ABSTRACT
Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification. Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH. Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence. Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001). Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.
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Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis. Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS. Results: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed. Conclusions: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS.
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Clinical risk scores based on traditional risk factors of atherosclerosis correlate imprecisely to an individual's complex pathophysiological predisposition to atherosclerosis and provide limited accuracy for predicting major adverse cardiovascular events (MACE). Over the past two decades, computed tomography scanners and techniques for coronary computed tomography angiography (CCTA) analysis have substantially improved, enabling more precise atherosclerotic plaque quantification and characterization. The accuracy of CCTA for quantifying stenosis and atherosclerosis has been validated in numerous multicentre studies and has shown consistent incremental prognostic value for MACE over the clinical risk spectrum in different populations. Serial CCTA studies have advanced our understanding of vascular biology and atherosclerotic disease progression. The direct disease visualization of CCTA has the potential to be used synergistically with indirect markers of risk to significantly improve prevention of MACE, pending large-scale randomized evaluation.
Subject(s)
Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease , Humans , Computed Tomography Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/diagnosis , Risk Assessment/methods , Coronary Angiography/methods , Plaque, Atherosclerotic/diagnostic imaging , Heart Disease Risk Factors , Prognosis , Coronary Stenosis/diagnostic imagingABSTRACT
Importance: Cardiovascular disease (CVD) is increased in people with HIV (PWH) and is characterized by premature noncalcified coronary plaque. In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular events (MACE) by 35% over a median of 5.1 years. Objective: To investigate the effects of pitavastatin on noncalcified coronary artery plaque by coronary computed tomography angiography (CTA) and on inflammatory biomarkers as potential mechanisms for MACE prevention. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial enrolled participants from April 2015 to February 2018 at 31 US clinical research sites. PWH without known CVD who were taking antiretroviral therapy and had low to moderate 10-year CVD risk were included. Data were analyzed from April to November 2023. Intervention: Oral pitavastatin calcium, 4 mg per day. Main Outcomes and Measures: Coronary CTA and inflammatory biomarkers at baseline and 24 months. The primary outcomes were change in noncalcified coronary plaque volume and progression of noncalcified plaque. Results: Of 804 enrolled persons, 774 had at least 1 evaluable CTA. Plaque changes were assessed in 611 who completed both CT scans. Of 611 analyzed participants, 513 (84.0%) were male, the mean (SD) age was 51 (6) years, and the median (IQR) 10-year CVD risk was 4.5% (2.6-7.0). A total of 302 were included in the pitavastatin arm and 309 in the placebo arm. The mean noncalcified plaque volume decreased with pitavastatin compared with placebo (mean [SD] change, -1.7 [25.2] mm3 vs 2.6 [27.1] mm3; baseline adjusted difference, -4.3 mm3; 95% CI, -8.6 to -0.1; P = .04; 7% [95% CI, 1-12] greater reduction relative to placebo). A larger effect size was seen among the subgroup with plaque at baseline (-8.8 mm3 [95% CI, -17.9 to 0.4]). Progression of noncalcified plaque was 33% less likely with pitavastatin compared with placebo (relative risk, 0.67; 95% CI, 0.52-0.88; P = .003). Compared with placebo, the mean low-density lipoprotein cholesterol decreased with pitavastatin (mean change: pitavastatin, -28.5 mg/dL; 95% CI, -31.9 to -25.1; placebo, -0.8; 95% CI, -3.8 to 2.2). The pitavastatin arm had a reduction in both oxidized low-density lipoprotein (-29% [95% CI, -32 to -26] vs -13% [95% CI, -17 to -9]; P < .001) and lipoprotein-associated phospholipase A2 (-7% [95% CI, -11 to -4] vs 14% [95% CI, 10-18]; P < .001) compared with placebo at 24 months. Conclusions and Relevance: In PWH at low to moderate CVD risk, 24 months of pitavastatin reduced noncalcified plaque volume and progression as well as markers of lipid oxidation and arterial inflammation. These changes may contribute to the observed MACE reduction in REPRIEVE. Trial Registration: ClinicalTrials.gov Identifier: NCT02344290.
