Genetic Predisposition to Stroke in Relatives of Hypertensives

Abstract

Background and Purpose-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. Methods-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. Results-The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio[OR]ϭ2.4; 95% CI, 1.8 to 3.4; ORϭ2.2; 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 (ORϭ7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (ORϭ1.6; 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 ϭ5.4; 95% CI, 2.6 to 11.2; OR siblings ϭ1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (ORϭ5.2; 95% CI, 2.8 to 9.7) and siblings (ORϭ5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (ORϭ0.7; 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 (ORϭ13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (ORϭ4.0). Conclusions-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. (Stroke. 2000;31:487-492.)

Familial aggregation and coaggregation of history of hypertension and stroke

“…The larger magnitude in the ORs for siblings than for parents (Table 2) may be due partly to this clustering effect. In fact, a previous clinic-based case-control study showed a higher observed risk in parents than in siblings of the probands, 8 a trend not consistent with out results. Another possibility is the effects related to the variability in age among parents and siblings: we previously found an aging-related decrease in the familial aggregation of both hypertension and stroke, and assumed that factors specific to individuals would have become more influential than shared familial factors in the development of the diseases at older ages.…”

“…Additionally, a common genetic basis for hypertension and stroke might be affected through genes underlying the risk factors for these traits (eg, obesity, atherosclerosis, diabetes). 8 This study is subject to some limitations. Since our population was community-based, there was a possibility that some probands are sibs to other probands born to the same parents.…”

Guidelines for the Primary Prevention of Stroke

“…Many of the established and emerging risk factors described in the sections that follow, such as hypertension, diabetes, and hyperlipidemia, have both genetic and environmental/behavioral components. [45][46][47] Elevations of blood homocysteine occur with 1 Class I Conditions for which there is evidence for and/or general agreement that the procedure or treatment is useful and effective.…”

Heritability of Ischemic Stroke in Relation to Age, Vascular Risk Factors, and Subtypes of Incident Stroke in Population-Based Studies

“…This is consistent with previous general population studies that have shown that FHx Stroke is more common in hypertensive than normotensive subjects 17,18 and a previous case-control study in which stroke patients were more likely to have a FHx of hypertension than controls. 19 Given that hypertension has a major genetic component, 12 heritability of stroke may partly be conferred by an inherited tendency for hypertension.…”