein cholesterol (LDL-C) values were calculated by the Friedewald equation [ 27 ]. Tocopherols and fatty acids were measured as dietary biomarkers because we anticipated that the walnut-enriched diet group could have different circulating concentrations compared to participants in the standard diet arm, reflecting differential intake of these dietary constituents due to regular walnut consumption. The detection and quantification of plasma tocopherols was accomplished by high performance liquid chromatography, using fluorescent detection at a wavelength of 295 nm excitation and 325 nm emission. Tocopherols were quantified by peak height using a standard curve prepared in bovine serum matrix from pure external compounds. Additionally, pooled in-house quality control samples were analyzed concurrently with batches of study samples, together with other commercially available reference samples, to monitor accuracy and precision. Also, the laboratory participates in the National Institute of Standards and Technology quality assurance program. Red blood cell (RBC) fatty acids were measured by OmegaQuant Laboratories (Sioux Falls, SD, USA) by gas chromatography (GC) with flame ionization detection. GC was carried out using a GC2010 Gas Chromatograph (Shimadzu Corporation, Columbia, MD, USA) equipped with a SP2560, 100-m fused silica capillary column (0.25 mm internal diameter, 0.2 um film thickness; Supelco, Bellefonte, PA, USA). Fatty acids were identified by comparison with a standard mixture of fatty acids characteristic of RBCs (GLC OQ-A, NuCheck Prep, Elysian, MN, USA) which was also used to determine individual fatty acid calibration curves. Fatty acid composition was expressed as a percent of total identified fatty acids. Statistical analysis Demographic characteristics were compared at baseline between groups using chi-square tests for categorical variables and t-tests for continuous variables. Body measurements (weight, BMI, waist circumference), blood pressure, physical activity, lipids, tocopherols and fatty acids were analyzed using repeated measures mixed models assuming unstructured covariance. Change in an indicator of adiposity between groups (weight change as a percentage of initial weight) was also analyzed. Study time, diet group, and the group by time interaction were modeled as fixed effects in each model. Variables that were skewed were log transformed in analysis. Lipid concentrations were examined by sex to assess significant differences at baseline. We tested to see which of the lipids changed between baseline and 6 months, and if a significant change was observed, we performed multivariate analysis to identify predictors of such a lipid change. Power analysis for our sample size was based on published literature for nut consumption in a weight loss intervention [ 15 – 17 ]. Significance was set at alpha = 0.05. All statistical analysis was performed using the SAS software version 9.4 for Windows (SAS Institute Inc., Cary, North Carolina, USA). Results During the course of the study, 3 participants dropped out (one in the standard diet group and 2 in the walnut-enriched diet group). Overall compliance with prescribed walnut consumption in that study arm was 98%; review of monitoring records indicated that of the 47 participants, 43 reported consuming 97–100%, 2 reported consuming 92–96%, and 2 reported consuming 67–69% of the walnuts prescribed during the study. As shown in Table 1 , the randomized study groups did not differ by sex, age, education, or race/ethnicity. Both groups demonstrated a reduction in body weight, BMI, and waist circumference (time effect p < 0.001 for each) during the course of the study, and the two diet groups did not differ in degree of weight lost, with no significant group by time interactions, as shown in Table 2 . Both groups decreased their systolic blood pressure at 3 months, but only those in the walnut-enriched diet group maintained a lower systolic blood pressure at 6 months compared to baseline (Table 3 ). Participants in both study groups also decreased their diastolic blood pressure at 3 and 6 months, and increased their physical activity ( p < 0.001 for each). There was no significant group by time interaction observed in the blood pressure or physical activity models (Table 3 ). Cardiopulmonary fitness, as indicated by the step test recovery heart rate, improved in both study groups. Table 1 Characteristics of study participants in the weight reduction intervention Standard reduced-energy-density diet ( n = 51) Walnut-enriched reduced-energy diet ( n = 49) p (between groups) * Sex (N [%]) 0.53 Female 27 (53%) 31 (63%) Male 24 (47%) 18 (37%) Age (years), mean (SE) 52.2 (1.6) 53.3 (1.4) 0.63 Education (years), mean (SE) 16.1 (0.3) 16.2 (0.3) 0.88 Race/ethnicity (%) 0.84 Non-Hispanic white 73 73 Hispanic/Latino 14 18 African-American 6 2 Asian-American 2 2 Mixed/other 6 4 Open in a separate window *p values are from chi-square tests (categorical variables), or t-tests (continuous variables) Table 2 Body measurements of study participants in the weight reduction intervention Standard reduced- energy-density diet Walnut-enriched reduced-energy diet p (between groups) n Mean (SE) n Mean (SE) Body weight, kg a Baseline 51 90.9 (1.8) 49 91.1 (2.3) 0.96 3 Months 51 84.7 (1.8) 48 85.9 (2.3) 0.70 6 Months 50 82.1 (2.0) 47 82.4 (2.2) 0.92 Body mass index, kg/m 2 a Baseline 51 32.4 (0.4) 49 32.4 (0.5) 0.96 3 Months 51 30.3 (0.5) 48 30.6 (0.5) 0.63 6 Months 50 29.4 (0.6) 47 29.6 (0.5) 0.77 