A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The ...PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease.
The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40–75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle—eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985.
Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study—3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5–92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio HR 0·66, 95% CI 0·55–0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49–0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51–1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33–0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up—ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group.
Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs.
Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.
Abstract
Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; ...weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004–2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4–20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR = 0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR = 0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity.
This study aimed to evaluate the superiority of anthropometric indices compared to others for predicting ischemic heart disease (IHD) or cardiometabolic risk factors. This study was a cross-sectional ...analysis of the Pars Cohort Study data. In total, 9229 Valashahr inhabitants aged 40–75 were included in the analysis. The area under the receiver operating characteristic curve (AUC) analyses was used to compare the predictive accuracy of four anthropometric measures, including body mass index, waist to height ratio (WHtR), waist to hip ratio (WHR), and waist circumference (WC). IHD prevalence was 10.4% in our sample. The prevalence of diabetes mellitus (DM), hypertension, dyslipidemia, and metabolic syndrome was 12.7%, 29.2%, 58.4%, and 22.3%, respectively. All anthropometric indices had poor to good accuracy in predicting IHD risk factors, with AUCs ranging between 0.580 and 0.818. WHR was the most accurate measure for predicting IHD in both genders. All indexes had a better accuracy for predicting DM, dyslipidemia, and metabolic syndrome (MetS) in males than in females. To conclude, anthropometric measures, especially WC and WHtR, are recommended for predicting metabolic syndrome in primary prevention settings. These simple indices could help physicians find those who need further evaluation for MetS.
Environmental exposures account for a growing proportion of global mortality. Large cohort studies are needed to characterize the independent impact of environmental exposures on mortality in ...low-income settings. We collected data on individual and environmental risk factors for a multiethnic cohort of 50,045 individuals in a low-income region in Iran. Environmental risk factors included: ambient fine particular matter air pollution; household fuel use and ventilation; proximity to traffic; distance to percutaneous coronary intervention (PCI) center; socioeconomic environment; population density; local land use; and nighttime light exposure. We developed a spatial survival model to estimate the independent associations between these environmental exposures and all-cause and cardiovascular mortality. Several environmental factors demonstrated associations with mortality after adjusting for individual risk factors. Ambient fine particulate matter air pollution predicted all-cause mortality (per mug/m.sup.3, HR 1.20, 95% CI 1.07, 1.36) and cardiovascular mortality (HR 1.17, 95% CI 0.98, 1.39). Biomass fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.23, 95% CI 0.99, 1.53) and cardiovascular mortality (HR 1.36, 95% CI 0.99, 1.87). Kerosene fuel use without chimney predicted all-cause mortality (reference = gas, HR 1.09, 95% CI 0.97, 1.23) and cardiovascular mortality (HR 1.19, 95% CI 1.01, 1.41). Distance to PCI center predicted all-cause mortality (per 10km, HR 1.01, 95% CI 1.004, 1.022) and cardiovascular mortality (HR 1.02, 95% CI 1.004, 1.031). Additionally, proximity to traffic predicted all-cause mortality (HR 1.13, 95% CI 1.01, 1.27). In a separate validation cohort, the multivariable model effectively predicted both all-cause mortality (AUC 0.76) and cardiovascular mortality (AUC 0.81). Population attributable fractions demonstrated a high mortality burden attributable to environmental exposures.
Coronary artery disease (CAD) is a universal public health challenge, more prominently so in the low- and middle-income countries. In this study, we aimed to determine prevalence and trends of CAD ...risk factors in patients with documented CAD and to determine their effects on the age of CAD diagnosis.
We conducted a registry-based, serial cross-sectional study using the coronary angiography data bank of the Tehran Heart Center. Adult patients who had obstructive (> 50% stenosis) CAD were included in the study. The prevalence and 11-year trends of conventional CAD risk factors were analyzed by sex and age, and their adjusted effects on the age of CAD diagnosis were calculated.
