Title Assessment of Coronary atherosclerosis in patients with familialhypercholesterolemia by coronary computed tomography angiography

The aims of this study were 1) to determine whether the accumulation of coronary plaque burden assessed with coronary computed tomography angiography (CCTA) can predict future events, and 2) to estimate the onset and progression of coronary atherosclerosis in patients with familial hypercholesterolemia (FH). Consecutive 101 Japanese heterozygous FH patients (male=52, mean age=56±16 years, mean LDL-C=264±58 mg/dL) who underwent 64-detector row CCTA without known coronary artery disease were retrospectively evaluated by assigning a score (0-5) to each of 17 coronary artery segments according to the Society of Cardiovascular Computed Tomography guidelines. Those scores were summed and subsequently natural log-transformed. The periods to major adverse cardiac events (MACE) were estimated using multivariable Cox proportional hazards models. During the follow-up period (median 941 days), 21 MACE had occurred. Receiver-operating characteristic curve analyses identified a plaque burden score of 3.35 (raw score 28.5) as the optimal cutoff for predicting a worse prognosis. Multivariate Cox regression analysis identified the presence of a plaque score ≥ 3.35 as a significant independent predictor of MACE (HR=3.65; 95% CI 1.32 to 25.84, p<0.05). The regression equations were Y=0. 68X-15.6 (r=0.54, p<0.05) in male and Y=0. 74X-24.8 (r=0. 69, p<0. 05) in female heterozygous FH patients. In conclusion, coronary plaque burden identified in a noninvasive, quantitative manner was significantly associated with future coronary events in Japanese patients with heterozygous FH and that coronary atherosclerosis may start to develop, on average, at 23 and 34 years of age in male and female heterozygous FH patients, respectively.