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JAMA Cardiology Oct 2023The association between changes in atherosclerotic plaque induced by lipid-lowering therapies (LLTs) and reduction in major adverse cardiovascular events (MACEs) remains... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The association between changes in atherosclerotic plaque induced by lipid-lowering therapies (LLTs) and reduction in major adverse cardiovascular events (MACEs) remains controversial.
OBJECTIVE
To evaluate the association between coronary plaque regression assessed by intravascular ultrasound (IVUS) and MACEs.
DATA SOURCES
A comprehensive, systematic search of publications in PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science was performed.
STUDY SELECTION
Clinical prospective studies of LLTs reporting change in percent atheroma volume (PAV) assessed by IVUS and describing MACE components were selected.
DATA EXTRACTION AND SYNTHESIS
Reporting was performed in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The association between mean change in PAV and MACEs was analyzed by meta-regression using mixed-effects, 2-level binomial logistic regression models, unadjusted and adjusted for clinical covariates, including mean age, baseline PAV, baseline low-density lipoprotein cholesterol level, and study duration.
MAIN OUTCOME AND MEASURES
Mean PAV change and MACE in intervention and comparator arms were assessed in an updated systematic review and meta-regression analysis of IVUS trials of LLTs that also reported MACEs.
RESULTS
This meta-analysis included 23 studies published between July 2001 and July 2022, including 7407 patients and trial durations ranging from 11 to 104 weeks. Mean (SD) patient age ranged from 55.8 (9.8) to 70.2 (7.6) years, and the number of male patients from 245 of 507 (48.3%) to 24 of 26 (92.3%). Change in PAV across 46 study arms ranged from -5.6% to 3.1%. The number of MACEs ranged from 0 to 72 per study arm (17 groups [37%] reported no events, 9 [20%] reported 1-2 events, and 20 [43%] reported ≥3 events). In unadjusted analysis, a 1% decrease in mean PAV was associated with 17% reduced odds of MACEs (unadjusted OR, 0.83; 95% CI, 0.71-0.98; P = .03), and with a 14% reduction in MACEs in adjusted analysis (adjusted OR, 0.86; 95% CI, 0.75-1.00; P = .050). Further adjustment for cardiovascular risk factors showed a 19% reduced risk (adjusted OR, 0.81; 95% CI, 0.68-0.96; P = .01) per 1% decrease in PAV. A 1% reduction of PAV change between intervention and comparator arms within studies was also associated with a significant 25% reduction in MACEs (OR, 0.75; 95% CI, 0.56-1.00; P = .046).
CONCLUSIONS AND RELEVANCE
In this meta-analysis, regression of atherosclerotic plaque by 1% was associated with a 25% reduction in the odds of MACEs. These findings suggest that change in PAV could be a surrogate marker for MACEs, but given the heterogeneity in the outcomes, additional data are needed.
Topics: Humans; Male; Middle Aged; Plaque, Atherosclerotic; Coronary Artery Disease; Prospective Studies; Regression Analysis
PubMed: 37647074
DOI: 10.1001/jamacardio.2023.2731 -
JACC. Cardiovascular Imaging Dec 2023The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesions remains... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesions remains uncertain.
OBJECTIVES
The authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE).
METHODS
Thirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling.
RESULTS
CPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the prevalence of CPCs among plaques was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes.
CONCLUSIONS
Characterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810).
Topics: Humans; Plaque, Atherosclerotic; Coronary Artery Disease; Coronary Angiography; Retrospective Studies; Prospective Studies; Coronary Vessels; Predictive Value of Tests; Ultrasonography, Interventional
PubMed: 37804276
DOI: 10.1016/j.jcmg.2023.08.006 -
Cardiovascular Diabetology Jul 2023The TyG index is an indicator of insulin resistance (IR), which is associated with the development and prognosis of cardiovascular disease. This study aimed to summarize... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The TyG index is an indicator of insulin resistance (IR), which is associated with the development and prognosis of cardiovascular disease. This study aimed to summarize the relationship between the TyG index and the risk, severity, and prognosis of coronary artery disease (CAD) by performing a systematic review and meta-analysis.
