Reviewed by Sophia Coveney

In a recent study published in the journal Nutrients, researchers conducted a prospective population-based analysis to understand whether vitamin D levels were associated with cardiovascular disease events and mortality, and overall mortality.

Study: Vitamin D Levels Are Associated with Cardiovascular Disease Events but Not with Cardiovascular Disease or Overall Mortality: A Prospective Population-Based Study. Image Credit: Ekaterina Markelova/Shutterstock.com

Background

Various meta-analyses have reported that vitamin D levels are associated with mortality, including a higher incidence of stroke, coronary heart disease, and all-cause mortality in vitamin D-deficient individuals.

Meta-analyses of various randomized trials have also shown a correlation between vitamin D supplementation and a decrease in overall mortality among the elderly and individuals suffering from diabetes, cancer, or coronavirus disease 2019 (COVID-19).

However, some studies have reported that while supplementation with vitamin D can decrease all-cause mortality risk, it has no impact on the risk of cardiovascular disease-associated mortality or morbidity.

The numerous differences and limitations in previous studies regarding vitamin D dosing, participant diversity, variations in the genes involved in vitamin D metabolism, and insufficient follow-up durations have also presented challenges in elucidating the link between vitamin D levels and cardiovascular disease risk.

Nonetheless, whether vitamin D deficiency increases the risk of cardiovascular disease events and related mortality remains unclear.

About the study

In the present study, the researchers sampled the healthy population of Lausanne, Switzerland, to examine the association between vitamin D deficiency and the risk of cardiovascular events, mortality related to cardiovascular disease, and overall mortality.

This prospective study examined the biological, genetic, and clinical factors of cardiovascular disease in individuals between the ages of 35 and 75 years.

The participants were required to fill out questionnaires, provide blood samples for various measurements, and undergo a clinical examination. The study was conducted over three-year periods starting in 2003, with the third follow-up ending in 2021.

Vitamin D levels were assessed using ultra-high-performance liquid chromatography-tandem mass spectrometry and classified as normal, insufficient, and deficient.

Data on cardiovascular events and mortality were collected during the follow-up visits. Information was also obtained for a wide range of covariates, including educational levels, marital status, nationality, and smoking behavior. However, the researchers did not collect information on sun exposure or dietary intake.

Height and body weight measurements were collected to calculate the body mass index (BMI), which was then used to categorize the participants as normal, overweight, and obese. Blood pressure measurements or the use of antihypertensive drugs were used to determine hypertension status.

Other biological measurements, such as total and high-density lipoprotein (HDL) cholesterol levels and blood glucose levels, were also obtained from the freshly collected blood samples.

The Systematic Coronary Risk Evaluation (SCORE) and SCORE-Older Persons (SCORE-OP) risk equations were used to compute the 10-year risk of developing cardiovascular disease. The medication list provided by the participants was examined to determine the use of multivitamins or vitamin D supplements.

Participants with missing data for vitamin D levels, any covariates, or from follow-ups, or those presenting with cardiovascular disease at the baseline visits were excluded. For the remaining data, Kaplan-Meyer curves were applied to calculate the bivariate associations between the outcomes of interest, such as morbidity and mortality related to cardiovascular disease and vitamin D levels.

Results

The findings reported that vitamin D levels were negatively correlated with cardiovascular disease events but showed no association with overall or cardiovascular disease-related mortality. Furthermore, no associations were observed for the categories of vitamin D levels, such as insufficiency or deficiency and overall mortality or cardiovascular outcomes.

Of the 5,684 participants, one-third had insufficient levels of vitamin D, and more than half were deficient. The results corroborated the findings from recent meta-analyses of various randomized controlled trials that reported that supplementation with vitamin D levels was linked to a lower risk of cardiovascular events but not of cardiovascular disease associated or overall mortality.

The researchers also discussed possible mechanisms through which vitamin D could influence the risk of cardiovascular disease, including the impact of vitamin D on the total and low-density lipoprotein cholesterol and triglyceride levels. However, findings on the impact of vitamin D on cholesterol levels have varied across studies and study populations, with differing results observed for elderly patients, postmenopausal women, and patients with metabolic syndrome.

Furthermore, one study has also reported an increase in HDL-cholesterol levels after vitamin D supplementation in cardiovascular disease patients. Supplementation with vitamin D has also been linked to improvements in insulin and glucose levels, with studies reporting a decrease in the evolution of prediabetes to diabetes after vitamin D supplementation.

Conclusions

Overall, the findings suggested that vitamin D levels were negatively correlated with the risk of cardiovascular events but showed no association with overall or cardiovascular disease-related mortality.

However, the inverse association with the incidence of cardiovascular events was not replicated when the participants were classified based on their vitamin D levels into categories such as normal, deficient, or insufficient.

Journal reference:

• Patriota P, Guessous I, Rezzi S, et al. (2023). Vitamin D Levels Are Associated with Cardiovascular Disease Events but Not with Cardiovascular Disease or Overall Mortality: A Prospective Population-Based Study. Nutrients, 15(18). doi:10.3390/nu15184046. https://www.mdpi.com/2072-6643/15/18/4046