Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

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

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

Free wall rupture (FWR) in patients with acute ST-elevation myocardial infarction (STEMI) receiving fibrinolytic therapy (FT): a 7-year prospective study.

Previous studies have shown a paradoxical increase in early mortality in older patients (>70 years) with acute STEMI treated with fibrinolytic therapy (FT), which has been attributed to the development of free wall rupture (FWR). Our aim was to assess occurrence of FWR in STEMI patients receiving FT. In this 7-year prospective study, data from 1701 consecutive patients were obtained. We analyzed predictors of the in-hospital mortality in patients>70 years old. The independent contribution of several variables to overall mortality and FWR development was assessed using multiple logistic regression analyses. The mortality of entire cohort was 18% (306/1701). Diabetes mellitus, anterior infarction, smoking, female gender and hypercholesterolemia were independent predictors of in-hospital mortality. FT was given to 18% of all patients (304/1701) of which 13% died (39/304). FWR was 18.4-times more often in patients who received FT. Among patients younger than 70 years who received FT there was no FWR, while in patients ≥ 70 years of age FWR was found in almost half of the deceased (30/68; 44%). Application of FT in STEMI patients is not associated with higher mortality, but significantly increases number of FWR, especially in patients over 70 years of age.

Estimating modifiable coronary heart disease risk in multiple regions of the world: the INTERHEART Modifiable Risk Score.

AIMS: Summating risk factor burden is a useful approach in the assessment of cardiovascular risk among apparently healthy individuals. We aimed to derive and validate a new score for myocardial infarction (MI) risk using modifiable risk factors, derived from the INTERHEART case-control study (n = 19 470). METHODS AND RESULTS: Multiple logistic regression was used to create the INTERHEART Modifiable Risk Score (IHMRS). Internal validation was performed using split-sample methods. External validation was performed in an international prospective cohort study. A risk model including apolipoproteins, smoking, second-hand smoke exposure, hypertension, and diabetes was developed. Addition of further modifiable risk factors did not improve score discrimination in an external cohort. Split-sample validation studies showed an area under the receiver-operating characteristic (ROC) curve c-statistic of 0.71 [95% confidence interval (CI): 0.70, 0.72]. The IHMRS was positively associated with incident MI in a large cohort of people at low risk for cardiovascular disease [12% increase in MI risk (95% CI: 8, 16%) with a 1-point increase in score] and showed appropriate discrimination in this cohort (ROC c-statistic 0.69, 95% CI: 0.64, 0.74). Results were consistent across ethnic groups and geographic regions. A non-laboratory-based score is also supplied. CONCLUSIONS: Using multiple modifiable risk factors from the INTERHEART case-control study, we have developed and validated a simple score for MI risk which is applicable to an international population.

Predictive impact of coronary risk factors in southern Croatia: a case control study.

The aim of study was to compare the impact of coronary risk factors on the incidence of acute myocardial infarction (MI) between Croatia, Central and Eastern Europe, and the rest of the world. As a part of the large international INTERHEART case-control study of acute MI in 52 countries (15,152 cases and 14,820 controls) we have investigated the relationship between several known risk factors (smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins, and psychosocial factors) and MI among patients without previously known coronary heart disease in Southern Croatia. The main identified MI risk factors in Southern Croatia were heavy smoking (>20 cig/day; OR 3.86; 95% CI 2.31-6.46), diabetes mellitus (OR 2.83; 95% CI 1.58-5.23), abnormal ratio of B-100 and A-1 apolipoproteins (OR 2.23; 95% CI 1.28-3.89), elevated waist to hip ratio (OR 1.96; 95% CI 1.21-3.18), and arterial hypertension (OR 1.68; 95% CI 1.15-2.45). Protective was moderate alcohol consumption (OR 0.63; 95% CI 0.40-0.99). The prevalence of major MI risk factors in Croatia is similar to that in the surrounding countries and in the world, accounting for over 90% of the population attributable risk. However, physical activity, dietary and psychosocial factors are seemingly less important in this country, while moderate alcohol consumption is more protective than regionally or globally.

[Coronary heart disease risk factors in Croatia and worldwide: results of the Interheart study]. / Koronarni cimbenici rizika u hrvatskoj i u svijetu: rezultati Interheart studije.

