胡梦巾
中国医学科学院阜外医院 心血管内科
BACKGROUND:The efficiency of invasive management in older patients (≥75 years) with non-ST-segment elevation myocardial infarction (NSTEMI) remains ambiguous.OBJECTIVES:To assess the efficiency of invasive management in older patients with NSTEMI based on meta-analysis and trial sequential analysis (TSA).METHODS:Relevant randomized controlled trials (RCT) and observational studies were included. The primary outcomes were all-cause death, myocardial infarction, stroke, and major bleeding. Pooled odd ratio (OR) and 95% confidence interval (CI) were calculated. P <0.05 was considered statistically significant.RESULTS:Five RCTs and 22 observational studies with 1017374 patients were included. Based on RCT and TSA results, invasive management was associated with lower risks of myocardial infarction (OR: 0.51; 95% CI: 0.40-0.65; I2=0%), major adverse cardiovascular events (MACE; OR: 0.61; 95% CI: 0.49-0.77; I2=27.0%), and revascularization (OR: 0.29; 95% CI: 0.15-0.55; I2=5.3%) compared with conservative management. Pooling results from RCTs and observational studies with multivariable adjustment showed consistently lower risks of all-cause death (OR: 0.57; 95% CI: 0.50-0.64; I2=86.4%), myocardial infarction (OR: 0.63; 95% CI: 0.56-0.71; I2=0%), stroke (OR: 0.59; 95% CI: 0.51-0.69; I2=0%), and MACE (OR: 0.64; 95% CI: 0.54-0.76; I2=43.4%). The better prognosis associated with invasive management was also observed in real-world scenarios. However, for patients aged ≥85 years, invasive management may increase the risk of major bleeding (OR: 2.68; 95% CI: 1.12-6.42; I2=0%).CONCLUSIONS:Invasive management was associated with lower risks of myocardial infarction, MACE, and revascularization in older patients with NSTEMI, yet it may increase the risk of major bleeding in patients aged ≥85 years.
Arquivos brasileiros de cardiologia 2023
BACKGROUND:Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV.METHODS:MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo.RESULTS:MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P < 0.01-0.0001). On day 28, MSCATV-EV much more significantly improved the cardiac function than MSC-EV with the infarct size markedly reduced (P < 0.05-0.0001). In vitro, MSCATV-EV also significantly reduced the protein and mRNA expressions of M1 markers but increased those of M2 markers in lipopolysaccharide-treated macrophages (P < 0.05-0.0001). EV miR-139-3p was identified as a potential cardiac repair factor mediating macrophage polarization. Knockdown of miR-139-3p in MSCATV-EV significantly attenuated while overexpression of it in MSC-EV enhanced the effect on promoting M2 polarization by suppressing downstream signal transducer and activator of transcription 1 (Stat1). Furthermore, MSCATV-EV loaded with miR-139-3p inhibitors decreased while MSC-EV loaded with miR-139-3p mimics increased the expressions of M2 markers and cardioprotective efficacy.CONCLUSIONS:We uncovered a novel mechanism that MSCATV-EV remarkably facilitate cardiac repair in AMI by promoting macrophage polarization via miR-139-3p/Stat1 pathway, which has the great potential for clinical translation.
BMC medicine 2023
AIMS:Several observational studies indicated that atrial fibrillation might aggravate other cardiovascular diseases apart from ischaemic stroke. However, it remains to be determined whether these associations reveal independent causation. Using Mendelian randomization (MR), we systematically investigated how genetically predicted atrial fibrillation affected other cardiovascular diseases and cardiac death.METHODS AND RESULTS:Summary-level data for atrial fibrillation and other cardiovascular diseases were obtained from public genome-wide association study data. The random inverse-variance weighted method was treated as the primary analysis. Sensitivity analyses (including weighted median, MR-Egger, and multivariable MR methods) were also performed. Atrial fibrillation was significantly associated with higher risks of heart failure [odds ratio (OR): 1.24; 95% confidence interval (CI): 1.19-1.28; P < 0.001], ischaemic stroke (OR: 1.21; 95% CI: 1.17-1.25; P < 0.001), transient ischaemic attack (OR: 1.10; 95% CI: 1.05-1.15; P < 0.001), peripheral artery diseases (OR: 1.09; 95% CI: 1.03-1.15; P = 0.002), cardiac death (OR: 1.08; 95% CI: 1.02-1.15; P = 0.008), and hypertension (OR: 1.06; 95% CI: 1.01-1.11; P = 0.010), without effects on coronary heart disease or pulmonary embolism. Associations for heart failure and ischaemic stroke remained robust to the sensitivity analyses. MR-Egger method (P > 0.05) and funnel plot yielded no indication of directional pleiotropy. The leave-one-out analysis suggested that the causal associations were not driven by individual single nucleotide polymorphism.CONCLUSIONS:This comprehensive MR analysis verified the causal associations between atrial fibrillation and high risks of heart failure, ischaemic stroke, transient ischaemic attack, peripheral artery diseases, cardiac death, and hypertension. Interventions to reduce cardiovascular diseases beyond ischaemic stroke are warranted in patients with atrial fibrillation.
