HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial

HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort,
whether this association remains when LDL-cholesterol concentrations are
reduced to the very low ranges with high-dose statin treatment.

Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline
concentrations of LDL cholesterol of less than 3·37 mmol/L and
high-sensitivity C-reactive protein of 2 mg/L or more. Participants were
randomly allocated by a computer-generated sequence to receive
rosuvastatin 20 mg per day or placebo, with participants and
adjudicators masked to treatment assignment. In the present analysis, we
divided the participants into quartiles of HDL-cholesterol or
apolipoprotein A1 and sought evidence of association between these
quartiles and the JUPITER primary endpoint of first non-fatal myocardial
infarction or stroke, hospitalisation for unstable angina, arterial
revascularisation, or cardiovascular death.

For 17 802 patients in the JUPITER trial, rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44% (p<0·0001). In
8901 (50%) patients given placebo (who had a median on-treatment
LDL-cholesterol concentration of 2·80 mmol/L [IQR 2·43—3·24]),
HDL-cholesterol concentrations were inversely related to vascular risk
both at baseline (top quartile vs bottom quartile hazard ratio
[HR] 0·54, 95% CI 0·35—0·83, p=0·0039) and on-treatment (0·55,
0·35—0·87, p=0·0047). By contrast, among the 8900 (50%) patients given
rosuvastatin 20 mg (who had a median on-treatment LDL-cholesterol
concentration of 1·42 mmol/L [IQR 1·14—1·86]), no significant
relationships were noted between quartiles of HDL-cholesterol
concentration and vascular risk either at baseline (1·12, 0·62—2·03,
p=0·82) or on-treatment (1·03, 0·57—1·87, p=0·97). Our analyses for
apolipoprotein A1 showed an equivalent strong relation to frequency of
primary outcomes in the placebo group but little association in the
rosuvastatin group.

Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations
are not predictive of residual vascular risk among patients treated with
potent statin therapy who attain very low concentrations of LDL
cholesterol.

More at Lancet