Sex-Specific Familial Clustering of Myocardial Infarction in Patients With Acute Coronary Syndromes

Abstract

Background-Family history of premature myocardial infarction (MI) in first-degree relatives is a risk factor for MI and an indication for primary prevention. Although excess mother-to-daughter "transmission" occurs in ischemic stroke, no published studies have considered sex-of-parent/sex-of-proband interactions in the heritability of MI. Methods and Results-In a population-based study (Oxford Vascular Study) of all patients with acute coronary syndromes (ACS), irrespective of age, family history of all acute vascular events and related risk factors were analyzed by sex and age of both probands and first-degree relatives. Premature events were categorized as occurring at age Ͻ65 years. Of 835 probands with 1 or more ACS, 623 (420 men) had incident events and complete family history data. In probands with premature ACS, maternal history of both MI and of all vascular events were more common in female than male probands (odds ratio Greater emphasis should be placed on maternal than paternal history of MI, particularly in women aged Ͻ65 years.

Familial History of Stroke Is Associated With Acute Coronary Syndromes in Women

“…17 We now show that maternal stroke is also a risk factor for MI in women. In men, a maternal history of MI has been shown to be less important than a paternal history of MI, 9 and our findings suggest that the same is true for maternal history of stroke. Previous studies have considered a sex-ofparent effect for FH of MI in MI probands, 26,27 but none have considered FH of stroke in MI probands or been truly population-based or studied sex-of-proband/sex-of-parent effects.…”

“…9 In addition, maternal history of stroke increases risk of stroke in women, 19 and family history of stroke may be a stronger predictor of risk of MI than risk of ischemic stroke. 17 We now show that maternal stroke is also a risk factor for MI in women.…”

“…A third explanation involves the "Carter effect," 30 which occurs in diseases (or their intermediate phenotypes) that one sex is less prone to develop, such as MI, which is less common in women. 9,30 Women with MI are likely to have required a greater number of genetic risk factors than men for MI to have occurred and would therefore transmit more MI susceptibility genes to their children than men with MI, which effect would be again most clearly manifest in female offspring. If there were shared risk factors between MI and stroke, a Carter effect might be expected for FH of stroke in ACS probands.…”

“…20 We also recently showed that maternal MI is a particularly important risk factor for MI in young women. 9 If some genes influence risk of both stroke and MI, FH of stroke may be more strongly associated with the etiology of MI in women than in men. We therefore conducted the first population-based study of sex-specific effects of FH of stroke in ACS, comparing with the effects of FH of stroke in stroke/transient ischemic attack (TIA).…”

Relative Familial Clustering of Cerebral Versus Coronary Ischemic Events

“…23,24 In the OXVASC study, reported family history in an FDR had 83.3% sensitivity and 100% specificity for medical record-confirmed events in the relative. 25 All patients with a diagnosis of ACS or TIA/stroke were enrolled from April 1, 2002, to September 30, 2008, and were eligible for the present study. So that similar numbers of TIA/stroke and ACS events were compared, ACS events until March 31, 2009, were eligible for the study.…”