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

O'Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, et al.

Lancet, 2016 Aug 20;388(10046):761-75.
PMID: 27431356 DOI: 10.1016/S0140-6736(16)30506-2

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.
Fulltext Specialist Referral for Cardiovascular Risk in Patients With Prostate Cancer: A Randomized Clinical Trial

Leong DP, Higano C, Cano Garcia C, Fradet V, Siemens DR, Niazi T, et al.

JAMA Intern Med, 2026 Nov 01;186(11):1381-1390.
PMID: 42669035 DOI: 10.1001/jamainternmed.2026.4773

IMPORTANCE: Patients with prostate cancer have a high burden of cardiovascular risk factors, often suboptimally controlled, and adverse cardiovascular outcomes.
OBJECTIVE: To determine whether the routine referral of patients with prostate cancer to a cardiovascular specialist to implement a systematic risk factor strategy is more likely to reduce adverse cardiovascular outcomes and improve risk factor control than usual care.
DESIGN, SETTINGS, AND PARTICIPANTS: This randomized clinical trial included patients with prostate cancer from 55 sites in 8 countries between 2015 and 2025. Eligible patients were diagnosed with prostate cancer during the past 12 months; had received treatment with androgen deprivation therapy (ADT) for the first time within the past 6 months; or planned to start ADT in the next month. Patients taking a statin with a systolic blood pressure of 130 mm Hg or lower were ineligible. Data were analyzed from May 25 to August 7, 2026.
INTERVENTION: Patients were allocated in a 1:1 ratio to receive usual care alone or usual care plus routine referral to an internist or cardiologist. The specialists provided a systematic intervention, including a target of systolic blood pressure of 130 mm Hg or lower and a statin medication, irrespective of the patient's cholesterol levels (even if not usual or guideline-driven practice); encourage smoking cessation; and provide guidance on diet and exercise.
MAIN OUTCOMES AND MEASURES: Hierarchical composite of cardiovascular death, myocardial infarction, stroke, heart failure, suboptimal cholesterol (total cholesterol, >155 mg/dL [to convert to mmol/L, multiply by 0.0259]) and suboptimal blood pressure (systolic blood pressure, >130 mm Hg) as evaluated by the win ratio.
RESULTS: The analysis included 2487 patients with prostate cancer (mean [SD] age, 68 [8] years). During median (IQR) follow-up of 5.8 (2.7-8.2) years, the win ratio in favor of the intervention was 1.60 (95% CI, 1.42-1.81), mostly attributable to lower cholesterol in the intervention group (mean difference, 12 mg/dL; 95% CI, 9-15 mg/dL) as a consequence of greater protocol-mandated statin use. Mean (SD) close-out systolic blood pressure values were 131.1 (16.9) mm Hg in the intervention group and 132.9 (18.3) mm Hg in the control group. There was no difference in time to cardiovascular death, myocardial infarction, stroke, or heart failure between groups (subdistribution hazard ratio, 1.08; 95% CI, 0.79-1.49).
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, routine referral of patients with prostate cancer to a cardiovascular specialist lead to improved outcomes, specifically through better cholesterol control. However, it is uncertain whether this reduced clinical cardiovascular events.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03127631.

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