Weight change, kg 3 Months 51 −6.0 (0.6) 48 −5.5 (0.5) 0.51 6 Months 50 −8.5 (0.9) 47 −7.9 (0.6) 0.58 % Weight change 3 Months 51 −6.6 (0.6) 48 −6.1 (0.6) 0.53 6 Months 50 −9.4 (0.9) 47 −8.9 (0.7) 0.63 Waist circumference, cm a Baseline 51 109.9 (1.2) 49 111.5 (1.6) 0.42 3 Months 51 101.7 (1.3) 48 104.6 (1.6) 0.16 6 Months 50 98.9 (1.4) 47 100.7 (1.5) 0.39 Open in a separate window a Body weight, body mass index, and waist circumference showed a significant time effect compared with baseline, p < 0.001 for each variable, in both study groups at each follow-up point Table 3 Blood pressure and physical activity variables for study participants in the weight reduction intervention Standard reduced-energy-density diet Walnut-enriched reduced-energy diet p (between groups) n Mean(SE) n Mean(SE) Systolic blood pressure, mm Hg Baseline 51 123 (2) 49 124 (3) 0.77 3 Months 49 117 (2) * 48 116 (2) * 0.73 6 Months 49 119 (2) 46 118 (2) * 0.68 Diastolic blood pressure, mm Hg Baseline 51 82 (1) 49 82 (2) 0.72 3 Months 49 77 (1) * 48 76 (1) * 0.57 6 Months 49 78 (2) * 46 77 (1) * 0.70 Moderate/strenuous physical activity, minutes/week Baseline 51 120 (22) 49 133 (18) 0.53 3 Months 51 328 (31) * 48 337 (33) * 0.84 6 Months 49 351 (31) * 47 321 (29) * 0.48 % Meeting physical activity recommendations Baseline 51 25 49 45 0.04 3 Months 51 78 48 79 0.93 6 Months 47 85 47 81 0.58 Step test, heart rate/30s Baseline 51 57 (2) 49 60 (2) 0.14 3 Months 47 47 (1) * 47 49 (1) * 0.33 6 Months 47 45 (1)* 45 47 (1) * 0.18 Open in a separate window * Different from baseline within group, p < 0.01 for each Participants assigned to the walnut-enriched diet group, but not the standard reduced-energy-density diet group, had a reduction in total cholesterol concentration at 6 months, from 203 to 194 mg/dL ( p = 0.04), as shown in Table 4 . Triglycerides decreased in the standard diet group at 3 months and in both groups at 6 months, which decreased an average of 22 mg/dL from 128 to 106 ( p < 0.01 in log-transformed analysis). HDL-C did not change significantly between baseline and 6 months in either of the diet groups. In a subgroup analysis among the 21 men in the study, those assigned to the walnut-rich diet group had lower HDL-C levels (42 [ 10 ] vs. 50 [ 7 ] mg/dL [mean (SD)]) than those assigned to the standard reduced-energy-density diet at baseline ( p = 0.05) and at 3 months, 41(9) vs 54 (13) mg/dL ( p = 0.02) (data not shown). By 6 months, the men assigned to the walnut-enriched diet group had increased their HDL-C to 49 (18) mg/dL, and those in the standard reduced-energy-density diet group had also increased HDL-C to 59 (13) mg/dL (data not shown). Although 27% of the cohort reported having been told by a doctor that they had high cholesterol, only 10% of the cohort reported taking prescription medications to lower lipids. Table 4 Biological measures of study participants in the weight reduction intervention Standard reduced-energy-density diet Walnut-enriched reduced-energy diet p (between groups) p (group x time interaction) Mean(SE) Mean(SE) Cholesterol, mg/dL 0.84 Baseline 200 (5) 203 (6) 0.76 3 Months 199 (5) 198 (5) 0.95 6 Months 194 (6) 194 (6) a 0.91 Triglycerides, mg/dL 0.50 Baseline 130 (10) 123 (7) 0.55 3 Months 110 (8) a 115 (9) 0.66 6 Months 109 (9) a 103 (6) a 0.61 HDL cholesterol, mg/dL 0.08 Baseline 58 (2) 59 (2) 0.70 3 Months 60 (2) 58 (2) 0.37 6 Months 60 (2) 61 (2) 0.94 LDL Cholesterol, mg/dL 0.60 Baseline 116 (4) 121 (5) 0.42 3 Months 116 (5) 116 (4) 0.80 6 Months 112 (5) 112 (5) a 0.96 Alpha-tocopherol, μmol/L 0.96 Baseline 30.5 (1.3) 30.8 (1.0) 0.83 3 Months 30.0 (1.1) 30.3 (1.2) 0.72 6 Months 31.6 (1.2) 32.2 (1.3) 0.84 Beta-tocopherol, μmol/L 0.70 Baseline 0.33 (0.02) 0.33 (0.01) 0.38 3 Months 0.38 (0.01) a 0.27 (0.01) a 0.38 6 Months 0.28 (0.01) a 0.26 (0.01) a 0.99 Gamma-tocopherol, μmol/L 0.48 Baseline 4.23 (0.29) 3.99 (0.27) 0.55 3 Months 4.04 (0.31) 4.13 (0.20) 0.82 6 Months 4.08 (0.33) 4.30 (0.29) 0.74 Delta-tocopherol, μmol/L 0.98 Baseline 0.11 (0.01) 0.11 (0.01) 0.82 3 Months 0.10 (0.01) 0.10 (0.01) 0.88 6 Months 0.09 (0.01) a 0.08 (0.01) a 0.76 Linoleic acid, % <0.001 Baseline 0.111 (0.002) 0.110 (0.002) 0.77 3 Months 0.104 (0.002) a 0.111 (0.002) 0.004 6 Months 0.107 (0.002) a 0.112 (0.001) a 0.01 Alpha-linolenic acid, % <0.001 Baseline 0.00122 (0.00006) 0.00118 (0.00004) 0.57 3 Months 0.00105 (0.00006) a 0.00147 (0.00005) a <0.001 6 Months 0.00118 (0.00005) 0.00158 (0.00007) a <0.001 Open in a separate window a Different from baseline within group, p < 0.05 The overall change (in both groups combined) in total cholesterol at 6 months was −7 mg/dL and for triglycerides was −20 mg/dL. A multivariate model for change in triglycerides did not show that diet group assignment, weight loss, age, sex, or level of physical activity were significantly associated; however, a model for change in total cholesterol showed that weight change and age were significantly associated. In the multivariate model for change in cholesterol at 6 months, R-squared was 0.17 and the two factors significantly associated were age ( p = 0.002) and weight change ( p = 0.02). Diet, baseline BMI, baseline physical activity, and change in physical activity were not significantly related to cholesterol change. Participants >50 years of age decreased their cholesterol by 2 mg/dL compared with a decrease of 19 mg/dL for subjects younger than 50 years of age. Those who lost ≥5% of initial weight decreased their cholesterol by an average of 13 mg/dL compared with