Family history of stroke in patients with transient ischemic attack in relation to hypertension and other intermediate phenotypes

Background and Purpose - Family history of stroke (FHx(stroke)) is a risk factor for ischemic stroke, but there are insufficient data on the relationship with stroke subtypes and intermediate phenotypes (IPs), such as hypertension. Specifically, there are no reliable data on the associations of FHx(stroke) in patients with transient ischemic attack (TIA) in whom relationships with IPs are likely to be determined most reliably. Methods - We studied FHx(stroke) and FHx of myocardial infarction (FHx(MI)) in TIA patients from 2 population-based incidence studies and 2 prospective consecutive hospital-referred series. We related the presence of FHx to baseline characteristics, clinical subtype, and IPs. Results - Results were similar in the 4 cohorts, and so data on all 783 patients were pooled. FHxstroke was less common than FHx(MI) (189 versus 254; P = 0.0003). FHx(stroke) and FHx(MI) were strongly related to history of hypertension in the proband ( odds ratio [OR], 1.78; 95% CI, 1.28 to 2.48; P = 0.0008; and OR, 2.10, 95% CI, 1.55 to 2.85; P < 0.0001, respectively). Highest recorded premorbid systolic and diastolic blood pressures ( mm Hg) were significantly higher in cases with FHx(stroke) than those without and increased with the number of affected first-degree relatives ( 0 181/100; 1 185/104; >= 2 198/109; P = 0.03). There was no association between FHxstroke and age, diabetes, smoking, plasma glucose, cholesterol, or territory of TIA, but FHx(stroke) was less common in patients with ocular TIA than in cases with cerebral TIA ( OR, 0.53; 95% CI, 0.34 to 0.82; P = 0.004), although the association was no longer significant after adjustment for hypertension. Conclusions - The strong association between hypertension and FHx(stroke) suggests that familial susceptibility to cerebral ischemia is attributable, at least partly, to familial predisposition to hypertension. This should be taken into account in studies of the genetics of ischemic stroke.