Associations of Antibiotics, Hormonal Therapies, Oral Contraceptives, and Long-Term NSAIDS With Inflammatory Bowel Disease: Results From the Prospective Urban Rural Epidemiology (PURE) Study.

BACKGROUND & AIMS: Several medications have been suspected to contribute to the etiology of inflammatory bowel disease (IBD). This study assessed the association between medication use and the risk of developing IBD using the Prospective Urban Rural Epidemiology cohort. METHODS: This was a prospective cohort study of 133,137 individuals between the ages of 20 and 80 from 24 countries. Country-specific validated questionnaires documented baseline and follow-up medication use. Participants were followed up prospectively at least every 3 years. The main outcome was the development of IBD, including Crohn's disease (CD) and ulcerative colitis (UC). Short-term (baseline but not follow-up use) and long-term use (baseline and subsequent follow-up use) were evaluated. Results are presented as adjusted odds ratios (aORs) with 95% CIs. RESULTS: During a median follow-up period of 11.0 years (interquartile range, 9.2-12.2 y), there were 571 incident IBD cases (143 CD and 428 UC). Incident IBD was associated significantly with baseline antibiotic (aOR, 2.81; 95% CI, 1.67-4.73; P = .0001) and hormonal medication use (aOR, 4.43; 95% CI, 1.78-11.01; P = .001). Among females, previous or current oral contraceptive use also was associated with IBD development (aOR, 2.17; 95% CI, 1.70-2.77; P < .001). Nonsteroidal anti-inflammatory drug users also were observed to have increased odds of IBD (aOR, 1.80; 95% CI, 1.23-2.64; P = .002), which was driven by long-term use (aOR, 5.58; 95% CI, 2.26-13.80; P < .001). All significant results were consistent in direction for CD and UC with low heterogeneity. CONCLUSIONS: Antibiotics, hormonal medications, oral contraceptives, and long-term nonsteroidal anti-inflammatory drug use were associated with increased odds of incident IBD after adjustment for covariates.

Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study.

BACKGROUND: Some studies, mainly from high-income countries (HICs), report that women receive less care (investigations and treatments) for cardiovascular disease than do men and might have a higher risk of death. However, very few studies systematically report risk factors, use of primary or secondary prevention medications, incidence of cardiovascular disease, or death in populations drawn from the community. Given that most cardiovascular disease occurs in low-income and middle-income countries (LMICs), there is a need for comprehensive information comparing treatments and outcomes between women and men in HICs, middle-income countries, and low-income countries from community-based population studies. METHODS: In the Prospective Urban Rural Epidemiological study (PURE), individuals aged 35-70 years from urban and rural communities in 27 countries were considered for inclusion. We recorded information on participants' sociodemographic characteristics, risk factors, medication use, cardiac investigations, and interventions. 168 490 participants who enrolled in the first two of the three phases of PURE were followed up prospectively for incident cardiovascular disease and death. FINDINGS: From Jan 6, 2005 to May 6, 2019, 202 072 individuals were recruited to the study. The mean age of women included in the study was 50·8 (SD 9·9) years compared with 51·7 (10) years for men. Participants were followed up for a median of 9·5 (IQR 8·5-10·9) years. Women had a lower cardiovascular disease risk factor burden using two different risk scores (INTERHEART and Framingham). Primary prevention strategies, such as adoption of several healthy lifestyle behaviours and use of proven medicines, were more frequent in women than men. Incidence of cardiovascular disease (4·1 [95% CI 4·0-4·2] for women vs 6·4 [6·2-6·6] for men per 1000 person-years; adjusted hazard ratio [aHR] 0·75 [95% CI 0·72-0·79]) and all-cause death (4·5 [95% CI 4·4-4·7] for women vs 7·4 [7·2-7·7] for men per 1000 person-years; aHR 0·62 [95% CI 0·60-0·65]) were also lower in women. By contrast, secondary prevention treatments, cardiac investigations, and coronary revascularisation were less frequent in women than men with coronary artery disease in all groups of countries. Despite this, women had lower risk of recurrent cardiovascular disease events (20·0 [95% CI 18·2-21·7] versus 27·7 [95% CI 25·6-29·8] per 1000 person-years in men, adjusted hazard ratio 0·73 [95% CI 0·64-0·83]) and women had lower 30-day mortality after a new cardiovascular disease event compared with men (22% in women versus 28% in men; p<0·0001). Differences between women and men in treatments and outcomes were more marked in LMICs with little differences in HICs in those with or without previous cardiovascular disease. INTERPRETATION: Treatments for cardiovascular disease are more common in women than men in primary prevention, but the reverse is seen in secondary prevention. However, consistently better outcomes are observed in women than in men, both in those with and without previous cardiovascular disease. Improving cardiovascular disease prevention and treatment, especially in LMICs, should be vigorously pursued in both women and men. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Association of estimated sleep duration and naps with mortality and cardiovascular events: a study of 116 632 people from 21 countries.

