Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries

Key Points

Question  Is there a difference in the association of fish consumption with risk of cardiovascular disease (CVD) or of mortality between individuals with and individuals without vascular disease?

Findings  In this analysis of 4 international cohort studies of 191 558 people from 58 countries on 6 continents, a lower risk of major CVD and total mortality was associated with higher fish intake of at least 175 g (2 servings) weekly among high-risk individuals or patients with vascular disease, but not in general populations without vascular disease; a similar pattern of results was observed for sudden cardiac death. Oily fish but not other types of fish were associated with greater benefits.

Meaning  Study findings suggest that fish intake of at least 175 g (2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD, but not in the general population.

Importance  Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown.

Objective  To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease.

Design, Setting, and Participants  This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies—147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020.

Exposures  Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish.

Main Outcomes and Measures  Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death).

Results  Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I² = 82.6 [P = .02]; for death, I² = 90.8 [P = .001]).

Conclusions and Relevance  Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

Dietary guidelines recommend at least 2 servings of fish per week for the prevention of cardiovascular disease (CVD).^1,2 Fish is a major source of the long-chain ω-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid, which have been suggested to have beneficial effects on cardiovascular health.^3-5 In interventional studies, fish and ω-3 consumption have been shown to improve some cardiovascular risk markers, including triglycerides and blood pressure, especially in people with triglycerides of 500 mg/dL or greater (to convert to millimoles per liter, multiply by 0.0113).^6,7 Two recent meta-analyses of randomized trials in high-risk individuals showed that ω-3 supplementation (typically approximately 1 g/d) was not associated with risk of cardiovascular events, coronary heart deaths, coronary heart disease events, stroke, heart irregularities, or all-cause mortality.^8,9 By contrast, another recent meta-analysis¹⁰ that included 3 new trials^11-13 showed that ω-3 supplementation was associated with significant benefit against risk of CVD outcomes (summary relative risk of 0.92; 95% CI, 0.86-0.98),¹⁰ even after excluding a recent trial of patients with elevated triglyceride levels that used a much higher dose of fish oil (4 g daily).¹³ Observational cohorts of participants without diagnosed vascular disease have found modest protective associations of moderate fish consumption (approximately ≥2 servings/wk) with fatal coronary heart disease (ie, summary relative risks in multiple meta-analyses ranging from 2% to 15% lower risk) and, usually less strongly, with total CVD.¹⁴ To date, most cohort studies evaluating fish consumption and CVD events have been conducted in Europe, North America, Japan, and China, with little information from other world regions, where varying amounts and types of fish are consumed. Furthermore, whether the associations of fish consumption with CVD events vary between those with and those without vascular disease is unclear.

Because increasing fish intake may improve blood lipid levels, especially among high-risk individuals,^6,7 we hypothesized that there would be differences in the association between fish intake and major CVD outcomes and mortality among individuals with vascular disease compared with those without vascular disease. In the present pooled analysis, we studied 191 558 people (51 731 with vascular disease and 139 827 generally healthy individuals) from 58 countries who had been included as participants in 4 large prospective studies.

Details of the studies’ designs and population characteristics have been published before and are described in the eAppendix in the Supplement.

In brief, the Prospective Urban Rural Epidemiology (PURE) study^15-19 is an ongoing large-scale epidemiologic cohort study that has enrolled 166 762 individuals, 35 to 70 years of age, in 21 low-, middle-, and high-income countries on 5 continents. For the present analysis, we included 147 645 participants (including 7818 [5.3%] with a history of CVD) with complete information on their diet (eFigure 1 in the Supplement). We included all outcome events known until July 31, 2019.

The Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) is a randomized clinical trial of antihypertension medication (ramipril, telmisartan, and their combination) for 25 620 patients aged 55 years or older with vascular disease or diabetes.²⁰ The Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) was a randomized clinical trial of telmisartan vs placebo for 5926 participants.²¹ For the present analysis, we included 31 491 participants from ONTARGET and TRANSCEND with dietary assessments in 40 countries on 6 continents.

The Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial was a randomized clinical trial of insulin glargine therapy or standard care and ω-3 fatty acid or placebo supplementation (2 × 2 factorial design) that included 12 537 people (mean [SD] age, 63.5 [7.8] years) with cardiovascular risk factors plus impaired fasting glucose or diabetes.^22,23 For the present analysis, we included 12 422 participants from ORIGIN with dietary assessments in 40 countries on 5 continents. We collected information on the type of fish consumed in ORIGIN but not in other studies. All studies were coordinated by the Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada.

The information about the study variables was collected with similar approaches and data collection forms in each of the studies. Information about demographic factors, lifestyle, health history, and medication use was recorded. Physical assessments included weight, height, waist and hip circumferences, and blood pressure.

In PURE, participants’ habitual food intake was recorded using country-specific validated food frequency questionnaires (FFQs; eAppendix in the Supplement).^24,25 In ONTARGET and TRANSCEND, dietary information was obtained using a 19-item qualitative FFQ.^20,21 In ORIGIN, a 25-item qualitative FFQ was used to obtain information on individual foods or food groups, except for fish.^22,23 A separate 28-item qualitative FFQ was used to assess fish intake (24 types of fish and 4 types of shellfish) (eAppendix in the Supplement).

Standardized case report forms were used to capture clinical data and to record major CVD events and death during follow-up in each study. Major cardiovascular events and deaths during follow-up were recorded and adjudicated centrally in each country using standard definitions. Events were classified according to the definitions used in each study, but these definitions were broadly similar.

Median fish intake was calculated overall and according to geographic region and country, with adjustment for age and sex. For all 3 cohorts, participants were grouped according to fish consumption into lower than 50 g/mo, 50 g/mo to lower than 175 g/wk, 175 to lower than 350 g/wk, and 350 g/wk or higher (ie, equivalent to fixed increments of about 25 g/d); the lowest intake group was used as the reference. Analysis of covariance was performed to calculate mean blood lipid levels and blood pressure levels among fish intake groups, adjusting for covariates.

We used a 2-stage individual participant data meta-analysis.²⁶ First, we assessed the associations between fish intake and events in each cohort separately. For the PURE cohort, estimates were obtained overall and separately for 2 subcohorts of people with or without CVD (the other 3 cohort studies were composed entirely of patients with vascular disease). Second, the cohort-specific hazard ratios (HRs) and 95% CIs were pooled (separately by cohort of people with or without CVD) in a random-effects meta-analysis.²⁷ The proportionality assumption was tested using the global goodness-of-fit test with Schoenfeld residuals in each cohort. No evidence of a violation was found. Tests of heterogeneity were conducted using the I² statistic.

In the PURE study, Cox frailty models with random effects (to account for clustering within study centers) were used to assess the association between fish intake and the outcomes.²⁸ In a minimally adjusted model, we adjusted for age, sex, and study center (as a random effect). The primary model adjusted for age, sex, study center (as a random effect), body mass index, educational level, wealth index, smoking status, urban or rural location, physical activity, history of diabetes, use of statin or antihypertension medication, and fruit, vegetables, red meat, poultry, dairy, and total energy intake, as in articles previously published by members of our group.^24,25,29 To test for linear trends, we used the median fish intake value in each of the categories of fish intake and included the variable as a quantitative risk factor. In ONTARGET and TRANSCEND, because the entry criteria and study conduct were similar for the 2 trials, we pooled the data from both studies in our analysis. As in the PURE analyses, in ONTARGET/TRANSCEND and in ORIGIN, we used Cox frailty models with similar adjustment models, but additionally adjusted for treatment allocation.

In sensitivity analyses for each study, estimates were assessed in the primary models after removing potential associated factors (body mass index, waist to hip ratio, diabetes, and hypertension). In addition, we assessed whether the association of fish intake varied by geographic region using tests of interaction. All statistical analyses were conducted using SAS, version 9.4 (SAS Institute Inc). A 2-sided P < .05 was considered statistically significant. The present analysis was conducted from January to June 2020.

Participant characteristics from each study are provided in Table 1.^15,19 Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] males) were included in the present analysis. The median duration of follow-up was 7.5 years (interquartile range [IQR], 4.9-9.4 years), with follow-up completed for 96% of the participants. The median follow-up in PURE was 9.1 years (IQR, 6.8-10.4 years), 4.5 years (IQR, 4.4-5.0 years) in ONTARGET and TRANSCEND, and 6.2 years (IQR, 5.8-6.7 years) in ORIGIN.

Overall, there were 8949 deaths (6.4%) among individuals without prior CVD and 6763 (13.1%) among individuals with prior CVD. There were 6825 (4.9%) major CVD events among individuals without prior CVD and 8565 (16.6%) among individuals with prior CVD.

Median fish intake ranged from 4.2 g/wk in South Asia to 468.3 g/wk in Southeast Asia (eFigure 2 in the Supplement). By country, fish intake was lowest in Argentina (0.7 g/wk) and India (1.4 g/wk) and highest in Malaysia (452.2 g/wk), Philippines (522.9 g/wk), and United Arab Emirates (1350 g/wk).

In PURE, no significant association between fish intake and any health outcome was found, after adjustment for known confounders. Compared with little or no fish intake (≤50 g/mo; reference category), an intake of 350 g/wk or more (approximately 4 servings) was not significantly associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04), CVD mortality (HR, 0.94; 95% CI, 0.80-1.10), non-CVD mortality (HR, 1.00; 95% CI, 0.90-1.12), or total mortality (HR, 0.96; 95% CI, 0.88-1.05) (Table 2; Figure 1). The association between fish intake and outcome events did not differ significantly by history of CVD status within PURE (Figure 1; eFigure 5 in the Supplement).

By contrast, in 2 cohorts of patients with vascular diseases (ONTARGET and TRANSCEND study, 40 countries, and 6 continents), a higher fish intake of at least 175 g/wk (approximately 2 servings/wk) was associated with lower risk of major CVD (HR, 0.89; 95% CI, 0.80-1.00), CVD mortality (HR, 0.87; 95% CI, 0.74-1.02), non-CVD mortality (HR, 0.83; 95% CI, 0.68-1.01), and total mortality (HR, 0.86; 95% CI, 0.76-0.98) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher (Table 2; eFigure 4 in the Supplement).

In the ORIGIN study of patients with vascular dieases (40 countries, 5 continents), a higher fish intake of at least 175 g/wk (approximately 2 servings/wk) was associated with lower risk of major CVD (HR, 0.77; 95% CI, 0.66-0.89), CVD mortality (HR, 0.66; 95% CI, 0.54-0.80), and total mortality (HR, 0.77; 95% CI, 0.66-0.90) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher (Table 2; eFigure 4 in the Supplement).

Collectively, in the 3 cohorts of patients with vascular disease, a minimal fish intake of 175 g/wk (approximately 2 servings/wk) was associated with lower major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) compared with 50 g/mo or lower, with no additional benefit with consumption of 350 g/wk or more.

Similar results were found when waist to hip ratio replaced body mass index in the multivariable models and also when waist to hip ratio, body mass index, hypertension, and diabetes were dropped from the models (eTable 2 in the Supplement). Lastly, when participants with an event in the first 2 years were excluded, the findings were unchanged (eTable 2 in the Supplement).

In the ORIGIN study, types of fish with higher amounts of ω-3 fats were strongly associated with a lower risk of major CVD events (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other types of fish were neutral (Figure 2).³⁰ Similar protective associations of high ω-3 fish were found for sudden cardiac death (HR, 0.91; 95% CI, 0.86-0.96 per 5-g increment of intake; P < .001), whereas other types of fish were found to be neutral (HR, 0.98; 95% CI, 0.88-1.09; P = .69).

The association of fish intake with major CVD and CVD death varied significantly by history of CVD status (for major CVD, I² = 82.6 [P = .02]; for death, I² = 90.8 [P = .001]; for composite of death or CVD, I² = 87.6 [P = .004]) (Figure 1; eFigure 4 in the Supplement).

