AIMS:Higher serum insulin-like growth factor binding protein 1 (IGFBP-1) is associated with insulin sensitivity and reduced risk of obesity, diabetes, and atherosclerosis. Epicardial (EAT) and intrathoracic adipose tissue (IAT) are associated with increased atherosclerosis. Whether there is an inverse association of IGFBP-1 with EAT and IAT is unknown. METHODS:We measured EAT, IAT, and IGFBP-1 from n = 102 participants from the LonGenity parent study at the Albert Einstein Institute of Aging, Bronx NY, who were enrolled to investigate healthy aging in Ashkenazi Jewish offspring of parents with exceptional longevity (OPEL) vs usual survival (OPUS). Participants underwent non-contrast electrocardiogram-gated computed tomography (CT) for fat volume quantification. Multiple linear regression models for the cross-sectional association of IGFBP-1 with EAT and IAT were adjusted for demographic, clinical, and laboratory factors. RESULTS:Higher IGFBP-1 levels were statistically significantly associated with lower EAT and IAT, particularly in the OPEL. This inverse relationship remained significant after adjusting for age, body mass index, high-density lipoprotein cholesterol, and cardiometabolic factors. In contrast, among the OPUS, the point estimates for these associations were directionally similar but not statistically significant. CONCLUSION:Circulating IGFBP-1 may be a novel biomarker for visceral adiposity and cardiometabolic risk stratification. Future studies should explore its role in cardiovascular aging.

Following technological developments and new landmark trials, the diagnostic work-up of symptomatic chronic coronary artery disease (CAD) has evolved. Clinical guidelines now favor noninvasive anatomical assessments by coronary CT angiography (CCTA) as the first-line modality to evaluate CAD in the majority of patients with chest pain. This shift from ischemia testing to stenosis and plaque characterization has resulted in the development of new imaging biomarkers reflecting a variety of coronary plaque features, many of which have proven to be important clinical risk markers. Consequently, there has been a transition from qualitative to semi-quantitative and fully quantitative plaque acquisitions over the entire coronary tree. With the integration of artificial intelligence, novel software enables rapid quantitative acquisitions of plaque components, making them feasible for use in clinical practice. CCTA has also enabled identification of precursor features associated with plaque development such as peri-coronary artery adipose tissue attenuation and epicardial adipose tissue volume. This review provides an overview of CCTA derived plaque features in CAD and associated imaging biomarkers of risk to highlight their potential applications in precision phenotyping and individualized management decisions. It further outlines anticipated future developments that may enable widespread clinical adoption of these novel imaging biomarkers.

Importance:Selection of patients with a bicuspid aortic valve and aortopathy for prophylactic aortic surgery remains challenging. In thoracic aortopathy, aortic medial elastin fiber fragmentation initially leads to microcalcification but later declines with progressive loss of elastin content and reduced structural integrity. Objective:To determine whether aortic microcalcification detected using fluorine F 18-labeled [18F]-sodium fluoride positron emission tomography (PET) is associated with future aortic diameter expansion. Design, Setting, and Participants:This prospective longitudinal cohort study was conducted in tertiary care centers across Scotland from April 4, 2019, to September 15, 2023. Participants included patients with a bicuspid aortic valve. Data analysis was performed from May 21, 2024, to March 4, 2025. Exposures:Hybrid [18F]-sodium fluoride PET and computed tomography. Main Outcomes and Measures:Baseline ascending aortic [18F]-sodium fluoride uptake was measured as mean tissue to background ratio. The primary outcome was ascending aortic diameter expansion during 24 months on cardiac magnetic resonance imaging (MRI). Results:Seventy-six patients with a bicuspid aortic valve (mean [SD] age, 52.6 [7.5] years; 57 [75.0%] male) underwent baseline [18F]-sodium fluoride PET and MRI. Fifty-six patients underwent follow-up MRI after a median of 723 (IQR, 515-787) days. There was an inverse correlation between baseline ascending aortic [18F]-sodium fluoride uptake and annual change in diameter (Pearson r = -0.37; P = .005), which remained after adjustment for confounders in multivariable regression analysis. Ascending aortic [18F]-sodium fluoride was not correlated with baseline diameter (Pearson r = 0.08; P = .50) but was moderately correlated with baseline ascending aortic stiffness index (Pearson r = 0.38; P < .001). Conclusion and Relevance:In this cohort study of patients with a bicuspid aortic valve, the most rapid aortic growth was seen in those with low [18F]-sodium fluoride ascending aortic uptake, indicating reduced aortic wall integrity. High ascending aortic [18F]-sodium fluoride uptake was associated with a stiffer and slow-growing ascending aortic phenotype. These findings suggest that [18F]-sodium fluoride PET imaging represents a promising new noninvasive approach to identify a microcalcified disease phenotype in thoracic aortopathy among patients with a bicuspid aortic valve.

