J Korean Med Sci.  2023 Aug;38(33):e260. 10.3346/jkms.2023.38.e260.

Circulating Vitamin D Level and Risk of Sudden Cardiac Death and Cardiovascular Mortality: A Dose-Response Meta-Analysis of Prospective Studies

• Kong SY
• Jung E
• Hwang Ss
• Ro YS
• Shin SD
• Cha Kc
• Hwang SO

• KMID: 2545212
• DOI: http://doi.org/10.3346/jkms.2023.38.e260

Abstract

Background
We conducted a comprehensive meta-analysis of prospective cohort studies to analyze the effect of circulating vitamin D level on the risk of sudden cardiac death (SCD) and cardiovascular disease (CVD) mortality.
Methods
Prospective cohort studies evaluating the association between circulating vitamin D and risk of SCD and CVD mortality were systematically searched in the PubMed and Embase. Extracted data were analyzed using a random effects model and results were expressed in terms of hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to estimate the dose-response relationships.
Results
Of the 1,321 records identified using the search strategy, a total of 19 cohort studies were included in the final meta-analysis. The pooled estimate of HR (95% CI) for low vs. high circulating vitamin D level was 1.75 (1.49–2.06) with I 2 value of 30.4%. In subgroup analysis, strong effects of circulating vitamin D were observed in healthy general population (pooled HR, 1.84; 95% CI, 1.43–2.38) and the clinical endpoint of SCD (pooled HRs, 2.68; 95% CI, 1.48– 4.83). The dose-response analysis at the reference level of < 50 nmol/L showed a significant negative association between circulating vitamin D and risk of SCD and CVD mortality.
Conclusion
Our meta-analysis of prospective cohort studies showed that lower circulating vitamin D level significantly increased the risk of SCD and CVD mortality.

Keyword

Vitamin D; Death; Sudden; Cardiac; Cardiovascular Disease; Meta-Analysis

Figure

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  Fig. 1 Flowchart of the study selection (PRISMA).NHANES = National Health and Nutrition Examination Survey, CHS = Cardiovascular Health Study, LURIC = Ludwigshafen Risk and Cardiovascular Health.

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  Fig. 2 Forest plot for study-specific and pooled hazard ratios and 95% confidence intervals of risk of sudden cardiac death and cardiovascular disease mortality for lowest versus highest categories of circulating vitamin D levels. The overall effect was obtained from a random-effect model.HR = hazard ratio, CI = confidence interval.

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  Fig. 3 Funnel plot of sudden cardiac death and cardiovascular disease mortality for lowest versus highest categories of circulating vitamin D level.

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  Fig. 4 Forest plot for stratified meta-analysis and their pooled hazard ratios and 95% confidence intervals of the risk of sudden cardiac death and cardiovascular disease mortality for lowest versus highest categories of circulating vitamin D levels by (A) pre-existing comorbidity status and (B) endpoints. The overall effects for each stratified group were obtained from a random-effect model.HR = hazard ratio, CI = confidence interval, CVD = cardiovascular disease, CKD = chronic kidney disease, SCD = sudden cardiac death.

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  Fig. 5 Dose-response meta-analysis between circulating vitamin D level and the hazard ratio of sudden cardiac death and cardiovascular disease mortality with reference value of (A) 100 nmol/L and (B) 50 nmol/L, which is the approximate sufficient level of serum 25(OH)D recommended by the Institute of Medicine. The solid line represents point estimates with the use of a restricted cubic splines model, and the dashed lines indicate 95% confidence intervals.HR = hazard ratio.

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