|Year : 2016 | Volume
| Issue : 3 | Page : 89-93
Study of vitamin D status in patients with dilated cardiomyopathy at a teaching hospital in North India
S Priya, Zeba Siddiqi, Ritu Karoli, Jalees Fatima, Saumya Gupta, Ritu Mishra
Department of Medicine, Era's Lucknow Medical College, Sarfarazganj, Lucknow, Uttar Pradesh, India
|Date of Web Publication||8-Aug-2016|
Dr. Ritu Karoli
Department of Medicine, Era's Lucknow Medical College, Sarfarazganj, Hardoi Road, Lucknow - 226 003, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Background/Introduction: Recent studies have indicated a much broader role to Vitamin D than simply the regulation of calcium metabolism alone. Vitamin D likely confers physiologically relevant pleiotropic functions that include cardioprotective and immunomodulatory effect, and its deficiency could lead to increased risk of cardiovascular disease and heart failure. Aim: The aim of our work was to evaluate the presence of hypovitaminosis D in patients with dilated cardiomyopathy (DCMP) and to study any correlation of echocardiographic parameters with Vitamin D deficiency. Patients and Methods: In an observational case-control hospital-based study, 56 patients diagnosed to have DCMP and 60 age-, gender-, and body mass index-matched controls who were patients of other medical illnesses were included in the study. Each subject underwent transthoracic two-dimensional guided M-mode echocardiography, and Vitamin D, parathyroid hormone (PTH), and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) were assessed. Results: Mean 25-hydroxyvitamin D3 [25(OH) D3] levels were significantly lower (14.5 ± 7.4 ng/ml vs. 28.2 ± 12 ng/ml, P = 0.001), whereas PTH (90.5 ± 28.5 pg/ml vs. 57 ± 20.2 pg/ml, P = 0.02) and NT-proBNP levels were significantly greater in patients with DCMP than controls. In DCMP group, 24/56 patients had severe Vitamin D deficiency, whereas in control group, 10/60 patients had severe hypovitaminosis D. There was a significant negative correlation between 25(OH) D3 concentrations and left ventricular (LV) end-diastolic and LV end-systolic dimensions. Conclusion: Patients with DCMP had lower Vitamin D levels than controls, and Vitamin D deficiency had a significant correlation with cardiac function. Therefore, screening for Vitamin D deficiency along with prompt treatment is recommended in patients with DCMP.
Keywords: Cardiomyopathy, heart failure, Vitamin D
|How to cite this article:|
Priya S, Siddiqi Z, Karoli R, Fatima J, Gupta S, Mishra R. Study of vitamin D status in patients with dilated cardiomyopathy at a teaching hospital in North India. J Cardiovasc Echography 2016;26:89-93
|How to cite this URL:|
Priya S, Siddiqi Z, Karoli R, Fatima J, Gupta S, Mishra R. Study of vitamin D status in patients with dilated cardiomyopathy at a teaching hospital in North India. J Cardiovasc Echography [serial online] 2016 [cited 2021 May 14];26:89-93. Available from: https://www.jcecho.org/text.asp?2016/26/3/89/187959
| Introduction|| |
Vitamin D plays a vital role in maintaining adequate serum calcium and phosphate levels for bone mineralization and optimal skeletal health. Recent literature, however, has indicated a much broader role of Vitamin D than simply the regulation of calcium metabolism as Vitamin D receptors (VDRs) are found in a variety of cells and tissues. These include malignant breast, colon, and prostate cells and normal cells of the immune system, kidney, heart, and vasculature. Vitamin D likely confers physiologically relevant pleiotropic functions that include cardioprotective and immunomodulatory effects as well as enhances antimicrobial function and its deficiency could lead to increased risk of cardiovascular disease and cancer. ,
The heart is particularly noteworthy in that plasma 25-hydroxyvitamin D3 [25(OH) D3] levels have been shown to correlate inversely with the incidence of a variety of cardiac disorders including ischemic heart disease and heart failure. , Role of Vitamin D in myocardial contractility was demonstrated in a community study of 870 elderly patients without heart disease during which higher circulating Vitamin D levels were found to correlate with better left ventricular (LV) systolic function and smaller LV end-systolic diameter (LVESD). 
