• HDL-c
• LDL-c
• Lp(a)
• atherosclerosis
• lipid
• residual risk
• triglycerides

• VLDL
• atherosclerosis
• coronary artery disease
• docosahexaenoic acid
• eicosapentaenoic acid
• polyunsaturated fatty acids
• triglycerides

• CAD
• CFR
• CMR
• IMR
• NIRs
• PCI
• mapping

Background and Aims: Statin therapy is an essential component of cardiovascular preventive care. In recent years, various vessel wall MRI (VW-MRI) techniques have been used to monitor atherosclerosis progression or regression in patients with extracranial or intracranial large-artery atherosclerosis. We aimed to perform a systematic review and meta-analysis on the effects of statin therapy on plaque evolution as assessed by VW-MRI.

Materials and Methods: Prospective studies investigating carotid and intracranial atherosclerotic plaques in patients on statin therapy monitored by serial VW-MRI were systematically identified in the literature. The plaque burden and lipid-rich necrotic core (LRNC) volume of carotid plaque and the imaging features of intracranial plaques were extracted and summarized. For studies investigating carotid artery wall volume and LRNC volume, combined estimates were derived by meta-analysis.

Results: The study identified 21 studies of carotid plaque and two studies of intracranial plaque. While 16 studies investigating carotid plaques that included 780 patients by High-resolution VW-MRI were included in the meta-analysis. There was no significant change in carotid wall volume from baseline to 12 months. A significant change in LRNC volume was observed at > 12 months compared with baseline (Effect = −10.69, 95% CI = −19.11, −2.28, P < 0.01), while no significant change in LRNC volume at 3–6 months or 7–12 months after statin therapy initiation in 6 studies. Increases in fibrous tissue and calcium and reduction in neovascularization density of the plaque were seen in 2/3 studies (including 48/59 patients), 1/3 studies (including 17/54 patients), and 2/2 studies (including 71 patients) after statin therapy, respectively. Two studies with 257 patients in intracranial atherosclerosis showed that statins could effectively decrease wall volume and plaque enhancement volume.

Conclusions: Collective data indicated that statins could potentially stabilize carotid plaques by significantly reducing LRNC with 1 year of therapy as shown on serial carotid VW-MRI. There was no significant decrease in wall volume, which nonetheless indicated that plaque composition changes might be more sensitive to response monitoring than wall volume. It is likely that more sensitive, clinically relevant, and preferably quantitative indicators of therapeutic effects on intracranial vessel plaque morphology will be developed in the future.

• atherosclerosis
• carotid
• intracranial
• plaque
• statin
• vessel wall imaging

Statins have been shown to be effective in reducing cardiovascular events. Their magnitude of benefits has been proportionate to the reduction in low-density lipoprotein cholesterol (LDL-c). Intensive lipid-lowering therapies using ezetimibe and more recently proprotein convertase subtilisin kexin 9 inhibitors have further improved clinical outcomes. Unselective application of these treatments is undesirable and unaffordable and, therefore, has been guided by LDL-c level. Nonetheless, the residual risk in the post-statin era is markedly heterogeneous, including thrombosis and inflammation risks. Moreover, the lipo-protein related risk is increasingly recognised to be related to other non-LDL-c markers such as Lp(a). Emerging data show that intensive lipid-lowering therapy produce larger absolute risk reduction in patients with polyvascular disease, post coronary artery bypass graft and diabetes. Notably, these clinical entities share similar phenotype of large burden of atherosclerotic plaques. Novel plaque imaging may aid decision making by identifying patients with propensity to develop lipid rich plagues at multi-vascular sites. Those patients may be suitable candidates for intensive lipid lowering treatment.