Among high-risk individuals or patients with existing vascular disease, a minimal fish intake of 175 g/week (approximately 2 servings/week) was associated with lower risk of major CVD (compared with ≤50 g/month; HR, 0.84; 95% CI, 0.77-0.92; P = .008), total mortality (HR, 0.83; 95% CI, 0.76-0.91; P < .001), and the composite of death or major CVD (HR, 0.86; 95% CI, 0.80-0.92; P = .002), after adjustment for known confounders (Figure 1; eFigure 4 in the Supplement), with no further apparent decrease in HR with consumption of 350 g/week or higher. No significant heterogeneity in the associations with the composite outcome was found across regions.

By contrast, in general populations without vascular disease, a higher fish intake was not significantly associated with major CVD (comparing ≥350 g/wk vs ≤50 g/mo; HR, 0.97; 95% CI, 0.88-1.08; P = .24), total mortality (HR, 0.97; 95% CI, 0.88-1.06; P = .48), or the composite of death or major CVD (HR, 0.97; 95% CI, 0.90-1.04; P = .18) (Figure 1; eFigure 4 in the Supplement).

Similarly, among high-risk individuals or patients with existing vascular disease, a higher fish intake was associated with lower risk of sudden cardiac death (comparing ≥350 g/wk with ≤50 g/mo; HR, 0.79; 95% CI, 0.63-0.99; P = .04). By contrast, in general populations without vascular disease, a higher fish intake was not significantly associated with these events (HR, 1.10; 95% CI, 0.64-1.89; P = .91).

In PURE, higher fish intake appeared to be associated with a lower risk of composite events in China and Africa but appeared to be neutral in other regions. For patients with vascular disease, similar associations were found across regions.

Higher fish intake was associated with lower triglyceride levels both among people with or without vascular disease (Figure 3; eTable 1 in the Supplement). However, no beneficial associations were found with other risk markers, and there were higher levels of low-density lipoprotein cholesterol (LDL-C) (Figure 3; eFigure 3 in the Supplement).

In this analysis of 4 international prospective cohort studies with 15 390 major CVD events and 15 712 deaths, among 191 558 people from 58 countries in 6 continents, we noted significant heterogeneity in the association between fish intake and major CVD events by history of CVD status. Lower risk of major CVD, total mortality, and their composite was found with higher fish intake of at least 175 g/wk (approximately 2 servings) among high-risk individuals or patients with vascular disease, but not in general populations without vascular disease. A similar pattern of results was found for sudden cardiac death, with significant protective associations observed among patients with vascular disease, but neutral in general populations without vascular disease. Furthermore, the data available from 1 study on types of fish suggested that oily fish but not other types of fish were associated with greater benefits.

Dietary guidelines generally encourage consumption of a variety of fish, preferably oily types (eg, salmon, sardines, tuna, and mackerel), at least twice a week for CVD prevention.^1,2,31-33 High-dose fish oil has been shown to lower triglyceride levels in people with severe hypertriglyceridemia.^6,7 Furthermore, short-term trials showed that 2 servings of fatty fish per week (roughly 112 g [4 oz] each) decreased triglyceride levels by 11.4% but also slightly increased LDL-C levels compared with the control diet.^34,35 Our findings are consistent with this information, both among people with and among persons without vascular disease (8% decrease in triglyceride level with approximately 2 standard servings of fish per week but with slightly higher LDL-C level). The increase in LDL-C level associated with fish intake may not suggest an increased CVD risk because this risk may be offset by the positive effects on lipoproteins.³⁶ Our finding of higher blood glucose levels associated with higher fish intake is consistent with some trial data for patients with diabetes,³⁷ but other trials of fish or fish oil consumption have been neutral regarding this factor.³⁸ Cohort studies of fish intake and incident diabetes have shown variable results.^39,40 Cooking methods, mercury levels, and the presence of polychlorinated biphenyls or other environmental contaminants in fish are potential factors associated with the different findings across studies,⁴¹ but further work is needed in this area. Given that there are associations with CVD risk markers, some of which may be protective and others harmful, and that some fish may contain contaminants,^42,43 studying the association of fish intake with outcome events is essential to inform recommendations for populations.

To our knowledge, there are no primary prevention trials on fish intake and CVD outcomes. Some prospective cohort studies among mostly healthy people have found an inverse association between fish intake and CVD mortality, whereas others do not.⁴⁴ A recent umbrella review of cohort studies found modest protective associations of fish consumption with fatal coronary heart disease (ie, summary relative risks ranging from 2% to 15% lower risk).¹⁴ Compared with fatal cardiac events, fish consumption has weaker associations with nonfatal cardiac events and stroke.^14,44 However, those meta-analyses were not based on combining individual data from each study and thus were not able to fully adjust for all potential confounders. In PURE, which covers fish intake in numerous world regions in which various amounts and types of fish are consumed, we found no significant association of fish intake with outcome events. In analyses by geographic region, we found considerable heterogeneity across geographic regions, but associations were neutral in most regions except for China and Africa, where protective associations between fish intake and composite events were detected. Taken together, the results suggest that higher fish consumption may be modestly associated with CVD outcomes or mortality in generally healthy populations.

Our findings of favorable associations of fish intake with CVD events and mortality among patients with vascular disease are consistent with the DART-1 (Diet and Reinfarction) trial,⁴⁵ but not the DART 2 study⁴⁶ or 2 recent meta-analyses of randomized clinical trials of fish oil supplementation for high-risk individuals, which showed that fish oil (approximately 1 g/d) had no association with CVD outcomes or total mortality.^8,9 More recently, in 2018, 2 trials of a 1-g/d ω-3 formulation found no significant effect of supplementation on major CVD, but there was significant lowering of fatal myocardial infarction, total coronary heart disease,¹² and fatal CVD.¹¹ In a 2019 meta-analysis¹⁰ that included those new trials,^11,12 individuals who received ω-3 supplementation had significantly better CVD outcomes, even after excluding the recent REDUCE-IT randomized clinical trial of patients with elevated triglyceride levels that used a much higher dose of fish oil (4 g daily).¹³ In our study, CVD risk was lowest with a moderate amount of fish (ie, at least 175 g/wk, or approximately 2 servings/wk), with no further apparent decrease in risk with higher fish intake (ie, >350 g/wk, or >3-4 servings/wk). Similarly, previous cohort studies of mostly generally healthy populations showed that approximately 2 or more servings/wk (150 g/wk) is associated with the lowest CVD risk.^14,44 On this basis, 2 servings of fish per week may be the minimal amount of fish needed to reach maximum benefit (an amount consistent with current recommendations for CVD prevention),^1,2,31-33 with little additional benefit with higher intakes among patients with vascular disease. As expected in ORIGIN, for which we collected information on types of fish, consumption of fish with higher amounts of ω-3 fats was strongly associated with a lower risk of major CVD, whereas consumption of other types of fish was found to be neutral. These findings are compatible with trials showing favorable effects of oily fish intake on CVD risk markers.⁶ In addition, fish may have selective antiarrhythmic effects and accompanying protection against sudden cardiac death.^3,4,8 Some⁴⁷ but not all^48,49 trials of patients with vascular disease found that fish oil use results in a lower risk of sudden cardiac death. In our cohorts of patients with vascular disease, we found protective associations of fish intake (mainly from high ω-3 fish) with sudden death (HR, 0.79; 95% CI, 0.63-0.99, comparing >350 g/wk vs <50 g/mo). Collectively, a possible modest cardiovascular benefit (ie, approximately 10%-15% risk lowering) was found to be associated with consuming an equivalent of at least 175 g (2 servings) of fish weekly and with similar protection for more than 350 g (approximately 4 servings) weekly for secondary prevention. However, our findings require confirmation from randomized clinical trials evaluating the effects of increasing fish consumption (especially oily fish) on the clinical outcomes of people with vascular disease.

The first potential limitation of this study is that diet was self-reported, and variations in reporting may lead to random errors that could dilute real associations between fish intake and clinical outcomes. Second, we were not able to consider cooking methods, how the fish was consumed (with sauces, smoked, salted, etc), or contaminants in fish, which may also affect the results. Furthermore, we were not able to conduct a separate assessment of oily fish in PURE, which could at least partly explain the overall null findings. Third, in observational studies, the possibility of residual confounding cannot be completely ruled out (eg, fish intake may be a proxy for poverty or access to health care). However, our results persisted despite extensive adjustments for all known confounders, including the use of 4 markers of socioeconomic status (educational level, wealth, urban vs rural location, and geographic location). In addition, we adjusted for study center as a random effect, which takes into account socioeconomic factors and clustering by community, leading to comparisons within countries (eAppendix in the Supplement). Lastly, some misclassification of fish intake cannot be ruled out because we did not have repeated measures of diet in all studies, and a full-length FFQ was used only in PURE. However, the ORIGIN study, in which we conducted repeated diet assessments at 2 years, showed similar results based on the first vs second diet assessments, indicating that misclassification of fish intake during follow-up was not a major factor in our findings (eTable 3 in the Supplement).

In summary, this study found that a minimal fish intake of 175 g (approximately 2 servings) weekly was associated with lower risk of major CVD events and total mortality among high-risk individuals or patients with existing vascular disease but not in the general population.

Accepted for Publication: December 18, 2020.

Published Online: March 8, 2021. doi:10.1001/jamainternmed.2021.0036

Correction: This article was corrected on May 3, 2021, to fix an error in an author affiliation.

Corresponding Author: Andrew Mente, PhD, Population Health Research Institute, Hamilton Health Sciences and McMaster University, Second Floor, Room C2-105, 237 Barton St East, Hamilton, ON L8L 2X2, Canada (andrew.mente@phri.ca).

Author Contributions: Drs D. Mohan and Mente are co–first authors. Drs D. Mohan and Mente had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Mente, Dehghan, O’Donnell, V. Mohan, Khatib, Chifamba, Dans, S. Yusuf.

Acquisition, analysis, or interpretation of data: D. Mohan, Mente, Rangarajan, O’Donnell, Hu, Dagenais, Wielgosz, Lear, Wei, Diaz, Avezum, Lopez-Jaramillo, Lanas, Swaminathan, Kaur, Krishnapillai, Gupta, Szuba, Iqbal, R. Yusuf, Mohammadifard, Khatib, Yusoff, Gulec, Rosengren, Yusufali, Wentzel-Viljoen, Alhabib, Yeates, Teo, Gerstein, S. Yusuf.

Drafting of the manuscript: D. Mohan, Mente, Dehghan, Dans.

Critical revision of the manuscript for important intellectual content: Rangarajan, O’Donnell, Hu, Dagenais, Wielgosz, Lear, Wei, Diaz, Avezum, Lopez-Jaramillo, Lanas, Swaminathan, Kaur, Krishnapillai, V. Mohan, Gupta, Szuba, Iqbal, R. Yusuf, Mohammadifard, Khatib, Yusoff, Gulec, Rosengren, Yusufali, Wentzel-Viljoen, Chifamba, Alhabib, Yeates, Teo, Gerstein, S. Yusuf.

Statistical analysis: Mente, Dehghan, Hu, Wei, Khatib.

Obtained funding: O’Donnell, Lear, Lanas, Rosengren, Yusufali, Alhabib, Yeates.

Administrative, technical, or material support: Rangarajan, Dagenais, Wielgosz, Diaz, Lanas, Swaminathan, Krishnapillai, Gupta, Yusoff, Gulec, Yusufali, Wentzel-Viljoen, Alhabib, S. Yusuf.

Supervision: Rangarajan, Wielgosz, Diaz, Kaur, V. Mohan, Gupta, Szuba, Iqbal, R. Yusuf, Khatib, Yusufali, Chifamba, Alhabib, Yeates, Teo, S. Yusuf.

