Omar Rahman

Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey

BACKGROUND Although most cardiovascular disease occurs in low-income and middle-income countries, little is known about the use of effective secondary prevention medications in these communities. We aimed to assess use of proven effective secondary preventive drugs (antiplatelet drugs, β blockers, angiotensin-converting-enzyme [ACE] inhibitors or angiotensin-receptor blockers [ARBs], and statins) in individuals with a history of coronary heart disease or stroke. METHODS In the Prospective Urban Rural Epidemiological (PURE) study, we recruited individuals aged 35-70 years from rural and urban communities in countries at various stages of economic development. We assessed rates of previous cardiovascular disease (coronary heart disease or stroke) and use of proven effective secondary preventive drugs and blood-pressure-lowering drugs with standardised questionnaires, which were completed by telephone interviews, household visits, or on patients presentation to clinics. We report estimates of drug use at national, community, and individual levels. FINDINGS We enrolled 153,996 adults from 628 urban and rural communities in countries with incomes classified as high (three countries), upper-middle (seven), lower-middle (three), or low (four) between January, 2003, and December, 2009. 5650 participants had a self-reported coronary heart disease event (median 5·0 years previously [IQR 2·0-10·0]) and 2292 had stroke (4·0 years previously [2·0-8·0]). Overall, few individuals with cardiovascular disease took antiplatelet drugs (25·3%), β blockers (17·4%), ACE inhibitors or ARBs (19·5%), or statins (14·6%). Use was highest in high-income countries (antiplatelet drugs 62·0%, β blockers 40·0%, ACE inhibitors or ARBs 49·8%, and statins 66·5%), lowest in low-income countries (8·8%, 9·7%, 5·2%, and 3·3%, respectively), and decreased in line with reduction of country economic status (p(trend)<0·0001 for every drug type). Fewest patients received no drugs in high-income countries (11·2%), compared with 45·1% in upper middle-income countries, 69·3% in lower middle-income countries, and 80·2% in low-income countries. Drug use was higher in urban than rural areas (antiplatelet drugs 28·7% urban vs 21·3% rural, β blockers 23·5%vs 15·6%, ACE inhibitors or ARBs 22·8%vs 15·5%, and statins 19·9%vs 11·6%; all p<0·0001), with greatest variation in poorest countries (p(interaction)<0·0001 for urban vs rural differences by country economic status). Country-level factors (eg, economic status) affected rates of drug use more than did individual-level factors (eg, age, sex, education, smoking status, body-mass index, and hypertension and diabetes statuses). INTERPRETATION Because use of secondary prevention medications is low worldwide-especially in low-income countries and rural areas-systematic approaches are needed to improve the long-term use of basic, inexpensive, and effective drugs. FUNDING Full funding sources listed at end of paper (see Acknowledgments).

Prognostic value of grip strength: findings from the Prospective Urban Rural Epidemiology (PURE) study.

BACKGROUND Reduced muscular strength, as measured by grip strength, has been associated with an increased risk of all-cause and cardiovascular mortality. Grip strength is appealing as a simple, quick, and inexpensive means of stratifying an individuals risk of cardiovascular death. However, the prognostic value of grip strength with respect to the number and range of populations and confounders is unknown. The aim of this study was to assess the independent prognostic importance of grip strength measurement in socioculturally and economically diverse countries. METHODS The Prospective Urban-Rural Epidemiology (PURE) study is a large, longitudinal population study done in 17 countries of varying incomes and sociocultural settings. We enrolled an unbiased sample of households, which were eligible if at least one household member was aged 35-70 years and if household members intended to stay at that address for another 4 years. Participants were assessed for grip strength, measured using a Jamar dynamometer. During a median follow-up of 4.0 years (IQR 2.9-5.1), we assessed all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, myocardial infarction, stroke, diabetes, cancer, pneumonia, hospital admission for pneumonia or chronic obstructive pulmonary disease (COPD), hospital admission for any respiratory disease (including COPD, asthma, tuberculosis, and pneumonia), injury due to fall, and fracture. Study outcomes were adjudicated using source documents by a local investigator, and a subset were adjudicated centrally. FINDINGS Between January, 2003, and December, 2009, a total of 142,861 participants were enrolled in the PURE study, of whom 139,691 with known vital status were included in the analysis. During a median follow-up of 4.0 years (IQR 2.9-5.1), 3379 (2%) of 139,691 participants died. After adjustment, the association between grip strength and each outcome, with the exceptions of cancer and hospital admission due to respiratory illness, was similar across country-income strata. Grip strength was inversely associated with all-cause mortality (hazard ratio per 5 kg reduction in grip strength 1.16, 95% CI 1.13-1.20; p<0.0001), cardiovascular mortality (1.17, 1.11-1.24; p<0.0001), non-cardiovascular mortality (1.17, 1.12-1.21; p<0.0001), myocardial infarction (1.07, 1.02-1.11; p=0.002), and stroke (1.09, 1.05-1.15; p<0.0001). Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure. We found no significant association between grip strength and incident diabetes, risk of hospital admission for pneumonia or COPD, injury from fall, or fracture. In high-income countries, the risk of cancer and grip strength were positively associated (0.916, 0.880-0.953; p<0.0001), but this association was not found in middle-income and low-income countries. INTERPRETATION This study suggests that measurement of grip strength is a simple, inexpensive risk-stratifying method for all-cause death, cardiovascular death, and cardiovascular disease. Further research is needed to identify determinants of muscular strength and to test whether improvement in strength reduces mortality and cardiovascular disease. FUNDING Full funding sources listed at end of paper (see Acknowledgments).

