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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 5  |  Issue : 3  |  Page : 166-170

Evaluation of Serum Vitamin D Level as a Prognostic Marker in the Clinical Manifestation of Acute Coronary Syndrome Patients


1 Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Center, Civil Hospital Campus, Ahmedabad, Gujarat, India
2 Department of Research, U. N. Mehta Institute of Cardiology and Research Center, Civil Hospital Campus, Ahmedabad, Gujarat, India

Date of Submission18-Jun-2019
Date of Decision28-Jul-2019
Date of Acceptance01-Sep-2019
Date of Web Publication20-Dec-2019

Correspondence Address:
Dr. Jayesh Prajapati
Department of Cardiology, U. N. Mehta Institute of Cardiology and Research Center, Civil Hospital Campus, Asarwa, Ahmedabad - 380 016, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpcs.jpcs_38_19

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  Abstract 


Introduction: Epidemiologic studies have shown a strong association between Vitamin D deficiency and cardiovascular risk factors, myocardial infarction, and all-cause cardiovascular mortality. The purpose of this study was to determine the clinical implications of serum Vitamin D levels in an unselected cohort of acute coronary syndrome (ACS) patients at the time of hospital admission. Methods: This was a prospective observational study which enrolled a total of 310 patients from December 2015 to March 2018. The consecutive in-hospital patients with ACS diagnosed by the typical history of angina, electrocardiography changes, with or without cardiac enzymes were included in the study. The primary endpoint of the study was all-cause death during hospitalization. The secondary endpoint was the in-hospital incidence of major adverse cardiac events (MACEs). Results: The number of patients with diabetes and dyslipidemia was significantly higher in the Vitamin D-deficient group (46.7%, P = 0.04 and 45.4%, P = <0.001, respectively). The blood glucose, hemoglobin A1C, low-density lipoprotein, and total cholesterol were significantly higher in Vitamin D-deficient group (P = 0.045, 0.048, 0.013, and 0.024, respectively). There was no any relation of mortality and MACE between normal Vitamin D and Vitamin D deficiency patients. Conclusion: Vitamin D deficiency and insufficiency were common in patients with the ACS. In the current study, ACS patients with diabetes and dyslipidemia were strongly associated with Vitamin D deficiency, but there was no correlation between Vitamin D deficiency and ACS outcomes.

Keywords: Acute coronary syndrome, diabetes, dyslipidemia, Vitamin D deficiency


How to cite this article:
Anghan H, Prajapati J, Patel IV, Thangasami S, Patel N. Evaluation of Serum Vitamin D Level as a Prognostic Marker in the Clinical Manifestation of Acute Coronary Syndrome Patients. J Pract Cardiovasc Sci 2019;5:166-70

How to cite this URL:
Anghan H, Prajapati J, Patel IV, Thangasami S, Patel N. Evaluation of Serum Vitamin D Level as a Prognostic Marker in the Clinical Manifestation of Acute Coronary Syndrome Patients. J Pract Cardiovasc Sci [serial online] 2019 [cited 2020 Jul 16];5:166-70. Available from: http://www.j-pcs.org/text.asp?2019/5/3/166/273736




  Introduction Top


Cardiovascular diseases (CVDs) are the most prevalent health problems that lead to extended mortality and morbidity worldwide.[1] Many traditional risk factors for the prognosis of coronary artery disease (CAD) exist; however, multiple novel risk factors have been assessed by previous studies and remain to be a subject of controversy for their interaction and relation involved in the pathophysiology of CVD.[2] Recently, Vitamin D deficiency was found to be the potential risk factor for underlying CVD.[3] Around one billion people have been found to suffer from Vitamin D deficiency. Hence, the research has shifted over the role of Vitamin D level in the pathophysiology of CVD. The prevalence of Vitamin D deficiency in India has been estimated to be 50%–90% according to earlier studies.[4]

Vitamin D has a fundamental role in bone metabolism, and calcium homeostasis may also influence several other conditions including CVD. Moreover, Vitamin D deficiency has been linked to conditions such as hypertension, diabetes mellitus, metabolic syndrome, cardiac hypertrophy, and chronic kidney disease, which are also risk factors for CVDs.[3],[4],[5],[6],[7],[8] Epidemiologic studies have shown a strong association between Vitamin D deficiency and not only CVD risk factors but also myocardial infarction and all cause including cardiovascular mortality.[3],[4],[5],[6] Shanker et al.[9] showed that patients in the lower Vitamin D quartile had a higher risk for CAD; they did not find an association with the severity of CAD. Levels of 25(OH) D in healthy volunteers are independently associated with various measures of endothelial function, arterial stiffness, and coronary flow reserve.[10] In a subgroup of participants with Vitamin D deficiency, normalization of 25(OH) D levels at 6 months was associated with a significant increase in reactive hyperemia indices (monitoring endothelium-dependent relaxation). Similarly, in other studies, treatment with Vitamin D improved arterial stiffness (pulse wave velocity).

