High calcium markedly associated with mortality in CHD patients

6 February 2012

MedWire News: High serum calcium levels are markedly associated with all-cause and cardiovascular (CV) mortality in coronary heart disease (CHD) patients, shows an analysis.

The calcium/albumin ratio may also be a promising predictor for both mortality and CV events, report Hermann Brenner (German Cancer Research Centre, Heidelberg, Germany) and colleagues in Heart.

“More research is needed not only to clarify the prognostic potential of serum calcium, phosphate and the calcium/albumin ratio in healthy subjects and CHD patients, but also to elucidate the corresponding causal pathways for cardiovascular disease (CVD) and mortality,” they write.

The researchers measured serum calcium and phosphate in 1206 patients who underwent a 3-week rehabilitation program after experiencing an acute CV event. They were subsequently followed-up for 8 years.

Patients in the highest quartile of phosphate levels (≥4.65 mg/dL) had a significant 1.63-fold increased risk for incident CV events (including nonfatal myocardial infarction or ischemic stroke, and CV death) compared with the lowest quartile (<3.72 mg/dL).

However, this association was only significant in a model adjusting for age, gender, and albumin, and not in the unadjusted model or in a model fully adjusted for a number of factors including smoking, ventricular function, and history of myocardial infarction.

Minimal (age, gender, and albumin) and maximal (plus all other factors) adjustment for possible confounders revealed that patients with calcium levels in the highest quartile (≥10.9 mg/dL) had a significant 2.39-fold higher risk for all-cause mortality than those with calcium levels in the lowest quartile (<10.2 mg/dL).

By contrast, the significantly elevated HR for phosphate levels in the highest versus lowest quartiles in unadjusted and minimally adjusted models for all-cause mortality (hazard ratios [HRs]=1.77 and 2.02, respectively) were attenuated after adjustment for confounders.

Multivariate analysis revealed that compared with those in the lowest quartile of the calcium/albumin ratio (<2.13), patients in the highest quartile of the calcium/albumin ratio (≥2.30) had significant 1.74- and 2.66-fold increased risks for incident CV events and all-cause mortality, respectively.

“The results of our analyses of cause specific mortality indicate a major role for calcium especially in the development of CV death,” write the authors.

They suggest that calcium may exert a direct influence on vascular calcification by inducing smooth muscle cell mineralization, or by interacting with other factors of bone metabolism that could in turn enhance or induce vascular calcification.

Brenner et al conclude that more research is needed to “elucidate the corresponding causal pathways for CVD and mortality, and to fully appreciate the risks and benefits of interventional approaches, including formerly widespread calcium, supplementation for bone health.”

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Heart 2012; Advance online publication