an increase in cholesterol of 18 mg/dL in subjects who did not lose at least 5% of initial body weight. As shown in Table 4 , we did not observe changes in alpha- or gamma-tocopherol, which are the major tocopherols in the plasma, and only minor changes in beta- and delta-tocopherol concentrations. Also, we observed increased concentrations of alpha-linolenic acid and linoleic acid in the walnut-enriched diet group over the study period, but not in the standard reduced-energy-density diet group (Table 4 ). Self-reported satiety was similar across the study in the diet groups (Table 5 ). Feelings of hunger decreased and fullness was greater at week 12 than week 1 in the standard reduced-energy-density diet group ( p < 0.05). Fullness was lower in the walnut-rich diet arm at week 12 ( p = 0.04). Table 5 Self-reported satiety (on a 100-point visual analog scale where Hunger is scored 0 = very hungry, 100 = not hungry at all; Fullness is scored 0 = not full, 100 = full; Quantity is scored 0 = nothing, 100 = a lot) in the weight reduction intervention Standard reduced-energy-density diet, mean(SEM) Walnut-enriched reduced-energy diet, mean(SEM) Lunch Dinner Lunch Dinner Hunger Week 1 43 (3) 40 (4) 49 (3) 40 (3) Week 6 50 (4) 43 (4) 42 (4) 45 (4) Week 12 53 (5) a 49 (4) a 44 (4) 44 (4) Fullness Week 1 44(4) 48 (5) 51(4) 51(5) Week 6 53 (5) 53 (42) 58 (4) 52 (5) Week 12 52 (6) a 61 (5) a 48 (4) b 49 (4) b Quantity Week 1 44(4) 50 (4) 49 (3) 55(4) Week 6 49 (4) 53 (4) 48 (4) 47 (4) Week 12 41 (4) 38 (5) 44 (3) 49 (4) Open in a separate window a Both hunger and fullness were greater at week 12 than week 1 in the standard reduced-energy-density diet group ( p < 0.05) b At week 12, fullness was lower in the walnut-rich diet arm than in the standard reduced-energy-density diet group ( p = 0.04) Discussion Findings from this study provide further evidence that a walnut-enriched reduced-energy diet can promote weight loss that is comparable to a standard reduced-energy-density diet in the context of a behavioral weight loss intervention. Although weight loss in response to both dietary strategies was associated with improvements in lipids and blood pressure, the walnut-enriched diet promoted more favorable effects on some cardiovascular disease risk factors, such as LDL-C and systolic blood pressure. Previous studies that have examined the effect of prescribing regular nut consumption on weight change in a weight loss intervention have had mixed results. Two studies found more weight loss in association with almond consumption (at doses of 50–84 g/day for 3 months) compared with controls [ 12 , 16 ], while a study examining the effect of a similar amount of almonds over a longer time frame (18 months) did not observe more weight loss compared to controls [ 15 ]. In a study that examined the effects of prescribing peanuts (16% of energy), weight loss was similar to controls, although the peanut-containing study arm had more favorable effects on cardiovascular disease risk factors [ 13 ]. Providing a daily snack of pistachios (53 g/day) vs. pretzels promoted a greater reduction of BMI and plasma triglyceride concentration but only a trend for a difference in body weight change in another study [ 14 ]. In a 12-month intervention study aimed to promote weight loss and healthy lifestyle, prescribing 30 g/day walnuts was associated with greater weight loss and improved diet quality compared to providing general dietary advice during the 3-month intensive phase of the intervention, although these differences were not evident at study end [ 17 ]. We recently examined the effects of a walnut-rich or higher-monounsaturated fat diet vs. a lower-fat diet prescription on weight loss and selected lipids and biomarkers in the context of a 12-month behavioral weight loss program [ 18 , 28 ]. Participants were stratified by insulin resistance status to allow examination of whether insulin resistance might be associated with differential response to diet composition. Similar to the present study, we observed that prescribing walnuts was associated with weight loss that was comparable to a standard lower fat diet, but better than a higher fat, lower carbohydrate diet without walnuts with regard to biomarker response [ 18 ]. In addition to promoting a similar degree of weight loss, we observed similar self-reported satiety in response to a walnut-enriched reduced-energy diet and a reduced-energy-density diet, that has been proposed to promote reduced energy intake without compromising meal satiety [ 21 ]. Notably, walnuts are very high in energy density, but when consumed as a component of a reduced-energy diet, this strategy may help to promote adherence to restricted total energy intake. The effects of tree nuts on blood lipids and several other cardiovascular disease risk factors were recently examined in a systematic review and meta-analysis [ 29 ], as well as in an earlier pooled analysis [ 30 ], and our observations of lower cholesterol and LDL-C in response to walnut consumption are in agreement with their conclusions. Across the 61 trials that met the eligibility criteria for the meta-analysis, that study found an average reduction of −4.7 and −4.8 mg/dL for total cholesterol and LDL-C, respectively, per one ounce/day serving of tree nuts in interventions ranging from 3 to 26 weeks [ 29 ]. Results of the present study, in which we observed this walnut-specific effect to be even greater in the context of a weight loss intervention, add to the evidence base. We