Lipid lowering drugs and inflammatory changes: an impact on cardiovascular outcomes?

Abstract

Inflammatory changes are responsible for maintenance of the atherosclerotic process and may underlie some of the most feared vascular complications. Among the multiple mechanisms of inflammation, the arterial deposition of lipids and particularly of cholesterol crystals is the one responsible for the activation of inflammasome NLRP3, followed by the rise of circulating markers, mainly C-reactive protein (CRP). Elevation of lipoproteins, LDL but also VLDL and remnants, associates with increased inflammatory changes and coronary risk. Lipid lowering medications can reduce cholesterolemia and CRP: patients with elevations of both are at greatest cardiovascular (CV) risk and receive maximum benefit from therapy. Evaluation of the major drug series indicates that statins exert the largest LDL and CRP reduction, accompanied by reduced CV events. Other drugs, mainly active on the triglyceride/HDL axis, for example, PPAR agonists, may improve CRP and the lipid pattern, especially in patients with metabolic syndrome. PCSK9 antagonists, the newest most potent medications, do not induce significant changes in inflammatory markers, but patients with the highest baseline CRP levels show the best CV risk reduction. Parallel evaluation of lipids and inflammatory changes clearly indicates a significant link, both guiding to patients at highest risk, and to the best pharmacological approach.

Key messages

• Lipid lowering agents with “pleiotropic” effects provide a more effective approach to CV prevention

• In CANTOS study, patients achieving on-treatment hsCRP concentrations ≤2 mg/L had a higher benefit in terms of reduction in major CV events

• The anti-inflammatory activity of PCSK9 antagonists appears to be of a minimal extent

Keywords:

• Ezetimibe
• CRP
• fibrates
• LDL-C
• PCSK9
• statin

Disclosure statement

MR, NF, CM and CS have nothing to disclose; AC has received honoraria from AstraZeneca, AMGEN, Sanofi, Recordati, Novartis, MSD, Mediolanum, DOC, Mylan and Pfizer.

Additional information

Funding

This work was supported by Fondazione Cariplo [grant number 2015-0552] and Fondazione Carlo Sirtori.