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ORIGINAL ARTICLE
Year : 2019  |  Volume : 10  |  Issue : 2  |  Page : 197-201  

Does serum Vitamin D status influence high-sensitivity c-reactive protein and gensini score in established coronary artery disease individuals


1 Department of Biochemistry, Yenepoya Medical College, Yenepoya University, Mangalore, MAHE, Karnataka, India
2 Department of Biochemistry, Kasturba Medical College, Mangalore, MAHE, Karnataka, India
3 Department of Biochemistry, Kanachur Medical College, Deralakatte, Mangalore, MAHE, Karnataka, India
4 Department of Cardiology, Kasturba Medical College, Mangalore, MAHE, Karnataka, India
5 Department of Internal Medicine, Kasturba Medical College, Mangalore, MAHE, Karnataka, India

Date of Web Publication18-Jul-2019

Correspondence Address:
Poornima A Manjrekar
Department of Biochemistry, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jnsbm.JNSBM_206_18

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   Abstract 


Introduction: Over the years, the extraskeletal effects of Vitamin D (vit D) are gaining prominence. The role of vit D deficiency (VDD) in coronary artery disease (CAD) is conflicting. Hence, the present study was aimed to correlate serum vit D levels with high-sensitivity C-reactive protein (hs-CRP) and Gensini score in CAD individuals. Materials and Methods: This cross-sectional study was conducted on 70 angiographically proven CAD individuals aged between 35 and 55 years of both sexes who presented with a history of myocardial injury or ischemia for the first time. The angiographic findings were graded using Gensini score. Serum vit D and hs-CRP were estimated using enzyme-linked immunosorbent assay. Results: The average serum vit D level was 15 ng/mL, and the ratio of diabetes and nondiabetes individuals was 52:18. Among the 70 patients, 66% (n = 46) were deficient, 20% (n = 14) were insufficient, and 14% (n = 10) had normal vit D status. Although insignificant, vit D levels had negative correlation with Gensini score (r = −0.17, P = 0.14) and hs-CRP levels (r = −0.03, P = 0.77) which was not sustained after multivariate logistic regression. A significant negative correlation (r = −0.35, P = 0.01) was found between serum vit D status and duration of diabetes. Conclusion: VDD observed in diabetes individuals is inversely related to the duration of diabetes which incidentally is associated with CAD. Thus, screening for vit D status may be vital for the management of CAD particularly in diabetes individuals.

Keywords: Coronary artery disease, Gensini score, high-sensitivity C-reactive protein, Vitamin D


How to cite this article:
Shaheena A P, Manjrekar PA, D'souza V, Kamath P, Rukmini M S, Chandran V, Yalla D, Srinivasan MP. Does serum Vitamin D status influence high-sensitivity c-reactive protein and gensini score in established coronary artery disease individuals. J Nat Sc Biol Med 2019;10:197-201

How to cite this URL:
Shaheena A P, Manjrekar PA, D'souza V, Kamath P, Rukmini M S, Chandran V, Yalla D, Srinivasan MP. Does serum Vitamin D status influence high-sensitivity c-reactive protein and gensini score in established coronary artery disease individuals. J Nat Sc Biol Med [serial online] 2019 [cited 2019 Aug 26];10:197-201. Available from: http://www.jnsbm.org/text.asp?2019/10/2/197/262949




   Introduction Top


Coronary artery disease (CAD) is one of the major causes of death in both developed and developing countries.[1] Inflammatory process begins from the earliest phase of atherosclerosis, and C-reactive protein plays an important role in cardiovascular disease.[2] The presence of Vitamin D (vit D) receptors on pancreatic β-cells, myocytes, cardiomyocytes, vascular endothelial cells, and immune cells underlined the importance of vit D for adequate functioning of these organ systems.[3],[4]

Vit D deficiency (VDD) has also been linked with an increased risk of hypertension, diabetes, and hyperlipidemia, which are the known risk factors for cardiovascular disease.[5] Vit D also has immune modulatory properties and is able to suppress the inflammatory milieu, including interleukin-6 (IL-6) and C-reactive protein (CRP) synthesis.[6] Since VDD is linked to CAD risk factors and inflammation, the present study was designed to correlate vit D levels with high-sensitivity CRP (hs-CRP) and severity of CAD using Gensini score in which scoring is done based on the artery involved and degree of blockade.


   Materials and Methods Top


This is a cross-sectional study conducted among 70 CAD individuals aged between 35 and 55 years of both genders who presented with a history of myocardial injury, infarction, or ischemia and subjected to angiography for the first time with prior informed consent during January 2013–December 2013. The sample size was calculated using G*Power version 3.1.9 with 0.30 effect size, 80% power, and 0.05 level of significance.

