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 (mm3 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 non-calcified plaque volumes increased from 27.5 ​mm3 [interquartile range [IQR]: 10.1-55.5] to 53.5 ​mm3 [24.0-97.9], with an annualized change of 4.9 ​mm3/year [1.4-9.6]. Calcified plaque volume increased from 0.3 ​mm3 [0.0-5.7] to 3.2 ​mm3 [0.1-18.2], with an annualized change of 0.4 ​mm3/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.