Relationship of adhesion molecules (ICAM-1 and E-selectin) with ABO blood groups in patients hospitalized with acute myocardial infarction.

Objectives: Adhesion molecules, sICAM-1 and sE-selectin appear to have a major role in the pathogenesis of coronary artery disease (CAD). The focus of this study was to investigate the relationship of sICAM-1 and sE-selectin with ABO blood groups in Pakistani patients hospitalized with acute myocardial infarction (AMI). Methods: In a case-control study, 116 patients of acute myocardial infarction (AMI) and 116 healthy controls (age range for both: 30 years to 70 years; both males and females) were randomly selected from the Aga Khan University and National Institute of Cardiovascular Diseases, Karachi with informed consent. The blood samples were obtained and analyzed for ABO blood groups and serum levels of sICAM-1 and sE-selectin using kit methods. Statistical tests including independent sample t-test and Two-way ANOVA were used to study the association of these adhesion molecules with blood groups in AMI patients and healthy controls. Duration of the study was from July 2021 to June 30, 2023. Results: Mean serum levels of sICAM-1 were significantly higher in AMI patients compared to healthy controls (342±159 mg/dl vs. 227±104 mg/dl; p-value<0.001). Similarly, serum levels of sE-selectin were also significantly higher in AMI patients compared to healthy controls (53.6±26.9 mg/dl vs. 40.7± mg/dl; p-value<0.001). Moreover, mean concentrations of sICAM-1 and sE-selectin for the interaction between subject type (cases and control) and blood groups were statistically significant (p-value = 0.007 and p-value = 0.035, respectively). Conclusion: There is an association of adhesion molecules, sICAM-1 and sE-selectin with ABO blood groups in Pakistani patients hospitalized with AMI.

Assessment of post-myocardial infarction lipid levels and management: Results from a tertiary care hospital of Pakistan.

BACKGROUND: Lipid treatment practices and levels in post-acute myocardial infarction (AMI) patients, which are crucial for secondary prevention. AIM: To evaluate the lipid treatment practices and lipid levels in post-myocardial infarction (MI) patients at a tertiary care hospital in Pakistan. METHODS: In this cross-sectional study, we analyzed patients who had experienced their first AMI event in the past 3 years. We assessed fasting and non-fasting lipid profiles, reviewed statin therapy prescriptions, and examined patient compliance. The recommended dose was defined as rosuvastatin ≥ 20 mg or atorvastatin ≥ 40 mg, with target total cholesterol levels set at < 160 mg/dL and target low-density lipoprotein cholesterol (LDL-C) at < 55 mg/dL. RESULTS: Among 195 patients, 71.3% were male, and the mean age was 57.1 ± 10.2 years. The median duration since AMI was 36 (interquartile range: 10-48) months and 60% were diagnosed with ST-segment elevation MI. Only 13.8% of patients were advised to undergo lipid profile testing after AMI, 88.7% of patients were on the recommended statin therapy, and 91.8% of patients were compliant with statin therapy. Only 11.5% had LDL-C within the target range and 71.7% had total cholesterol within the target range. Hospital admission in the past 12 months was reported by 14.4%, and the re-admission rate was significantly higher among non-compliant patients (37.5% vs 5.6%). Subsequent AMI event rate was also significantly higher among non-compliant patients (43.8% vs 11.7%). CONCLUSION: Our study highlights that while most post-AMI patients received the recommended minimum statin therapy dose, the inadequate practice of lipid assessment may compromise therapy optimization and raise the risk of subsequent events.

School Health Education Program in Pakistan (SHEPP): findings from a feasibility trial in pre-adolescent school children from a lower middle-income country.

