Xiaohe Zhang

Dietary Patterns and the Risk of Acute Myocardial Infarction in 52 Countries Results of the INTERHEART Study

Background— Diet is a major modifiable risk factor for cardiovascular disease, but it varies markedly in different regions of the world. The objectives of the present study were to assess the association between dietary patterns and acute myocardial infarction (AMI) globally. Methods and Results— INTERHEART is a standardized case-control study involving participants from 52 countries. The present analysis included 5761 cases and 10 646 control subjects. We identified 3 major dietary patterns using factor analysis: Oriental (high intake of tofu and soy and other sauces), Western (high in fried foods, salty snacks, eggs, and meat), and prudent (high in fruit and vegetables). We observed an inverse association between the prudent pattern and AMI, with higher levels being protective. Compared with the first quartile, the adjusted ORs were 0.78 (95% CI 0.69 to 0.88) for the second quartile, 0.66 (95% CI 0.59 to 0.75) for the third, and 0.70 (95% CI 0.61 to 0.80) for the fourth (P for trend <0.001). The Western pattern showed a U-shaped association with AMI (compared with the first quartile, the adjusted OR for the second quartile was 0.87 [95% CI 0.78 to 0.98], whereas it was 1.12 [95% CI 1.00 to 1.25] for the third quartile and 1.35 [95% CI 1.21 to 1.51] for the fourth quartile; P for trend <0.001), but the Oriental pattern demonstrated no relationship with AMI. Compared with the first quartile, the OR of a dietary risk score derived from meat, salty snacks, fried foods, fruits, green leafy vegetables, cooked vegetables, and other raw vegetables (higher score indicating a poorer diet) increased with each quartile: second quartile 1.29 (95% CI 1.17 to 1.42), third quartile 1.67 (95% CI 1.51 to 1.83), and fourth quartile 1.92 (95% CI 1.74 to 2.11; P for trend <0.001). The adjusted population-attributable risk of AMI for the top 3 quartiles compared with the bottom quartile of the dietary risk score was 30%. Conclusions— An unhealthy dietary intake, assessed by a simple dietary risk score, increases the risk of AMI globally and accounts for ≈30% of the population-attributable risk.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

BACKGROUND Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

The Effect of Chromosome 9p21 Variants on Cardiovascular Disease May Be Modified by Dietary Intake: Evidence from a Case/Control and a Prospective Study

Ron Do and colleagues find that a prudent diet high in raw vegetables may modify the increased genetic risk of cardiovascular disease conferred by the chromosome 9p21 SNP.

The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression

Candidate gene and genome-wide association studies have not identified common variants, which are reliably associated with depression. The recent identification of obesity predisposing genes that are highly expressed in the brain raises the possibility of their genetic contribution to depression. As variation in the intron 1 of the fat mass- and obesity-associated (FTO) gene contributes to polygenic obesity, we assessed the possibility that FTO gene may contribute to depression in a cross-sectional multi-ethnic sample of 6561 depression cases and 21 932 controls selected from the EpiDREAM, INTERHEART, DeCC (depression case–control study) and Cohorte Lausannoise (CoLaus) studies. Major depression was defined according to DSM IV diagnostic criteria. Association analyses were performed under the additive genetic model. A meta-analysis of the four studies showed a significant inverse association between the obesity risk FTO rs9939609 A variant and depression (odds ratio=0.92 (0.89, 0.97), P=3 × 10−4) adjusted for age, sex, ethnicity/population structure and body-mass index (BMI) with no significant between-study heterogeneity (I2=0%, P=0.63). The FTO rs9939609 A variant was also associated with increased BMI in the four studies (β 0.30 (0.08, 0.51), P=0.0064) adjusted for age, sex and ethnicity/population structure. In conclusion, we provide the first evidence that the FTO rs9939609 A variant may be associated with a lower risk of depression independently of its effect on BMI. This study highlights the potential importance of obesity predisposing genes on depression.

Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study

BACKGROUND Alcohol consumption is proposed to be the third most important modifiable risk factor for death and disability. However, alcohol consumption has been associated with both benefits and harms, and previous studies were mostly done in high-income countries. We investigated associations between alcohol consumption and outcomes in a prospective cohort of countries at different economic levels in five continents. METHODS We included information from 12 countries participating in the Prospective Urban Rural Epidemiological (PURE) study, a prospective cohort study of individuals aged 35-70 years. We used Cox proportional hazards regression to study associations with mortality (n=2723), cardiovascular disease (n=2742), myocardial infarction (n=979), stroke (n=817), alcohol-related cancer (n=764), injury (n=824), admission to hospital (n=8786), and for a composite of these outcomes (n=11,963). FINDINGS We included 114,970 adults, of whom 12,904 (11%) were from high-income countries (HICs), 24,408 (21%) were from upper-middle-income countries (UMICs), 48,845 (43%) were from lower-middle-income countries (LMICs), and 28,813 (25%) were from low-income countries (LICs). Median follow-up was 4.3 years (IQR 3.0-6.0). Current drinking was reported by 36,030 (31%) individuals, and was associated with reduced myocardial infarction (hazard ratio [HR] 0.76 [95% CI 0.63-0.93]), but increased alcohol-related cancers (HR 1.51 [1.22-1.89]) and injury (HR 1.29 [1.04-1.61]). High intake was associated with increased mortality (HR 1.31 [1.04-1.66]). Compared with never drinkers, we identified significantly reduced hazards for the composite outcome for current drinkers in HICs and UMICs (HR 0.84 [0.77-0.92]), but not in LMICs and LICs, for which we identified no reductions in this outcome (HR 1.07 [0.95-1.21]; pinteraction<0.0001). INTERPRETATION Current alcohol consumption had differing associations by clinical outcome, and differing associations by income region. However, we identified sufficient commonalities to support global health strategies and national initiatives to reduce harmful alcohol use. 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.

The association between ownership of common household devices and obesity and diabetes in high, middle and low income countries

Background: Household devices (e.g., television, car, computer) are common in high income countries, and their use has been linked to obesity and type 2 diabetes mellitus. We hypothesized that device ownership is associated with obesity and diabetes and that these effects are explained through reduced physical activity, increased sitting time and increased energy intake. Methods: We performed a cross-sectional analysis using data from the Prospective Urban Rural Epidemiology study involving 153 996 adults from high, upper-middle, lower-middle and low income countries. We used multilevel regression models to account for clustering at the community and country levels. Results: Ownership of a household device increased from low to high income countries (4% to 83% for all 3 devices) and was associated with decreased physical activity and increased sitting, dietary energy intake, body mass index and waist circumference. There was an increased odds of obesity and diabetes with the ownership of any 1 household device compared to no device ownership (obesity: odds ratio [OR] 1.43, 95% confidence interval [CI] 1.32–1.55; diabetes: OR 1.38, 95% CI 1.28–1.50). Ownership of a second device increased the odds further but ownership of a third device did not. Subsequent adjustment for lifestyle factors modestly attenuated these associations. Of the 3 devices, ownership of a television had the strongest association with obesity (OR 1.39, 95% CI 1.29–1.49) and diabetes (OR 1.33, 95% CI 1.23–1.44). When stratified by country income level, the odds of obesity and diabetes when owning all 3 devices was greatest in low income countries (obesity: OR 3.15, 95% CI 2.33–4.25; diabetes: OR 1.97, 95% CI 1.53–2.53) and decreased through country income levels such that we did not detect an association in high income countries. Interpretation: The ownership of household devices increased the likelihood of obesity and diabetes, and this was mediated in part by effects on physical activity, sitting time and dietary energy intake. With increasing ownership of household devices in developing countries, societal interventions are needed to mitigate their effects on poor health.

Validation of a semi-quantitative Food Frequency Questionnaire for Argentinean adults.