The purpose of this study was to determine the clinical implications of 25-hydroxy (OH) D levels in an unselected cohort of acute coronary syndrome (ACS) patients at the time of hospital admission and its possible association with in-hospital complications including morbidity and mortality. To do so, we have evaluated the plasma Vitamin D level and the correlation of plasma Vitamin D level as a prognostic marker with the clinical outcomes in patients with ACS.


  Methods Top


Study population

This was a prospective observational study enrolled a total of 310 patients from December 2015 to March 2018. The consecutive in-hospital patients with ACS diagnosed by the typical history of angina, electrocardiography changes, with or without cardiac enzymes were included in the study. ACS patients who had acute ST-segment elevation myocardial infarction (STEMI) were diagnosed according to third universal definition of myocardial infarction.[11] We have also enrolled patients with a history of ischemic heart diseases. ACS patients with chronic kidney disease, valvular heart disease, chronic heart disease, liver cirrhosis, alcoholic liver disease, use of corticosteroids and rifampicin, and patients who failed to give written consent were excluded from the study. The study was approved by the institutional ethics committee UNMICRC/CARDIO/2015/81.

Procedure and data collection

The detailed history, previous medications, another baseline, and demographic data have been collected from patients at the time of enrollment. Patients were followed up at the scheduled and unscheduled visits at the department of cardiology.

Laboratory measurements

For all the enrolled patients, a venous blood sample was collected at the time of hospital admission for biological measurement of 25(OH) D level. Architect 25-OH Vitamin D assay (Abbott Diagnostics, Wiesbaden, Germany), with a limit of detection of 7 ng/ml, was used for serum 25(OH) D measurement. The cutoff values for classifying Vitamin D status were >30 ng/mL were considered normal Vitamin D level; between 29 and 21 ng/mL were classified as Vitamin D insufficiency, and <20 ng/mL as Vitamin D deficiency.[6],[7],[8],[12] All patients received standard medical treatment and coronary revascularization on the basis of the current standards of care recommended by published guidelines.[13]

Study endpoints

The primary endpoint of the study was all-cause death during hospitalization. The secondary endpoint was the in-hospital incidence of major adverse clinical events (MACEs). The MACE included major bleeding requiring a blood transfusion, acute pulmonary edema (with or without the need for mechanical ventilation), cardiogenic shock, clinically significant tachyarrhythmias (ventricular fibrillation, sustained ventricular tachycardia, and atrial fibrillation), and bradyarrhythmias (requiring pacemaker implantation and acute kidney injury).

Statistical analysis

The data analysis was done with “IBM SPSS version 20” (IBM Corp., New York, USA).

Quantitative variables are expressed as the mean ± standard deviation, and qualitative variables were expressed as a percentage (%). A comparison of parametric values between groups was performed using the independent sample t-test. Categorical variables were compared using the Chi-square test. A nominal significance was taken as a two-tailed P < 0.05.


  Results Top


The baseline characteristics of the study population were stratified according to normal, insufficient, and deficient Vitamin D level as shown in [Table 1]. The baseline characteristics did not differ statistically between the three groups. There was no gender difference in Vitamin D deficiency in our study population.
Table 1: Baseline characteristics

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[Table 2] shows the relation of different cardiac risk factors with Vitamin D value. The number of patients with diabetes and dyslipidemia was significantly (P = 0.04; P ≤ 0.001) higher in the Vitamin D-deficient group.
Table 2: Risk factor profile in patients according to Vitamin D level

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[Table 3] presents the laboratory profile of patients according to Vitamin D levels. The blood glucose, hemoglobin A1C (HbA1C), low-density lipoprotein (LDL), and total cholesterol (T. CHL.) increased consecutively within the three groups and were significantly (P = 0.045, 0.048, 0.013, and 0.024) higher in Vitamin D-deficient group, as represented in [Table 3].
Table 3: Laboratory profile

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The relations of the severity of left ventricular ejection fraction (LVEF) and vessel involvement with the level of Vitamin D are shown in [Figure 1]. The severity of LVEF was higher in patients with Vitamin D deficiency. [Figure 2] presents the number of blocked vessels involved with Vitamin D deficiency was higher compared to the normal Vitamin D value patients, but there was no significant correlation between the degree of vessel involvement in ACS and the level of Vitamin D.
Figure 1: Echocardiographic profile.

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Figure 2: Vessels involved. SVD: Single vessel disease, DVD: Double vessel disease, TVD: Triple vessel disease.

