NATURal history of coronary PlaquE on cardiac computed tomography in individuals without MACE or lipid-lowering therapy: NATURE-CTstudy.
Authors
Affiliations (6)
Affiliations (6)
- Cardiovascular Research Foundation of Southern California, Beverly Hills, CA, USA; Division of Cardiology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, USA.
- Division of Cardiology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, USA; Department of Medicine, Division of Cardiology, University of California Los Angeles, 757 Westwood Plaza, Los Angeles, CA, USA.
- Division of Cardiology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, USA.
- Division of Radiology, University of California Los Angeles, 757 Westwood Plaza, Los Angeles, CA, USA.
- Department of Medicine, Division of Cardiology, University of California Los Angeles, 757 Westwood Plaza, Los Angeles, CA, USA.
- Cardiovascular Research Foundation of Southern California, Beverly Hills, CA, USA; Division of Cardiology, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: [email protected].
Abstract
Coronary artery disease (CAD) progression has been examined mainly in cohorts enriched for major adverse cardiovascular events (MACE), a high burden of traditional risk factors, or prior exposure to risk-modifying therapies. In contrast, plaque progression is poorly described in patients without prior MACE and receiving no anti-atherosclerotic treatment who undergo cardiac computed tomography angiography (CCTA) for clinical indications. We therefore investigated atherosclerosis progression in this understudied population using serial CCTA. The NATURE-CT study retrospectively identified 205 participants from two outpatient cardiovascular imaging centers in Los Angeles. Eligible participants had ≥ two clinically indicated CCTAs at least 24 months apart, had a baseline coronary artery calcium score (CAC) ≤ 100, and experienced no interim MACE. Use of lipid-lowering or other anti-atherosclerotic medications was absent between scans. Individuals with diabetes mellitus, familial hypercholesterolemia, or chronic kidney disease were excluded. Plaque volume and luminal stenosis on each scan were quantified with a validated artificial-intelligence quantitative CT platform (AI-QCT; Cleerly Labs). The primary endpoint was the annualized change in total plaque volume (mm<sup>3</sup> per year). The cohort had a mean age of 54.9 ± 10.2 years and 72% were White men; 24 % had hypertension, 28 % dyslipidemia, and 15 % were current or former smokers. Mean baseline LDL was 111.6 ± 32.0 mg/dL. The median time between CCTA scans was 4.9 ± 2.2 years. At baseline, 54% had a CAC = 0. Median non-calcified plaque volumes increased from 27.5 mm<sup>3</sup> [interquartile range [IQR]: 10.1-55.5] to 53.5 mm<sup>3</sup> [24.0-97.9], with an annualized change of 4.9 mm<sup>3</sup>/year [1.4-9.6]. Calcified plaque volume increased from 0.3 mm<sup>3</sup> [0.0-5.7] to 3.2 mm<sup>3</sup> [0.1-18.2], with an annualized change of 0.4 mm<sup>3</sup>/year [0.0-2.4]. Low attenuation plaque (LAP) was present in 9% at baseline, and 23% at follow-up. Rapid plaque progression (annual percent atheroma volume (PAV) ≥ 1 % per PARADIGM) occurred in 6 participants (3 %), while 23 participants (11 %) exhibited an annual PAV increase ≥0.59 % (PARADIGM-derived intermediate threshold). Over a median 5-year interval, atherosclerotic burden increased even in patients with minimal baseline CAC, no prior MACE, and no lipid-lowering therapy. Non-calcified plaque accumulated faster than calcified plaque. While rare in healthy individuals, LAP became more prevalent, and a small subset experienced rapid plaque progression.