Cardiovascular Risk and Events in 17 Low-, Middle-, and High-Income Countries

BACKGROUND More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown. METHODS We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years. RESULTS The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001). CONCLUSIONS Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).

Prevalence of a Healthy Lifestyle Among Individuals With Cardiovascular Disease in High-, Middle- and Low-Income Countries The Prospective Urban Rural Epidemiology (PURE) Study

IMPORTANCE Little is known about adoption of healthy lifestyle behaviors among individuals with a coronary heart disease (CHD) or stroke event in communities across a range of countries worldwide. OBJECTIVE To examine the prevalence of avoidance or cessation of smoking, eating a healthy diet, and undertaking regular physical activities by individuals with a CHD or stroke event. DESIGN, SETTING, AND PARTICIPANTS Prospective Urban Rural Epidemiology (PURE) was a large, prospective cohort study that used an epidemiological survey of 153,996 adults, aged 35 to 70 years, from 628 urban and rural communities in 3 high-income countries (HIC), 7 upper-middle-income countries (UMIC), 3 lower-middle-income countries (LMIC), and 4 low-income countries (LIC), who were enrolled between January 2003 and December 2009. MAIN OUTCOME MEASURES Smoking status (current, former, never), level of exercise (low, <600 metabolic equivalent task [MET]-min/wk; moderate, 600-3000 MET-min/wk; high, >3000 MET-min/wk), and diet (classified by the Food Frequency Questionnaire and defined using the Alternative Healthy Eating Index). RESULTS Among 7519 individuals with self-reported CHD (past event: median, 5.0 [interquartile range {IQR}, 2.0-10.0] years ago) or stroke (past event: median, 4.0 [IQR, 2.0-8.0] years ago), 18.5% (95% CI, 17.6%-19.4%) continued to smoke; only 35.1% (95% CI, 29.6%-41.0%) undertook high levels of work- or leisure-related physical activity, and 39.0% (95% CI, 30.0%-48.7%) had healthy diets; 14.3% (95% CI, 11.7%-17.3%) did not undertake any of the 3 healthy lifestyle behaviors and 4.3% (95% CI, 3.1%-5.8%) had all 3. Overall, 52.5% (95% CI, 50.7%-54.3%) quit smoking (by income country classification: 74.9% [95% CI, 71.1%-78.6%] in HIC; 56.5% [95% CI, 53.4%-58.6%] in UMIC; 42.6% [95% CI, 39.6%-45.6%] in LMIC; and 38.1% [95% CI, 33.1%-43.2%] in LIC). Levels of physical activity increased with increasing country income but this trend was not statistically significant. The lowest prevalence of eating healthy diets was in LIC (25.8%; 95% CI, 13.0%-44.8%) compared with LMIC (43.2%; 95% CI, 30.0%-57.4%), UMIC (45.1%, 95% CI, 30.9%-60.1%), and HIC (43.4%, 95% CI, 21.0%-68.7%). CONCLUSION AND RELEVANCE Among a sample of patients with a CHD or stroke event from countries with varying income levels, the prevalence of healthy lifestyle behaviors was low, with even lower levels in poorer countries.

Availability and affordability of cardiovascular disease medicines and their effect on use in high-income, middle-income, and low-income countries: an analysis of the PURE study data

