Ventricular filling or decreased blood ejection as a result of cardiac dysfunction frequently results in heart failure (HF), a complex clinical condition [1]. Approximately 64.3 million individuals worldwide suffer from heart failure, and its incidence is on the rise [2]. One nutrient that can be acquired by diet, supplements, and sunlight is vitamin D. While vitamin D deficiency seems to raise the risk of heart failure, vitamin D supplementation lowers the risk of myocardial infarction and improves hypertension [3]. In the pathophysiology of heart failure, vitamin D plays a pleiotropic role [4]. According to recent data, inadequate vitamin D levels have a negative impact on the cardiovascular system and are linked to the activation of many pathways that aggravate heart failure, cause inflammation, and cause unfavorable cardiac remodeling. Low vitamin D levels because endothelial dysfunction, triggers an inflammatory response, and activates the renin-angiotensin-aldosterone system [5]. As a result, vitamin D levels and CHF are tightly related. Furthermore, vitamin D deficiency is common and linked to a poor prognosis for individuals with congestive heart failure, according to clinical investigations [6]. Both in the US and around the world, vitamin D insufficiency is very common. Up to one-third to one-half of otherwise healthy middle-aged to older persons have low levels of 25-hydroxyvitamin D (25-OH D), the main circulating storage form of vitamin D [7]. The main reasons of low 25-OH D levels are limited cutaneous synthesis brought on by insufficient sun exposure or pigmented skin, as well as inadequate food intake. Vitamin D comes in two main types. Cholecalciferol, often known as vitamin D3, is a first form of vitamin D that is produced industrially and found naturally in fatty fish, fish oils, and egg yolks. Ergosterol, a membrane sterol present in the ergot fungus, is irradiated to create ergocalciferol, also known as vitamin D2. Vitamins D2 and D3 are physiologically inactive and must be activated by a series of hydroxylation processes, regardless of whether they are obtained by diet or cutaneous synthesis. Numerous investigations have demonstrated that vitamin D influences the turnover of extracellular matrix in the heart and functions as a negative regulator of the rennin-angiotensin-aldosterone system (RAAS) [8]. Vitamin D receptor (VDR) knockout mice consistently exhibit elevated metallo-protease activity, which encourages the breakdown of myocardial tissue and results in ventricular remodeling [9], as well as increased RAAS activity, which causes hypertension, cardiac hypertrophy, increased water intake, and sodium retention [10]. As a result, low vitamin D levels may cause heart function to deteriorate and myocardial remodeling to accelerate. Currently, there are conflicting findings from several researches about how vitamin D affects ventricular remodeling in HF patients.

Aims & objectives: The current study assesses the relationship between vitamin D levels and heart failure patients.

This cross-sectional observational study was conducted in the Department of Biochemistry at Dr Ulhas Patil Medical College and associated hospital, Jalgaon, Maharashtra, India. Participants in this study were hospitalized patients with HF diagnosed during the data collection period.

Inclusion criteria:

• Women and males between the ages of 30 and 70.
• Patients with HF determined by echocardiography, laboratory and clinical criteria.
• Patients who gave written informed consent for the study.

Exclusion criteria:

• Patients who have been diagnosed with lipodystrophies or hereditary disorders of bone metabolism.
• Patients taking vitamin D supplements and long-term glucocorticoid use.
• Patients who now smoke or have a history of alcoholism.
• Patients suffering from severe kidney or liver disorders, thyroid issues, or cancer
• Patients who did not give their consent for the research

A clinical examination was conducted, along with the patient's sociodemographic profile, history of alcohol use, smoking and chronic statin use. Using the Chronic Kidney Disease Epidemiology Collaboration formula, the quantitative variables that were assessed included age, body mass index (BMI), hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), serum PTH, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides and LVEF.  Serum vitamin D level, electrocardiogram (ECG), echocardiography (2D ECHO) and fasting blood analysis were all recorded.

We considered Vit. D deficiency, if serum 25OHD <20 ng/mL (<50 nmol/L), insufficiency between 20–30 ng/mL (50–75 nmol/L) and sufficiency if 25OHD ≥30 ng/mL (≥75 nmol/L) [11].

Statistical analysis: The Statistical Package for Social Sciences (SSPS) was used to conduct the statistical analysis. Frequencies and proportions were used to present the qualitative variables, and Pearson's chi-square test was used for comparison. A statistically significant P value is one that is less than 0.05.