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Furthermore, the relation between the incidence of a major adverse cardiac event (MACE) and the level of Vitamin D is represented in [Table 4]. There was no significant difference in the incidences of MACE and the level of Vitamin D.
Table 4: In-hospital complications in acute coronary syndrome patients

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  Discussion Top


The present study reported that the majority (82.9%) of the enrolled patients with ACS were Vitamin D deficient, which confirms that ACS patients constitute Vitamin D deficiency. Moreover, our study found that patients with cardiovascular risk factors such as diabetes and dyslipidemia were Vitamin D deficient. It was further supported by the significantly higher blood levels of glucose, Hba1c, LDL, and T. CHOL. in Vitamin D-deficient patients. However, we found no significant correlation between in-hospital complications, death, and MACE in ACS patients with Vitamin D level.

In the current study of 310 patients, 62% had STEMI, 16.7% had non-STEMI (NSTEMI), and 21.3% had unstable angina. This was supported by Indian study which evaluated the clinical profile of ACS patients in the tertiary care center and reported 76% of STEMI, 18.2% of NSTEMI, and 5% of unstable angina patients.[14]

Dziedzic et al. reported that in a group of ACS patients with diabetes, the lowest Vitamin D level was exhibited.[15] In the present study, 46.7% and 35.1% diabetic ACS patients were diagnosed with Vitamin D deficiency and insufficiency, respectively, and the difference was clinically significant (P = 0.047). Moreover, the level of blood glucose (P = 0.045) and HbA1c (P = 0.048) was significantly higher in Vitamin D insufficient and deficient groups.

Gagnon et al. found that the mean serum concentration of Vitamin D in diabetic patients was lower than the nondiabetic individuals.[16]

In our study, 63.4% of patients with Vitamin D deficiency had severe left ventricular dysfunction (LVD) compared to 31.5% of patients with normal Vitamin D level who had severe LVD. The difference was statistically significant (P = 0.04). The results were supported by Khademvatani et al. published in 2017.[17]

The higher T. CHL. and LDL levels are a high-risk factor for CVDs. In the present study, we found that the level of Total Cholesterol and LDL were significantly (P = 0.024 & P = 0.013 respectively) higher in patients with Vitamin D deficiency group and increased gradually from normal to Vitamin D deficient group. The study conducted by Wang et al. found that Vitamin D deficiency is positively associated with T. CHL.(β coefficient = 0.35, P < 0.002) and inversely associated with triglyceride (β coefficient = −0.24, P < 0.001) and LDL (β coefficient = −0.34, P < 0.001).[18] The fact is further supported by the study done by Dziedzic et al. studying the effects of Vitamin D on the severity of coronary artery atherosclerosis and lipid profile of cardiac patients. They found significant (β = −0.13, P 0.05) inverse relation between 25(OH) D level and hyperlipidemia (hyperlipidaemia was defined as T. CHL. >200 mg/dl or triglyceride >150 mg/dl).[15],[18]

The previous review suggested that deficient Vitamin D level potentiates atherosclerosis by increasing vascular inflammation, endothelial dysfunction, and proliferation of smooth muscle cells.[19] The multivariate analysis study conducted by Wang et al. reported that Vitamin D deficiency is a potential and a graded risk factor for CVD. These findings may potentially broaden the public health, given the high prevalence of Vitamin D-deficient population.[18]

Vitamin D deficiency is associated with the risk of mortality.[19],[20],[21] In our study, among 257 Vitamin D-deficient patients, 20 (7.7%) died. The rate of mortality was not statistically significant between the groups. It was probably due to the small sample size enrolled in our study. In addition, in our study, no correlation was evident between Vitamin D level and age as well as gender. A similar observation was reported by Karur et al. who stated that no significant heterogeneity was observed between Vitamin D deficiency and age or gender, but it was more commonly seen in those with lower socioeconomic status, higher cholesterol level, in dyslipidemias and diabetic patients.[22]

Limitation of the study

While interpreting the results, limitations of the study should be considered. First, the small sample size included in the study was underpowered to detect in-hospital mortality. Second, the study was conducted in a single large high volume tertiary care center; hence, the results might not be applicable to the general population. Third, we studied only in-hospital outcomes, and no follow-up was done. Fourth, factors such as latitude, season, sunlight exposure, skin color, and serum albumin affect Vitamin D status, which was not taken into account in the study.


  Conclusion Top


Vitamin D deficiency and insufficiency were common in patients with the ACS. In the current study, diabetic and dyslipidemic ACS patients were strongly associated with Vitamin D deficiency; however, there was no correlation between Vitamin D deficiency and MACE. Further, large, multicenter, studies are needed to assess the relationship between Vitamin D level and ACS and its long-term prognosis. Such confirmation is required in interventional trials with Vitamin D supplementation.