AIMS: To investigate the association of estimated total daily sleep duration and daytime nap duration with deaths and major cardiovascular events. METHODS AND RESULTS: We estimated the durations of total daily sleep and daytime naps based on the amount of time in bed and self-reported napping time and examined the associations between them and the composite outcome of deaths and major cardiovascular events in 116 632 participants from seven regions. After a median follow-up of 7.8 years, we recorded 4381 deaths and 4365 major cardiovascular events. It showed both shorter (≤6 h/day) and longer (>8 h/day) estimated total sleep durations were associated with an increased risk of the composite outcome when adjusted for age and sex. After adjustment for demographic characteristics, lifestyle behaviours and health status, a J-shaped association was observed. Compared with sleeping 6-8 h/day, those who slept ≤6 h/day had a non-significant trend for increased risk of the composite outcome [hazard ratio (HR), 1.09; 95% confidence interval, 0.99-1.20]. As estimated sleep duration increased, we also noticed a significant trend for a greater risk of the composite outcome [HR of 1.05 (0.99-1.12), 1.17 (1.09-1.25), and 1.41 (1.30-1.53) for 8-9 h/day, 9-10 h/day, and >10 h/day, Ptrend < 0.0001, respectively]. The results were similar for each of all-cause mortality and major cardiovascular events. Daytime nap duration was associated with an increased risk of the composite events in those with over 6 h of nocturnal sleep duration, but not in shorter nocturnal sleepers (≤6 h). CONCLUSION: Estimated total sleep duration of 6-8 h per day is associated with the lowest risk of deaths and major cardiovascular events. Daytime napping is associated with increased risks of major cardiovascular events and deaths in those with >6 h of nighttime sleep but not in those sleeping ≤6 h/night.

Trend of salt intake measured by 24-hour urine collection samples among Iranian adults population between 1998 and 2013: The Isfahan salt study.

BACKGROUND AND AIM: Few population-based studies conducted in the Eastern Mediterranean region assessed salt intake by the measurement of 24-h sodium urine excretion (24-hUNa). The current study aimed to assess the trend of mean salt intake in Iranian adults between 1998 and 2013. METHODS AND RESULTS: These cross-sectional studies were performed on 564, 157, 509 and 837 randomly selected healthy adults aged >18 years from Isfahan city, Iran, in 1998, 2001, 2007 and 2013, respectively. BP was measured using a mercury sphygmomanometer according to a standard protocol. Single 24-h urine was collected to assess 24-hUNa as a surrogate of salt intake, and 24-h urinary K (24-hUK). The estimated trend of salt intake was 9.5, 9.7, 9.6 and 10.2 g/day in total population (P < 0.001). The increase in salt intake between 1998 and 2013 was significant only in men, (P < 0.001). The risk of pre-hypertension was 21% and 18% significantly greater in the highest quartiles of UNa/UK after adjustment for potential confounders in 2001 and 2013, respectively, [OR (95% CI): 1.21 (1.03-1.64) and 1.18 (1.02-1.38), respectively]. CONCLUSIONS: This population-based study indicated that mean salt intake was about two times of recommendation in Isfahan city, Iran, and suggest that it would be essential to implement a salt reduction strategy program in Iranian population. Longitudinal national studies with larger samples examining the trend of salt intake are warranted.

Associations of urinary sodium excretion with cardiovascular events in individuals with and without hypertension: a pooled analysis of data from four studies.

