In the past, patients with heterozygous familial hypercholesterolemia (HeFH) were believed to be an ideal population to study changes in carotid intima media thickness (cIMT) based on their aggressive lipid disorder and high incidence of atherosclerotic events. However, following publication of recent cIMT trials in this population, the feasibility of demonstrating a reduction of cIMT progression in statin-treated HeFH patients has come under scrutiny. To inform future study designs, we evaluated cIMT progression and baseline predictors of cIMT progression (change in mean cIMT for all segments and common carotid artery (CCA) cIMT over 1 and 2 years), in merged data of 1257 patients from the statin arms of the ASAP, RADIANCE 1, CAPTIVATE and ENHANCE studies and performed backward regression analyses with prespecified co-variates. Based on this analysis, bootstrap analyses were performed to estimate cIMT progression for various hypothetical in- and exclusion criteria. For all studies combined, 2-year mean cIMT progression was 0.0102 ± 0.1348 mm. Positive predictors of this progression were prior use of high dose statins and use of other lipid-modifying therapy. Positive predictors of 1-year mean cIMT progression and 1 & 2 year CCA cIMT progression were age, history of hypertension, Framingham risk score, female gender, high dose statin use and history of CAD; negative predictors were screening LDL-C and ApoA-I. In simulations, HeFH patients previously taking statin and over 50 years of age had an estimated 2-year mean cIMT progression of 0.0216 ± 0.155 mm (based on n = 380). Two year progression for patients with a history of CAD or a Framingham risk score ≥ 10 would be estimated at 0.0197 ± 0.158 mm (based on n = 334). This study shows that cIMT progression in a contemporary HeFH patient population is substantially lower than anticipated, limiting the usefulness of cIMT studies to test new therapies in this population. While focus on individual subgroups characterized by population-specific predictors of cIMT progression results in slightly higher cIMT progression, the current analysis suggests that other patient populations should be considered for future cIMT studies.
GENDER DIFFERENCES IN VASCULAR ENDOTHELIAL FUNCTION AND CAROTID INTIMA MEDIA THICKNESS BY FRAMINGHAM RISK SCORE
