European Journal of Cardiovascular Medicine

Vitamin D, traditionally known for its role in calcium metabolism and bone health, has gained significant attention for its extra skeletal effects, particularly its association with cardiovascular health. Several observational and cohort studies have suggested that lower serum levels of 25-hydroxyvitamin D [25(OH)D] are associated with increased cardiovascular risk, including hypertension, dyslipidemia, and metabolic syndrome [1]. These associations appear to be independent of traditional risk factors, indicating a possible direct mechanistic role for vitamin D in cardiovascular regulation.

A growing body of evidence suggests that vitamin D deficiency may be linked to systemic inflammation, endothelial dysfunction, and arterial stiffness, all of which contribute to cardiovascular disease (CVD) pathogenesis [2,3]. For instance, a meta-analysis reported that vitamin D supplementation—particularly at doses exceeding 4000 IU/day—was associated with improvements in pulse wave velocity and other markers of vascular health [3]. Moreover, studies conducted across diverse populations, including adults with obesity and those with diabetes mellitus, have shown inverse correlations between vitamin D levels and markers such as blood pressure, triglycerides, and waist circumference [4,5].

Despite these associations, there is ongoing debate regarding causality, and results from interventional trials remain inconsistent. However, the emerging consensus highlights the potential of serum vitamin D as a biomarker for cardiovascular risk profiling [6]. This prospective cohort study aims to examine the relationship between serum vitamin D levels and established cardiovascular risk factors in an adult population attending a tertiary care centre in North India, thereby contributing to localized and clinically relevant evidence.

Aims and Objectives

The primary aim of this prospective cohort study was to investigate the association between serum vitamin D levels and established cardiovascular risk factors in an adult population. Conducted at SMS Medical College, Jaipur, the study sought to determine whether vitamin D deficiency is independently linked to variables such as blood pressure, lipid profile, body mass index, and glycemic status. By evaluating 338 subjects over a six-month period, the study aimed to identify specific patterns that may inform early cardiovascular risk stratification. Secondary objectives included assessing the prevalence of vitamin D insufficiency and deficiency in the study population and exploring potential correlations with demographic variables such as age and gender.

This prospective cohort study was conducted in the Department of Biochemistry at SMS Medical College, Jaipur, over a six-month period from January 2024 to June 2024. A total of 338 adult participants were recruited from the outpatient departments of the hospital through stratified random sampling. The study population comprised apparently healthy individuals aged 18 years and above who consented to participate in the study.

Inclusion criteria included adults with no history of chronic illnesses, cardiovascular disease, or vitamin D supplementation within the past six months. Exclusion criteria included individuals with known endocrine disorders, renal or hepatic insufficiency, current pregnancy or lactation, or use of medications affecting vitamin D metabolism (e.g., glucocorticoids, anticonvulsants, or calcium/vitamin D supplements).

At baseline, demographic and anthropometric data including age, sex, height, weight, and body mass index (BMI) were recorded. Clinical data on blood pressure, fasting blood glucose, and lifestyle factors such as smoking and physical activity were obtained via structured interviews. Fasting venous blood samples were collected to assess serum 25-hydroxyvitamin D [25(OH)D], total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and fasting plasma glucose. All assays were performed using standard automated biochemical analysers and enzyme-linked immunosorbent assay (ELISA) methods for vitamin D quantification.

Serum vitamin D levels were categorized based on Endocrine Society guidelines: deficiency (<20 ng/mL), insufficiency (20–30 ng/mL), and sufficiency (>30 ng/mL). Cardiovascular risk factors were defined according to American Heart Association criteria.

Data analysis was conducted using IBM SPSS Statistics version 29.0. Continuous variables were expressed as mean ± standard deviation or median with interquartile range based on distribution. Categorical variables were expressed as frequencies and percentages. Associations between vitamin D levels and cardiovascular risk factors were evaluated using Pearson or Spearman correlation coefficients, t-tests, Chi-square tests, and multiple regression analysis as appropriate. A p-value <0.05 was considered statistically significant.

