Fast track — ArticlesReduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial
Introduction
Present guidelines for statin therapy emphasise the need to achieve specific goals for LDL cholesterol to maximise clinical outcomes.1, 2 However, statin therapy has greatest efficacy in the presence of inflammation,3, 4 and several studies show that statins reduce the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) largely independently of LDL cholesterol.5, 6, 7, 8 Furthermore, in both the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT–TIMI 22)9 and Aggrastat-to-Zocor (A to Z)10 trials of patients with acute coronary ischaemia treated with statin therapy, the best clinical outcomes were in those who not only achieved LDL cholesterol less than 1·8 mmol/L (<70 mg/dL), but who also achieved hsCRP less than 2 mg/L. These findings are consistent with the pathophysiological understanding that atherothrombosis is a disorder of both hyperlipidaemia and inflammation11 and that statins have anti-inflammatory and lipid-lowering properties.12, 13
Despite the consistency of these results, whether achieving lower concentrations of hsCRP after initiation of statin therapy is associated with improved clinical outcomes, in a similar manner to that associated with achieving lower concentrations of LDL cholesterol, remains controversial. We prospectively tested this hypothesis in the large-scale JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial.14
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Patients and procedures
The study population was derived from JUPITER—a randomised, double-blind, placebo-controlled trial that was designed to investigate whether rosuvastatin 20 mg daily decreased the rate of first cardiovascular events compared with placebo in apparently healthy men and women with LDL cholesterol less than 3·37 mmol/L (<130 mg/dL) who are at increased vascular risk due to hsCRP concentration of 2 mg/L or more. Full details of the trial protocol and procedures have been previously presented.14 The
Results
Table 1 shows baseline characteristics of the study population in the placebo and rosuvastatin groups according to achieved LDL cholesterol and achieved hsCRP concentrations. Baseline age, blood pressure, HDL cholesterol, triglycerides, glucose, and haemoglobin A1c were much the same between groups (table 1).
As expected, baseline LDL cholesterol values were lower in particpants given rosuvastatin who subsequently achieved LDL cholesterol less than 1·8 mmol/L compared with those who did not;
Discussion
In healthy men and women starting rosuvastatin therapy in the JUPITER trial, achievement of target concentrations of LDL cholesterol less than 1·8 mmol/L and hsCRP less than 2 mg/L was associated with improved event-free survival compared with achievement of neither target or with achievement of reduced LDL cholesterol alone. The differential outcomes that we recorded on the basis of achieved concentrations of LDL cholesterol and hsCRP remained significant and unchanged in magnitude after
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