A total of 60 patients of HF were enrolled and analysed in this study. Majority of the patients (35.8%) were 51-60 years age group with mean age was 55.63 years, slightly female predominance. Most of them resided in urban area (58.3%) and belong to middle socio-economic class (39.2%). Maximum no of patients was overweight (38.2%).

Table 1: General characteristics of the study patients

Prevalence of vitamin d deficiency was 28.4% cases, insufficiency in 35% cases and sufficiency in 36.6% heart failure cases.

Graph 1: Estimation of serum vitamin D level in heart failure patients

Vitamin d deficiency were significantly associated with female sex (68.6% vs. 47.1%; p=0.031) and diabetes mellitus (65.7% vs. 40%, p=0.01). There were no differences between the groups with and without Vitamin d deficiency regarding NYHA-FC, classification of LVEF or presence of hypertension (p>0.05). Likewise, there were no associations between Vitamin d deficiency with body mass index, history of smoking and alcohol ingestion (p>0.05). eGFR was significantly lower and PTH was significantly higher in vitamin d deficiency patients (p<0.05). Details were shown in Tables 2.

Table 2: Characteristics of heart failure patients with or without vitamin D deficiency

Table 3: Vitamin D supplementation and outcome of HF patients

Vitamin D and the prognosis of heart failure (HF) are related. Heart failure inhibits the heart's ability to contract and relax because of an excess of ionized calcium (Ca2+) in myocardial cells. Conversely, a lack of vitamin D may impact the Ca2+ activities in cardiac cells, resulting in intra-organizational inflammation, fibrosis, and hypertrophy of the cardiomyocyte. Furthermore, endothelial dysfunction, renin-angiotensin system activation, and inflammation can all result from low vitamin D levels [12].

The majority of patients in this study were female and in the 51–60 age range; their mean age was 55.63±4.3 years, which is comparable with findings from Szymanski MK, et al [13] and Witham MD, et al [14]. The current study found that vitamin D shortage was more common among heart failure patients (29.2%), which is equivalent to the findings of Gotsman I, et al. [15], who found that vitamin D deficiency was 27.2% in their study. The reduced amount of sun exposure from outside activities is one of the potential causes of the lower vitamin D levels in HF patients. In line with Li YC et al. [16], our investigation revealed that vitamin D deficiency was substantially higher in female patients than in male patients (p<0.05). The current evidence also suggests that vitamin D insufficiency and hypertension may interact. According to Chen S, et al. [17], hypertension is a major factor in the development of left ventricular hypertrophy and vascular remodelling. Similar to a study by Rauchhaus M, et al. [18], we have discovered a correlation between vitamin D insufficiency and decreased eGFR and greater levels of PTH. According to study done by Liu LC. et al, [19], there are no significant correlations between vitamin D insufficiency and either BMI or abdominal obesity. This investigation found significant correlations between vitamin D insufficiency and the presence of diabetes mellitus or worse glycemic control, consistent with findings by Schroten NF. et al. [20]. In this investigation, as in many others, such as Boxer RS, et al [21], and Schleithoff SS, et al [22], vitamin D insufficiency was strongly linked to heart failure. Our investigation found that HF patients with vitamin D insufficiency had a greater mortality rate than those without; this conclusion is consistent with Agarwal M, et al. [23]. It was discovered that vitamin D was a separate predictor of HF patients' survival rates. The causes of increased hospitalization and mortality rates in HF patients are vitamin D insufficiency.

In individuals with CHF, vitamin D has a marginally significant and unclear effect on heart function and ventricular remodelling. Even after accounting for any confounding variables, people with CHF who receive adequate vitamin D had a lower risk of dying from any cause. Additionally, we discovered that among patients with heart failure, a vitamin D deficit is linked to a higher risk of hospitalizations, mortality and poor clinical outcomes.