also observed the effect to be modulated by age and degree of weight loss, with a greater reduction in cholesterol in younger individuals (<50 years) and those with greater weight loss (≥5% of initial weight). Previous meta-analyses of the effects of nut consumption on blood pressure are not in agreement, with one of them concluding that there are no significant effects [ 29 ] and another showing a reduction in systolic blood pressure in participants without type 2 diabetes [ 31 ] as observed in the present study. Walnuts are rich in gamma-tocopherol and polyunsaturated fatty acids, particularly alpha-linolenic and linoleic fatty acids [ 32 ]. In previous studies, an increase in gamma-tocopherol concentration has been observed in participants who were prescribed daily walnut consumption [ 33 , 34 ]. In our previous trial that prescribed walnuts in a weight loss intervention [ 18 , 35 ], we observed that walnut prescription minimized the reduction in plasma gamma-tocopherol that occurs in association with reduced energy intake and weight loss, as was observed in the present study. The increase in RBC alpha-linolenic and linoleic fatty acid concentrations in those assigned to the walnut-enriched reduced-energy study arm, and the differences across diet groups, is consistent with previous walnut feeding and walnut-rich diet interventions [ 18 , 33 , 36 ]. These changes in dietary biomarkers also provide strong support for the self-reported high level of adherence in participants instructed to consume walnuts daily in the present study. Notably, replacing saturated fats with polyunsaturated fats has been consistently associated with reduced risk for cardiovascular disease [ 37 , 38 ]. This study has some strengths and limitations. A strength is the heterogeneity of the study sample, which included both men and women and participants across racial/ethnic groups. Also, the retention rate was very high, which is not typical of weight loss intervention studies, and this reduces ambiguity in drawing inferences from this study. A limitation of the study is the lack of detailed information about dietary intake. We encouraged study participants to self-monitor dietary intake as a component of the behavioral strategies to promote weight control, but we did not collect detailed dietary data in an effort to minimize subject burden. Because this was a sample of free-living individuals, some variability in adherence to the prescribed diet is likely. However, the weight loss demonstrated by study participants suggests that most were consuming a reduced-energy diet, and the RBC fatty acid biomarker is indicative of good compliance by participants in the walnut-enriched diet group. Conclusions In conclusion, findings from this study provide further evidence that a walnut-enriched reduced-energy diet can promote weight loss that is comparable to a standard reduced-energy-density diet in the context of a behavioral weight loss intervention. Weight loss in response to both of these dietary strategies was associated with improvements in lipids and blood pressure, although the walnut-enriched diet promoted more favorable effects on LDL-C and systolic blood pressure. Acknowledgements We thank David Wang, Sam Sobrevinas, Jamie Fletcher, Daniel Wang, Jessica Hawks, and Pey-Lih Littler for their valuable assistance with the conduct of this study. We also thank Lita Hinton for her assistance with manuscript preparation and submission. Funding This study was funded by the American Institute for Cancer Research (AICR) and the California Walnut Commission through the AICR Matching Grant Program. The funding agencies had no role in the design of study, data collection and analysis, or presentation of the results. The California Walnut Commission provided the walnuts that were distributed to the participants in that study group. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to the private (and not public) sponsorship but are available from the corresponding author on reasonable request. Abbreviations BMI Body mass index CV Coefficient of variation GC Gas chromatography HDL-C High-density lipoprotein cholesterol LDL-C Low-density lipoprotein RBC Red blood cell REDcap Research Electronic Data Capture SE Standard error UCSD University of California, San Diego VAS Visual analog scale Authors’ contributions CLR designed and led the study throughout all phases, including the interpretation of the results and the development of the manuscript. SWF was responsible for data management, statistical analysis and interpretation, and presentation of the findings and results. HSB coordinated and operationalized the study, including screening, recruitment and enrollment, data collection and management, and conducted the intervention and dietary counseling of participants. BP contributed to the study design and analysis, and was responsible for all necessary intramural study activities, including institutional review board approval and monitoring. DDH conducted the laboratory analysis and contributed to interpretation of those data. All authors contributed to the writing of the manuscript, and all authors read and approved the final manuscript. Notes Ethics approval and consent to participate The UCSD institutional review board approved the study protocol (#151015), and all participants provided written informed consent. Prior to recruitment and operationalizing the study, the trial was registered at http://www.clinicaltrials.gov ( {"type":"clinical-trial","attrs":{"text":"NCT02501889","term_id":"NCT02501889"}} NCT02501889 ). Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. References 1. Jensen MD, Ryan DH, Apovian CM, et al. Guidelines (2013) for managing overweight and obesity in adults. Obesity. 2014; 22 :i–xvi. doi: 10.1002/oby.20778. [ PubMed ] [ CrossRef ] [ Google Scholar ] 2. Fleming JA, Kris-Etherton PM. Macronutrient content of the diet: what do we know about energy balance and weight maintenance? Curr Obes Rep. 2016; 5 :208–213. doi: 10.1007/s13679-016-0209-8. [ PubMed ] [ CrossRef ] [ Google Scholar ] 3. Delzenne N, Blundell J, Brouns F, et al. 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2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease - American College of Cardiology Guidelines JACC ACC.24 Members About Join Create Free Account or Log in to MyACC Menu Home Clinical Topics Acute Coronary Syndromes Anticoagulation Management Arrhythmias and Clinical EP Cardiac Surgery Cardio-Oncology Cardiovascular Care Team Congenital Heart Disease and Pediatric Cardiology COVID-19 Hub Diabetes and Cardiometabolic Disease Dyslipidemia Geriatric Cardiology Heart Failure and Cardiomyopathies Invasive Cardiovascular Angiography and Intervention Noninvasive Imaging Pericardial Disease Prevention Pulmonary Hypertension and Venous Thromboembolism Sports and Exercise Cardiology Stable Ischemic Heart Disease Valvular Heart Disease Vascular Medicine Latest In Cardiology Clinical Updates & Discoveries Advocacy & Policy Perspectives & Analysis Meeting Coverage ACC Member Publications ACC Podcasts View All Cardiology Updates Education and Meetings Online Learning Catalog Earn Credit View the Education Catalog Products ACC Anywhere: The Cardiology Video Library ACCSAP ACCEL CardioSource Plus for Institutions and Practices CathSAP ECG Drill and Practice EchoSAP EP SAP HF SAP Heart Songs Nuclear Cardiology Online Courses Collaborative Maintenance Pathway (CMP) Resources Understanding MOC Image and Slide Gallery Meetings Annual Scientific Session and Related Events Chapter Meetings Live Meetings Live Meetings - International Webinars - Live Webinars - OnDemand Certificates and Certifications Tools and Practice Support ACC Accreditation Services ACC Quality Improvement for Institutions Program CardioSmart National Cardiovascular Data Registry (NCDR) MedAxiom Advocacy at the ACC Cardiology as a Career Path Cardiology Careers Cardiovascular Buyers Guide Clinical Solutions Clinician Well-Being Portal Diversity and Inclusion Infographics Innovation Program Mobile and Web Apps < Back to Listings 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease Mar 17, 2019

  | Melvyn Rubenfire, MD, FACC Print Font Size A A A Authors: Arnett DK, Blumenthal RS, Albert MA, et al. Citation: 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2019;March 17:[Epub ahead of print]. The following are key perspectives from the 2019 American College of Cardiology/American Heart Association (ACC/AHA) Guideline on the Primary Prevention of Cardiovascular Disease (CVD): Scope of Guideline The guideline is a compilation of the most important studies and guidelines for atherosclerotic CVD (ASCVD) outcomes related to nine topic areas. The focus is primary prevention in adults to reduce the risk of ASCVD (acute coronary syndromes, myocardial infarction, stable or unstable angina, arterial revascularization, stroke/transient ischemic attack, peripheral arterial disease), as well as heart failure and atrial fibrillation. The guideline emphasizes patient-physician shared decisions with a multidisciplinary team-based approach to the implementation of recommended preventive strategies with sensitivities to the social determinants of health that may include specific barriers to care, limited health literacy, financial distress, cultural influences, education level, and other socioeconomic risk factors related to short- and long-term health goals. Assessment of ASCVD Risk Assessment of ASCVD risk is the foundation of primary prevention. For those aged 20-39 years, it is reasonable to measure traditional risk factors every 4-6 years to identify major factors (e.g., tobacco, dyslipidemia, family history of premature ASCVD, chronic inflammatory diseases, hypertension, or type 2 diabetes mellitus [T2DM]) that provide rationale for optimizing lifestyle and tracking risk factor progression and need for treatment. For adults aged 20-39 years and those aged 40-59 years who are not already at elevated (≥7.5%) 10-year risk, estimating a lifetime or 30-year risk for ASCVD may be considered ( ASCVD Risk Estimator Plus ). For those aged 20-59 years not at high short-term risk, the 30-year and lifetime risk would be reasons for a communication strategy for reinforcing adherence to lifestyle recommendations and for some drug therapy (e.g., familial hypercholesterolemia, hypertension, prediabetes, family history of premature ASCVD with dyslipidemia or elevated lipoprotein [a] Lp[a]). Estimating Risk of ASCVD Electronic and paper chart risk estimators are available that utilize population-based and clinical trial outcomes with the goal of matching need and intensity of preventive therapies to absolute risk (generally 10 years) for ASCVD events. The guideline suggests the race- and sex-specific Pooled Cohort Equation (PCE) ( ASCVD Risk Estimator Plus ) to estimate 10-year ASCVD risk for asymptomatic adults aged 40-79 years. Adults should be categorized into low (<5%), borderline (5 to <7.5%), intermediate (≥7.5 to <20%), or high (≥20%) 10-year risk. The PCEs