Subject(s)
Cardiovascular Diseases , Coronary Artery Disease , HIV Infections , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Plaque, Atherosclerotic , Quinolines , Humans , Male , Middle Aged , Female , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Double-Blind Method , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/drug therapy , Inflammation/drug therapy , Cardiovascular Diseases/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Biomarkers , Lipoproteins, LDLABSTRACT
AIMS: The incremental impact of atherosclerosis imaging-quantitative computed tomography (AI-QCT) on diagnostic certainty and downstream patient management is not yet known. The aim of this study was to compare the clinical utility of the routine implementation of AI-QCT versus conventional visual coronary CT angiography (CCTA) interpretation. METHODS AND RESULTS: In this multi-centre cross-over study in 5 expert CCTA sites, 750 consecutive adult patients referred for CCTA were prospectively recruited. Blinded to the AI-QCT analysis, site physicians established patient diagnoses and plans for downstream non-invasive testing, coronary intervention, and medication management based on the conventional site assessment. Next, physicians were asked to repeat their assessments based upon AI-QCT results. The included patients had an age of 63.8 ± 12.2 years; 433 (57.7%) were male. Compared with the conventional site CCTA evaluation, AI-QCT analysis improved physician's confidence two- to five-fold at every step of the care pathway and was associated with change in diagnosis or management in the majority of patients (428; 57.1%; P < 0.001), including for measures such as Coronary Artery Disease-Reporting and Data System (CAD-RADS) (295; 39.3%; P < 0.001) and plaque burden (197; 26.3%; P < 0.001). After AI-QCT including ischaemia assessment, the need for downstream non-invasive and invasive testing was reduced by 37.1% (P < 0.001), compared with the conventional site CCTA evaluation. Incremental to the site CCTA evaluation alone, AI-QCT resulted in statin initiation/increase an aspirin initiation in an additional 28.1% (P < 0.001) and 23.0% (P < 0.001) of patients, respectively. CONCLUSION: The use of AI-QCT improves diagnostic certainty and may result in reduced downstream need for non-invasive testing and increased rates of preventive medical therapy.
Subject(s)
Computed Tomography Angiography , Coronary Angiography , Coronary Artery Disease , Cross-Over Studies , Humans , Male , Female , Middle Aged , Coronary Artery Disease/diagnostic imaging , Computed Tomography Angiography/methods , Coronary Angiography/methods , Prospective Studies , Aged , Myocardial Revascularization , Tomography, X-Ray Computed/methodsABSTRACT
BACKGROUND: In the last 15 years, large registries and several randomized clinical trials have demonstrated the diagnostic and prognostic value of coronary computed tomography angiography (CCTA). Advances in CT scanner technology and developments of analytic tools now enable accurate quantification of coronary artery disease (CAD), including total coronary plaque volume and low attenuation plaque volume. The primary aim of CONFIRM2, (Quantitative COroNary CT Angiography Evaluation For Evaluation of Clinical Outcomes: An InteRnational, Multicenter Registry) is to perform comprehensive quantification of CCTA findings, including coronary, non-coronary cardiac, non-cardiac vascular, non-cardiac findings, and relate them to clinical variables and cardiovascular clinical outcomes. DESIGN: CONFIRM2 is a multicenter, international observational cohort study designed to evaluate multidimensional associations between quantitative phenotype of cardiovascular disease and future adverse clinical outcomes in subjects undergoing clinically indicated CCTA. The targeted population is heterogenous and includes patients undergoing CCTA for atherosclerotic evaluation, valvular heart disease, congenital heart disease or pre-procedural evaluation. Automated software will be utilized for quantification of coronary plaque, stenosis, vascular morphology and cardiac structures for rapid and reproducible tissue characterization. Up to 30,000 patients will be included from up to 50 international multi-continental clinical CCTA sites and followed for 3-4 years. SUMMARY: CONFIRM2 is one of the largest CCTA studies to establish the clinical value of a multiparametric approach to quantify the phenotype of cardiovascular disease by CCTA using automated imaging solutions.