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

Masoura, Constantina; Pitsavos, Christos; Aznaouridis, Konstantinos; Skoumas, Ioannis; Vlachopoulos, Charalambos; Stefanadis, Christodoulos

doi:10.1016/j.atherosclerosis.2010.10.008

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Volume 214, Issue 1 , Pages 129-138, January 2011

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

Lipid and Peripheral Vessels Units, 1st Department of Cardiology, Athens Medical School, Hippokration Hospital, Athens, Greece

Received 31 May 2010; received in revised form 23 September 2010; accepted 8 October 2010. published online 15 November 2010.

Abstract

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.

Keywords: Familial hypercholesterolemia, Familial combined hyperlipidemia, Atherosclerosis, Endothelium, Flow-mediated dilation, Intima-media thickness, Meta-analysis