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


Kammerlander AA(1)(2), Mayrhofer T(3)(4), Ferencik M(3)(5), Pagidipati NJ(6), Karady J(3), Ginsburg GS(7), Lu MT(3), Bittner DO(3)(8), Puchner SB(3)(9), Bihlmeyer NA(10), Meyersohn NM(3), Emami H(3), Shah SH(6)(10), Douglas PS(6), Hoffmann U; PROMISE Investigators.
Author information:
(1)Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA [Email]
(2)Division of Cardiology, Medical University of Vienna, Vienna, Austria.
(3)Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
(4)School of Business Studies, Stralsund University of Applied Sciences, Stralsund, Germany.
(5)Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR.
(6)Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
(7)Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC.
(8)Department of Cardiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
(9)Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria.
(10)Duke Molecular Physiology Institute, Durham, NC.


OBJECTIVE: Obesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE. RESEARCH DESIGN AND 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 ≥30 kg/m2 and metabolically healthy as less than or equal to one metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and nonobese/obese (MHN, MHO, MUN, and MUO). Differences in severe calcification (coronary artery 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 ± 8.1 years of age), 49.4% were metabolically healthy (30.7% MHN and 18.7% MHO) and 50.6% unhealthy (22.3% MUN and 28.4% MUO). MHO had similar coronary CT findings as compared with MHN (severe CAC/CAD and HRP; P > 0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared with nonobese (P > 0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared with MHN (P ≤ 0.017 for all). A total of 130 events occurred during follow-up (median 26 months). Compared with MHN, MUN (hazard ratio [HR] 1.61 [95% CI 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. CONCLUSIONS: In patients with stable chest pain, 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.