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Background: Few population-based studies have ascertained both cerebral and coronary events or considered their relative heritability. Differences in heritability of transient ischemic attack and ischemic stroke versus acute coronary syndromes (ACS) may inform risk prediction, genetic studies, and understanding of disease mechanisms., Methods and Results: In a population-based study of all acute vascular events, irrespective of age, we studied family history of myocardial infarction (MI), stroke, and related risk factors in first-degree relatives. To allow for differences in rates of affected first-degree relatives caused by differences in disease incidence, we looked at the extent to which parental history was associated with affected siblings within disease category. Nine hundred six probands (604 men; mean age, 70 years) with ACS and 1015 (484 men; mean age, 73 years) with cerebral events had complete family history data. In ACS probands, parental MI was associated with MI in ≥1 sibling (1 parent with MI: odds ratio, 1.48; 1.04 to 2.10; P=0.03; both parents with MI: odds ratio, 5.97; 3.23 to 11.03; P<0.0001). In probands with cerebral events, however, parental stroke was not associated with sibling stroke. The overall frequency of ≥2 siblings with the same condition was also greater in probands with ACS than in those with cerebral events (odds ratio, 5.43; 3.03 to 9.76; P<0.00001), despite similar overall incidence of MI and stroke in our study population. One hundred forty-two (15.7%) cases of ACS occurred in families with ≥2 affected first-degree relatives compared with 56 (5.1%) transient ischemic attack/strokes. All results were similar when analyses were confined to probands with MI only versus stroke only, and independent of smoking., Conclusions: Heritability of coronary events was greater than that of cerebral events, such that MI was more likely to cluster in families than was stroke.

Background: Stroke in female first-degree relatives (FDRs) is a powerful risk factor for ischemic stroke in women, but its association with acute coronary syndromes (ACS) is unknown. Family history (FH) of stroke is omitted from existing myocardial infarction risk prediction tools, which perform less well in women than in men. Our objective was to study the sex-of-parent and sex-of-proband interactions for FH of stroke in ACS patients., Methods and Results: In a prospective, population-based study (Oxford Vascular Study) of all patients with ACS or stroke/transient ischemic attack, FH data for stroke and myocardial infarction were analyzed by sex of proband and FDRs, and coronary angiograms were reviewed, where available; 942 of 1058 ACS probands and 1015 of 1152 stroke/transient ischemic attack probands had complete FH data; 24.1% of ACS probands and 24.3% of stroke/transient ischemic attack probands had history of stroke in ≥1 FDR. Maternal stroke was more common than paternal stroke in female ACS probands (odds ration [OR], 2.53; 1.39 to 4.61) but not in male probands (OR, 0.92; 0.64 to 1.32) (difference-P=0.004). Overall, female ACS probands were more likely to have female than male FDRs with stroke (OR, 2.09; 1.29 to 3.37), whereas the opposite trend was seen in male ACS probands (OR, 0.69; 0.50 to 0.97) (difference-P=0.0002). However, there was no association between parental history of stroke and disease localization or presence of multivessel disease on coronary angiography., Conclusions: FH of stroke is as common in ACS patients as in stroke/transient ischemic attack patients and sex-of-parent/sex-of-proband interactions are similar. Stroke in female FDRs may help to identify women at increased risk of ACS as well as ischemic stroke.

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 <65 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 [OR], 2.25; 95% CI, 1.02 to 4.94; P=0.04 and OR, 3.03; 95% CI, 1.47 to 6.26; P=0.002, respectively). No such effect existed for paternal history (OR, 1.00; 95% CI, 0.46 to 2.10; P=0.99 and OR, 1.19; 95% CI, 0.58 to 2.43; P=0.63, respectively). Age at ACS in probands was highly correlated with age at MI in mothers (r=0.46, P<0.001), regardless of the proband's sex. Consequently, history of premature maternal MI was strongly associated with premature ACS and premature MI in female (OR, 10.52; 95% CI, 2.17 to 56.6; P=0.001 and OR, 7.31; 95% CI, 1.55 to 34.6; P=0.004, respectively) and male probands (OR, 3.88; 95% CI, 1.20 to 12.6; P=0.01 and OR, 3.63; 95% CI, 1.13 to 11.60; P=0.02, respectively)., Conclusions: Important sex-of-parent/sex-of-proband interactions exist in the family history of MI in patients with ACS. Greater emphasis should be placed on maternal than paternal history of MI, particularly in women aged <65 years.