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More Favorable Midlife Cardiovascular Risk Factor Levels in Male Twins and Mortality After 25 Years of Follow-Up Is Related to Longevity of Their Parents

¹ Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis.
² Center for Health Sciences, SRI International, Menlo Park, California.
³ Division of Statistics, University of Idaho, Moscow.

Background. Genetic studies of life span in humans have used broad survival measures, most commonly longevity, which is moderately correlated between parents and offspring. We examined whether genetic cardiovascular disease risk factors in male twin offspring are related to longevity of their parents in the National Heart, Lung, and Blood Institute twin study.

Methods. Cholesterol levels, body mass index, blood pressures, and pulmonary function measured over the first three examinations (average subject age 48, 58, and 63 years, respectively) were compared with the twins' paternal, maternal, and parental mean longevity divided into upper versus lower quintiles. The presence of an apolipoprotein E 4 allele typed from DNA collected at Exam 3 and mortality in the twin cohort through 1997 were also examined in relation to parental longevity quintiles.

Results. Twins, particularly whose fathers died at younger ages, had significantly higher total cholesterol (p <.05), ratio of total cholesterol to high-density lipoprotein (p <.01), and blood pressures (p <.01) in middle age. This relationship decreased at the subsequent two examinations, but consistently, twins with longer-lived parents tended to have better risk factor profiles. A twin death (mean age 65) was significantly more common in families with mothers (p <.001) and, to a lesser extent, fathers who died early. An apolipoprotein 4 allele was more common in families with parents' age at death in the lowest quintile (p <.05).

Conclusions. Systolic blood pressures, cholesterol levels, and the presence of the apolipoprotein E 4 allele likely contribute to the observed familial correlations in longevity that have been reported in the literature.