Abstract

Background: The absolute burden of stroke is increasing due to an ageing population, as well as an increased incidence of stroke in young adults. We aimed to determine whether age modifies the magnitude of association between vascular risk factors and stroke in the INTERSTROKE study. Methods: INTERSTROKE is an international case–control study of risk factors for first acute stroke. Cases and controls (matched by age and sex) were recruited in 32 countries (between Jan 11, 2007, and Aug 8, 2015). Participants completed a clinical assessment and provided blood and urine samples within 72 h of recruitment. Odds ratios (ORs) for vascular risk factors and their population attributable fractions (PAFs) were calculated among age groups. We tested for an interaction of age by each risk factor. Findings: Among 26 950 participants, the mean age of cases was 62·2 years (SD 13·6) and of controls 61·3 years (13·3). Increasing age was associated with a significant increased prevalence for seven vascular risk factors (hypertension, physical inactivity, diabetes, atrial fibrillation, high waist-to-hip ratio, high apolipoprotein B concentration [p<0·0001 for all], and obesity [p=0·016]), reduced prevalence for four vascular risk factors (smoking, alcohol use, psychosocial stress [p<0·0001 for all], and unhealthy diet [p=0·0081]) and unchanged prevalence for one vascular risk factor (depression). Increasing age was associated with a reduced magnitude of OR of stroke for hypertension (pinteraction<0·0001), high apolipoprotein B concentration (pinteraction<0·001), high waist-to-hip ratio (pinteraction 0·011), alcohol use (pinteraction<0·0001), and psychosocial stress (pinteraction=0·033). No vascular risk factor was associated with a higher odds of stroke with increased age. Hypertension, high waist-to-hip ratio, and physical inactivity accounted for the largest PAF among all age groups. Interpretation: Vascular risk factors exhibit different patterns of association with stroke by age, with consequent variations in their relative PAF. This information could be used to prioritise risk factor screening and modification by age group. Funding: Canadian Institutes of Health Research; Heart and Stroke Foundation of Canada; Canadian Stroke Network; AFA Insurance, 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 UK Stroke Association. © 2025 The Author(s)