ESC heart failure 2023
AIM:Some observational studies suggested that atherosclerosis increased the risk of venous thromboembolism (VTE), and vice versa. However, the results were conflicting, and the causal relationship is yet to be established. Therefore, we applied Mendelian randomization (MR) analyses to assess the bidirectional causality between coronary heart disease (CHD) and VTE, deep venous thrombosis (DVT), and pulmonary embolism (PE).METHODS:A total of 184,305 individuals with CHD were included from the CARDIoGRAMplusC4D Consortium. Information on VTE, DVT, and PE were obtained from the FinnGen biobank. Genetic instruments for CHD and VTE were constructed using 37 and 12 single-nucleotide polymorphisms, respectively. Inverse-variance weighted meta-analysis under a random-effect model was used as the preliminary estimate. Five complementary MR methods were also used, including weighted median, MR-Egger, multivariable MR (adjusted for the body mass index), simple mode, and weighted mode methods.RESULTS:The genetically instrumented VTE (odds ratio [OR]: 1.05; 95% confidence interval [CI]: 1.00-1.11; P=0.06), DVT (OR: 1.03; 95% CI: 0.99-1.08; P=0.19), or PE (OR: 1.07; 95% CI: 0.98-1.16; P=0.11) showed no causal relationships with CHD. There was also no clear evidence showing the causal effects of CHD on VTE (OR: 1.00; 95% CI: 0.82-1.22; P=0.98), DVT (OR: 1.00; 95% CI: 0.79-1.27; P=0.97), or PE (OR: 0.98; 95% CI: 0.82-1.18; P=0.87). No pleiotropic bias was found in the MR analyses. As heterogeneity was significant, a random model was used to minimize the effect of heterogeneity.CONCLUSIONS:No causal associations existed between CHD and VTE. Arterial and venous thromboses may represent separate entities.
Journal of atherosclerosis and thrombosis 2023
OBJECTIVE: The aim of the study is to assess the causal effects of cardiovascular risk factors on venous thromboembolism (VTE) and its subtypes including deep vein thrombosis (DVT) and pulmonary embolism (PE).METHODS: A summary-level Mendelian randomization (MR) analysis was performed by extracting data from public and large-scale genome-wide association studies for cardiovascular risk factors (hypertension, systolic blood pressure [SBP], diastolic blood pressure [DBP], total cholesterol, triglycerides, high-density lipoprotein [HDL], low-density lipoprotein [LDL], type 2 diabetes, fasting glucose, body mass index [BMI], smoking, alcohol, and physical activity), VTE, DVT, and PE to identify genetic instruments.RESULTS: BMI (per standard deviation [SD] increase; odds ratio [OR]: 1.39; 95% confidence interval [CI]: 1.25-1.54; p = 8.02 × 10-10) could increase the VTE risk, whereas SBP (per SD increase; OR: 0.99; 95% CI: 0.98-0.99; p = 0.0005) could decrease the VTE risk. For DVT, BMI (per SD increase; OR: 1.48; 95% CI: 1.28-1.72; p = 1.53 × 10-7) could increase the risk, whereas physical activity (per SD increase; OR: 0.05; 95% CI: 0.01-0.33; p = 0.0020) could decrease the risk. For PE, BMI (per SD increase; OR: 1.29; 95% CI: 1.12-1.49; p = 0.0005) could increase the risk, whereas SBP (per SD increase; OR: 0.99; 95% CI: 0.98-1.00; p = 0.0032) could decrease the risk. Suggestive evidence between smoking and higher risks of VTE and DVT was also observed.CONCLUSION: Our study supports that BMI is a causal risk factor for VTE, DVT, and PE. SBP is a protective factor for VTE and PE. Physical activity is a protective factor for DVT. However, the effects of other cardiovascular risk factors are not identified.
