Abstract
Background
Plant sterols are suspected to exert atherosclerotic propensity. Modern drug-eluting stents are superior to bare metal stents but show a late catch up phenomenon for restenosis. Due to its superb resolution, optical coherence tomography (OCT) has the capability to identify and quantifiy very early patterns of in-stent proliferation. Studies have shown that in-stent neointimal proliferation is linked to late in-stent stenosis.
Purpose
This study aimed to analyze associations of plasma levels for markers of cholesterol homeostasis such as campesterol and sitosterol (markers for cholesterol absorption) as well as lanosterol (marker for cholesterol synthesis)and and their respective oxides with In-stent restenosis after stent deployment in stable coronary artery disease.
Methods
Plasma cholesterol was measured by gas chromatography-flame ionization detection. Plasma campesterol, sitosterol and lanosterol and their oxides were analyzed by gas chromatography-mass selective detection. In-stent proliferation (restenosis) was assessed after six months by OCT in 33 patients (21 males). A quantitative OCT algorithm was applied to each stent by steps of one mm and in-stent proliferation volumes and areas were calculated and normalized to stent length and area. In-stent proliferation can be measured by OCT as global volumes and focal areas.
Results
No clinically significant restenosis or angiographic restenosis of >30% was observed at 6-month f/u. Mean cholesterol level was 166,5±62,8 mg/dl and positively correlated with proliferation volume/cm (r=0.316, p=0.037) and absolute median proliferation area (r=0.322, p=0.029). Absolute median proliferation area and relative median proliferation area correlated positively with markers for cholesterol absorption such as campesterol-to-cholesterol (r=0.277, p=0.07 and 0.315, p=0.037) and sitosterol-to-cholesterol (r=0.237, p=0.092 and 0.322, p=0.034), whereas lanosterol (a marker for cholesterol synthesis) and its ratio to cholesterol correlated negatively with proliferation volumes and areas (p<0.05; table). Moreover, 7-beta-OH-campesterol correlated positively with proliferation volumes and areas (p<0.05, table). Also, the ratio of 7-beta-OH-campesterol-to-cholesterol correlated positively with proliferation volumes and areas (p<0.1,; table), but did not reach significance in this relatively small sample size. Morevover, there was a positive association of the sum of all plant sterol oxides with In-stent restenosis (data not shown).
Conclusions
In this hypothesis-generating study, in-stent proliferation assessed by OCT at six months follow-up was positively associated with markers for cholesterol absorption and negatively associated with markers for cholesterol synthesis. Larger studies will have to evaluate whether patients with high cholesterol absorption might benefit in particular from combined-lipid-lowering therapy with a statin and a cholesterol absorption Inhibitor.
Association of the ITGB3 gene T1565C polymorphism with the development of atherosclerosis and in-stent restenosis in patients with stable coronary artery disease