Conflict of Interest Disclosures: Dr Diaz reported receiving grants from Amgen and Sanofi; recieiving personal fees from Sanofi; and receiving grants from Amarin outside the submitted work. Dr Szuba reported receiving grants from the Polish Ministry of Science and Higher Education and from the Population Health Research Institute during the conduct of the study. Dr Gulec reported receiving personal fees from Amgen, Astra Zeneca, Boehringer Ingelheim, Daichii Sankyo, Menarini, Pfizer, and Recordati outside the submitted work. Dr Yusufali reported receiving grants from Sheikh Hamdan bin Rashid AlMakhtoum Medical Research Award during the conduct of the study. Dr Gertstein reported recieving grants from Sanofi during the conduct of the study; grants and personal fees from AstraZeneca, Lilly, Novo Nordisk and Sanofi; and receiving personal fees from Abbot, Boehringer Ingelheim, Kowa Pharmaceuticals America Inc, and Merck & Co outside the submitted work. Dr S. Yusuf reported recieving support from the Mary W Burke endowed chair of the Heart and Stroke Foundation of Ontario. No other disclosures were reported.

Funding/Support: Dr S. Yusuf is supported by the Marion W Burke endowed chair of the Heart and Stroke Foundation of Ontario. The PURE study is an investigator-initiated study that is funded by the Population Health Research Institute, Hamilton Health Sciences Research Institute (HHSRI), the Canadian Institutes of Health Research, Heart and Stroke Foundation of Ontario, Support from Canadian Institutes of Health Research’s Strategy for Patient Oriented Research, through the Ontario SPOR Support Unit, as well as the Ontario Ministry of Health and Long-Term Care and through unrestricted grants from several pharmaceutical companies (with major contributions from AstraZeneca [Canada], Sanofi-Aventis [France and Canada], Boehringer Ingelheim [Germany and Canada], Servier, and GlaxoSmithKline), and additional contributions from Novartis and King Pharma and from various national or local organisations in participating countries. These include: Argentina: Fundacion ECLA (Estudios Clínicos Latino America) ; Bangladesh: Independent University, Bangladesh and Mitra and Associates; Brazil: Unilever Health Institute, Brazil; Canada: This study was supported by an unrestricted grant from Dairy Farmers of Canada and the National Dairy Council (US), Public Health Agency of Canada and Champlain Cardiovascular Disease Prevention Network; Chile: Universidad de La Frontera [DI13-PE11]; China: National Center for Cardiovascular Diseases and ThinkTank Research Center for Health Development; Colombia: Colciencias (grant 6566-04-18062 and grant 6517-777-58228); India: Indian Council of Medical Research; Malaysia: Ministry of Science, Technology and Innovation of Malaysia (grants 100-IRDC/BIOTEK 16/6/21 [13/2007] and 07-05-IFN-BPH 010), Ministry of Higher Education of Malaysia (grant 600-RMI/LRGS/5/3 [2/2011]), Universiti Teknologi MARA, Universiti Kebangsaan Malaysia (UKM-Hejim-Komuniti-15-2010); occupied Palestinian territory: the United Nations Relief and Works Agency for Palestine Refugees in the Near East, occupied Palestinian territory; International Development Research Centre, Canada; Philippines: Philippine Council for Health Research and Development; Poland: Polish Ministry of Science and Higher Education (grant 290/W-PURE/2008/0), Wroclaw Medical University; Saudi Arabia: Saudi Heart Association, Dr.Mohammad Alfagih Hospital, The Deanship of Scientific Research at King Saud University (Research group RG -1436-013), Riyadh; Saleh Hamza Serafi Chair for Research of Coronary Heart Disease, Umm AlQura University, Makkah, Saudi Arabia; South Africa: The North-West University, SA and Netherlands Programme for Alternative Development, National Research Foundation, Medical Research Council of South Africa, The South Africa Sugar Association, Faculty of Community and Health Sciences; Sweden: Grants from the Swedish state under the Agreement concerning research and education of doctors; the Swedish Heart and Lung Foundation; the Swedish Research Council; the Swedish Council for Health, Working Life and Welfare, King Gustaf V’s and Queen Victoria Freemason’s Foundation, AFA Insurance; Turkey: Metabolic Syndrome Society, AstraZeneca, Sanofi Aventis; United Arab Emirates: Sheikh Hamdan Bin Rashid Al Maktoum Award For Medical Sciences and Dubai Health Authority, Dubai.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The PURE, ONTARGET, TRANSCEND, and ORIGIN investigators are as follows. An asterisk denotes a national coordinator, and a hashtag denotes deceased person. PURE Project Office Staff, National Coordinators, Investigators, and Key Staff: Project office (Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada): S. Yusuf* (Principal Investigator), S. Rangarajan (Program Manager); K.K. Teo, S.S. Anand, C.K. Chow, M. O’Donnell, A. Mente, D. Leong, A. Smyth, P. Joseph, M. Duong, R. D’Souza, M. Walli-Attaei, S. Islam (Statistician), W. Hu (Statistician), C. Ramasundarahettige (Statistician), P. Sheridan (Statistician), S. Bangdiwala, L. Dyal, B. Liu (Biometric Programmer), C. Tang (Biometric Programmer), X. Yang (Biometric Programmer), R. Zhao (Biometric Programmer), L. Farago (ICT), M. Zarate (ICT), J. Godreault (ICT), M. Haskins (ICT), M. Jethva (ICT), G. Rigitano (ICT), A. Vaghela (ICT), M. Dehghan (Nutrition Epidemiologist), A. Aliberti, A. Reyes, A. Zaki, B. Connolly, B. Zhang, D. Agapay, D. Krol, E. McNeice, E. Ramezani, F. Shifaly, G. McAlpine, I. Kay, J. Rimac, J. Swallow, M. Di Marino, M. Jakymyshyn, M(a). Mushtaha, M(o). Mushtaha, M. Trottier, N. Aoucheva, N. Kandy, P. Mackie, R. Buthool, R. Patel, R. Solano, S. Gopal, S. Ramacham, S. Trottier. Core Laboratories: G. Pare, M. McQueen, S. Lamers, J. Keys (Hamilton), X. Wang (Beijing, China), A. Devanath (Bangalore, India). Argentina: R. Diaz*, A. Orlandini, P. Lamelas, M.L. Diaz, A. Pascual, M. Salvador, C. Chacon; Bangladesh: O. Rahman*, R. Yusuf*, S.A.K.S. Ahmed, T. Choudhury, M. Sintaha, A. Khan, O. Alam, N. Nayeem, S.N. Mitra, S. Islam, F. Pasha; Brazil: A. Avezum*, C.S. Marcilio, A.C. Mattos, G.B. Oliveira; Canada: K. Teo*, S. Yusuf*, Sumathy Rangarajan, A. Arshad, B. Bideri, I. Kay, J. Rimac, R. Buthool, S. Trottier, G. Dagenais, P. Poirier, G. Turbide, A.S. Bourlaud, A. LeBlanc De Bluts, M. Cayer, I. Tardif, M. Pettigrew, S. Lear, V. de Jong, A.N. Saidy, V. Kandola, E. Corber, I. Vukmirovich, D. Gasevic, A. Wielgosz, A. Pipe, A. Lefebvre, A. Pepe, A. Auclair, A. Prémont, A.S. Bourlaud; Chile: F. Lanas*, P. Serón, M.J. Oliveros, F. Cazor, Y. Palacios; China: Liu Lisheng*, Li Wei*, Chen Chunming^#, Zhao Wenhua. Hu Bo, Yin Lu, Zhu Jun, Liang Yan, Sun Yi, Wang Yang, Deng Qing, Jia Xuan, He Xinye, Zhang Hongye, Bo Jian, Wang Xingyu, Liu Xu, Gao Nan, Bai Xiulin, Yao Chenrui, Cheng Xiaoru, Wang Chuangshi, Li Sidong, Liu Weida, Lang Xinyue, Liu Xiaoyun, Zhu Yibing, Xie Liya, Liu Zhiguang, Ren Yingjuan, Dai Xi, Gao Liuning, Wang Liping, Su yuxuan, Han Guoliang, Song Rui, Cao Zhuangni, Sun Yaya, Li Xiangrong, Wang Jing, Wang Li, Peng Ya, Li Xiaoqing, Li Ling, Wang Jia, Zou Jianmei, Gao Fan, Tian Shaofang, Liu Lifu, Li Yongmei, Bi Yanhui, Li Xin, Zhang Anran, Wu Dandan, Cheng ying, Xiao Yize, Lu Fanghong, Li Yindong, Hou Yan, Zhang Liangqing, Guo Baoxia, Liao Xiaoyang, Chen Di, Zhang Peng, Li Ning, Ma Xiaolan, Lei Rensheng, Fu Minfan, Liu Yu, Xing Xiaojie, Yang Youzhu, Zhao Shenghu, Xiang Quanyong, Tang Jinhua, Liu Zhengrong, Qiang Deren, Li Xiaoxia, Xu Zhengting, Aideeraili.Ayoupu, Zhao Qian; Colombia: P. Lopez-Jaramillo*, P.A. Camacho-Lopez, M. Perez, J. Otero-Wandurraga, D. I Molina, C. Cure-Cure, J.L. Accini, E. Hernandez, E. Arcos, C. Narvaez, A. Sotomayor, F. Manzur, H. Garcia, G. Sanchez, F. Cotes, A. Rico, M. Duran, C. Torres; India: Bangalore - P. Mony *, M. Vaz*, S. Swaminathan, A.V. Bharathi, K. Shankar, A. V. Kurpad, K.G. Jayachitra, H.A.L. Hospital, A.R. Raju, S. Niramala, V. Hemalatha, K. Murali, C. Balaji, A. Janaki, K. Amaranadh, P. Vijayalakshmi, Chennai - V. Mohan*, R.M. Anjana, M. Deepa, K. Parthiban, L. Dhanasekaran, S.K. Sundaram, M. Rajalakshmi, P. Rajaneesh, K. Munusamy, M. Anitha, S. Hemavathy, T. Rahulashankiruthiyayan, D. Anitha, R. Dhanasekar, S. Sureshkumar, D. Anitha, K. Sridevi, Jaipur - R. Gupta, R.B. Panwar, I. Mohan, P. Rastogi, S. Rastogi, R. Bhargava, M. Sharma, D. Sharma, Trivandrum - V. Raman Kutty, K. Vijayakumar, S. Nair, Kamala R., Manu M.S., Arunlal A.R., Veena A., Sandeep P. Kumar, Leena Kumari, Tessi R., Jith S., K. Ajayan, G. Rajasree, A.R. Renjini, A. Deepu, B. Sandhya, S. Asha, H.S. Soumya, Chandigarh- R. Kumar, M. Kaur, P.V.M. Lakshmi, V. Sagar J.S. Thakur, B. Patro, R. Mahajan, A. Josh, G. Singh, K. Sharma, P. Chaudary, Iran: R. Kelishadi*, A. Bahonar, N. Mohammadifard, H. Heidari, Kazakhstan: K. Davletov*, B. Assembekov, B. Amirov; Kyrgyzstan: E. Mirrakhimov*, S. Abilova, U. Zakirov, U. Toktomamatov; Malaysia: UiTM - K. Yusoff*, T.S. Ismail, K. Ng, A. Devi, N. Mat-Nasir, A.S. Ramli, M.N.K. Nor-Ashikin, R. Dasiman, M.Y. Mazapuspavina, F. Ariffin, M. Miskan, H. Abdul-Hamid, S. Abdul-Razak, N. Baharudin, N.M.N. Mohd-Nasir, S.F. Badlishah-Sham, M.S. Mohamed-Yassin, M. Kaur, M. Koshy, F.A. Majid, N.A. Bakar, N. Zainon, R. Salleh, S.R. Norlizan, N.M. Ghazali, M. Baharom, H. Zulkifli, R. Razali, S. Ali, C.W.J.C.W. Hafar, F. Basir; UKM - Noorhassim Ismail, M.J. Hasni, M.T. Azmi, M.I. Zaleha, R. Ismail, K.Y. Hazdi, N. Saian, A. Jusoh, N. Nasir, A. Ayub, N. Mohamed, A. Jamaludin, Z. Rahim; Occupied Palestinian Territory: R. Khatib*, U. Khammash, R. Giacaman; Pakistan: R. Iqbal*, R. Khawaja, I. Azam, K. Kazmi; Peru: J. Miranda*, A. Bernabe Ortiz, W. Checkley, R.H. Gilman, L. Smeeth, R.M. Carrillo, M. de los Angeles, C. Tarazona Meza; Philippines: A. Dans*, H.U. Co, J.T. Sanchez, L. Pudol, C. Zamora-Pudol, L.A. M Palileo-Villanueva, M.R. Aquino, C. Abaquin, S.L. Pudol, K. Manguiat, S. Malayang; Poland: W. Zatonski*, A. Szuba, K. Zatonska, R. Ilow^#, M. Ferus, B. Regulska-Ilow, D. Różańska, M. Wolyniec; Saudi Arabia: K.F. AlHabib*, M. Alshamiri, H.B. Altaradi, O. Alnobani, N. Alkamel, M. Ali, M. Abdulrahman, R. Nouri; South Africa: L. Kruger^*, A. Kruger^#, P. Bestra, H. Voster, A.E. Schutte, E. Wentzel-Viljoen, F.C. Eloff, H. de Ridder, H. Moss, J. Potgieter, A. Roux, M. Watson, G. de Wet, A. Olckers, J.C. Jerling, M. Pieters, T. Hoekstra, T. Puoane, R. Swart*, E. Igumbor, L. Tsolekile, K. Ndayi, D. Sanders, P. Naidoo, N. Steyn, N. Peer, B. Mayosi^#, B. Rayner, V. Lambert, N. Levitt, T. Kolbe-Alexander, L. Ntyintyane, G. Hughes, J. Fourie, M. Muzigaba, S. Xapa, N. Gobile, K. Ndayi, B. Jwili, K. Ndibaza, B. Egbujie; Sweden A. Rosengren*, K. Bengtsson Boström, A. Rawshani, A. Gustavsson, M. Andreasson, L. Wirdemann; Tanzania: K. Yeates*, M. Oresto, N. West Turkey: A. Oguz*, N. Imeryuz, Y. Altuntas, S. Gulec, A. Temizhan, K. Karsidag, K.B.T. Calik, A.K. Akalin, O.T. Caklili, M.V. Keskinler, K. Yildiz; United Arab Emirates: A.H. Yusufali, F. Hussain, M.H.S. Abdelmotagali, D.F. Youssef, O.Z.S. Ahmad, F.H.M. Hashem, T.M. Mamdouh, F.M. AbdRabbou, S.H. Ahmed, M.A. AlOmairi, H.M. Swidan, M. Omran, N.A. Monsef; Zimbabwe: J. Chifamba*, T. Ncube, B. Ncube, C. Chimhete, G.K. Neya, T. Manenji, L. Gwaunza, V. Mapara, G. Terera, C. Mahachi, P. Murambiwa, R. Mapanga, A. Chinhara. ONTARGET/TRANSCEND Office Staff, National Coordinators, Investigators, and Key Staff: Current members of the Operations Committee are denoted by an asterisk. Previous members of the Operations Committee are denoted by a dagger. NC denotes National Coordinator, and NL National Leader. Steering Committee: S. Yusuf (Chair and Principal Investigator),* P. Sleight,* C. Anderson,* K. Teo,* I. Copland,* B. Ramos,† L. Richardson,* J. Murphy,* M. Haehl,* L. Hilbrich,† R.Svaerd,* K. Martin,† D. Murwin,* T. Meinicke,† A. Schlosser,* G. Schmidt,† R. Creek,* H. Schumacher,* M. Distel,† B. Aubert, J.Pogue, L. Dyal, R. Schmieder, T. Unger, R. Asmar, G. Mancia, R. Diaz, E. Paolasso, L. Piegas, A. Avezum, G. Dagenais, E. Cardona Munoz, J. Probstfield, M. Weber, J. Young, R. Fagard, P. Jansky, J. Mallion, J. Mann, M. Böhm, B. Eber, N.B. Karatzas, M. Keltai, B.Trimarco, P. Verdecchia, A. Maggioni, F.W.A. Verheugt, N.J. Holwerda, L. Ceremuzynski, A. Budaj, R. Ferreira, I. Chazova, L. Rydén, T.L. Svendsen, K. Metsärinne, K. Dickstein, G. Fodor, P. Commerford, J. Redon, T.R. Luescher, A. Oto, A. Binbrek, A. Parkhomenko, G. Jennings, L.S. Liu, C.M. Yu, A.L. Dans, R. Shah, J.-H. Kim, J.-H. Chen, S. Chaithiraphan. Data and Safety Monitoring Board: J. Cairns (Chair), L. Wilhelmsen, J. Chalmers, J. Wittes, M. Gent, C.H. Hennekens. Adjudication Committee: G. Dagenais (Chair), N. Anderson, A. Avezum, A. Budaj, G. Fodor, M. Keltai, A. Maggioni, J. Mann, A. Parkhomenko, K. Yusoff, P. Auger, V. Bernstein, E. Lonn, A. Panju, I. Anand, J.T. Bigger, P. Linz, J. Healey, C. Held, C. McGorrian, M. Rokoss, J. Villar. Substudies/Publication Committee: P. Sleight (Chair), C. Anderson, R. Creek, A. Dans, R. Diaz, R. Fagard, J. Probstfield, R. Svaerd, K. Teo, T. Unger, S. Yusuf. Coordinating Centers: Hamilton: K. Teo, I. Copland, B. Ramos, A. McDonald, J. Pogue, L. Dyal, R. Afzal, F. Zhao, S. Yusuf; Oxford: P. Sleight, L. Richardson; Auckland: C. Anderson, J. Murphy. Sites and Principal Investigators by Country: Argentina: R. Diaz (NC), E. Paolasso (NL), R.A. Ahuad Guerrero, M. Amuchastegui, H.P. Baglivo, M. Bendersky, J. Bono, B. Bustos, A. Caccavo, L.R. Cartasegna, C.R. Castellanos, M.A. Cipullo, P. Crunger, C.A. Cuneo, M. Focaccia, J.J. Fuselli, E. Hasbani, M.A. Hominal, J. Humphreys, F. Inserra, C.R. Killinger, E. Kuschnir, C.R. Majul, O.D. Manuale, G. Martinez, E.M. Marzetti, R. Nordaby, A.D. Orlandini, J.C. Pomposiello, G.M. Rodríguez, J. Salas, O.A. Salomone, R.A. Sanchez, C. Serra, M.L. Vico; Australia: G.L.R. Jennings (NC), J.V. Amerena, L.F. Arnolda, G.M. Aroney, P.E. Aylward, C.F. Bladin, J.C. Bridgeman, B.R. Chambers, A.J. Corbett, D.S. Crimmins, D.B. Cross, L. Davies, S.M. Davis, G.A. Donnan, D.S. Eccleston, J.H. Frayne, R. Hendriks, G.K. Herkes, A.T. Hill, I.M. Jeffery, J.A. Karrasch, G. Koshy, T.H. Marwick, D.A. Owensby, M.W. Parsons, D.M. Rees, A. Russell, R. Schwartz, B. Singh, P.L. Thompson, J.H. Waites, W.F. Walsh, D.L. Walters, R.W. Watts, A.P. Whelan; Austria: M. Böhm (NC), B.E. Eber (NL), J.B. Bonelli, P. Dolliner, J.H. Hohenecker, G.S. Steurer, W.W. Weihs; Belgium: R. Fagard (NC), I. Bekaert, C. Brohet, P. Chaumont, P. Cheron, V. Crasset, J.-P. Degaute, P. Dendale, K. Dujardin, S. Elshot, S. Hellemans, M. Herssens, G. Heyndrickx, P. Laloux, H. Lesseliers, P. Noyens, M. Quinonez, F. Stammen, H. Striekwold, J. Thoeng, W. Van Mieghem, G. Vanhooren, G. Vervoort, M. Vrolix, B. Wollaert; Brazil: L. Piegas (NC), A. Avezum (NL), J.A.M. Abrantes, D. Armaganijan, J.C. Ayoub, L.C. Bodanese, A.C. Carvalho, M. Coutinho, J.P. Esteves, R.J.S. Franco, P.C.B.V. Jardim, J.F. Kerr Saraiva, P.E. Leães, L.N. Maia, J.A. Marin-Neto, R.L. Marino, D. Mion, Jr., J.R. Moreira, Jr., W. Oigman, R.C. Pedrosa, E.A. Pelloso, F.L. Plavnik, C.A. Polanczyk, Á. Rabelo, Jr., S. Rassi, G. Reis, A.B. Ribeiro, J.M. Ribeiro, J.C. Rocha, P.R.F. Rossi, R.D. Santos, J.C.E. Tarastchuk, M.N. Villalón; Canada: K. Teo (NC), G. Dagenais (NC), B. Abramson, M. Arnold, T. Ashton, P. Auger, I. Bata, K. Bayly, J. Beauchef, A. Bélanger, V. Bernstein, R. Bhargava, A.W. Booth, S. Bose, M. Boulianne, M. Cameron, Y.K. Chan, C. Constance, P. Costi, D. Dion, J. Douketis, D. Fell, J.P. Giannoccaro, A. Glanz, G. Gosselin, D. Gould, S. Goulet, F. Grondin, M. Gupta, G. Gyenes, J.W. Heath, V.A. Heath, A. Hess, J.G. Hiscock, G. Hoag, G. Honos, J. Imrie, R. Kuritzky, C. Lai, A. Lalani, A. Lamy, P. LeBouthillier, H. Lochnan, E. Lonn, B. Lubelsky, A. Mackey, M. Meunier, A. Milot, L.B. Mitchell, S. Nawaz, M. Omichinski, A. Panju, C. Pilon, D. Pilon, P. Polasek, G. Proulx, T. Rebane, A.J. Ricci, D.W. Rupka, É. Sabbah, D. Savard, N.K. Sharma, D. Shu, R. St. Hilaire, F. St. Maurice, R. Starra, B. Sussex, T. Szaky, P. Talbot, K.