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A Prospective Study of Parents and Offspring

Donald M. Lloyd-Jones, MD, ScM; Byung-Ho Nam, PhD; Ralph B. D'Agostino Sr, PhD; Daniel Levy, MD; Joanne M. Murabito, MD, ScM; Thomas J. Wang, MD; Peter W. F. Wilson, MD; Christopher J. O'Donnell, MD, MPH

JAMA. 2004;291:2204-2211.

Context  Whether parental cardiovascular disease confers increased risk independent of other risk factors remains controversial. Prior studies relied on offspring report, without complete validation of parental events.

Objective  To determine whether parental cardiovascular disease predicts offspring events independent of traditional risk factors, using a prospective design for both parents and offspring, and uniform criteria to validate events.

Design  Inception cohort study.

Setting  Framingham Heart Study, a US population-based epidemiologic cohort begun in 1948 with the offspring cohort established in 1971.

Participants  All Framingham Offspring Study participants (aged 30 years) who were free of cardiovascular disease and both parents in the original Framingham cohort.

Main Outcome Measures  We examined the association of parental cardiovascular disease with 8-year risk of offspring cardiovascular disease, using pooled logistic regression.

Results  Among 2302 men and women (mean age, 44 years), 164 men and 79 women had cardiovascular events during follow-up. Compared with participants with no parental cardiovascular disease, those with at least 1 parent with premature cardiovascular disease (onset age <55 years in father, <65 years in mother) had greater risk for events, with age-adjusted odds ratios of 2.6 (95% confidence interval [CI], 1.7-4.1) for men and 2.3 (95% CI, 1.3-4.3) for women. Multivariable adjustment resulted in odds ratios of 2.0 (95% CI, 1.2-3.1) for men and 1.7 (95% CI, 0.9-3.1) for women. Nonpremature parental cardiovascular disease and parental coronary disease were weaker predictors. Addition of parental information aided in discriminating event rates, notably among offspring with intermediate levels of cholesterol and blood pressure, as well as intermediate predicted multivariable risk.

Conclusions  Using validated events, we found that parental cardiovascular disease independently predicted future offspring events in middle-aged adults. Addition of parental information may help clinicians and patients with primary prevention of cardiovascular disease, when treatment decisions may be difficult in patients at intermediate risk based on levels of single or multiple risk factors. These data also support further research into genetic determinants of cardiovascular risk.

Author Affiliations: Department of Preventive Medicine and Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Ill (Dr Lloyd-Jones); National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Mass (Drs Lloyd-Jones, Nam, D'Agostino, Levy, Murabito, Wang, Wilson, and O'Donnell); Statistics and Consulting Unit (Drs Nam and D'Agostino), Department of Epidemiology and Preventive Medicine, Boston University (Drs D'Agostino, Levy, Murabito, Wilson, and O'Donnell), and Section of General Internal Medicine, Boston University School of Medicine (Dr Murabito); Cardiology Division (Drs Wang and O'Donnell), Massachusetts General Hospital, Harvard Medical School, Boston; and National Heart, Lung, and Blood Institute, Bethesda, Md (Drs Levy and O'Donnell).

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