Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years

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 (P_interaction = 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.