Abstract 4139340: Atherosclerotic Plaque Progresses Over Time in Healthy Individuals Without MACE, Risk Factors, or Interventions

Introduction: Studies on the natural history of coronary artery disease have traditionally evaluated the progression of the disease in the presence of MACE, risk factors or risk modifying interventions including pharmacological and non-pharmacological treatment. It is not known how atherosclerotic plaque progresses over the time in the absence of MACE, risk factors or risk modifying interventions. Aim: To evaluate the natural history of atherosclerosis in healthy populations on serial CCTA. Methods: NATURE-CT retrospectively selected 205 participants from two sites in Los Angeles. Subjects underwent at least two CCTA scans, the initial scan showing CAC ≤100, absence of MACE, not placed on lipid modifying therapy in the first and last scan, and at least 2 years apart. Patients with diabetes, familial hypercholesterolemia or chronic kidney disease were excluded. FDA cleared automated software Cleerly Labs (Cleerly.Inc, NY, NY) quantified plaque and stenosis. Primary outcome will be the observed annualized rate of change in the atherosclerotic plaque during the observation period. Results: At baseline visit, the mean age of the cohort was 54.9±10.2 (years), 72% (147) being white males, 0% had DM, 0% had lipid modifying therapy, 24% (49) had hypertension, 28% (57) reported hyperlipidemia and 15% (30) were ever smokers. Mean LDL was 111.6±32.0 mg/dl and the average time between CCTA scans was 4.9±2.2 years. Over half (54%) of the cohort had a CAC=0 at the baseline visit. At baseline, total non-calcified plaque volume was (median and IQR in mm3) [27.5 (10.1, 55.5)] versus at follow-up [53.5 (24.0, 97.9)], with a calculated annualized median change of [4.9 (1.4, 9.6)] in non-calcified plaque. Total calcified plaque volume was [0.3 (0.0, 5.7)] and at follow-up [3.2 (0.1, 18.2)], with a calculated annualized median change of [0.4 (0.0, 2.4)] in calcified plaque. At baseline, 9% (19 subjects) had low attenuation plaque greater than zero, and at follow-up, 23% (48 subjects). 6 subjects had annual change in PAV>=1% (3%) and 23 subjects had annual change in PAV >=0.59% (11%). Conclusions: Atherosclerotic plaque in the absence of MACE, risk factors or risk modifying interventions progresses overtime. The burden of non-calcified plaque has greater progression than calcified plaque. In healthy subjects, the presence of low attenuation plaque is infrequent. When observed, its progression is present overtime. Rapid plaque progression is present in some healthy subjects.