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Association of elevated circulating fibroblast growth factor 21 levels with prevalent and incident metabolic syndrome: The Multi-Ethnic Study of Atherosclerosis.

ABSTRACT: BACKGROUND AND AIMS:Fibroblast growth factor 21 (FGF21) plays an important role in glucose and lipid metabolism. We have investigated the relationship of plasma FGF21 levels with both prevalent and incident metabolic syndrome (MetS) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS:5783 participants from four major ethnic groups (non-Hispanic white, African American, Hispanic American, and Chinese American) were included in the cross-sectional analysis. Longitudinal analysis involved 3479 participants without MetS at baseline, of whom 1100 participants developed incident MetS over 9.2 years. RESULTS:Elevated FGF21 levels were found in participants with prevalent MetS (median [interquartile range]?=?189.4 [114.4-302.1] vs. 123.7 [65.9-210.3] pg/mL, p?

SUBMITTER: Ong KL

PROVIDER: S-EPMC6399036 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Association of elevated circulating fibroblast growth factor 21 levels with prevalent and incident metabolic syndrome: The Multi-Ethnic Study of Atherosclerosis.

Ong Kwok-Leung KL McClelland Robyn L RL Allison Matthew A MA Kokkinos John J Wu Ben J BJ Barter Philip J PJ Rye Kerry-Anne KA

Atherosclerosis 20181017

<h4>Background and aims</h4>Fibroblast growth factor 21 (FGF21) plays an important role in glucose and lipid metabolism. We have investigated the relationship of plasma FGF21 levels with both prevalent and incident metabolic syndrome (MetS) in participants from the Multi-Ethnic Study of Atherosclerosis (MESA).<h4>Methods</h4>5783 participants from four major ethnic groups (non-Hispanic white, African American, Hispanic American, and Chinese American) were included in the cross-sectional analysis ...[more]

PMID: 30446181

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The relationship of circulating fibroblast growth factor 21 levels with incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis.

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| S-EPMC5812825 | biostudies-literature

Relationship of fibroblast growth factor 21 with kidney function and albuminuria: multi-ethnic study of atherosclerosis.

Project description:BackgroundFibroblast growth factor 21 (FGF21) may play a role in the development of chronic kidney disease (CKD). We therefore investigated the relationship of plasma FGF21 levels with kidney function and albuminuria in the Multi-Ethnic Study of Atherosclerosis (MESA).MethodsThe analysis included 5724 MESA participants ages 45-84 years between 2000 and 2002, free of clinically apparent cardiovascular disease (CVD). Participants were followed up in person at four additional clinic visits over 10 years. Plasma FGF21 levels were measured at baseline examination by enzyme-linked immunosorbent assay. Kidney function was assessed by estimated glomerular filtration rate (eGFR). Outcomes were urinary albumin:creatinine ratio (UACR) progression, incident CKD by eGFR (reaching eGFR <60 mL/min/1.73 m2 with eGFR loss rate ≥1 mL/min/1.73 m2 per year) and rapid kidney function decline (eGFR decline >5%/year).ResultsAt baseline, higher FGF21 levels, assessed as both continuous and categorical quartile variables, were significantly associated with lower eGFR and higher UACR, after adjusting for demographic, socioeconomic and other confounding factors [adjusted mean differences of -2.63 mL/min/1.73 m2 in eGFR and 0.134 in log normally transformed UACR (mg/g) for the highest FGF21 quartile compared with the lowest quartile, all P < 0.001]. However, in longitudinal analyses, baseline FGF21 levels did not predict incident CKD by eGFR, rapid kidney function decline or UACR progression. No significant interaction with sex and race/ethnicity was found (all P > 0.05).ConclusionsOur study does not support a role of FGF21 as a biomarker for predicting kidney function decline or albuminuria in adults free of clinically apparent CVD at baseline.

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Age at menopause and incident heart failure: the Multi-Ethnic Study of Atherosclerosis.

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| S-EPMC4031284 | biostudies-literature

Metabolic syndrome and incident peripheral artery disease - the Multi-Ethnic Study of Atherosclerosis.

