Phosphate: a novel cardiovascular risk factor

Abstract

It has recently been recognized that even in the normal population high normal phosphate concentrations are associated with increased all-cause and cardiovascular mortality. Organic phosphates in unprocessed food items are less efficiently absorbed than food additives in the form of inorganic phosphate salts. This is of relevance because even high normal and even more so elevated phosphate concentrations are correlated with reduced life expectancy and cardiovascular events. The underlying pathophysiology includes endothelial dysfunction, vascular calcification, and cardiac hypertrophy. Phosphate intake and serum phosphate concentrations must be considered as novel cardiovascular risk factors (although the causality of the correlation has not been definitely established). In patients with chronic kidney disease (CKD), it was recognized some time ago that an elevated serum phosphate concentration is a powerful risk factor for all-cause and cardiovascular mortality.1,2 As a consequence, dietary phosphate restriction is recommended in this population.3 This advice is based on the view that reduction in dietary phosphate intake is associated with a survival benefit. What is new in this context is the recent observation that the relation between high serum phosphate and survival is not restricted to patients with CKD, but is also seen in patients with cardiovascular disease and even in the normal population: high normal phosphate levels predict coronary calcification even in healthy young men.4 In the Framingham study as well high normal phosphate levels at baseline predicted cardiovascular events.5 Finally, in individuals with cardiac disease and normal renal function, Tonelli et al .6 found a relation between the serum phosphate concentration and the cardiovascular event rate. In this study, the adjusted mortality risk was 22% higher per 1 mg/dL of higher serum phosphate concentration. The major determinant of serum phosphate is renal phosphate …