Urinary phosphate is associated with cardiovascular disease incidence

• Published in: Journal of internal medicine 2023-09, Vol.294 (3), p.358-369
• Main Authors: Donat‐Vargas, Carolina, Guallar‐Castillon, Pilar, Nyström, Jenny, Larsson, Susanna C., Kippler, Maria, Vahter, Marie, Faxén‐Irving, Gerd, Michaelsson, Karl, Wolk, Alicja, Stenvinkel, Peter, Åkesson, Agneta
• Format: Article
• Language: English
• Subjects: Calcification; Calcification (ectopic); Cardiovascular disease; cardiovascular disease incidence; Cardiovascular diseases; Confidence intervals; Creatinine; Diet; Dietary intake; dietary phosphate intake; Diuretics; Food additives; Food processing; Glomerular filtration rate; Hazard assessment; Heart diseases; Mammography; Nutritional requirements; phosphate-based additives; Plasma; plasma phosphate; Population studies; Processed foods; Questionnaires; Statistical analysis; Toxicity; ultra-processed food; urinary phosphate; Urine
• ISSN: 0954-6820; 1365-2796; 1365-2796
• DOI: 10.1111/joim.13686

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.