Patients with stable chest pain had four distinct patterns of metabolic phenotypes which had unique coronary artery disease (CAD) trajectories and major adverse cardiovascular event (MACE) risk profiles. These findings, from a prospective, multicenter study, were published in Diabetes Care.

Researchers recruited 4381 patients with stable chest pain for the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE; Identifier: NCT01174550) study. Patients were assessed by computed tomography (CT) and at a median of 25 months, participants were evaluated for clinical outcomes. Study participants were aged 60.5±8.1 years and 51.6% were women.

Patients were stratified by whether they were considered metabolically healthy (diabetes, hypertension, or hyperlipidemia status) and whether they were obese. Cohorts comprised metabolically healthy non-obese (MHN; n=1345) or obese (MHO; n=818) and metabolically unhealthy non-obese (MUN; n=975) or obese (MUO; n=1243) individuals.

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Among metabolically healthy or unhealthy individuals, those who were obese were younger (all P <.001), lived sedentary lifestyles (all P <.001), and had lower prevalence of hyperlipidemia (healthy: P <.001; unhealthy: P =.0028). Among all patients, those who had diabetes were more likely to have severe calcification (P <.05), CAD (P <.05), and high-risk plaques (P <.05). Metabolically unhealthy cohorts had higher proportions of non-White participants (P <.001).

During baseline CT, MHO individuals had lower Leaman scores than MHN (P =.032) and fewer MUN patients had evidence of calcification compared with MUO (P =.007).

Compared with MHN, no outcomes were more likely among MHO, MUO individuals were at increased risk for severe CA calcification (adjusted odds ratio [aOR], 2.29; 95% CI, 1.75-3.00), severe CAD (aOR, 1.61; 95% CI, 1.15-2.17), and high-risk plaques (aOR, 1.44; 95% CI, 1.22-1.70), and MUN individuals were at an increased risk for severe CA calcification (aOR, 1.84; 95% CI, 1.39-2.44), severe CAD (aOR, 1.53; 95% CI, 1.08-2.17), high risk plaques (aOR, 1.39; 95% CI, 1.16-1.66), and MACE (hazard ratio [HR], 1.61; 95% CI, 1.02-2.53).

A total of 130 events occurred during follow-up (25 nonfatal myocardial infarctions, 47 hospitalizations due to unstable angina, and 60 deaths). Among all groups, those who were considered MUN had the highest proportion of adverse events (log-rank, P =.042). This study may have been limited by the choice to exclude all patients with a BMI higher than 40.

These data indicated patients with stable chest pain who were metabolically unhealthy but not obese were at an increased risk for poorer clinical outcomes, followed by patients who were metabolically unhealthy and obese. Metabolically healthy patients had the lowest risk for adverse clinical outcomes, regardless of obesity status.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Kammerlander AA, Mayrhofer T, Ferencik M, et al; on behalf of the PROMISE Investigators. Association of metabolic phenotypes with coronary artery disease and cardiovascular events in patients with stable chest pain. Diabetes Care. Published online February 8, 2021. doi:10.2337/dc20-1760

This article originally appeared on Endocrinology Advisor