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Correlation of Serum Vitamin-D Level with Coronary Angiographic Severity In Patients with Acute Coronary Syndrome

Background: Acute Coronary Syndrome includes to a group of conditions compatible with acute myocardial ischemia and/or infarction that are usually due to an abrupt reduction in coronary blood flow. In the last decade vitamin-D deficiency as a predisposing factor for coronary artery disease is in growing interest. Prospective studies give conflicting results regarding correlation of serum vitamin D level with coronary angiographic severity in patients with acute coronary syndrome. Objective: To study the correlation between serum vitamin-D level with coronary angiographic severity in patients with acute coronary syndrome. Methodology: This cross sectional observational study was done between November 2018 and October 2019. Total 71 patients with diagnosis of first incident of acute coronary syndrome in department of cardiology, BSMMU who were underwent coronary angiogram included in this study considering the inclusion and exclusion criteria. Vitamin D was measured by chemiluminescent immunoassay after collection of venous blood at Department of Biochemistry, BSMMU. Angiographic severity was assessed by using Gensini score. Statistical analyses were carried out by using the Statistical Package for Social Sciences version 23.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Results: The mean age was found 55.9±10.7 years with a range from 36 to 82 years. Majority (83.1%) patients were male. The male-female ratio was 4.9:1. Thirty (42.3%) of the patients had STEMI, 28(39.4%) had NSTEMI and 13(18.3%) had unstable angina. Negative correlation (r=-0.479; p=0.001) was found between serum vitamin D level and Gensini score in patients with acute coronary syndrome. Conclusion: In this study found that serum vitamin-D level is inversely correlated with angiographic severity in patients with acute coronary syndrome.

Several studies have found that systemic inflammation in ACS as assessed by the biomarker CRP. 3 Laboratory studies and observations on human plaques point to inflammatory mechanisms as key regulators of the fragility of the fibrous cap and of the thrombogenic potential of the lipid core.
Vitamin D is a fat-soluble vitamin. It exists in many forms but two forms are very important: 25-hydroxycholecalciferol and 1, 25 dihydroxycholecalciferol. 4 In the skin provitamin D is photo-isomerized to vitamin D3. Calcitriol mediates its biological effects by binding to the vitamin D receptor (VDR), located in the nuclei of target cells in most organs. The binding of calcitriol to the VDR allows the VDR to act as a transcription factor that modulates the gene expression of transport proteins involved in a multitude of different tasks. 5 Vitamin D suppresses inflammation via several pathways, such as inhibition of prostaglandin and cyclooxygenase pathways, upregulation of anti-inflammatory cytokines, decrease of cytokine induced expression of adhesion molecules, reduction of matrix metalloproteinase 9 and down regulation of the RAAS. 6,7 Vitamin D deficiency stimulates systemic and vascular inflammation, enabling atherogenesis. 8 The Gensini score was developed by Gensini and takes into consideration the geometrical severity of lesions by angiography, the cumulative effects of multiple obstructions and the significance of jeopardized myocardium. 9 Recent studies provide conflicting results regarding correlation of serum vitamin-D level with angiographic severity in patient with acute coronary syndrome. The aim of this study was to correlate serum vitamin-D level with angiographic severity by Gensini score in patient with acute coronary syndrome.

