"Although our results were able to confirm an approximately 27% increased total CV risk in subjects with vitamin D deficiency, they indicate that the risk is much stronger for (and possibly even confined to) fatal CVD events," write the researchers, led by co–first authors Laura Perna, PhD, and Ben Schottker, PhD, from the German Cancer Research Center, Heidelberg.
The findings were published in the December issue of theJournal of Clinical Endocrinology and Metabolism.
Previous observational and randomized trials linking serum 25-hydroxyvitamin D (25(OH)D) concentrations with increased CVD risk have typically used only a single vitamin-D measurement and did not separately examine fatal and nonfatal outcomes, they note.
The current population-based cohort study enrolled 9949 adults aged 50 to 74 years recruited during regular health checkups at primary-care practices in 2000 to 2002. There were more women than men (59% vs 41%); most participants (59%) had inadequate vitamin-D levels (<50 nmol/L). Blood samples were collected at baseline, 5, and 8 years.
Mean follow-up was 9.2 years for mortality and 6.5 years for the end points of CVD, CHD, and stroke. A total of 854 patients had a nonfatal CVD event, 176 had a fatal CVD event, 460 had a nonfatal CHD event, 79 had a fatal CHD event, 313 had a nonfatal stroke, and 41 had a fatal stroke.
Overall, the proportion of individuals who had no events was significantly lower among those with vitamin-D deficiency. The association continued after adjustment for age, sex, and season of blood drawn, with hazard ratios ranging from 1.46 for total CVD to 1.58 for total stroke.
Even after adjustment for other potential confounders, including smoking and physical activity, vitamin-D deficiency still conferred a significant 27% increased risk for total CVD and a 62% increased risk for fatal CVD. However, there was no association between vitamin-D deficiency and nonfatal CVD events.
Individuals with low vitamin-D levels also had a significant 36% increased risk of total CHD and a nonsignificant 33% increased risk of total stroke.
A possible explanation for the stronger association between 25(OH)D and CVD mortality than nonfatal CVD end points is that low vitamin-D levels could lead to more severe events and perhaps also reduce capacity to cope with the events. Alternatively, the association of 25(OH)D with mortality may be more strongly affected by confounders linking to both low vitamin D and poor health status, such as diabetes or chronic kidney disease, the authors suggest.
This study was funded by the State Ministry of Science, Research, and Arts of Baden–Württemberg; German Cancer Aid; and CHANCES project, funded in the FP7 framework program of DG-RESEARCH, European Commission. The authors have disclosed no relevant financial relationships.
Graham
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