Dilated cardiomyopathy (DCMP) is the third most common cause of heart failure with a wide range of etiologies such as genetic, infectious, autoimmune, toxic, metabolic, nutritional, endocrine, and mitochondrial in origin. However, in some cases, the exact etiology remains unclear.  B-type natriuretic peptide (BNP) is a hormone released by ventricular cardiomyocytes in response to increased myocardial stretch and volume overload and can be considered quantitative markers of hemodynamic cardiac stress. BNP and N-terminal-proBNP (NT-proBNP) activation have been shown to be a diagnostic marker and predictor of poor outcome and in patients with heart failure.  the aim of our work was to evaluate the presence of hypovitaminosis D in patients with DCMP and to study any correlation of echocardiographic parameters with Vitamin D deficiency.
| Patients and Methods|| |
In an observational case-control hospital-based study, 56 patients diagnosed to have DCMP and 60 age-, gender-, and body mass index-matched controls who were patients of other medical illnesses were included in the study between January 2012 and December 2015 at Era's Lucknow Medical College and Hospital, Lucknow. DCMP patients were diagnosed strictly according to American Heart Association Scientific Statement on the Classification of Cardiomyopathy.  The patients were excluded if they simultaneously suffered from the following disorders: (1) Ischemic dysfunctions (e.g. coronary artery disease, chronic hypertension, valvulopathy, and tachyarrhythmia); (2) toxins (e.g. chemotherapy drug, alcohol, and deficiency of trace elements); (3) endocrine and metabolic disturbances (e.g. pheochromocytoma, diabetes, and thyroid disease); (4) infections (e.g. viral myocarditis); (5) autoimmune diseases (e.g. systemic lupus erythematosus, scleroderma, and dermatomyositis); (6) peripartum cardiomyopathy. The patients with DCMP were classified by various grades of New York Heart Association (NYHA) depending on their functional status. 
Exclusion criteria also included concurrent cytotoxic chemotherapy, pregnancy or lactation, sarcoidosis, hyperparathyroidism, current or recent (<1 year) use of Vitamin D and/or calcium supplements, and patients on anticonvulsants thiazide or any other drug interfering with Vitamin D, patients with chronic liver disease, renal disease, gastric or bowel resection, malabsorption states such as chronic pancreatitis and inflammatory bowel disease.
All study participants underwent physical examinations, blood analysis, and echocardiographic evaluation. The Local Ethics Committee approved the study and written informed consent was obtained from all study participants.
Each subject underwent transthoracic two-dimensional-guided M-mode echocardiography. Echocardiography was performed with equipment (General Electric, Vingmed, Horten, Norway) using a 2.5-MHz probe. The images were acquired in parasternal long and short axis as well as in apical four- and two-chamber projections. Left atrial and LV dimensions and function were assessed by standard methods, and LV volumes and LV ejection fraction (LVEF) were calculated by the Simpson's method, averaging values from three consecutive cardiac cycles. 
Vitamin D status of the study participants was defined as per the Endocrine Society clinical practice guidelines by Holick on evaluation, treatment, and prevention of Vitamin D deficiency.  Vitamin D deficiency, severe Vitamin D deficiency, very severe Vitamin D deficiency, Vitamin D insufficiency, and normal Vitamin D levels were defined as serum 25(OH) D concentrations ≤20 ng/ml, <10 ng/ml, <5 ng/ml, 21-29 ng\ml, and ≥30 ng/ml, respectively.
The serum 25(OH) D concentrations were determined by an immunoassay technique using the Elecsys Vitamin D3 assay. It is an electrochemiluminescence immunoassay supplied by Roche diagnostics. It measures the serum 25(OH) D concentrations in the range of 4-100 ng/ml. Serum parathyroid hormone (PTH) concentration was assessed by immunoassay method (Siemens Immulite, Siemens Healthcare Diagnostics, Deerfield, IL, USA). NT-proBNP was measured using a commercially available ELISA kit (Uscn Life Science Inc.).
