Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study

BACKGROUND AND AIMS Previous epidemiological studies have shown positive associations between serum calcium concentration and risk of cardiovascular disease (CVD), but results differ by definition of CVD. We examined the association of circulating calcium with incident and fatal CVD, myocardial infarction (MI), and stroke in the Swedish AMORIS cohort. METHODS We included 441,738 participants of the AMORIS database linked for follow-up information on morbidity and mortality. Concentrations of total calcium were fully automated measured using a colorimetric method; concentrations of albumin were measured with a bromocresol green method between 1985 and 1995. The association of albumin-corrected calcium concentration and risk of incident and fatal CVD, MI, and stroke, respectively, was assessed with multivariable adjusted Cox proportional hazards models. RESULTS Until December 31, 2011, during a median follow-up time of 21 years, 90,866 incident cases of CVD, 21,271 of MI, and 25,810 of stroke were identified. High serum calcium concentrations were associated with increased risk of non-fatal CVD (Hazard ratio [HR] = 1.12, 95% CI 1.10-1.14, top [≥2.40 nmol/L] vs. bottom [≤2-25 nmol/L] quintile), MI (1.19, 1.14-1.25), and stroke (1.11, 1.06-1.15) and fatal disease (CVD: 1.41, 1.35-1.47; MI: 1.41, 1.31-1.51; stroke: 1.30, 1.20-1.41). Effect modification by sex was observed for incident disease such that associations were stronger among women than men. Serum calcium was positively associated with both incident and fatal ischemic stroke and with fatal hemorrhagic stroke, but not with incident hemorrhagic stroke. In a sub-groups analysis, the results remained significant after adjustment for smoking. CONCLUSIONS The results support a modest positive association between serum calcium and risk of CVD, but the underlying mineral metabolism and the exact mechanisms are currently unclear