Alberto J Lorenzatti1,2, Maria Luz Servato3. 1. DAMIC Medical Institute/Rusculleda Foundation for Research. 2. Cardiology Department, Cordoba Hospital. 3. DAMIC Medical Institute/Rusculleda Foundation for Research, Cordoba, Argentina.
Abstract
PURPOSE OF REVIEW: Based on compelling data from animal and human studies, over the past few decades, the viewpoint of atherosclerosis as an exclusively lipid-driven disease, has been gradually replaced by the concept of a chronic low-grade inflammatory process of the arterial wall. This review presents a brief description on the role of inflammation in atherosclerosis, and examines selected anti-inflammatory interventions that have been tested in clinical trials designed to prevent adverse cardiovascular disease (CVD) events and excess CVD risk. RECENT FINDINGS: The Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial has provided convincing evidence that neutralization of the interleukin (IL)-1β inflammatory pathway by the selective antibody canakinumab reduces major CVD events and significantly lowers IL-1β, IL-6 and high-sensitivity C-reactive protein, without affecting low-density lipoprotein cholesterol levels. In contrast, in the latest Cardiovascular Inflammation Reduction Trial, low-dose methotrexate compared with placebo did not reduce CVD events, probably because there was no reduction in IL-1β, or in downstream inflammatory biomarker levels either. SUMMARY: Notwithstanding the utilization of effective medical treatments including statins and proprotein convertase subtilisin/kexin type 9 inhibitors or precise revascularizations, the recurrence of CVD events remains unacceptably high. Canakinumab is, at present, the only anti-inflammatory agent that has been proven to reduce cardiovascular events in patients with elevated markers of inflammation without modifying cholesterol levels. Nevertheless, clinical application related to this new evidence and associated knowledge has not yet been implemented in daily practice.
PURPOSE OF REVIEW: Based on compelling data from animal and human studies, over the past few decades, the viewpoint of atherosclerosis as an exclusively lipid-driven disease, has been gradually replaced by the concept of a chronic low-grade inflammatory process of the arterial wall. This review presents a brief description on the role of inflammation in atherosclerosis, and examines selected anti-inflammatory interventions that have been tested in clinical trials designed to prevent adverse cardiovascular disease (CVD) events and excess CVD risk. RECENT FINDINGS: The Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial has provided convincing evidence that neutralization of the interleukin (IL)-1β inflammatory pathway by the selective antibody canakinumab reduces major CVD events and significantly lowers IL-1β, IL-6 and high-sensitivity C-reactive protein, without affecting low-density lipoprotein cholesterol levels. In contrast, in the latest Cardiovascular Inflammation Reduction Trial, low-dose methotrexate compared with placebo did not reduce CVD events, probably because there was no reduction in IL-1β, or in downstream inflammatory biomarker levels either. SUMMARY: Notwithstanding the utilization of effective medical treatments including statins and proprotein convertase subtilisin/kexin type 9 inhibitors or precise revascularizations, the recurrence of CVD events remains unacceptably high. Canakinumab is, at present, the only anti-inflammatory agent that has been proven to reduce cardiovascular events in patients with elevated markers of inflammation without modifying cholesterol levels. Nevertheless, clinical application related to this new evidence and associated knowledge has not yet been implemented in daily practice.
Authors: Gayathree Murugappan; Stephanie A Leonard; Leslie V Farland; Emily S Lau; Aladdin H Shadyab; Robert A Wild; Peter Schnatz; Suzan L Carmichael; Marcia L Stefanick; Nisha I Parikh Journal: Fertil Steril Date: 2022-03-16 Impact factor: 7.490