Background The Food Frequency Questionnaire (FFQ) is the most commonly used method for ranking individuals based on long term food intake in large epidemiological studies. The validation of an FFQ for specific populations is essential as food consumption is culture dependent. The aim of this study was to develop a Semi-quantitative Food Frequency Questionnaire (SFFQ) and evaluate its validity and reproducibility in estimating nutrient intake in urban and rural areas of Argentina. Methods/Principal Findings Overall, 256 participants in the Argentinean arm of the ongoing Prospective Urban and Rural Epidemiological study (PURE) were enrolled for development and validation of the SFFQ. One hundred individuals participated in the SFFQ development. The other 156 individuals completed the SFFQs on two occasions, four 24-hour Dietary Recalls (24DRs) in urban, and three 24DRs in rural areas during a one-year period. Correlation coefficients (r) and de-attenuated correlation coefficients between 24DRs and SFFQ were calculated for macro and micro-nutrients. The level of agreement between the two methods was evaluated using classification into same and extreme quartiles and the Bland-Altman method. The reproducibility of the SFFQ was assessed by Pearson correlation coefficients and Intra-class Correlation Coefficients (ICC). The SFFQ consists of 96 food items. In both urban and rural settings de-attenuated correlations exceeded 0.4 for most of the nutrients. The classification into the same and adjacent quartiles was more than 70% for urban and 60% for rural settings. The Pearson correlation between two SFFQs varied from 0.30–0.56 and 0.32–0.60 in urban and rural settings, respectively. Conclusion Our results showed that this SFFQ had moderate relative validity and reproducibility for macro and micronutrients in relation to the comparison method and can be used to rank individuals based on habitual nutrient intake.

Refinement and validation of an FFQ developed to estimate macro- and micronutrient intakes in a south Indian population

OBJECTIVE Potential error sources in nutrient estimation with the FFQ include inaccurate or biased recall and overestimation or underestimation of intake due to too many or too few items on the FFQ, respectively. Here we report the refinement of an FFQ that overestimated nutrient intake and its validation against multiple 24 h recalls. STUDY DESIGN Data on 2527 participants in south India (Trivandrum) were available for the original FFQ (OFFQ) that overestimated nutrient intake (132 food items). After excluding participants with implausible energy intake estimates (<2.72 MJ/d (<650 kcal/d), >15.69 MJ/d (>3750 kcal/d)) we ran stepwise regression analyses with selected nutrients as the outcomes and food intake (servings/d) as predictor variables (n 1867). From these results and expert consultation we refined the FFQ (RFFQ), and validated it by comparing intakes obtained with it and the mean of two 24 h recalls among 100 participants. RESULTS The OFFQ overestimated usual daily nutrient intake before and after exclusions [for energy: 13.39 (sd 5.46) MJ (3201 (sd 1305) kcal) and 10.96 (sd 2.65) MJ (2619 (sd 634) kcal), respectively]. In stepwise analyses, fifty-seven food items explained 90 % of the variance in nutrients; we retained thirteen food items because participants consumed them at least twice monthly and twelve food items that local nutritionists recommended. Mean energy intake estimated from the RFFQ (eighty-two food items) was 7.94 (sd 2.05) MJ (1897 (sd 489) kcal). The de-attenuated correlations between mean 24 h recall and RFFQ intakes ranged from 0.25 (vitamin A) to 0.82 (fat). CONCLUSION We refined an FFQ that overestimated nutrient intake by shortening and redesigning, and validated it by comparisons with 24 h dietary recall data.

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.

Development, reproducibility and validity of the food frequency questionnaire in the Poland arm of the Prospective Urban and Rural Epidemiological (PURE) study.

BACKGROUND A food frequency questionnaire (FFQ) is the most commonly used method in large epidemiological studies. The validation of an FFQ is essential for specific populations because foods are culture-dependent. The present study aimed to develop an FFQ and evaluate its validity and reproducibility in estimating the intake of nutrients in urban and rural areas of Poland. METHODS Adult participants (n = 146) in the Polish arm of the ongoing Prospective Urban and Rural Epidemiological (PURE) study completed FFQs on two occasions, as well as four 24-h dietary recalls (DRs) during a 12-month period. Correlation coefficients (r) and de-attenuated correlation coefficients between dietary recalls and both FFQs were calculated for selected macro- and micronutrients. Agreement between the two methods was evaluated by classification into quartiles and the Bland-Altman method. Reproducibility was assessed by the intra-class correlation coefficient (ICC). RESULTS The final food list contained 134 food items. For urban participants, FFQ2 generally underestimated energy, protein and fat compared to the FFQ1 and mean of DRs. In rural areas, compared to DRs, both FFQs overestimated energy and macronutrients. For both urban and rural settings, de-attenuated correlation exceeded 0.4 for almost all nutrients and the exact agreement in quartile categorisation was >66%. When assessing repeatability, ICC varied from 0.39-0.63 in an urban setting and 0.19-0.45 in a rural setting. CONCLUSIONS This 134-item FFQ has good validity and reproducibility in relation to the reference method and can be used to rank individuals based on their macro- and micronutrient intake.