The SPSS 13.0 (SPSS Inc., Chicago, IL, USA) statistical software package was used for statistical analyses. Results are presented as a mean ± standard deviation or as percentages and numbers for categorical data. Normality tests were used for all variables. Continuous variables that were normally distributed were analyzed with using t-test for independent samples, and unequally distributed variables were analyzed with Mann-Whitney U-test. Correlations between 25(OH) D and other variables were determined by Spearman's correlation test.
| Results|| |
In the present study, 56 DCMP patients (29 males and 27 females, mean age: 48.6 ± 12.7) and 60 healthy controls (30 males and 30 female, mean age: 50.6 ± 10.8) were recruited Baseline characteristics of the two groups have been shown in [Table 1]. There were no differences in age, gender, body mass index, and sun exposure within the groups. Biochemical parameters were not significantly different in all study participants except that patients with DCMP had low calcium levels than the control group.
The DCMP patients were classified into various grades according to NYHA. Grade I-II had 20 patients, Grade III had 14, and Grade IV had 22 patients.
[Table 2] shows mean 25(OH) D3 levels were significantly lower (14.5 ± 7.4 ng/ml vs. 28.2 ± 12 ng/ml, P = 0.001), whereas PTH (90.5 ± 28.5 pg/ml vs. 57 ± 20.2 pg/ml, P = 0.02) and NT-proBNP levels were significantly greater in patients with DCMP than controls.
|Table 2: Biochemical parameters of patients with dilated cardiomyopathy and controls |
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In DCMP group, 24/56 patients had severe Vitamin D deficiency, whereas in control group, 10/60 patients had severe hypovitaminosis D.
As far as echocardiographic parameters were concerned, LV fractional shortening (LVFS) and LVEF were significantly lower in patients with DCMP and LV end-diastolic and LVESDs were significantly higher in patients with DCMP compared to the controls. There was a significant negative correlation between 25(OH) D3 concentrations and LV end-diastolic dimensions and LV end-systolic dimensions (r = −0.35; P = 0.01, r = −0.38; P = 0.01, respectively, as shown in [Table 3]) and serum NT-proBNP levels (r = −0.32; P = 0.02). On the contrary, 25(OH) D3 levels were positively correlated with LVEF and LVFS (r = 0.36; P = 0.01, r = 0.32; P = 0.04, respectively).
| Discussion|| |
Several studies from different parts of our country have pointed toward widespread Vitamin D deficiency in Indians of all age groups residing in rural or urban areas. , Skin complexion, poor sun exposure, vegetarian food habits, and lack of Vitamin D food fortification program in the country explain the high prevalence of VDD in India despite its sunny climate. We also conducted a study to assess the Vitamin D status in patients with pulmonary tuberculosis who were sputum positive. 
In the present study, it was observed that 25(OH) D3 levels were lower than normal in both the groups and very significantly low in patients with DCMP than controls who were also the patients with other medical illnesses. There was a negative correlation between 25(OH) D3 and LV dimensions in DCMP patients. This observation was in concordance with Ameri et al. who also reported that 25(OH) D3 level had inverse relation with LVESD and LV volume in patients with heart failure. 
Calcium directly affects the strength of myocardial contraction via excitation-contraction coupling. Hypocalcemia due to Vitamin D deficiency has been incriminated as a reversible cause of cardiomyopathy in the pediatric population, , whereas hypocalcemic DCMP was reported due to hypoparathyroidism in the adult population. ,
Vitamin D exerts multiple effects on the cardiovascular system including antihypertrophic effects on cardiomyocytes via diminishing the expression of relevant genes.  Cardiomyocytes possess VDRs as well as calcitriol-dependent Ca 2+ binding protein. Therefore, Vitamin D deficiency may play a role in the pathogenesis of the DCMP. 