BACKGROUND: Several studies reported a U-shaped association between urinary sodium excretion and cardiovascular disease events and mortality. Whether these associations vary between those individuals with and without hypertension is uncertain. We aimed to explore whether the association between sodium intake and cardiovascular disease events and all-cause mortality is modified by hypertension status. METHODS: In this pooled analysis, we studied 133,118 individuals (63,559 with hypertension and 69,559 without hypertension), median age of 55 years (IQR 45-63), from 49 countries in four large prospective studies and estimated 24-h urinary sodium excretion (as group-level measure of intake). We related this to the composite outcome of death and major cardiovascular disease events over a median of 4.2 years (IQR 3.0-5.0) and blood pressure. FINDINGS: Increased sodium intake was associated with greater increases in systolic blood pressure in individuals with hypertension (2.08 mm Hg change per g sodium increase) compared with individuals without hypertension (1.22 mm Hg change per g; pinteraction<0.0001). In those individuals with hypertension (6835 events), sodium excretion of 7 g/day or more (7060 [11%] of population with hypertension: hazard ratio [HR] 1.23 [95% CI 1.11-1.37]; p<0.0001) and less than 3 g/day (7006 [11%] of population with hypertension: 1.34 [1.23-1.47]; p<0.0001) were both associated with increased risk compared with sodium excretion of 4-5 g/day (reference 25% of the population with hypertension). In those individuals without hypertension (3021 events), compared with 4-5 g/day (18,508 [27%] of the population without hypertension), higher sodium excretion was not associated with risk of the primary composite outcome (≥ 7 g/day in 6271 [9%] of the population without hypertension; HR 0.90 [95% CI 0.76-1.08]; p=0.2547), whereas an excretion of less than 3 g/day was associated with a significantly increased risk (7547 [11%] of the population without hypertension; HR 1.26 [95% CI 1.10-1.45]; p=0.0009). INTERPRETATION: Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension. These data suggest that lowering sodium intake is best targeted at populations with hypertension who consume high sodium diets. FUNDING: Full funding sources listed at end of paper (see Acknowledgments).

Wealth and cardiovascular health: a cross-sectional study of wealth-related inequalities in the awareness, treatment and control of hypertension in high-, middle- and low-income countries.

BACKGROUND: Effective policies to control hypertension require an understanding of its distribution in the population and the barriers people face along the pathway from detection through to treatment and control. One key factor is household wealth, which may enable or limit a household's ability to access health care services and adequately control such a chronic condition. This study aims to describe the scale and patterns of wealth-related inequalities in the awareness, treatment and control of hypertension in 21 countries using baseline data from the Prospective Urban and Rural Epidemiology study. METHODS: A cross-section of 163,397 adults aged 35 to 70 years were recruited from 661 urban and rural communities in selected low-, middle- and high-income countries (complete data for this analysis from 151,619 participants). Using blood pressure measurements, self-reported health and household data, concentration indices adjusted for age, sex and urban-rural location, we estimate the magnitude of wealth-related inequalities in the levels of hypertension awareness, treatment, and control in each of the 21 country samples. RESULTS: Overall, the magnitude of wealth-related inequalities in hypertension awareness, treatment, and control was observed to be higher in poorer than in richer countries. In poorer countries, levels of hypertension awareness and treatment tended to be higher among wealthier households; while a similar pro-rich distribution was observed for hypertension control in countries at all levels of economic development. In some countries, hypertension awareness was greater among the poor (Sweden, Argentina, Poland), as was treatment (Sweden, Poland) and control (Sweden). CONCLUSION: Inequality in hypertension management outcomes decreased as countries became richer, but the considerable variation in patterns of wealth-related inequality - even among countries at similar levels of economic development - underscores the importance of health systems in improving hypertension management for all. These findings show that some, but not all, countries, including those with limited resources, have been able to achieve more equitable management of hypertension; and strategies must be tailored to national contexts to achieve optimal impact at population level.

The environmental profile of a community's health: a cross-sectional study on tobacco marketing in 16 countries.

OBJECTIVE: To examine and compare tobacco marketing in 16 countries while the Framework Convention on Tobacco Control requires parties to implement a comprehensive ban on such marketing. METHODS: Between 2009 and 2012, a kilometre-long walk was completed by trained investigators in 462 communities across 16 countries to collect data on tobacco marketing. We interviewed community members about their exposure to traditional and non-traditional marketing in the previous six months. To examine differences in marketing between urban and rural communities and between high-, middle- and low-income countries, we used multilevel regression models controlling for potential confounders. FINDINGS: Compared with high-income countries, the number of tobacco advertisements observed was 81 times higher in low-income countries (incidence rate ratio, IRR: 80.98; 95% confidence interval, CI: 4.15-1578.42) and the number of tobacco outlets was 2.5 times higher in both low- and lower-middle-income countries (IRR: 2.58; 95% CI: 1.17-5.67 and IRR: 2.52; CI: 1.23-5.17, respectively). Of the 11,842 interviewees, 1184 (10%) reported seeing at least five types of tobacco marketing. Self-reported exposure to at least one type of traditional marketing was 10 times higher in low-income countries than in high-income countries (odds ratio, OR: 9.77; 95% CI: 1.24-76.77). For almost all measures, marketing exposure was significantly lower in the rural communities than in the urban communities. CONCLUSION: Despite global legislation to limit tobacco marketing, it appears ubiquitous. The frequency and type of tobacco marketing varies on the national level by income group and by community type, appearing to be greatest in low-income countries and urban communities.