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Plaque, Atherosclerotic , Humans , Computed Tomography Angiography/methods , Predictive Value of Tests , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Coronary Stenosis/diagnostic imaging , Prognosis , RegistriesABSTRACT
AIMS: Quality-of-care and safety of patients with suspected acute coronary syndrome (ACS) would benefit if management was independent of which high-sensitivity cardiac troponin (hs-cTn) assay was used for risk stratification. We aimed to determine the concordance of hs-cTn assays to risk-stratify patients with suspected ACS according to the European Society of Cardiology (ESC) 2020 Guidelines. METHODS AND RESULTS: Blood samples were obtained at arrival and at 2â h from patients with suspected ACS using four hs-cTn assays. The patients were classified into rule-out/observe/rule-in strata based on the ESC 2020 Guidelines. Concordance was determined among the assays for rule-out/observe/rule-in strata. The prevalences of significant underlying disease (≥50% stenosis on coronary computed tomography or inducible myocardial ischaemia on stress testing) and adjudicated ACS, plus quality-of-care outcomes, were compared. Among 238 patients (52.7 ± 8.0 years; 40.3% female), the overall concordance across assays to classify patients into rule-out/observe/rule-in strata was 74.0% (176/238). Platforms significantly differed for rule-out (89.9 vs. 76.5 vs. 78.6 vs. 86.6%, P < 0.001) and observe strata (6.7 vs. 20.6 vs. 17.7 vs. 9.2%, P < 0.001), but not for rule-in strata (3.4 vs. 2.9 vs. 3.8 vs. 4.2%, P = 0.62). Among patients in ruled-out strata, 19.1-21.6% had significant underlying disease and 3.3-4.2% had ACS. The predicted disposition of patients and cost-of-care differed across the assays (all P < 0.001). When compared with observed strata, conventional troponin-based management and predicted quality-of-care outcomes significantly improved with hs-cTn-based strategies (direct discharge: 21.0 vs. 80.3-90.8%; cost-of-care: $3889 ± 4833 vs. $2578 ± 2896-2894 ± 4371, all P < 0.001). CONCLUSION: Among individuals with suspected ACS, patient management may differ depending on which hs-cTn assay is utilized. More data are needed regarding the implications of inter-assay differences. TRAIL REGISTRATION: NCT01084239.
Subject(s)
Acute Coronary Syndrome , Troponin , Female , Humans , Male , Middle Aged , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Biomarkers , CardiologyABSTRACT
It is unknown whether gender influences the atherosclerotic plaque characteristics (APCs) of lesions of varying angiographic stenosis severity. This study evaluated the imaging data of 303 symptomatic patients from the derivation arm of the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic Determinants of Myocardial IsChEmia) trial, all of whom underwent coronary computed tomographic angiography and clinically indicated nonemergent invasive coronary angiography upon study enrollment. Index tests were interpreted by 2 blinded core laboratories, one of which performed quantitative coronary computed tomographic angiography using an artificial intelligence application to characterize and quantify APCs, including percent atheroma volume (PAV), low-density noncalcified plaque (LD-NCP), noncalcified plaque (NCP), calcified plaque (CP), lesion length, positive arterial remodeling, and high-risk plaque (a combination of LD-NCP and positive remodeling ≥1.10); the other classified lesions as obstructive (≥50% diameter stenosis) or