Women whose mothers had a stroke are at increased risk for both stroke and myocardial infarction, new research has shown.
In a study of sex-of-parent and sex-of-proband interactions for family history of stroke in acute coronary syndrome (ACS) patients, Amitava Banerjee of the University of Oxford, England, and colleagues evaluated the family histories of 1,957 patients who had suffered a stroke, transient ischemic attack, myocardial infarction, or unstable angina. They determined that maternal history of stroke was more than twice as common than paternal stroke history in women with ACS, with an odds ratio of 2.53. Additionally, women with ACS were more likely to have female vs. male first-degree relatives with stroke history (odds ratio 2.09), while the opposite was true for males with ACS (odds ratio 0.69), the authors reported Feb. 1 in Circulation: Cardiovascular Genetics.
Previous studies have shown that women face a higher risk of myocardial infarction before age 65 if their mothers had a myocardial infarction at an early age, and that stroke in female first-degree relatives is a powerful risk factor for ischemic stroke in women; however, this is the first study to point toward sex-specific heritability of vascular disease across different arterial territories, the authors wrote. The current study is also the first to consider "the full spectrum of ACS without age restrictions on the proband or parent at time of vascular event," they stated.
The findings are especially noteworthy because "family history of stroke is omitted from existing MI risk prediction tools, which perform less well in women than in men," the authors stressed.
Among the possible explanations for the excess of maternal stroke vs. paternal stroke in ACS probands include the tendency of women to be more accurate in their reports of family history than males, and the fact that women with myocardial infarction likely have a greater number of genetic risk factors for ACS than do men. Thus, they would potentially transmit more susceptibility genes to their offspring, the authors hypothesized, noting that, "if there were shared risk factors between MI and stroke, a Carter effect might be expected for [family history] of stroke in ACS probands."
It’s also possible that sex-specific associations might be a function of sex-specific genes or sex-specific behaviors "which predispose to vascular disease across arterial territories," the authors wrote. "Future analyses should consider sex-of-parent/sex-of-offspring associations in prospective studies to better understand how sex-specific differences in [family history] lead to sex-specific differences in pathogenesis [such as localization of disease on coronary angiography and prothrombotic markers] and outcomes of CHD."
Because genome-wide scans are yet to produce data useful for clinical risk prediction of vascular disease, "more detailed use of [family history] data may provide a low-cost, low-technology alternative in the interim," they concluded.
The Oxford Vascular Study is funded by the U.K. Medical Research Council, the Dunhill Medical Trust, the Stroke Association, the BUPA Foundation, the National Institute for Health Research (NIHR), the Thames Valley Primary Care Research Partnership and the NIHR Biomedical Research Centre, Oxford. Author A.P. Banning is supported by the NIHR Biomedical Research Centre, Oxford. The authors reported having no financial conflicts of interest.