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

JAMA. 2005;294:3117-3123.

Context  While parental cardiovascular disease (CVD) doubles the risk for CVD in offspring, the extent of increased risk associated with sibling CVD is unclear.

Objective  To determine, using validated events, whether sibling CVD predicts outcome in middle-aged adults independent of other risk factors.

Design, Setting, and Participants  The Framingham Offspring Study, an inception cohort of the Framingham Heart Study, a prospective population-based cohort study initiated in 1948 with the offspring cohort initiated in 1971. Participants (n = 2475) were members of the offspring cohort aged 30 years or older, free of CVD, and with at least 1 sibling in the study; all were followed up for 8 years.

Main Outcome Measures  Association of sibling CVD with 8-year personal risk for CVD using pooled logistic regression. A secondary analysis restricted to offspring with both parents in the study assessed the joint impact of parental and sibling CVD occurrence.

Results  Among 973 person-examinations in the sibling CVD group (mean age, 57 years) and 4506 person-examinations in the no sibling CVD group (mean age, 47 years), 329 CVD events occurred during follow-up. Baseline risk factors were more prevalent in the sibling CVD group compared with the no sibling CVD group. Sibling CVD was associated with a significantly increased risk for incident CVD (age- and sex-adjusted odds ratio [OR], 1.55; 95% confidence interval [CI], 1.19-2.03). Adjustment for risk factors did not substantially attenuate the risk (adjusted OR, 1.45; 95% CI, 1.10-1.91). In the analysis restricted to persons with both parents in the study, in models adjusting for both sibling and parental CVD, the multivariable-adjusted OR for sibling CVD (1.99; 95% CI, 1.32-3.00) exceeded that for parental CVD (1.45; 95% CI, 1.02-2.05).

Conclusion  Using validated events, sibling CVD conferred increased risk of future CVD events above and beyond established risk factors and parental CVD in middle-aged adults.

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

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