1. Gardner DG, Chen S, Glenn DJ. Vitamin D and the heart. Am J Physiol Regul Integr Comp Physiol. 2013;305(9):969-77. doi: 10.1152/ajpregu.00322.2013.
2. Smith GD, Ebrahim S. Mendelian randomization: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003; 32:1–22. doi: 10.1093/ije/dyg070.
3. Pourdjabbar A, Dwivedi G, Haddad H. The role of vitamin D in chronic heart failure. Curr Opin Cardiol. 2013;28(2):216-22. doi: 10.1097/HCO.0b013e32835bd480.
4. Volterrani M, Rosano G, Iellamo F. Testosterone and heart failure. Endocrine. 2012;42(2):272-7. doi: 10.1007/s12020-012-9725-9.
5. Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab. 1988;67(2):373-8. doi: 10.1210/jcem-67-2-373.
6. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM; Endocrine Society. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011 Jul;96(7):1911-30. doi: 10.1210/jc.2011-0385.
7. Orwoll E, Nielson CM, Marshall LM, Lambert L, Holton KF, Hoffman AR, Barrett-Connor E, Shikany JM, Dam T, Cauley JA; Osteoporotic Fractures in Men (MrOS) Study Group. Vitamin D deficiency in older men. J Clin Endocrinol Metab. 2009;94(4):1214-22. doi: 10.1210/jc.2008-1784.
8. Zia AA, Komolafe BO, Moten M, Ahokas RA, McGee JE, William Rosenberg E, Bhattacharya SK, Weber KT. Supplemental vitamin D and calcium in the management of African Americans with heart failure having hypovitaminosis D. Am J Med Sci. 2011 ;341(2):113-8. doi: 10.1097/MAJ.0b013e3182058864.
9. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117(4):503-11. doi: 10.1161/CIRCULATIONAHA.107.706127.
10. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007 Sep 10;167(16):1730-7. doi: 10.1001/archinte.167.16.1730.
11. Giovannucci E. Can vitamin D reduce total mortality? Arch Intern Med. 2007;167(16):1709-10. doi: 10.1001/archinte.167.16.1709.
12. Ross AC, Taylor CL, Yaktine AL, Del Valle HB. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.
13. Szymanski MK, Damman K, van Veldhuisen DJ, van Gilst WH, Hillege HL, de Boer RA. Prognostic value of renin and prorenin in heart failure patients with decreased kidney function. Am Heart J. 2011;162(3):487-93. doi: 10.1016/j.ahj.2011.06.001.
14. Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo ME. The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Circ Heart Fail. 2010;3(2):195-201. doi: 10.1161/CIRCHEARTFAILURE.109.907899.
15. Gotsman I, Shauer A, Zwas DR, Hellman Y, Keren A, Lotan C, Admon D. 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(4):357-66. doi: 10.1093/eurjhf/hfr175.
16. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110(2):229-38. doi: 10.1172/JCI15219,
17. Chen S, Glenn DJ, Ni W, Grigsby CL, Olsen K, Nishimoto M, Law CS, Gardner DG. Expression of the vitamin d receptor is increased in the hypertrophic heart. Hypertension. 2008;52(6):1106-12 doi: 10.1161/HYPERTENSIONAHA.108.119602.
18. Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, Niebauer J, Hooper J, Volk HD, Coats AJ, Anker SD. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation. 2000 Dec 19;102(25):3060-7. doi: 10.1161/01.cir.102.25.3060.
19. Liu LC, Voors AA, van Veldhuisen DJ, van der Veer E, Belonje AM, Szymanski MK, Sillje HH, van Gilst WH, Jaarsma T, de Boer RA. Vitamin D status and outcomes in heart failure patients. Eur J Heart Fail. 2011;13(6):619-25. doi: 10.1093/eurjhf/hfr032.
20. Schroten NF, Ruifrok WP, Kleijn L, Dokter MM, Silljé HH, Lambers Heerspink HJ, Bakker SJ, Kema IP, van Gilst WH, van Veldhuisen DJ, Hillege HL, de Boer RA. Short-term vitamin D3 supplementation lowers plasma renin activity in patients with stable chronic heart failure: an open-label, blinded end point, randomized prospective trial (VitD-CHF trial). Am Heart J. 2013;166(2):357-364.e2. doi: 10.1016/j.ahj.2013.05.009
21. Boxer RS, Kenny AM, Schmotzer BJ, Vest M, Fiutem JJ, Piña IL. A randomized controlled trial of high dose vitamin D3 in patients with heart failure. JACC Heart Fail. 2013;1(1):84-90. doi: 10.1016/j.jchf.2012.11.003.
22. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2006 ;83(4):754-9. doi: 10.1093/ajcn/83.4.754.
23. Agarwal M, Phan A, Willix R Jr, Barber M, Schwarz ER. Is vitamin D deficiency associated with heart failure? A review of current evidence. J Cardiovasc Pharmacol Ther. 2011;16(3-4):354-63. doi: 10.1177/1074248410390214.