Dataset Information

5-Lipoxygenase Gene Variants Are Not Associated With Atherosclerosis or Incident Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis Cohort.

ABSTRACT: BACKGROUND:The arachidonate 5-lipoxygenase enzyme plays a crucial role in mediating inflammation to maintain homeostasis, yet certain allelic variants of the 5-lipoxygenase gene, ALOX5, may increase risk of atherosclerosis and coronary heart disease (CHD). Further, relations between ALOX5 and disease outcomes may be enhanced or attenuated depending on the bioavailability of 5-lipoxygenase enzyme substrates. By using a candidate gene approach in 6153 Multi-Ethnic Study of Atherosclerosis (MESA) participants, associations were determined among 1348 ALOX5 single nucleotide polymorphisms (SNPs) and carotid intima-media thickness (cIMT) as well as incident CHD, and interactions with plasma concentrations of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid were tested. METHODS AND RESULTS:Multivariable linear regression was used to test for associations between cIMT and ALOX5 SNPs, and Cox regression was used for incident CHD. Bonferroni correction was used for multiple hypothesis testing. No significant associations between ALOX5 SNPs and cIMT or CHD events were observed. Levels of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid concentrations did not modify the relations of ALOX5 with either outcome. CONCLUSIONS:ALOX5 gene variants do not appear to be related to clinical CHD events or subclinical atherosclerosis regardless of bioavailable enzyme substrate levels in this multiethnic cohort. Further studies that directly examine protein expression or enzyme activity may better define the arachidonate 5-lipoxygenase pathway in disease development and progression.

SUBMITTER: Tsai MY

PROVIDER: S-EPMC4943258 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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5-Lipoxygenase Gene Variants Are Not Associated With Atherosclerosis or Incident Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis Cohort.

Tsai Michael Y MY Cao Jing J Steffen Brian T BT Weir Natalie L NL Rich Stephen S SS Liang Shuang S Guan Weihua W

Journal of the American Heart Association 20160329 3

<h4>Background</h4>The arachidonate 5-lipoxygenase enzyme plays a crucial role in mediating inflammation to maintain homeostasis, yet certain allelic variants of the 5-lipoxygenase gene, ALOX5, may increase risk of atherosclerosis and coronary heart disease (CHD). Further, relations between ALOX5 and disease outcomes may be enhanced or attenuated depending on the bioavailability of 5-lipoxygenase enzyme substrates. By using a candidate gene approach in 6153 Multi-Ethnic Study of Atherosclerosis ...[more]

PMID: 27025886

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Project description:ObjectivesThis study sought to compare various measures of adiposity with risk for incident hospitalized heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).BackgroundObesity is a risk factor for HF, particularly HFpEF. It is unknown which measures of adiposity, including anthropometrics and computed tomography (CT)-measured fat area, are most predictive of HF subtypes.MethodsThe authors studied 1,806 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) study without baseline cardiovascular disease who underwent anthropometrics (body mass index [BMI] and waist circumference) and an abdominal CT. Subcutaneous and visceral adipose tissue (VAT) were measured from a single CT slice at L2-L3. Cox hazard models were used to examine associations of adiposity with incident hospitalized HFpEF and HFrEF events. Fully adjusted models included demographics, HF risk factors, and N-terminal pro-B-type natriuretic peptide.ResultsOver a mean follow-up of 11 years, there were 34 HFpEF and 36 HFrEF events. The fully adjusted hazard ratio (95% confidence interval [CI]) per 1-SD higher of each anthropometric and CT-measured adiposity measures for incident HFpEF were as follows: BMI HR: 1.66; 95% CI: 1.12 to 2.45; waist circumference HR: 1.59; 95% CI: 1.05 to 2.40; and VAT HR: 2.24; 95% CI: 1.44 to 3.49. None of these adiposity measures were associated with HFrEF. Even among overweight/obese adults (BMI ≥25 kg/m2), assessment of VAT (per 1-SD) was strongly associated with HFpEF (HR: 2.78; 95% CI: 1.62 to 4.76). Subcutaneous adipose tissue was neither associated with HFpEF nor HFrEF.ConclusionsIn a multiethnic cohort free of cardiovascular disease, CT-measured VAT was independently associated with incident hospitalized HFpEF but not HFrEF. Measuring visceral fat at the time of CT imaging for other indications may offer additional prognostication of HF risk. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Project description:Background: Although left atrial (LA) and left ventricular (LV) structural and functional parameters have independent prognostic value as predictors of heart failure (HF), the close physiological relationship between the LA and LV suggest that the assessment of LA/LV coupling could better reflect left atrioventricular dysfunction and be a better predictor of HF. Aim: We investigated the prognostic value of a left atrioventricular coupling index (LACI), measured by cardiovascular magnetic resonance (CMR), as well as change in LACI to predict incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA). Materials and Methods: In the MESA, 2,250 study participants, free of clinically recognized HF and cardiovascular disease (CVD) at baseline, had LACI assessed by CMR imaging at baseline (Exam 1, 2000-2002), and 10 years later (Exam 5, 2010-2012). Left atrioventricular coupling index was defined as the ratio of LA to LV end-diastolic volumes. Univariable and multivariable Cox proportional hazard models were used to evaluate the associations of LACI and average annualized change in LACI (ΔLACI) with incident HF after adjustment for traditional MESA-HF risk factors. The incremental risk prediction was calculated using C-statistic, categorical net reclassification index (NRI) and integrative discrimination index (IDI). Results: Among the 2,250 participants (mean age 59.3 ± 9.3 years and 47.6% male participants), 50 incident HF events occurred over 6.8 ± 1.3 years after the second CMR exam. After adjustment, greater LACI and ΔLACI were independently associated with HF (adjusted HR 1.44, 95% CI [1.25-1.66] and adjusted HR 1.55, 95% CI [1.30-1.85], respectively; both p < 0.0001). Adjusted models for LACI showed significant improvement in model discrimination and reclassification compared to currently used HF risk score model for predicting HF incidence (C-statistic: 0.81 vs. 0.77; NRI = 0.411; IDI = 0.043). After adjustment, ΔLACI showed also significant improvement in model discrimination compared to the multivariable model with traditional MESA-HF risk factors for predicting incident HF (C-statistic: 0.82 vs. 0.77; NRI = 0.491; IDI = 0.058). Conclusions: In a multi-ethnic population, atrioventricular coupling (LACI), and coupling change (ΔLACI) are independently associated with incident HF. Both have incremental prognostic value for predicting HF events over traditional HF risk factors.

Dataset Information

5-Lipoxygenase Gene Variants Are Not Associated With Atherosclerosis or Incident Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis Cohort.

Publications

5-Lipoxygenase Gene Variants Are Not Associated With Atherosclerosis or Incident Coronary Heart Disease in the Multi-Ethnic Study of Atherosclerosis Cohort.

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