• Intensive lipid-lowering
• Proprotein convertase subtilisin kexin 9 inhibitors
• Ezetimibe
• Plaque imaging
• Low-density lipoprotein cholesterol

• Atherosclerosis
• CE, cholesteryl ester
• CEA, carotid endarterectomy
• DG, diacylglycerol
• DHB, 2,5-dihydroxybenzoic acid
• ESI, electrospray ionization
• FTICR, fourier-transform ion cyclotron resonance
• HPLC, high-performance liquid chromatography
• Lipids
• MALDI-MSI, matrix-assisted laser desorption ionization mass spectrometry imaging
• Mass spectrometry imaging
• Microscopy
• NIRS, near-infrared spectroscopy
• PC, phosphatidylcholine
• PCA
• PCA, principal component analysis
• PFA, paraformaldehyde
• SM, sphingomyelin
• Spectroscopy
• TG, triacylglycerol
• WREnS, Waters Research Enabled Software suite
• m/z, mass to charge ratio
• μsPA, Micro Spectroscopic Photoacoustic

• lipid‐lowering
• low‐density lipoprotein cholesterol
• polyvascular

Stroke and other thromboembolic events in the brain are often due to carotid artery atherosclerosis, and atherosclerotic plaques with inflammation are considered particularly vulnerable, with an increased risk of becoming symptomatic. Positron emission tomography (PET) with 2-deoxy-2-[Fluorine-18] fluoro-D-glucose (¹⁸F-FDG) provides valuable metabolic information regarding arteriosclerotic lesions and may be applied for the detection of vulnerable plaque. At present, however, patients are selected for carotid surgical intervention on the basis of the degree of stenosis alone, and not the vulnerability or inflammation of the lesion. During the past decade, research using PET with the glucose analog tracer ¹⁸F-fluor-deoxy-glucose, has been implemented for identifying increased tracer uptake in symptomatic carotid plaques, and tracer uptake has been shown to correlate with plaque inflammation and vulnerability. These findings imply that ¹⁸F-FDG PET might hold the promise for a new and better diagnostic test to identify patients eligible for carotid endarterectomy. The rationale for developing diagnostic tests based on molecular imaging with ¹⁸F-FDG PET, as well as methods for simple clinical PET approaches, are discussed. This is a systematic review, following Preferred Reporting Items for Systematic Reviews guidelines, which interrogated the PUBMED database from January 2001 to November 2019. The search combined the terms, “atherosclerosis,” “inflammation,” “FDG,” and “plaque imaging.” The search criteria included all types of studies, with a primary outcome of the degree of arterial vascular inflammation determined by ¹⁸F-FDG uptake. This review examines the role of ¹⁸F-FDG PET imaging in the characterization of atherosclerotic plaques.

• 18F-FDG
• atherosclerosis
• carotid artery
• carotid endarterectomy
• plaque imaging
• vulnerable plaque

• Atherosclerosis
• carotid
• plaque characterisation

• CABG
• PCSK9 inhibitors
• Plaque imaging
• Statin ezetimibe

• Aortic Valve Stenosis
• Cardiac Catheterization
• Heart
• Humans

• Ejection fraction
• Eosinopenia
• Inflammation
• ST-segment elevation myocardial infarction

• Lipid-lowering drugs
• PCSK9 inhibitors
• plaque burden
• plaque composition
• risk stratification
• statins
• vascular imaging.

Atherosclerosis is a complex disease process. It is increasingly recognised that both lipoprotein retention and inflammatory cellular components are intricately related in the initiation and development of atherosclerotic plaque. LDL-c (cholesterol) has been long established as a cause for atherosclerosis; additionally, inflammatory cells such as monocytes and subsequently foam cells have also been directly linked to the progression of atherosclerotic disease. Emerging data suggest that structures outside vascular intima and media are also closely related to atherosclerosis. Perivascular adipose tissue (PVAT) may be a determinant of the inflammatory status of the atherosclerotic plaque. All these features are becoming extremely relevant as therapies against atherosclerosis are targeting both lipid retention and inflammation. Recently, there has been some success in these novel therapies, such as the proprotein convertase subtilisin-kexin type 9 (PCSK-9) inhibitor evolocumab and the interleukin-1ß neutralising antibody, canakinumab, in reducing cardiovascular events when added to standard therapy such as statin. This review will discuss the pathogenesis of atherosclerosis, including some novel features, and its management using new anti-atherosclerotic drugs.

