Objectives No indices are available to facilitate clinicians to identify patients who need either statin monotherapy or statin-ezetimibe combined treatment. We aimed to test whether cholesterol synthesis and absorption markers can predict the cholesterol-lowering response to statin.

Methods A total of 306 statin naïve patients with high risk of coronary heart disease (CHD) were treated with atorvastatin 20 mg/day for 1 month. Cholesterol synthesis markers (desmosterol and lathosterol), absorption markers (campesterol and sitosterol) and low-density lipoprotein cholesterol (LDL-C) levels were measured before and after treatment. The association of these markers with baseline LDL-C levels and its changes were analysed.

Results Atorvastatin decreased LDL-C by 36.8% (range: decrease of 74.5% to increase of 31.9%). Baseline lathosterol and campesterol levels co-determined baseline LDL-C levels and the effect of atorvastatin treatment. The inhibiting effects of atorvastatin on cholesterol synthesis and related LDL-C lowering were significantly associated with baseline lathosterol levels. However, the effect of atorvastatin treatment on LDL-C was modified bi-directionally by baseline campesterol levels. In patients with the highest baseline campesterol levels, atorvastatin treatment decreased cholesterol absorption by 46.1%, which enhanced the effect of LDL-C lowering. Atorvastatin treatment increased cholesterol absorption by 52.3% in those with the lowest baseline campesterol levels, which attenuated the effect of LDL-C reduction. Those with the highest lathosterol but the lowest campesterol levels at baseline had significantly less LDL-C reduction than those with the same baseline lathosterol levels but the highest campesterol levels (27.3% vs. 42.4%, P = 0.002).

Conclusions Our findings suggest that combined patterns of cholesterol synthesis/absorption markers rather than the single value of each marker are potential predictors of the LDL-C lowering effects of statins in high-risk CHD patients.