Ridker PM， Danielson E， Fonseca FA， Genest J， Gotto AM Jr， Kastelein JJ， Koenig W， Libby P， Lorenzatti AJ， Macfadyen JG， Nordestgaard BG， Shepherd J， Willerson JT， Glynn RJ; JUPITER Trial Study Group.
    Center for Cardiovascular Disease Prevention， Brigham and Women’s Hospital， Harvard Medical School， Boston， MA， USA.
Abstract
    BACKGROUND: Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations， and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.8 mmol/L (<70 mg/dL). However， the benefit of lowering both LDL cholesterol and hsCRP after the start of statin therapy is controversial. We prospectively tested this hypothesis.
    METHODS: In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial (87% of full cohort)， we prospectively assessed the effects of rosuvastatin 20 mg versus placebo on rates of non-fatal myocardial infarction， non-fatal stroke， admission for unstable angina， arterial revascularisation， or cardiovascular death (prespecified endpoints) during a maximum follow-up of 5 years (median 1.9 years)， according to on-treatment concentrations of LDL cholesterol (>/=1.8 mmol/L or <1.8 mmol/L) and hsCRP (>/=2 mg/L or <2 mg/L). We included all events occurring after randomisation. This trial is registered with ClinicalTrials.gov， number NCT00239681.
    FINDINGS: Compared with placebo， participants allocated to rosuvastatin who achieved LDL cholesterol less than 1.8 mmol/L had a 55% reduction in vascular events (event rate 1.11 vs 0.51 per 100 person-years; hazard ratio [HR] 0.45， 95% CI 0.34-0.60， p<0.0001)， and those achieving hsCRP less than 2 mg/L a 62% reduction (event rate 0.42 per 100 person-years; HR 0.38， 95% CI 0.26-0.56， p<0.0001). Although LDL cholesterol and hsCRP reductions were only weakly correlated in individual patients (r values <0.15)， we recorded a 65% reduction in vascular events in participants allocated to rosuvastatin who achieved both LDL cholesterol less than 1.8 mmol/L and hsCRP less than 2 mg/L (event rate 0.38 per 100 person-years; adjusted HR 0.35， 95% CI 0.23-0.54)， versus a 33% reduction in those who achieved one or neither target (event rate 0.74 per 100 person-years; HR 0.67， 95% CI 0.52-0.87) (p across treatment groups <0.0001). In participants who achieved LDL cholesterol less than 1.8 mmol/L and hsCRP less than 1 mg/L， we noted a 79% reduction (event rate 0.24 per 100 person-years; HR 0.21， 95% CI 0.09-0.52). Achieved hsCRP concentrations were predictive of event rates irrespective of the lipid endpoint used， including the apolipoprotein B to apolipoprotein AI ratio.
    INTERPRETATION: For people choosing to start pharmacological prophylaxis， reduction in both LDL cholesterol and hsCRP are indicators of successful treatment with rosuvastatin.