Several studies have shown associations of low Vitamin D concentrations with cardiovascular events including sudden cardiac death and mortality with heart failure patients. ,,, In a study drawn from the NHANES III database, Vitamin D insufficiency was associated with heart failure.  In another study of patients, Vitamin D levels were negatively correlated with NT-proBNP, a marker of cardiac dysfunction and failure, and negatively correlated with NYHA classification and impaired LV function. After correction for cardiovascular risk factors, the hazard ratio for death due to heart failure was significantly higher when Vitamin D deficient patients with 25(OH) D levels <10 ng/ml were compared with replete patients with levels >30 ng/ml.  Interestingly, a recent report linked a functional polymorphism in the 1-(OH) ase gene, the rate-limiting step in the synthesis of active 1,25(OH) 2 with increased risk for heart failure. 
Lack of Vitamin D could can cause diastolic dysfunction, and the Hoorn study found a trend toward increased risk of diastolic dysfunction in persons with Vitamin D deficiency, considering 614 persons from a population-based cohort of older men and women. 
Vitamin D deficiency causes hypocalcemia and secondary hyperparathyroidism In our study, DCMP patients had significantly higher serum PTH concentrations compared to controls, and there was a significant inverse relationship between 25(OH) D3 and PTH concentrations. Similar observation was reported by Laguardia et al. in another study,  where serum parathormone (PTH) was elevated in patients with congestive heart failure due to ischemic or DCMP and hypovitaminosis D was present in them. Wannamethee et al. demonstrated in their study that elevated PTH was related with increased risk of incident heart failure in older men with and without CV disease. 
A meta-analysis concluded that PTH might contribute independently to myocardial dysfunction in patients with DCMP. 
The majority of congestive heart failure patients have insufficient Vitamin D, due to reduced sunlight exposure, difficult mobilization and outdoor activity, nutritional factors, and malabsorption of Vitamin D due to intestinal edema in severe right heart failure and comorbidities such as obesity and renal and hepatic failure.
Our study has got several limitations. Being a cross-sectional one, neither we could prove a causal relationship between Vitamin D deficiency and the DCMP nor we could demonstrate the exact role of Vitamin D in pathogenesis of heart failure. In view of small sample size of our study, we would suggest a prospective study having a large number of patients with a long follow-up to determine the precise role of Vitamin D in the pathogenesis of DCMP.
| Conclusion|| |
Patients with DCMP had lower Vitamin D levels than controls, and Vitamin D deficiency had a significant correlation with cardiac function. Therefore, screening for Vitamin D deficiency along with prompt treatment is recommended in patients with DCMP. Future studies are needed to address the precise role of Vitamin D deficiency in the causation of DCMP.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, et al.
Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice. Autoimmun Rev 2010;9:709-15.
Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al.
Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med 2008;168:1340-9.
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.
Karakas M, Thorand B, Zierer A, Huth C, Meisinger C, Roden M, et al.
Low levels of serum 25-hydroxyvitamin D are associated with increased risk of myocardial infarction, especially in women: Results from the MONICA/KORA Augsburg case-cohort study. J Clin Endocrinol Metab 2013;98:272-80.
Fall T, Shiue I, Bergeå af Geijerstam P, Sundström J, Ärnlöv J, Larsson A, et al.
Relations of circulating Vitamin D concentrations with left ventricular geometry and function. Eur J Heart Fail 2012;14:985-91.
Maron BJ, Towbin JA, Thiene G, Antzelevitch C, Corrado D, Arnett D, et al.
Contemporary definitions and classification of the cardiomyopathies: An American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation 2006;113:1807-16.
Thygesen K, Mair J, Mueller C, Huber K, Weber M, Plebani M, et al.
Recommendations for the use of natriuretic peptides in acute cardiac care: A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care. Eur Heart J 2012;33:2001-6.