METHODS
The PubMed, EMBASE, The Cochrane Library, and Web of Science databases were searched for articles published from inception until May 1, 2023. Cross-sectional studies, retrospective or prospective cohort studies recruiting patients with CAD were included. For the analysis of CAD severity, the outcomes were coronary artery calcification, coronary artery stenosis, coronary plaque progression, multi-vessel CAD, and in-stent re-stenosis. For the analysis of CAD prognosis, the primary outcome was major adverse cardiovascular events (MACE).
RESULTS
Forty-one studies were included in this study. Compared to patients with the lowest TyG index, those with the highest TyG index had a higher CAD risk [odds ratio (OR): 1.94, 95% confidence interval (CI) 1.20-3.14, I = 91%, P = 0.007]. Additionally, these patients were more likely to have stenotic coronary arteries (OR: 3.49, 95% CI 1.71-7.12, I = 0%, P = 0.0006), progressed plaques (OR: 1.67, 95% CI 1.28-2.19, I = 0%, P = 0.002), and with more vessels involved (OR: 2.33, 95% CI 1.59-3.42, I = 0%, P < 0.0001). When calculated as a categorized variable, it appears that acute coronary syndrome (ACS) patients with higher TyG index levels may have a higher incidence rate of MACE [hazard ratio (HR): 2.09, 95% CI 1.68-2.62, I = 87%, P < 0.00001], whereas chronic coronary syndrome (CCS) or stable CAD patients with higher TyG index levels showed a trend towards an increased incidence rate of MACE (HR: 1.24, 95% CI 0.96-1.60, I = 85%, P = 0.09). When calculated as a continuous variable, ACS patients had an HR of 2.28 per 1-unit/1-standard deviation increment of the TyG index (95% CI 1.44-3.63, I = 95%, P = 0.0005). Similarly, CCS or stable CAD patients had an HR of 1.49 per 1-unit/1-standard deviation increment of the TyG index (95% CI 1.21-1.83, I = 75%, P = 0.0001). Myocardial infarction with non-obstructive coronary arteries patients had an HR of 1.85 per 1-unit increment of the TyG index (95% CI 1.17-2.93, P = 0.008).
CONCLUSIONS
The TyG index is a simple new synthetic index that has been proven to be a valuable tool in the whole-course management of CAD patients. Patients with higher TyG index levels are at a higher risk of CAD, more severe coronary artery lesions, and worse prognosis compared to those with lower TyG index levels.
Topics: Humans; Coronary Artery Disease; Glucose; Retrospective Studies; Triglycerides; Prospective Studies; Cross-Sectional Studies; Risk Factors; Risk Assessment; Prognosis; Plaque, Atherosclerotic; Acute Coronary Syndrome; Blood Glucose; Biomarkers
PubMed: 37415168
DOI: 10.1186/s12933-023-01906-4 -
Stroke Oct 2023Although coronary calcification quantification is an established approach for cardiovascular risk assessment, the value of quantifying carotid calcification is less... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although coronary calcification quantification is an established approach for cardiovascular risk assessment, the value of quantifying carotid calcification is less clear. As a result, we performed a systematic review and meta-analysis to evaluate the association between extracranial carotid artery plaque calcification burden and ipsilateral cerebrovascular ischemic events.
METHODS
A comprehensive literature search was performed in the following databases: Ovid MEDLINE(R) 1946 to July 6, 2022; OVID Embase 1974 to July 6, 2022; and The Cochrane Library (Wiley). We performed meta-analyses including studies in which investigators performed a computed tomography assessment of calcification volume, percentage, or other total calcium burden summarizable in a single continuous imaging biomarker and determined the association of these features with the occurrence of ipsilateral stroke or transient ischemic attack.
RESULTS
Our overall meta-analysis consisted of 2239 carotid arteries and 9 studies. The presence of calcification in carotid arteries ipsilateral to ischemic stroke or in stroke patients compared with asymptomatic patients did not demonstrate a significant association with ischemic cerebrovascular events (relative risk of 0.75 [95% CI, 0.44-1.28]; =0.29). When restricted to studies of significant carotid artery stenosis (>50%), the presence of calcification was associated with a reduced risk of ischemic stroke (relative risk of 0.56 [95% CI, 0.38-0.85]; =0.006). When the analysis was limited to studies of patients with mainly nonstenotic plaques, there was an increased relative risk of ipsilateral ischemic stroke of 1.72 ([95% CI, 1.01-2.91]; =0.04). Subgroup meta-analyses of total calcium burden and morphological features of calcium showed wide variability in their strength of association with ischemic stroke and demonstrated significant heterogeneity.
