Nicolaou M, DeStefano A L, Gavras I, Cupples L A, Manolis A J, Baldwin C T, Gavras H, Farrer L A
Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Stroke. 2000 Feb;31(2):487-92. doi: 10.1161/01.str.31.2.487.
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.
中风的遗传基础尚不清楚。我们评估了高血压和中风的家族聚集模式，以检验以下假设：对这些疾病的遗传易感性可能由一组共同因素决定。
获取了一组在临床环境中确诊的354例高血压先证者、他们的1427名一级亲属以及239名配偶的家谱和病史信息。将生物学和非生物学亲属中中风和高血压的风险与根据年龄和性别调整的广义估计方程的逻辑模型进行比较。
先证者的父母和兄弟姐妹患高血压的风险高于配偶（优势比[OR]=2.4；95%可信区间[CI]，1.8至3.4；OR=2.2；95%CI，1.6至3.0）。以配偶作为参照组时，高血压先证者的父母患中风的风险高7.3倍（OR=7.3；95%CI，3.6至14.8），而兄弟姐妹的风险虽无统计学意义但略有增加（OR=1.6；95%CI，0.8至3.3）。对高血压、肥胖、吸烟、冠心病、糖尿病和胆固醇进行控制后，父母和兄弟姐妹中风风险的估计值降低（父母的OR=5.4；95%CI，2.6至11.2；兄弟姐妹的OR=1.2；95%CI，0.6至2.5）。高血压父母和兄弟姐妹患中风的风险显著高于非高血压父母（OR=5.2；95%CI，2.8至9.7）和兄弟姐妹（OR=5.8；95%CI，2.1至15.9）。配偶中有高血压病史与中风风险增加无关（OR=0.7；95%CI，0.2至3.1）。中风先证者的高血压亲属患中风的风险高于血压正常的亲属（OR=13.4）。在没有中风的先证者的亲属中观察到风险比升高幅度较小（OR=4.0）。
我们的数据显示，与配偶相比，高血压先证者的父母中高血压和中风的发生率更高，这表明导致这些情况的一些遗传因素可能相同。与配偶相比，兄弟姐妹的风险略有增加但无统计学意义，这表明由于高血压治疗水平的长期改善趋势性变化，通过中风家族研究阐明这些因素可能很困难。尽管高血压病史会增加父母和兄弟姐妹中风的风险，但多变量分析显示中风存在独立于高血压的家族成分。