Ethics clearance

The study is approved by the institutional ethics committee.

Financial support and sponsorship

This study was financially supported by U. N. Mehta Institute of Cardiology and Research Centre, Ahmedabad, Gujarat, India.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Harikrishnan S, Sanjay G. Vitamin D and cardiovascular disease – have we found the answers? Indian Heart J 2015;67:11-3.  Back to cited text no. 3
    
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Nainby-Luxmoore JC, Langford HG, Nelson NC, Watson RL, Barnes TY. A case-comparison study of hypertension and hyperparathyroidism. J Clin Endocrinol Metab 1982;55:303-6.  Back to cited text no. 4
    
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Saleh FN, Schirmer H, Sundsfjord J, Jorde R. Parathyroid hormone and left ventricular hypertrophy. Eur Heart J 2003;24:2054-60.  Back to cited text no. 5
    
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Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.  Back to cited text no. 6
    
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González EA, Sachdeva A, Oliver DA, Martin KJ. Vitamin D insufficiency and deficiency in chronic kidney disease. A single center observational study. Am J Nephrol 2004;24:503-10.  Back to cited text no. 7
    
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Gotsman I, Shauer A, Zwas DR, Hellman Y, Keren A, Lotan C, et al. Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome. Eur J Heart Fail 2012;14:357-66.  Back to cited text no. 8
    
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Shanker J, Maitra A, Arvind P, Nair J, Dash D, Manchiganti R, et al. Role of vitamin D levels and vitamin D receptor polymorphisms in relation to coronary artery disease: The Indian atherosclerosis research study. Coron Artery Dis 2011;22:324-32.  Back to cited text no. 9
    
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Gupta R. Recent trends in coronary heart disease epidemiology in India. Indian Heart J 2008;60:B4-18.  Back to cited text no. 10
    
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Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD. Third universal definition of myocardial infarction. Circulation 2012;126:2020-35.  Back to cited text no. 11
    
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Holick MF, Chen TC. Vitamin D deficiency: A worldwide problem with health consequences. Am J Clin Nutr 2008;87:1080S-6.  Back to cited text no. 12
    
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Patel MR, Calhoon JH, Dehmer GJ, Grantham JA, Maddox TM, Maron DJ, et al. ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria for coronary revascularization in patients with Stable ischemic heart Disease: A Report of the American college of cardiology appropriate use criteria task force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American society of Nuclear Cardiology, society for cardiovascular angiography and interventions, society of cardiovascular computed tomography, and society of thoracic surgeons. J Am Coll Cardiol 2017;69:2212-41.  Back to cited text no. 13
    
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Sarkari M, Singh AP. Clinical profile of ACS patients and their outcome at tertiary centre in North-Eastern Uttar Pradesh, India. Int J Adv Med 2018;5:487-91.  Back to cited text no. 14
    
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Dziedzic EA, Gąsior JS, Pawłowski M, Dąbrowski M. Association of vitamin D deficiency and degree of coronary artery disease in cardiac patients with type 2 diabetes. J Diabetes Res 2017;2017:3929075.  Back to cited text no. 15
    
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Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, et al. Serum 25-hydroxyvitamin D, calcium intake, and risk of type 2 diabetes after 5 years: Results from a national, population-based prospective study (the australian diabetes, obesity and lifestyle study). Diabetes Care 2011;34:1133-8.  Back to cited text no. 16
    
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Khademvatani K, Mohammadzad MS, Yekta Z, Hadizadeh O. The association of serum vitamin D concentration and ventricular dysfunction among patients with acute coronary syndrome. Ther Clin Risk Manag 2017;13:1455-61.  Back to cited text no. 17
    
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Wang Y, Si S, Liu J, Wang Z, Jia H, Feng K, et al. The associations of serum lipids with vitamin D status. PLoS One 2016;11:e0165157.  Back to cited text no. 18
    
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Mozos I, Marginean O. Links between vitamin D deficiency and cardiovascular diseases. Biomed Res Int 2015;2015:109275.  Back to cited text no. 19
    
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Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117:503-11.  Back to cited text no. 20
    
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Wang J, Zhou JJ, Robertson GR, Lee VW. Vitamin D in vascular calcification: A Double-edged sword? Nutrients 2018;10: pii: E652.  Back to cited text no. 21
    
22.
Karur S, Veerappa V, Nanjappa MC. Study of vitamin D deficiency prevalence in acute myocardial infarction. Int J Cardiol Heart Vessel 2014;3:57-9.  Back to cited text no. 22
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

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



 

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