Genetic predisposition to stroke in relatives of hypertensives

The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors.

Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex.

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 reference 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 observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR(parents)=5.4; 95% CI, 2.6 to 11.2; OR(siblings)=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher 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 history 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 hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0).

Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.