BACKGROUND: The school environment plays an essential role in promoting health education and physical activity for children and adolescents. We aim to assess the feasibility of threefold health education program in children and its potential efficacy on physical activity and diet and cardiometabolic risk factors including blood pressure, body mass index (BMI), and waist circumference. METHODS: The SHEPP was a parallel group feasibility intervention trial conducted in two schools over 23 months. All children aged 9-11 years enrolled in the schools were included. The SHEPP intervention comprised of health education on healthy lifestyle and physical activity sessions for children, training of teachers, and awareness sessions for parents conducted over 10 months. One school received the intervention of SHEPP while the other school continued routine activity. The primary outcome was the feasibility of SHEPP in terms of recruitment, retention, and treatment fidelity. Secondary outcomes were physical activity levels, dietary intake (of fruits and vegetables), and cardiometabolic risk factors (blood pressure, BMI, and waist circumference (WC)). RESULTS: A total of 1280 preadolescent children were assessed for eligibility and 1191 were found eligible. The overall recruitment n (%) was 982/1191(82.5%) with 505(51.4) from SHEPP intervention school and 477(48.6) in routine activity school. The overall retention rate n (%) at 10-month follow-up was 912/982(92.8), with 465/505(92) in SHEPP intervention school and 447/477(93.7) in routine activity school. In treatment fidelity, 132/144(92) %). Physical activity sessions and all (100%) health education sessions were conducted for each of the twelve classes. Mean (SD) Seven-day Physical activity increased by 134 (196) min in the SHEPP intervention school v 29.8(177) in the routine activity school (P value < 0.001) from baseline to follow-up. Overall, there was an increase in vegetable intake (> 3 serving /day) in SHEPP intervention school of 5.5 to 21.4% from baseline to follow-up compared to 7.5 to 14.9% in routine activity school. The mean change (SD) in systolic blood pressure was 1.3(12) mmHg, 2.2(19.0) mm Hg in in diastolic blood pressure, - 0.09(5.4) kg/m2 in BMI and 6.2 cm in waist circumference in the intervention arm versus - 3.4(11.1) mm Hg in SBP, - 4.3(9.9) mm Hg in DBP, - 0.04((4.6) kg/m2 in BMI, and 3.8 cm in WC in the control arm. CONCLUSION: We found that intervention using SHEPP is feasible in schools and may help children to adopt a healthy lifestyle as they age by increasing physical activity. However, the potentially beneficial effect on diet, MI, and BP needs further exploration and a longer follow-up, more specifically at the juncture of teenage and adulthood. TRIAL REGISTRATION: NCT03303287.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Association of the BB genotype of the ABO gene with the risk of acute myocardial infarction in hospital-based study.

Objectives: The ABO gene locus has been identified to be associated with myocardial infarction in patients with coronary heart disease. The primary focus of this hospital-based study was to explore the relationship of ABO blood groups and ABO genotypes with acute myocardial infarction (AMI) in Karachi, Pakistan. Methods: In a comparative cross-sectional study, an equal number of adult AMI patients and healthy controls (n=275 in each group; age range 30-70 years, both males and females) were recruited from the Aga Khan University and NICVD, Karachi, with informed consent. The blood samples were analyzed for ABO blood groups and other biomarkers. PCR followed by RFLP techniques were employed for determining the ABO genotypes. Multinomial regression was used to evaluate the association of genotypes with the risk of AMI. Results: Thirteen different combinations of ABO genotypes were observed while the O2O2 and A2A2 genotypes were not detected. No significant association based on the distribution of blood groups A, B, O and AB among AMI patients and healthy individuals was observed. The odds of AMI were 3.32 times in subjects with BB genotype as compared to subjects with OO genotypes after adjustment of age, gender, body mass index, heart rate, total cholesterol, and waist circumference [AOR (95% CI) =3.32 (1.36-8.08), p-value =0.008]. Conclusion: Our hospital-based study indicates that ABO genotype BB was significantly associated with the risk of AMI. This harmful effect of the BB genotype could have a possible relationship with AMI's development in the Pakistani population.

Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Cardiovascular disease, mortality, and their associations with modifiable risk factors in a multi-national South Asia cohort: a PURE substudy.

