Relationship between insulin resistance, coronary plaque, and clinical outcomes in patients with acute coronary syndromes: an analysis from the PROSPECT study

Serdar Farhan, Björn Redfors, Akiko Maehara, Thomas McAndrew, Ori Ben-Yehuda, Bernard De Bruyne, Roxana Mehran, Birgit Vogel, Gennaro Giustino, Patrick W Serruys, Gary S Mintz, Gregg W Stone, Serdar Farhan, Björn Redfors, Akiko Maehara, Thomas McAndrew, Ori Ben-Yehuda, Bernard De Bruyne, Roxana Mehran, Birgit Vogel, Gennaro Giustino, Patrick W Serruys, Gary S Mintz, Gregg W Stone

Abstract

Background: We investigated the association of insulin resistance (IR) with coronary plaque morphology and the risk of cardiovascular events in patients enrolled in the Providing Regional Observations to Study Predictors of Events in Coronary Tree (PROSPECT) study.

Methods: Patients with acute coronary syndromes (ACS) were divided based on DM status. Non-DM patients were further stratified according to homeostasis-model-assessment IR (HOMA-IR) index as insulin sensitive (IS; HOMA-IR ≤ 2), likely-IR (LIR; 2 < HOMA-IR < 5), or diabetic-IR (DIR; HOMA-IR ≥ 5). Coronary plaque characteristics were investigated by intravascular ultrasound. The primary endpoint was major adverse cardiac events (MACE); a composite of cardiac death, cardiac arrest, myocardial infarction, and rehospitalization for unstable/progressive angina.

Results: Among non-diabetic patients, 109 patients (21.5%) were categorized as LIR, and 65 patients (12.8%) as DIR. Patients with DIR or DM had significantly higher rates of echolucent plaque compared with LIR and IS. In addition, DIR and DM were independently associated with increased risk of MACE compared with IS (adjusted hazard ratio [aHR] 2.29, 95% confidence interval [CI] 1.22-4.29, p = 0.01 and aHR 2.12, 95% CI 1.19-3.75, p = 0.009, respectively).

Conclusions: IR is common among patients with ACS. DM and advanced but not early stages of IR are independently associated with increased risk of adverse cardiovascular events. Trial Registration ClinicalTrials.gov Identifier: NCT00180466.

Keywords: Acute coronary syndrome; Culprit and non-culprit lesion events; Glucose; Insulin; Insulin resistance.

Conflict of interest statement

Akiko Maehara: Grant support from Abbott Vascular and Boston Scientific, consultant for Conavi Medical Inc. Bernard De Bruyne: Institutional grant support from Abbott, Boston Scientific, and Biotronik AG; institutional consulting fees from Abbott, Opsens, and Boston Scientific. Roxana Mehran: Institutional Grant Support (funding to the institution)—AstraZeneca, Bayer, Beth Israel Deaconess, BMS, CSL Behring, DSI, BSC, Novartis Pharmaceuticals, OrbusNeich; Consulting Fees—Medscape, Regeneron Pharmaceuticals (no fee, Sanofi, Abbott Laboratories (personal fees for speaking engagements; consultant (paid to the institution), Abiomed and The Medicines Company (consultant – spouse); Scientific Advisory Board/Advisory Board—PLx Opco Inc./PLx Pharma Inc. (scientific advisory board), Bristol Myers Squibb (advisory board; funding to the institution); Equity < 1%—Claret Medical, Elixir Medical; Executive Committee (paid to the institution)—Janssen Pharmaceuticals; DSMB Membership—Watermark Research Partners. Patrick W. Serruys: Consultant – Abbott, Biosensors, Medtronic, Micell Technologies, SINOMED, Philips/Volcano, Xeltis, HeartFlow. Gary S. Mintz: Honoraria—Boston Scientific, Philips, Terumo, and Medtronic. The rest of the authors: none.

Figures

Fig. 1
Fig. 1
Clinical Outcomes Through 3 Years of Follow-up. a Overall major adverse cardiac events (MACE), b culprit lesion MACE, and (c) non-culprit lesion MACE stratified by homeostasis model assessment insulin resistance and diabetes mellitus status. DIR = diabetic insulin resistance; DM = diabetes mellitus; IS = insulin sensitive; LIR = likely insulin resistant
Fig. 2
Fig. 2
Predictors of 3-Year Outcomes. Adjusted for risk of (a) overall major adverse cardiac events (MACE), b culprit lesion MACE, and (c) non-culprit lesion MACE. aHR = adjusted hazard ratio; CI = confidence interval; DIR = diabetic insulin resistance; DM = diabetes mellitus; LIR = likely insulin resistant. b and c were adjusted for age, sex, use of aspirin in the preceding 7 days, and history of percutaneous coronary intervention due to the low number of events in each group

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