Flossmann Enrico, Schulz Ursula G R, Rothwell Peter M
Stroke Prevention Research Unit, University Department of Clinical Neurology, Radcliffe Infirmary, Oxford 0X2 6HE, UK.
Cerebrovasc Dis. 2005;19(1):1-10. doi: 10.1159/000081905. Epub 2004 Nov 3.
Family history (FHx) of stroke is perceived to be an important risk factor for ischaemic stroke. However, there are several intermediate phenotypes that are often involved in the aetiology of ischaemic stroke and that have a substantial genetic component themselves. We studied FHx of ischaemic heart disease (IHD), hypertension (HTN) and diabetes mellitus (DM) as risk factors for ischaemic stroke.
We performed a systematic review of case-control and cohort studies reporting on FHx(IHD), FHx(HTN) or FHx(DM) as risk factors for stroke using bibliographic databases, and by hand searching reference lists and journals. Odds ratios of FHx as a risk factor for stroke were calculated within individual studies. We included unpublished data from two Oxfordshire population-based studies to assess effects on subtypes of ischaemic stroke.
We identified 54 studies that investigated the odds of stroke conferred by a positive FHx, 24 of which reported data on FHx of one or more intermediate phenotypes in addition to FHx of stroke. Most studies reported an increased frequency of FHx(IHD) and FHx(HTN) in stroke patients versus controls. The association was significant in 6 out of 14 studies for FHx(IHD) and 4 out of 11 studies for FHx(HTN). In contrast, FHx(DM) was not associated with stroke. FHx(IHD) was particularly associated with large vessel strokes (OR 1.72, CI 1.3-2.2, p = 0.00004).
FHx(IHD) and FHx(HTN) are both risk factors for stroke. It is likely that the apparent heritability of stroke is partly accounted for by heritability of HTN and large vessel atherosclerosis. Analyses of heritability of stroke and candidate gene studies should be adjusted accordingly.
中风家族史（FHx）被认为是缺血性中风的一个重要风险因素。然而，有几种中间表型经常参与缺血性中风的病因学，并且它们自身也有很大的遗传成分。我们研究了缺血性心脏病（IHD）、高血压（HTN）和糖尿病（DM）的家族史作为缺血性中风的风险因素。
我们使用文献数据库，并通过手工搜索参考文献列表和期刊，对报告FHx（IHD）、FHx（HTN）或FHx（DM）作为中风风险因素的病例对照研究和队列研究进行了系统评价。在各个研究中计算了FHx作为中风风险因素的比值比。我们纳入了两项基于牛津郡人群研究的未发表数据，以评估对缺血性中风亚型的影响。
我们确定了54项研究，这些研究调查了阳性FHx导致中风的几率，其中24项除了报告中风家族史外，还报告了一种或多种中间表型的家族史数据。大多数研究报告，与对照组相比，中风患者中FHx（IHD）和FHx（HTN）的频率增加。在14项研究中有6项研究中FHx（IHD）的关联显著，在11项研究中有4项研究中FHx（HTN）的关联显著。相比之下，FHx（DM）与中风无关。FHx（IHD）与大动脉中风特别相关（比值比1.72，可信区间1.3 - 2.2，p = 0.00004）。
FHx（IHD）和FHx（HTN）都是中风的风险因素。中风明显的遗传度可能部分由HTN和大动脉动脉粥样硬化的遗传度所解释。中风遗传度分析和候选基因研究应相应调整。
