U-shaped relationship between serum phosphate and cardiovascular risk: A retrospective cohort study

BACKGROUND: High serum phosphate is associated with coronary artery disease in patients with normal and impaired renal function. We asked: Does the serum phosphate range provide prediction of primary cardiac events? We extracted coded primary care data for over 100,000 patients from a database of 135 primary medical practices. Patients aged between 18 and 90 years without pre-existing cardiovascular diagnoses were included from a potential sample of over 1·2 million individuals. METHODS AND FINDINGS: Binary logistic regression models were used to evaluate the contribution of QRISK factors and electrolytes, including serum phosphate, to cardiac outcomes at five and nine years following an initial phosphate measurement. At five-year review (n = 113,993), low serum phosphate (OR 1·75, 95%CI 1·36–2·23, p<0·001), high-normal (OR 1·50, 95%CI 1·29–1·74, p<0·001), and high serum phosphate (OR 1·74, 95%CI 1·06–2·70, p = 0·02) were long-term risk factors for primary cardiac disease events after adjusting for confounding variables. A similar pattern was seen at our nine-year review. CONCLUSIONS: The extremes of serum phosphate may confer cardiac event risk with a U-shaped trend. In particular, we raise new cardiac concerns for low serum phosphate in the general population. Also, the normal range for phosphate may require redefinition among healthy adults.