General cardiovascular risk profile identifies advanced coronary artery calcium and is improved by family history: The multiethnic study of atherosclerosis

Background-The General Cardiovascular Risk Profile is a multivariable model that predicts global cardiovascular disease risk. Our goal was to assess the ability of the General Cardiovascular Risk Profile to identify individuals with advanced coronary artery calcification (CAC) and determine whether identification is improved with family history. Methods and Results-Using data from the Multiethnic Study of Atherosclerosis, 3 sex-specific models were developed with ordinal logistic regressions to relate risk factors to CAC scores. Model 1 included covariates in the General Cardiovascular Risk Profile. Then family history was added, defined as having at least 1 first-degree relative with premature coronary heart disease (model 2) or as a weak, moderate, or strong family history based on number of relatives with coronary heart disease, age at onset, and the presence of stroke or diabetes in the family (model 3). For each model, we estimated mathematical CAC risk functions, derived CAC score sheets, evaluated the ability to discriminate persons having positive CAC scores, and assessed reclassification of individuals with low, intermediate, or high probability of CAC >300. Model 1 worked well to identify women and men with positive CAC scores; c-statistics were 0.752 and 0.718 and X² values were 821.2 (P<0.0001) and 730.6 (P<0.0001), respectively. Addition of family history improved discrimination and fit of model 1. However, reclassification of participants with advanced CAC was significantly improved with model 3 only. Conclusions-The General Cardiovascular Risk Profile identifies advanced CAC, an emerging indication for aggressive risk factor modification. Incorporation of family history, especially comprehensive familial risk stratification, provides incremental prognostic value.