Dataset Information

Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study.

ABSTRACT: We aimed to examine the prospective association between plasma FAs, oxylipins, and risk of acute myocardial infarction (AMI) in a Singapore Chinese population. A nested case-control study with 744 incident AMI cases and 744 matched controls aged 47-83 years was conducted within the Singapore Chinese Health Study. Nineteen plasma FAs and 12 oxylipins were quantified using MS. These were grouped into 12 FA clusters and 5 oxylipin clusters using hierarchical clustering, and their associations with AMI risk were assessed. Long-chain n-3 FAs [odds ratio (OR) = 0.67 per SD increase, 95% confidence interval (CI): 0.53-0.84, P < 0.001] and stearic acid (OR = 0.65, 95% CI: 0.44-0.97, P = 0.03) were inversely associated with AMI risk, whereas arachidonic acid (AA) was positively associated with AMI risk (OR = 1.25, 95% CI: 1.03-1.52, P = 0.02) in the multivariable model with adjustment for other FAs. Further adjustment for oxylipins did not substantially change these associations. An inverse association was observed between AA-derived oxylipin, thromboxane (TX)B2, and AMI risk (OR = 0.81, 95% CI: 0.71-0.93, P = 0.003). Circulating long-chain n-3 FAs and stearic acid were associated with a lower and AA was associated with a higher AMI risk in this Chinese population. The association between the oxylipin TXB2 and AMI requires further research.

SUBMITTER: Sun Y

PROVIDER: S-EPMC4918858 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study.

Sun Ye Y Koh Hiromi W L HW Choi Hyungwon H Koh Woon-Puay WP Yuan Jian-Min JM Newman John W JW Su Jin J Fang Jinling J Ong Choon Nam CN van Dam Rob M RM

Journal of lipid research 20160524 7

We aimed to examine the prospective association between plasma FAs, oxylipins, and risk of acute myocardial infarction (AMI) in a Singapore Chinese population. A nested case-control study with 744 incident AMI cases and 744 matched controls aged 47-83 years was conducted within the Singapore Chinese Health Study. Nineteen plasma FAs and 12 oxylipins were quantified using MS. These were grouped into 12 FA clusters and 5 oxylipin clusters using hierarchical clustering, and their associations with ...[more]

PMID: 27371261

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Project description:ST-segment elevation myocardial infarction (STEMI) occurs as a result of acute occlusion of the coronary artery. Despite successful reperfusion using primary percutaneous coronary intervention (PPCI), a large percentage of myocardial cells die after reperfusion, which is recognized as ischemia/reperfusion injury (I/R). There are rapid changes in plasma lipidome during myocardial reperfusion injury. However, the impact of coronary artery reperfusion on plasma oxylipins is unknown. This study aimed to investigate alterations in the oxylipin profiles of STEMI patients during ischemia and at various reperfusion time points following PPCI. Blood samples were collected from patients presenting with STEMI prior to PPCI (Isch, n = 45) and subsequently 2 h following successful reperfusion by PPCI (R-2 h, n = 42), after 24 h (R-24 h, n = 44), after 48 h (R-48 h, n = 43), and then 30 days post PPCI (R-30 d, n = 29). As controls, blood samples were collected from age- and sex-matched patients with non-obstructive coronary artery disease after diagnostic coronary angiography. High-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) using deuterated standards was used to identify and quantify oxylipins. In patients presenting with STEMI prior to reperfusion (Isch group), the levels of docosahexaenoic acid (DHA)-derived oxylipins were significantly higher when compared with controls. Their levels were also significantly correlated with the peak levels of creatine kinase (CK) and troponin T(TnT) before reperfusion (CK: r = 0.33, p = 0.046, TnT: r = 0.50, p = 1.00 × 10-3). The total concentrations of oxylipins directly produced by 5-lipoxygenase (5-LOX) were also significantly elevated in the Isch group compared with controls. The ratio of epoxides (generated through epoxygenase) to diols (generated by soluble epoxide hydrolysis (sEH)) was significantly lower in the Isch group compared with the controls. Following reperfusion, there was an overall reduction in plasma oxylipins in STEMI patients starting at 24 h post PPCI until 30 days. Univariate receiver operating characteristic (ROC) curve analysis also showed that an elevated ratio of epoxides to diols during ischemia is a predictor of smaller infarct size in patients with STEMI. This study revealed a large alteration in plasma oxylipins in patients presenting with STEMI when compared with controls. Total oxylipin levels rapidly reduced post reperfusion with stable levels reached 24 h post reperfusion and maintained for up to 30 days post infarct. Given the shifts in plasma oxylipins following coronary artery reperfusion, further research is needed to delineate their clinical impact in STEMI patients.

Project description:Polyunsaturated fatty acid-derived oxylipins regulate systemic inflammation and exert cardiovascular effects, yet their role in ST-segment elevation myocardial infarction (STEMI) remains unclear. Herein, we used targeted metabolomics and machine learning algorithms to develop an oxylipin-based risk model to accurately predict recurrent major adverse cardiovascular events (MACE) after STEMI in two independent prospective cohorts with 2 years of follow-up. The in vivo effects of significant oxylipin predictors were explored via a murine myocardial ischemia‒reperfusion model and functional metabolomics. Among the 130 plasma oxylipins detected in discovery cohort (n = 645), patients with and without recurrent MACE exhibited significant differences in a variety of oxylipin subclasses. We constructed an oxylipin-based prediction model that showed powerful performance in predicting recurrent MACE in the discovery cohort (predictive accuracy: 91.5%). The predictive value of the oxylipin marker panel was confirmed in an independent external validation cohort (predictive accuracy: 89.9%; n = 401). Furthermore, we found that the anti-inflammatory/pro-resolving oxylipin (ARO) predictor panel showed better prognostic performance than the pro-inflammatory oxylipin predictor panel in both cohorts. Compared with the treatment of pro-inflammatory oxylipin predictor panel, combined treatment of six ARO predictors, including 14,15 epoxy-eicosatrienoic acid, 14(15)-epoxy-eicosatetraenoic acid, 12,13-epoxy-octadecenoic acid, lipoxin A4, resolving D1, and 6 keto-prostaglandin F1 showed significant cardiac activities and synergistic metabolic actions in myocardial infarction‒reperfusion model mice. We also mechanistically identified an important role of ARO predictors in restraining ceramide/lysophosphatidylcholine synthesis and inhibiting inflammatory responses. Overall, the present study depicted the landscape of oxylipin profiles in the largest panel of STEMI patients worldwide. Our results also highlight the great potential of bioactive oxylipins in prognostic prediction and therapeutics after STEMI.

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Dataset Information

Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study.

Publications

Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study.

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