Quantification of Atherosclerotic Plaque Volume in Coronary Arteries by Computed Tomographic Angiography in Subjects with and without Diabetes
Diabetes mellitus (DM) is a well-established risk factor for cardiovascular disease, with individuals affected by diabetes facing a two- to three-fold higher risk of cardiac events compared to non-diabetic individuals. Despite this association, detailed insights into the characteristics of coronary atherosclerotic plaques in diabetic patients, particularly regarding plaque composition and volumetric quantification, remain limited. This study leverages advancements in computed tomographic angiography (CCTA) to comprehensively evaluate the prevalence, volume, and subtypes of coronary artery plaques in a large cohort of diabetic and non-diabetic patients.
Study Design and Patient Population
The research enrolled 6,676 consecutive patients referred for CCTA between October 2016 and November 2017. After excluding individuals with incomplete clinical data (n=212), non-diagnostic coronary images (n=45), or acute coronary syndrome (n=38), the final cohort comprised 6,381 patients. Among these, 931 (14.59%) were diagnosed with DM based on American Diabetes Association criteria, while 5,450 (85.41%) comprised the non-diabetic group. Baseline characteristics revealed that diabetic patients exhibited a higher prevalence of traditional cardiovascular risk factors, including hypertension (58.97% vs. 48.42%), dyslipidemia (62.30% vs. 38.04%), smoking (37.92% vs. 31.61%), and elevated body mass index (BMI: 26.31 vs. 25.45 kg/m²). Age and gender distribution also differed, with diabetic patients being older (57.5 vs. 55.0 years) and more likely to be male (59.72% vs. 51.28%).
Imaging Protocol and Plaque Analysis
All participants underwent non-enhanced CT scans to assess coronary artery calcium (CAC) scores, followed by prospective electrocardiogram (ECG)-gated CCTA. Imaging parameters included a detector width of 0.6 mm, gantry rotation time of 280 ms, and reconstruction field of view ranging from 200 to 250 mm. Contrast media were administered via a double-head power injector. Plaque analysis was performed using a dedicated workstation (ADW4.6, GE Healthcare), with two radiologists evaluating images.
Plaques were classified and quantified based on Hounsfield unit (HU) thresholds:
- Calcified plaques: >130 HU, defined as regions with at least three contiguous pixels.
- Non-calcified plaques: Further subdivided into lipid-rich plaques (lower HU range) and fibrous plaques (intermediate HU range).
Total plaque volume was calculated as the sum of all plaque subtypes. The coronary tree was segmented according to the modified American Heart Association classification, ensuring systematic evaluation across all vascular segments.
Prevalence and Volume of Coronary Plaques
The study identified coronary plaques in 35.25% of the total cohort (2,249/6,381). Diabetic patients demonstrated a significantly higher prevalence of plaques compared to non-diabetic subjects (48.34% vs. 33.01%, χ²=81.84, P<0.001). This disparity persisted across all plaque subtypes:
- Lipid plaques: 47.37% in DM vs. 32.22% in non-DM.
- Fibrous plaques: 48.23% in DM vs. 33.00% in non-DM.
- Calcified plaques: 37.92% in DM vs. 24.97% in non-DM.
Multivariate logistic regression confirmed DM as an independent predictor of plaque presence (adjusted odds ratio [OR]=1.465, 95% CI: 1.258–1.706, P<0.001), even after adjusting for age, gender, hypertension, dyslipidemia, and smoking.
Volumetric analysis revealed substantial differences in plaque burden between groups. Diabetic patients exhibited larger median volumes for all plaque subtypes:
- Lipid plaques: Interquartile range (IQR)=25.2 mm³ in DM vs. 6.3 mm³ in non-DM (P<0.001).
- Fibrous plaques: IQR=171.7 mm³ in DM vs. 73.0 mm³ in non-DM (P<0.001).
- Calcified plaques: IQR=5.3 mm³ in DM vs. 0.1 mm³ in non-DM (P<0.001).
Total plaque volume was also markedly higher in diabetic subjects (IQR=222.2 mm³ vs. 91.8 mm³, P<0.001).
Clinical Implications and Pathophysiological Insights
The findings underscore the accelerated atherosclerotic burden in diabetic patients, characterized by both a higher prevalence and greater volume of coronary plaques. Notably, non-calcified plaques—comprising lipid-rich and fibrous components—were disproportionately elevated in DM. These plaques are considered more vulnerable to rupture, potentially explaining the heightened risk of acute coronary syndromes in diabetic populations.
The study aligns with prior autopsy and imaging data suggesting that diabetes promotes diffuse coronary atherosclerosis, particularly in distal arterial segments. The increased calcified plaque volume in DM may reflect advanced disease stages, where chronic inflammation and metabolic dysregulation drive plaque calcification. However, the coexistence of abundant non-calcified plaques highlights the complexity of diabetic atherosclerosis, which involves both destabilizing lipid accumulation and stabilizing fibrous remodeling.
Limitations and Future Directions
While the study provides robust volumetric data, several limitations warrant consideration. First, the cross-sectional design precludes causal inferences between DM and plaque progression. Second, the absence of oral glucose tolerance testing in non-diabetic patients may have resulted in misclassification of individuals with impaired glucose tolerance. Third, the duration of diabetes and glycemic control parameters were not analyzed, leaving unanswered questions about the relationship between disease chronicity and plaque characteristics.
Future research should incorporate longitudinal assessments to evaluate plaque progression and clinical outcomes. Additionally, integrating biomarkers of glycemic variability and insulin resistance could elucidate mechanistic links between metabolic dysfunction and plaque morphology.
Conclusion
This large-scale CCTA study demonstrates that diabetic patients harbor a significantly greater burden of coronary atherosclerosis, encompassing both calcified and non-calcified plaque subtypes. The quantitative differences in plaque volume and composition underscore the need for aggressive cardiovascular risk management in diabetic populations. CCTA emerges as a valuable non-invasive tool for stratifying risk and guiding therapeutic interventions in this high-risk cohort.
doi.org/10.1097/CM9.0000000000000733
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