Effect of high-dose atorvastatin on the cardiovascular risk associated with individual components of metabolic syndrome: a subanalysis of the Treating to New Targets (TNT) study

Aims: To investigate the impact of intensive lipid-lowering with high-dose atorvastatin on the cardiovascular risk associated with individual metabolic syndrome components [high body mass index (BMI), elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension and elevated fasting glucose] in patients with coronary heart disease (CHD). Methods: Patients with clinically evident, stable CHD and low-density lipoprotein (LDL) cholesterol <3.4 mmol/l (130 mg/dl) were randomized to double-blind therapy with atorvastatin 10mg/day (n=5006) or 80 mg/day (n=4995) after an 8-week open-label run-in with atorvastatin 10mg. The median follow-up was 4.9 years. The impact of individual metabolic syndrome risk factors was tested on the primary endpoint, which was the occurrence of a first major cardiovascular event. Results: On-treatment LDL cholesterol was 2.6 mmol/l (101 mg/dl) with atorvastatin 10mg and 2.0 mmol/l (77 mg/dl) with atorvastatin 80mg. Among patients receiving atorvastatin 10mg, the presence of each individual metabolic syndrome component significantly increased the risk of major cardiovascular events compared with the absence of each (BMI, p=0.014; triglycerides, p=0.006; HDL cholesterol, p=0.0006; hypertension, p<0.0001; and fasting glucose p<0.0001). In patients receiving atorvastatin 80mg, elevated triglycerides and fasting glucose were no longer significant predictors of major cardiovascular events. The predictive power of hypertension on the risk of major cardiovascular events was reduced in patients treated with atorvastatin 80mg, although it remained a significant predictor. Conclusions: Treatment with high-dose atorvastatin to a mean LDL cholesterol level of 2.0 mmol/l (77 mg/dl) considerably attenuated the predictive power associated with three metabolic syndrome components.