The Framingham risk estimation (FRE) serves as the basis for identifying which asymptomatic adults should be treated with aspirin and lipid-lowering therapy in primary prevention. However, the FRE generally yields low estimates of 10-year “hard” coronary heart disease (CHD) event risk with few women (<70 years) qualifying for preventive pharmacologic therapy despite relatively high lifetime risk. We postulated that traditional risk factor assessment might fail to identify a sizeable portion of women with a sibling history for premature CHD as having advanced subclinical atherosclerosis.

We studied 102 asymptomatic women (mean age 51 ± 7 years) who were the sisters of a proband hospitalized with documented premature CHD. Participants underwent risk factor assessment and multidetector computed tomography for coronary artery calcium (CAC) scoring. Based on FRE prediction of 10-year risk for hard CHD events, participants were classified as low risk (<10%) (n = 100), intermediate risk (10%-20%) (n = 2), or high risk (>20%) (n = 0). Significant subclinical atherosclerosis was defined as age-sex adjusted >75th percentile CAC scores.

Ninety-eight percent were at low risk (mean FRE of only 2% ± 2%). However, 40% had detectable CAC, 12% had CAC >100, and 6% had CAC ≥400. Based on CAC score percentiles, 32% had significant subclinical atherosclerosis and 17% ranked above the 90th percentile.

Among women classified as low risk by FRE, a third had significant subclinical atherosclerosis. Sisters of probands with premature CHD appear to be a high-risk group and may warrant noninvasive screening for subclinical atherosclerosis to appropriately target individuals for more aggressive primary prevention therapy than what is currently recommended.