Urinary sodium concentration predicts time to major adverse coronary events and all-cause mortality in men with heart failure over a 28–33-year period: a prospective cohort study

Background: Lower urinary sodium concentrations (U_Na) may be a biomarker for poor prognosis in chronic heart failure (HF). However, no data exist to determine its prognostic association over the long-term. We investigated whether U_Na predicted major adverse coronary events (MACE) and all-cause mortality over 28–33 years. 

Methods: One hundred and eighty men with chronic HF from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) were included. Baseline data was collected between 1984 and 1989. MACE and all-cause outcomes were obtained using hospital linkage data (1984–2017) with a follow-up of 28–33 years. Cox proportional hazards models were generated using 24-h U_Na tertiles at baseline (1 ≤ 173 mmol/day; 2 = 173-229 mmol/day; 3 = 230-491 mmol/day) as a predictor of time-to-MACE outcomes, adjusted for relevant covariates. 

Results: Overall, 63% and 83% of participants (n = 114 and n = 150) had a MACE event (median 10 years) and all-cause mortality event (median 19 years), respectively. On multivariable Cox Model, relative to the lowest U_Na tertile, no significant difference was noted in MACE outcome for individuals in tertiles 2 and 3 with events rates of 28% (HR:0.72; 95% CI: 0.46–1.12) and 21% (HR 0.79; 95% CI: 0.5–1.25) respectively. Relative to the lowest U_Na tertile, those in tertile 2 and 3 were 39% (HR: 0.61; 95% CIs: 0.41, 0.91) and 10% (HR: 0.90; 95% CIs: 0.62, 1.33) less likely to experience to experience all-cause mortality. The multivariable Cox model had acceptable prediction precision (Harrell's C concordance measure 0.72). 

Conclusion: U_Na was a significant predictor of all-cause mortality but not MACE outcomes over 28–33 years with 173–229 mmol/day appearing to be the optimal level. U_Na may represent an emerging long-term prognostic biomarker that warrants further investigation.