AIM: To examine the incidence of cardiovascular disease (CVD), of death, and the comparative effects of 12 common modifiable risk factors for both outcomes in South Asia. METHODS AND RESULTS: Prospective study of 33 583 individuals 35-70 years of age from India, Bangladesh, or Pakistan. Mean follow-up period was 11 years. Age and sex adjusted incidence of a CVD event and mortality rates were calculated for the overall cohort, by urban or rural location, by sex, and by country. For each outcome, mutually adjusted population attributable fractions (PAFs) were calculated in 32 611 individuals without prior CVD to compare risks associated with four metabolic risk factors (hypertension, diabetes, abdominal obesity, high non-HDL cholesterol), four behavioural risk factors (tobacco use, alcohol use, diet quality, physical activity), education, household air pollution, strength, and depression. Hazard ratios were calculated using Cox regression models, and average PAFs were calculated for each risk factor or groups of risk factors. Cardiovascular disease was the most common cause of death (35.5%) in South Asia. Rural areas had a higher incidence of CVD (5.41 vs. 4.73 per 1000 person-years) and a higher mortality rate (10.27 vs. 6.56 per 1000 person-years) compared with urban areas. Males had a higher incidence of CVD (6.42 vs. 3.91 per 1000 person-years) and a higher mortality rate (10.66 vs. 6.85 per 1000 person-years) compared with females. Between countries, CVD incidence was highest in Bangladesh, while the mortality rate was highest in Pakistan. The modifiable risk factors studied contributed to approximately 64% of the PAF for CVD and 69% of the PAF for death. Largest PAFs for CVD were attributable to hypertension (13.1%), high non-HDL cholesterol (11.1%), diabetes (8.9%), low education (7.7%), abdominal obesity (6.9%), and household air pollution (6.1%). Largest PAFs for death were attributable to low education (18.9%), low strength (14.6%), poor diet (6.4%), diabetes (5.8%), tobacco use (5.8%), and hypertension (5.5%). CONCLUSION: In South Asia, both CVD and deaths are highest in rural areas and among men. Reducing CVD and premature mortality in the region will require investment in policies that target a broad range of health determinants.

Personal and household PM2.5 and black carbon exposure measures and respiratory symptoms in 8 low- and middle-income countries.

BACKGROUND: Household air pollution (HAP) from cooking with solid fuels has been associated with adverse respiratory effects, but most studies use surveys of fuel use to define HAP exposure, rather than on actual air pollution exposure measurements. OBJECTIVE: To examine associations between household and personal fine particulate matter (PM2.5) and black carbon (BC) measures and respiratory symptoms. METHODS: As part of the Prospective Urban and Rural Epidemiology Air Pollution study, we analyzed 48-h household and personal PM2.5 and BC measurements for 870 individuals using different cooking fuels from 62 communities in 8 countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Self-reported respiratory symptoms were collected after monitoring. Associations between PM2.5 and BC exposures and respiratory symptoms were examined using logistic regression models, controlling for individual, household, and community covariates. RESULTS: The median (interquartile range) of household and personal PM2.5 was 73.5 (119.1) and 65.3 (91.5) µg/m3, and for household and personal BC was 3.4 (8.3) and 2.5 (4.9) x10-5 m-1, respectively. We observed associations between household PM2.5 and wheeze (OR: 1.25; 95%CI: 1.07, 1.46), cough (OR: 1.22; 95%CI: 1.06, 1.39), and sputum (OR: 1.26; 95%CI: 1.10, 1.44), as well as exposure to household BC and wheeze (OR: 1.20; 95%CI: 1.03, 1.39) and sputum (OR: 1.20; 95%CI: 1.05, 1.36), per IQR increase. We observed associations between personal PM2.5 and wheeze (OR: 1.23; 95%CI: 1.00, 1.50) and sputum (OR: 1.19; 95%CI: 1.00, 1.41). For household PM2.5 and BC, associations were generally stronger for females compared to males. Models using an indicator variable of solid versus clean fuels resulted in larger OR estimates with less precision. CONCLUSIONS: We used measurements of household and personal air pollution for individuals using different cooking fuels and documented strong associations with respiratory symptoms.

The Anti-Coronavirus Therapies (ACT) Trials: Design, Baseline Characteristics, and Challenges.

Background: Effective treatments for COVID-19 are urgently needed, but conducting randomized trials during the pandemic has been challenging. Methods: The Anti-Coronavirus Therapy (ACT) trials are parallel factorial international trials that aimed to enroll 3500 outpatients and 2500 inpatients with symptomatic COVID-19. The outpatient trial is evaluating colchicine vs usual care, and aspirin vs usual care. The primary outcome for the colchicine randomization is hospitalization or death, and for the aspirin randomization, it is major thrombosis, hospitalization, or death. The inpatient trial is evaluating colchicine vs usual care, and the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily vs usual care. The primary outcome for the colchicine randomization is need for high-flow oxygen, need for mechanical ventilation, or death, and for the rivaroxaban plus aspirin randomization, it is major thrombotic events, need for high-flow oxygen, need for mechanical ventilation, or death. Results: At the completion of enrollment on February 10, 2022, the outpatient trial had enrolled 3917 patients, and the inpatient trial had enrolled 2611 patients. Challenges encountered included lack of preliminary data about the interventions under evaluation, uncertainties related to the expected event rates, delays in regulatory and ethics approvals, and in obtaining study interventions, as well as the changing pattern of the COVID-19 pandemic. Conclusions: The ACT trials will determine the efficacy of anti-inflammatory therapy with colchicine, and antithrombotic therapy with aspirin given alone or in combination with rivaroxaban, across the spectrum of mild, moderate, and severe COVID-19. Lessons learned from the conduct of these trials will inform planning of future trials.