-W. Tan, T.B. To, S. Tobe, R. Tytus, R. Vexler, P. Whitsitt, V. Woo; China: L. Liu (NC), X. Bai, X. Chen, J. Feng, S. Fu, Y. Ge, L. Gong, Z. He, J. Huang, Y. Jiang, L. Li, Q.H. Li, Y. Liao, Z. Lu, F. Lu, S. Ma, F. Niu, C. Pan, F. Qian, X. Shi, N. Sun, M. Sun, G. Sun, J. Wang, S. Wang, Y. Wang, Z. Wu, X. Yan, X. Yang, H. Yang, X. Ye, S. Yuan, T. Zhang, C. Zhang, F. Zhang, S. Zhang, D. Zhao, B. Zheng, H.Y. Zhou, S. Zhou, J. Zhu; Czech Republic: P. Janský (NC), V. Dedek, J. Dvorák, R. Holaj, J. Kotouš, E. Pederzoliová, M. Polák, J. Povolný, K. Smetana, J. Špác; Denmark: T.L. Svendsen (NC), L. Götzsche, H.F. Juhl, K. Koelendorf, P. Lund, F. Pedersen, O.L. Perdersen, T. Pindborg, L.H. Rasmussen, S.L. Rasmussen, K. Thygesen, C. Tuxen; Finland: K. Metsärinne (NL), R. Antikainen, M. Jääskivi, I. Kantola, M. Kastarinen, P. Kohonen-Jalonen, A. Koistinen, E. Lehmus, R. Nuuttila, M.-L. Tuominen, H. Ylihärsilä; France: J. Mallion (NC), N. Abenhaim, J. Allix, L. Boucher, M. Bourgoin, A. Boye, N. Breton, D. Cadinot, A. Campagne, J. Churet, G. Constantin, E. De Sainte Lorette, A. El Sawy, G. Etchegarray, S. Farhat, F. Lacoin, T. Latte, C. Magnani, D. Pineau-Valenciennes, M. Pithon, A. Quéguiner, J. Sicard, G. Sorbe, D. Taminau, H. Vilarem, J.Y. Vogel; Germany: H.H. Ebert, S. Genth-Zotz, N. Hermanns, C. Holzer, J. Minnich, D. Schimkus, M. Boehm (NC), J. Mann (NC), B. Brado, G. Claus, U. Dietz, R. Griebenow, T. Haak, K. Hahn, R. Hampel, H. Heitzer, G. Holle, T. Horacek, J. Jordan, C. Klein, R. Kolloch, S. Ludewig, W. Motz, T. Muenzel, H.P. Nast, M. Nauck, H. Nebelsieck, K. Rybak, H. Samer, T. Schaefer, J. Scholze, B. Schulze, Schleppinghoff, R. Schmieder, B. Schwaab, U. Sechtem, W. Sehnert, E. Steinhagen-Thiessen, G. Stenzel, P. Trenkwalder, B. Wedler, J. Zippel; Greece: N. Karatzas (NC), A. Achimastos, E. Diamantopoulos, A. Efstratopoulos, M. Elisaf, H. Karvounis, D. Mentzikof, D. Mytas, D. Papadogiannis, V. Pyrgakis, C. Stefanadis, D. Symeonidis, A. Tsoukas, I. Vogiatzis, S. Voyaki, C. Zamboulis; Hong Kong: C.-M. Yu (NC), C.K.H. Chan, L. Lam, Y.K. Lau, J. Sanderson, J. Wong, E.B. Wu, C.S. Yue; Hungary: M. Keltai (NC), I. Czuriga, I. Édes, C.S. Farsang, Á. Kalina, K. Karlócai, K. Keltai, M. Kozma, Z. László, V. Nagy, A. Papp, G.Y. Polák, I. Préda, A. Rónaszéki, M. Sereg, K. Simon, S. Sonkodi, J. Szegedi, S. Timár, K. Tóth, G.Y. Vándorfi, A. Vértes; Ireland: J. Feely, V.M.G. Maher, A.V. Stanton, P. Sullivan; Italy: B. Trimarco (NC), P. Verdecchia (NC), A. Maggioni (NL), E. Agabiti Rosei, G.B. Ambrosio, M. Bentivoglio, A. Branzi, P. Cavallo Perin, M. Chiariello, V. Cirrincione, R. Ferrari, R. Gattobigio, E. Giovannini, D. Giugliano, A. Lacchè, R. Lauro, G. Lembo, G. Marchetti, L. Moretti, L. Pancaldi, L. Partemi, S. Pede, G. Pettinati, G. Reboldi, R. Ricci, G. Rosiello, F. Rozza, M.G. Sardone, E.V. Scabbia, G. Selvetella, L. Tavazzi, P. Terrosu, A. Venco, A. Vetrano, M. Volpe, G. Zilio; Malaysia: T. Ismail, R.P. Shah, M. Singaraveloo, W.A. Wan Ahmad, Z. Yusof, K. Yusoff, I. Zainal Abidin, R. Zambahari; Mexico: E. Cardona Munoz (NC), L. Alcocer Diaz, S. Pascoe-Gonzalez, R. Arriaga Nava, G. De La Peña Topete, L.A. Elizondo Sifuentes, H.R. Hernández García, J. Illescas-Diaz, M.A. Macías Islas, J.A. Noriega Arellano, R. Olvera Ruiz, J.Z. Parra Carrillo, G. Velasco Sánchez, M. Vidrio Velásquez; the Netherlands: F.W.A. Verheugt (NC), N.J. Holwerda (NL), D.C.G. Basart, A.J.M. Boermans, H.A. Bosker, K.P. Bouter, C.P. Buiks, W.A. de Backer, J. J. de Graaf, J.H.M. Deppenbroek, F.D. Eefting, F.C.N.M. Gunneweg, H.R. Michels, D. Poldermans, G. Schrijver, M.I. Sedney, T. Slagboom, J.G. Smilde, G.E.M.G. Storms, R.M. Tjon, P.F.M.M. van Bergen, G.J.M. van Doesburg, L.H.J. van Kempen, H.F.C.M. van Mierlo, A. Veerman, F.A.A.M. Vermetten, A. Wester; New Zealand: W. Bagg, J. Benatar, R.J. Coxon, R.N. Doughty, D.H. Friedlander, R.A. Luke, P.L. Nairn, Y. Ratnasabapathy, A.M. Richards, G.P. Singh, R.A.H. Stewart, R.W. Troughton, H.D. White, M. Williams, S.P. Wong; Norway: K. Dickstein (NL), N. Bogale, J.O. Lier, J.E. Otterstad, P.K. Rønnevik, S. Skeie, P.O. Walle; Philippines: A.L. Dans (NC), M.T.B. Abola, J.C. Añonuevo, J.M. Jaro, D.R. Marañon, V.L. Mendoza, D.R. Morales, E.P. Pacheco, E.B. Reyes, A.A. Roxas, M.B. Sedurante; Poland: L. Ceremuzynski (NC), A. Budaj (NC), Z. Binio, M. Bronisz, P. Buszman, T. Czerski, M. Dalkowski, J. Gessek, A. Gieroba, K. Janik, M. Janion, T. Kawka-Urbanek, R. Klabisz, M. Krauze-Wielicka, S. Malinowski, P. Miekus, J. Mormul, M. Ogorek, G. Opolski, M. Skura, M. Szpajer, M. Tendera, T. Waszyrowski, M. Wierzchowiecki, B. Zalska; Portugal: R. Ferreira (NC), R. Capucho, C. Correia, L. Cunha, J.M. Ferro, V. Gama Ribeiro, V. Gil, P. Marques da Silva, M. Oliveira Carrageta, R. Sebra Gomes, M. Veloso Gomes; Russia: I. Chazova (NC), F. Ageev, Y. Belenkov, A. Ivleva, Y. Karpov, M. Shestakova, E. Shlyakhto, S. Shustov, B. Sidorenko; Singapore: H.M. Chang, B. Kwok; Slovakia: G. Fodor (NC), A. Dukát, J. Gonsorcík, M. Hranai, J. Lietava, D. Pella, R. Rybar, L. Ruffini; South Africa: P. Commerford (NC), F. Bonnici, B. Brown, A.J. Dalby, G.J. Gibson, L. Herbst, J. King, E. Klug, M. Middle, D. P. Naidoo, M. Pretorius, G. Podgorski, N. Ranjith, K. Silwa-Hahnle, H. Theron; South Korea: J.H. Kim (NC), S.C. Chae, N.S. Chung, K.P. Hong, M.H. Jeong, H.J. Kang, J.J. Kim, M.H. Kim, H.S. Seo, E.K. Shin; Spain: J. Redón (NC), J. Abellán, P. Aranda, V. Barrios, C. Calvo, M. De La Figuera, E. De Teresa, R. Durá, F. Escobar, F. Fernandez-Cruz, E. Galve, J. Garcia-Puig, B. Gil-Extremera, R. Gomis, O. Gonzalez-Albarran, J.R. González-Juanatey, A. Llacer, L. López-Bescós, J. Oliván, A. Picó, A. Pose, A. Roca-Cusachs, L.M. Ruilope; Sweden: L. Rydén (NC), A. Alvång, P.-Å. Boström, M. Dellborg, U.-B. Ericsson, J. Herlitz, T. Juhlin, K. Pedersen, B. Sträng, B. Sundqvist, B.-O. Tengmark, G. Ulvenstam, B. Westerdahl, L. Winberg; Switzerland: T.R. Luescher (NC), I. Baumgartner, P. Dubach, A. Gallino, T. Moccetti, G. Noll, A. Nordmann, H. Rickli, H. Schläpfer, K. Weber; Taiwan: J.-H. Chen (NC), T.H. Chao, C.Y. Chen, J.J. Cheng, H.C. Chiou, C.C. Fu, M. Fu, W.T. Lai, Y.H. Li, L.M. Lien, C.D. Tsai, J.H. Wang, P.S. Yeh; Thailand: S. Chaithiraphan (NC), T. Chantadansuwan, K. Jirasirirojanakorn, R. Krittayaphong, P. Laothavorn, N. Mahanonda, S. Sitthisook, S. Tanomsup, S. Tansuphaswadikul, P. Tatsanavivat, S. Yamwong; Turkey: A. Oto (NC), M. Akin, N.T. Caglar, A. Ergin, H. Müderrisoglu, A. Oguz, Z. Ongen, V. Sansoy, T. Tetiker, A. Uysal; Ukraine: A. Parkhomenko (NC), E. Amosova, O. Cherkasova, Y. Dykun, G. Dzyak, A. Galystska, O. Grishyna, O. Jaremenko, L. Kononenko, E. Koval, V. Kovalenko, V. Netyazhenko, T. Pertseva, A. Prokhorov, G. Radchenko, Y.U. Rudyk, Y. Sirenko, A. Skarzhevsky; United Arab Emirates: A.S. Binbrek (NC), A.A.R. Al Hajiri, E. Al Hatou, A.A.S. Al-Sousi, M. Alomairi, I. Maqsood Wajib; United Kingdom: P. Sleight (NC), A.A.J. Adgey, R. Andrews, S.G. Ball, D.H. Barer, A.H. Barnett, A.B. Bridges, V. Bryson, A.S. Cowie, A.J. De Belder, R. Donnelly, C.M. Francis, J. Furnace, S.K. Glen, N. Gough, A.M. Heagerty, P.R. Jackson, S.H.D. Jackson, E. Joyce, D.J. McEneaney, A.J. Moriarty, D.L. Murdoch, J.P. O’Hare, W.J. Penny, C.J. Reid, J. Tilley, J.P. Vora, J. Webster, B. Williams; United States: J. Probstfield (NC), M. Weber (NC), J. Young (NC), I. Ahmed, I.S. Anand, J.L. Anderson, J.S. Aponte Pagán, J. Barzilay, J.N. Basile, P.F. Bass III, S.S. Blumenthal, W.J. Bommer, D.F. Brautigam, C.D. Brown, N. Brown, J.D. Byrum, A.A. Carr, J. Chinn, D. Chiu, N.R. Cho, J.O. Ciocon, P.J. Colón-Ortíz, J.B. Cruz, W.D. Dachman, G.M. Dolson, S.G. Dorfman, W. Drummond, C. East, F. Eelani, H.S. Ellison, J.V. Felicetta, M.H. Fishbach, R.W. Force, S.J. Giddings, M.C. Goldberg, S. Goldman, R. Gomez