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      Differences in risk factors for 3 types of stroke : UK prospective study and meta-analyses

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          To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke.


          A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999–2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ 2 tests. When appropriate, meta-analyses were done of published prospective studies.


          After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84–2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04–1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26–0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30–1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12–5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94–2.72] or ischemic stroke [RR 2.50, 95% CI 2.29–2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke.


          Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke.

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          Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.

          The age-specific relevance of blood pressure to cause-specific mortality is best assessed by collaborative meta-analysis of individual participant data from the separate prospective studies. Information was obtained on each of one million adults with no previous vascular disease recorded at baseline in 61 prospective observational studies of blood pressure and mortality. During 12.7 million person-years at risk, there were about 56000 vascular deaths (12000 stroke, 34000 ischaemic heart disease [IHD], 10000 other vascular) and 66000 other deaths at ages 40-89 years. Meta-analyses, involving "time-dependent" correction for regression dilution, related mortality during each decade of age at death to the estimated usual blood pressure at the start of that decade. Within each decade of age at death, the proportional difference in the risk of vascular death associated with a given absolute difference in usual blood pressure is about the same down to at least 115 mm Hg usual systolic blood pressure (SBP) and 75 mm Hg usual diastolic blood pressure (DBP), below which there is little evidence. At ages 40-69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) is associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. All of these proportional differences in vascular mortality are about half as extreme at ages 80-89 years as at ages 40-49 years, but the annual absolute differences in risk are greater in old age. The age-specific associations are similar for men and women, and for cerebral haemorrhage and cerebral ischaemia. For predicting vascular mortality from a single blood pressure measurement, the average of SBP and DBP is slightly more informative than either alone, and pulse pressure is much less informative. Throughout middle and old age, usual blood pressure is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.
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            Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study.

            To examine the relation between body mass index (kg/m2) and cancer incidence and mortality. Prospective cohort study. 1.2 million UK women recruited into the Million Women Study, aged 50-64 during 1996-2001, and followed up, on average, for 5.4 years for cancer incidence and 7.0 years for cancer mortality. Relative risks of incidence and mortality for all cancers, and for 17 specific types of cancer, according to body mass index, adjusted for age, geographical region, socioeconomic status, age at first birth, parity, smoking status, alcohol intake, physical activity, years since menopause, and use of hormone replacement therapy. 45,037 incident cancers and 17 203 deaths from cancer occurred over the follow-up period. Increasing body mass index was associated with an increased incidence of endometrial cancer (trend in relative risk per 10 units=2.89, 95% confidence interval 2.62 to 3.18), adenocarcinoma of the oesophagus (2.38, 1.59 to 3.56), kidney cancer (1.53, 1.27 to 1.84), leukaemia (1.50, 1.23 to 1.83), multiple myeloma (1.31, 1.04 to 1.65), pancreatic cancer (1.24, 1.03 to 1.48), non-Hodgkin's lymphoma (1.17, 1.03 to 1.34), ovarian cancer (1.14, 1.03 to 1.27), all cancers combined (1.12, 1.09 to 1.14), breast cancer in postmenopausal women (1.40, 1.31 to 1.49) and colorectal cancer in premenopausal women (1.61, 1.05 to 2.48). In general, the relation between body mass index and mortality was similar to that for incidence. For colorectal cancer, malignant melanoma, breast cancer, and endometrial cancer, the effect of body mass index on risk differed significantly according to menopausal status. Increasing body mass index is associated with a significant increase in the risk of cancer for 10 out of 17 specific types examined. Among postmenopausal women in the UK, 5% of all cancers (about 6000 annually) are attributable to being overweight or obese. For endometrial cancer and adenocarcinoma of the oesophagus, body mass index represents a major modifiable risk factor; about half of all cases in postmenopausal women are attributable to overweight or obesity.
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              Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people

              Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. Methods We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at, number NCT01164371. Findings During 5·2 years median follow-up, we recorded 83 098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32–1·58]), subarachnoid haemorrhage (1·43 [1·25–1·63]), and stable angina (1·41 [1·36–1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00–1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86–0·98]) and strongest for peripheral arterial disease (1·23 [1·20–1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9–63·8) compared with 46·1% (45·5–46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8–5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. Funding Medical Research Council, National Institute for Health Research, and Wellcome Trust.

                Author and article information

                Lippincott Williams & Wilkins (Hagerstown, MD )
                23 January 2018
                23 January 2018
                : 90
                : 4
                : e298-e306
                From the Nuffield Department of Population Health (A.J.P., F.L.W., J.G., A.B., S.W.K., T.Y.O.Y., S.F., R.S., V.B., G.K.R.) and National Perinatal Epidemiology Unit (M.E.K.), University of Oxford; London School of Hygiene and Tropical Medicine (A.J.P.); and Centre for Clinical Brain Science (C.L.M.S.), University of Edinburgh, UK.
                Author notes
                Correspondence Dr. Price alison.price@

                These authors contributed equally to this work.

                Go to for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

                The Article Processing Charge was funded by the Medical Research Council and Cancer Research UK.

                Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

                This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: Wellcome Trust
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