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CCTA Features of Nonobstructive Coronary Lesions Progressing to Obstructive CAD
Study Questions:
What are the features of nonobstructive coronary lesions seen on coronary computed tomography angiography (CCTA) that are associated with progression to obstructive lesions, and is the presence of high-risk plaque (HRP) an independent predictor for lesion progression?
Methods:
This study is an analysis of the PARADIGM (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging) registry. In the PARADIGM registry, 2,252 patients were enrolled who underwent clinically indicated serial CCTA. Patients with an absence of laboratory data, follow-up CCTA, uninterpretable CCTA, prior coronary artery disease (CAD) (defined as myocardial infarction or revascularization), patients who experienced a clinical event, and patients with obstructive lesions (defined as ≥50% diameter stenosis [%DS]) were excluded. Serial CCTA examinations were evaluated for %DS, lesion length, plaque volume, and vessel volume. Plaque volume was further divided into noncalcified plaque, fibrofatty plaque, fibrous plaque, and calcified plaque. Percent atheroma volume (PAV) for total and each plaque component was measured. Lesions were further divided into high-risk plaque (HRP) and non-HRP based on the presence or absence of two or three of the following HRP features: positive arterial remodeling, low-attenuation plaque, or spotty calcification. Lesion progression was measured by the annual change in PAV, and the cut-off point of ≥50% DS was used to define obstructive CAD.
To determine CCTA measures predicting development of an obstructive lesion, marginal Cox models were constructed. Adjustment was made for age, sex, smoking history, hypertension, diabetes, hyperlipidemia, family history of CAD, body mass index, change in low-density lipoprotein levels, statin use, beta-blocker use, and antiplatelet use.
Results:
The final study population included 1,297 patients (aged 60.3 ± 9.3 years, 56.8% male). The time between interval CCTA was 3.8 ± 1.6 years. Patients who had at least one HRP lesion were more likely to be male, with a history of hypertension, diabetes, family history of CAD, smoking history, and treated with statins and antiplatelet drugs. During the follow-up of 4.5 ± 21 years from the second CCTA, 6.8% of patients experienced a major adverse cardiac event.
In the study population, there were 3,049 nonobstructive lesions, of which 86.1% were non-HRP. Stenosis severity was higher in HRP lesions (19.1 ± 11.6% vs. 17.1 ± 11.5%, p < 0.001). Obstructive lesions developed in 1.8% of non-HRP lesions (n = 48) and 5.2% of HRP lesions (n = 22, p < 0.001), although the change in %DS was not different between groups. A multivariate model to predict progression to obstructive lesions which included total PAV, %DS, and presence of HRP had a C-statistic of 0.873, with total PAV and %DS at baseline being significant risk factors for development of obstructive lesions (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.02-1.07, and HR, 1.07; 95% CI, 1.04-1.10; p < 0.05). In the model using HRP alone (instead of baseline total PAV or %DS), the C-statistic of the model was decreased to 0.753.
In non-HRP lesions, both baseline and total PAV and %DS were independent predictors for progression to obstructive lesion (HR, 1.035; 95% CI, 1.002-1.067 and HR, 1.081; 95% CI, 1.049-1.115). In HRP lesions, only baseline PAV was an independent predictor of progression to an obstructive lesion (HR, 1.102; 95% CI, 1.035-1.174; p = 0.003).
Conclusions:
In nonobstructive coronary artery plaques, PAV and %DS at baseline were the most important factors in determining progression into obstructive lesions. While a higher percentage of HRP progressed to obstructive lesions compared to non-HRP, the presence of high-risk plaque features was not an independent predictor of lesion progression.
Perspective:
This analysis of the PARADIGM registry demonstrates that total PAV and %DS were strong predictors of progression of nonobstructive coronary lesions to obstructive coronary lesions. HRP alone was not an independent predictor for progression to an obstructive lesion. These findings highlight the question of whether HRP features (positive arterial remodeling, low-attenuation plaque, and spotty calcification) are co-existing markers of atherosclerosis versus direct indicators of lesions that will cause future events.
The present analysis excluded patients with prior cardiac events and obstructive disease. In addition, patients who developed interval clinical events or developed obstructive disease may not have received a second CCTA, making the study population overall low risk. In order to fully test prediction models for PAV, %DS, and HRP characteristics, large, population-based prospective cohorts that can track changes in coronary atherosclerotic plaque are needed. With that being said, the data presented in this work suggest that instead of qualitative plaque characteristics, quantitative evaluation of atherosclerotic plaque burden may improve methods of identifying lesions that may progress to obstructive CAD.
Keywords: Acute Coronary Syndrome, Angiography, Atherosclerosis, Constriction, Pathologic, Coronary Artery Disease, Diabetes Mellitus, Diagnostic Imaging, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypertension, Metabolic Syndrome, Myocardial Infarction, Plaque, Atherosclerotic, Platelet Aggregation Inhibitors, Primary Prevention, Risk Factors, Smoking, Tomography, X-Ray Computed
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