Adrover, S.L. Goss, S.P. Graham, C.B. Granger, M.M. Greenspan, R.H. Grimm, G.B. Habib, M.R. Hagen, P.D. Hart, T.J. Hartney, M.A. Henriquez, J.J. Holland, B.J. Hoogwerf, M. Hossfeld, A.K. Jacobson, M.J. Jelley, T.V. Jones, R.A. Kaplan, D.G. Karalis, L.A. Katz, D.J. Kereiakes, M. Khan, R.M. Kipperman, M.J. Kozinn, J.G. Kozlowski, E.W. Lader, C. Landau, J.S. Landzberg, D. Laughrun, S.J. Lewis, C.S. Liang, M.C. Limacher, P.E. Linz, T.S. Lo, F. Lopez-Arostegui, R.R. Maddox, P.R. Mahrer, M.S. Maurer, D.K. McGuire, A.D. Mercando, J.H. Mersey, M. Meyer, A.N. Mooss, P. Narayan, S. Oparil, D.N. Padhiar, A.L. Phillips, M. Prisant, N. Qureshi, M.P. Raghuwanshi, R.R. Randall, T.M. Retta, R.E. Ringrose, A.A. Rizvi, M.D. Rizvi, M.G. Saklayen, S. Sastrasinh, I.K. Savani, A. Schlau, H.S. Schultz, M.J. Schweiger, R.D. Smith, M. Sosa-Padilla, D. Streja, T.P. Stuver, D.C. Subich, F.C. Sulak, W.A. Swagler III, M. Taitano, J.A. Tavarez-Valle, E.M. Taylor, M.L. Tuck, W.B. White, W.J. Wickemeyer, T.B. Wiegmann, P.A. Zee, X.Q. Zhao. ORIGIN Office Staff, National Coordinators, Investigators, and Key Staff: Operations committee: H. Gerstein (Co-chair and Co-PI), S. Yusuf (Co-chair and Co-PI), L. Rydén (European Co-chair), J. Bosch (Project Director), L. Richardson (European Project Office), G. Dagenais, R. Diaz, P Johnston, A. Maggioni, J Probstfield, A. Ramachandran, M. Riddle, R. Vige. Steering committee: H. Gerstein (Co-chair and Co-PI), S. Yusuf (co-chair and co-PI), L. Rydén (European co-chair), K. Birkeland, J. Bosch (project director), A. Budaj, E. Cardona, I. Chazova, P. Commerford, G. Dagenais, R. Diaz, L. Danilova, M. Davies, R. Fernando, G. Fodor, R. Gilbert, R. Gomis, N. Hâncu, M. Hanefeld, P. Hildebrandt, P. Johnston, G. Kacerovsky-Bielesz, M. Keltai, J.H. Kim, H. Krum, H. Kültürsay, F. Lanas, B.S. Lewis, E. Lonn, P. López-Jaramillo, A. Maggioni, J. Marin-Neto, M. Marre, R McKelvie, M. McQueen, I. Mendoza, C. Morillo, C. Pan, V. Pīrāgs, J. Probstfield, V. Profozic, A. Ramachandran, R. Ratner, M. Riddle, L. Richardson (European Project Office), J. Rosenstock, G.A. Spinas, S. Sreenan, I. Stoel, M. Syvänne, R. Vige, J.F. Yale. Event adjudication committee: G. Dagenais (chair), R. McKelvie (co-chair), A. Avezum, M.C. Bahit, P. Bogaty, L. Bordeleau, C. Chacόn, M. Corson, G. Fodor, W.L. Harper, D. Halon, P. Hildebrandt, P Magloire, J. Mann, C. Morillo, V. Pavlova, Z. Punthakee, J. Silva, M. Syvänne, B. Tsang, N. Yakubovich. Substudy and publications committee: A. Maggioni (co-chair), J. Probstfield (co-chair), P. Commerford, M. Davies, R. Gilbert, P. Johnston, J. Marin-Neto, M. McQueen; Glycemia management committee: H. Gerstein, M. Hanefeld, P. Johnston, A. Ramachandran, R. Ratner, M. Riddle, J. Rosenstock, J.F. Yale; Global project office: A. Abdallah, S. Ahmad, J. Bosch, J. Chandra, R. Chandra, T. Cukierman-Yaffee, L. Dyal, H. Gerstein, H. Jung, L. Joldersma, L. MacRae, S. MacRae, S. Malik, A. Mead, F. Pasha, J. Pazmino-Canizares, J. Pogue, K. Pohl, L. Richardson, A. Sakalas, J. Tyrwhitt, S. Yusuf. Site investigators by country: Argentina: R. Diaz, R. Ahuad Guerrero, A. Alebuena, N. Alvarez, M. Alzogaray, M. Amuchastegui, M. Andres, M. Angos, H. Baglivo, M. Barbieri, F. Bassi, F. Bello, J. Bono, M. Bustamante Labarta, B. Bustos, A. Caccavo, M. Calveira, A. Camino, M. Cantero, M. Capozzi, M. Cardone, L. Cartasegna, A. Cassetari, R. Castellanos, R. Chavez Caballero, M. Cipullo, A. Contreras, J. Coria, F. Corinaldesi, G. Costa, C. Crespo, M. Cruz, J. Cuello, C. Cuneo, I. Del Corro, R. Diez, C. Dituro, A. Dominguez, A. Facta, C. Faingold, M. Farah, A. Fares Taie, A. Fernandez, A. Ferrari, N. Ferrari, C. Garcia Monteverde, M. Garrido, C. Giachello, M. Gonzalez, N. Gutierrez, L. Guzman, P. Guzman, E. Hasbani, R. Henquin, A. Hershon, A. Hirschon Alvarez Prado, M. Hominal, A. Hrabar, H. Imposti, M. La Grutta, P. Lanchiotti, L. Lobo Marquez, R. Lopez Santi, J. Lowenstein, M. Lugo, M. Luqueci, S. Mainini, C. Majul, R. Manzano, S. Manzur, G. Marcucci, M. Marino, F. Massari, N. Mendez, M. Molina, O. Montaña, M. Mulazzi, L. Nardone, I. Odetto, A. Orlandini, A. Oviedo, O. Paez, A. Parnas, F. Risso Patron, C. Pedernera, M. Pelagagge, M. Plastino, P. Polari, J. Pomposiello, A. Porta, A. Prado, M. Quiroz, A. Ramirez, C. Rodriguez, M. Rodriguez, R. Ronderos, L. Sago, A. Sanchez, R. Sanchez, A. Sandrin, P. Schygiel, V. Sernia, I. Sinay, T. Smith Casabella, A. Sosa Liprandi, M. Sosa Liprandi, L. Soso, G. Sposetti, D. Stisman, P. Streitenberger, G. Suarez, H. Tonin, M. Ulla, J. Valdez, M. Vico, A. Villamil, A. Villarino, A. Viscaya Castro, V. Visco, D. Vogel, F. Waisman, C. Zaidman; Australia: H. Krum, J. Amerena, A. Applebe, P. Aylward, M. Binnekamp, I. Bruce, C. Burdeniuk, R. Burnet, P. Colman, D. Colquhoun, S. Davis, F. De Looze, C. De Pasquale, M. D'Emden, H. Eaton, A. Farshid, S. Foulanos, J. Galanos, G. Gordon, M. Guhu, J. Ho, I. Jeffery, G. Jerums, M. Kwan, J. Lefkovits, S. Luu, R. MacIsaac, J. Marjason, V. Mohabbati, A. Nankervis, D. O'Neal, N. Perera, A. Poynten, A. Rahman, S. Razak, T. Roberts, M. Sebastian, R. Simpson, G. Soldatos, D. Sullivan, H. Teede, F. Tiong, D. Topliss, D. Torpy, K. Waddell-Smith, J. Waites, J. Wenman, A. Whelan, L. Williams, B. Yeap, W. Yeow, G. Yong; Austria: G. Kacerovsky-Bielesz, S. Aczel, N. Azimy, P. Bertha, J. Blocher, C. Bohnel, H. Brath, J. Breuss, A. De Campo, H. Drexel, Y. Ettmuller, A. Feder, C. Feinboeck, E. Gulz, M. Hofmann, F. Hoppichler, H. Jahnel, V. Jankovic, T. Kann, T. Kathrein, T. Kotter, E. Kratz, E. Kreuzwieser, C. Loreck, B. Ludvik, T. Marte, K. Mellitzer, S. Nistler, G. Placher-Sorko, R. Prager, P. Rein, M. Riedl, C. Säly, G. Schernthaner, E. Schichka, C. Seidlhofer, M. Sonnenfeld, H. Stefan, K. Steiner, B. Thomas, H. Toplak, K. Urstoger, B. Vetter, A. Vonbank, W. Waldschutz, F. Wallner, F. Winkler; Belarus: L. Danilova, D. Goncharik, I. Lazareva, N. Lichorad, A. Mrochek, N. Murashko, D. Radyuk, A. Ramanovski, S. Sudzhaeva, V. Sujayeva, N. Yarashevich; Bermuda: G. Campbell, S. Marshall, A. West; Brazil: J. Marin-Neto, F. Abreu, M. Alves, J. Ayoub-Aidar, M. Barros, J. Barros-Silveira, M. Blacher, E. Costa, F. Costa, C. Daltro, J. Delana, F. Eliaschewitz, C. Facanha, G. Feitosa, J. Figueiredo, A. Forti, D. Franco, M. Franken, F. Freire, V. Garcia, A. Gouvea-Neto, S. Grofallo, N. Kanedlai, J. Kerr-Saraiva, R. Ladeira, P. Leaes, M. Lemos, F. Lima, M. Lima Filho, L. Macedo, E. Manenti, J. Marin-Neto, O. Monte, A. Mossman, F. Mothe, O. Mouco, M. Moyses Golbert, L. Nasser Hissa, M. Nasser-Hissa, J. Nicolau, L. Nigro Maia, T. Ninno, C. Nunes, C. Oliveira, O. Oliveira, R. Passos da Silva, J. Pericles-Esteves, L. Rabelo, A. Rabelo-Alves Jr., S. Rassi, R. Rech, F. Roldan, J. Salles, C. Sampaio, A. Seabra, N. Sealissi, A. Seixas, R. Sena, I. Shehadeh, M. Teixeira, H. Turin, C. Vicente Serrano Jr., M. Vidigal, M. Vilela, B. Wajchenberg; Canada: G. Dagenais, E. Lonn, C. Abbott, A. Abu-Bakare, J. Ardilouze, E. Auersperg, A. Bailey, G. Bailey, J. Baillargeon, C. Beaurivage, J. Belair, A. Belanger, D. Bellabarba, J. Berlingieri, F. Bernier, R. Bhargava, T. Bhesania, W. Booth, S. Bose, M. Boulianne, S. Bourgeois, D. Breton, R. Brossoit, J. Buithieu, J. Campeau, B. Carlson, A. Carpentier, R. Cavalcanti, J. Cha, P. Chagnon, Y. Chan, C. Chessex, J. Chiasson, S. Chouinard, D. Clayton, J. Conway, J. Crepeau, D. Cudmore, G. D'Ignazio, G. Doig, M. Dominguez, F. Dube, R. Dumas, R. Dupuis, I. Dyrda, D. Eddy, D. Eiley, H. Fox, S. Fratesi, S. Gallant, C. Garceau, N. Garfield, C. Germain, S. Glazer, G. Gosselin, D. Gould, G. Grills, J. Halle, P. Hardin, W. Harper, J. Heath, V. Heath, M. Hivert, K. Ho, G. Houde, I. Hramiak, A. Hutchinson, T. Huynh, R. Ilie-Haynes, S. Imran, A. Islam, M. Iwanochko, C. Jones, C. Joyce, I. Kirouac, R. Kumar, M. Lamothe, M. Langlois, C. Lauzon, M. Lavoie, R. Leader, S. Lecours, S. Lepage, H. Lochnan, P. Ma, S. Malik, A. McLean, S. Mecci, P. Mehta, M. Mercier, D. Miller, A. Morisset, S. Nawaz, W. Nisker, G. Nyomba, D. O'Keefe, J. Palardy, P. Parekh, T. Paul, P. Perron, M. Pesant, R. Phillips, G. Pruneau, I. Quintin, K. Raby, C. Richard, G. Rosenfeld, D. Saulnier, J. Shaban, A. Shah, D. Shu, R. Sigal, M. Silverman, J. Singh, W. Sivucha, A. Skamene, D. Sliwowicz, R. Smith, R. St. Hilaire, D. Steinson, B. Sussex, K. Tan, R. Tannous, A. Telner, P. Theroux, C. Tsoukas, G. Tsoukas, J. van