Contexte: Il est urgent de mettre au point des traitements efficaces contre la COVID-19, mais il n'est pas facile de réaliser des essais à répartition aléatoire dans un contexte pandémique. Méthodologie: Les essais internationaux factoriels ACT (Anti-Coronavirus Therapy) avaient un objectif d'inscription de 3 500 patients externes et de 2 500 patients hospitalisés présentant une COVID-19 symptomatique. L'essai mené auprès de patients externes visait à évaluer la colchicine par rapport aux soins habituels, et l'aspirine par rapport aux soins habituels. Le paramètre d'évaluation principal au terme de la répartition aléatoire des patients était l'hospitalisation ou le décès dans le groupe traité par la colchicine, et la thrombose majeure, l'hospitalisation ou le décès dans le groupe traité par l'aspirine. L'essai mené auprès de patients hospitalisés visant à évaluer la colchicine par rapport aux soins habituels, et un traitement associant le rivaroxaban à 2,5 mg deux fois par jour et l'aspirine à 100 mg une fois par jour par rapport aux soins habituels. Le paramètre d'évaluation principal au terme de la répartition aléatoire des patients était le recours à l'oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par la colchicine, et la survenue de manifestations thrombotiques majeures, le recours à l'oxygénothérapie à haut débit ou à la ventilation mécanique ou le décès dans le groupe traité par l'association rivaroxaban-aspirine. Résultats: À la fin de la période d'inscription, le 10 février 2022, 3 917 patients externes et 2 611 patients hospitalisés formaient la population des essais. Certains aspects se sont révélés problématiques, notamment le manque de données préliminaires sur les interventions à évaluer, les incertitudes liées aux taux d'événements prévus, les retards touchant les approbations réglementaires et éthiques et les interventions de recherche, de même que l'évolution de la pandémie de COVID-19. Conclusions: Les essais ACT détermineront l'efficacité du traitement anti-inflammatoire par la colchicine et du traitement antithrombotique par l'aspirine, administrée seule ou en association avec le rivaroxaban, contre la COVID-19 légère, modérée ou sévère. Les leçons tirées de ces essais orienteront la planification d'essais ultérieurs.

Multinational prediction of household and personal exposure to fine particulate matter (PM2.5) in the PURE cohort study.

INTRODUCTION: Use of polluting cooking fuels generates household air pollution (HAP) containing health-damaging levels of fine particulate matter (PM2.5). Many global epidemiological studies rely on categorical HAP exposure indicators, which are poor surrogates of measured PM2.5 levels. To quantitatively characterize HAP levels on a large scale, a multinational measurement campaign was leveraged to develop household and personal PM2.5 exposure models. METHODS: The Prospective Urban and Rural Epidemiology (PURE)-AIR study included 48-hour monitoring of PM2.5 kitchen concentrations (n = 2,365) and male and/or female PM2.5 exposure monitoring (n = 910) in a subset of households in Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania and Zimbabwe. PURE-AIR measurements were combined with survey data on cooking environment characteristics in hierarchical Bayesian log-linear regression models. Model performance was evaluated using leave-one-out cross validation. Predictive models were applied to survey data from the larger PURE cohort (22,480 households; 33,554 individuals) to quantitatively estimate PM2.5 exposures. RESULTS: The final models explained half (R2 = 54%) of the variation in kitchen PM2.5 measurements (root mean square error (RMSE) (log scale):2.22) and personal measurements (R2 = 48%; RMSE (log scale):2.08). Primary cooking fuel type, heating fuel type, country and season were highly predictive of PM2.5 kitchen concentrations. Average national PM2.5 kitchen concentrations varied nearly 3-fold among households primarily cooking with gas (20 µg/m3 (Chile); 55 µg/m3 (China)) and 12-fold among households primarily cooking with wood (36 µg/m3 (Chile)); 427 µg/m3 (Pakistan)). Average PM2.5 kitchen concentration, heating fuel type, season and secondhand smoke exposure were significant predictors of personal exposures. Modeled average PM2.5 female exposures were lower than male exposures in upper-middle/high-income countries (India, China, Colombia, Chile). CONCLUSION: Using survey data to estimate PM2.5 exposures on a multinational scale can cost-effectively scale up quantitative HAP measurements for disease burden assessments. The modeled PM2.5 exposures can be used in future epidemiological studies and inform policies targeting HAP reduction.

