Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.

BACKGROUND: Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis. METHOD: APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area. RESULTS: Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively. CONCLUSIONS: Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.

Birthplace in area with high coronary heart disease mortality predicts the severity of coronary atherosclerosis among middle-aged Finnish men who had migrated to capital area: the Helsinki sudden death study.

BACKGROUND: Reasons why eastern-born male Finns have higher coronary heart disease (CHD) mortality than do western-born men are still unsettled. Recently, eastern birthplace was found to be an independent predictor of pre-hospital sudden cardiac death (SCD) in the new low-mortality area of residence. AIM: To investigate the association of birthplace with high CHD mortality attributes to more severe coronary atherosclerosis among men migrated to the low-mortality capital area. METHOD: Coronary atherosclerosis was measured in 373 western-born and 314 eastern-born out-of-hospital male deaths aged 33-70 years in Helsinki (The Helsinki Sudden Death Study), covering 24.6% of male deaths within this age-group. CHD risk factors were obtained from an interview of a next of kin. RESULTS: In multivariate analysis there was a strong birthplace-by-age interaction with atherosclerosis (P = 0.0005). Eastern-born men <54 years had larger areas of fatty streaks (P = 0.0195), fibrotic plaque (P = 0.0133), calcification (P = 0.0009), total plaque area (P = 0.0011), and greater stenosis (P = 0.0004) in the left coronary compared to western-born men, independent of CHD risk factors. Amongst older men (>or=54 years) such an association no longer appeared. CONCLUSION: Higher CHD mortality among eastern-born men may be due to more severe coronary atherosclerosis independently of CHD risk factors, reflecting Finns' two-phase settlement history.

Birthplace predicts risk for prehospital sudden cardiac death in middle-aged men who migrated to metropolitan area: The Helsinki Sudden Death Study.

BACKGROUND: Eastern-born male Finns, irrespective of their place of residence, have high mortality from coronary heart disease (CHD), and half of such deaths are sudden. AIM: To study whether eastern birthplace alone or combined with life-style factors predicts risk for prehospital sudden cardiac death (SCD) in the new (west) low-mortality area of residence. METHOD: Prospective case-control autopsy study of all (700) out-of-hospital deaths of men aged 35-69 years in metropolitan Helsinki during 1981-82 and 1991-92. Data on CHD risk factors were obtained for 405, of whom 149 died of SCD (cases) and 256 of other causes (controls). RESULTS: A birthplace-by-age interaction with SCD (P=0.024) and with myocardial infarction (P=0.005) appeared. Men < or =54 years born in the east were more often victims of SCD (odds ratio 2.99, 95% confidence interval 1.38-6.49, P=0.006) than were men born in the west, independently of CHD risk factors. SCD was predicted also by alcohol consumption, age, smoking, and hypertension. Amongst older (>54 years) men no association with birthplace was any longer evident, but alcohol and socio-economic status predicted SCD. CONCLUSIONS: Birthplace-based risk for SCD suggests the contribution of early life environment or genetic east-west differences, reflecting Finns' two-phase settlement history.