Buuren, N. Van Rossum, R. Vexler, S. Vizel, W. Warnica, M. Weingert, R. Wilson, R. Wilson, W. Wong, V. Woo, J. Yale; Chile: F. Lanas, M. Acevedo, C. Alwyn, E. Baier, S. Baier, R. Galloso, R. Lahsen, G. Lorenas, A. Montecinos, M. Montecinos, P. Pineda, F. Pollak, J. Sapunar, V. Serrano, B. Stockins, P. Varleta, J. Yovanovich, F. Zambra; China: C. Pan, J. Ba, Y. Bao, Y. Bi, S. Bu, B. Chen, H. Chen, H. Chen, J. Chen, L. Chen, L. Chen, M. Chen, Y. Chen, Y. Chen, J. Cui, M. Dong, P. Feng, Z. Feng, C. Gao, F. Gao, X. Gao, Z. Gao, Y. Gong, L. Guang, X. Guo, F. Han, X. Han, X. Hou, R. Hu, L. JI, J. Jia, W. Jia, X. Jiao, X. Jin, J. Kuang, M. Li, Q. Li, X. Li, Y. Li, Y. Ling, F. Liu, Z. Liu, B. Lu, J. Lu, Z. Lu, X. Lv, G. Ning, Y. Peng, Y. Ren, Y. Shao, Y. Shi, X. Shu, H. Sun, L. Sun, X. Sun, K. Tang, H. Tian, H. Tian, C. Wang, F. Wang, L. Wang, Q. Wang, W. Wang, X. Wang, Y. Wang, Y. Wang, J. Wen, C. Wu, H. Wu, H. Wu, J. Wu, M. Wu, X. Xing, Y. Xue, L. Yan, S. Yan, H. Yang, N. Yang, W. Yang, Z. Yang, J. Yao, J. Yao, L. Yao, D. Yu, H. Yu, M. Yu, X. Yu, L. Yuan, M. Yuan, S. Yuan, W. Yuan, Y. Yuan, Z. Yuan, T. Zeng, J. Zhang, R. Zhang, X. Zhang, X. Zhang, L. Zhao, B. Zheng, J. Zheng, J. Zheng, W. Zhou, N. Zhu, Y. Zhu, D. Zou, J. Zou; Colombia: P. Lopez-Jaramillo, C. Morillo, J.L. Accini, R. Bohorquez, R. Botero, C. Cure, M. Figueredo, E. Hernandez, W. Kattah, A. Llamas, L. Orozco, L. Pava, M. Perez, M. Pineda, A. Quintero, R. Quiros, M. Urina, S. Velez: Croatia: V. Profozic, V. Altabas, I. Baotic, M. Berkovic, V. Goldoni, T. Kerum, G. Mirosevic, D. Tarle, I Vidovic, V. Zjacic-Rotkvic; Denmark: P. Hildebrandt, R. Abbas, H. Andersen, S. Auscher, L. Baumbach, H. Brockstedt, P. Christensen, M. Christiansen, K. Clemmensen, K. Egstrup, G. Gislason, D. Haar, K. Hansen, P. Heden Andersen, K. Helleberg, K. Hermansen, J. Holmer, J. Jeppesen, I. Klausen, T. Koustrup-Sonder, T. Krarup, S. Lerche, H. Lervang, B. Linde, P. Lund, S. Lund, S. Madsbed, J. Molvig, C. Orskov, O. Ostergaaard, H. Perrild, A. Pietraszek, N. Ralfkjaer, H. Roenne, J. Rokkedal Nielsen, M. Seibaek, H. Soendergaard, L. Sorensen, L. Sundahl Mortensen, C. Torp-Pedersen, C. Tuxen, S. Urhammer, E. Vadstrup; Estonia: V. Pirags, A. Ambos, A. Janson, P. Rudenko, L. Viitas; Finland: M. Syvänne, S. Aranko, M. Badeau, J. Eriksson, H. Haapamäki, O. Kajander, A. Kuusisto, S. Luukkonen, J. Mäkelä, S. Nieminen, L. Niskanen, J. Ripatti, S. Ruotsalainen, J. Saltevo, K. Sävelä, J. Strand, T. Valle, A. Virkamäki; France: M. Marre, E. Aboud, L. Alavoine, A. Bekherraz, P. Bohme, H. Bourezane, B. Catargi, G. Charpentier, A. Clergeot, J. Courreges, T. Delmas, F. Duengler, C. Feknous, D. Gendre, B. Guerci, S. Hadjadj, V. Kerlan, N. Laguerre, J. Le Potier, F. Lombardo, E. Malville, R. Marechaud, C. Mattei, J. Moreira, A. Penfornis, C. Petit, J. Pinel, X. Piquel, D. Raccah, Y. Reznik, A. Rod, N. Roudaut, E. Rousseau, F. Schillo, B. Schmitt, E. Sonnet, F. Torremocha, F. Travert, C. Vanhoute, M. Vimeux; Germany: M. Hanefeld, R. Abdollahnia, A. Adamidou, S. Arslan, B. Bach-Kliegel, B. Bartusch, N. Bauer, T. Bieler, H. Blankenfeld, U. Boeckmann, K. Busch, R. Butzer, M. Chenchanna-Merzhaeuser, R. Denger, C. Deutsch, S. Diessel, I. Donati-Hirsch, M. Dornisch, K. Enghofer, T. Fleig, T. Forst, M. Frommherz, K. Goeller, J. Habbig, S. Hadziselimovic, A. Hamann, T. Hampel, S. Heger, C. Helmes, C. Hoffman, C. Hohberg, P. Humpert, A. Kamke, W. Kamke, P. Kindermann, C. Klein, D. Klein, A. Koehler, A. Kuehn, K. Langer, S. Limmer, A. Loew, A. Maimer, C. Marck, G. Meier, M. Methner-Friederich, W. Metzler, K. Meyer, N. Miftari, J. Milde, J. Minnich, M. Molkewehrum, M. Morcos, C. Mueller-Hoff, M. Nguyen, M. Nishwitz, J. Oldenburg, P. Ott, K. Pauli, B. Pauly, A. Pfeiffer, A. Pfuetzner, U. Pischa, R. Radke, P. Reismann, M. Riemer, H. Rochlitz, G. Rudofsky, S. Ruhla, A. Sammler, F. Schaper, K. Schiemenz, G. Scholz, P. Schumm-Draeger, T. Segiet, A. Segner, J. Seissler, S. Spahn, U. Stier, G. Tonon, S. von Amelunxen, C. von Schacky, B. Wilhelm, K. Wilhelm, K. Witt, S. Wuechner-Hofmann; Hungary: M. Keltai, M. Baranyai, Z. Birkus, I. Foldesi, Z. Gaal, E. Harcsa, K. Hati, Z. Hohmann, I. Istenes, I. Jozsef, E. Juhasz, P. Kempler, B. Keresztes, K. Keresztes, P. Kis-Gombos, I. Kovacs, T. Kozma, Z. Laszlo, E. Noori, G. Nyirati, Z. Papp, J. Patkay, F. Poor, P. Pusztai, Z. Putz, E. Rigo, M. Sereg, K. Simon, A. Somogyi, J. Sumegi, A. Szabo, J. Szabo, S. Szigeti, D. Szilveszter, M. Tarko, C. Varga, L. Varga Szabo, P. Voros; India: A. Ramachandran, Arathi, S. Aravind, M. Badgandi, M. Balaji, V. Balaji, S. Chamukuttan, Devi Manduva, S. Fatima, B. Ganapathy, O. George, P. George, M. Jaffar, P. Jain, P. Kamath, V. Karthik, G. Koshy, L. Krishnan, H. Kumar, P. Lal, A. Mithal, S. Modi, V. Mohan, V. Moses, R. Oomen, P. Pais, P. Pati, S. Pendsey, P. Rai, R. Rajagopal, M. Ramu, U. Ranjit, P. Rao, V. Senthil, V. Seshaiah, B. Sethi, P. Shah, R. Sharma, S. Shetty, A. Shobha, R. Siddharth, G. Sridhar, K. Sudeep, C. Sunil, S. Sunitha, S. Suresh, N. Thomas, A. Vageesh; Ireland: S. Sreenan, Z. Anwer, J. Barton, L. Behan, M. Bell, M. Cullen, S. Dineen, M. Draman Yusof, F. Dunne, J. Gibney, T. Hussain, M. Khan, B. Kinsley, P. Kyithar, F. Lavin, A. McGowan, C. McGurk, A. Mirza, B. Mohammadi, T. O'Brien, J. O'Connell, D. O'Halloran, D. O'Shea, G. Roberts, G. Tomkin, W. Wan Mahmood; Israel: B.S. Lewis, R. Abramod-Ness, F. Adawi, B. Aharon, M. Backer, A. Beniashvili, A. Berliner, L. Bloch, D. Bugelman, A. Butnaru, O. Cohen, Y. Cohen, M. Frenkel, M. Glant, B. Gustava, H. Guttman, S. Halabi, D. Halon, I. Harman-Boehm, J. Ilany, B. Karkabi, N. Khader, A. Khaskia, Y. Khudyak, E. Klainman, N. Kogan, D. Lender, I. Levin, T. Mardi, A. Marmor, M. Mosseri, D. Nabriski, M. Omary, S. Orlovsky, D. Peres, M. Quasim, I. Raz, M. Remesnik, O. Rogowski, I. Rozenfeld, D. Scharr, I. Shnifer, T. Shuster, R. Solomon, H. Steiner, D. Tzivoni, N. Wolfson, Z. Yossef, D. Zahger, D. Zeltser, R. Zimlichman; Italy: A. Maggioni, Aina, C. Ariatti, R. Bonetti, F. Cacciatore, F. Calcinaro, G. Corona, P. De Maria, S. Del Prato, G. Derosa, G. Di Pasquale, A. Falorni, R. Fanelli, D. Fedele, G. Filorizzo, R. Fogari, G. Furgi, A. Ghio, C. Giorda, G. Gregori, G. Iannuzzi, A. Lapolla, B. Luciano, P. Lucotti, A. Maggi, L. Marafetti, T. Marchese, G. Martino, S. Marzotti, R. Miccoli, L.D. Monti, L. Moretti, M. Palvarini, R. Petacchi, F. Piarulli, P.M. Piatti, S. Rudi, F. Santeusanio, G. Sesti, E. Setola, A. Sforza, E. Shehaj, M. Veniani, G. Viviani, E. Zigoura; Korea: J.H. Kim, S. Chae, D. Cho, E. Cho, Y. Cho, Y. Choi, M. Chung, E. Hong, Y. Hong, M. Jeong, B. Kim, D. Kim, H. Kim, I. Kim, J. Kim, J. Kim, P. Kim, S. Kim, S. Kim, B. Koo, S. Kwok, H. Kwon, J. Lee, J. Lee, J. Lim, S. Oh, J. Ohn, C. Park, H. Park, K. Park, K. Seung, H. Son, J. Woo, K. Yoon; Latvia: V. Pirags, B. Ansmite, I. Balcere, A. Bumbure, K. Ducena, A. Lejnieks, I. Rasa, R. Ritenberga, M. Romanova, I. Salmina, S. Steina; Lithuania: V. Pirags, J. Badariene, S. Gailiuniene, S. Grigonis, R. Juskiene, Z. Petrulioniene, G. Sakalyte, T. Stasiunas, M. Sulskiene, B. Urbonaite, R. Zarankiene, R Ziukaite; Mexico: E. Cardona, R. Arechavaleta, T. Beltran-Jaramillo, C. Calvo-Vargas, C. Campillo-Cardenas, D. Cardona, J. Carmona-Huerta, M. Cedano-Limon, M. Comellas-De Armas, C. Dominguez, J. Gomez-Cruz, R. Gonzalez-Perez, J. Illescas, S. Jimenez-Ramos, A. Lopez-Alvarado, E. Marquez-Rodriguez, G. Martinez, S. Pascoe, O. Plascencia Vazquez, H. Rodriguez, M. Ruiz-Cornejo, G. Velasco-Sanchez, M. Vidrio-Velazquez, E. Villeda-Espinosa; Netherlands: I. Stoel, E. Badings, G. Bartels, P. Bruggink-Andre de la Porte, E. Bruijns, J. Cornel, P. De