Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers: JACC State-of-the-Art Review

Abstract

A new cardiometabolic-based chronic disease (CMBCD) model is presented that provides a basis for early and sustainable, evidence-based therapeutic targeting to promote cardiometabolic health and mitigate the development and ravages of cardiovascular disease. In the first part of this JACC State-of-the-Art Review, a framework is presented for CMBCD, focusing on 3 primary drivers (genetics, environment, and behavior) and 2 metabolic drivers (adiposity and dysglycemia) with applications to 3 cardiovascular endpoints (coronary heart disease, heart failure, and atrial fibrillation). Specific mechanistic pathways are presented configuring early primary drivers with subsequent adiposity, insulin resistance, β-cell dysfunction, and metabolic syndrome, leading to cardiovascular disease. The context for building this CMBCD model is to expose actionable targets for prevention to achieve optimal cardiovascular outcomes. The tactical implementation of this CMBCD model is the subject of second part of this JACC State-of-the-Art Review.

Keywords: adipokines; adiposity; atherosclerosis; atrial fibrillation; cardiomyopathy; cardiovascular; chronic disease; dysglycemia; insulin resistance; obesity; type 2 diabetes.

FIGURE 1

The Intermediating Roles of Insulin Resistance and Metabolic Syndrome in Cardiometabolic-Based Chronic Disease

FIGURE 2. Insulin Resistance at the Intersection of ABCD and DBCD

Shaded areas and arrows indicate main causal relationships: abnormal adiposity to insulin resistance to dysglycemia. Asterisks indicate exertions of other metabolic syndrome traits. ABCD = adiposity-based chronic disease; ABNL = abnormal; BMI = body mass index; DBCD = dysglycemia-based chronic disease.

CENTRAL ILLUSTRATION. Cardiometabolic-Based Chronic Disease: Adiposity and Dysglycemia Drivers

The 4 stages of CMBCD are depicted at the top. In CMBCD Stage I (first column), adiposity, dysglycemia, and other metabolic drivers act concurrently and independently to produce cardiovascular disease. For cardiovascular disease pre-disease (bottom row, second column), subclinical coronary heart disease is suspected by interrogating 3 vascular beds: increased coronary calcium score, 3-dimensional carotid ultrasound, and ankle-brachial index; left ventricular dysfunction by echo-cardiography; and left atrial abnormality by electrocardiogram and echocardiogram. Stages are currently defined by artificial boundaries, determined by thresholds of detectability, and positioned along a continuum. Arrows indicate complex causal relationships among drivers and stages. Insulin resistance (red) occupies a critical integrating pathophysiological role. AF = atrial fibrillation; CHD = coronary heart disease; LA = left atrial; LV = left ventricular; CMBCD = cardiometabolic-based chronic disease.