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

Pilz, Stefan
März, Winfried
Wellnitz, Britta
Seelhorst, Ursula
Fahrleitner-Pammer, Astrid
Dimai, Hans P.
Boehm, Bernhard O.
Dobnig, Harald

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: [email protected].; or Harald Dobnig, Department of Internal Medicine, Division of Endocrinology and Nuclear Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. E-mail: [email protected].

This work was supported by The LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study, a nonprofit LLC, and was funded by grants from the Deutsche Forschungsgemeinschaft (GRK 1041 and SFB 518). B.O.B. is supported by the Centre of Excellence “Metabolic Diseases,” Baden-Wuerttemberg.

Disclosure Statement: The authors have nothing to disclose.

Received April 10, 2008. Accepted July 21, 2008. August 5, 2008.

First Published Online August 5, 2008.

Abbreviations: CAD, Coronary artery disease; CI, confidence interval; CRP, C-reactive protein; GFR, glomerular filtration rate; HDL, high-density lipoprotein; HR, hazard ratio; LDL, low-density lipoprotein; LV, left ventricular; NT-pro-BNP, N-terminal pro-B-type natriuretic peptide; NYHA, New York Heart Association; 1,25(OH)2D, 1,25-dihydroxyvitamin D; 25(OH)D, 25-hydroxyvitamin D; SCD, sudden cardiac death.

Journal of Clinical Endocrinology & Metabolism 93(10):p 3927-3935, October 2008.

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.