Bennett JA, Riegel B, Bittner V, Nichols J. Validity and reliability of the NYHA classes for measuring research outcomes in patients with cardiac disease. Heart Lung 2002;31:262-70.
Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux R, Feigenbaum H, et al.
Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358-67.
Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81.
Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N. Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr 2000;72:472-5.
Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, et al.
High prevalence of low dietary calcium, high phytate consumption, and Vitamin D deficiency in healthy South Indians. Am J Clin Nutr 2007;85:1062-7.
Karoli R, Fatima J, Gupta SS, Shukla V, Moidurrehman, Manhar M. Vitamin D deficiency in medical patients at a teaching hospital in North India. J Assoc Physicians India 2015;63:35-9.
Ameri P, Ronco D, Casu M, Denegri A, Bovio M, Menoni S, et al.
High prevalence of Vitamin D deficiency and its association with left ventricular dilation: An echocardiography study in elderly patients with chronic heart failure. Nutr Metab Cardiovasc Dis 2010;20:633-40.
Cox GF, Sleeper LA, Lowe AM, Towbin JA, Colan SD, Orav EJ, et al.
Factors associated with establishing a causal diagnosis for children with cardiomyopathy. Pediatrics 2006;118:1519-31.
Maiya S, Sullivan I, Allgrove J, Yates R, Malone M, Brain C, et al.
Hypocalcaemia and Vitamin D deficiency: An important, but preventable, cause of life-threatening infant heart failure. Heart 2008;94:581-4.
Jung YJ, Kim SE, Hong JY, Lee JH, Park DG, Han KR, et al.
Reversible dilated cardiomyopathy caused by idiopathic hypoparathyroidism. Korean J Intern Med 2013;28:605-8.
Csanády M, Forster T, Julesz J. Reversible impairment of myocardial function in hypoparathyroidism causing hypocalcaemia. Br Heart J 1990;63:58-60.
Chen S, Glenn DJ, Ni W, Grigsby CL, Olsen K, Nishimoto M, et al.
Expression of the Vitamin D receptor is increased in the hypertrophic heart. Hypertension 2008;52:1106-12.
Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Körfer R, Stehle P. Low Vitamin D status: A contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003;41:105-12.
Pilz S, März W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, et al.
Association of Vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab 2008;93:3927-35.
Cozzolino M, Ketteler M, Zehnder D. The Vitamin D system: A crosstalk between the heart and kidney. Eur J Heart Fail 2010;12:1031-41.
Pilz S, Tomaschitz A, Drechsler C, Dekker JM, März W. Vitamin D deficiency and myocardial diseases. Mol Nutr Food Res 2010;54:1103-13.
Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol 2008;102:1540-4.
Wilke RA, Simpson RU, Mukesh BN, Bhupathi SV, Dart RA, Ghebranious NR, et al.
Genetic variation in CYP27B1 is associated with congestive heart failure in patients with hypertension. Pharmacogenomics 2009;10:1789-97.
Pilz S, Henry RM, Snijder MB, van Dam RM, Nijpels G, Stehouwer CD, et al.
Vitamin D deficiency and myocardial structure and function in older men and women: The Hoorn study. J Endocrinol Invest 2010;33:612-7.
Laguardia SP, Dockery BK, Bhattacharya SK, Nelson MD, Carbone LD, Weber KT. Secondary hyperparathyroidism and hypovitaminosis D in African-Americans with decompensated heart failure. Am J Med Sci 2006;332:112-8.
Wannamethee SG, Welsh P, Papacosta O, Lennon L, Whincup PH, Sattar N. Elevated parathyroid hormone, but not vitamin D deficiency, is associated with increased risk of heart failure in older men with and without cardiovascular disease. Circ Heart Fail 2014;7:732-9.
van Ballegooijen AJ, Reinders I, Visser M, Brouwer IA. Parathyroid hormone and cardiovascular disease events: A systematic review and meta-analysis of prospective studies. Am Heart J 2013;165:655-64, 664.e1-5.
[Table 1], [Table 2], [Table 3]
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