NATURal history of coronary PlaquE on cardiac computed tomography in individuals without MACE or lipid-lowering therapy: NATURE-CTstudy

Background: 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.Methods: 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 3 per year).Results: 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 noncalcified plaque volumes increased from 27.5 mm 3 [interquartile range [IQR]: 10.1-55.5] to 53.5 mm 3 [24.0-97.9],with an annualized change of 4.9 mm 3 /year [1.4-9.6].Calcified plaque volume increased from 0.3 mm 3 [0.0-5.7] to 3.2 mm 3 [0.1-18.2],with an annualized change of 0.4 mm 3 /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).Conclusion: 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.