nonobstructive (<50% diameter stenosis) based on quantitative invasive coronary angiography. The relation between APCs and angiographic stenosis was further examined by gender. The mean age of the study cohort was 64.4 ± 10.2 years (29.0% female). In patients with obstructive disease, men had more LD-NCP PAV (0.5 ± 0.4 vs 0.3 ± 0.8, p = 0.03) and women had more CP PAV (11.7 ± 1.6 vs 8.0 ± 0.8, p = 0.04). Obstructive lesions had more NCP PAV compared with their nonobstructive lesions in both genders, however, obstructive lesions in women also demonstrated greater LD-NCP PAV (0.4 ± 0.5 vs 1.0 ± 1.8, p = 0.03), and CP PAV (17.4 ± 16.5 vs 25.9 ± 18.7, p = 0.03) than nonobstructive lesions. Comparing the composition of obstructive lesions by gender, women had more CP PAV (26.3 ± 3.4 vs 15.8 ± 1.5, p = 0.005) whereas men had more NCP PAV (33.0 ± 1.6 vs 26.7 ± 2.5, p = 0.04). Men had more LD-NCP PAV in nonobstructive lesions compared with women (1.2 ± 0.2 vs 0.6 ± 0.2, p = 0.02). In conclusion, there are gender-specific differences in plaque composition based on stenosis severity.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Plaque, Atherosclerotic , Humans , Female , Male , Middle Aged , Aged , Plaque, Atherosclerotic/diagnostic imaging , Constriction, Pathologic , Artificial Intelligence , Coronary Angiography/methods , Computed Tomography Angiography/methods , Predictive Value of Tests , Severity of Illness IndexABSTRACT
BACKGROUND: Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population. METHODS: In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates. RESULTS: Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001). CONCLUSIONS: Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.
Subject(s)
Coronary Artery Disease , HIV Infections , Plaque, Atherosclerotic , Humans , Male , Middle Aged , Adipose Tissue/diagnostic imaging , Biomarkers , Coronary Angiography , Coronary Artery Disease/epidemiology , Coronary Artery Disease/complications , Coronary Vessels/diagnostic imaging , HIV , HIV Infections/complications , HIV Infections/epidemiology , Inflammation/complications , Plaque, Atherosclerotic/diagnostic imaging , Plaque, Atherosclerotic/epidemiology , Plaque, Atherosclerotic/complicationsABSTRACT
BACKGROUND: The risk of cardiovascular disease is increased among persons with human immunodeficiency virus (HIV) infection, so data regarding primary prevention strategies in this population are needed. METHODS: In this phase 3 trial, we randomly assigned 7769 participants with HIV infection with a low-to-moderate risk of cardiovascular disease who were receiving antiretroviral therapy to receive daily pitavastatin calcium (at a dose of 4 mg) or placebo. The primary outcome was the occurrence of a major adverse cardiovascular event, which was defined as a composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause. RESULTS: The median age of the participants was 50 years (interquartile range, 45 to 55); the median CD4 count was 621 cells per cubic millimeter (interquartile range, 448 to 827), and the HIV RNA value was below quantification in 5250 of 5997 participants (87.5%) with available data. The trial was stopped early for efficacy after a median follow-up of 5.1 years (interquartile range, 4.3 to 5.9). The incidence of a major adverse cardiovascular event was 4.81 per 1000 person-years in the pitavastatin group and 7.32 per 1000 person-years in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.48 to 0.90; P = 0.002). Muscle-related symptoms occurred in 91 participants (2.3%) in the pitavastatin group and in 53 (1.4%) in the placebo group; diabetes mellitus occurred in 206 participants (5.3%) and in 155 (4.0%), respectively. CONCLUSIONS: Participants with HIV infection who received pitavastatin had a lower risk of a major adverse cardiovascular event than those who received placebo over a median follow-up of 5.1 years. (Funded by the National Institutes of Health and others; REPRIEVE ClinicalTrials.gov number, NCT02344290.).