Spatial distribution of coronary artery calcium (CAC) may provide additional prognostic value in patients undergoing SPECT and PET myocardial perfusion imaging (MPI). We aimed to automatically identify CAC in proximal segments from attenuation correction CT (CTAC) scans using artificial intelligence (AI) and to evaluate prognostic significance in two large international multicenter registries. From hybrid MPI/CT imaging (N = 43,099) across 15 sites, we included 4,552 most relevant patients with (1) no prior coronary artery disease; (2) AI-derived mild CAC scores (1–99); and (3) normal perfusion (stress total perfusion deficit < 5

Increased right ventricular (RV) radiotracer uptake on perfusion imaging has been recognized as a marker of increased cardiovascular risk. However, this uptake is challenging to quantify because of the variable intensity of uptake in a thin structure. We used a validated artificial intelligence-enhanced method for segmenting the right ventricle from CT attenuation correction (CTAC) imaging to automatically quantify RV activity and then evaluated its prognostic significance. Methods: We evaluated consecutive patients from 11 sites who underwent PET myocardial perfusion imaging with available CTAC. We segmented the RV and left ventricular myocardium from CTAC images using deep learning and then quantified RV activity measures on coregistered PET images. We evaluated associations between RV activity measures and the incidence of death or myocardial infarction (MI). Results: In total, 25,444 patients were included in our analysis (median age, 67 y). During a median follow-up of 4.1 y, 6009 patients (23.6%) experienced death or MI. Most RV activity measures were associated with the risk of death or MI. Higher maximum RV rest activity was associated with an increased risk of death or MI (unadjusted hazard ratio, 1.17 per SD for 13N-ammonia and 1.19 per SD for 82Rb). These associations persisted after adjusting for age, sex, medical history, perfusion, function, and myocardial flow reserve. Conclusion: Deep learning can extract RV activity from hybrid PET/CT myocardial perfusion imaging. These measures are associated with myocardial flow reserve and provide complementary information regarding cardiovascular risk.

Background:Anemia is an established marker of cardiovascular disease severity and risk which leads to elevations in resting myocardial blood flow (MBF) and impaired myocardial flow reserve (MFR) in patients without obstructive coronary artery disease (CAD). Anemia can potentially be detected opportunistically from blood pool density changes on computed tomography (CT) imaging. Objectives:We evaluated relationships between chamber density measurements with hemoglobin, positron emission tomography (PET) findings, and cardiovascular events. Methods:We included 33460 patients from 13 sites in the REFINE-PET who underwent PET and 24368 patients undergoing lung cancer screening chest CT. A deep learning model segmented cardiac chambers from CT images, then quantified chamber density. We evaluated the relationship between chamber density measures with resting MBF and MFR, as well as associations with death or myocardial infarction (MI). Results:We included a total of 57,828 patients. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR (adjusted odds ratio 3.02 per SD increase, 95% confidence interval[CI] 2.72 - 3.38) and an increased risk of death or MI in (adjusted hazard ratio[HR] 1.38 per SD increase, 95% CI 1.26-1.51). Having myocardial density higher than blood pool density was also associated with cardiovascular death in patients undergoing low-dose chest CT (adjusted HR 1.73, 95% CI 1.20-2.52). Conclusions:In a large multimodality dataset, lower cardiac chamber density is associated with impaired MFR and independently associated with cardiovascular events. These biomarkers can be automatically extracted from CT to provide physiologic insights and potentially guide patient care.

