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Independent metabolic syndrome variants predict new-onset coronary artery disease.

ABSTRACT: Any combination of metabolic abnormalities may constitute the metabolic syndrome (MetS), conferring coronary artery disease (CAD) risk, but the independent effect of different combinations on CAD onset remains unknown. RESEARCH DESIGN AND METHODS" Healthy adult siblings (n = 987) of premature CAD (<60 years) case subjects were followed for 9.8 +/- 3.8 years. Baseline MetS variables (insulin sensitivity index, waist circumference, systolic blood pressure, HDL cholesterol, and triglycerides) were recombined into five principal components (PC1-5), and risk factor-adjusted proportional hazards for CAD onset of median-dichotomized PCs were estimated.The significant hazard ratios were as follows: for PC1 (all abnormalities except blood pressure) 1.66 (P = 0.036), PC2 (high blood pressure levels, high HDL cholesterol) 1.71 (P = 0.016), and PC4 (low HDL cholesterol, high insulin sensitivity, low triglycerides) 2.0 (P = 0.001). Traditionally defined MetS had a hazard ratio of 1.32 (P = 0.18).Independent MetS variants identified by PC analysis may explain metabolic mechanisms that increase CAD risk better than the presence of traditional MetS.

SUBMITTER: Vaidya D

PROVIDER: S-EPMC2875458 | biostudies-other | 2010 Jun

REPOSITORIES: biostudies-other

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Independent metabolic syndrome variants predict new-onset coronary artery disease.

Vaidya Dhananjay D Mathias Rasika A RA Kral Brian G BG Yanek Lisa R LR Becker Lewis C LC Becker Diane M DM

Diabetes care 20100318 6

<h4>Objective</h4>Any combination of metabolic abnormalities may constitute the metabolic syndrome (MetS), conferring coronary artery disease (CAD) risk, but the independent effect of different combinations on CAD onset remains unknown. RESEARCH DESIGN AND METHODS" Healthy adult siblings (n = 987) of premature CAD (<60 years) case subjects were followed for 9.8 +/- 3.8 years. Baseline MetS variables (insulin sensitivity index, waist circumference, systolic blood pressure, HDL cholesterol, and tr ...[more]

PMID: 20299483

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Project description:BACKGROUND:The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. METHODS:1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. RESULTS:Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. CONCLUSIONS:Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research.

Project description:IntroductionIndividuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS via serum metabolomics to provide insight into potential associations.MethodsNon-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD vs. 121 healthy controls (HCs) as cohort 1, 55 MetS vs. 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student's t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values >1.0 and p values <0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites.ResultsThirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis.ConclusionSerum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS.

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Independent metabolic syndrome variants predict new-onset coronary artery disease.

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Independent metabolic syndrome variants predict new-onset coronary artery disease.

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