Subject(s)
Cardiovascular Diseases , HIV Infections , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Middle Aged , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Double-Blind Method , HIV Infections/complications , HIV Infections/drug therapy , Myocardial Infarction/epidemiology , Myocardial Infarction/prevention & control , Quinolines/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic useABSTRACT
Background The interplay between branched-chain amino acid (BCAA) metabolism, an important pathway in adiposity and cardiometabolic disease, and visceral adipose depots such as hepatic steatosis (HS) and epicardial adipose tissue is unknown. We leveraged the PROMISE clinical trial with centrally adjudicated coronary computed tomography angiography imaging to determine relationships between adipose depots, BCAA dysregulation, and coronary artery disease (CAD). Methods and Results The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial randomized 10 003 outpatients with stable chest pain to computed tomography angiography versus standard-of-care diagnostics. For this study, we included 1798 participants with available computed tomography angiography data and biospecimens. Linear and logistic regression were used to determine associations between a molar sum of BCAAs measured by nuclear magnetic resonance spectroscopy with body mass index, adipose traits, and obstructive CAD. Mendelian randomization was then used to determine if BCAAs are in the causal pathway for adipose depots or CAD. The study sample had a mean age of 60 years (SD, 8.0), body mass index of 30.6 (SD, 5.9), and epicardial adipose tissue volume of 57.3 (SD, 21.3) cm3/m2; 27% had HS, and 14% had obstructive CAD. BCAAs were associated with body mass index (multivariable beta 0.12 per SD increase in BCAA [95% CI, 0.08-0.17]; P=4×10-8). BCAAs were also associated with HS (multivariable odds ratio [OR], 1.46 per SD increase in BCAAs [95% CI, 1.28-1.67]; P=2×10-8), but BCAAs were associated only with epicardial adipose tissue volume (odds ratio, 1.18 [95% CI, 1.07-1.32]; P=0.002) and obstructive CAD (OR, 1.18 [95% CI, 1.04-1.34]; P=0.009) in univariable models. Two-sample Mendelian randomization did not support the role of BCAAs as within the causal pathways for HS or CAD. Conclusions BCAAs have been implicated in the pathogenesis of cardiometabolic diseases, and adipose depots have been associated with the risk of CAD. Leveraging a large clinical trial, we further establish the role of dysregulated BCAA catabolism in HS and CAD, although BCAAs did not appear to be in the causal pathway of either disease. This suggests that BCAAs may serve as an independent circulating biomarker of HS and CAD but that their association with these cardiometabolic diseases is mediated through other pathways.
Subject(s)
Coronary Artery Disease , Humans , Middle Aged , Coronary Artery Disease/etiology , Adiposity , Amino Acids, Branched-Chain/metabolism , Prospective Studies , Risk Factors , Biomarkers/metabolism , Tomography, X-Ray Computed , Obesity/complications , Chest Pain , Coronary Angiography/methods , Adipose Tissue/diagnostic imaging , Adipose Tissue/metabolismABSTRACT
Study Objective: Aortic arch geometry changes with age, including an increase in aortic arch width (AAW). High AAW is a predictor of incident adverse cardiovascular disease (CVD) events, but its distribution and determinants are unknown. We hypothesized that traditional CVD risk factors, in addition to age, are associated with increased AAW in community-dwelling adults. Study Design: Framingham Offspring and Third Generation cohort participants (N=3026, 52% Men) underwent thoracic multidetector computed tomography (MDCT). A referent group (733M, 738W) free of clinical CVD, hypertension, dyslipidemia, smoking, and diabetes was used to generate sex and 10-year age-group specific upper 90th percentile (P90) cut-points for AAW. AAW was measured as the distance between the cross-sectional centroids of the ascending and descending thoracic aorta. Multivariable logistic regression models were used to identify clinical correlates of high AAW (≥referent P90) in the overall study group. Results: Among referent participants, AAW increased with greater age-group, p for trend <0.0001 in each sex. Overall and within each age group, AAW was greater in men than women, p<0.0001 all comparisons. Across all participants, high AAW was associated with greater age (odds ratio, OR=1.34/10y; 95% confidence interval 1.20 - 1.50), body surface area (OR=1.97/SD; 1.62 - 2.40), diastolic blood pressure (OR=1.59/10mmHg; 1.40 - 1.81), pack-years smoked (OR=1.07; 1.02 - 1.13), and prevalent CVD (OR=1.64; 1.08 - 2.49). Conclusion: AAW increases with greater age, body size, diastolic blood pressure and burden of smoking. High AAW (≥referent P90) is also associated with prevalent (clinically apparent) CVD. AAW is often seen on and easily measured from tomographic thoracic images and has prognostic value.
