Low Plasma Marine N-3 Polyunsaturated Fatty Acids are Associated With Increased Risk of Cardiovascular Events in Patients Treated With Maintenance Hemodialysis

OBJECTIVE: This study investigated the association between the plasma marine n-3 polyunsaturated fatty acids (n-3 PUFAs) eicosapentaenoic acid and docosahexaenoic acid and cardiovascular (CV) events and all-cause mortality in patients treated with hemodialysis.

METHODS: Prospective multicenter cohort study with 5 years of follow-up. Primary outcome was CV events and secondary outcomes were all-cause mortality and each component of CV events. The sum of plasma eicosapentaenoic acid and docosahexaenoic acid was expressed as marine n-3 PUFAs in weight percentage (wt%). The population was divided into tertiles according to plasma n-3 PUFA levels: lower tertile <5.06 wt%, middle tertile 5.06-6.52 wt%, and upper tertile >6.52 wt%.

RESULTS: In total, 336 patients were included. Median follow-up was 5.05 (5.02-5.07) years. Generally, the lower tertile was associated with a higher risk of CV events. Unadjusted, the middle tertile was associated with a 36% lower risk of CV events [hazard ratio (HR) 0.64 (95% confidence interval (CI) 0.43-0.96)], and the upper tertile was associated with a 34% lower risk of CV events [HR 0.66 (95% CI 0.44-0.98)]. After adjusting for confounders, the middle tertile was associated with a lower risk of CV events [HR 0.60 (95% CI 0.40-0.92)], peripheral arterial disease [HR 0.44 (95% CI 0.22-0.88)], and all-cause mortality [HR 0.61 (95% CI 0.42-0.86)]. A restricted cubic spline showed that the CV risk was higher in patients with levels below the median of 5.7 wt%, indicating a potential threshold effect.

CONCLUSION: Low plasma marine n-3 PUFA levels were associated with a higher risk of CV events, peripheral arterial disease, and all-cause mortality in patients treated with hemodialysis.