Associations of the glycaemic index and the glycaemic load with risk of type 2 diabetes in 127 594 people from 20 countries (PURE): a prospective cohort study.

BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets. METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs). FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030). INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes. FUNDING: Full funding sources are listed at the end of the Article.

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.

Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries.

IMPORTANCE: Hypertension is the most important preventable cause of morbidity and mortality globally, yet there are relatively few data collected using standardized methods. OBJECTIVE: To examine hypertension prevalence, awareness, treatment, and control in participants at baseline in the Prospective Urban Rural Epidemiology (PURE) study. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study of 153,996 adults (complete data for this analysis on 142,042) aged 35 to 70 years, recruited between January 2003 and December 2009. Participants were from 628 communities in 3 high-income countries (HIC), 10 upper-middle-income and low-middle-income countries (UMIC and LMIC), and 4 low-income countries (LIC). MAIN OUTCOMES AND MEASURES: Hypertension was defined as individuals with self-reported treated hypertension or with an average of 2 blood pressure measurements of at least 140/90 mm Hg using an automated digital device. Awareness was based on self-reports, treatment was based on the regular use of blood pressure-lowering medications, and control was defined as individuals with blood pressure lower than 140/90 mm Hg. RESULTS: Among the 142,042 participants, 57,840 (40.8%; 95% CI, 40.5%-41.0%) had hypertension and 26,877 (46.5%; 95% CI, 46.1%-46.9%) were aware of the diagnosis. Of those who were aware of the diagnosis, the majority (23,510 [87.5%; 95% CI, 87.1%-87.9%] of those who were aware) were receiving pharmacological treatments, but only a minority of those receiving treatment were controlled (7634 [32.5%; 95% CI, 31.9%-33.1%]). Overall, 30.8%, 95% CI, 30.2%-31.4% of treated patients were taking 2 or more types of blood pressure-lowering medications. The percentages aware (49.0% [95% CI, 47.8%-50.3%] in HICs, 52.5% [95% CI, 51.8%-53.2%] in UMICs, 43.6% [95% CI, 42.9%-44.2%] in LMICs, and 40.8% [95% CI, 39.9%-41.8%] in LICs) and treated (46.7% [95% CI, 45.5%-47.9%] in HICs, 48.3%, [95% CI, 47.6%-49.1%] in UMICs, 36.9%, [95% CI, 36.3%-37.6%] in LMICs, and 31.7% [95% CI, 30.8%-32.6%] in LICs) were lower in LICs compared with all other countries for awareness (P <.001) and treatment (P <.001). Awareness, treatment, and control of hypertension were higher in urban communities compared with rural ones in LICs (urban vs rural, P <.001) and LMICs (urban vs rural, P <.001), but similar for other countries. Low education was associated with lower rates of awareness, treatment, and control in LICs, but not in other countries. CONCLUSIONS AND RELEVANCE: Among a multinational study population, 46.5% of participants with hypertension were aware of the diagnosis, with blood pressure control among 32.5% of those being treated. These findings suggest substantial room for improvement in hypertension diagnosis and treatment.

Prediction of blood pressure based on anthropometric measurements in adolescents.

BACKGROUND: Recently, an important health issue in children is obesity, leading to hypertension. The aim of this study was to determine association of blood pressure with anthropometric variables in adolescents. METHODS: In this study, 1992 adolescents aged 11-18 years old between 2000 and 2007 were included. Cut point of anthropometric indices of waist circumference (WC), waist-to-stature ratio (WSR) and body mass index (BMI) was identified using Youden's index. RESULTS: Cut point of BMI for identification of hypertension was 19.69, 25.5, 20.65 and 24.13 for boys at middle and high school, girls at middle and high school, respectively. This measure for WSR was 0.44, 0.50, 0.45 and 0.517 for boys at middle and high school, girls at middle and high school, respectively. Regarding WC, it was 69.50, 96.5, 65.5 and 77.5 for boys at middle and high school, girls at middle and high school, respectively. CONCLUSIONS: In middle school boys, WSR, WC and BMI are associated with DBP but by increasing age, only BMI and weight are associated with DBP. BMI is the consistent anthropometric determinant of DBP. We also observed the relationship between WSR and SBP in boys, which could be applied as a predictive measure.