ABSTRACT
Background Patients presenting to the emergency department (ED) with acute chest pain (ACP) syndrome undergo additional testing to exclude acute coronary syndrome (ACS), pulmonary embolism (PE), or aortic dissection (AD), often yielding negative results. Purpose To assess whether deep learning (DL) analysis of the initial chest radiograph may help triage patients with ACP syndrome more efficiently. Materials and Methods This retrospective study used electronic health records of patients with ACP syndrome at presentation who underwent a combination of chest radiography and additional cardiovascular or pulmonary imaging or stress tests at two hospitals (Massachusetts General Hospital [MGH], Brigham and Women's Hospital [BWH]) between January 2005 and December 2015. A DL model was trained on 23 005 patients from MGH to predict a 30-day composite end point of ACS, PE, AD, and all-cause mortality based on chest radiographs. Area under the receiver operating characteristic curve (AUC) was used to compare performance between models (model 1: age + sex; model 2: model 1 + conventional troponin or d-dimer positivity; model 3: model 2 + DL predictions) in internal and external test sets from MGH and BWH, respectively. Results At MGH, 5750 patients (mean age, 59 years ± 17 [SD]; 3329 men, 2421 women) were evaluated. Model 3, which included DL predictions, significantly improved discrimination of those with the composite outcome compared with models 2 and 1 (AUC, 0.85 [95% CI: 0.84, 0.86] vs 0.76 [95% CI: 0.74, 0.77] vs 0.62 [95% CI: 0.60 0.64], respectively; P < .001 for all). When using a sensitivity threshold of 99%, 14% (813 of 5750) of patients could be deferred from cardiovascular or pulmonary testing for differential diagnosis of ACP syndrome using model 3 compared with 2% (98 of 5750) of patients using model 2 (P < .001). Model 3 maintained its diagnostic performance in different age, sex, race, and ethnicity groups. In external validation at BWH (22 764 patients; mean age, 57 years ± 17; 11 470 women), trends were similar and improved after fine tuning. Conclusion Deep learning analysis of chest radiographs may facilitate more efficient triage of patients with acute chest pain syndrome in the emergency department. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Goo in this issue.
Subject(s)
Acute Coronary Syndrome , Deep Learning , Male , Humans , Female , Middle Aged , Triage , Retrospective Studies , Radiography , Chest Pain/etiology , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/diagnostic imagingABSTRACT
OBJECTIVES: To compare the prognostic value of individual CT-derived coronary artery disease (CAD) characteristics across categories of clinical cardiovascular risk. METHODS: The central core laboratory assessed coronary artery calcium (CAC), obstructive CAD (stenosis ≥ 50%), and high-risk plaque (HRP) in stable outpatients with suspected CAD enrolled in the PROMISE trial. Multivariable Cox regression models (endpoint: unstable angina, nonfatal myocardial infarction, or all-cause mortality; median follow-up: 2 years) were used to compare hazard ratios (HR) of the CT measures between low-borderline (< 7.5%) and moderate-high (≥ 7.5%) atherosclerotic cardiovascular disease (ASCVD) risk based on the pooled cohort equation. RESULTS: Among 4356 included patients (aged 61 ± 8 years, 52% women), 67% had ASCVD risk ≥ 7.5%. Stratified by ASCVD risk, CAD ≥ 50% had nearly threefold greater HR in individuals with ASCVD < 7.5% (aHR, 6.85; 95% CI, 2.33-20.15; p < 0.001) vs. ASCVD ≥ 7.5% (aHR: 2.66, 95% CI: 1.67-4.25, p < 0.001; interaction p = 0.041). CAC predicted events solely in ASCVD ≥ 7.5% patients (aHR: 1.92, 95% CI: 1.01-3.63, p = 0.045; interaction p = 0.571), while HRP predicted events only in ASCVD < 7.5% (aHR: 3.11, 95% CI: 1.09-8.85, p = 0.034; interaction p = 0.034). CONCLUSIONS: Prognostic values of CT-derived CAD characteristics differ by ASCVD risk categories. While CAD ≥ 50% has the highest prognostic value regardless of ASCVD risk, CAC is prognostic in high and HRP in low ASCVD risk. These findings suggest that CAD ≥ 50% and HRP detection rather than CAC scoring may better risk-stratify symptomatic low-risk patients and thus potentially improve downstream care. KEY POINTS: ⢠Prognostic value of individual CT-derived CAD characteristics differs by categories of cardiovascular risk. ⢠Presence of obstructive coronary artery stenosis ≥ 50% has the highest prognostic value regardless of cardiovascular risk. ⢠Coronary artery calcium is independently prognostic in high and high-risk plaque features in low cardiovascular risk.