Measuring and predicting personal and household Black Carbon levels from 88 communities in eight countries.

Black Carbon (BC) is an important component of household air pollution (HAP) in low- and middle- income countries (LMICs), but levels and drivers of exposure are poorly understood. As part of the Prospective Urban and Rural Epidemiological (PURE) study, we analyzed 48-hour BC measurements for 1187 individual and 2242 household samples from 88 communities in 8 LMICs (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Light absorbance (10-5 m-1) of collected PM2.5 filters, a proxy for BC concentrations, was calculated via an image-based reflectance method. Surveys of household/personal characteristics and behaviors were collected after monitoring. The geometric mean (GM) of personal and household BC measures was 2.4 (3.3) and 3.5 (3.9)·10-5 m-1, respectively. The correlation between BC and PM2.5 was r = 0.76 for personal and r = 0.82 for household measures. A gradient of increasing BC concentrations was observed for cooking fuels: BC increased 53% (95%CI: 30, 79) for coal, 142% (95%CI: 117, 169) for wood, and 190% (95%CI: 149, 238) for other biomass, compared to gas. Each hour of cooking was associated with an increase in household (5%, 95%CI: 3, 7) and personal (5%, 95%CI: 2, 8) BC; having a window in the kitchen was associated with a decrease in household (-38%, 95%CI: -45, -30) and personal (-31%, 95%CI: -44, -15) BC; and cooking on a mud stove, compared to a clean stove, was associated with an increase in household (125%, 95%CI: 96, 160) and personal (117%, 95%CI: 71, 117) BC. Male participants only had slightly lower personal BC (-0.6%, 95%CI: -1, 0.0) compared to females. In multivariate models, we were able to explain 46-60% of household BC variation and 33-54% of personal BC variation. These data and models provide new information on exposure to BC in LMICs, which can be incorporated into future exposure assessments, health research, and policy surrounding HAP and BC.

Sex-stratified outcomes of primary percutaneous coronary intervention: A tertiary care experience.

BACKGROUND: ST elevation myocardial infarction (STEMI) is an acute cardiac manifestation that requires immediate revascularization preferably through primary percutaneous coronary intervention (PCI). This study aims to describe gender stratified outcomes and epidemiological profile of STEMI patients undergoing treatment at a tertiary care hospital in Karachi, Pakistan. METHODS: A 5-year, retrospective analysis of hospital records was undertaken on confirmed STEMI patients admitted between 2010 and 2014, undergoing primary PCI. Information was retrieved on demographic variables, risk factors, total ischemia time, door to balloon time, angiographic findings, and treatment strategy and in-hospital outcomes. RESULTS: A total of 603 patients were available for analysis. Mean age of the participants was 58 ± 11 years, with 78.6% being males. The most common risk factors were hypertension (48.1%), diabetes (37%), and smoking (22.2%). Gender stratified analysis revealed poorer clinical presentation and prolonged ischemia time among women when compared to men (410 vs. 310 min, respectively). Total in-hospital mortality was 9.6% and was higher in women (19.3%), patients with non-anterior infarction (12%), Killip class >2 (39%), advanced age (14.6%), and multi-vessel disease (12%). CONCLUSION: Our study describes the common risk factors and treatment outcomes for STEMI patients undergoing primary PCI at a tertiary care hospital in Karachi. In-hospital mortality and total ischemia time were higher among women compared to men in our study. Moreover, the risk profile, treatment related complications, and outcomes were poorer in women compared to men. We suggest further research to investigate the effect of prolonged ischemia time on long-term clinical outcomes.

Global variations in the prevalence, treatment, and impact of atrial fibrillation in a multi-national cohort of 153 152 middle-aged individuals.

