Phosphorus and Cardiovascular Disease

Abstract

During the last two decades, it has become increasingly clear that chronic kidney disease (CKD) represents one of the most powerful cardiovascular (CV) and mortality risk factors. When trying to single out CKD-associated metabolic disturbances with immediate pathophysiological impact in this context, mineral and bone disorders (CKD-MBD) and especially hyperphosphatemia were identified as potential candidate triggers for cardiovascular disease and clinical events. Large epidemiological trials were supportive that elevated serum phosphate concentrations are associated with all-cause and cardiovascular mortality, especially in patients on dialysis, but also in predialysis patients and even in normal populations. Hyperphosphatemia is strongly linked to cardiovascular calcification by a pathobiological phenomenon termed “osteochondrogenic transdifferentiation” of vascular smooth muscle cells (VSMC) leading to an unwanted bone-like remodeling of the arterial vessel wall. The functional consequences of this process are arterial stiffness and an increased pulse wave velocity, contributing to the development of left ventricular hypertrophy and heart failure. Dietary phosphate restriction and phosphate binder treatments are thus applied in order to modify this risk factor, although randomized controlled trials are currently still missing, which prove the concept that phosphate lowering leads to improved longevity and prevents cardiovascular events. However, because of its high biological plausibility and an overwhelming observational data basis, current guidelines recommend that phosphate management is among the key therapeutic goals in the prevention of CKD-associated cardiovascular disease.