are best validated among non-Hispanic whites and non-Hispanic blacks living in the United States. In other race/ethnic groups and some non-US populations, the PCE may over- or under-estimate risk (e.g., HIV infection, chronic inflammatory or autoimmune disease, and low socioeconomic levels). Consideration should be given to use of other risk prediction tools if validated in a population with similar characteristics. Examples include the general Framingham CVD risk score, Reynolds risk score, SCORE, and QRISK/JBS3 tools. Among borderline and intermediate-risk adults, one may consider additional individual "risk-enhancing" clinical factors that can be used to revise the 10-year ASCVD risk estimate. For initiating or intensifying statin therapy, include: family history of premature ASCVD (men <55 years, women <65 years); low-density lipoprotein cholesterol (LDL-C) ≥160 mg/dl or non-high-density lipoprotein cholesterol (non-HDL-C) ≥190 mg/dl; chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m 2 ); metabolic syndrome; pre-eclampsia and premature menopause (<40 years); inflammatory diseases including rheumatoid arthritis, lupus, psoriasis, HIV; South Asian ancestry; biomarkers including fasting triglycerides ≥175 mg/dl, Lp(a) ≥50 mg/dl, high-sensitivity C-reactive protein ≥2 mg/L, apolipoprotein B >130 mg/dl, and ankle-brachial index (ABI) <0.9. After considering these clinically available risk-enhancing factors, if there is still uncertainty about the reliability of the risk estimate for individuals in the borderline or intermediate-risk categories, further testing to document subclinical coronary atherosclerosis with computed tomography-derived coronary artery calcium score (CACs) is reasonable to more accurately reclassify the risk estimate upward or downward. For persons at intermediate predicted risk (≥7.5 to <20%) by the PCE or borderline (5 to <7.5%) predicted risk, CACs helps refine risk assessment. CACs can re-classify risk upward (particularly when score is ≥100 or ≥75th age/sex/race percentile) or downward (if CACs = 0), which is not uncommon, particularly in men <50 and women <60 years. In MESA (Multi-Ethnic Study of Atherosclerosis), the CACs was strongly associated with 10-year ASCVD risk in a graded fashion across age, sex, and race/ethnic groups, and independent of traditional risk factors. CAC may refine ASCVD risk estimates among lower-risk women (<7.5% 10-year risk), younger adults (<45 years), and older adults (≥75 years), but more data are needed to support its use in these subgroups. A CACs = 0 identifies individuals at lower risk of ASCVD events and mortality over a ≥10-year period, who appear to derive little or no benefit from statins and for which drug interventions can be delayed. The absence of CAC does not rule out noncalcified plaque, and clinical judgment about risk should prevail. CAC might also be considered in refining risk for selected low-risk adults (<5% 10-year risk) such as those with a strong family history of premature coronary heart disease (CHD). There are Internet-available risk estimation tools (MESA and ASTROCHARM), which incorporate both risk factors and CAC for estimating 10-year CHD or ASCVD risk, respectively. CAC measurement is not intended as a "screening" test for all, but rather is a decision aid in select adults to facilitate the clinician-patient risk discussion. Nutrition Dietary patterns associated with CVD mortality include—sugar, low-calorie sweeteners, high-carbohydrate diets, low-carbohydrate diets, refined grains, trans fat, saturated fat, sodium, red meat, and processed red meat (such as bacon, salami, ham, hot dogs, and sausage). All adults should consume a healthy plant-based or Mediterranean-like diet high in vegetables, fruits, nuts, whole grains, lean vegetable or animal protein (preferably fish), and vegetable fiber, which has been shown to lower the risk of all-cause mortality compared to control or standard diet. Longstanding dietary patterns that focus on low intake of carbohydrates and a high intake of animal fat and protein as well as high carbohydrate diets are associated with increased cardiac and noncardiac mortality. The increased availability of affordable, palatable, and high-calorie foods along with decreased physical demands of many jobs have fueled the epidemic of obesity and the consequent increases in hypertension and T2DM. Obesity Adults diagnosed as obese (body mass index [BMI] ≥30 kg/m 2 ) or overweight (BMI 25-29.9 kg/m 2 ) are at increased risk of ASCVD, heart failure, and atrial fibrillation compared with those of a normal weight. Obese and overweight adults are advised to participate in comprehensive lifestyle programs for 6 months that assist participants in adhering to a low-calorie diet (decrease by 500 kcal or 800-1500 kcal/day) and high levels of physical activity (200-300 minutes/week). Clinically meaningful weight loss (≥5% initial weight) is associated with improvement in blood pressure (BP), LDL-C, triglycerides, and glucose levels among obese or overweight individuals, and delays the development of T2DM. In addition to diet and exercise, FDA-approved pharmacologic therapies and bariatric surgery may have a role for weight loss in select patients. Physical Activity Despite the public health emphasis for regular exercise based on extensive observational data that aerobic physical activity lowers ASCVD, approximately 50% of adults in the United States do not meet minimum recommendations. There is a strong inverse dose-response relationship