AIMS: To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine antithrombotic use and clinical outcomes. METHODS AND RESULTS: Baseline ECGs were collected in 153 152 middle-aged participants (ages 35-70 years) to document AF in two community-based studies, spanning 20 countries. Medication use and clinical outcome data (mean follow-up of 7.4 years) were available in one cohort. Cross-sectional analyses were performed to document the prevalence of AF and medication use, and associations between AF and clinical events were examined prospectively. Mean age of participants was 52.1 years, and 57.7% were female. Age and sex-standardized prevalence of AF varied 12-fold between regions; with the highest in North America, Europe, China, and Southeast Asia (270-360 cases per 100 000 persons); and lowest in the Middle East, Africa, and South Asia (30-60 cases per 100 000 persons) (P < 0.001). Compared with low-income countries (LICs), AF prevalence was 7-fold higher in middle-income countries (MICs) and 11-fold higher in high-income countries (HICs) (P < 0.001). Differences in AF prevalence remained significant after adjusting for traditional AF risk factors. In LICs/MICs, 24% of participants with AF and a CHADS2 score ≥1 received antithrombotic therapy, compared with 85% in HICs. AF was associated with an increased risk of stroke [hazard ratio (HR) 2.29; 95% confidence interval (CI) 1.49-3.52] and death (HR 2.97; 95% CI 2.25-3.93); with similar rates in different countries grouped by income level. CONCLUSIONS: Large variations in AF prevalence occur in different regions and countries grouped by income level, but this is only partially explained by traditional AF risk factors. Antithrombotic therapy is infrequently used in poorer countries despite the high risk of stroke associated with AF.

Availability and affordability of medicines and cardiovascular outcomes in 21 high-income, middle-income and low-income countries.

OBJECTIVES: We aimed to examine the relationship between access to medicine for cardiovascular disease (CVD) and major adverse cardiovascular events (MACEs) among people at high risk of CVD in high-income countries (HICs), upper and lower middle-income countries (UMICs, LMICs) and low-income countries (LICs) participating in the Prospective Urban Rural Epidemiology (PURE) study. METHODS: We defined high CVD risk as the presence of any of the following: hypertension, coronary artery disease, stroke, smoker, diabetes or age >55 years. Availability and affordability of blood pressure lowering drugs, antiplatelets and statins were obtained from pharmacies. Participants were categorised: group 1-all three drug types were available and affordable, group 2-all three drugs were available but not affordable and group 3-all three drugs were not available. We used multivariable Cox proportional hazard models with nested clustering at country and community levels, adjusting for comorbidities, sociodemographic and economic factors. RESULTS: Of 163 466 participants, there were 93 200 with high CVD risk from 21 countries (mean age 54.7, 49% female). Of these, 44.9% were from group 1, 29.4% from group 2 and 25.7% from group 3. Compared with participants from group 1, the risk of MACEs was higher among participants in group 2 (HR 1.19, 95% CI 1.07 to 1.31), and among participants from group 3 (HR 1.25, 95% CI 1.08 to 1.50). CONCLUSION: Lower availability and affordability of essential CVD medicines were associated with higher risk of MACEs and mortality. Improving access to CVD medicines should be a key part of the strategy to lower CVD globally.

Household and personal air pollution exposure measurements from 120 communities in eight countries: results from the PURE-AIR study.