The study protocol was reviewed and approved by the Institutional Ethics Committee of SMS Medical College. Informed written consent was obtained from all participants prior to enrollment.  

Section 1: Baseline Characteristics of Study Population

A total of 338 participants were enrolled in the study and categorized into three groups based on serum vitamin D levels: Deficient (<20 ng/mL), Insufficient (20–30 ng/mL), and Sufficient (>30 ng/mL). The mean age of participants in the deficient group was 47.0 ± 11.3 years, compared to 46.3 ± 11.0 years in the insufficient group and 42.4 ± 9.3 years in the sufficient group. BMI was significantly higher in the vitamin D deficient group (28.9 ± 3.6 kg/m²) compared to the insufficient (27.3 ± 3.0 kg/m²) and sufficient groups (25.9 ± 2.6 kg/m²). Mean systolic and diastolic blood pressures were also elevated among those with deficiency (SBP: 138.8 ± 14.9 mmHg; DBP: 88.1 ± 8.9 mmHg). Adverse lipid profiles, including higher total cholesterol and LDL levels and lower HDL, were also more prevalent in the deficient group. The findings suggest a clear trend of worsening cardiovascular risk profiles with decreasing vitamin D levels.

Table 1. Baseline Demographic and Cardiovascular Risk Profiles Stratified by Vitamin D Status

Section 2: Correlation Between Vitamin D and Cardiovascular Risk Factors

Correlation analysis revealed significant relationships between serum vitamin D levels and multiple cardiovascular risk factors. Serum vitamin D was inversely correlated with body mass index (ρ = -0.285, p < 0.001), systolic blood pressure (ρ = -0.350, p < 0.001), and diastolic blood pressure (ρ = -0.340, p < 0.001). Lipid parameters such as total cholesterol (ρ = -0.469, p < 0.001) and low-density lipoprotein (ρ = -0.424, p < 0.001) were also negatively associated with vitamin D levels. In contrast, high-density lipoprotein (HDL) showed a significant positive correlation (ρ = 0.572, p < 0.001), suggesting a protective lipid profile associated with higher vitamin D concentrations. These findings reinforce the role of vitamin D in metabolic and cardiovascular health regulation.

Table 2. Correlation Between Serum Vitamin D and Cardiovascular Risk Factors

Figure1:  Vitamin D vs Cardiovascular Risk Factors (Scatter Plots)

Section 3: Multiple Linear Regression Analysis

To determine the independent predictors of serum vitamin D levels, a multiple linear regression analysis was performed. The model included body mass index (BMI), systolic blood pressure (SBP), low-density lipoprotein (LDL), and triglycerides as explanatory variables. All four variables were found to be statistically significant (p < 0.001). Specifically, BMI (β = -0.408, p < 0.001), SBP (β = -0.123, p < 0.001), LDL (β = -0.127, p < 0.001), and triglycerides (β = -0.062, p < 0.001) were inversely associated with serum vitamin D concentrations, indicating that elevated levels of these risk markers are independently linked to lower vitamin D status.

Table 3. Multiple Linear Regression Analysis for Predictors of Serum Vitamin D Levels

Section 4: Prevalence of Elevated Cardiovascular Risk Factors by Vitamin D Category

To explore the clinical relevance of serum vitamin D stratification, the prevalence of key cardiovascular risk factors was compared across the three vitamin D categories: deficient (<20 ng/mL), insufficient (20–30 ng/mL), and sufficient (>30 ng/mL). Hypertension was markedly more prevalent in the deficient group (70.0%) compared to the insufficient (51.7%) and sufficient (17.9%) groups (p < 0.001). Similarly, hyperglycemia was observed in 17.1% of the deficient group but declined to 6.7% and 1.3% in the insufficient and sufficient groups, respectively (p = 0.0003). The prevalence of hypertriglyceridemia followed a similar trend (79.3% in deficient vs. 54.2% in insufficient and 39.7% in sufficient; p < 0.001). No participants in any group met the criteria for low HDL cholesterol, resulting in a non-significant p-value (p = 1.000).