between the amount of moderate-to-vigorous physical activity and incident ASCVD events and mortality. Adults should engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous-intensity physical activity including resistance exercise. Diabetes T2DM, defined as a hemoglobin A1c (HbA1c) >6.5%, is a metabolic disorder characterized by insulin resistance leading to hyperglycemia. The development and progression are heavily influenced by dietary pattern, physical activity, and body weight. All with T2DM should undergo dietary counseling for a heart-healthy diet that in T2DM lowers CVD events and CVD mortality. Among options include the Mediterranean, DASH, and vegetarian/vegan diets that achieve weight loss and improve glycemic control. At least 150 minutes/week of moderate to vigorous physical activity (aerobic and resistance) in T2DM lowers HbA1c about 0.7% with an additional similar decrease by weight loss. Other risk factors should be identified and treated aggressively. For younger individuals, or those with a mildly elevated HbA1c at the time of diagnosis of T2DM, clinicians can consider a trial of lifestyle therapies for 3-6 months before drug therapy. First-line therapy to improve glycemic control and reduce CVD risk is metformin. Compared to lifestyle modifications, metformin resulted in a 32% reduction in micro- and macrovascular diabetes-related outcomes, a 39% reduction in myocardial infarction, and a 36% reduction in all-cause mortality. The goal is a HbA1c 6.5-7%. Several classes of medications have been shown to effectively lower blood glucose but may not affect ASCVD risk including the often-used sulfonylureas. Two classes of glucose-lowering medications have recently demonstrated a reduction in ASCVD events in adults with T2DM and ASCVD. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors act in the proximal tubule to increase urinary excretion of glucose and sodium, leading to a reduction in HbA1c, weight, and BP and in randomized clinical trials, significant reduction in ASCVD events and heart failure. The majority of patients studied had established CVD at baseline, although limited data suggest this class of medications may be beneficial for primary prevention. The glucagon-like peptide-1 receptor (GLP-1R) agonists increase insulin and glucagon production in the liver, increase glucose uptake in muscle and adipose tissue, and decrease hepatic glucose production. GLP-1R agonists have been found to significantly reduce the risk of ASCVD events in adults with T2DM at high ASCVD risk. In patients with T2DM and additional risk factors for CVD, it may be reasonable to initiate these two classes of medications for primary prevention of CVD. Lipids Primary ASCVD prevention requires assessing risk factors beginning in childhood. For those <19 years of age with familial hypercholesterolemia, a statin is indicated. For young adults (ages 20-39 years), priority should be given to estimating lifetime risk and promoting a healthy lifestyle. Statin should be considered in those with a family history of premature ASCVD and LDL-C ≥160 mg/dl. ASCVD risk-enhancing factors, (see risk estimate section), should be considered in all patients. Statin Treatment Recommendations The following are guideline recommendations for statin treatment: Patients ages 20-75 years and LDL-C ≥190 mg/dl, use high-intensity statin without risk assessment. T2DM and age 40-75 years, use moderate-intensity statin and risk estimate to consider high-intensity statins. Risk-enhancers in diabetics include ≥10 years for T2DM and 20 years for type 1 DM, ≥30 mcg albumin/mg creatinine, eGFR <60 ml/min/1.73 m 2 , retinopathy, neuropathy, ABI <0.9. In those with multiple ASCVD risk factors, consider high-intensity statin with aim of lowering LDL-C by 50% or more. Age >75 years, clinical assessment and risk discussion. Age 40-75 years and LDL-C ≥70 mg/dl and <190 mg/dl without diabetes, use the risk estimator that best fits the patient and risk-enhancing factors to decide intensity of statin. Risk 5% to <7.5% (borderline risk). Risk discussion: if risk-enhancing factors are present, discuss moderate-intensity statin and consider coronary CACs in select cases. Risk ≥7.5-20% (intermediate risk). Risk discussion: use moderate-intensity statins and increase to high-intensity with risk enhancers. Option of CACs to risk stratify if there is uncertainty about risk. If CAC = 0, can avoid statins and repeat CAC in the future (5-10 years), the exceptions being high-risk conditions such as diabetes, family history of premature CHD, and smoking. If CACs 1-100, it is reasonable to initiate moderate-intensity statin for persons ≥55 years. If CAC >100 or 75th percentile or higher, use statin at any age. Risk ≥20% (high risk). Risk discussion to initiate high-intensity statin to reduce LDL-C by ≥50%. Both moderate- and high-intensity statin therapy reduce ASCVD risk, but a greater reduction in LDL-C is associated with a greater reduction in ASCVD outcomes. The dose response and tolerance should be assessed in about 6-8 weeks. If LDL-C reduction is adequate (≥30% reduction with intermediate- and 50% with high-intensity statins), regular interval monitoring of risk factors and compliance with statin therapy are necessary to determine adherence and adequacy of effect (about 1 year). For patients aged >75 years, assessment of risk status and a clinician-patient risk discussion are needed to decide whether to continue or initiate statin treatment. The CACs may help refine ASCVD risk