Carotid Artery Plaque Progression: Proposal of a New Predictive Score and Role of Carotid Intima-Media Thickness

Background: We aimed to investigate if the carotid intima-media thickness (IMT) at baseline and the HAD2S score, composed of the sum of single risk factors (hypertension, age ≥ 75 years, diabetes, dyslipidemia, smoking), were predictive of plaque progression. Methods: We performed a retrospective analysis on real-life prospectively collected data from patients with any detectable carotid plaque at follow up. The plaque score, calculated at baseline (T0) and at a median follow up of 36.6 months (IQR 39.6–34.3) (T3), was defined as 0: no plaque or stenosis < 30%; 1: stenosis in the range 30–49%; 2: in the range 50–69%; 3: in the range 70–99% and 4: occlusion. Carotid IMT was measured at T0 and T3; HAD2S score was calculated at baseline. Results: We included 340 patients with a mean age of 69.9 (9.1) years and 25.3% subjects had plaque progression. Individuals with progression had a median HAD2S score of 3 (1) while those without progression had 2 (1). Patients with progression had a mean baseline IMT of 0.86 (0.17) while those without progression had 0.77 (0.18) (p < 0.0001). A correlation between progression and baseline IMT was found (p = 0.002). Conclusion: Baseline IMT could be considered a predictor of progression. Patients with progression had an HAD2S score higher than those without evolution.

Tanyu Tongzhi Formula Delays Atherosclerotic Plaque Progression by Promoting Alternative Macrophage Activation via PPARγ and AKT/ERK Signal Pathway in ApoE Knock-Out Mice

We previously demonstrated that the Tanyu Tongzhi Formula (TTF) significantly alleviated the clinical symptoms of patients with coronary heart disease and lowered serum lipid and inflammatory factor levels in patients with coronary heart disease and atherosclerosis model rats. However, the mechanism underlying TTF remains unknown. In this study, we examined the effect of TTF on atherosclerotic plaques in ApoE-/- mice and underlying mechanisms involved in macrophage polarization. Sixty male ApoE-/- mice were randomly divided into four groups. Mice in the control group were fed a regular diet, whereas experimental mice were fed a high-fat diet and received either saline (HFD group) or TTF at concentrations of 0.60 (TTF-L group) or 2.25 g/ml (TTF-H group) by daily oral gavage for 16 weeks. In the TTF-L and TTF-H groups, the levels of serum cholesterol, triglyceride, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were decreased, lipid content was significantly decreased, and percentage area of collagen/lipid increased in atherosclerotic plaque compared to in the HFD group. Moreover, we found TTF promoted the expression of alternative macrophage markers (Fizz1, Arg1, and Mrc) and suppressed the expression of M1 macrophage markers (TNF-α, IL-1β, and IL-6) by regulating peroxisome proliferator-activated receptor γ (PPARγ) expression and AKT/extracellular signal-regulated kinase (ERK) activation. We further investigated whether alternative macrophage was reduced when PPARγ was inhibited or the AKT/ERK signaling pathway was activated. TTF delayed atherosclerotic plaque progression by promoting alternative macrophage activation through increasing PPARγ expression and inhibiting AKT/ERK phosphorylation, providing a theoretical basis for its clinical application.

Risk factors for carotid plaque progression after optimising the risk factor treatment: substudy results of the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the carotid Bifurcation Plaque Study (ANTIQUE)

Background and aimCarotid plaque progression contributes to increasing stroke risk. The study aims to identify factors influencing carotid plaque thickness progression after changing the preventive treatment to the ‘treating arteries instead of risk factors’ strategy, that is, change in treatment depending on the progression of atherosclerosis.MethodsThe study participants who completed sonographic controls over the course of 3 years were enrolled to the analysis. Duplex sonography of cervical arteries was performed in 6-month intervals with measurement of carotid plaque thickness. Plaque thickness measurement error (σ) was set as 3 SD. Only evidently stable and progressive plaques (defined as plaque thickness difference between initial and final measurements of ˂σ and >2σ, respectively) were included to analysis. Univariate and multivariate logistic regression analysis was performed to identify factors influencing plaque progression.ResultsA total of 1391 patients (466 males, age 67.2±9.2 years) were enrolled in the study. Progressive plaque in at least one carotid artery was detected in 255 (18.3%) patients. Older age, male sex, greater plaque thickness, coronary heart disease, vascular surgery/stenting history and smoking were more frequently present in patients with progressive plaque (p˂0.05 in all cases). Multivariate logistic regression analysis identified only the plaque thickness (OR 1.850 for left side, 95% CI 1.398 to 2.449; and OR 1.376 for right side, 95% CI 1.070 to 1.770) as an independent factor influencing plaque progression.ConclusionCarotid plaque thickness corresponding to stenosis severity is the only independent risk factor for plaque thickness progression after optimising the prevention treatment.Trial registration numberNCT02360137.