OBJECTIVES: In the past 30 years, an increased cardiovascular disease (CVD) mortality has been observed in both industrialized and transition countries. The latter countries, such as Croatia, are considered to be in the third stage of epidemiological transition, defined as having 35%-65% of total as CVD mortality, predominantly ischemic heart disease and cerebrovascular disease. The CVD epidemic in transition countries is due to increasing rates of hypertension, obesity, smoking and sedentary lifestyle. Among CVD diagnoses, the most important is coronary heart disease (CHD), which varies in incidence among different ethnic groups and countries. Worldwide, it is estimated that nine potentially modifiable risk factors contribute to more than 90% of myocardial infarctions. Approximately 80%-90% of patients with symptomatic CHD and more than 95% of patients who died from CHD had at least one of the four traditional risk factors (smoking, hypertension, hyperlipidemia, and diabetes). AIM: Little research has been done to quantify the relationship between the prevalence of CHD risk factors and acute myocardial infarction (AMI) in Croatia. In south Croatia, we expected that specific dietary patterns and lifestyle would have favorable effects on CHD risk. Therefore, we have conducted a case-control study to examine the relationship between several CHD risk factors (smoking, hypertension, hyperlipidemia, diabetes, obesity, alcohol, fruit and vegetable consumption, and physical activity) in AMI patients and persons without previously known CHD in south Croatia. METHODS: We took part in the INTERHEART study over 4 years (1999-2002). Cases were all eligible patients with first AMI admitted to the Coronary Care Unit, Split University Hospital. Within one month of admission at least one control was recruited and matched to every AMI case by age (+/-5 years) and sex. Exclusion criteria were the same for cases and controls. Structured questionnaires were administered and physical examinations were undertaken in the same manner in cases and controls. Relationship between the risk factors and AMI are presented by odds ratios, estimated by multivariate logistic regression. RESULTS: During the study period 263 cases and 264 controls were enrolled. The proportion of males (74.6%) was threefold that of females. The highest relative difference between the case and control risk factors was noted for current smoking (16.6%; p<0.001), diabetes (10.5%; p<0.001), hypertension (9.0%; p=0.038) and abdominal obesity (18.5%; p<0.001). Ever smoking accounted for 75% higher AMI risk than non-smoking (OR 1.74; p=0.006), while current smoking accounted for a 2.6 time higher risk in comparison to non-smoking (OR 2.58; p<0.001). Diabetes had a threefold risk (OR 2.83; p<0.001). Hypertension accounted for a 70% higher risk (OR 1.68; p=0.007). Abdominal obesity was associated with a significantly increased AMI risk (OR 1.96; p=0.007). The highest apolipoprotein B/apolipoprotein A-1 (ApoB/ApoA-1) tertile accounted for nearly 2.5-fold risk (OR 2.23; p=0.005). Physical activity and daily consumption of fruits and vegetables did not prove to be significant factors in Croatia. Regular consumption of alcohol decreased coronary risk by approximately one third (OR 0.63; p=0.044). CONCLUSIONS: The most important AMI risk factor in south Croatia is current smoking, followed by diabetes, abnormal ApoB/ApoA-1 ratio, abdominal obesity, and hypertension. A protective risk factor is alcohol consumption, while physical activity and fruit and vegetable consumption are less important. These results are similar to the global INTERHEART data showing that most of AMI risk could be predicted with nine simple, measurable risk factors worldwide. Protective measures for CHD, including increased daily consumption of fruits and vegetables, moderate physical activity and particularly smoking cessation should be implemented worldwide. In specific regions such as south Croatia, moderate alcohol consumption (mostly red wine) may be included among protective measures due to sociologic and cultural reasons.

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.

Premature parental heart attack is heralding elevated risk in their offspring.

A small subgroup of children, whose parents have suffered a heart attack in their late thirties and early forties, may be at particularly high cardiovascular risk. University Hospital "Split" gives tertiary health care to some 700,000 people in southern Croatia and treats about 300 acute myocardial infarctions per year, with a 3-5% share in the age under 45 years. This cross-sectional, clinical and laboratory study included all the patients below the age limit of 45 years, treated for acute myocardial infarction between 1990 and 1995, complexively 55 of them, and their natural children, 97 all in all. The results were compared to those of a stratified children's sample taken from the population of the same region. The relative weight, blood pressure, and plasma cholesterol were significantly higher in these children than in the control group (p < 0.05). In 50 of these offspring (51.5%), in addition to the obviously positive family history, detected were further cardiovascular risk factors, defined as values above the 95th distribution percentile for age and gender. The average blood pressure, relative weight and cholesterol levels were even higher in these, "risky" children than in the studied sample (p < 0.05), and much more elevated than in the matching control pupils (p < 0.001). The most often detected risk factors were elevated cholesterol (in 44%), arterial hypertension (in 40%), obesity (in 32%), and smoking (in 24%). Most of the children (64%) had only one additional risk factor, while in the remaining 36% the most prevalent risk factors were overweight (in 14 out of 18) and arterial hypertension (in 11 out of 18). It is concluded that cardiovascular risk factor screening among children with a positive family history of premature atherosclerotic complications is appropriate and cost-effective.

[Smoking cessation using the transdermal nicotine system]. / Odvikavanje od pusenja transdermalnim nikotinskim sustavom.

There are a lot of methods for smoking cessation but transdermal nicotine system (TNS) is one of the most popular. On a sample of more than 300 smokers we have formerly shown that TNS achieves higher abstinence rate than placebo (38%:21%). In the present study we have tested the optimal administration of TNS. 160 smokers were subdivided in 4 groups of 40, receiving either TNS or placebo, for 3 or 6 weeks. The abstinence rate was evaluated by appropriate questionnaires and measuring CO in the exhaled air. After 3 weeks of TNS 60% of the examinees were abstaining compared to 50% after 6 weeks; the abstinence rates in the placebo groups were 17.5% and 20%, respectively (p < 0.05). Short TNS treatment (3 weeks) is at least as effective as a longer one (6 weeks), which is relevant both medically and economically.

Smoking cessation with nicotine replacement therapy among health care workers: randomized double-blind study.

AIM: To assess the smoking prevalence and efficacy of nicotine replacement therapy on the quitting rate after 3 weeks of therapy and after 1- and 5-year follow-up among health care workers with a smoking habit in Split, Croatia. METHODS: Among 311 hospital health professionals included in the study, there were 112 (36%) smokers; 44 (39%) of them were physicians and 68 (61%) nurses. In a randomized double-blind study, 112 smokers were divided in 2 groups, applying daily either a transdermal nicotine system (TNS) or placebo patch over 3 weeks. Abstinence was evaluated via questionnaire and on the basis of carbon monoxide concentration measured in the exhaled breath. RESULTS: The abstinence rates after the 3-week intervention period were 39% in the TNS group and almost 20% in the control group (chi-square test, p=0.038). After one year, these rates declined to 23% and 16%, respectively (p=0.476), and converged to 18% and 14% (p=0.797), respectively, at 5-year follow-up. CONCLUSIONS: Short-term TNS treatment is effective in smoking cessation, although the effects steadily wane over time and the relapse rate is high. Continuous, structured, and composite efforts are needed for the maintenance of the non-smoking behavior.