BACKGROUND WHO has targeted that medicines to prevent recurrent cardiovascular disease be available in 80% of communities and used by 50% of eligible individuals by 2025. We have previously reported that use of these medicines is very low, but now aim to assess how such low use relates to their lack of availability or poor affordability. METHODS We analysed information about availability and costs of cardiovascular disease medicines (aspirin, β blockers, angiotensin-converting enzyme inhibitors, and statins) in pharmacies gathered from 596 communities in 18 countries participating in the Prospective Urban Rural Epidemiology (PURE) study. Medicines were considered available if present at the pharmacy when surveyed, and affordable if their combined cost was less than 20% of household capacity-to-pay. We compared results from high-income, upper middle-income, lower middle-income, and low-income countries. Data from India were presented separately given its large, generic pharmaceutical industry. FINDINGS Communities were recruited between Jan 1, 2003, and Dec 31, 2013. All four cardiovascular disease medicines were available in 61 (95%) of 64 urban and 27 (90%) of 30 rural communities in high-income countries, 53 (80%) of 66 urban and 43 (73%) of 59 rural communities in upper middle-income countries, 69 (62%) of 111 urban and 42 (37%) of 114 rural communities in lower middle-income countries, eight (25%) of 32 urban and one (3%) of 30 rural communities in low-income countries (excluding India), and 34 (89%) of 38 urban and 42 (81%) of 52 rural communities in India. The four cardiovascular disease medicines were potentially unaffordable for 0·14% of households in high-income countries (14 of 9934 households), 25% of upper middle-income countries (6299 of 24,776), 33% of lower middle-income countries (13,253 of 40,023), 60% of low-income countries (excluding India; 1976 of 3312), and 59% households in India (9939 of 16,874). In low-income and middle-income countries, patients with previous cardiovascular disease were less likely to use all four medicines if fewer than four were available (odds ratio [OR] 0·16, 95% CI 0·04-0·57). In communities in which all four medicines were available, patients were less likely to use medicines if the household potentially could not afford them (0·16, 0·04-0·55). INTERPRETATION Secondary prevention medicines are unavailable and unaffordable for a large proportion of communities and households in upper middle-income, lower middle-income, and low-income countries, which have very low use of these medicines. Improvements to the availability and affordability of key medicines is likely to enhance their use and help towards achieving WHOs targets of 50% use of key medicines by 2025. FUNDING Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Availability, affordability, and consumption of fruits and vegetables in 18 countries across income levels: findings from the Prospective Urban Rural Epidemiology (PURE) study

BACKGROUND Several international guidelines recommend the consumption of two servings of fruits and three servings of vegetables per day, but their intake is thought to be low worldwide. We aimed to determine the extent to which such low intake is related to availability and affordability. METHODS We assessed fruit and vegetable consumption using data from country-specific, validated semi-quantitative food frequency questionnaires in the Prospective Urban Rural Epidemiology (PURE) study, which enrolled participants from communities in 18 countries between Jan 1, 2003, and Dec 31, 2013. We documented household income data from participants in these communities; we also recorded the diversity and non-sale prices of fruits and vegetables from grocery stores and market places between Jan 1, 2009, and Dec 31, 2013. We determined the cost of fruits and vegetables relative to income per household member. Linear random effects models, adjusting for the clustering of households within communities, were used to assess mean fruit and vegetable intake by their relative cost. FINDINGS Of 143 305 participants who reported plausible energy intake in the food frequency questionnaire, mean fruit and vegetable intake was 3·76 servings (95% CI 3·66-3·86) per day. Mean daily consumption was 2·14 servings (1·93-2·36) in low-income countries (LICs), 3·17 servings (2·99-3·35) in lower-middle-income countries (LMICs), 4·31 servings (4·09-4·53) in upper-middle-income countries (UMICs), and 5·42 servings (5·13-5·71) in high-income countries (HICs). In 130 402 participants who had household income data available, the cost of two servings of fruits and three servings of vegetables per day per individual accounted for 51·97% (95% CI 46·06-57·88) of household income in LICs, 18·10% (14·53-21·68) in LMICs, 15·87% (11·51-20·23) in UMICs, and 1·85% (-3·90 to 7·59) in HICs (ptrend=0·0001). In all regions, a higher percentage of income to meet the guidelines was required in rural areas than in urban areas (p<0·0001 for each pairwise comparison). Fruit and vegetable consumption among individuals decreased as the relative cost increased (ptrend=0·00040). INTERPRETATION The consumption of fruit and vegetables is low worldwide, particularly in LICs, and this is associated with low affordability. Policies worldwide should enhance the availability and affordability of fruits and vegetables. FUNDING Population Health Research Institute, the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, AstraZeneca (Canada), Sanofi-Aventis (France and Canada), Boehringer Ingelheim (Germany and Canada), Servier, GlaxoSmithKline, Novartis, King Pharma, and national or local organisations in participating countries.

Reference ranges of handgrip strength from 125,462 healthy adults in 21 countries: a prospective urban rural epidemiologic (PURE) study

The measurement of handgrip strength (HGS) has prognostic value with respect to all‐cause mortality, cardiovascular mortality and cardiovascular disease, and is an important part of the evaluation of frailty. Published reference ranges for HGS are mostly derived from Caucasian populations in high‐income countries. There is a paucity of information on normative HGS values in non‐Caucasian populations from low‐ or middle‐income countries. The objective of this study was to develop reference HGS ranges for healthy adults from a broad range of ethnicities and socioeconomically diverse geographic regions.

