Parental Occurrence of Premature Cardiovascular Disease Predicts Increased Coronary Artery and Abdominal Aortic Calcification in the Framingham Offspring and Third Generation Cohorts

Abstract

Parental premature cardiovascular disease (CVD) is a risk factor for coronary heart disease (CHD). We related validated parental premature CVD with the subclinical measures of coronary artery (CAC) and abdominal aortic (AAC) calcification in the community. We studied 2 generations of Framingham Heart Study subjects who underwent multidetector computed tomography measurements of CAC and AAC and who had 2 parents in the study. Subjects included 797 Framingham Offspring (mean age, 63 years; 56% women) and 1238 Third Generation (Gen3) (mean age, 46 years; 47% women) participants free of CVD. Generalized estimating equations adjusted for major CVD risk factors were used to relate validated parental premature CVD and CHD to CAC and AAC, defined by >90th percentile age- and sex-specific cut points from a healthy subsample. Parental premature CVD was associated with CAC among Gen3 (odds ratio=2.17 [1.41 to 3.33]; P<0.001) and nonsignificantly among Offspring (odds ratio=1.42 [0.91 to 2.22]; P=0.12). Parental premature CHD was associated with CAC among Gen3 (odds ratio=2.22 [1.22 to 4.01]) but not Offspring. Parental premature CVD was not associated with AAC in either cohort. Parental premature CHD was associated with AAC among Gen3 (odds ratio=1.65 [0.99 to 2.75]; P=0.05) but not among Offspring. The magnitude of risk conferred was greater for paternal than maternal premature CVD. Parental premature CVD is associated with CAC, and premature CHD is associated with AAC, after adjustment for risk factors, particularly in younger middle-aged adults. Risk conferred by parental premature CVD on vascular calcification may be mediated through novel mechanisms not accounted for by classic CVD risk factors known to cause atherosclerosis.