Key Findings
Chronic kidney disease (CKD) affects 8–16% of the global population and approximately 30% of patients requiring percutaneous coronary intervention for acute coronary syndrome or stable angina. Cardiovascular disease is by far the leading cause of death in CKD patients. Studies have linked a high plasma level of the phosphaturic hormone fibroblast growth factor 23 (FGF23) with an increased risk of cardiovascular disease in CKD patients. A higher FGF23 level has also been associated with an impaired response to intensified renin–angiotensin–aldosterone system (RAAS)-blockade-based therapy, the key therapy in patients with both kidney and cardiovascular disease. This study explored if intervention with dietary n-3 fatty acid supplementation for 41 months may reduce plasma FGF23 levels in post-myocardial infarction patients participating in the Alpha Omega Trial, a large randomized controlled trial that compared treatment with low-dose eicosapentaenoic acid-docosahexaenoic acid (EPA-DHA) or alpha-linoleic acid (ALA) supplementation with placebo. The current study was performed in a subgroup of patients with chronic kidney disease stage 3 (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2).
The main finding of this study is that in post-myocardial infarction patients with chronic kidney disease (eGFR < 60 mL/min/1.73 m2), low dose n-3 fatty acid supplementation did not reduce plasma C-terminal FGF23 levels. The data do not support n-3 fatty acid supplementation to reduce FGF23 levels in post-myocardial infarction patients with CKD. Whether n-3 fatty acids, particularly when given in a higher dose, affect FGF23 levels in other populations remains to be addressed in future prospective studies.
ABSTRACT:
Fibroblast growth factor 23 (FGF23) is an independent risk factor for cardiovascular mortality in chronic kidney disease. Omega-3 (n-3) fatty acid consumption has been inversely associated with FGF23 levels and with cardiovascular risk. We examined the effect of marine n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and plant-derived alpha-linolenic acid (ALA) on plasma FGF23 levels in post-myocardial infarction patients with chronic kidney disease. In the randomized double-blind Alpha Omega Trial, 4837 patients with a history of myocardial infarction aged 60-80 years (81% men) were randomized to one of four trial margarines supplemented with a targeted additional intake of 400 mg/day EPA and DHA, 2 g/day ALA, EPA-DHA plus ALA, or placebo for 41 months. In a subcohort of 336 patients with an eGFR < 60 mL/min/1.73 m² (creatinine-cystatin C-based CKD-EPI formula), plasma C-terminal FGF23 was measured by ELISA at baseline and end of follow-up. We used analysis of covariance to examine treatment effects on FGF23 levels adjusted for baseline FGF23. Patients consumed 19.8 g margarine/day on average, providing an additional amount of 236 mg/day EPA with 158 mg/day DHA, 1.99 g/day ALA or both, in the active intervention groups. Over 79% of patients were treated with antihypertensive and antithrombotic medication and statins. At baseline, plasma FGF23 was 150 (128 to 172) RU/mL (mean (95% CI)). After 41 months, overall FGF23 levels had increased significantly (p < 0.0001) to 212 (183 to 241) RU/mL. Relative to the placebo, the treatment effect of EPA-DHA was indifferent, with a mean change in FGF23 (95% CI) of -17 (-97, 62) RU/mL (p = 0.7). Results were similar for ALA (36 (-42, 115) RU/mL) and combined EPA-DHA and ALA (34 (-44, 113) RU/mL). Multivariable adjustment, pooled analyses, and subgroup analyses yielded similar non-significant results. Long-term supplementation with modest quantities of EPA-DHA or ALA does not reduce plasma FGF23 levels when added to cardiovascular medication in post-myocardial patients with chronic kidney disease.
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