How does the impact of a community trial on cardio-metabolic risk factors differ in terms of gender and living area? Findings from the Isfahan healthy heart program.

OBJECTIVE: To assess the impact of gender and living area on cardiovascular risk factors in the context of a comprehensive lifestyle intervention program. DESIGN: Data from independent sample surveys before (2000--2001) and after (2007) a community trial, entitled the Isfahan Healthy Heart Program (IHHP) were used to compare differences in the intervention area (IA) and reference area (RA) by gender and living area. SETTING: The interventions targeted the population living in Isfahan and Najaf-Abad counties as IA and Arak as RA. PARTICIPANTS: Overall, 12 514 individuals who were more than 19 years of age were studied at baseline, and 9570 were studied in postintervention phase. INTERVENTIONS: Multiple activities were conducted in connection with each of the four main strategies of healthy nutrition, increasing physical activity, tobacco control, and coping with stress. MAIN OUTCOMES: Comparing serum lipids levels, blood pressure, blood glucose and obesity indices changes between IA and RA based on sex and living areas during the study. RESULTS: In IA, while the prevalence of hypertension declined in urban and rural females (P < 0.05). In IA, the prevalence of hypercholesterolemia and hypertriglyceridemia decreased in both females and males of urban and rural areas except for hypercholesterolemia in rural males (P < 0.01). In RA, the significant changes include both decrease in the hypercholesterolemia among rural males (P < 0.001) and hypertriglyceridemia in urban females (P < 0.01), while hypertriglyceridemia was significantly increased in rural females (P < 0.01). CONCLUSIONS: This comprehensive community trial was effective in controlling many risk factors in both sexes in urban and rural areas. These findings also reflect the transitional status of rural population in adopting urban lifestyle behaviors.

Medications for blood pressure, blood glucose, lipids, and anti-thrombotic medications: relationship with cardiovascular disease and death in adults from 21 high-, middle-, and low-income countries with an elevated body mass index.

AIMS: Elevated body mass index (BMI) is an important cause of cardiovascular disease (CVD). The population-level impact of pharmacologic strategies to mitigate the risk of CVD conferred by the metabolic consequences of an elevated BMI is not well described. METHODS AND RESULTS: We conducted an analysis of 145 986 participants (mean age 50 years, 58% women) from 21 high-, middle-, and low-income countries in the Prospective Urban and Rural Epidemiology study who had no history of cancer, ischaemic heart disease, heart failure, or stroke. We evaluated whether the hazards of CVD (myocardial infarction, stroke, heart failure, or cardiovascular death) differed among those taking a cardiovascular medication (n = 29 174; including blood pressure-lowering, blood glucose-lowering, cholesterol-lowering, or anti-thrombotic medications) vs. those not taking a cardiovascular medication (n = 116 812) during 10.2 years of follow-up. Cox proportional hazard models with the community as a shared frailty were constructed by adjusting age, sex, education, geographic region, physical activity, tobacco, and alcohol use. We observed 7928 (5.4%) CVD events and 9863 (6.8%) deaths. Cardiovascular medication use was associated with different hazards of CVD (interaction P < 0.0001) and death (interaction P = 0.0020) as compared with no cardiovascular medication use. Among those not taking a cardiovascular medication, as compared with those with BMI 20 to <25 kg/m2, the hazard ratio (HR) [95% confidence interval (95% CI)] for CVD were, respectively, 1.14 (1.06-1.23); 1.45 (1.30-1.61); and 1.53 (1.28-1.82) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the HR (95% CI) for CVD were, respectively, 0.79 (0.72-0.87); 0.90 (0.79-1.01); and 1.14 (0.98-1.33). Among those not taking a cardiovascular medication, the respective HR (95% CI) for death were 0.93 (0.87-1.00); 1.03 (0.93-1.15); and 1.44 (1.24-1.67) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the respective HR (95% CI) for death were 0.77 (0.69-0.84); 0.88 (0.78-0.99); and 1.12 (0.96-1.30). Blood pressure-lowering medications accounted for the largest population attributable benefit of cardiovascular medications. CONCLUSION: To the extent that CVD risk among those with an elevated BMI is related to hypertension, diabetes, and an elevated thrombotic milieu, targeting these pathways pharmacologically may represent an important complementary means of reducing the CVD burden caused by an elevated BMI.