Project description:We evaluated whether metabolic syndrome (MetS) is associated with an increased incidence of lower extremity peripheral artery disease (PAD) in community dwelling people free of clinical cardiovascular disease at baseline. We assessed whether higher levels of inflammatory biomarkers may mediate the association of MetS with incident PAD.MetS was defined at baseline as the presence of three or more of the following components: elevated waist circumference, triglycerides ?150 mg/dL, reduced high-density lipoprotein (HDL) cholesterol, blood pressure ?130/85 mm Hg or taking blood pressure medication, and fasting glucose ?100 mg/dL and <126 mg/dL. People with diabetes were excluded. Incident New PAD was defined among people with a normal ankle brachial index (ABI) at baseline (i.e. baseline ABI of 0.90 to 1.40) and consisted of one of the following outcomes during 3-year follow-up: ABI decline to < 0.90 combined with a decline ?0.15 or medical record confirmed PAD outcome. Multivariable Poisson regression was used to estimate the association between MetS and incident PAD.Among 4817 participants without PAD at baseline, 1382 (29%) had MetS. Adjusting for age, sex, race, smoking, physical activity, low-density lipoprotein cholesterol, baseline ABI, and other confounders, 23/1382 (1.7%) people with MetS developed PAD vs. 30/3435 (0.87%) people without MetS (risk ratio = 1.78 [95% Confidence Interval (CI), 1.04 to 2.82], P = 0.031). Adjusting for C-reactive protein, fibrinogen, or interleukin-6 did not attenuate this association.People free of clinical cardiovascular disease with MetS are at increased risk for PAD. Our findings suggest that this association is not mediated by inflammation.

| S-EPMC5656388 | biostudies-literature

Liver fat, statin use, and incident diabetes: The Multi-Ethnic Study of Atherosclerosis.

Project description:Background and aimsTo balance competing cardiovascular benefits and metabolic risks of statins, markers of type 2 diabetes (T2D) susceptibility are needed. We sought to define a competing risk/benefit of statin therapy on T2D and cardiovascular disease (CVD) events using liver attenuation and coronary artery calcification (CAC).Methods and results3153 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) without CVD, T2D/impaired fasting glucose, or baseline statin therapy had CT imaging for CAC and hepatic attenuation (hepatic steatosis). Cox models and rates of CVD and T2D were calculated to assess the role of liver attenuation in T2D and the relative risks/benefits of statins on CVD and T2D. 216 T2D cases were diagnosed at median 9.1 years follow-up. High liver fat and statin therapy were associated with diabetes (HR 2.06 [95%CI 1.52-2.79, P < 0.0001] and 2.01 [95%CI 1.46-2.77, P < 0.0001], respectively), after multivariable adjustment. With low liver fat and CAC = 0, the number needed to treat (NNT) for statin to prevent one CVD event (NNT 218) was higher than the number needed to harm (NNH) with an incident case of T2D (NNH 68). Conversely, those with CAC >100 and low liver fat were more likely to benefit from statins for CVD reduction (NNT 29) relative to T2D risk (NNH 67). Among those with CAC >100 and fatty liver, incremental reduction in CVD with statins (NNT 40) was less than incremental risk increase for T2D (NNH 24).ConclusionsLiver fat is associated with incident T2D and stratifies competing metabolic/CVD risks with statin therapy. Hepatic fat may inform T2D surveillance and lipid therapeutic strategies.

| S-EPMC4546884 | biostudies-literature

Association of SCARB1 variants with subclinical atherosclerosis and incident cardiovascular disease: the multi-ethnic study of atherosclerosis.

Project description:OBJECTIVE:We previously reported a statistically significant association of SCARB1 intronic single nucleotide polymorphism (SNP) rs10846744 with common carotid intimal-medial artery thickness in each of the 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups (white, Chinese, black, and Hispanic). METHODS AND RESULTS:Using an expanded sample of 7936 Multi-Ethnic Study of Atherosclerosis participants, phenotyped for measures of subclinical atherosclerosis, incident myocardial infarction, and cardiovascular disease, and genotyped through the SNP Health Association Resource project, we have now examined the genetic association of these phenotypes with 126 genotyped and imputed SCARB1 SNPs. We also performed stratified analyses to examine whether SCARB1 SNP effects differed by sex. Our analysis of the full Multi-Ethnic Study of Atherosclerosis cohort provides strong evidence for the association of rs10846744 with common carotid intimal-medial thickness (P=1.04E-4 in combined analysis of all 4 Multi-Ethnic Study of Atherosclerosis racial/ethnic groups). In sex-stratified analysis, we observed statistically significant association of rs10846744 with incident cardiovascular disease events in males (P=0.01). Examining analytical results from the Myocardial Infarction Genetics Consortium for replication, we observed further support for the association of rs10846744 with myocardial infarction. CONCLUSIONS:The SCARB1 SNP, rs10846744, exerts a major effect on subclinical atherosclerosis and incident cardiovascular disease in humans.

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