Review Article
Published: 04 January 2024
Atherosclerotic plaque stabilization and regression: a review of clinical evidence
Ashish Sarraju & Steven E. Nissen
Nature Reviews Cardiology volume 21, pages487–497 (2024)
Abstract
Atherosclerotic plaque results from a complex interplay between lipid deposition, inflammatory changes, cell migration and arterial wall injury. Over the past two decades, clinical trials utilizing invasive arterial imaging modalities, such as intravascular ultrasonography, have shown that reducing levels of atherogenic lipoproteins, mainly serum LDL-cholesterol (LDL-C), to very low levels can safely reduce overall atherosclerotic plaque burden and favourably modify plaque composition. Classically, this outcome has been achieved with intensive statin therapy. Since 2016, newer and potent lipid-lowering strategies, such as proprotein convertase subtilisin–kexin type 9 inhibition, have shown incremental effects on plaque regression and risk of clinical events.
Originally Published 8 September 2023
Open Access
Regression of Coronary Fatty Plaque and Risk of Cardiac Events According to Blood Pressure Status: Data From a Randomized Trial of Eicosapentaenoic Acid and Docosahexaenoic Acid in Patients With Coronary Artery Disease
Francine K. Welty er al.
Journal of the American Heart Association
Volume 12, Number 18
https://doi.org/10.1161/JAHA.123.030071
Regressors had a 14.9% reduction in triglycerides that correlated with fatty plaque regression (r=0.135; P=0.036). Baseline non–high‐density lipoprotein cholesterol level <2.59 mmol/L (100 mg/dL) and systolic blood pressure <125 mm Hg were significant independent predictors of fatty plaque regression.
Normotensive patients taking eicosapentaenoic acid plus docosahexaenoic acid had regression of noncalcified coronary plaque that correlated with triglyceride reduction (r=0.35; P=0.034) and a significant decrease in neutrophil/lymphocyte ratio. In contrast, hypertensive patients had no change in noncalcified coronary plaque or neutrophil/lymphocyte ratio.
To Convert From mmol/L to mg/dL
For total, HDL, and LDL cholesterol multiply mmol/L by 38.67
e.g. 3.5 mmol/L = 3.5 mmol/L * 38.67 = 135 mg/dL
For triglycerides multiply mmol/L by 88.57
e.g. 1.9 mmol/L = 1.9 mmol/L * 88.57 = 168 mg/dL
https://www.ncbi.nlm.nih.gov/books/NBK83505/
JACC Journals › JACC › Archives › Vol. 82 No. 22
Next
Determinants of Progression and Regression of Subclinical Atherosclerosis Over 6 Years
OPEN ACCESS
Original Investigation
Guiomar Mendieta, Stuart Pocock, Virginia Mass, Andrea Moreno, Ruth Owen, Inés García-Lunar, Beatriz López-Melgar, Jose J. Fuster, Vicente Andres, Cristina Pérez-Herreras, Hector Bueno, Antonio Fernández-Ortiz, Javier Sanchez-Gonzalez, Ana García-Alvarez, Borja Ibáñez, and Valentin Fuster
JACC. 2023 Nov, 82 (22) 2069–2083
Editorial Comment: Charting a Course for Atherosclerosis Regression: Shifting the Paradigm∗
https://www.jacc.org/doi/10.1016/j.jacc.2023.09.814
Objectives
This study sought to investigate early subclinical atherosclerosis disease dynamics within a cohort of middle-aged, asymptomatic individuals.
Methods
A total of 3,471 participants (baseline age 40-55 years; 36% female) underwent 3 serial imaging assessments of peripheral arteries at 3-year intervals (0,3, 6 years0. Subclinical atherosclerosis was quantified as global plaque volume (mm3) (bilateral carotid and femoral plaque burden).
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).
The remaining 2,214 participants (63.8%), who had neither progression nor regression of disease, were termed “stable.” Among stable participants, 879 (39.7%) had prevalent disease at enrollment, whereas 1,335 (60.3%) remained free of disease in the carotid and femoral territories throughout the study period.
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.
Atherosclerosis is a progressive disease characterized by a long asymptomatic course, often first manifesting as an acute atherothrombotic event (myocardial infarction or stroke). Recent data suggest that ASCVD event rates are likely to improve if preventive interventions are begun at younger ages.2,3 Because atherosclerosis frequently begins early in life and progresses silently,4 detection of the disease during its subclinical phase seems key to initiating timely preventive measures to mitigate its progression effectively and potentially avoid ASCVD events.