Variations in Diabetes Prevalence in Low-, Middle-, and High-Income Countries: Results From the Prospective Urban and Rural Epidemiological Study

OBJECTIVE The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors. RESEARCH DESIGN AND METHODS The prevalence of diabetes, defined as self-reported or fasting glycemia ≥7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses. RESULTS Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 [95% CI 1.28–1.31]), male sex (1.19 [1.13–1.25]), urban residency (1.24 [1.11–1.38]), low versus high education level (1.10 [1.02–1.19]), low versus high physical activity (1.28 [1.20–1.38]), family history of diabetes (3.15 [3.00–3.31]), higher waist-to-hip ratio (highest vs. lowest quartile; 3.63 [3.33–3.96]), and BMI (≥35 vs. <25 kg/m2; 2.76 [2.52–3.03]). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher- versus lower-income country groups (P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%). CONCLUSIONS Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.

Socioeconomic factors and use of secondary preventive therapies for cardiovascular diseases in South Asia: The PURE study

Objective The purpose of this study was to determine the association of socioeconomic factors on use of cardioprotective medicines in known coronary heart disease (CHD) or stroke in South Asia. Methods We enrolled 33,423 subjects aged 35–70 years (women 56%, rural 53%, low education 51%, low household wealth 25%) in 150 communities in India, Pakistan and Bangladesh during 2003–2009. Information regarding socioeconomic status, disease conditions and treatments was recorded. We studied influence of rural location, educational status and household wealth on use of drug therapies. Odds ratios (ORs) and 95% confidence intervals were calculated. Results CHD was reported in 683 (2.0%), stroke 316 (0.9%), and CHD/stroke in 970 (2.9%). Median duration since diagnosis was four years. Participants with CHD/stroke were older with greater prevalence of smoking, overweight, hypertension and diabetes (p < 0.01). In patients with CHD, stroke and CHD/stroke, respectively, use (%) of antiplatelets was 11.6, 3.8 and 9.3, beta-blockers 11.9, 7.0 and 10.4, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers 6.4, 1.9 and 5.3 and statins 4.8, 0.6 and 3.5. In CHD/stroke patients any one of these drugs was used in 18.1%, any two in 7.2%, any three in 2.8% and none in 81.5%. Details of drug dose were not available. Use of drugs was significantly lower in rural low education and low wealth index participants (all p < 0.01). Low wealth index participants had the lowest use of these therapies with no attenuation after multiple adjustments. Conclusion The use of secondary preventive drug therapies in patients with known CHD or stroke in South Asia is low with over 80% receiving none of the effective drug treatments. Low household wealth is the most important determinant.

Tobacco control environment: cross-sectional survey of policy implementation, social unacceptability, knowledge of tobacco health harms and relationship to quit ratio in 17 low-income, middle-income and high-income countries

Objectives This study examines in a cross-sectional study ‘the tobacco control environment’ including tobacco policy implementation and its association with quit ratio. Setting 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Communitys Health (EPOCH) study from 2009 to 2014. Participants Community audits and surveys of adults (35–70 years, n=12 953). Primary and secondary outcome measures Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models. Results Average tobacco control policy score was greater in communities from HIC. Overall 56.1% (306/545) of communities had >2 outlets selling cigarettes and in 28.6% (154/539) there was access to cheap cigarettes (<5cents/cigarette) (3.2% (3/93) in HIC, 0% UMIC, 52.6% (90/171) LMIC and 40.4% (61/151) in LIC). Effective bans (no tobacco advertisements) were in 63.0% (341/541) of communities (81.7% HIC, 52.8% UMIC, 65.1% LMIC and 57.6% LIC). In 70.4% (379/538) of communities, >80% of participants disapproved youth smoking (95.7% HIC, 57.6% UMIC, 76.3% LMIC and 58.9% LIC). The average knowledge score was >80% in 48.4% of communities (94.6% HIC, 53.6% UMIC, 31.8% LMIC and 35.1% LIC). Summary scores of policy implementation, social unacceptability and knowledge were positively and significantly associated with quit ratio and the associations varied by gender, for example, communities in the highest quintile of the combined scores had 5.0 times the quit ratio in men (Odds ratio (OR) 5·0, 95% CI 3.4 to 7.4) and 4.1 times the quit ratio in women (OR 4.1, 95% CI 2.4 to 7.1). Conclusions This study suggests that more focus is needed on ensuring the tobacco control policy is actually implemented, particularly in LMICs. The gender-related differences in associations of policy, social unacceptability and knowledge suggest that different strategies to promoting quitting may need to be implemented in men compared to women.