Glycemic progression was associated with increased odds of ≥1 major adverse cardiovascular event within 4 years compared to stable glycemia (OR 1.63; 95% CI 1.36-1.94; p<0.001).
Cohort (n=6,578)
Does baseline clinical and proteomic profiling predict glycemic progression and subsequent MACE risk in patients from the SELECT trial?
Baseline clinical and proteomic data can accurately identify patients at risk for glycemic progression, who have a significantly higher risk of subsequent major adverse cardiovascular events.
Odds Ratio: 1.63 (95% CI 1.36–1.94)
p-value: p=<0.001
Introduction and Objective: This post hoc analysis identified patients (pts) at high risk of glycemic progression (GP) using baseline (BL) clinical and proteomic data and evaluated their risk of major adverse cardiovascular events (MACE). Methods: Pts receiving placebo (n=6578) in SELECT with complete 2-yr HbA1c profiles and BL proteomics were included. Pts receiving glucose-lowering rescue therapy during the 2-yr period were defined as clinical progressors (CP). Temporal clustering (TC) identified HbA1c (%) trajectories in the remaining pts. A validated random forest classifier identified BL clinical and proteomic factors predicting HbA1c progression. High-power predictive proteins were chosen. MACE risk was evaluated. Results: TC revealed 3 clusters with stable glycemia and 1 with metabolic progression (MP) (Fig. A). Four BL variables (HbA1c %, leptin/adiponectin, TG/HDL, GGT) and 31 proteins (covering insulin sensitivity and liver function signaling pathways) identified pts with GP (CP + MP) from those without (Fig. B). The model predicted GP with 81.8% sensitivity, 87.1% specificity, and 84.9% precision, outperforming HbA1c cutoffs of 5.7% and 6.0% (94.4% and 66.3% sensitivity, 54.8% and 95.5% specificity). Pts with GP had higher odds of ≥1 MACE within 4 yrs vs all other clusters combined (OR = 1.63 95% CI 1.36, 1.94; p0.001; Fig. C). Conclusion: Pts with GP have increased MACE risk and can be identified with high precision using BL clinical and proteomic data. Disclosure F. Palluzzi: Employee; Current; Novo Nordisk A/S. I. Lingvay: Consultant; Current; Aadvarak Therapeutics, Abbvie, Alveus Therapeutics, Amgen, Antag Therapeutics, Arrowhead Pharmaceuticals, Astra Zeneca, Baim Institute, Bain Capital, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringe. Research Support; Current; Novo Nordisk A/S, Dexcom, Inc., Boehringer Ingelheim International GmbH. Consultant; Current; Eli Lilly, Genentech, Janssen/J Ended; Novo Nordisk A/S. Board Member; Current; ChemoMetec. Stock/Shareholder; Current; Novo Nordisk A/S, ChemoMetec. S. Kahn: Advisory Panel; Current; AltPep, Amgen Inc., Congruence Therapeutics, Eli Lilly and Company, General Medicines, Kayothera, Merck Current; Novo Nordisk. A. Gjesing: Employee; Current; Novo Nordisk. D.M. Belmont-Rausch: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Viking Therapeutics. Stock/Shareholder; Ended; Madrigal Pharmaceuticals, Inc. H. Amadid: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. K.X. Lim: Employee; Current; Novo Nordisk A/S. Employee; Ended; Roche Pharmaceuticals. K.C. Soh: None. M. Quiroga: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Eli Lilly and Company, Genmab, Coloplast, Novo Nordisk. M.S. Ostenfeld: Employee; Current; Novo Nordisk. T.J. Bari: Employee; Current; Novo Nordisk A/S. Stock/Shareholder; Current; Novo Nordisk A/S. L. Bjerre Knudsen: Employee; Current; Novo Nordisk. N.B. Jorgensen: Employee; Current; Novo Nordisk A/S.
Palluzzi et al. (Fri,) conducted a cohort in Glycemic progression and MACE risk (n=6,578). Glycemic progression vs. All other clusters combined (stable glycemia) was evaluated on ≥1 MACE within 4 yrs (OR 1.63, 95% CI 1.36-1.94, p=<0.001). Glycemic progression was associated with increased odds of ≥1 major adverse cardiovascular event within 4 years compared to stable glycemia (OR 1.63; 95% CI 1.36-1.94; p<0.001).