Association of Metabolic Phenotypes With Coronary Artery Disease and Cardiovascular Events in Patients With Stable Chest Pain

Objectives. Determine the association of distinct metabolic phenotypes with coronary artery disease (CAD) and major adverse cardiovascular events (MACE).

Background. Obesity and metabolic syndrome are associated with MACE. However, whether distinct metabolic phenotypes differ in risk for CAD and MACE is unknown.

Methods. We included patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain·(PROMISE) who underwent coronary computed tomography (CT) angiography. Obesity was defined as a BMI≥30kg/m², and metabolically healthy as ≤1 metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and non-obese/obese (MHN·
MHO·MUN·MUO). Differences in severe calcification (CAC≥400), severe CAD (≥70% stenosis), high-risk plaque (HRP), and MACE were assessed using adjusted logistic and Cox-regression models.

Results. Of 4,381 patients (48.4% male, 60.5±8.1y/o), 49.4% were metabolically healthy (30.7% MHN; 18.7% MHO) and 50.6% unhealthy (22.3% MUN; 28.4% MUO). MHO had similar coronary-CT findings as compared to MHN (severe CAC/CAD and HRP, p>0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared to non-obese (p>0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared to MHN (p≤0.017 for all).

130 events occurred during follow-up (median 26 months). Compared to MHN, MUN (HR 1.61·[1.02–2.53]) but not MHO (HR 1.06·[0.62–1.82) or MUO (HR 1.06·[0.66–1.72]) had higher risk for MACE.

Conclusion. In stable chest pain patients, four metabolic phenotypes exhibit distinctly different CAD characteristics and risk for MACE. Individuals who are metabolically unhealthy despite not being obese were at highest risk in our cohort.