CONCLUSIONS
The presence of calcification in carotid plaque confers a reduced association with ipsilateral ischemic events, although these results seem to be limited among carotid arteries with higher degrees of stenosis. Adoption of carotid calcification measures in clinical decision-making will require additional studies providing more reproducible and standardized methods of calcium characterization and testing these imaging strategies in prospective studies.
Topics: Humans; Prospective Studies; Calcium; Brain Ischemia; Stroke; Carotid Arteries; Carotid Artery Diseases; Plaque, Atherosclerotic; Carotid Stenosis; Risk Assessment; Calcinosis; Ischemic Stroke; Risk Factors
PubMed: 37638399
DOI: 10.1161/STROKEAHA.123.042807 -
Frontiers in Cardiovascular Medicine 2023Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein... (Review)
Review
INTRODUCTION
Individuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.
METHODS
We conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).
RESULTS
We encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (-14.06 mg/dl; 95% CI -18.0 to -10.0; = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.
CONCLUSIONS
Our study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.
PubMed: 38075958
DOI: 10.3389/fcvm.2023.1269172 -
Frontiers in Cardiovascular Medicine 2023Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are...
INTRODUCTION
Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque.
METHODS
A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.
RESULTS
After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between 4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; = .003]. Additionally, there was a significant association between patients possessing at least one 4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; = .03). Lastly, there was no association between 4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; = .30).
CONCLUSION
APOE 4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.
PubMed: 38034385
DOI: 10.3389/fcvm.2023.1155916 -
Journal of the American Heart... Dec 2023Complex aortic plaque (CAP) is a potential embolic source in patients with cryptogenic stroke (CS). We review CAP imaging criteria for transesophageal echocardiogram...
BACKGROUND
Complex aortic plaque (CAP) is a potential embolic source in patients with cryptogenic stroke (CS). We review CAP imaging criteria for transesophageal echocardiogram (TEE), computed tomography angiography (CTA), and magnetic resonance imaging and calculate CAP prevalence in patients with acute CS.
METHODS AND RESULTS
PubMed and EMBASE databases were searched up to December 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Two independent reviewers extracted data on study design, imaging techniques, CAP criteria, and prevalence. The Cochrane Collaboration tool and Guideline for Reporting Reliability and Agreement Studies were used to assess risk of bias and reporting completeness, respectively. From 2293 studies, 45 were reviewed for CAP imaging biomarker criteria in patients with acute CS (N=37 TEE; N=9 CTA; N=6 magnetic resonance imaging). Most studies (74%) used ≥4 mm plaque thickness as the imaging criterion for CAP although ≥1 mm (N=1, CTA), ≥5 mm (N=5, TEE), and ≥6 mm (N=2, CTA) were also reported. Additional features included mobility, ulceration, thrombus, protrusions, and assessment of plaque composition. From 23 prospective studies, CAP was detected in 960 of 2778 patients with CS (0.32 [95% CI, 0.24-0.41], =94%). By modality, prevalence estimates were 0.29 (95% CI, 0.20-0.40; =95%) for TEE; 0.23 (95% CI, 0.15-0.34; =87%) for CTA and 0.22 (95% CI, 0.06-0.54; =92%) for magnetic resonance imaging.
CONCLUSIONS
TEE was commonly used to assess CAP in patients with CS. The most common CAP imaging biomarker was ≥4 mm plaque thickness. CAP was observed in one-third of patients with acute CS. However, high study heterogeneity suggests a need for reproducible imaging methods.
Topics: Humans; Brain Ischemia; Prevalence; Prospective Studies; Reproducibility of Results; Stroke; Plaque, Atherosclerotic; Ischemic Stroke; Biomarkers
PubMed: 38014682
DOI: 10.1161/JAHA.123.031797 -
International Journal of Cardiology Jul 2024Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features.
METHODS
A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis.
RESULTS
The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03).
CONCLUSION
This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.