BACKGROUND: Approximately 2·8 billion people are exposed to household air pollution from cooking with polluting fuels. Few monitoring studies have systematically measured health-damaging air pollutant (ie, fine particulate matter [PM2·5] and black carbon) concentrations from a wide range of cooking fuels across diverse populations. This multinational study aimed to assess the magnitude of kitchen concentrations and personal exposures to PM2·5 and black carbon in rural communities with a wide range of cooking environments. METHODS: As part of the Prospective Urban and Rural Epidemiological (PURE) cohort, the PURE-AIR study was done in 120 rural communities in eight countries (Bangladesh, Chile, China, Colombia, India, Pakistan, Tanzania, and Zimbabwe). Data were collected from 2541 households and from 998 individuals (442 men and 556 women). Gravimetric (or filter-based) 48 h kitchen and personal PM2·5 measurements were collected. Light absorbance (10-5m-1) of the PM2·5 filters, a proxy for black carbon concentrations, was calculated via an image-based reflectance method. Surveys of household characteristics and cooking patterns were collected before and after the 48 h monitoring period. FINDINGS: Monitoring of household air pollution for the PURE-AIR study was done from June, 2017, to September, 2019. A mean PM2·5 kitchen concentration gradient emerged across primary cooking fuels: gas (45 µg/m3 [95% CI 43-48]), electricity (53 µg/m3 [47-60]), coal (68 µg/m3 [61-77]), charcoal (92 µg/m3 [58-146]), agricultural or crop waste (106 µg/m3 [91-125]), wood (109 µg/m3 [102-118]), animal dung (224 µg/m3 [197-254]), and shrubs or grass (276 µg/m3 [223-342]). Among households cooking primarily with wood, average PM2·5 concentrations varied ten-fold (range: 40-380 µg/m3). Fuel stacking was prevalent (981 [39%] of 2541 households); using wood as a primary cooking fuel with clean secondary cooking fuels (eg, gas) was associated with 50% lower PM2·5 and black carbon concentrations than using only wood as a primary cooking fuel. Similar average PM2·5 personal exposures between women (67 µg/m3 [95% CI 62-72]) and men (62 [58-67]) were observed. Nearly equivalent average personal exposure to kitchen exposure ratios were observed for PM2·5 (0·79 [95% 0·71-0·88] for men and 0·82 [0·74-0·91] for women) and black carbon (0·64 [0·45-0·92] for men and 0·68 [0·46-1·02] for women). INTERPRETATION: Using clean primary fuels substantially lowers kitchen PM2·5 concentrations. Importantly, average kitchen and personal PM2·5 measurements for all primary fuel types exceeded WHO's Interim Target-1 (35 µg/m3 annual average), highlighting the need for comprehensive pollution mitigation strategies. FUNDING: Canadian Institutes for Health Research, National Institutes of Health.

Prevalence of Cardiac Risk Factors and Attitude toward Self-Risk Assessment among Cardiac Care Givers.

OBJECTIVE: Aim of this survey was to assess the prevalence of cardiovascular diseases (CVD) risk factors and attitude toward self-risk assessment among cardiac care physicians (who did not have CVD history), at a tertiary care cardiac center in Pakistan. DESIGN: In this survey we included cardiac care givers who had a minimum of 1 year of working experience in a cardiac care center. PARTICIPANTS: Participants with self-reported history of established diagnosis of CVD were excluded. Face-to-face interviews were conducted with the help of a structured questionnaire which consisted of demographic information, data regarding established CVD risk factors, self-awareness, and attitude toward CVD risk assessment. RESULTS: A total of 126 participants were interviewed, out of which 20.6% (26) were females and mean age was 36.1±7.6 years. The most prevalent CVD risk factor was family history of CVD (33.3%) followed by smoking (14.3%) and 23.8% had body mass index of ≥27.5 kg/m2. Around 23% of the participants did not know their cholesterol levels, similarly more than 74% were not aware of their high-density lipoproteins levels. More than 76% had never assessed their CVD risk and more than 37% don't know or don't have any opinion about their own CVD risk. CONCLUSIONS: The present study reveals low prevalence of conventional cardiac risk factors and marginally higher tendency of modifiable risk factors, such as smoking and obesity, among the cardiac physicians. A large proportion of these cardiac physicians have not yet assessed their CVD risk.

School health education program in Pakistan (SHEPP)-a threefold health education feasibility trial in schoolchildren from a lower-middle-income country.

