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. 2023 Nov 28;82(22):2069-2083.
doi: 10.1016/j.jacc.2023.09.814.

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years

Guiomar Mendieta  1 , Stuart Pocock  2 , Virginia Mass  3 , Andrea Moreno  3 , Ruth Owen  2 , Inés García-Lunar  4 , Beatriz López-Melgar  5 , Jose J Fuster  6 , Vicente Andres  6 , Cristina Pérez-Herreras  7 , Hector Bueno  8 , Antonio Fernández-Ortiz  9 , Javier Sanchez-Gonzalez  10 , Ana García-Alvarez  11 , Borja Ibáñez  12 , Valentin Fuster  13
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Free article

Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years

Guiomar Mendieta et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Atherosclerosis is a systemic disease that frequently begins early in life. However, knowledge about the temporal disease dynamics (ie, progression or regression) of human subclinical atherosclerosis and their determinants is scarce.

Objectives: This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals by using multiterritorial 3-dimensional vascular ultrasound (3DVUS) imaging.

Methods: A total of 3,471 participants from the PESA (Progression of Early Subclinical Atherosclerosis) cohort study (baseline age 40-55 years; 36% female) underwent 3 serial 3DVUS imaging assessments of peripheral arteries at 3-year intervals. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden). Multivariable logistic regression models for progression and regression were developed using stepwise forward variable selection.

Results: Baseline to 6-year subclinical atherosclerosis progression occurred in 32.7% of the cohort (17.5% presenting with incident disease and 15.2% progressing from prevalent disease at enrollment). Regression was observed in 8.0% of those patients with baseline disease. The effects of higher low-density lipoprotein cholesterol (LDL-C) and elevated systolic blood pressure (SBP) on 6-year subclinical atherosclerosis progression risk were more pronounced among participants in the youngest age stratum (Pinteraction = 0.04 and 0.02, respectively).

Conclusions: Over 6 years, subclinical atherosclerosis progressed in one-third of middle-age asymptomatic subjects. Atherosclerosis regression is possible in early stages of the disease. The impact of LDL-C and SBP on subclinical atherosclerosis progression was more pronounced in younger participants, a finding suggesting that the prevention of atherosclerosis and its progression could be enhanced by tighter risk factor control at younger ages, with a likely long-term impact on reducing the risk of clinical events. (Progression of Early Subclinical Atherosclerosis [PESA; also PESA-CNIC-Santander]; NCT01410318).

Keywords: 3D vascular ultrasound; LDL; blood pressure; progression; regression; risk factors; subclinical atherosclerosis.

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Conflict of interest statement

Funding Support and Author Disclosures The PESA study is funded by the National Center for Cardiovascular Investigations (CNIC) and Santander Bank. The CNIC is supported by the Carlos III Institute of Health (ISCIII), the Ministry of Science and Innovation, and the Pro CNIC Foundation. CNIC is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). Dr Sánchez-González is an employee of Philips. Dr Ibáñez has received support from the European Commission (ERC-CoG 819775, and H2020-HEALTH 945118), the Spanish Ministry of Science and Innovation (PID2019-110369RB-I00), and the Community of Madrid (P2022/BMD-7403, RENIM-CM). Dr Mendieta was recipient of the 2020 “CardioJoven” Fellowship funded by the Spanish Society of Cardiology and the Centro Nacional de Investigaciones Cardiovasculares. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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