From January 2005 to December 2015, data for 90,094 patients were included in this analysis. A total of 61,684 (68.5%) were men and 28,410 (31.5%) were women. Men were younger at diagnosis than women, with a mean age of 60.1 in men and 63.2 in women (p < 0.001), and had fewer risk factors at the time of diagnosis. Mean age at diagnosis had an overall increasing trend during the study period. Increasing trend was seen in body-mass index, hypertension prevalence, diabetes mellitus. All lipid profile components (total cholesterol, low-density lipoprotein cholesterol, triglycerides, and high-density lipoprotein cholesterol) decreased over time. Of particular interest, opium consumption was associated with 2.2 year earlier age of CAD diagnosis.
The major results of this study (lower age of CAD diagnosis in men, lower age of diagnosis associated with most risk factors, and lower prevalence of serum lipids over time) were expected. A prominent finding of this study is confirming opium use was associated with a much younger age of CAD onset, even after adjusting for all other risk factors. In addition to recommendations for control of the traditional risk factors, spreading information about the potential adverse effect of opium use, which has only recently been associated with higher risk of CAD, may be necessary.
Little is known about the predictors of left ventricular ejection fraction (LVEF) -an important predictor of mortality- after primary percutaneous coronary intervention (PCI) in low- and ...middle-income countries.
In a prospective cohort study at Imam Ali hospital, Kermanshah, Iran, we enrolled consecutive ST-elevation myocardial infarction (STEMI) patients treated with primary PCI (2016-2018) and followed them up to one year. LVEF levels were measured by echocardiography, at baseline and one-year follow-up. Determinants of preserved/improved LVEF were assessed using multi-variable logistic regression models.
Of 803 patients (mean age 58.53±11.7 years, 20.5% women), baseline LVEF levels of ≤35% were reported in 44%, 35- 50% in 40%, and ≥50% in 16% of patients. The mean ± SD of LVEF increased from 38.13%±9.2% at baseline to 41.49%±9.5% at follow-up. LVEF was preserved/improved in 629 (78.3%) patients. Adjusted ORs (95% CIs) for predictors of preserved/improved LVEF showed positive associations with creatinine clearance, 1.01 (1.00-1.02) and adherence to clopidogrel, 2.01 (1.33-3.02); and inverse associations with history of myocardial infarction (MI), 0.44 (0.25-0.78); creatine kinase MB (CK-MB), 0.997 (0.996- 0.999); door-balloon time (3
vs. 1
tertile), 0.62 (0.39-0.98); number of diseased vessels (2 and 3 vs. 1: 0.63 (0.41-0.99) and 0.58 (0.36-0.93), respectively); and baseline LVEF (35-50% and ≥50% vs. ≤35%: 0.45 (0.28-0.71) and 0.19 (0.11-0.34), respectively).
Adherence to clopidogrel, short door-balloon time, high creatinine clearance, and lower baseline LVEF were associated with preserved/improved LVEF, while history of MI, high CK-MB, and multi-vessel disease were predictors of reduced LVEF. Long-term drug adherence should be considered for LVEF improvement in low- and middle-income countries.
Background: Abdominal obesity is associated with increased risk of myocardial infarction and death events. Thus, obtaining data on the status of abdominal obesity is important in risk factor ...assessment and prevention of non-communicable diseases. This study aimed to evaluate the validity of using pictograms to classify abdominal obesity indices (waist circumference WC, waist-hip ratio WHR, and waist-height ratio WHtR) into normal and at-risk categories and determine the effects of demographic characteristics on this validity. Methods: This cross-sectional study used data from Pars Cohort Study (PCS). Participants chose the most similar pictogram scores to their body size at 15, 30 years, and current age. Optimal normal/at-risk cut-off values for pictograms were calculated using sensitivity/specificity plots. Receiver operating characteristic curves were used to evaluate the validity of pictograms. Validity measures were analyzed across different subgroups of demographic characteristics. Results: A total of 9263 participants (46% males) were included in the study. The estimated area under the curves were 84% for WC, 77% for WHR, and 89% for WHtR in males, and 84% for WC, 73% for WHR, and 90% for WHtR in females. Optimal pictogram cutoffs to classify central obesity for WC, WHR, and WHtR were 4, 4, and 5 in males and 4, 4, and 6 in females, respectively. The majority of demographic characteristics were not associated with the validity of pictograms. Conclusion: Using pictograms to determine normal and at-risk categories of abdominal obesity indices is valid among adult population with a wide range of demographic characteristics. However, the results need to be interpreted with caution in those with a positive history of weight fluctuation.
