cardiovascular disorders
Atherosclerosis
Risk Factors for Atherosclerosis
There are numerous risk factors for atherosclerosis ( Risk factor references —see table Dyslipidemia (high total, high LDL, or low high-density lipoprotein [HDL] cholesterol), hypertension, and diabetes promote atherosclerosis by amplifying or augmenting endothelial dysfunction and inflammatory pathways in vascular endothelium. Dyslipidemia , Hypertension None Diabetes Mellitus (DM) None Chronic Kidney Disease None (see Overview of Thrombotic Disorders ) increase likelihood of atherothrombosis. Tobacco smokecontainsnicotineand other chemicals that are toxic to vascular endothelium. Smoking, including passive smoking, increases platelet reactivity (possibly promoting platelet thrombosis) and plasma fibrinogen levels and hematocrit (increasing blood viscosity). Smoking increases LDL and decreases HDL; it also promotes vasoconstriction, which is particularly dangerous in arteries already narrowed by atherosclerosis. HDL increases rapidly within 1 month of smoking cessation. Endogenous lipid metabolism None Apolipoprotein (B)(apoB) is a particle with two isoforms: apoB-100, which is synthesized in the liver, and apoB-46, which is synthesized in the intestine. ApoB-100 is able to bind the LDL receptor and is responsible for cholesterol transport. It is also responsible for transport of oxidized phospholipids and has proinflammatory properties. Presence of the apoB particle within the arterial wall is thought to be the initiating event for the development of atherosclerotic lesions. Ahigh level of small, dense LDL,characteristic of diabetes, is highly atherogenic. Mechanisms may include increased susceptibility to oxidation and nonspecific endothelial binding. Ahigh C-reactive protein (CRP) leveldoes not reliably predict extent of atherosclerosis but can predict increased likelihood of ischemic events. In the absence of other inflammatory disorders, elevated levels may indicate increased risk of atherosclerotic plaque rupture, ongoing ulceration or thrombosis, or increased activity of lymphocytes and macrophages. CRP itself does not appear to have a direct role in atherogenesis. Heart Transplantation None Chlamydia None Several common and raregenetic variants(eg, near 9p21,LPAandLDLRgene)have been robustly associated with atherosclerosis and cardiovascular events. Although each variant has a small effect individually, genetic risk scores that sum the total number of risk variants have been shown to strongly associate with more advanced atherosclerosis as well as both primary and recurrent cardiovascular events Hyperhomocysteinemia None The presence of atherosclerotic disease in one vascular territory increases the likelihood of disease in other vascular territories. Patients with noncoronary atherosclerotic vascular disease have cardiac event rates comparable to those of patients with known CAD, and they are now considered to have a CAD risk equivalent and should be treated as aggressively. 1.Yusuf S, Hawken S, Ounpuu S, et al: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.Lancet364: 937–952, 2004. 2.White J, Swedlow DI, Preiss D, et al: Association of lipid fractions with risks for coronary artery disease and diabetes.JAMA Cardiol1: 692–699, 2016. 3.Emerging risk factors collaboration, Eroquo S, Kaptoge S, Perry PL, et al: Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.JAMA302: 412–423, 2009. 4.Thanassoulis, G, Campbell CY, Owens DS, et al for the CHARGE Extracoronary Calcium Working Group: Genetic associations with valvular calcification and aortic stenosis.N Engl J Med368: 503–512, 2013. 5.Nordestgaard BG, Chapman MJ, Ray K, et al and the European Atherosclerosis Society Consensus Panel: Lipoprotein(a) as a cardiovascular risk factor: current status.Eur Heart J31: 2844–2853, 2010. 