C-Reactive Protein, but not Low-Density Lipoprotein Cholesterol Levels, Associate with Coronary Atheroma Regression and Cardiovascular Events Following Maximally Intensive Statin Therapy
Background—Baseline C-reactive protein (CRP) levels predict major adverse cardiovascular events [MACE; death, myocardial infarction, stroke, coronary revascularization and hospitalization for unstable angina]. The association between changes in CRP levels with plaque progression and MACE in the setting of maximally intensive statin therapy is unknown.
Methods and Results—SATURN employed serial intravascular ultrasound (IVUS) measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The treatment groups did not differ significantly in the change from baseline of percent atheroma volume (PAV) on IVUS, CRP-modulating effects or MACE rates, thus allowing for a (prespecified) post-hoc analysis to test associations between changes in CRP levels with coronary disease progression and MACE. Patients with non-increasing CRP levels (n=621) had higher baseline [2.3 (1.1, 4.7) vs. 1.1 (0.5, 1.8) mg/L, p<0.001] and lower follow-up CRP levels [0.8 (0.5, 1.7) vs. 1.6 (0.7, 4.1) mg/L, p<0.001] versus those with increasing CRP levels (n=364). Multivariable analysis revealed a non-increasing CRP level to independently associate with greater PAV regression (p=0.01). While the (log) change in CRP did not associate with MACE [HR 1.18 (95% CI 0.93, 1.50), p=0.17], the (log) on-treatment CRP associated significantly with MACE [HR 1.28 (95% CI 1.04, 1.56, p=0.02). On-treatment LDL-C levels did not correlate with MACE [HR 1.09 (95% CI 0.88, 1.35, p=0.45).
Conclusions—Following 24 months of potent statin therapy, on-treatment CRP levels associated with MACE. Inflammation may be an important driver of residual cardiovascular risk in patients with coronary artery disease despite aggressive statin therapy.
Clinical Trial Registration Information—ClinicalTrials.gov. Identifier: NCT000620542.
- C-reactive protein
- low-density lipoprotein cholesterol
- intravascular ultrasound
- Received June 3, 2013.
- Revision received August 8, 2013.
- Accepted August 29, 2013.