Those with a history of previous angiography, any acute inflammation other than cardiac event, recent major surgery/trauma/burns in the past 2 months, and malignancy and patients on vit D supplementation were excluded from the study. Measurement of blood pressure and pulse rate, followed by systemic examination, was done for all individuals. Body mass index was calculated using standard formula: weight (kg)/height (m)2. Lipid profile, fasting plasma glucose, glycosylated hemoglobin, blood urea (urease-glutamate dehydrogenase), serum creatinine (Jaffe colorimetry), hemoglobin (photometric measurement), and the angiographic findings were collected from the patients' records, and the severity was assessed using Gensini score.

Under aseptic conditions, 4 ml of blood was collected in a sterile plain Vacutainer. Serum was obtained after centrifugation at 3000 rpm for 5 min. Serum 25-hydroxyvitamin D (25[OH] D) and hs-CRP were estimated using commercially available enzyme-linked immunosorbent assay kits on ELx 800 (BioTek ® Instruments, Inc.). As per the Institute of medical guidelines,[7] serum 25(OH) D levels <20 ng/ml range were considered as vit D deficient, 21–29 ng/ml as vit D insufficient, and ≥30 ng/ml range as sufficient.

Statistical analysis

Data analysis was performed in the Statistical Package for the Social Sciences (SPSS) version 20.0 (IBM, Armonk, New York, USA). Results were presented as mean ± standard deviation/standard error or median (interquartile range). Categorical variables were compared using the Chi-square test. Independent t-test was used to compare two groups. Multiple groups were compared using ANOVA followed by post hoc Tukey's test. Correlation analysis was done using Pearson's/Spearman's correlation test. P < 0.05 was considered significant.


   Results Top


The mean age and men: women ratio were 55 ± 6.1 years and 54:16, respectively. The mean vit D level was 15 (7.4, 24.1) ng/mL. Among the 70, 52 (74%) had diabetes and 32 (46%) had a history of hypertension. The ratio of alcoholics: smokers was 14:15 [Table 1]. Grouping based on serum vit D status revealed that 46 (66%) were deficient, 14 (20%) were insufficient, and 10 (14%) were sufficient [Figure 1]. Although insignificant, vit D levels had negative correlation with Gensini score (r = −0.17, P = 0.14) and hs-CRP levels (r = −0.03, P = 0.77). In diabetes group, vit D had a significant negative correlation (r = −0.35, P = 0.01) with duration of diabetes [Table 2]. Vit D-deficient individuals had abnormally diseased coronary arteries (triple-vessel disease > single-vessel disease > double-vessel disease (DVD) compared to other two groups, but the association was statistically insignificant [Table 3].
Table 1: Characteristics of overall study population, diabetes and nondiabetes participants

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Figure 1: Groups based on serum Vitamin D status

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Table 2: Correlation of vitamin D with high-sensitivity C-reactive protein, Gensini score, number of coronaries, and duration of diabetes

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Table 3: Effect of serum vitamin D status on high-sensitivity C-reactive protein, Gensini score, and number of coronaries involved

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   Discussion Top


In the present study, vit D levels were negatively correlated with hs-CRP and Gensini score an indicative of low vit D status-related worsening of inflammatory milieu and higher CAD risk. Furthermore, low vit D status results in secondary parathyroidism which could lead to elevated parathyroid hormone levels that in turn accentuate CAD risk. Our finding is similar to earlier studies that reported VDD association with increased risk of cardiovascular death. In Framingham Offspring Study, participants with low 25(OH) D levels were found to have higher risk of cardiovascular disease.[8] Postfollow-up of 7.7 years, LURIC study participants with severe and moderate VDD showed a higher death rate and death due to cardiovascular disease, respectively.[9] The probable reasons for the observed insignificant negative association are the inclusion of disproportionately distributed heterogeneous population (both diabetes and nondiabetes patients) and inadequate sample size. Multivariate logistic regression analysis nullified the association between vit D hs-CRP and Gensini score [Table 4].
Table 4: Multinominal logistic regression analysis

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Among diabetes patients (74%), there was a significant negative association between serum vit D status and duration of diabetes [Table 2]. The age of the study population was limited to 55 years to exclude the effect of increasing age on vit D status. The average vit D level in the study population was 15 ng/mL [Table 1]. Sixty-six percent of CAD patients were vit D deficient, 20% were insufficient, and only 14% had normal vit D levels [Figure 1]. This result is in accordance with previous studies where they found a significantly lower mean 25(OH) D concentrations in CAD patients.[5],[10],[11],[12] A study by Irfan et al.[10] reported a mean 25(OH) D concentration of 18.7 ng/mL in CAD patients which is almost similar to our result.

