Increased cholesterol absorption is associated with In-stent-restenosis after stent implantation for stable coronary artery disease

Background and aims: Blood cholesterol levels are regulated by competing mechanisms of cholesterol synthesis, absorption and excretion. Plant sterols are natural constituents of plants, are not synthesized in humans, and serve as markers for cholesterol absorption. Ezetimibe lowers the intestinal absorption of cholesterol and plant sterols. We analyzed the associations of differences in cholesterol metabolism, in particular increased cholesterol absorption, and the occurrence of in-stent restenosis (ISR) in patients with stable coronary artery disease.Methods: Elective stent implantation of de novo stenosis was conducted in 59 patients (74.6 % males, 67.2 +/- 9.6 years). Cholesterol and non-cholesterol sterols were quantified in serum samples by gas chromatography or mass spectrometry. ISR was assessed by optical coherence tomography (OCT) and quantitative angiography (QCA) after six months.Results: Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were positively associated with ISR measured by QCA (%diameter stenosis, late lumen loss) and OCT (proliferation volume, %area stenosis), whereas markers for cholesterol synthesis (e.g. lathosterol-to-cholesterol) were negatively associated with ISR (%area stenosis: r = -0.271, p = 0.043). There was no association between ISR and total cholesterol, LDL, HDL, triglycerides. Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were significantly lower in ezetimibe-treated patients compared to patients on a statin only (1.29 +/- 0.69 vs. 2.22 +/- 1.23; p = 0.007). Combined lipid-lowering with ezetimibe plus statin reduced ISR compared to statin only (13.7 +/- 10.4 vs. 22.5 +/- 12.1 %diameter stenosis, p = 0.015).Conclusions: Differences in cholesterol metabolism, more specifically increased cholesterol absorption, are associated with ISR.