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Background The triglyceride-glucose (TyG) index is a new alternative measure for insulin resistance. This meta-analysis was conducted to assess the associations of the TyG index with the risks of cardiovascular diseases and mortality in the general population. Methods The PubMed, Cochrane Library and Embase databases were searched for randomized controlled trials or observational cohort studies reporting associations of the TyG index with cardiovascular diseases and mortality from inception to April 16, 2022. Effect sizes were pooled using random-effects models. Robust error meta-regression methods were applied to fit nonlinear dose–response associations. Evidence quality levels and recommendations were assessed using the Grading of Recommendations Assessment, Development and Evaluation system (GRADE). Results Twelve cohort studies (6 prospective and 6 retrospective cohorts) involving 6,354,990 participants were included in this meta-analysis. Compared with the lowest TyG index category, the highest TyG index was related to a higher incidence of coronary artery disease (CAD) (3 studies; hazard ratio [HR] = 2.01; 95% confidence interval [CI] 1.68–2.40; I2 = 0%), myocardial infarction (MI) (2 studies; HR = 1.36; 95% CI 1.18–1.56; I2 = 35%), and composite cardiovascular disease (CVD) (5 studies; HR = 1.46; 95% CI 1.23–1.74; I2 = 82%). However, there was no association between the TyG index and mortality (cardiovascular mortality [3 studies; HR = 1.10; 95% CI 0.82–1.47; I2 = 76%] or all-cause mortality [4 studies; HR = 1.08; 95% CI 0.92–1.27; I2 = 87%]). In the dose–response analysis, there was a linear association of the TyG index with the risk of CAD (Pnonlinear = 0.3807) or CVD (Pnonlinear = 0.0612). GRADE assessment indicated very low certainty for CVD, MI, cardiovascular mortality and all-cause mortality, and moderate certainty for CAD. Conclusions Based on our current evidence, a higher TyG index may be associated with an increased incidence of CAD (moderate certainty), MI (very low certainty) and CVD (very low certainty) in the general population. There is a potential linear association of the TyG index with CAD and the composite CVD incidence. Further prospective studies (especially in non-Asians) are needed to confirm our findings.

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Diabetic hearts are vulnerable to myocardial ischemia/reperfusion injury (IRI), but are insensitive to sevoflurane postconditioning (SPC), activating peroxiredoxins that confer cardioprotection. Previous studies have demonstrated that hydrogen sulfide (H2S) can suppress oxidative stress of diabetic rats through increasing the expression of silent information regulator factor 2‐related enzyme 1 (SIRT1), but whether cardioprotection by SPC can be restored afterward remains unclear. Diabetic rat was subjected to IRI (30 min of ischemia followed by 120 min reperfusion). Postconditioning treatment with sevoflurane was administered for 15 min upon the onset of reperfusion. The diabetic rats were treated with GYY4137 (H2S donor) 5 days before the experiment. Myocardial infarct size, mitochondrial structure and function, ATP content, activities of complex I‐IV, marker of oxidative stress, SIRT1, nuclear factor E2‐related factor 2 (Nrf2), heme oxygenase‐1 (HO‐1), and NADPH Oxidase‐2 (Nox‐2) protein expression were detected after reperfusion, and cardiac function was evaluated by echocardiography at 24 h after reperfusion. After H2S activated SIRT1 in the impaired myocardium of diabetic rats, SPC significantly upregulated the expression of Nrf2 and its downstream mediator HO‐1, thus reduced the expression of Nox‐2. In addition, H2S remarkably increased cytoplasmic and nuclear SIRT1 which was further enhanced by SPC. Furthermore, H2S combined with SPC reduced the production of reactive oxygen species, increased the content of ATP, and maintained mitochondrial enzyme activity. Finally, myocardial infarct size and myocardium damage were decreased, and cardiac function was improved. Taken together, our study proved that H2S could restore SPC‐induced cardioprotection in diabetic rats by enhancing and promoting SIRT1/Nrf2 signaling pathway mediated mitochondrial dysfunction and oxidative stress.

Objective The triglyceride–glucose (TyG) index has been shown to be a new alternative measure for insulin resistance. However, no study has attempted to investigate the association of the TyG index with incident atrial fibrillation (AF) in the general population without known cardiovascular diseases. Methods Individuals without known cardiovascular diseases (heart failure, coronary heart disease, or stroke) from the Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The association between the baseline TyG index and incident AF was examined using Cox regression. Results Of 11,851 participants, the mean age was 54.0 years; 6586 (55.6%) were female. During a median follow-up of 24.26 years, 1925 incidents of AF cases (0.78/per 100 person-years) occurred. An increased AF incidence with a graded TyG index was found by Kaplan‒Meier curves (P < 0.001). In multivariable-adjusted analysis, both < 8.80 (adjusted hazard ratio [aHR] = 1.15, 95% confidence interval [CI] 1.02, 1.29) and > 9.20 levels (aHR 1.18, 95% CI 1.03, 1.37) of the TyG index were associated with an increased risk of AF compared with the middle TyG index category (8.80–9.20). The exposure-effect analysis confirmed the U-shaped association between the TyG index and AF incidence (P = 0.041). Further sex-specific analysis showed that a U-shaped association between the TyG index and incident AF still existed in females but not in males. Conclusions A U-shaped association between the TyG index and AF incidence is observed in Americans without known cardiovascular diseases. Female sex may be a modifier in the association between the TyG index and AF incidence. Graphical Abstract

Background The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy. Methods and Results Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69–0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69–0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74–1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79–1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy. Conclusion In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.