#233 Marine n-3 polyunsaturated fatty acids and cardiovascular events in patients with end-stage renal disease receiving hemodialysis

Cardiovascular (CV) disease is the leading cause of death in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). The two major marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may have cardioprotective effects. This study aimed to investigate the predictive value of plasma n-3 PUFAs on CV events and all-cause mortality in patients with ESRD receiving HD.A validated prospective multicenter cohort study of 336 patients with ESRD receiving HD with 5 years of follow-up was conducted. Blood samples were collected at baseline and analyzed for the plasma levels of EPA and DHA expressed as a weight percentage (wt%) of total plasma fatty acids. The primary outcome was CV events defined as acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease (PAD), or cardiovascular mortality. The secondary outcomes were all-cause mortality and each individual component of CV events. The sum of EPA and DHA (EPA+DHA) was used in all analyses and expressed as n-3 PUFAs in wt%. The population was divided into three groups according to n-3 PUFA tertiles. Kaplan-Meier curves and multivariable Cox regressions adjusted for relevant confounders were used to analyze the association between plasma n-3 PUFA levels and study outcomes.Median follow-up time was 5.05 years (IQR, 5.02-5.07). Mean age was 65 ± 15 years and plasma n-3 PUFA levels ranged from 2.1 to 16.8 wt%, with a median of 5.7 wt% (IQR, 4.72-6.96 wt%). During follow-up 60% of the cohort died, 17% died of CV disease, and 42% had a CV event. Figure 1 shows the unadjusted associations between the plasma n-3 PUFA tertiles and the risk of CV events. A n-3 PUFA level between 5.06-6.52 wt% was associated with a 36% lower risk of CV events unadjusted HR 0.64 (95% CI 0.43-0.96). Additionally, a n-3 PUFA level above 6.52 wt% was associated with a 34% lower risk of CV events unadjusted HR 0.66 (95% CI 0.44-0.98), both in comparison to levels below 5.06 wt%. After adjusting for relevant confounders, as shown in Figure 2, n-3 PUFA levels between 5.06 to 6.52 wt% were associated with a significantly lower risk of CV events adjusted HR 0.60 (95% CI 0.40-0.92), PAD adjusted HR 0.44 (95% CI 0.22-0.88), and all-cause mortality adjusted HR 0.61 (95% CI 0.42-0.86), when compared to levels below 5.06 wt%.In this study of patients with ESRD receiving HD, a low plasma level of n-3 PUFA was associated with a higher risk of CV events, peripheral artery disease, and all-cause mortality.Figure 1:Kaplan-Meier curves illustrating the absolute risk of cardiovascular (CV) events according to n-3 PUFA tertiles. CV events were defined as acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease, or cardiovascular mortality. Years on the X-axis and absolute risk of CV events on the Y-axis. The number of patients alive during follow-up is illustrated below the figure. N-3 PUFA n-3 polyunsaturated fatty acid.Figure 2:Event rates and multivariable Cox regressions examining the associations between n-3 PUFA tertiles and cardiovascular outcomes. Adjusted for age, sex, diabetes mellitus, smoking status, and a history of previous cardiovascular disease. N-3 PUFA n-3 polyunsaturated fatty acid, HR hazard ratio, CI confidence interval. *Cardiovascular events include acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, peripheral artery disease, and cardiovascular mortality.