Stephanie Ôunpuu

Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study

BACKGROUND Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. METHODS We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. FINDINGS Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. INTERPRETATION Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.

Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study

BACKGROUND Obesity is a major risk factor for cardiovascular disease, but the most predictive measure for different ethnic populations is not clear. We aimed to assess whether markers of obesity, especially waist-to-hip ratio, would be stronger indicators of myocardial infarction than body-mass index (BMI), the conventional measure. METHODS We did a standardised case-control study of acute myocardial infarction with 27 098 participants in 52 countries (12,461 cases and 14,637 controls) representing several major ethnic groups. We assessed the relation between BMI, waist and hip circumferences, and waist-to-hip ratio to myocardial infarction overall and for each group. FINDINGS BMI showed a modest and graded association with myocardial infarction (OR 1.44, 95% CI 1.32-1.57 top quintile vs bottom quintile before adjustment), which was substantially reduced after adjustment for waist-to-hip ratio (1.12, 1.03-1.22), and non-significant after adjustment for other risk factors (0.98, 0.88-1.09). For waist-to-hip ratio, the odds ratios for every successive quintile were significantly greater than that of the previous one (2nd quintile: 1.15, 1.05-1.26; 3rd quintile: 1.39; 1.28-1.52; 4th quintile: 1.90, 1.74-2.07; and 5th quintiles: 2.52, 2.31-2.74 [adjusted for age, sex, region, and smoking]). Waist (adjusted OR 1.77; 1.59-1.97) and hip (0.73; 0.66-0.80) circumferences were both highly significant after adjustment for BMI (p<0.0001 top vs bottom quintiles). Waist-to-hip ratio and waist and hip circumferences were closely (p<0.0001) associated with risk of myocardial infarction even after adjustment for other risk factors (ORs for top quintile vs lowest quintiles were 1.75, 1.33, and 0.76, respectively). The population-attributable risks of myocardial infarction for increased waist-to-hip ratio in the top two quintiles was 24.3% (95% CI 22.5-26.2) compared with only 7.7% (6.0-10.0) for the top two quintiles of BMI. INTERPRETATION Waist-to-hip ratio shows a graded and highly significant association with myocardial infarction risk worldwide. Redefinition of obesity based on waist-to-hip ratio instead of BMI increases the estimate of myocardial infarction attributable to obesity in most ethnic groups.

Global Burden of Cardiovascular Diseases Part I: General Considerations, the Epidemiologic Transition, Risk Factors, and Impact of Urbanization

This two-part article provides an overview of the global burden of atherothrombotic cardiovascular disease. Part I initially discusses the epidemiologic transition which has resulted in a decrease in deaths in childhood due to infections, with a concomitant increase in cardiovascular and other chronic diseases; and then provides estimates of the burden of cardiovascular (CV) diseases with specific focus on the developing countries. Next, we summarize key information on risk factors for cardiovascular disease (CVD) and indicate that their importance may have been underestimated. Then, we describe overarching factors influencing variations in CVD by ethnicity and region and the influence of urbanization. Part II of this article describes the burden of CV disease by specific region or ethnic group, the risk factors of importance, and possible strategies for prevention.

Association of psychosocial risk factors with risk of acute myocardial infarction in 11 119 cases and 13 648 controls from 52 countries (the INTERHEART study): case-control study

BACKGROUND Psychosocial factors have been reported to be independently associated with coronary heart disease. However, previous studies have been in mainly North American or European populations. The aim of the present analysis was to investigate the relation of psychosocial factors to risk of myocardial infarction in 24767 people from 52 countries. METHODS We used a case-control design with 11119 patients with a first myocardial infarction and 13648 age-matched (up to 5 years older or younger) and sex-matched controls from 262 centres in Asia, Europe, the Middle East, Africa, Australia, and North and South America. Data for demographic factors, education, income, and cardiovascular risk factors were obtained by standardised approaches. Psychosocial stress was assessed by four simple questions about stress at work and at home, financial stress, and major life events in the past year. Additional questions assessed locus of control and presence of depression. FINDINGS People with myocardial infarction (cases) reported higher prevalence of all four stress factors (p<0.0001). Of those cases still working, 23.0% (n=1249) experienced several periods of work stress compared with 17.9% (1324) of controls, and 10.0% (540) experienced permanent work stress during the previous year versus 5.0% (372) of controls. Odds ratios were 1.38 (99% CI 1.19-1.61) for several periods of work stress and 2.14 (1.73-2.64) for permanent stress at work, adjusted for age, sex, geographic region, and smoking. 11.6% (1288) of cases had several periods of stress at home compared with 8.6% (1179) of controls (odds ratio 1.52 [99% CI 1.34-1.72]), and 3.5% (384) of cases reported permanent stress at home versus 1.9% (253) of controls (2.12 [1.68-2.65]). General stress (work, home, or both) was associated with an odds ratio of 1.45 (99% CI 1.30-1.61) for several periods and 2.17 (1.84-2.55) for permanent stress. Severe financial stress was more typical in cases than controls (14.6% [1622] vs 12.2% [1659]; odds ratio 1.33 [99% CI 1.19-1.48]). Stressful life events in the past year were also more frequent in cases than controls (16.1% [1790] vs 13.0% [1771]; 1.48 [1.33-1.64]), as was depression (24.0% [2673] vs 17.6% [2404]; odds ratio 1.55 [1.42-1.69]). These differences were consistent across regions, in different ethnic groups, and in men and women. INTERPRETATION Presence of psychosocial stressors is associated with increased risk of acute myocardial infarction, suggesting that approaches aimed at modifying these factors should be developed.

Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study: a case-control study.

BACKGROUND Tobacco use is one of the major avoidable causes of cardiovascular diseases. We aimed to assess the risks associated with tobacco use (both smoking and non-smoking) and second hand tobacco smoke (SHS) worldwide. METHODS We did a standardised case-control study of acute myocardial infarction (AMI) with 27,089 participants in 52 countries (12,461 cases, 14,637 controls). We assessed relation between risk of AMI and current or former smoking, type of tobacco, amount smoked, effect of smokeless tobacco, and exposure to SHS. We controlled for confounders such as differences in lifestyles between smokers and non-smokers. FINDINGS Current smoking was associated with a greater risk of non-fatal AMI (odds ratio [OR] 2.95, 95% CI 2.77-3.14, p<0.0001) compared with never smoking; risk increased by 5.6% for every additional cigarette smoked. The OR associated with former smoking fell to 1.87 (95% CI 1.55-2.24) within 3 years of quitting. A residual excess risk remained 20 or more years after quitting (1.22, 1.09-1.37). Exclusion of individuals exposed to SHS in the never smoker reference group raised the risk in former smokers by about 10%. Smoking beedies alone (indigenous to South Asia) was associated with increased risk (2.89, 2.11-3.96) similar to that associated with cigarette smoking. Chewing tobacco alone was associated with OR 2.23 (1.41-3.52), and smokers who also chewed tobacco had the highest increase in risk (4.09, 2.98-5.61). SHS was associated with a graded increase in risk related to exposure; OR was 1.24 (1.17-1.32) in individuals who were least exposed (1-7 h per week) and 1.62 (1.45-1.81) in people who were most exposed (>21 h per week). Young male current smokers had the highest population attributable risk (58.3%; 95% CI 55.0-61.6) and older women the lowest (6.2%, 4.1-9.2). Population attributable risk for exposure to SHS for more than 1 h per week in never smokers was 15.4% (12.1-19.3). CONCLUSION Tobacco use is one of the most important causes of AMI globally, especially in men. All forms of tobacco use, including different types of smoking and chewing tobacco and inhalation of SHS, should be discouraged to prevent cardiovascular diseases.

Telmisartan to Prevent Recurrent Stroke and Cardiovascular Events

BACKGROUND Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke. In addition, inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events, including stroke. However, the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established. We evaluated the effects of therapy with an angiotensin-receptor blocker, telmisartan, initiated early after a stroke. METHODS In a multicenter trial involving 20,332 patients who recently had an ischemic stroke, we randomly assigned 10,146 to receive telmisartan (80 mg daily) and 10,186 to receive placebo. The primary outcome was recurrent stroke. Secondary outcomes were major cardiovascular events (death from cardiovascular causes, recurrent stroke, myocardial infarction, or new or worsening heart failure) and new-onset diabetes. RESULTS The median interval from stroke to randomization was 15 days. During a mean follow-up of 2.5 years, the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group. A total of 880 patients (8.7%) in the telmisartan group and 934 patients (9.2%) in the placebo group had a subsequent stroke (hazard ratio in the telmisartan group, 0.95; 95% confidence interval [CI], 0.86 to 1.04; P=0.23). Major cardiovascular events occurred in 1367 patients (13.5%) in the telmisartan group and 1463 patients (14.4%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.87 to 1.01; P=0.11). New-onset diabetes occurred in 1.7% of the telmisartan group and 2.1% of the placebo group (hazard ratio, 0.82; 95% CI, 0.65 to 1.04; P=0.10). CONCLUSIONS Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062.)

Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study

BACKGROUND Whether lipoproteins are better markers than lipids and lipoproteins for coronary heart disease is widely debated. Our aim was to compare the apolipoproteins and cholesterol as indices for risk of acute myocardial infarction. METHODS We did a large, standardised case-control study of acute myocardial infarction in 12,461 cases and 14,637 age-matched (plus or minus 5 years) and sex-matched controls in 52 countries. Non-fasting blood samples were available from 9345 cases and 12,120 controls. Concentrations of plasma lipids, lipoproteins, and apolipoproteins were measured, and cholesterol and apolipoprotein ratios were calculated. Odds ratios (OR) and 95% CI, and population-attributable risks (PARs) were calculated for each measure overall and for each ethnic group by comparison of the top four quintiles with the lowest quintile. FINDINGS The apolipoprotein B100 (ApoB)/apolipoprotein A1 (ApoA1) ratio had the highest PAR (54%) and the highest OR with each 1 SD difference (1.59, 95% CI 1.53-1.64). The PAR for ratio of LDL cholesterol/HDL cholesterol was 37%. PAR for total cholesterol/HDL cholesterol was 32%, which was substantially lower than that of the ApoB/ApoA1 ratio (p<0.0001). These results were consistent in all ethnic groups, men and women, and for all ages. INTERPRETATION The non-fasting ApoB/ApoA1 ratio was superior to any of the cholesterol ratios for estimation of the risk of acute myocardial infarction in all ethnic groups, in both sexes, and at all ages, and it should be introduced into worldwide clinical practice.

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.

Risk Factors Associated With Myocardial Infarction in Africa The INTERHEART Africa Study

Background— Cardiovascular disease (CVD) is rising in low-income countries. However, the impact of modifiable CVD risk factors on myocardial infarction (MI) has not been studied in sub-Saharan Africa (SSA). Therefore, we conducted a case-control study among patients with acute MI (AMI) in SSA to explore its association with known CVD risk factors. Methods and Results— First-time AMI patients (n=578) were matched to 785 controls by age and sex in 9 SSA countries, with South Africa contributing ≈80% of the participants. The relationships between risk factors and AMI were investigated in the African population and in 3 ethnic subgroups (black, colored, and European/other Africans) and compared with those found in the overall INTERHEART study. Relationships between common CVD risk factors and AMI were found to be similar to those in the overall INTERHEART study. Modeling of 5 risk factors (smoking history, diabetes history, hypertension history, abdominal obesity, and ratio of apolipoprotein B to apolipoprotein A-1) provided a population attributable risk of 89.2% for AMI. The risk for AMI increased with higher income and education in the black African group in contrast to findings in the other African groups. A history of hypertension revealed higher MI risk in the black African group than in the overall INTERHEART group. Conclusions— Known CVD risk factors account for ≈90% of MI observed in African populations, which is consistent with the overall INTERHEART study. Contrasting gradients found in socioeconomic class, risk factor patterns, and AMI risk in the ethnic groups suggest that they are at different stages of the epidemiological transition.

Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study

BACKGROUND The treatment of ischaemic stroke with neuroprotective drugs has been unsuccessful, and whether these compounds can be used to reduce disability after recurrent stroke is unknown. The putative neuroprotective effects of antiplatelet compounds and the angiotensin II receptor antagonist telmisartan were investigated in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial. METHODS Patients who had had an ischaemic stroke were randomly assigned in a two by two factorial design to receive either 25 mg aspirin (ASA) and 200 mg extended-release dipyridamole (ER-DP) twice a day or 75 mg clopidogrel once a day, and either 80 mg telmisartan or placebo once per day. The predefined endpoints for this substudy were disability after a recurrent stroke, assessed with the modified Rankin scale (mRS) and Barthel index at 3 months, and cognitive function, assessed with the mini-mental state examination (MMSE) score at 4 weeks after randomisation and at the penultimate visit. Analysis was by intention to treat. The study was registered with ClinicalTrials.gov, number NCT00153062. FINDINGS 20,332 patients (mean age 66 years) were randomised and followed-up for a median of 2.4 years. Recurrent strokes occurred in 916 (9%) patients randomly assigned to ASA with ER-DP and 898 (9%) patients randomly assigned to clopidogrel; 880 (9%) patients randomly assigned to telmisartan and 934 (9%) patients given placebo had recurrent strokes. mRS scores were not statistically different in patients with recurrent stroke who were treated with ASA and ER-DP versus clopidogrel (p=0.38), or with telmisartan versus placebo (p=0.61). There was no significant difference in the proportion of patients with recurrent stroke with a good outcome, as measured with the Barthel index, across all treatment groups. Additionally, there was no significant difference in the median MMSE scores, the percentage of patients with an MMSE score of 24 points or less, the percentage of patients with a drop in MMSE score of 3 points or more between 1 month and the penultimate visit, and the number of patients with dementia among the treatment groups. There were no significant differences in the proportion of patients with cognitive impairment or dementia among the treatment groups. INTERPRETATION Disability due to recurrent stroke and cognitive decline in patients with ischaemic stroke were not different between the two antiplatelet regimens and were not affected by the preventive use of telmisartan.