Rizwan Kalani, MD

Mahyar Khaleghi, Iyad N. Isseh, Hayan Jouni, Sunghwan Sohn, Kent R. Bailey, and Iftikhar J. Kullo. Family History as a Risk Factor for Carotid Artery Stenosis. Stroke. 2014

The impact of family history on ischemic stroke and its risk factors has been demonstrated. The risk conferred beyond that of traditional vascular risk factors, however, has been challenging to elucidate.

In this study, Khaleghi et al evaluated whether family history of stroke or coronary heart disease (CHD) was associated with carotid artery stenosis (CAS). They compared 864 patients with CAS (defined as 70% stenosis) and 1698 controls (who did not have CAS or atherosclerotic vascular disease history) that completed carotid artery doppler ultrasound over a six year period at a single institution. History of stroke/CHD in first-degree relatives before age 65 was obtained by questionnaire at the time of study recruitment. The principal finding was the prevalence of family history of stroke and CHD were significantly higher in patients with CAS compared with controls (stroke: OR 2.02; CHD: OR 2.01); sibling history of stroke/CHD was a stronger risk factor than parental history. The association was still significant after adjusting for age, sex and vascular risk factors (stroke: OR 1.41, CHD: OR 1.69). Having a greater number of affected relatives was associated with a higher odds of having CAS, independent of family size. Patients with the combination of 2 relatives with CHD and 2 relatives with stroke had an OR >7 compared to those who did not have this history.

This study demonstrates the role of family history of premature stroke/CHD in CAS risk. It suggests that there are likely genetic and environmental factors contributing to the development of CAS and that these are likely to be shared with CHD. Important limitations include the possibility of recall bias and predominant patient population being non-Hispanic Caucasian.
The authors note that future studies should address the utility of screening asymptomatic individuals for CAS who have a significant family history of vascular disease. I think that it also provides further evidence that the combination of next-generation sequencing methodologies and international collaborative efforts may identify novel genetic determinants of CAS. The potential to identify distinct pathophysiological mechanisms involved in CAS and allow for improved study of gene-environment interaction could pave the way for new stroke preventative and therapeutic options in the future.