Association of Serum 25-Hydroxyvitamin D Concentrations With All-Cause and Cause-Specific Mortality Among Adult Patients With Existing Cardiovascular Disease

Abstract

Background: Vitamin D insufficiency and deficiency are common in patients with cardiovascular disease (CVD). We aimed to prospectively examine the associations of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among adult patients with existing CVD.Methods: We included 37,079 patients with CVD from the UK Biobank study, a prospective cohort of half a million participants aged 40–69 years. We defined patients with CVD as those who suffered coronary heart disease, atrial fibrillation, heart failure, or stroke. The associations of serum 25(OH)D concentration with all-cause and cause-specific mortality were examined by using multivariable Cox regression models and competing risk analyses.Results: Among 37,079 patients with CVD at baseline, 57.5% were subjected to vitamin D deficiency (i.e., 25[OH]D <50 nmol/L). During a median follow-up of 11.7 years, 6,319 total deaths occurred, including 2,161 deaths from CVD, 2,230 deaths from cancer, 623 deaths from respiratory disease, and 1,305 other-cause deaths. We observed non-linear inverse associations for all-cause, cancer, respiratory disease, and other-cause mortality (P-non-linearity <0.01) and approximately linear inverse associations for CVD mortality (P-non-linearity = 0.074). Among CVD patients with vitamin D deficiency, per 10 nmol/L increment in serum 25(OH)D concentrations was associated with an 12% reduced risk for all-cause mortality and 9% reduced risk for CVD mortality.Conclusion: Among patients with existing CVD, increasing levels in serum 25(OH)D were independently associated with a decreased risk of all-cause and cause-specific mortality. These findings suggest that elevated serum 25(OH)D concentration benefits CVD patients with vitamin D deficiency.

A Narrative Review of the Evidence for Variations in Serum 25-Hydroxyvitamin D Concentration Thresholds for Optimal Health

“…Similarly, a study based on UK Biobank participants who had CVD followed for a median of 11.7 years showed a linear inverse association of CVD mortality ( P -non-linearity = 0.07) with 25(OH)D, the adjusted HR decreasing from 1.31 (95% CI, 1.14 to 1.43) at 4 ng/mL to 0.83 (95% CI, 0.77 to 0.88) at 15 ng/mL and then (linearly) to 0.37 (95% CI, 0.22 to 0.62) at 60 ng/mL [ 9 ].…”

“…All-cause mortality rate Observational study of 25(OH)D concentration due to vitamin D supplementation >30 ng/mL [8] Alzheimer's disease and dementia Meta-analysis of observational studies >25 ng/ml [93] Breast cancer Observational study of 25(OH)D concentration due to vitamin D supplementation >60 ng/mL [33] Colorectal cancer Meta-analysis of observational studies 30-40 ng/mL [34] Cardiovascular disease Observational study of the CVD mortality rate for CVD patients >30 ng/mL [9] Myocardial infarction Observational study of 25(OH)D concentration due to vitamin D supplementation'1n >30 ng/mL [8] SARS-CoV-2 infection Retrospective observational study >50 ng/mL [75] COVID-19 mortality Retrospective cohort study >60 ng/mL [82] Diabetes mellitus type 2 RCT with an analysis of intratrial 25(OH)D for prediabetes patients >50 ng/mL [70] Gene expression Clinical trial >40 ng/mL [45] Hypertension Observational study of 25(OH)D concentration due to vitamin D supplementation >40 ng/mL [16] Preterm delivery Observational study of 25(OH)D concentration due to vitamin D supplementation >40 ng/mL [106] It has been shown experimentally that humans can produce between 10,000 and 25,000 IU of vitamin D through whole-body exposure to one minimal erythemal dose of simulated sunlight, i.e., one instance of mid-day sun exposure without burning [107]. Thus, doses to those levels should be considered inherently safe.…”

Association of Serum 25(OH)D, Cadmium, CRP With All-Cause, Cause-Specific Mortality: A Prospective Cohort Study

“…Studies have shown that daily vitamin D supplementation to maintain serum 25(OH)D levels ≥100 nmol/L is a promising approach to reduce the risk of diabetes in adults with prediabetes ( 26 ). Studies have shown that in CVD patients, elevated serum 25(OH)D levels are associated with a reduced risk of all-cause and cause-specific mortality ( 27 ). Studies have shown that in patients with vitamin D deficiency and no history of myocardial infarction, maintaining (25-OH)D levels at 30 ng/mL at the time of treatment is associated with a lower risk of myocardial infarction ( 28 ).…”

Dietary Recommendations for Post-COVID-19 Syndrome

“…Notably, vitamin D deficiency has been reported to be common in patients with cardiovascular disease (CVD) [ 90 , 91 ]. The Mendelian randomization analyses performed in four population-based cohort studies found an inverse association between the results of coronary heart disease, stroke, and all-cause mortality with a low serum concentration of this vitamin [ 92 ].…”