BACKGROUND: The school environment plays an essential role in promoting health education and physical activity for children and adolescence, and they are more likely to adapt it into their adulthood. School health education program has been endorsed and emphasized by the World Health Organization has not been implemented in true spirit in Pakistan yet. We aim to test feasibility of threefold health education program in children and its potential efficacy on physical activity and diet and cardiometabolic risk factors by including BP, BMI, and waist circumference. METHODS: It is a parallel-group feasibility intervention trial. It is being conducted in two schools from lower to middle-income areas, at different locations but having the same school curriculum under the Aga Khan Education Service, Pakistan (AKESP). All children aged 9-11 years enrolled from the schools mentioned above were included. Children with any physical disability were excluded. One school received threefold intervention (focused on children, parents, and teachers) of school health education program in Pakistan (SHEPP) while the other school continued routine activity. Intervention of SHEPP is directed towards educating children, parents, and teachers about healthy behaviors. Children will receive interactive educational sessions and specially designed physical activity sessions. A 3-h health education session focusing on same healthy behaviors as for children will be conducted for both parents and teachers. Primary outcome is feasibility of SHEPP in terms of recruitment, retention, and treatment fidelity. Secondary outcomes are physical activity levels, dietary intake (of fruits, vegetable), and cardiometabolic risk factors (blood pressure, BMI, and waist circumference (WC)). The total number of children recruited were 982 (82.5 %); 505 from school A and 477 from school B and 496 (50.5) were boys. CONCLUSION: SHEPP is a unique health education program for children as it focuses on children while involving the parents and teachers in the behavior change process. If found feasible and demonstrating potential efficacy on physical activity, dietary behaviors, and cardiometabolic parameters, we will be able to replicate this on a larger scale in public sector schools also. TRIAL REGISTRATION: NCT03303287.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Higher DNA methylation of ABO gene promoter is associated with acute myocardial infarction in a hospital-based population in Karachi.

OBJECTIVE: To find out if there is any relationship of methylation status of ABO gene promoter with the risk of acute myocardial infarction (AMI) in a hospital-based Pakistani population in Karachi, Pakistan. METHODS: A case control study comprising of 39 adult AMI patients (both males and females; age range 30-70 years) and 39 normal healthy controls (both males and females and similar age range) nested in a large study (to see the relationship of ABO genotypes with AMI) was designed to investigate the methylation status of ABO gene promoter and its association with AMI. The study was carried out at the Aga Khan University, Karachi during July 2018 to June 2019. DNA isolated from samples of AMI patients and normal healthy controls were converted into bisulphite DNA using a kit method. Methylation specific polymerase chain reaction was carried out to determine the methylation status of ABO gene promoter in both cases and controls. Logistic regression was used to find out any association between increased methylation status of ABO gene promoter and risk of AMI. RESULTS: A significantly higher percentage of DNA methylation of the ABO gene promoter was observed in AMI patients as compared to normal healthy controls (82.1% vs. 35.9%; p value <0.001). This higher methylation status of ABO gene promoter was associated with AMI and the odds of AMI in this population were more than 6-fold in subjects with methylated gene promoter compared to those with unmethylated gene promoter after adjusting with age and waist circumference [AOR (95% CI) = 6.27 (1.76-22.3); p value = 0.005]. CONCLUSION: The ABO gene promoter's hypermethylation appears to be increasing the risk of AMI in a hospital-based Pakistani population in Karachi, Pakistan.

Ten years risk assessment of atherosclerotic cardiovascular disease using Astro-CHARM and pooled cohort equation in a south Asian sub-population.

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVD) are on the rise in low and middle-income countries attributed to modern sedentary lifestyle and dietary habits. This has led to the need of assessment of the burden of at-risk population so that prevention measures can be developed. The objective of this study was to assess ten years risk assessment of ASCVD using Astro-CHARM and Pooled Cohort Equation (PCE) in a South Asian sub-population. METHODS: A total of 386 residents of all six districts of Karachi with no ASCVD were enrolled in the study through an exponential non-discriminative referral snowball sampling technique. The inclusion criteria consisted of age 40 years or above and either gender. Study participants were enrolled after obtaining informed written consent and those study participants who were found to have either congenital heart disease or valvular heart diseases or ischemic heart disease were excluded from the study based on initial screening. For the calculation of 10 years risk of ACVD based on Astro-CHARM and PCE, the variables were obtained including medical history and coronary artery calcium and C-reactive protein measurements. RESULTS: Mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the Astro-CHARM was 13.98 ± 8.01%, while mean estimated 10-year risk of fatal or non-fatal myocardial infarction or stroke as per the PCE was 22.26 ± 14.01%. Based on Astro-CHARM, 11.14% of the study participants were labeled as having high risk, while PCE estimated 20.73% of study participants as having high risk of ASCVD. CONCLUSION: Despite the fact that our findings showed substantial differences in ten-year risk of ASCVD between Astro-CHARM and PCE, both calculators can be used to develop a new population and specific risk estimators for this South Asian sub-population. Our study provides the first step towards developing a risk assessment guided decision-making protocol for primary prevention of ASCVD in this population.