To evaluate the reproducibility of plaque quantification from serial cardiac computed tomography (CCTA) scans by a systematic side-by-side approach using validated AI-enabled software with both scan-specific and fixed attenuation thresholds. Thirty participants from two centers underwent serial CCTA within a short timeframe (median 6 days [IQR 0–30]). Volumes and burden (defined as plaque volume indexed by vessel volume) of total plaque (TP), calcified plaque (CP), non-calcified plaque (NCP), and low-density NCP (LD-NCP) were quantified per-patient while comparing the serial scans side-by-side. Analyses were done by two assessors using consensus readings to reduce individual bias, and inter-scan differences were compared using mean differences and the repeatability coefficient (RC, defined as 1.96 × standard deviation). Mean age was 59 years (70

BACKGROUND:Photon-counting detector (PCD)-computed tomography (CT) offers higher spatial resolution and spectral capability compared with energy-integrating (EID)-CT. In coronary computed tomography angiography (CTA), these features may mitigate calcium blooming, enhance stenosis quantification, limit stenosis overestimation, and reduce low-yield referrals to invasive coronary angiography (ICA). OBJECTIVES:This meta-analysis compared diagnostic outcomes between PCD-CT and EID-CT in adults with stable coronary artery disease undergoing coronary CTA. METHODS:The authors' protocol was preregistered and followed the PRISMA 2020 guidelines. Primary outcomes were vessel-level stenosis reclassification, downstream ICA referral, and revascularization rates among those referred. Where multiple studies with compatible definitions were available, random-effects meta-analysis was performed; otherwise, results were described narratively. RESULTS:Fifteen studies (N = 11,350) met inclusion criteria. At the vessel level, PCD-CT down-classified stenosis severity in a pooled absolute proportion of 34.2% of vessels compared with EID-CT (95% CI: 27.3-41.9; P < 0.0001). This was associated with fewer downstream ICA referrals (pooled OR: 0.71; 95% CI; 0.63-0.79; P < 0.0001) and higher rates of revascularization among those undergoing ICA (OR: 1.43; 95% CI: 1.14-1.79; P = 0.0017). Stratified by coronary artery calcium score (CACS), ICA referrals were lower with PCD-CT when CACS was <400 (OR: 0.62; 95% CI: 0.52-0.75; P < 0.0001) and trended lower when CACS ≥400 (OR: 0.42; 95% CI: 0.16-1.11; P = 0.08). CONCLUSIONS:Compared against conventional EID-CT, PCD-CT was associated with down-classification of stenosis severity, translating to fewer referrals for ICA and a greater rate of revascularization when angiography is undertaken.

OBJECTIVE:Recent studies have demonstrated a greater prevalence of coronary atherosclerosis in male masters endurance athletes, but the underlying contributors remain unclear. We explored the relationship between occult resting and exercise-induced hypertension with coronary atherosclerosis characteristics. METHODS:198 male masters endurance athletes with a low Framingham risk score (<10%) and no clinical diagnosis of hypertension underwent 24-hour ambulatory blood pressure (ABP) monitoring and exercise BP assessment. Coronary CT angiography assessed coronary artery calcification (CAC) score, luminal stenosis and high-risk plaque features. RESULTS:Seventy-eight (39%) athletes were hypertensive on ABP monitoring and 93 (47%) demonstrated a hypertensive response to exercise. A CAC score of 1-99 Agatston units (AU), 100-399 AU and ≥400 AU was present in 94 (47%), 32 (16%) and 15 (8%) athletes, respectively. Twenty-four (12%) athletes had coronary stenoses >50%. Sixty-two athletes (31%) had calcified plaque, 32 (16%) had mixed plaque, 2 (1%) had non-calcified plaque and 26 (13%) had markers of high-risk plaque. Hypertension on ABP monitoring was significantly associated with a CAC score ≥100 AU (OR: 2.56; 1.08 to 6.04) and coronary stenosis >50% (OR: 2.92; 1.17 to 7.33). A hypertensive response to exercise was significantly associated with coronary stenosis >50% (OR: 4.72; 1.65 to 13.5) and the presence of high-risk plaque (OR: 3.27; 1.27 to 8.43). CONCLUSION:Masters male endurance athletes have a high prevalence of occult hypertension, which is associated with high-risk features of coronary atherosclerosis. Both ambulatory and exercise-induced hypertension are associated with a higher prevalence of atherosclerotic coronary artery disease in male endurance athletes. Early identification and timely clinical management of this classic cardiovascular disease risk factor may reduce the burden of coronary atherosclerosis in athletes.

