To determine whether available lipid-modifying medication can increase high-density lipoprotein (HDL) cholesterol in well-defined genetic or familial HDL-deficiency states, we studied 19 men with HDL deficiency (HDL cholesterol <5th percentile for age and gender) 55 ± 10 years of age. Concomitant risk factors included diabetes (n = 3) and hypertension (n = 7) and 8 patients had coronary artery disease. Molecular analysis revealed that 4 patients had a mutation in the ABCA1 gene. Patients were assigned to sequentially receive atorvastatin 20 mg/day, fenofibrate 200 mg/day, and extended-release niacin 2 g/day for 8 weeks, with a 4-week washout period between each treatment. Patients in whom a statin was required, according to current treatment guidelines, were kept on atorvastatin throughout the study. Baseline HDL cholesterol level was 0.63 ± 0.12 mmol/L (24 ± 5 mg/dl), triglycerides 2.01 ± 0.98 mmol/L (180 ± 86 mg/dl), and low-density lipoprotein (LDL) cholesterol 2.29 ± 0.95 mmol/L (94 ± 39 mg/dl). Mean percent changes in HDL cholesterol on atorvastatin, fenofibrate, and niacin were -6% (p = NS), +6% (p = NS), and +22% (p <0.05), respectively. Furthermore, niacin significantly increased the large α-1 apolipoprotein A-I-containing HDL subspecies (12 to 17 nm). In conclusion, niacin was the only effective drug to increase HDL cholesterol. The absolute increase in HDL cholesterol, ∼0.10 mmol/L (3.9 mg/dl), is of uncertain clinical significance. Biomarkers of HDL-mediated cellular cholesterol efflux were not changed by niacin therapy. Atorvastatin or fenofibrate had little effect on HDL cholesterol; atorvastatin decreased the total cholesterol/HDL cholesterol ratio by 26%. Fenofibrate did not change HDL cholesterol levels and caused an increase in LDL cholesterol. Aggressive LDL cholesterol lowering may be the strategy of choice in such patients.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine