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Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial.

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.

SUBMITTER: de Borst MH

PROVIDER: S-EPMC5707705 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial.

de Borst Martin H MH Baia Leandro C LC Hoogeveen Ellen K EK Giltay Erik J EJ Navis Gerjan G Bakker Stephan J L SJL Geleijnse Johanna M JM Kromhout Daan D Soedamah-Muthu Sabita S SS

Nutrients 20171111 11

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 d ...[more]

PMID: 29137111

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Project description:Background and objectivesKidney function gradually decreases with age, and myocardial infarction accelerates this deterioration. Omega-3 (n-3) fatty acids may slow down the decline of kidney function. The effect of marine and plant-derived n-3 fatty acids on kidney function in patients after myocardial infarction was examined.Design, setting, participants, & measurementsIn the Alpha Omega Trial, 2344 patients with history of myocardial infarction ages 60-80 years old (81% men) were randomized to one of four trial margarines. The patients received an additional targeted amount of 400 mg/d eicosapentaenoic acid and docosahexaenoic acid, 2 g/d α-linolenic acid, eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid, or placebo for 40 months. Serum cystatin C and serum creatinine were assessed at baseline and after 40 months. Creatinine-cystatin C-based GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration equation.ResultsPatients consumed 19.9 g margarine/d, providing an additional 239 mg/d eicosapentaenoic acid with 159 mg/d docosahexaenoic acid, 1.99 g/d α-linolenic acid, or both in the active treatment groups. After 40 months, compared with baseline, mean (±SD) creatinine-cystatin C-based GFR was -6.9 (±12.6), -4.8 (±13.4), -6.2 (±12.8), and -6.0 (±13.0) ml/min per 1.73 m(2) in the placebo, eicosapentaenoic acid-docosahexaenoic acid, α-linolenic acid, and eicosapentaenoic acid-docosahexaenoic acid plus α-linolenic acid groups, respectively. After 40 months, in patients receiving eicosapentaenoic acid-docosahexaenoic acid compared with placebo, the decline in creatinine-cystatin C-based GFR was 2.1 less (95% confidence interval, 0.6 to 3.6; P<0.01) ml/min per 1.73 m(2); other comparisons were not statistical significant. Odds ratios (95% confidence intervals) of incident CKD (<60 ml/min per 1.73 m(2)) and rapid decline of kidney function (≥3 ml/min per year) for eicosapentaenoic acid-docosahexaenoic acid compared with placebo were 0.83 (0.58 to 1.18) and 0.85 (0.67 to 1.08), respectively.ConclusionsLong-term supplementation with 400 mg/d eicosapentaenoic acid-docosahexaenoic acid provides a small beneficial effect on kidney function in patients with a history of myocardial infarction.

Project description:BackgroundReplacement of saturated fatty acids (SFAs) with unsaturated fatty acids (UFAs), especially polyunsaturated fatty acids (PUFAs), has been associated with a lower risk of ischemic heart disease (IHD). Whether this replacement is beneficial for drug-treated patients with cardiac disease is not yet clear.ObjectiveIn a prospective study of Dutch patients with cardiac disease (Alpha Omega Cohort), we examined the risk of cardiovascular disease (CVD) and IHD mortality when the sum of SFAs and trans fatty acids (TFAs) was theoretically replaced by total UFAs, PUFAs, or cis monounsaturated fatty acids (MUFAs).DesignWe included 4146 state-of-the-art drug-treated patients aged 60-80 y with a history of myocardial infarction (79% male patients) and reliable dietary data at baseline (2002-2006). Cause-specific mortality was monitored until 1 January 2013. HRs for CVD mortality and IHD mortality for theoretical, isocaloric replacement of dietary fatty acids (FAs) in quintiles (1-5) and continuously (per 5% of energy) were obtained from Cox regression models, adjusting for demographic factors, medication use, and lifestyle and dietary factors.ResultsPatients consumed, on average, 17.5% of energy of total UFAs, 13.0% of energy of SFAs, and <1% of energy of TFAs. During ∼7 y of follow-up, 372 CVD deaths and 249 IHD deaths occurred. Substitution modeling yielded significantly lower risks of CVD mortality when replacing SFAs plus TFAs with total UFAs [HR in quintile 5 compared with quintile 1: 0.45 (95% CI: 0.28, 0.72)] or PUFAs [HR: 0.66 (95% CI: 0.44, 0.98)], whereas HRs in cis MUFA quintiles were nonsignificant. HRs were similar for IHD mortality. In continuous analyses, replacement of SFAs plus TFAs with total UFAs, PUFAs, or cis MUFAs (per 5% of energy) was associated with significantly lower risks of CVD mortality (HRs between 0.68 and 0.75) and IHD mortality (HRs between 0.55 and 0.70).ConclusionShifting the FA composition of the diet toward a higher proportion of UFAs may lower CVD mortality risk in drug-treated patients with cardiac disease. This study was registered at clinicaltrials.gov as NCT03192410.

