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Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits ( P  < 5 × 10 −8 ) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance ( Meta P  = 7.09 × 10 −10 , OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5 . We further replicated 10 loci previously identified among predominantly Europeans ( P: 1.33 × 10 −7 –0.047). Seven pathways ( P : 1.10 × 10 −5 –0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.

In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world's most populous ethnicities: Whites, Chinese, Indians and Malays. The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis. We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1-1.7], p = 0.008) and Malay (OR 1.9 [1.4-2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups. In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality.

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017–2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28–7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18–4.96), lower arterial pH (aOR 0.02, CI 0.00–0.31), higher lactate (aOR 2.42, CI 1.00–1.19), and lower hemoglobin (aOR 0.83, CI 0.71–0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS.

ObjectiveST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention.MethodsData from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young (<50 years old) or older (≥50 years old) groups.ResultsOf the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were <50 years old. Young compared with older patients were more likely to be male, current smokers, of Indian ethnicity, have family history of ischaemic heart disease (IHD) and had lower 1 year mortality (3.4% vs 10.4%, p<0.0001). Although diabetes, hypertension or dyslipidaemia was less common among young patients, the prevalence of having any one of these risk factors was high in the range of 28% to 38%. Age was an independent predictor of mortality in the older but not younger patients with STEMI, and diabetes showed a trend towards mortality in both groups.ConclusionYoung patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p < 0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p < 0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y12 antagonists (97.6% vs 98.5%, p = 0.039), but there were no significant sex differences in other discharge medications. After adjusting for differences in baseline characteristics and treatment, sex differences in risk of rehospitalization for HF attenuated (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.79 to 1.40), but persisted for MI (HR 1.68, 95% CI 1.22 to 2.33), with greater disparity in patients aged ≥60 years (HR 1.83, 95% CI 1.18 to 2.85) than those aged <60 years (HR 1.45, 95% CI 0.84 to 2.50). In conclusion, in a setting of universal access to pPCI, the adjusted risk of 1-year rehospitalization for HF was similar in both sexes, but women had significantly higher adjusted risk of 1-year rehospitalization for MI, especially older women.

Although coronary angiography is an established technique in the assessment of atherosclerosis, it is limited by 2-dimensional imaging and poor differentiation between plaque types. Optical coherence tomography enables visualization of plaque architecture at the microscopic level, and in this review the possibilities of its use as an alternative modality are discussed. The understanding of concepts in coronary artery disease, such as the vulnerable or high-risk plaque, which accounts for many acute coronary events arising from non-flow-limiting coronary lesions, has advanced remarkably. Although coronary angiography is an established imaging technique for visualizing atherosclerotic disease, it is limited by its two-dimensional imaging aspect and a low sensitivity for identifying lesions in the presence of positive remodeling and diffuse disease. Moreover, coronary atherosclerotic plaques cannot be characterized. Although intravascular ultrasound is currently the most commonly employed adjunctive method to better define lesions, it is limited by low resolution. The development of new technologies for improved coronary plaque characterization has, thus, been desired. Optical coherence tomography is a developing technique that uses near-infrared light for the cross-sectional visualization of the vessel wall at the microscopic level. It enables excellent resolution of coronary architecture and precise characterization of plaque architecture. Quantification of macrophages within the plaque is also possible. These capabilities allow precise identification of the most common type of vulnerable plaque, the thin-cap fibroatheroma. Here, we discuss results from clinical studies which indicate that optical coherence tomography is a promising imaging technique for improved characterization of the coronary atherosclerotic plaque. Key Points Optical coherence tomography is an optical analog of intravascular ultrasound, but with a much higher resolution This new imaging modality allows in vivo study of coronary vascular structures at the microscopic level, which include plaque characteristics, fibrous cap thickness, and macrophage density The results of optical coherence tomography might help us to understand the vascular response to percutaneous intervention and might eventually improve clinical outcome Current limitations, such as red-blood-cell interference and limited penetration depth, might be overcome in the near future by optical frequency domain imaging

Background Haptoglobin (Hp) is a plasma protein with strong anti‐inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown. Methods We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models. Results Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (β = 0.073, SE = 0.030, p = 0.015) and non‐hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607–0.980), p = 0.033). Conclusion HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non‐hypertensive individuals with the same allele had lower risk for mortality in the Chinese population. Hp genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele which is associated with higher Hp levels had more severe CAD, while non‐hypertensive individuals with the same allele had lower risk for mortality in the Chinese population.

Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p <0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD. Percutaneous coronary intervention versus coronary artery bypass graft in patients with left main coronary artery disease. CABG: coronary artery bypass graft; DES: drug-eluting stent; LIMA: left internal mammary artery; PCI: percutaneous coronary intervention. [Display omitted]

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel’s antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug–drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95–1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70–2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76–1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83–1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68–3.52]) and Chinese (AHR 2.06 [95%CI 1.63–2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06–2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.