JOURNAL ARTICLE

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

S Tonstad, O Joakimsen, E Stensland-Bugge, L Ose, K H Bønaa, T P Leren
European Journal of Clinical Investigation 1998, 28 (12): 971-9
9893006

BACKGROUND: In individuals with familial hypercholesterolaemia (FH), ultrasonographic measurement of carotid intima-media thickness (IMT) and plaque may provide a non-invasive assessment of cardiovascular risk.

METHODS: We examined carotid artery IMT and its determinants in 79 non-smoking, 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 subjects. FH was verified by molecular genetic analyses. The underlying mutation in the low-destiny lipoprotein receptor gene included a splice-site mutation, 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 +/- 0.13 mm vs. 0.55 +/- 0.14 mm respectively; 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 lipoprotein-cholesterol, cholesterol-years score and xanthoma were associated with IMT 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 lifetime cholesterol levels in relation to carotid atherosclerosis in FH. Whether the type of mutation causing FH modulates carotid artery IMT and plaque requires further study.

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