Topics: Humans; Plaque, Atherosclerotic; Coronary Artery Disease; Endothelium, Vascular; Disease Progression; Stress, Mechanical; Coronary Vessels
PubMed: 38641263
DOI: 10.1016/j.ijcard.2024.132061 -
Current Problems in Cardiology Jan 2024Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and its prevention is more cost-effective than the treatment of its... (Review)
Review
BACKGROUND
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and its prevention is more cost-effective than the treatment of its complications. Although cardiovascular (CV) risk assessment based on conventional risk factors is the general recommendation, a significant percentage of the population, irrespective of these risk factors, present with subclinical atherosclerosis during carotid Doppler ultrasound (US) imaging. Subclinical atherosclerotic lesions at the carotid bifurcations may be related to the incidence of future CV events and occult atherosclerotic coronary disease. Such patients might benefit from preventive measures if the carotid Doppler US is allowed as a screening tool to detect the extent of carotid stenosis. We aimed to conduct a comprehensive and systematic evaluation of the impact of carotid US screening on CV risk stratification.
METHODS
We searched PubMed, Scopus, and ScienceDirect from inception until July 2023. We included literature that examined the impact of carotid US screening on cardiovascular risk factor (CVRF) prevention, CV events, and mortality in adults of all age groups free of symptomatic carotid artery disease.
RESULTS
We identified 2 randomized controlled trials (RCTs) and 9 observational studies, including 21,046 participants. The mean age of the participants was 49, and 53% were female. Two RCTs, with 7,064 participants, examined the impact of pictorial knowledge about subclinical carotid atherosclerosis using carotid US versus traditional CVD risk evaluation without any US evidence in primary cardiovascular prevention. Both studies reported remarkable improvement in medication adherence at 1 to 3-year follow-up after carotid US screening with a decrease in Framingham risk score (FRS). Nine observational studies with 13, 982 participants analyzed the evidence of atherosclerosis on carotid US screening and demonstrated that it is a beneficial tool in the early identification of subclinical atherosclerosis and effective therapeutic intervention.
CONCLUSION
This systematic review found that pictorial presentation of silent atherosclerosis using carotid US screening has a contributory role in CV risk stratification and prevention of CVD.
Topics: Adult; Female; Humans; Male; Atherosclerosis; Carotid Artery Diseases; Risk Assessment; Risk Factors; Cardiovascular Diseases; Ultrasonography, Carotid Arteries
PubMed: 37863454
DOI: 10.1016/j.cpcardiol.2023.102147 -
Frontiers in Cardiovascular Medicine 2024The diagnostic performance and clinical validity of automatic intracoronary imaging (ICI) tools for atherosclerotic plaque assessment have not been systematically...
BACKGROUND
The diagnostic performance and clinical validity of automatic intracoronary imaging (ICI) tools for atherosclerotic plaque assessment have not been systematically investigated so far.
METHODS
We performed a scoping review including studies on automatic tools for automatic plaque components assessment by means of optical coherence tomography (OCT) or intravascular imaging (IVUS). We summarized study characteristics and reported the specifics and diagnostic performance of developed tools.
RESULTS
Overall, 42 OCT and 26 IVUS studies fulfilling the eligibility criteria were found, with the majority published in the last 5 years (86% of the OCT and 73% of the IVUS studies). A convolutional neural network deep-learning method was applied in 71% of OCT- and 34% of IVUS-studies. Calcium was the most frequent plaque feature analyzed (26/42 of OCT and 12/26 of IVUS studies), and both modalities showed high discriminatory performance in testing sets [range of area under the curve (AUC): 0.91-0.99 for OCT and 0.89-0.98 for IVUS]. Lipid component was investigated only in OCT studies ( = 26, AUC: 0.82-0.86). Fibrous cap thickness or thin-cap fibroatheroma were mainly investigated in OCT studies ( = 8, AUC: 0.82-0.94). Plaque burden was mainly assessed in IVUS studies ( = 15, testing set AUC reported in one study: 0.70).
CONCLUSION
A limited number of automatic machine learning-derived tools for ICI analysis is currently available. The majority have been developed for calcium detection for either OCT or IVUS images. The reporting of the development and validation process of automated intracoronary imaging analyses is heterogeneous and lacks critical information.
SYSTEMATIC REVIEW REGISTRATION
Open Science Framework (OSF), https://osf.io/nps2b/.Graphical AbstractCentral Illustration.
PubMed: 38742173
DOI: 10.3389/fcvm.2024.1332925