Subject(s)
Atherosclerosis , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Female , Male , Coronary Artery Disease/diagnostic imaging , Prognosis , Calcium , Coronary Angiography , Risk Assessment , Plaque, Atherosclerotic/diagnostic imaging , Tomography, X-Ray Computed , Risk Factors , Predictive Value of TestsABSTRACT
BACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high-risk coronary atherosclerotic plaque (HRP). Blood-based biomarkers that associate with imaging-defined HRP and predict MACE are lacking. METHODS AND RESULTS Nuclear magnetic resonance-based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP-associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high-density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56-0.85]; P<0.001) and medium HDL (OR, 0.84 [95% CI, 0.72-0.98]; P=0.028) and HDL size (OR, 0.82 [95% CI, 0.69-0.96]; P=0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; P=0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88-0.94]; P<0.001). CONCLUSIONS Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT01174550.
Subject(s)
Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Coronary Artery Disease/diagnostic imaging , Prospective Studies , Lipoproteins , Lipoproteins, HDL , Coronary Angiography , Biomarkers , Chest Pain , Risk FactorsABSTRACT
BACKGROUND: Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. METHODS: REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. RESULTS: The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055). CONCLUSIONS: Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).
Subject(s)
Atherosclerosis , Coronary Artery Disease , Plaque, Atherosclerotic , Humans , Female , Male , United States/epidemiology , HIV , Sex Characteristics , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Atherosclerosis/epidemiology , Plaque, Atherosclerotic/complications , Risk Factors , Inflammation/complications , Biomarkers , Coronary Artery Disease/complications , Coronary Artery Disease/epidemiologyABSTRACT
Coronary computed tomography angiography (CTA) improves the quality of care for patients presenting with acute chest pain (ACP) to the emergency department (ED), particularly in patients with low to intermediate likelihood of acute coronary syndrome (ACS). The Society of Cardiovascular Computed Tomography Guidelines Committee was formed to develop recommendations for acquiring, interpreting, and reporting of coronary CTA to ensure appropriate, safe, and efficient use of this modality. Because of the increasing use of coronary CTA testing for the evaluation of ACP patients, the Committee has been charged with the development of the present document to assist physicians and technologists. These recommendations were produced as an educational tool for practitioners evaluating acute chest pain patients in the ED, in the interest of developing systematic standards of practice for coronary CTA based on the best available data or broad expert consensus. Due to the highly variable nature of medical care, approaches to patient selection, preparation, protocol selection, interpretation or reporting that differs from these guidelines may represent an appropriate variation based on a legitimate assessment of an individual patient's needs.
