Arterial endothelial function and wall thickness in familial hypercholesterolemia and familial combined hyperlipidemia and the effect of statins. A systematic review and meta-analysis.

BACKGROUND: To evaluate the impact of familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH) on arterial properties and the effects of statins.

METHODS: We meta-analyzed 51 studies providing data for 4,057 FH patients and 732 FCH patients with random-effects models, meta-regression analysis and publication bias analysis. The main outcomes of interest were (1) brachial artery flow-mediated dilation (FMD), (2) intima-media thickness (IMT), and (3) change of IMT and FMD after treatment with statins.

RESULTS: Compared to normolipidemic controls, FH patients had lower FMD [pooled mean difference (MD): -5.31%, 95% CI -7.09 to -3.53%, P<0.001] and higher carotid IMT (pooled MD: 0.12mm, 95% CI 0.09-0.15mm, P<0.001) and femoral IMT (pooled MD: 0.35mm, 95% CI 0.18-0.51mm, P<0.001). FCH patients had lower FMD and increased IMT (pooled MD: -3.60%, 95% CI -6.69 to -0.50%, P=0.023; and 0.06mm, 95% CI 0.04-0.08mm, P<0.001, respectively). Total and LDL-cholesterol was a significant determinant of FMD and carotid IMT in FCH patients and of FMD and femoral IMT in FH patients. In FH patients, statins improved FMD (pooled MD of change: 5.39%, 95% CI 2.86-7.92%, P<0.001) and decreased carotid IMT (pooled MD of change: -0.025mm, 95% CI -0.042 to -0.009mm, P=0.003). Changes of both FMD and IMT with statins correlated with the duration×treatment intensity product in FH patients (both P<0.01). Additionally, statins improved FMD in FCH patients (pooled MD of change: 2.06%, 95% CI 0.43-3.69%, P=0.013). No significant publication bias was detected.

CONCLUSION: Arterial properties are impaired in subjects with FH or FCH. Statins improve arterial function and structure in FH patients in a treatment intensity-related manner.