Variations in risks from smoking between high-income, middle-income, and low-income countries: an analysis of data from 179 000 participants from 63 countries.

BACKGROUND: Separate studies suggest that the risks from smoking might vary between high-income (HICs), middle-income (MICs), and low-income (LICs) countries, but this has not yet been systematically examined within a single study using standardised approaches. We examined the variations in risks from smoking across different country income groups and some of their potential reasons. METHODS: We analysed data from 134 909 participants from 21 countries followed up for a median of 11·3 years in the Prospective Urban Rural Epidemiology (PURE) cohort study; 9711 participants with myocardial infarction and 11 362 controls from 52 countries in the INTERHEART case-control study; and 11 580 participants with stroke and 11 331 controls from 32 countries in the INTERSTROKE case-control study. In PURE, all-cause mortality, major cardiovascular disease, cancers, respiratory diseases, and their composite were the primary outcomes for this analysis. Biochemical verification of urinary total nicotine equivalent was done in a substudy of 1000 participants in PURE. FINDINGS: In PURE, the adjusted hazard ratio (HR) for the composite outcome in current smokers (vs never smokers) was higher in HICs (HR 1·87, 95% CI 1·65-2·12) than in MICs (1·41, 1·34-1·49) and LICs (1·35, 1·25-1·46; interaction p<0·0001). Similar patterns were observed for each component of the composite outcome in PURE, myocardial infarction in INTERHEART, and stroke in INTERSTROKE. The median levels of tar, nicotine, and carbon monoxide displayed on the cigarette packs from PURE HICs were higher than those on the packs from MICs. In PURE, the proportion of never smokers reporting high second-hand smoke exposure (≥1 times/day) was 6·3% in HICs, 23·2% in MICs, and 14·0% in LICs. The adjusted geometric mean total nicotine equivalent was higher among current smokers in HICs (47·2 µM) than in MICs (31·1 µM) and LICs (25·2 µM; ANCOVA p<0·0001). By contrast, it was higher among never smokers in LICs (18·8 µM) and MICs (11·3 µM) than in HICs (5·0 µM; ANCOVA p=0·0001). INTERPRETATION: The variations in risks from smoking between country income groups are probably related to the higher exposure of tobacco-derived toxicants among smokers in HICs and higher rates of high second-hand smoke exposure among never smokers in MICs and LICs. FUNDING: Full funding sources are listed at the end of the paper (see Acknowledgments).

Validity and reproducibility of a semi-quantitative food frequency questionnaire for Iranian adults.

AIM: To validate a semi-quantitative food frequency questionnaire (SFFQ) and assess the dietary intake of Iranian adults. METHODS: This study was conducted among 113 healthy adults in Iran. We administered twelve 24-hour dietary recalls (24DRs) during a year as a reference method. The 165-item SFFQ was administered twice, along with the first and last 24DRs. To examine validity and reproducibility of SFFQ, the correlation coefficients (r) and de-attenuated correlation coefficients and intra-class correlation coefficient (ICC) between 24DRs and SFFQ were calculated. The Bland-Altman method was used to assess agreement between the two methods. RESULTS: De-attenuated correlations varied from 0.42 (polyunsaturated fatty acids) to 0.62 (energy) (all P < .001) for nutrients and from 0.48 (oils and fats) to 0.65 (sweets) for food groups (all P < .05). We found reasonable reproducibility of SFFQ for both nutrients and food groups. ICC (95%CI) varied from 0.47 (0.15-0.74) for saturated fatty acids to 0.64 (0.47-0.76) for energy and from 0.43 (0.15-0.62) for oils and fats to 0.58 for grains (0.31-0.69). According to the Bland-Altman plots, we observed an acceptable level of agreement between the two methods. CONCLUSIONS: We found reasonable relative validity and acceptable reproducibility of SFFQ. This SFFQ can be used to classify individuals based on their dietary intake in our population.

Association of bedtime with mortality and major cardiovascular events: an analysis of 112,198 individuals from 21 countries in the PURE study.