Materials & Methods:
This was cross sectional observational study done between November 2018 and October 2019. Total 75 patients with diagnosis of first incident of acute coronary syndrome in department of cardiology, BSMMU who were underwent coronary angiogram included in this study.Patients with (history of recent vitamin D supplement, receiving any medications that may alter Vitamin-D level, history of any malignancies, endocrine disorders like Hyperthyroidism, Hyperparathyroidism, chronic liver disease, chronic kidney disease, heart failure, connective tissue diseases like gout, malabsorption syndrome, pregnancy and lactation were exclusion criteria. The purpose and procedure of the study was discussed with the patient and informed written consent was taken. After getting consent, meticulous history including demographic data, risk factors profile was taken and relevant clinical examination was performed and recorded in predesigned structured data sheet. Standard 12 lead ECG was recorded at a 25 mm/s paper speed and a gain of 10 mm/mV with the patient fully relaxed in the supine position. Serum Troponin-I concentration was done. Transthoracic echocardiography was done to assess the RWMA, LV dysfunction, LVEF & Mechanical complication with standard echocardiographic measurements was done before coronary angiogram. Vitamin-D level was measured by chemiluminescent immunoassay after collection of 02 ml of venous blood in department of biochemistry, BSMMU. The ARCHITECT 25(OH) vitamin-D assay is a chemiluminescent microparticle immunoassay for the quantitative determination of 25(OH) vitamin D in human serum and plasma. Serum vitamin D levels were categorized according to Institute of Medicine Report and Society of Endocrine Guideline 2011. All the enrolled patients were undergone invasive evaluation by coronary angiography during index hospitalization. Diagnostic coronary angiography was performed via either the trans-femoral or trans-radial approach by expert interventional cardiologist using standard techniques. Then angiographic severity was assessed by using Gensini score. Finally 71 data were analyzed and 04 data were discarded due to in complete information.
Statistical analysis: were carried out by using the Statistical Package for Social Sciences (SPSS) version 23.0 for Windows Software. Continuous data were expressed as mean ± standard deviation (SD) and categorical data were expressed as frequency and percentages. Mean and standard deviation were computed for quantitative variables and was analyzed by unpaired t-test. The correlation of vitamin D level with the Gensini score was done by Pearson's correlation coefficient test. P values <0.05 was considered as statistically significant.

Results:
The mean age was found 55.9±10.7 years with a range from 36 to 82 years. Majority (83.1%) patients were male. The male-female ratio was 4.9:1. Thirty (42.3%) of the patients had STEMI, 28(39.4%) had NSTEMI and 13(18.3%) had unstable angina. Negative correlation (r = -0.479; p=0.001) was found between serum vitamin D level and Gensini score in patients with acute coronary syndrome.    This little difference between our study and previous study may due to most of the patients in BSMMU, UCC admitted from referral hospital with STEMI for PCI.
This study found that majority of the 46(64.7%) patients were found serum vitamin D level 10-19.9 ng/ml in Gensini score ≥36 and 5(25.0%) in Gensini score <36. Mean serum vitamin D was 18.6±5.3 ng/ml in Gensini score ≥36 and 26.3±8.0 ng/ml in Gensini score <36. The difference was statistically significant (p<0.05) between two groups. 10 also revealed that major proportion (75%) of patients with vitamin D deficiency and 64.1% with vitamin D insufficiency had Gensini score ≥36. All the patients with normal vitamin D level (≥30 ng/mL) had Gensini score <36. The difference was statistically highly significant between the two groups (p=0.001) and was comparable with our findings.
In this study negative correlation (r=-0.479; p=0.001) was found between serum vitamin D level and Gensini score in patients with acute coronary syndrome 12 studied the correlation between serum vitamin D level with coronary angiographic severity with 239 patients who underwent coronary angiogram, They observed significant inverse correlation between serum 25(OH) D levels and the severity of coronary artery disease assessed by Gensini score (r = -0.416, P<0.001), which is comparable to this study result. 10 studied the correlation between serum vitamin D level with angiographic severity in 102 patients with documented coronary artery disease by Gensini score. Where they found serum vitamin D level is inversely

Discussion:
This study observed that the mean age was found 55.9±10.7 years with a range from 36 to 82 years and the majority 27(38.0%) of the patients belonged to age 51-60 years. 10 study showed that age of the patients with documented coronary artery disease ranged between 29 -70 years with a mean of 51.6 ± 10.3 years. Out of 102, 77 (75.5%) patients' age was 45 years or more. 11 Also found mean age was 63.3±18.5 yearsThese study results were similar with our findings.
This study found that the majority 59(83.1%) patients were male and 12(16.9%) were female. The male-female ratio  cor-related with Gensiniscore (r = -0.667, p=0.001), which have similarity to this study result. 13 studied the relationship between combination of serum vit -D deficiency and hyperuricemia and severity of coronary artery disease in 502 myocardial infraction patients. From sub group analysis they found that low serum vitamin-D level had higher gensini score than control group (p=0.019), which also support this study result.

Conclusion:
This study found that serum vitamin-D level is inversely correlated with angiographic severity in patients with acute coronary syndrome. A high prevalence of hypovitaminosis was observed in the study population.

Limitations
Sample was taken from a single centre, so result may not represent the whole country. Observational nature of the study and there was lack of randomization, so causality cannot be assessed. Vitamin-D levels can also change depending on seasons which were not evaluated in this study.