Effect of atorvastatin on high density lipoprotein cholesterol and its relationship with coronary events: a subgroup analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) Study.
OBJECTIVE
To investigate the relationship between changes in high density lipoprotein cholesterol(HDL-C) levels after statin treatment and the risk for coronary heart disease (CHD)-related events in the secondary CHD prevention GREek Atorvastatin and Coronary heart disease Evaluation (GREACE) Study. These findings suggested that dose titration with atorvastatin (10-80 mg/day, mean 24 mg/day)achieves the National Cholesterol Educational Program treatment goals and significantly reduces morbidity and mortality, in comparison to usual care.


METHODS
Analysis of variance was used to assess the effect of atorvastatin on HDL-C over time (up to 48 months) in 1600 CHD patients. The time-dependent multivariate Cox predictive model,involving backward stepwise logistic regression,was used to evaluate the relation between coronary events and HDL-C changes.


RESULTS
The mean increase in HDL-C levels during the study was 7%. All doses of atorvastatin significantly increased HDL-C levels. Increases were greater in men (7.8 vs 6.1%; p = 0.02), in combined hyperlipidaemia (7.9 vs 6.4% for hypercholesterolaemia; p = 0.04), and in the lower baseline HDL-C quartile (9.2 vs 5.3%, 1st vs 4th quartile; p = 0.001). After adjustment for 24 predictors of coronary events, multivariate analysis revealed a Hazards Ratio of 0.85 (95% confidence interval 0.76-0.94; p = 0.002) for every 4 mg/dL(0.1 mmol/L) increase in HDL-C.


CONCLUSIONS
There was a significant beneficial effect on HDL-C levels across the dose range of atorvastatin. Clinical outcomes in the structured care arm of GREACE were determined in part by the extent of atorvastatin-induced HDL-C increase. This effect was independent from benefit induced by low density lipoprotein cholesterol (LDL-C)reduction, suggesting that the CHD risk reduction associated with a rise in a low HDL-C at baseline remains significant under aggressive (-46%) LDL-C lowering conditions. However, the relationship between HDL-C and vascular risk may be weaker when LDL-C levels are aggressively lowered.
Athyros
Vasilios G
VG
Atherosclerosis Unit, Aristotelian University, Hippocration Hospital, Thessaloniki, Greece. athyros@med.auth.gr
Mikhailidis
Dimitri P
DP
Papageorgiou
Athanasios A
AA
Symeonidis
Athanasios N
AN
Mercouris
Bodosakis R
BR
Pehlivanidis
Anthimos
A
Bouloukos
Vasilios I
VI
Elisaf
Moses
M
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood*; D003327:Coronary Disease / Q000097:blood / Q000517:prevention & control*; D005260:Female; D006115:Greece; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009313:National Health Programs; D016016:Proportional Hazards Models; D011758:Pyrroles / Q000494:pharmacology*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin