Is family history an independent risk factor for stroke?

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.)

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Genetic Predisposition to Stroke in Relatives of Hypertensives

Nicolaou

DeStefano

Gavras

et al. 2000

“…Five case-control studies 41,48,50,63,64 recruited only patients aged Ͻ70 years, 1 study recruited patients with stroke onset at Ͻ65 years, 60 1 study recruited patients with stroke onset at Ͻ50 years, 55 and 1 study reported family histories separately for patients aged Ͻ54 and Ն54 years. 68 The combined OR for these younger patient groups was nonsignificantly (Pϭ0.10) higher (OR, 1.93; 95% CI, 1.7 to 2.2; PϽ0.00001; heterogeneity Pϭ0.0001; 1240 patients; Figure 6) than the remainder (OR, 1.69; 95% CI, 1.6 to 1.8; PϽ0.00001; heterogeneity Pϭ0.00001).…”

Section: Influence Of Agementioning

confidence: 99%

Systematic Review of Methods and Results of Studies of the Genetic Epidemiology of Ischemic Stroke

Floßmann

Schulz

Rothwell

2004

341

251

Background and Purpose-To design appropriate molecular genetic studies, we first need to understand the genetic epidemiology of stroke. We therefore performed a systematic review of the literature to assess the heritability of stroke according to methodological quality of studies and to determine any heterogeneity in findings between studies and possible publication bias. Methods-We searched for twin studies and studies of family history of stroke using bibliographic databases and by hand-searching reference lists and journals. Odds ratios (ORs) for family history as a risk factor for stroke were calculated within studies and combined by meta-analysis. Heterogeneity between studies, methodological quality of studies, and the influence of the age at which stroke occurred in both probands and relatives were assessed. Results-We identified 53 independent studies (3 twin, 33 case-control, and 17 cohort). Monozygotic twins were more likely to be concordant than dizygotic twins (OR, 1.65; 95% CI, 1.2 to 2.3; Pϭ0.003). A positive family history was a risk factor for stroke in both case-control (OR, 1.76; 95% CI, 1.7 to 1.9; PϽ0.00001) and cohort (OR, 1.30; 95% CI, 1.2 to 1.5; PϽ0.00001) studies. However, there was major heterogeneity between studies (cohort Pϭ0.0001; case-control PϽ0.00001), with much stronger associations in small studies and methodologically less rigorous studies. Moreover, studies that reported insufficient data to allow meta-analysis tended to have found weaker associations. Family history of stroke was more frequent in studies that were confined to probands or relatives aged Ͻ70 years. However, few studies considered the number of affected and unaffected relatives, only 2 studies considered stroke phenotypes in detail, and only 19 studies (38%) adjusted associations for intermediate phenotypes.No twin study, only 5 cohort studies (26%), and 20 case-control studies (61%) differentiated between ischemic and hemorrhagic stroke in the proband. Family history of stroke was more frequent in large-and small-vessel stroke than in cardioembolic stroke. There were very few data on the influence of family history on stroke severity and no data on stroke recovery. Conclusions-Twin studies suggest a small genetic contribution to stroke, but reliable interpretation of published family history studies is undermined by major heterogeneity, insufficient detail, and potential publication and reporting bias.More detailed large-scale genetic epidemiology is required.

“…Data for hypercholesterolemia were conflicting. Thrift et al 34 found a negative association; Giroud et al 16 found no association; and Zodpey et al 20 and Kubota et al 17 found a positive association for hypercholesterolemia. The difference might be explained by the use of different definitions of hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 98%

“…13,16,17,20,23,26,28,30 The overall OR crude was 1.27 (95% CI, 0.98 to 1.65) (Figure 4). Leppälä et al 7 reported on diabetes and risk of ICH; the RR adjusted was 1.64 (95% CI, 0.77 to 3.51).…”

Section: Diabetes Mellitusmentioning

confidence: 99%

Editorial Comment—Minor Risk Factors for Intracerebral Hemorrhage: The Jury Is Still Out

Thrift

2003

Background and Purpose-Although data on some risk factors for intracerebral hemorrhage (ICH) already are beyond doubt, for other factors, the evidence is less clear. We performed a systematic overview of case-control and cohort studies on risk factors for ICH. Methods-We searched MEDLINE, LILACS, EXTRAMED, and Pascal from 1966 to 2001 to identify studies. Studies were included if they met predefined methodological criteria. When possible, 2ϫ2 tables were extracted and combined with the Mantel-Haenszel method. Summary odds ratios (ORs) were calculated for case-control studies, and summary relative risks (RRs) were found for cohort studies and for case-control and cohort studies combined. Results-Fourteen case-control and 11 cohort studies were identified. We could not always combine the results of case-control and cohort studies. In cohort studies, the crude RR for age (every 10-year increase) was 1.97 (95% confidence interval [CI], 1.79 to 2.16). In case-control studies, the crude OR for high alcohol intake was 3.36 (95% CI, 2.21 to 5.12) and for hypertension was 3.68 (95% CI, 2.52 to 5.38). Two cohort studies showed an increasing risk of ICH with increasing degree of hypertension. In cohort and case-control studies combined, the crude RR for sex (male versus female) was 3.73 (95% CI, 3.28 to 4.25); for current smoking, 1.31 (95% CI, 1.09 to 1.58); and for diabetes, 1.30 (95% CI, 1.02 to 1.67). Conclusions-Risk factors for ICH appeared to be age, male sex, hypertension, and high alcohol intake. High cholesterol tends to be associated with a lower risk of ICH. We could not assess whether these risk factors are independent. (Stroke.