Rapid Plaque Progression Is Independently Associated With Hyperglycemia and Low HDL Cholesterol in Patients With Stable Coronary Artery Disease: A PARADIGM Study
Authors: Neglia Danilo , Caselli Chiara , Maffei Erica , Cademartiri Filippo , Meloni Antonella , Bossone Eduardo , Saba Luca , Lee Sang-Eun , Sung Ji Min , Andreini Daniele , Al-Mallah Mouaz H. , Budoff Matthew J. , Chinnaiyan Kavitha , Choi Jung Hyun , Chun Eun Ju , Conte Edoardo , Gottlieb Ilan , Hadamitzky Martin , Kim Yong Jin , Lee Byoung Kwon , Leipsic Jonathon A. , Marques Hugo , de Araújo Gonçalves Pedro , Pontone Gianluca , Shin Sanghoon , Stone Peter H. , Samady Habib , Virmani Renu , Narula Jagat , Shaw Leslee J. , Bax Jeroen J. , Lin Fay Y. , Min James K. , Chang Hyuk-Jae 
Published: July 2024

BACKGROUND:
We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease.

METHODS:

Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm
3
) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization.

RESULTS:

In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12–2.03];
P
=0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56–3.61];
P
<0.001). In a follow-up of 8.23 years (interquartile range, 5.92–9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10–2.90];
P
=0.018) together with family history, baseline percent atheroma volume, and rapid PP.

CONCLUSIONS:
In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02803411.