Influence of low HDL on progression of coronary artery disease and response to fluvastatin therapy

Backgrounds - Patients with coronary artery disease (CAD) commonly have low HDL cholesterol (HDL-C) and mildly elevated LDL cholesterol (LDL-C), leading to uncertainty as to whether the appropriate goal of therapy should be lowering LDL-C or raising HDL-C. Methods and Results - Patients in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) had mildly to moderately elevated LDL-C; many also had low HDL-C, providing an opportunity to compare angiographic progression and the benefits of the HMG-CoA reductase inhibitor fluvastatin in patients with low versus patients with higher HDL- C. Of the 339 patients with biochemical and angiographic data, 68 had baseline HDL-C <0.91 mmol/L (35 mg/dL), mean 0.82 ± 0.06 mmol/L, (31.7 ± 2.2 mg/dL), versus 1.23 ± 0.29 mmol/L (47.4 ± 11.2 mg/dL) in patients with baseline HDL-C ≥ 0.91 mmol/L. Among patients on placebo, those with low HDL- C had significantly more angiographic progression than those with higher HDL- C. Fluvastatin significantly reduced progression among low-HDL-C patients: 0.065 ± 0.036 mm versus 0.274 ± 0.045 mm in placebo patients (P = 0.0004); respective minimum lumen diameter decreases among higher-HDL-C patients were 0.036 ± 0.021 mm and 0.083 ± 0.019 mm (P = 0.09). The treatment effect of fluvastatin on minimum lumen diameter change was significantly greater among low-HDL-C patients than among higher-HDL-C patients (P = 0.01); among low- HDL-C patients, fluvastatin patients had improved event-free survival compared with placebo patients. Conclusions - Although the predominant lipid- modifying effect of fluvastatin is to decrease LDL-C, patients with low HDL- C received the greatest angiographic and clinical benefit.