Seminars in thrombosis and hemostasis 2023
BACKGROUND: Diabetes was considered as a risk factor for venous thromboembolism (VTE), but conflicting findings have been reported from observational studies. This study aimed at investigating the causal associations of type 1 and type 2 diabetes with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE).METHODS: We designed a bidirectional two-sample Mendelian randomization (MR) analysis by using summary-level data from large genome-wide association studies performed in European individuals. Inverse variance weighting with multiplicative random effect method was used to obtain the primary causal estimates, and weighted median, weighted mode, and MR egger regression were replenished as sensitivity analyses to test the robustness of the results.RESULTS: We found no significant causal effects of type 1 diabetes on VTE (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-1.00, p = 0.043), DVT (OR: 0.98, 95% CI: 0.95-1.00, p = 0.102), and PE (OR: 0.98, 95% CI: 0.96-1.01, p = 0.160). Similarly, no significant associations of type 2 diabetes with VTE (OR: 0.97, 95% CI: 0.91-1.03, p = 0.291), DVT (OR: 0.96, 95% CI: 0.89-1.03, p = 0.255), and PE (OR: 0.97, 95% CI: 0.90-1.04, p = 0.358) were also observed. Results from multivariable MR analysis were consistent with the findings in univariable analysis. In the other direction, the results showed no significant causal effects of VTE on type 1 and type 2 diabetes.CONCLUSION: This MR analysis demonstrated no significant causal associations of type 1 and type 2 diabetes with VTE in both directions, in conflict with previous observational studies reporting positive association, which provided clues for understanding the underlying pathogenesis of diabetes and VTE.
Thrombosis and haemostasis 2023
Previous studies have shown conflicting results about the impact of moderate to vigorous physical activity on the risk of venous thromboembolism (VTE). Using Mendelian randomization, we assessed whether moderate to vigorous physical activity causally affects VTE from genetic level. Genetic instruments associated with moderate to vigorous physical activity at the genome-wide significance level (P < 5×10- 8) were selected from the UK Biobank. Summary-level data for VTE were obtained from the FinnGen consortium. Univariable and multivariable Mendelian randomization analyses were conducted. Genetically predicted moderate to vigorous physical activity had no effect on VTE [odds ratio (OR) = 1.08; 95% confidence interval (CI) 0.66-1.78; P = 0.75] under a multiplicative random-effects inverse-variance weighted model. MR-Egger (OR = 0.20; 95% CI 0.01-4.70; P = 0.33), weighted median (OR = 1.08; 95% CI 0.52-2.25; P = 0.84), simple mode (OR = 2.53; 95% CI 0.59-10.92; P = 0.23), weighted mode (OR = 2.21; 95% CI 0.50-9.74; P = 0.31), and multivariable Mendelian randomization (OR = 0.74; 95% CI 0.46-1.19; P = 0.22) also yielded no significant association. The overall estimate was not influenced by individual single nucleotide polymorphism. No evidence of heterogeneity or horizontal pleiotropy was observed. Therefore, moderate to vigorous physical activity had no causal association with VTE in the general population.