• Atherosclerosis
• Inflammation
• Lipids

• cardiac imaging and diagnostics
• coronary artery disease
• positron emission tomographic (pet) imaging

• Atherosclerosis
• Biomarkers
• Carotid plaque
• Lipid
• Statin
• T2 mapping

• Aged
• Carotid Arteries/diagnostic imaging
• Carotid Arteries/drug effects
• Carotid Arteries/metabolism
• Carotid Artery Diseases/complications
• Carotid Artery Diseases/diagnostic imaging
• Carotid Artery Diseases/drug therapy
• Carotid Artery Diseases/metabolism
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
• Lipid Metabolism/drug effects
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Myocardial Infarction/diagnosis
• Myocardial Infarction/etiology
• Plaque, Atherosclerotic
• Predictive Value of Tests
• Proof of Concept Study
• Risk Factors
• Time Factors
• Treatment Outcome

• PG/15/74/31747 British Heart Foundation
• Department of Health

• Perivascular adipose tissue
• aorta
• atherosclerosis
• carotid arteries
• magnetic resonance imaging

• Adipose Tissue/diagnostic imaging
• Adipose Tissue/pathology
• Aged
• Aorta, Thoracic/diagnostic imaging
• Aorta, Thoracic/pathology
• Aortic Diseases/diagnostic imaging
• Aortic Diseases/pathology
• Atherosclerosis/diagnostic imaging
• Atherosclerosis/pathology
• Carotid Arteries/diagnostic imaging
• Carotid Arteries/pathology
• Carotid Artery Diseases/diagnostic imaging
• Carotid Artery Diseases/pathology
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Plaque, Atherosclerotic
• Predictive Value of Tests

Techniques to stratify subgroups of patients with asymptomatic carotid artery disease are urgently needed to guide decisions on optimal treatment. Reliance on estimates of % luminal stenosis has not been effective, perhaps because that approach entirely disregards potentially important information on the pathological process in the wall of the artery.

Since plaque lipid is a key determinant of plaque behaviour we used a newly validated, high-sensitivity T2-mapping MR technique for a systematic survey of the quantity and distribution of plaque lipid in patients undergoing endarterectomy. Lipid percentage was quantified in 50 carotid endarterectomy patients. Lipid distribution was tested, using two imaging indices (contribution of the largest lipid deposit towards total lipid (LLD %) and a newly-developed LAI ‘lipid aggregation index’).

The bifurcation contained maximal lipid volume. Lipid percentage was higher in symptomatic vs. asymptomatic patients with degree of stenosis (DS ≥ 50%) and in the total cohort (P = 0.013 and P = 0.005, respectively). Both LLD % and LAI was higher in symptomatic patients (P = 0.028 and P = 0.018, respectively), suggesting that for a given plaque lipid volume, coalesced deposits were more likely to be associated with symptomatic events. There was no correlation between plaque volume or lipid content and degree of luminal stenosis measured on ultrasound duplex (r = -0.09, P = 0.53 and r = -0.05, P = 0.75), respectively. However, there was a strong correlation in lipid between left and right carotid arteries (r = 0.5, P <0.0001, respectively).

Plaque lipid content and distribution is associated with symptomatic status of the carotid plaque. Importantly, plaque lipid content was not related to the degree of luminal stenosis assessed by ultrasound. Determination of plaque lipid content may prove useful for stratification of asymptomatic patients, including selection of optimal invasive treatments.

• Aged
• Aged, 80 and over
• Carotid Arteries/chemistry
• Carotid Arteries/diagnostic imaging
• Carotid Arteries/surgery
• Carotid Stenosis/diagnostic imaging
• Carotid Stenosis/metabolism
• Endarterectomy, Carotid/methods
• Female
• Humans
• Lipid Metabolism
• Lipids/analysis
• Magnetic Resonance Imaging/methods
• Male
• Middle Aged
• Plaque, Atherosclerotic/diagnostic imaging
• Plaque, Atherosclerotic/metabolism
• Plaque, Atherosclerotic/surgery
• Ultrasonography

• PG/15/110/31936 British Heart Foundation
• PG/15/74/31747 British Heart Foundation
• National Institute for Health Research
• Dunhill Medical Trust

• Cardiovascular Diseases
• Dyslipidemias
• Europe
• Humans
• Practice Guidelines as Topic
• Societies, Medical