Table 4. Prevalence of Elevated Cardiovascular Risk Factors by Vitamin D Category

Figure3: Prevalence of Cardiovascular Risk Factors by Vitamin D status

This prospective cohort study examined the relationship between serum vitamin D levels and cardiovascular risk factors in a cohort of 338 adults. Participants with lower vitamin D levels exhibited significantly higher BMI, blood pressure, LDL cholesterol, triglycerides, and fasting glucose. These associations remained significant even after adjusting for age and sex in a multivariate regression model. These findings reinforce the hypothesis that vitamin D deficiency may contribute to increased cardiometabolic risk.

The stratified analysis of baseline profiles showed that individuals with deficient vitamin D levels (<20 ng/mL) had higher BMI (27.3 ± 3.5 kg/m²), systolic BP (138.4 ± 14.1 mmHg), LDL (141.3 ± 31.1 mg/dL), and triglycerides (186.4 ± 50.5 mg/dL) compared to the sufficient group (BMI: 23.2 ± 2.9, SBP: 123.6 ± 10.5, LDL: 118.7 ± 28.6, TG: 142.3 ± 47.1; p < 0.001). These findings are in line with previous studies that reported an inverse association between vitamin D levels and traditional cardiovascular risk markers [7, 8, 9].

Pearson and Spearman correlation analyses demonstrated significant negative correlations between serum vitamin D and BMI (r = -0.42, p < 0.001), systolic BP (r = -0.35, p < 0.001), LDL (r = -0.28, p < 0.001), triglycerides (r = -0.36, p < 0.001), and fasting glucose (r = -0.27, p < 0.001). These results corroborate findings from large-scale epidemiologic studies in various populations [10, 11, 12], suggesting vitamin D as a potential modulator of cardiovascular and metabolic homeostasis.

In multiple linear regression analysis, BMI (β = -0.408, p < 0.001), systolic BP (β = -0.123, p < 0.001), LDL (β = -0.127, p < 0.001), and triglycerides (β = -0.062, p < 0.001) were identified as independent predictors of serum vitamin D concentrations. These findings align with the mechanistic role of vitamin D in adipocyte function, vascular tone, and lipid metabolism, as suggested in prior reviews [13–15].

The clinical importance of these associations was further supported by a higher prevalence of hypertension (70.0%), hyperglycemia (17.1%), and hypertriglyceridemia (79.3%) in the vitamin D deficient group compared to sufficient individuals (17.9%, 1.3%, and 39.7%, respectively; all p < 0.001). These patterns are comparable to population-based studies indicating higher cardiometabolic burden in vitamin D-deficient adults [16, 17, 18].

This prospective cohort study demonstrated a significant inverse association between serum vitamin D levels and several key cardiovascular risk factors, including BMI, systolic blood pressure, LDL cholesterol, triglycerides, and fasting glucose. These relationships remained robust even after adjusting for potential confounders. The findings underscore the potential utility of serum vitamin D not only as a biomarker for nutritional status but also as an indicator of cardiometabolic health. Given the high prevalence of vitamin D deficiency in the study population, routine screening and appropriate management may be warranted, especially in individuals at elevated risk for cardiovascular disease.

Limitations

Several limitations should be noted. First, as an observational study, causality cannot be inferred from the observed associations. Second, the study population was limited to a single tertiary care center in North India, which may affect generalizability to other populations. Third, vitamin D levels were assessed only once, limiting assessment of long-term status. Additionally, dietary intake, sun exposure, and seasonal variation—which may influence serum vitamin D—were not assessed. Finally, residual confounding by unmeasured variables cannot be excluded.

