Evolving determinants of carotid atherosclerosis vulnerability in asymptomatic patients from the MAGNETIC observational study

Abstract

MRI can assess plaque composition and has demonstrated an association between some atherosclerotic risk factors (RF) and markers of plaque vulnerability in naive patients. We aimed at investigating this association in medically treated asymptomatic patients. This is a cross-sectional interim analysis (August 2013-September 2016) of a single center prospective study on carotid plaque vulnerability (MAGNETIC study). We recruited patients with asymptomatic carotid atherosclerosis (US stenosis > 30%, ECST criteria), receiving medical treatments at a tertiary cardiac rehabilitation. Atherosclerotic burden and plaque composition were quantified with 3.0 T MRI. The association between baseline characteristics and extent of lipid-rich necrotic core (LRNC), fibrous cap (CAP) and intraplaque hemorrhage (IPH) was studied with multiple regression analysis. We enrolled 260 patients (198 male, 76%) with median age of 71-y (interquartile range: 65-76). Patients were on antiplatelet therapy, ACE-inhibitors/angiotensin receptor blockers and statins (196-229, 75-88%). Median LDL-cholesterol was 78 mg/dl (59-106), blood pressure 130/70 mmHg (111-140/65-80), glycosylated hemoglobin 46 mmol/mol (39-51) and BMI 25 kg/m² (23-28); moreover, 125 out of 187 (67%) patients were ex-smokers. Multivariate analysis of a data-set of 487 (94%) carotid arteries showed that a history of hypercholesterolemia, diabetes, hypertension or smoking did not correlate with LRNC, CAP or IPH. Conversely, maximum stenosis was the strongest independent predictor of LRNC, CAP and IPH (p < 0.001). MRI assessment of plaque composition in patients on treatment for asymptomatic carotid atherosclerosis shows no correlation between plaque vulnerability and the most well-controlled modifiable RF. Conversely, maximum stenosis exhibits a strong correlation with vulnerable features despite treatment.

Figure 1

Trends of atherosclerotic burden and vulnerable plaque components by modifiable risk factors, maximum stenosis, familial history of premature CAD, sex, age, renal function and carotid side (univariate analysis). NWI normalized wall index, CAD coronary artery disease, LRNC lipid-reach necrotic core, CAP fibrous cap, IPH intraplaque hemorrhage, RF risk factors, EGFR estimated glomerular filtration rate. Bars are the median value. Kruskal–Wallis test was used to test differences, with Bonferroni correction for multiple comparisons; ***p < 0.001; **p < 0.01; *p < 0.05.

Figure 2

Processed images of a carotid axis. Color coded areas identify different plaque components. CA calcification (white), LRNC lipid reach necrotic core (yellow), FM fibrous matrix (pink), and IPH intraplaque hemorrhage (green). The layer of tissue separating a LRNC area from the lumen is considered fibrous cap.