Genetic predisposition to stroke in relatives of hypertensives

Background and Purpose-The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to t est the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors. Methods-Genealogical and medical history information was obtained for a coh ort of 354 hypertensive probands ascertained in a clinic-based setting, the ir 1427 first-degree relatives, and 239 of their spouses. Risks of stroke a nd hypertension in biological and nonbiological relatives were compared wit h the logistic model of the generalized estimating equations adjusted for a ge and sex. Results-The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR =2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a re ference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings(OR=1.6; 95% CI, 0.8 to 3.3) was ob served. Controlling for hypertension, obesity, smoking, coronary heart dise ase, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (ORparents=5.4; 95% CT, 2.6 to 11.2; ORs iblings=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly high er for hypertensive parents and siblings than for nonhypertensive parents ( OR=5.2; 95% CI, 2.8 to 9.7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A h istory of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensiv e relatives of probands with stroke was higher than that of the normotensiv e relatives (OR=13.4). A less elevated risk ratio was observed in the relat ives of probands who did not have a stroke (OR=4.0). Conclusions-Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that som e of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not signi ficant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treat ment for hypertension. Although a history of hypertension increases the ris k of stroke among parents and siblings, multivariate analyses revealed a fa milial component to stroke independent of hypertension.