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Association of Vitamin D Deficiency with Heart Failure and Sudden Cardiac Death in a Large Cross-Sectional Study of Patients Referred for Coronary Angiography

Department of Public Health, Social and Preventive Medicine (S.P., W.M.), Mannheim Medical Faculty, University of Heidelberg, 68135 Mannheim, Germany; Department of Internal Medicine (S.P., A.F.-P., H.P.D., H.D.), Division of Endocrinology and Nuclear Medicine, Medical University of Graz, 8010 Graz, Austria; Synlab Center of Laboratory Diagnostics (W.M.), 69037 Heidelberg, Germany; LURIC Study Nonprofit LLC (B.W., U.S.), Freiburg, Germany; and Department of Internal Medicine I (B.O.B.), Division of Endocrinology and Diabetes, Ulm University, 89070 Ulm, Germany

Address all correspondence and requests for reprints to: Stefan Pilz, Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. E-mail: stefan.pilz{at}chello.at.; or Harald Dobnig, Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. E-mail: harald.dobnig{at}meduni-graz.at.

Context: Vitamin D has been shown to influence cardiac contractility and myocardial calcium homeostasis.

Objectives: We aimed to elucidate whether insufficient vitamin D status is associated with heart failure and sudden cardiac death (SCD).

Design, Setting, and Participants: We measured 25-hydroxyvitamin D [25(OH)D] levels in 3299 Caucasian patients who were routinely referred to coronary angiography at baseline (1997–2000).

Main Outcome Measures: The main outcome was cross-sectional associations of 25(OH)D levels with measures of heart failure and Cox proportional hazard ratios for deaths due to heart failure and for SCD according to vitamin D status.

Results: 25(OH)D was negatively correlated with N-terminal pro-B-type natriuretic peptide and was inversely associated with higher New York Heart Association classes and impaired left ventricular function. During a median follow-up time of 7.7 yr, 116 patients died due to heart failure and 188 due to SCD. After adjustment for cardiovascular risk factors, the hazard ratios (with 95% confidence intervals) for death due to heart failure and for SCD were 2.84 (1.20–6.74) and 5.05 (2.13–11.97), respectively, when comparing patients with severe vitamin D deficiency [25(OH)D <25 nmol/liter)] with persons in the optimal range [25(OH)D 75 nmol/liter]. In all statistical analyses, we obtained similar results with 25(OH)D and with 1,25-dihydroxyvitamin D.

Conclusions: Low levels of 25(OH)D and 1,25-dihydroxyvitamin D are associated with prevalent myocardial dysfunction, deaths due to heart failure, and SCD. Interventional trials are warranted to elucidate whether vitamin D supplementation is useful for treatment and/or prevention of myocardial diseases.