Milliano, M. De Mulder, J. De Swart, A. Derks, A. Dirkali, J. Droste, M. Galjee, R. Hautvast, W. Hermans, N. Holwerda, B. Ilmer, M. Kofflard, J. Kooistra-Huizer, M. Kurvers, J. Langerveld, C. Leenders, A. Liem, D. Lok, D. Neumann, P. Nierop, K. Plomp, J. Posma, C. Reichert, H. Roeters Van Lennep, E. Ronner, S. Said, L. Takens, V. Umans, A.A. Van der Sluis, C. Van der Zwaan, J. Van Dobbenburgh, A. Van Es, M. Van Hessen, R. Van Mechelen, A. Van Miltenburg-Van Zijl, L. Van Zeijl, M. Veerhoek, E. Viergever, E.E. Weijers, F. Willems; Norway: K. Birkeland, I. Blix, J. Cooper, A. Debowska, K. Erichsen, J. Fossum, E. Gjertsen, V. Grill, S. Gudnason, K. Hoye, H. Istad, J. Winther, R. Joakimsen, R. Jorde, I. Larsen, B. Mella, J. Otterstad, K. Risberg, K. Skare, S. Skeie, L. Sommervoll, A. Tandberg, R. Whitfield, C. Wium; Philippines: R. Fernando, E. Cunanan, E. Fernando-Catindig, M. Gomez, C. Jaring, F. Lantion-Ang, M. Licaros, J. Lim, M. Lim-Abrahan, E. Madronio, A. Panelo, J. Raboca, G. Ramos, S. Tugna; Poland: A. Budaj, E. Aksamit-Bialoszewska, E. Bandurska-Stankiewicz, M. Baranska, A. Bronisz, M. Bronisz, W. Chrustowski, B. Cieslak, L. Czupryniak, B. Drazkowicz-Gozdzik, A. Galuszka-Bilinska, M. Gmytrasiewicz, K. Janik, K. Jedynasty, G. Kania, T. Kawka-Urbanek, I. Kinalska, K. Kincel, U. Kleszczewska, J. Kruszewski, J. Loba, J. Malicka, M. Mielecka-Kincel, A. Milczarczyk, D. Milosz, A. Mrowczynska, M. Mytnik, A. Nowakowski, P. Nowakowski, L. Oleskowska, E. Omelanczuk-Wiech, M. Pawlowski, A. Poplawska, M. Rucinska, M. Rucinski, J. Rutkowska, M. Saryusz-Wolska, K. Siewko, M. Sikora-Frac, J. Stecka-Wierzbicka, M. Swiatkowski, R. Swierczynski, M. Szpajer, K. Szymkowiak, J. Tarach, U. Tarasiewicz, D. Wiatr, P. Wojewoda, H. Woszczak-Marcinkowska, J. Zadrozny; Romania: N. Hancu, A. Albota, C. Bala, D. Barbonta, G. Botnariu, O. Bradescu, M. Busegeanu, M. Bzduch, D. Catrinoiu, R. Caziuc, A. Cerghizan, D. Cheta, A. Cif, D. Ciomos, D. Cosma, G. Creteanu, I. Crisan, R. Danciulescu, C. Dobjanschi, R. Dodan, L. Duma, I. Ferariu, T. Ghenes, G. Ghise, M. Graur, M. Ilinca, R. Marton, N. Mindrescu, A. Morosanu, M. Morosanu, M. Mota, V. Nafornita, G. Negrisan, S. Nicodim, A. Nicolau, C. Nita, A. Onaca, C. Panus, N. Pletea, C. Pop, L. Pop, B. Popa, G. Roman, M. Rosu, N. Sandu, V. Serban, A. Sima, L. Stamoran, M. Strugariu, G. Suciu, I. Szilagyi, G. Vacaru, I. Veresiu, A. Vlad; Russia: I. Chazova, T. Adasheva, F. Ageev, N. Akhmedganov, A. Akinina, A. Alexandrov, L. Ambatiello, A. Ametov, A. Ausheva, L. Babaeva, A. Babenko, E. Balyasnikova, B. Bart, J. Belova, L. Berstein, I. Bondarenko, E. Bondarev, O. Bulkina, N. Chernikova, B. Chumak, T. Deeva, O. Demicheva, T. Demidova, E. Doskina, A. Duganova, N. Dzhaiani, I. Egorova, O. Ettinger, S. Feofanova, T. Fofanova, P. Galaktionov, N. Gavrilova, S. Gilyarevsky, N. Gnidkina, A. Golubev, N. Gornyakova, S. Grigorova, E. Grineva, V. Gurevich, N. Irtuganov, L. Ivanova, N. Jaiani, M. Kalashnikova, Y. Karpov, Y. Khalimov, G. Khorocheva, E. Kirillova, J. Kistner, Z. Kobalava, I. Kochergina, T. Kravchenko, K. Krylov P. Kulkova, I. Kuparev, E. Kurbanova, T. Lysenko, A. Markovich, I. Martyanova, T. Martynyuk, M. Masiinvets, E. Mavlyavieva, E. Maychuk, G. Melnichenko, M. Mikhailusova, A. Mkrtumyan, V. Mychka, D. Nebieridze, E. Nesterova, V. Orlov, V. Orlova, Y. Orlova, F. Papov, I. Patroucherva, N. Petunina, S. Pirozhinskaya, S. Podachina, S. Postnikova, O. Pshikova, L. Rogova, B. Romashevskiy, N. Runikhina, I. Sadulayeva, A. Safaryan, E. Sakovich, T. Saprikina, V. Sargsyan, O. Semikozova, E. Shkolnik, A. Shubina, S. Shustov, I. Sinitsina, E. Solovyeva, G. Storogakov, O. Stovpyuk, A. Sussekov, M. Telnova, A. Temirov, V. Terekhov, S. Tereschenko, T. Tiourina, V. Tolkacheva, U. Tsoy, S. Urazgyldeeva, Y. Vasyuk, N. Vinnitskay, E. Voevodina, A. Volkova, V. Zadionchenko, A. Zalevskaya, T. Zhelninova, N. Zhukova, A. Zilov; Slovakia: G. Fodor, J. Bernatova, T. Duris, I. Markova, E. Martinka, L. Michalova, P. Minarik, L. Peter, K. Raslova, D. Silvia, M. Subadova, J. Tisonova, B. Vohnout; South Africa: P. Commerford, M. Adam, A. Badat, A. Bester, F. Bester, L. Blacking, D. Bouwer, B. Brice, S. Cassimjee, T. Cronje, J. Deftereos, L. Distiller, G. Ellis, O. Forster, M. Fulat, M. Gani, G. Gibson, S. Hansa, N. Hendricks, L. Herbst, J. Hitzeroth, B. Joffe, C. Kelbe, D. Kelbe, J. King, B. Kramer, S. Landau, N. Levitt, S. Meyer-Nell, R. Moore, D. Muller, H. Nell, M. Omar, H. Randeree, M. Seeber, Seedat, D. Segynu, M. Siebert, E. Van Den Berg, P. Van Der Walt, C. Van Dyk, F. Van Niekerk, L. Van Zyl, H. Wellman Spain: R. Gomis, V. Bertomeu, M. Botella, M. Buño, A. Calle, J. Cano Perez, M. Coves, J.G. Juanatey, R. Garcia-Mayor, S. Gaztambide, A. Gippini, I. Goikolea, J. Gonzalez, N. Hillman, V. Lopez Garcia Aranda, I. Magueda, J. Mato, P. Mazon, P. Morillas, A. Novials, L. Pallardo, L. Perez, J. Rodriguez, L. Romero, E. Sagarra, L. Shamagian, A. Soto, H. Torrealday, R. Valero; Sweden: L. Rydén, S. Agergaard, S. Agewall, K. Andersson, O. Bergstrom, M. Bjornstedt Bennermo, J. Blomgren, K. Boman, G. Brohall, C. Cherfan, C. Dahlen, A. Dotevall, P. Enander, U. Ericsson, P. Hallgren, A. Hansson, L. Henareh, P. Henriksson, J. Herlitz, J. Holmqvist, G. Jarevi, C. Linderfalk, L. Jonasson, S. Jovinge, J. Kalen, M. Kilstrup, M. Leosdotir, J. Leppert, B. Linde, J. Ljungberg, B. Löfdahl, P. Lundman, C. LysellBergstrom, U. Mathiesen, L. Mellbin, S. Mörner, D. Nathanson, L. Nilsson, M. Peterson, S. Quittenbaum, A. Rosengren, B. Ryttberg, S. Scheel, K. Svensson, Å. Tenerz, P. Vasko, A. Waldenström, M. Wieloch; Switzerland: G. Spinas, M. Braendle, B. Felix, P. Gerber, T. Moccetti, N. Pitteloud; Turkey: H. Kultursay, A. Aydinalp, M. Balci, M. Cayli, E. Hatipoglu, H. Ilkova, M. Kayikcioglu, M. Koc, H. Muderrisoglu, R. Sari, F. Saygili, K. Tekin, N. Tutuncu, B. Yurekli; United Kingdom: M. Davies, A. Adler, A. Ali, Balasubramanian, P. Bandypadhyay, O. Barakat, A. Barnett, L. Borthwick, Brookes, J. Burton, J. Cecil, S. Chaterjee, J. Clark, D. Collinson, S. Collinson, W. Crasto, R. Donnelly, J. du Plessis, S. Egan, A. Ellery, R. Evans, J. Ewing, C. Fox, M. Gibson, T. Hall, E. Higgs, M. Hollway, E. Hughes, N. Jackson, H. Jalihawi, G. Jones, H. Knights, S. Korsheed, R. Kumar Singh, D. Laithwaite, I. Lawrence, J. Litchfield, G. Manning, P. McNally, M. Millar-Craig, I. Mohammed, R. Narayanan, G. Nayani, A. Norris, J. Purohit, M. Quinn, Ramtoola, J. Randall, R. Rea, J. Reckless, T. Richardson, D. Robertson, A. Robinson, K. Salem, M. Sampson, M. Savage, J. Shaker, T. Srinivasan, I. Tracy, J. Tringham, A. Viljoen, A. Ward, H. Waterhouse, N. Wijenaike, P. Wiles; United States of America: J. Probstfield, M. Riddle, A. Ahmann, I. Ahmed, A. Alam, R. Arakaki, S. Asad, S. Banarer, H. Baum, K. Belew, R. Bergenstal, M. Bethel, C. Boyer, S. Catton, P. Challans, B. Childs, R. Christian, S. Clement, R. Cuddihy, G. Dailey III, G. Damberg, C. De Bold, J. De Lemos, D. Donovan, J. Dudl, J. Dunbar, S. Ebner, R. Failor, M. Feinglos, G. Flaker, M. Freiburghaus, K. Furlong, D. Gardner, E. Gillespie, R. Goland, R. Goldberg, A. Gotham, R. Guthrie, M. Hamaty, I. Hirsch, S. Jabbour, M. Janci, B. Javorsky, S. Jones, V. Kamana, M. Kashyap, S. Kaufman, P. Kearns, A. Khera, B. Klopfenstein, W. Kniffen, P. Kringas, A. Licata, C. LopezJimenez, M. Madden, C. Marx, A. McCall, J. McCallum, S. McFarlane, D. McGuire, J. Melish, L. Meneghini, S. Miller, B. Miranda-Palma, R. Mitchell, C. Nasr, J. Nelson, P. Niblack, E. Nylen, K. Osei, A. Pandey, V. Papademetriou, M. Pilar Solano, R. Ratner, J. Rosenstock, L. Sameshima, V. Savarese, J. Schnure, D. Schuster, J. Shin, A. Taylor, P. Thomson, M. Ting-Ryan, D. Trence, A. Vo, K. Weiland, K. Wells, P. Wu, M. Zimering, R. Zimmerman Venezuela: I. Mendoza, P. Ascanio, I. Brajkovich, E. Carrillo, J. Coll, K. Gonzalez, N. Gonzalez, E. Jimenez, R. Lopez, D. Marante, I. Morr, M. Paolillo, D. Perche, M. Portillo, H. Valbuena, M. Velarde, G. Vergara.