Journal of thrombosis and thrombolysis 2023
BACKGROUND:Epidemiological studies demonstrated that multiple amino acids (AAs) were associated with cardiovascular diseases (CVDs), but whether these associations were causal remains unclear. This study aims to investigate the causal relationships between circulating levels of 20 AAs and 10 CVDs in European and East Asian populations by Mendelian randomization (MR).METHODS:This MR study utilized single-nucleotide polymorphisms that were significantly associated with AAs as instrumental variables. Summary-level data for AAs and CVDs were obtained from public genome-wide association studies. The causal effects were primarily estimated by inverse variance weighting with multiplicative random effect method. Sensitivity analyses, including weighted median, weighted mode, and MR Egger regression, were used to test the robustness of our results.RESULTS:In the European population, alanine and serine were inversely associated with angina pectoris (AP) and chronic heart failure, respectively. With each unit increase of leucine, the risk of ischemic stroke increased by 10%. Moreover, tyrosine was positively associated with AP and deep vein thrombosis. In the East Asian population, each unit increase in glycine was associated with 4.1% and 9.0% decreased risks of coronary artery disease (CAD) and myocardial infarction (MI), respectively. A unit increase in serine was associated with 13.1%, 12.6% and 15.5% decreased risks of AP, CAD and MI, respectively. Sensitivity analyses supported the robustness of our results.CONCLUSIONS:This MR study demonstrated significant causal effects of circulating levels of AAs on CVDs, indicating the potential use of AAs as biomarkers or as therapeutic targets for CVD in clinical scenarios.
Journal of translational medicine 2023
BACKGROUND AND AIMS:Diabetes is associated with increased risk of certain cardiovascular diseases, yet the causality remains to be determined. Meanwhile, given that first-degree relatives share 50% of genes, the effect of familial diabetes is also worthy of attention. Therefore, we sought to investigate the causal relations of individual or familial diabetes with eight cardiovascular diseases, including myocardial infarction, hypertension, atrial fibrillation, heart failure, cardiac death, pulmonary embolism, transient ischemic attack, and ischemic stroke.METHODS AND RESULTS:Applying two-sample Mendelian randomization, we selected instruments for genetic predisposition to individual or familial diabetes based on published genome-wide association studies. The primary analyses were conducted using the random-effects inverse-variance weighted method. We found that genetically predicted individual diabetes was causally associated with higher risks of myocardial infarction (odd ratio [OR] = 1.09; 95% confidence interval [CI]: 1.05-1.13; P < 0.0001), hypertension (OR = 1.08; 95% CI: 1.03-1.13; P = 0.0006), and ischemic stroke (OR = 1.10; 95% CI: 1.05-1.15; P < 0.0001). Genetically predicted paternal diabetes could increase the risk of ischemic stroke (OR = 1.16; 95% CI: 1.04-1.30; P = 0.0061). Genetically predicted maternal diabetes could increase the risk of myocardial infarction (OR = 1.18; 95% CI: 1.09-1.29; P = 0.0001). Genetically predicted siblings' diabetes was causally associated with higher risks of myocardial infarction (OR = 1.17; 95% CI: 1.08-1.27; P = 0.0001) and hypertension (OR = 1.19; 95% CI: 1.06-1.34; P = 0.0036). No significant differences were observed in other outcomes.CONCLUSION:This study supports causal effects of not only individual but also familial diabetes on the development of cardiovascular diseases, which will help realize the potential effect of family history in the prevention of cardiovascular diseases.
Nutrition, metabolism, and cardiovascular diseases : NMCD 2023
To determine whether late percutaneous coronary intervention (PCI) of an infarct-related artery >12 h after ST-segment elevation myocardial infarction onset is beneficial, patients were included from the prospective, nationwide, multicenter China Acute Myocardial Infarction registry. The number of patients who underwent PCI or received drug therapy alone was 4791 and 1149, respectively. Hazard ratio (HR) and associated 95% confidence interval (CI) were calculated. Compared with drug therapy, PCI was associated with lower incidences of 2-year major adverse cardiac and cerebrovascular events (MACCE; 6.43 vs 20.19%; HR, .27; 95% CI, .23-.32; P < .001), all-cause death (4.13 vs 15.74%; HR, .24; 95% CI, .20-.30; P < .001), myocardial infarction (1.73 vs 3.31%; HR, .49; 95% CI, .33-.72; P = .0003), stroke (1.02 vs 2.00%; HR, .47; 95% CI, .28-.77; P = .0026), and revascularization (10.96 vs 27.56%; HR, .32; 95% CI, .26-.39; P < .001). Subgroup analysis consistently indicated that PCI was superior to drug therapy. Moreover, the left ventricular ejection fraction in the PCI group was increased after 2-year follow-up, whereas there was no significant increase in the drug therapy group. In conclusion, late PCI is common in Chinese clinical practice, and it is associated with significant improvements in cardiac function and survival compared with drug therapy alone.
Angiology 2023
