Urinary phosphate is associated with cardiovascular disease incidence

Abstract

Introduction: Elevated phosphate (P) in urine may reflect a high intake of inorganic P salts from food additives. Elevated P in plasma is linked to vascular dysfunction and calcification.

Objective: To explore associations between P in urine as well as in plasma and questionnaire-estimated P intake, and incidence of cardiovascular disease (CVD).

Methods: We used the Swedish Mammography Cohort-Clinical, a population-based cohort study. At baseline (2004-2009), P was measured in urine and plasma in 1625 women. Dietary P was estimated via a food-frequency questionnaire. Incident CVD was ascertained via register-linkage. Associations were assessed using Cox proportional hazards regression.

Results: After a median follow-up of 9.4 years, 164 composite CVD cases occurred (63 myocardial infarctions [MIs] and 101 strokes). Median P (percentiles 5-95) in urine and plasma were 2.4 (1.40-3.79) mmol/mmol creatinine and 1.13 (0.92-1.36) mmol/L, respectively, whereas dietary P intake was 1510 (1148-1918) mg/day. No correlations were observed between urinary and plasma P (r = -0.07) or dietary P (r = 0.10). Urinary P was associated with composite CVD and MI. The hazard ratio of CVD comparing extreme tertiles was 1.57 (95% confidence interval 1.05, 2.35; P trend 0.037)-independently of sodium excretion, the estimated glomerular filtration rate, both P and calcium in plasma, and diuretic use. Association with CVD for plasma P was 1.41 (0.96, 2.07; P trend 0.077).

Conclusion: Higher level of urinary P, likely reflecting a high consumption of highly processed foods, was linked to CVD. Further investigation is needed to evaluate the potential cardiovascular toxicity associated with excessive intake of P beyond nutritional requirements.

Keywords: cardiovascular disease incidence; dietary phosphate intake; phosphate-based additives; plasma phosphate; ultra-processed food; urinary phosphate.