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Insights from CIRT into management of residual cardiovascular risk

Future treatments for prevention of atherosclerotic cardiovascular disease should target both inflammation and additional cholesterol reduction, according to this latest analysis from the Cardiovascular Inflammation Reduction Trial (CIRT). CIRT tested whether the addition of low-dose methotrexate 15 mg/day reduced major adverse cardiovascular events (MACE) in patients with stable coronary artery disease (CAD) and either diabetes mellitus or metabolic syndrome or both. The topline results of the trial did not shown any benefit from this intervention, with no reduction in interleukin (IL)-1β, IL-6, or high-sensitivity C-reactive protein (hs-CRP). A major factor was that CIRT did not mandate high residual inflammation as an entry criterion for the study.

This subsequent analysis from CIRT compared baseline levels of IL-6, hs-CRP and low-density lipoprotein cholesterol (LDL-C) as markers of residual risk in 4168 patients enrolled in the study. Baseline levels of IL 6, hs-CRP, and LDL-C were all predictors of major recurrent cardiovascular events. Adjusted hazard ratios [HR; 95% confidence interval (CI)] for increasing quartiles of IL-6 were 1.0 (referent), 1.66 (1.18-2.35), 1.92 (1.36-2.70), and 2.11 (1.49-2.99), p<0.0001); for increasing quartiles of hs-CRP were 1.0 (referent), 1.28 (0.92-1.79), 1.73 (1.25-2.38), and 1.79 (1.28-2.50; p<0.0001) and for increasing quartiles of LDL-C were 1.0 (referent), 1.12 (0.78-1.62), 1.25 (0.87-1.79), and 2.38 (1.72-3.30; p<0.0001). Patients with both elevated levels of LDL-C and inflammation were at highest risk. The authors concluded that targeting both inflammation and LDL-C is needed to reduce cardiovascular risk.
Comparison of interleukin-6, C-reactive protein, and low-density lipoprotein cholesterol as biomarkers of residual risk in contemporary practice: secondary analyses from the Cardiovascular Inflammation Reduction Trial

Ridker PM, MacFadyen JG, Glynn RJ et al.