BACKGROUND:Half of women with ischemic symptoms have non-obstructive coronary artery disease (CAD), while the pathophysiology of their condition has not been characterized. Noncalcified (NCP) and low-attenuation plaque (CT density<30 Hounsfield units, LAP) burden quantified from coronary computed tomography angiography (CCTA) is associated with ischemia in patients with obstructive CAD. We hypothesize that NCP burden is related to angina in women with ischemic symptoms and Non-Obstructive Coronary Arteries (INOCA). METHODS:Women with INOCA enrolled in the WARRIOR trial were evaluated for angina severity with Seattle Angina Questionnaire (SAQ) at study entry. Baseline CCTA of 117 women were quantitatively analyzed with AI-based software for NCP, LAP and calcified plaque (CP) volumes and burdens (%, normalized to vessel volume) across the coronary tree. Machine-learning ischemia risk score (ML-IRS) integrating quantitative lumen and plaque features from CCTA was automatically measured. RESULTS:Among 109 women with visible plaque on CCTA (age 61.9, SD 10.3 years) median total plaque burden is 26.6% (IQR 18.6,32.0) and median SAQ score is 61.4 (IQR 54.6,69.1). Patients with more severe angina (SAQ ≤ 60) are younger (58.1 vs 62.0 years, p = 0.015), have higher total cholesterol (195 vs 165 mg/dL, p = 0.006), but less frequently receive statins (31.8 vs 64.4%, p = 0.006) compared with patients with SAQ > 60. Patients with SAQ ≤ 60 have higher total plaque (33.3 vs 24.3%, p = 0.001), and NCP burden (33.3 vs. 23.2%, p = 0.00065), and lower CP burden (0.0 vs. 0.3%, p = 0.005) compared with patients with SAQ > 60. On multivariable linear regression adjusted for risk factors, higher NCP burden (β = -0.50, p = 0.001), LAP burden (β = -4.50, p = 0.008) and ML-IRS (β = -3.09, p = 0.04) are associated with lower SAQ score, i.e. more severe angina. CONCLUSIONS:In women with INOCA, high-risk atherosclerotic plaque phenotypes are related to more severe angina.

BACKGROUND:Coronary plaque progression persists in some patients despite effective low-density lipoprotein cholesterol (LDL-C) lowering. Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot that may influence coronary atherosclerosis through inflammatory signaling. The authors hypothesized that longitudinal changes in EAT would influence plaque progression. METHODS:Plaque and EAT quantification with paired baseline and follow-up coronary computed tomography angiography was attainable in 313 asymptomatic, statin-naive participants (aged 58.8 ± 6.8 years, 44% female) in the CAUGHT-CAD (Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease) trial. Associations between longitudinal changes in EAT volume and attenuation (ΔEAT) and coronary plaque outcomes were evaluated using analysis of covariance models, with adjustment for baseline plaque burden, treatment allocation, and changes in cardiometabolic risk factors. Exploratory analyses evaluated the relationship between ΔEAT attenuation and Δ pericoronary adipose tissue (PCAT) attenuation. An LDL-C-based reference model of achieved LDL-C (Reference: <1.4 mmol/L [<55 mg/dL], 1.4-1.8 mmol/L [55-70 mg/dL], and >1.8 mmol/L [>70 mg/dL]) was used, and incremental discrimination with ΔEAT attenuation was assessed using nested model comparison and likelihood ratio testing. RESULTS:Higher ΔEAT attenuation, but not EAT volume change, remained independently associated with progression of noncalcified plaque (NCP) and adverse plaque remodeling. Per 1-SD increase in ΔEAT attenuation, NCP volume was higher by 4.21 mm3 (95% CI: 0.67-7.74; P = 0.020), fibrous plaque volume by 3.55 mm3 (95% CI: 0.67-6.43; P = 0.016), and NCP percent atheroma volume by 1.08% (95% CI: 0.47-1.69; P < 0.001). In participants with high baseline EAT volume (tertile 3 ≥67.1 cm3), the addition of ΔEAT attenuation to LDL-C-based analysis of covariance models resulted in a statistically significant improvement in model fit (Δ Akaike information criterion -4.8; likelihood ratio test P = 0.012). In exploratory analyses, ΔEAT attenuation was also associated with increasing PCAT attenuation (β = 2.44 HU per SD; P < 0.001), suggesting that changes in PCAT may partly explain the observed association with plaque progression. CONCLUSIONS:The association of serial changes in EAT attenuation with coronary plaque remodeling, independent of LDL-C lowering, supports a potential mechanistic role for EAT inflammation in residual plaque progression.

BACKGROUND:Non-contrast T1-weighted cardiovascular MR (CMR) enables assessment of coronary atherosclerotic plaques by exploiting elevated signal intensity within high-risk plaque components. The novel iT2prep-BOOST sequence provides co-registered coronary lumen and vessel wall whole-heart imaging, potentially facilitating plaque assessment. However, direct comparison of quantitative plaque measures between iT2prep-BOOST and coronary computed tomography angiography (CCTA), the non-invasive standard for plaque assessment, remains limited. This study aimed to compare coronary plaque burden and plaque signal intensity measured by iT2prep-BOOST with plaque burden and plaque attenuation characteristics derived from CCTA. METHODS:In this prospective, observational study, patients with stable coronary artery disease confirmed by diagnostic CCTA were recruited and subsequently underwent CMR using the iT2prep-BOOST sequence. Using semi-automated software, per-lesion cross-sectional areas of total, calcified, non-calcified, and low-density non-calcified plaque (≤30 Hounsfield unit) together with measures of plaque burden (percentage vessel atheroma) were quantified on CCTA. The corresponding coronary atherosclerotic lesion was analysed on T1-weighted black-blood iT2prep-BOOST CMR to assess cross-sectional plaque area, burden, and plaque-to-myocardial signal intensity ratio (PMR). RESULTS:A total of 188 lesions in 85 patients were analysed and compared between iT2prep-BOOST and CCTA. Plaque burden estimates derived from iT2prep-BOOST demonstrated moderate correlation with CCTA-derived total plaque burden (r = 0.58) and non-calcified plaque burden (r = 0.54). However, agreement between modalities was limited. For total plaque burden, the mean difference was -4% (95% CI: -7% to -2%) with limits of agreement ranging from -38% to 29%. For non-calcified plaque burden, the mean difference was 3% (95% CI: 0% to 5%) with limits of agreement from -34% to 39%. In univariate regression analyses, PMR was associated with increasing total, non-calcified, and low-density non-calcified plaque areas and decreasing CT attenuation values. CONCLUSION:Coronary plaque burden assessed by iT2prep-BOOST demonstrated modest correlation and limited agreement with CCTA-derived plaque burden, indicating that the two modalities are not directly interchangeable for plaque burden quantification. Nevertheless, the observed associations between PMR and adverse CCTA plaque characteristics support the potential role of T1-weighted CMR as a complementary, non-invasive tool for coronary plaque characterization.

Background: Body composition is recognized as a major determinant of health outcomes, but its multidimensional nature makes clinical adoption challenging. We sought to develop and validate a body composition index (BCI) for all-cause mortality risk assessment, integrating variables of six body composition tissues. Methods: We analyzed 28509 consecutive patients undergoing myocardial perfusion imaging with routine low-dose chest CT attenuation correction (CTAC) scans acquired during myocardial perfusion imaging (MPI) at 12 centers across four countries. An artificial intelligence-based BCI was developed in a cohort of 15037 patients CTACs by integrating the CT-derived metrics of bone, skeletal muscle, and four adipose tissue compartments, coronary artery calcium score, and basic demographic variables (age, sex, BMI). The performance of BCI for mortality prediction was validated in an internal cohort of 6444 patients and an external cohort of 7028 patients by prognosis, calibration, net benefit, and explainability. Model-based simulation of tissue metrics modification was performed to evaluate estimated mortality risk reduction. Findings: During a median of 3.5 (IQR [1.9, 5.1]) years, 4697 (16%) patients died. In the external testing cohort, the BCI demonstrated excellent discrimination for mortality (area under receiver operating characteristic curve 0.78 (95% CI [0.76, 0.79]) and Harrell concordance index 0.75 [0.73, 0.76]), calibration, and net benefit overall and across pre-specified subgroups stratified by patient characteristics and imaging protocols. Visceral adipose tissue attenuation was the most influential body composition measure, followed by skeletal muscle volume. Simulated improvement in body composition was associated with significant mortality risk reduction. Interpretation: An index combining six body composition measures obtained opportunistically from routine chest CT provides robust mortality risk stratification. By converting complex body composition information into a single interpretable score, the BCI can facilitate clinical implementation of opportunistic CT biomarkers and guide individualized preventive strategies.