ABSTRACT
Background: Although several observational studies have suggested positive associations between constipation and cardiovascular disease (CVD), a solid causal association has not been demonstrated. Therefore, a two-sample Mendelian randomization (MR) study was performed to investigate the causal associations between constipation and CVD. Methods: Independent genetic variants strongly associated with constipation were obtained from the FinnGen consortium. Summary-level data for CVD, including coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), atrial fibrillation (AF), stroke, and its subtypes, were collected from a few extensive genome-wide association studies (GWASs). The inverse-variance weighted methods, weighted median, and MR-Egger were used for the MR estimates. The Cochran's Q test, MR-Egger intercept tests, MR-PRESSO, MR Steiger test, leave-one-out analyses, and funnel plot were used in the sensitivity analysis. Results: Genetically determined constipation was suggestively associated with AF risk (odds ratio (OR), 1.07; 95% confidence interval (CI), 1.01, 1.14; p = 0.016). Constipation and other CVD do not appear to be causally related. It was demonstrated that the results were robust through sensitivity analyses. Conclusion: This MR study demonstrated suggestive causal associations of constipation on AF, despite no associations achieving a significance value after multiple testing corrections. There was no evidence of an association between constipation and the risk of CAD, MI, HF, stroke, or stroke subtypes.
ABSTRACT
BACKGROUND: The 2020 European Society of Cardiology guidelines do not recommend pretreatment for nonST-segment elevation myocardial infarction (NSTEMI) patients with unclear coronary anatomy, which is inconsistent with our routine preoperative approach to loading P2Y12 receptor inhibitors (e.g., preoperative loading of 300 mg of clopidogrel). OBJECTIVES: The purpose of our study was to compare the safety and effectiveness of P2Y12 inhibitors administered before coronary angiography or at least before percutaneous coronary intervention (PCI) with during or after PCI. METHODS: Cochrane, PubMed, and Embase databases were searched. The primary effect endpoint and safety endpoint were any-cause death and major bleeding, respectively. Major adverse cardiovascular events, myocardial infarction and revascularization were also analyzed. RESULTS: Our search identified 9 trials. P2Y12 inhibitor pretreatment was associated with lower death from any cause (OR 0.62, 95% CI 0.53-0.72, P < 0.00001) without increasing the risk of bleeding (OR 1.02, 95% CI 0.80-1.30, P = 0.89). However, prasugrel or ticagrelor pretreatment was not associated with a lower risk of mortality (OR 0.70, 95% CI 0.31-1.59, P = 0.40) and increased the risk of bleeding (OR 1.67, 95% CI 1.10-2.54, P = 0.02). CONCLUSIONS: In summary, clopidogrel pretreatment was associated with significantly lower mortality, major adverse cardiovascular events, myocardial infarction and revascularization with no increase in major bleeding. However, these advantages were not observed with prasugrel or ticagrelor pretreatment.