estimates among lower-risk women (<7.5%) and younger adults (<45 years), particularly in the setting of risk enhancers. Hypertension In the United States, hypertension accounts for more ASCVD deaths than any other modifiable risk factor. The prevalence of stage I hypertension defined as systolic BP (SBP) ≥130 or diastolic BP (DBP) ≥80 mm Hg among US adults is 46%, higher in blacks, Asians, and Hispanic Americans, and increases dramatically with increasing age. A meta-analysis of 61 prospective studies observed a log-linear association between SBP levels <115 to >180 mm Hg and DBP levels <75 to 105 mm Hg and risk of ASCVD. In that analysis, 20 mm Hg higher SBP and 10 mm Hg higher DBP were each associated with a doubling in the risk of death from stroke, heart disease, or other vascular disease. An increased risk of ASCVD is associated with higher SBP and SBP has been reported across a broad age spectrum, from 30 to >80 years of age. In adults with elevated or borderline hypertension (BP 120-129/<80 mm Hg) or hypertension, the initial recommendations include weight loss, heart-healthy diet (DASH or DASH Mediterranean), sodium restriction of 1000 mg reduction and optimal <1500 mg/d), diet rich in potassium with supplements as necessary, exercise as described including aerobic, isometric resistance (hand-grip), dynamic resistance (weights), and limited alcohol (men <3 and women <2 per day). In adults with stage I hypertension (BP 130-139/80-89 mm Hg) and estimated 10-year ASCVD risk of <10%, nonpharmacologic therapy is recommended. In those with a 10% or higher 10-year ASCVD risk, use of BP-lowering medication is recommended with a BP target of <130/80 mm Hg including persons with chronic kidney disease and diabetes. A target of <130/80 mm Hg is also recommended for Stage 2 hypertension, defined as BP ≥140/90 mm Hg with nonpharmacological and BP-lowering medication. Tobacco Tobacco use is the leading preventable cause of disease, disability, and death in the United States. Smoking and smokeless tobacco (e.g., chewing tobacco) increases the risk for all-cause mortality and causal for ASCVD. Secondhand smoke is a cause of ASCVD and stroke, and almost one third of CHD deaths are attributable to smoking and exposure to secondhand smoke. Even low levels of smoking increase risks of acute myocardial infarction; thus, reducing the number of cigarettes per day does not totally eliminate risk. Electronic Nicotine Delivery Systems (ENDS), known as e-cigarettes and vaping, are a new class of tobacco products that emit aerosol containing fine and ultrafine particulates, nicotine, and toxic gases that may increase risk for CV and pulmonary diseases. Arrhythmias and hypertension with e-cigarette use have been reported. Chronic use is associated with persistent increases in oxidative stress and sympathetic stimulation in the healthy young. All adults should be assessed at every visit for tobacco use, and those who use tobacco should be assisted and strongly advised to quit on every visit. Referral to specialists is helpful for both behavioral modification, nicotine replacement, and drug treatments. Amongst the treatments include varieties of nicotine replacement, the nicotine receptor blocker varenicline, and bupropion, an antidepressant. Aspirin For decades, low-dose aspirin (75-100 mg with US 81 mg/day) has been widely administered for ASCVD prevention. By irreversibly inhibiting platelet function, aspirin reduces risk of atherothrombosis but at the risk of bleeding, particularly in the gastrointestinal (GI) tract. Aspirin is well established for secondary prevention of ASCVD and is widely recommended for this indication, but recent studies have shown that in the modern era, aspirin should not be used in the routine primary prevention of ASCVD due to lack of net benefit. Most important is to avoid aspirin in persons with increased risk of bleeding including a history of GI bleeding or peptic ulcer disease, bleeding from other sites, age >70 years, thrombocytopenia, coagulopathy, chronic kidney disease, and concurrent use of nonsteroidal anti-inflammatory drugs, steroids, and anticoagulants. The following are recommendations based on meta-analysis and three recent trials: Low-dose aspirin might be considered for primary prevention of ASCVD in select higher ASCVD adults aged 40-70 years who are not at increased bleeding risk. Low-dose aspirin should not be administered on a routine basis for primary prevention of ASCVD among adults >70 years. Low-dose aspirin should not be administered for primary prevention among adults at any age who are at increased bleeding risk. Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Atrial Fibrillation/Supraventricular Arrhythmias, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Acute Heart Failure, Diet, Exercise, Hypertension, Smoking Keywords: ACC Annual Scientific Session, ACC19, Aspirin, Atherosclerosis, Atrial Fibrillation, Bariatric Surgery, Blood Pressure, Cholesterol, LDL, Coronary Disease, Diabetes Mellitus, Type 2, Diet, Dyslipidemias, Exercise, Heart Failure, HIV, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperglycemia, Hypertension, Inflammation, Kidney Failure, Chronic, Lipids, Lipoproteins, Metabolic Syndrome, Metformin, Myocardial Infarction, Obesity, Plaque, Atherosclerotic, Pre-Eclampsia, Primary Prevention, Risk Factors, Smoking, Stroke, Tobacco, Triglycerides, Weight Loss < Back to Listings x You must be logged in to save to your library. 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