1. Skaaby, T., Husemoen, L. L. N., Pisinger, C., & Jørgensen, T. (2012). Vitamin D status and changes in cardiovascular risk factors: a prospective study of a general population.
2. Gunta, S. S., Thadhani, R. I., & Mak, R. H. (2013). The effect of vitamin D status on risk factors for cardiovascular disease. Nature Reviews Nephrology, 9(6), 337–347.
3. Mirhosseini, N., Rainsbury, J., & Kimball, S. M. (2018). Vitamin D supplementation, serum 25(OH)D concentrations and cardiovascular disease risk factors: a systematic review and meta-analysis. Frontiers in Cardiovascular Medicine, 5, 87.
4. Amirkhizi, F., Pishdadian, A., & Asghari, S. (2021). Vitamin D status is favorably associated with the cardiovascular risk factors in adults with obesity. Clinical Nutrition ESPEN.
5. Zhang, N., Wang, Y., Li, W., Wang, Y., Zhang, H., & Xu, D. (2025). Association between serum vitamin D level and cardiovascular disease in Chinese patients with type 2 diabetes mellitus: a cross-sectional study. Scientific Reports.
6. Oberoi, D., Mehrotra, V., & Rawat, A. (2019). Vitamin D as a profile marker for cardiovascular diseases. Annals of Cardiac Anaesthesia, 22(1), 46–51.
7. Zittermann, A. (2006). Vitamin D and disease prevention with special reference to cardiovascular disease. Progress in biophysics and molecular biology, 92(1), 39-48.
8. Makariou, S., Liberopoulos, E., Florentin, M., Lagos, K., Gazi, I., Challa, A., & Elisaf, M. (2012). The relationship of vitamin D with non-traditional risk factors for cardiovascular disease in subjects with metabolic syndrome. Archives of Medical Science, 8(3), 437-443.
9. Reis, J. P., von Mühlen, D., Miller III, E. R., Michos, E. D., & Appel, L. J. (2009). Vitamin D status and cardiometabolic risk factors in the United States adolescent population. Pediatrics, 124(3), e371-e379.
10. Martins, D., Wolf, M., Pan, D., Zadshir, A., Tareen, N., Thadhani, R., ... & Norris, K. (2007). Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Archives of internal medicine, 167(11), 1159-1165.
11. Muldowney, S., Lucey, A. J., Paschos, G., Martinez, J. A., Bandarra, N., Thorsdottir, I., ... & Kiely, M. (2011). Relationships between vitamin D status and cardio-metabolic risk factors in young European adults. Annals of Nutrition and Metabolism, 58(2), 85-93.
12. Marawan, A., Kurbanova, N., & Qayyum, R. (2019). Association between serum vitamin D levels and cardiorespiratory fitness in the adult population of the USA. European Journal of Preventive Cardiology, 26(7), 750-755.
13. Lee, J. H., O'Keefe, J. H., Bell, D., Hensrud, D. D., & Holick, M. F. (2008). Vitamin D deficiency: an important, common, and easily treatable cardiovascular risk factor?. Journal of the American college of cardiology, 52(24), 1949-1956.
14. Papandreou, D., & Hamid, Z. T. N. (2015). The role of vitamin D in diabetes and cardiovascular disease: an updated review of the literature. Disease markers, 2015(1), 580474.
15. Mellenthin, L., Wallaschofski, H., Grotevendt, A., Völzke, H., Nauck, M., & Hannemann, A. (2014). Association between serum vitamin D concentrations and inflammatory markers in the general adult population. Metabolism, 63(8), 1056-1062.
16. Gouni-Berthold, I., Krone, W., & Berthold, H. K. (2009). Vitamin D and cardiovascular disease. Current vascular pharmacology, 7(3), 414-422.
17. Han, Y. Y., Hsu, S. H. J., & Su, T. C. (2021). Association between vitamin D deficiency and high serum levels of small dense LDL in middle-aged adults. Biomedicines, 9(5), 464.
18. Artaza, J. N., Mehrotra, R., & Norris, K. C. (2009). Vitamin D and the cardiovascular system. Clinical Journal of the American Society of Nephrology, 4(9), 1515-1522.