Subject(s)
Computed Tomography Angiography , Radiology , Humans , United States , Consensus , Predictive Value of Tests , Chest Pain/diagnostic imaging , Chest Pain/etiology , Emergency Service, Hospital , Angiography , North America , Coronary Angiography/methodsABSTRACT
BACKGROUND: In patients with suspected obstructive coronary artery disease (CAD), the risk factor-weighted clinical likelihood (RF-CL) model and the coronary artery calcium score-weighted clinical likelihood (CACS-CL) model improves the identification of obstructive CAD compared with basic pretest probability (PTP) models. OBJECTIVES: The aim of this study was to assess the prognostic value of the new models. METHODS: The incidences of myocardial infarction and death were stratified according to categories by the RF-CL and CACS-CL and compared with categories by the PTP model. We used cohorts from a Danish register (n = 41,177) and a North American randomized study (n = 3,952). All patients were symptomatic and were referred for diagnostic testing because of clinical indications. RESULTS: Despite substantial down-reclassification of patients to a likelihood ≤5% of CAD with either the RF-CL (45%) or CACS-CL (60%) models compared with the PTP (18%), the annualized event rates of myocardial infarction and death were low using all 3 models; RF-CL 0.51% (95% CI: 0.46-0.56), CACS-CL 0.48% (95% CI: 0.44-0.56), and PTP 0.37% (95% CI: 0.31-0.44), respectively. Overall, comparison of the predictive power of the 3 models using Harrell's C-statistics demonstrated superiority of the RF-CL (0.64 [95% CI: 0.63-0.65]) and CACS-CL (0.69 [95% CI: 0.67-0.70]) compared with the PTP model (0.61 [95% CI: 0.60-0.62]). CONCLUSIONS: The simple clinical likelihood models that include classical risk factors or risk factors combined with CACS provide improved risk stratification for myocardial infarction and death compared with the standard PTP model. Hence, the optimized RF-CL and CACS-CL models identify 2.5 and 3.3 times more patients, respectively, who may not benefit from further diagnostic testing.
Subject(s)
Coronary Artery Disease , Myocardial Infarction , Humans , Coronary Artery Disease/diagnosis , Coronary Artery Disease/epidemiology , Coronary Angiography , Calcium , Risk Assessment , Predictive Value of Tests , Risk Factors , Arteries , Myocardial Infarction/diagnosis , Myocardial Infarction/epidemiologyABSTRACT
Cardiovascular disease (CVD) is the leading cause of mortality in adults with hepatic steatosis (HS). However, risk factors for CVD in HS are unknown. We aimed to identify factors associated with coronary artery disease (CAD) and incident major adverse cardiovascular events (MACE) in individuals with HS. We performed a nested cohort study of adults with HS detected on coronary computed tomography in the PROspective Multicenter Imaging Study for Evaluation of chest pain (PROMISE) trial. Obstructive CAD was defined as ≥50% coronary stenosis. MACE included hospitalization for unstable angina, nonfatal myocardial infarction, or all-cause death. Multivariate modeling, adjusted for age, sex, atherosclerotic CVD (ASCVD) risk score and body mass index, identified factors associated with obstructive CAD. Cox regression, adjusted for ASCVD risk score, determined the predictors of MACE. A total of 959 of 3,756 (mean age 59.4 years, 55.0% men) had HS. Obstructive CAD was present in 15.2% (145 of 959). Male sex (adjusted odds ratio [aOR] = 1.83, 95% confidence interval [CI] 1.18-1.2.84; p = 0.007), ASCVD risk score (aOR = 1.05, 95% CI 1.03-1.07; p < 0.001), and n-terminal pro-b-type natriuretic peptide (NT-proBNP; aOR = 1.90, 95% CI 1.38-2.62; p < 0.001) were independently associated with obstructive CAD. In the 25-months median follow-up, MACE occurred in 4.4% (42 of 959). Sedentary lifestyle (adjusted hazard ratio [aHR] = 2.53, 95% CI 1.27-5.03; p = 0.008) and NT-proBNP (aOR = 1.50, 95% CI 1.01-2.25; p = 0.046) independently predicted MACE. Furthermore, the risk of MACE increased by 3% for every 1% increase in ASCVD risk score (aHR = 1.03, 95% CI 1.01-1.05; p = 0.02). Conclusion: In individuals with HS, male sex, NT-pro-BNP, and ASCVD risk score are associated with obstructive CAD. Furthermore, ASCVD, NT-proBNP, and sedentary lifestyle are independent predictors of MACE. These factors, with further validation, may help risk-stratify adults with HS for incident CAD and MACE.