Even a Small Decrease in Plaque Levels Can Drop Heart Attack Risk by 25%
Aug 31, 2023
https://www.healthline.com/health-news/even-a-small-decrease-in-plaque-levels-can-drop-heart-attack-risk-by-25#The-bottom-line
JACC Journals › JACC › Archives › Vol. 79 No. 1
Coronary Atherosclerotic Plaque Regression: JACC State-of-the-Art Review
FREE ACCESS
Luke P. Dawson, Mark Lum, Nitesh Nerleker, Stephen J. Nicholls, and Jamie Layland
JACC. 2022 Jan, 79 (1) 66–82
https://www.jacc.org/doi/10.1016/j.jacc.2021.10.035
Mechanisms of Plaque Formation.
Initiation and progression of atherosclerosis
The formation of atherosclerotic plaque begins with endothelial dysfunction that results from sustained exposure to a range of pathogenic factors, such as diabetes, hypertension, tobacco smoking, and stress. Damaged endothelium becomes increasingly permeable allowing the movement of lipoproteins such as low-density lipoprotein-cholesterol (LDL-C) into the intima, recruitment of inflammatory cells that ingest LDL-C to form foam cells, and vascular smooth muscle cell proliferation, which leads to fibrous cap formation eventually resulting in an established atherosclerotic plaque.
The natural history of atherosclerosis is generally progression, which may be complicated by a variety of adverse events such as plaque rupture or erosion. Stages of plaque progression include asymptomatic disease (intimal thickening, intimal xanthoma, and thick cap fibroatheroma); unstable lesions that may result in myocardial infarction (thin fibrous cap atheroma and calcified nodules); and subsequently, stable stenosis (fibrocalcific plaque).
Subclinical atherosclerosis is a process that commences years before clinical events or symptoms. Previously, it was widely believed that acute coronary syndromes (ACS) were caused by the rupture of small volume plaque that produce angiographically mild stenoses. However, recent data suggest that plaque enlarges rapidly within a few months of the acute event and progression is a necessary step prior to plaque rupture. Of relevance to these findings is the Glagov phenomenon, whereby coronary arteries will typically enlarge in parallel with plaque size (positive remodeling) until the plaque area to internal elastic lamina area increases above 40%, after which they often begin to encroach on the lumen producing an evident stenosis.
Several imaging studies of nonculprit lesions in patients presenting with ACS have shown that approximately 10%-20% of nonculprit lesions progress within 8-12 months of initial presentation. Lesions with large plaque burden, or with high-risk features, such as thin-cap fibroatheroma, low-attenuation, and positive vessel remodeling, are more likely to progress. Among patients with plaque progression, rates of further coronary events are substantially higher, in the vicinity of 15%-20% at 12 months compared with <1% among patients without progression.
Taken collectively, these data suggest identifying and preventing plaque progression and development of high-risk plaque early in the course of disease can reduce the risk of CV events.
Plaque regression
Plaque regression may occur as a result of a reductions in plaque lipid content, macrophage content, and inflammatory state (14). Traditionally, plaque regression has been defined as increases in luminal diameter measured by coronary angiography as a surrogate measure for reducing plaque size (6).
Therefore, the goal of plaque regression as a prevention strategy encompasses both the reduction of total plaque volume and the modification of plaque components to decrease the risk of plaque rupture. Importantly, not all plaque is modifiable (eg, calcified plaque is rarely modifiable), so it is important to address changes early in a patient’s life.
Plaque Regression Strategies
Treatments targeting plaque regression can broadly be divided into 2 main categories: 1) dietary and lifestyle; and 2) pharmacological (Central Illustration). Pharmacological treatments have had by far the most success. *Combining both increases success.
Exercise
In one trial’s post hoc analysis, patients that walked ≥7,000 steps per day had greater plaque regression compared with patients who walked <7,000 steps per day (−12.5% vs <3.6%; P < 0.05). 1 study identified that reductions in IVUS-measured total atheroma volumes over 6 months were associated with a lifestyle modification score (comprised of exercise frequency, body mass index, smoking history) in multivariable analysis. Cross-sectional studies assessing plaque composition among athletes using CCTA demonstrated higher calcific plaque volume in athletes, whereas sedentary participants had greater mixed plaque morphologies, which are of higher risk for coronary events. Taken together, these data would support the promotion of exercise as offering modest benefits in plaque regression.
Wight Reduction and Plaque Reduction Articles
2024
https://www.mdpi.com/2075-4418/14/6/615
2015
https://journals.sagepub.com/doi/abs/10.1177/0267659114567934
2010
https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.109.879254
2001
https://onlinelibrary.wiley.com/doi/full/10.1038/oby.2001.67
Low-attenuation Noncalcified Plaque (LAP)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388871/
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044720
https://www.dicardiology.com/article/low-attenuation-coronary-plaque-burden-may-become-next-big-cardiac-risk-assessment
https://heart.bmj.com/content/109/9/702
https://www.frontiersin.org/articles/10.3389/fcvm.2022.824470
https://ajronline.org/doi/abs/10.2214/AJR.07.2988
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374741/
Ud. 21.7.2024, 27.6.2024
Pub. 25.6.2024