Project description:IntroductionImpaired kidney function is a robust risk factor for cardiovascular mortality. Age-related annual kidney function decline of 1.0 ml/min per 1.73 m2 after age 40 years is doubled in post-myocardial infarction (MI) patients.MethodsWe investigated the impact of the number of cardiovascular risk factors (including unhealthy lifestyle) on annual kidney function decline, in 2426 post-MI patients (60-80 years) of the prospective Alpha Omega Cohort study. Glomerular filtration rate was estimated by serum cystatin C (eGFRcysC) and combined creatinine-cystatin C (eGFRcr-cysC), using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations from 2012. Data were analyzed by multivariable linear and logistic regression.ResultsAt baseline, mean (SD) eGFRcysC and eGFRcr-cysC were 81.5 (19.6) and 78.5 (18.7) ml/min per 1.73 m2, respectively. Of all patients, 79% were men, 19% had diabetes, 56% had high blood pressure (≥140/90 mm Hg), 16% were current smokers, 56% had high serum low-density lipoprotein (LDL of ≥2.5 mmol/l), and 23% were obese (body mass index of ≥30.0 kg/m2). After multivariable adjustment, the additional annual eGFRcysC decline (95% confidence interval) was as follows: in patients with versus without diabetes, -0.90 (-1.23 to -0.57) ml/min per 1.73 m2; in patients with high versus normal blood pressure, -0.50 (-0.76 to -0.24) ml/min per 1.73 m2; in obese versus nonobese patients, -0.31 (-0.61 to 0.01) ml/min per 1.73 m2; and in current smokers versus nonsmokers, -0.19 (-0.54 to 0.16) ml/min per 1.73 m2. High LDL was not associated with accelerated eGFRcysC decline. Similar results were obtained with eGFRcr-cysC.ConclusionIn older, stable post-MI patients without cardiovascular risk factors, the annual kidney function decline was -0.90 (-1.16 to -0.65) ml/min per 1.73 m2. In contrast, in post-MI patients with ≥3 cardiovascular risk factors, the annual kidney function decline was 2.5-fold faster, at -2.37 (-2.85 to -1.89) ml/min per 1.73 m2.

Project description:Background Habitual intake of long-chain omega-3 fatty acids, especially eicosapentaenoic and docosahexaenoic acid (EPA+DHA) from fish, has been associated with a lower risk of fatal coronary heart disease (CHD) in population-based studies. Whether that is also the case for patients with CHD is not yet clear. We studied the associations of dietary and circulating EPA+DHA and alpha-linolenic acid, a plant-derived omega-3 fatty acids, with long-term mortality risk after myocardial infarction. Methods and Results We analyzed data from 4067 Dutch patients with prior myocardial infarction aged 60 to 80 years (79% men, 86% on statins) enrolled in the Alpha Omega Cohort from 2002 to 2006 (baseline) and followed through 2018. Baseline intake of fish and omega-3 fatty acids were assessed through a validated 203-item food frequency questionnaire and circulating omega-3 fatty acids were assessed in plasma cholesteryl esters. Hazard ratios (HRs) with 95% CIs were obtained from Cox regression analyses. During a median follow-up period of 12 years, 1877 deaths occurred, of which 515 were from CHD and 834 from cardiovascular diseases. Dietary intake of EPA+DHA was significantly inversely associated with only CHD mortality (HR, 0.69 [0.52-0.90] for >200 versus ≤50 mg/d; HR, 0.92 [0.86-0.98] per 100 mg/d). Similar results were obtained for fish consumption (HRCHD, 0.74 [0.53-1.03] for >40 versus ≤5 g/d; Ptrend: 0.031). Circulating EPA+DHA was inversely associated with CHD mortality (HR, 0.71 [0.53-0.94] for >2.52% versus ≤1.29%; 0.85 [0.77-0.95] per 1-SD) and also with cardiovascular diseases and all-cause mortality. Dietary and circulating alpha-linolenic acid were not significantly associated with mortality end points. Conclusions In a cohort of Dutch patients with prior myocardial infarction, higher dietary and circulating EPA+DHA and fish intake were consistently associated with a lower CHD mortality risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03192410.

Dataset Information

Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial.

Publications

Effect of Omega-3 Fatty Acid Supplementation on Plasma Fibroblast Growth Factor 23 Levels in Post-Myocardial Infarction Patients with Chronic Kidney Disease: The Alpha Omega Trial.

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