ObjectivesTo examine the causes of premature mortality (<70 years) and associated risk factors in the Golestan Cohort Study.DesignProspective.SettingThe Golestan Cohort Study in northeastern ...Iran.Participants50 045 people aged 40 or more participated in this population-based study from baseline (2004–2008) to August 2017, with over 99% success follow-up rate.Main outcome measuresThe top causes of premature death, HR and their 95% CI and population attributable fraction (PAF) for risk factors.ResultsAfter 444 168 person-years of follow-up (median of 10 years), 6347 deaths were reported, of which 4018 (63.3%) occurred prematurely. Ischaemic heart disease (IHD) accounted for 33.9% of premature death, followed by stroke (14.0%), road injuries (4.7%), stomach cancer (4.6%) and oesophageal cancer (4.6%). Significant risk/protective factors were: wealth score (HR for highest vs lowest quintile: 0.57, PAF for lowest four quintiles vs top quintile: 28%), physical activity (highest vs lowest tertile: 0.67, lowest two tertiles vs top tertile: 22%), hypertension (1.50, 19%), opium use (1.69, 14%), education (middle school or higher vs illiterate: 0.84, illiterate or primary vs middle school or higher: 13%), tobacco use (1.38, 11%), diabetes (2.39, 8%) and vegetable/fruit consumption (highest vs lowest tertile: 0.87, lowest two tertiles vs top tertile: 8%). Collectively, these factors accounted for 76% of PAF in men and 69% in women.ConclusionIHD and stroke are the leading causes of premature mortality in the Golestan Cohort Study. Enhancing socioeconomic status and physical activity, reducing opium and tobacco use, increasing vegetable/fruit consumption and controlling hypertension and diabetes are recommended to reduce premature deaths.
Background: Considerable variability in survival rate after ST-segment elevation myocardial infarction (STEMI) is present and outcomes remain suboptimal, especially in low- and middle-income ...contraries. This study aimed to investigate predictors of 30- day mortality after STEMI, including reperfusion therapy, in a tertiary hospital in western Iran. Methods: In this registry-based cohort study (2016–2019), we investigated reperfusion therapies – primary percutaneous coronary intervention (PPCI), pharmaco-invasive (thrombolysis followed by angiography/percutaneous coronary intervention), and thrombolysis alone – used in Imam-Ali hospital, the only hospital with a PPCI capability in the Kermanshah Province. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs), using Cox proportional-hazard models, to investigate the potential predictors of 30-day mortality including reperfusion therapy, admission types (direct admission/referral from non-PPCI-capable hospitals), demographic variables, coronary risk factors, vital signs on admission, medical history, and laboratory tests. Results: Data of 2428 STEMI patients (mean age: 60.73; 22.9% female) were available. Reperfusion therapy was performed in 84% of patients (58% PPCI, 10% pharmaco-invasive, 16% thrombolysis alone). Only 17% of the referred patients had received thrombolysis at non-PPCI-capable hospitals. Among patients with thrombolysis, only 38.2% underwent coronary angiography/ percutaneous coronary intervention. The independent predictors of mortality were: no reperfusion therapy (HR: 2.01, 95% CI: 1.36–2.97), referral from non-PPCI-capable hospitals (1.73, 1.22–2.46), age (1.03, 1.01–1.04), glomerular filtration rate (0.97, 0.96–0.97), heart rate>100 bpm (1.94, 1.22–3.08), and systolic blood pressure<100 mm Hg (4.92, 3.43–7.04). Mortality was lower with the pharmaco-invasive approach, although statistically non-significant, than other reperfusion therapies. Conclusion: Reperfusion therapy, admission types, age, glomerular filtration rate, heart rate, and blood pressure were independently associated with 30-day mortality. Using a comprehensive STEMI network to increase reperfusion therapy, especially pharmaco-invasive therapy, is recommended.
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