Carotid intima-media thickness and plaque in patients with familial hypercholesterolaemia mutations and control subjects

Background In individuals with familial hypercholesterolaemia (FH), ultraso nographic measurement of carotid intima-media thickness (IMT) and plaque ma y provide a noninvasive assessment of cardiovascular risk. Methods We examined carotid artery IMT and its determinants in 79 non-smoki ng, normotensive, treated men and women with FH aged 26-46 years, and in 79 non-smoking, normotensive sex-, age- and body mass index-matched control s ubjects. FH was verified by molecular genetic analyses. The underlying muta tion in the low-destiny lipoprotein receptor gene included a splice-site mu tation, mutations predicted or shown to lead to class 2B mutations or other mutations that probably represent class I mutations (null alleles). Results The carotid bifurcation and common carotid artery IMT was increased in men with FH compared with control subjects (0 . 81 +/- 0 . 15 mm vs. 0 . 74 +/- 0 . 19 mm and 0 . 61 +/- 013 mm vs. 0 . 55 +/- 0 . 14mm respective ly; P < 0 . 05). The carotid bifurcation IMT was increased in women with FH compared with control subjects (0 . 74 +/- 0 . 17 vs. 0 . 66 +/- 0 . 15; P = 0 . 005). More subjects with FH had carotid plaque (54% vs. 14%; P = 0 . 0001). In multivariate analysis, male gender, level of low-density lipopro tein-cholesterol, cholesterol-years score and xanthoma were associated with IA IT and plaque in subjects with FH. FH subjects with class 2B mutations had lower cholesterol levels than subjects with mutations belonging to the other classes. They also had a tendency towards a decreased common carotid artery IMT. Conclusion These findings confirm the importance of gender, xanthoma and li fetime cholesterol levels in relation to carotid atherosclerosis in FH. Whe ther the type of mutation causing FH modulates carotid artery IMT and plaqu e requires further study.