CAD is one of the major causes of death in developed as well as developing countries. To identify new predictors of CAD, various studies have concentrated on vit D and its association with various established risk factors including hypertension, diabetes, obesity, metabolic syndrome, and congestive heart failure.[13] Hypovitaminosis D affects the cardiovascular system through various mechanisms. Prolonged VDD causes hyperparathyroidism leading to the release of excess parathormone [4] which in turn promotes inflammation, renin–angiotensin system (RAS), and insulin resistance [6] ultimately affecting vasculature and myocardium. Syal et al.[14] reported a higher prevalence of double-vessel, triple-vessel, and diffuse CAD among VDD patients in India. Chen et al.[15] reaffirmed these findings and showed a significant correlation between severity of coronary artery stenosis and low vit D levels. Although insignificant, vit D-deficient individuals of the present study had elevated hs-CRP levels and higher Gensini score a suggestive of severe CAD compared to the sufficient group [Table 3]. They also demonstrated a higher prevalence of triple-vessel, single-vessel, and DVD as compared to the participants with normal vit D levels. There exists a decreasing trend in both hsCRP and Gensini score with an increase in serum vit D levels [Table 3]. This suggests that normal vit D status could be essential for the attenuation of subchronic inflammation associated with type 2 diabetes and CAD. Contradictory to this, Ho et al.[16] demonstrated no link between 25(OH) D levels and coronary artery calcification or severity of obstructive stenosis. Whereas, Al Mheid et al.[17] attributed the observed low vit D levels in CVD patients to the established disease itself rather than projecting it as the cause for the same.

The role of vit D in calcium homeostasis is well known. By virtue of the same action and also by direct β-cell stimulation, it regulates insulin secretion [18] which occurs through calcium-mediated exocytosis. Thus, VDD has been linked to type 2 diabetes. Vit D increases β-cell function and insulin sensitivity of the certain cells such as skeletal muscle, adipose tissue, and liver.[19] The identification of the vit D receptors and the enzyme 1-α hydroxylase further emphasizes the functional role of active vit D in these tissues.

In a case–control study conducted by Siadat et al.,[12] they compared 25(OH) D levels among CAD patients and controls and found that individuals with low vit D levels had 5.8 times higher risk of cardiovascular disease than those with normal vit D levels. A meta-analysis study conducted by Parker et al.[20] reviewed 28 independently published studies and found a relationship of vit D level with cardiovascular disease and diabetes. The results showed that high serum vit D concentration resulted in significant reduction in the risk of cardiovascular diseases, diabetes, and metabolic syndrome with an evidence of 33% (16 studies), 55% (9 studies), and 51% (8 studies), respectively. In agreement with the results of the meta-analysis, the present study also demonstrated greater VDD in diabetes individuals (11.7 vs. 22.5 ng/mL) [Table 1] and also showed an inverse relation (r = −0.35, P = 0.01) [Table 2] between serum vit D status and duration of diabetes, suggesting that diabetes individuals of longer duration had greater risk for VDD.

Inflammation plays a central role in the pathogenesis of type 2 diabetes and CAD. Systemic inflammation encountered in type 2 diabetes is characterized by elevated levels of cytokines and inflammatory markers [21] and chronic subacute inflammation predispose to cardiovascular risk.[22] Vit D has immune modulatory properties and is able to suppress the inflammatory milieu, including IL-6 and CRP synthesis.[6] The median hs-CRP levels were high (6.6 mg/dL) an indicative of underlying inflammation in the study participants. Atherosclerosis being an inflammatory state, and thus, many studies have demonstrated an association of inflammatory markers with CAD.[23],[24] The present study showed negative association between vit D and hs-CRP (r = −0.03, P = 0.77) [Table 2]. This suggested that VDD might have contributed to chronic inflammation which in turn could have increased cardiovascular risk. Witham et al.[25] found that Vit D supplementation for 6 months resulted in significant decline in hs-CRP compared to placebo. The observed effect was attributed to the anti-inflammatory activity of vit D.

Limitations

The limitations include cross-sectional design, so the cause-effect relationship between VDD and CAD could not be confirmed. CAD is multifactorial in origin, and our study participants had other risk factors of CAD such as diabetes and hypertension. Hence, VDD as an independent risk factor of CAD could not be established. Further prospective studies with large sample size should be conducted to elucidate the exact role of VDD in CADs with an emphasis on the risk factors with better study designs.


   Conclusion Top


We found a significant degree of VDD in diabetes patients and is inversely related to the duration of diabetes. The observed VDD can be linked to diabetes which incidentally is frequently associated with CAD. Although vit D levels were negatively correlated with hs-CRP and Gensini score, the association was not sustained after adjustment with major variables. Therefore, vit D might have an indirect role in the pathogenesis of CAD. This is important because screening for VDD may be critical for CAD in the future, especially in diabetes patients.

Informed consent

A written informed consent was obtained from all participants included in the study.

Acknowledgments

The authors are thankful to Manipal University (award number – CK MU 274777) for financial assistance.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was financially supported by Manipal University (award number – CK MU 274777).

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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