OBJECTIVES: This study aimed to examine the association of bedtime with mortality and major cardiovascular events. METHODS: Bedtime was recorded based on self-reported habitual time of going to bed in 112,198 participants from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study. Participants were prospectively followed for 9.2 years. We examined the association between bedtime and the composite outcome of all-cause mortality, non-fatal myocardial infarction, stroke and heart failure. Participants with a usual bedtime earlier than 10PM were categorized as 'earlier' sleepers and those who reported a bedtime after midnight as 'later' sleepers. Cox frailty models were applied with random intercepts to account for the clustering within centers. RESULTS: A total of 5633 deaths and 5346 major cardiovascular events were reported. A U-shaped association was observed between bedtime and the composite outcome. Using those going to bed between 10PM and midnight as the reference group, after adjustment for age and sex, both earlier and later sleepers had a higher risk of the composite outcome (HR of 1.29 [1.22, 1.35] and 1.11 [1.03, 1.20], respectively). In the fully adjusted model where demographic factors, lifestyle behaviors (including total sleep duration) and history of diseases were included, results were greatly attenuated, but the estimates indicated modestly higher risks in both earlier (HR of 1.09 [1.03-1.16]) and later sleepers (HR of 1.10 [1.02-1.20]). CONCLUSION: Early (10 PM or earlier) or late (Midnight or later) bedtimes may be an indicator or risk factor of adverse health 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.

Obesity and cardiometabolic risk factors in a representative population of Iranian adolescents and adults in comparison to a Western population: the Isfahan Healthy Heart Programme.

OBJECTIVE: The aim of the present study was to develop reference data for the Iranian population for anthropometric values and cardiometabolic data in comparison with those in Americans, as representative of a Western population. DESIGN: The present cross-sectional survey, conducted as part of the baseline survey of a community-based interventional study (the Isfahan Healthy Heart Programme), used a two-stage clustering design and was conducted in 12 600 randomly selected adults (> or =19 years of age) and 2000 adolescents (aged 11-18 years) living in three cities in the central part of Iran. For comparison with a Western population, comparable data for Americans were derived from the data sets of the Second and Third National Health and Nutrition Examination Surveys (NHANES II and NHANES III). RESULTS: Iranian women had significantly higher mean BMI, waist circumference (WC), hip circumference (HC) and waist:hip ratio (WHR) than Iranian men and American women; but the mean BMI of Iranian men was lower than that of American men. The mean serum TAG level of Iranian men was significantly higher than that of Iranian women, whereas the mean serum total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels were significantly higher in Iranian women than in men. The Iranian population had lower mean TC, LDL-C and TAG levels than the Americans, but such difference was not documented for HDL-C. Iranian adolescents had significantly lower mean BMI and higher mean TAG than did American adolescents. CONCLUSIONS: Our findings provide serious evidence for health professionals and policy makers about the very high prevalence of generalized and abdominal obesity in Iran. Controlling this emerging health problem, notably in women, should become a national priority in Iran and necessitates comprehensive public health programmes.

Gender differences in obesogenic behaviour, socioeconomic and metabolic factors in a population-based sample of Iranians: the IHHP study.

This study investigated the gender differences in association of some behavioural and socioeconomic factors with obesity indices in a population-based sample of 12,514 Iranian adults. The mean body mass index (BMI), waist circumference (WC), and the waist-to-hip ratio (WHR) were significantly higher in women than in men. Current and passive smoking had an inverse association with BMI among males whereas current smoking, transportation by a private car, and longer duration of watching television (TV) had a positive association with BMI among females. Current and passive smoking, cycling, and Global Dietary Index (GDI) had an inverse association with WC among males. Higher consumption of fruits and vegetables, current and passive smoking, duration of daily sleep, and GDI had an inverse association with WC among females. Using a private car for transportation had a significant positive association with WHR among both males and females. Living in an urban area, being married, and having a higher education level increased the odds ratio of obesity among both the genders. Non-manual work also increased this risk among males whereas watching TV and current smoking increased this risk among females. Such gender differences should be considered for culturally-appropriate interventional strategies to be implemented at the population level for tackling obesity and associated cardiometabolic risk factors.

Contrasting Associations Between Diabetes and Cardiovascular Mortality Rates in Low-, Middle-, and High-Income Countries: Cohort Study Data From 143,567 Individuals in 21 Countries in the PURE Study.

OBJECTIVE: We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income. RESEARCH DESIGN AND METHODS: The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years. RESULTS: Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34]). CONCLUSIONS: CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society.