Addition of a Novel, Protective Family History Category Allows Better Profiling of Cardiovascular Risk and Atherosclerotic Burden in the General Population. The Asklepios Study

OBJECTIVES Whereas the importance of family history (FH) is widely recognized in cardiovascular risk assessment, its full potential could be underutilized, when applied with its current simple guidelines-based definition (cFH): presence of premature cardiovascular disease (CVD) in a first-degree relative. We tested the added value of a new, extended family history definition (eFH), also taking into account later onset of disease, second-degree relatives and number of affected relatives, on profiling cardiovascular risk and atherosclerotic burden in the general population. DESIGN Longitudinal population study. SETTING Random, representative population sample from Erpe-Mere and Nieuwerkerken (Belgium, primary care). SUBJECTS 2524 male/female volunteers, aged 35-55 years, free from overt CVD. MAIN OUTCOME MEASURES Subjects were extensively phenotyped including presence of atherosclerosis (ultrasound) and a newly developed FH questionnaire (4 generations). RESULTS Compared to cFH, eFH was superior in predicting an adverse risk profile (glycemic state, elevated blood pressure, lipid abnormalities, presence of metabolic syndrome components) and presence of atherosclerosis (all age & sex-adjusted p<0.05). Unlike cFH, eFH remained a significant predictor of subclinical atherosclerosis after adjusting for confounders. Most relations with eFH were not graded but showed clear informational breakpoints, with absence of CVD (including late onset) in any first-degree relative being a negative predictor of atherosclerosis, and a particularly interesting phenotype for further study. CONCLUSIONS A novel, extended FH definition is superior to the conventional definition in profiling cardiovascular risk and atherosclerotic burden in the general population. There remain clear opportunities to refine and increase the performance and informational content of this simple, readily-available inexpensive tool.