Abstract and Introduction
Abstract
Background Small vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between those with and those without diabetes in the subtypes of stroke. We determined the rates and predictors of risk of stroke and its subtypes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.
Methods 9795 patients aged 50–75 years with type 2 diabetes were followed up for a median of 5 years. Annual rates were derived by the Kaplan–Meier method and independent predictors of risk by Cox proportional hazards regression analyses.
Results The annual rate of stroke was 6.7 per 1000 person years; 82% were ischaemic and caused by small artery disease (36%), large artery disease (17%) and embolism from the heart (13%); 10% were haemorrhagic. Among the strongest baseline predictors of ischaemic or unknown stroke were age (60–65 years, HR 1.98; >65 years, HR 2.35) and a history of stroke or transient ischaemic attack (TIA) (HR 2.06). Other independent baseline predictors were male sex, smoking, history of hypertension, ischaemic heart disease, nephropathy, systolic blood pressure and blood low density lipoprotein (LDL) cholesterol, HbA1c and fibrinogen. A history of peripheral vascular disease, low high density lipoprotein, age and history of hypertension were associated with large artery ischaemic stroke. A history of diabetic retinopathy, LDL cholesterol, male sex, systolic blood pressure, smoking, diabetes duration and a history of stroke or TIA were associated with small artery ischaemic stroke.
Conclusions Older people with a history of stroke were at highest risk of stroke, but the prognosis and prognostic factors of subtypes were heterogeneous. The results will help clinicians quantify the absolute risk of stroke and its subtypes for typical diabetes patients.
Introduction
The major contributor to the burden and cost of diabetes is vascular disease of the brain, eye, heart, kidneys and peripheral nerves. The Emerging Risk Factors Collaboration's meta-analysis indicated that a history of diabetes increased the hazard for ischaemic stroke and haemorrhagic stroke. HRs for ischaemic stroke in people with diabetes, adjusted for baseline covariates, were higher in women, patients aged 40–59 years and patients with above average body mass index (BMI); HRs did not change significantly after additional adjustment for lipids, and fasting blood glucose concentration was not linearly related to the risk of ischaemic stroke. The annual rate of stroke in a cohort of 41 799 people with diabetes in the UK was 11.9 per 1000 person years, compared with 5.5 per 1000 person years in 202 733 controls.
The debate over which factors increase the risk of stroke in diabetic people is controversial. In the Diabetes and Informatics Study of 14 432 people with type 2 diabetes, the rate of stroke was much higher among people with a history of cardiovascular disease than those with no history of cardiovascular disease. The only other consistently significant and independent prognostic factor for stroke in people with diabetes is age, but some studies have shown that the risk of stroke decreases with age beyond 35–54 years and others that the risk increases with age. Other adverse prognostic factors reported in some, but not all, studies include sex, smoking, obesity, atrial fibrillation, hypertension, systolic blood pressure, total to high density lipoprotein (HDL) cholesterol ratio, waist circumference, microvascular complications, duration of diabetes and therapy with insulin plus oral agents.
There also is uncertainty about the frequency with which the different aetiological subtypes of ischaemic stroke occur in diabetes patients. Ischaemic stroke caused by intracranial small vessel disease (lacunar infarction) is reported to be more common in diabetic people than others, presumably because of their higher prevalence of microvascular disease. However, the few population based studies of incident cases of stroke have shown no significant difference in the subtypes of stroke between diabetic and non-diabetic people. Although the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was not a population based study, it provided an opportunity to determine the rate and predictors of risk of stroke in a large cohort of diabetes patients followed-up over a long period, with outcome events systematically assessed by a panel of stroke experts. Our study design and data also allowed us to ascertain the risks of pathological and aetiological subtypes of stroke in this cohort.