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Background: Aortic valve calcification (AVC) shares pathological features with atherosclerosis. Lipoprotein components have been detected in aortic valve tissue, including HDL (high-density lipoprotein). HDL measures have inverse associations with cardiovascular disease, but relationships with long-term AVC progression are unclear. We investigated associations of HDL cholesterol, HDL-particle number and size, apoC3-defined HDL subtypes, and, secondarily, CETP (cholesteryl ester transfer protein) mass and activity, with long-term incidence and progression of AVC. Methods: We used linear mixed-effects models to evaluate the associations of baseline HDL indices with AVC. AVC was quantified by Agatston scoring of up to 3 serial computed tomography scans over a median of 8.9 (maximum 11.2) years of follow-up in the Multi-Ethnic Study of Atherosclerosis (n=6784). Results: After adjustment, higher concentrations of HDL-C (high-density lipoprotein cholesterol), HDL-P (HDL particles), large HDL-P, and apoC3-lacking HDL-C were significantly associated with lower incidence/progression of AVC. Neither small or medium HDL-P nor apoC3-containing HDL-C was significantly associated with AVC incidence/progression. When included together, a significant association was observed only for HDL-C, but not for HDL-P. Secondary analyses showed an inverse relationship between CETP mass, but not activity, and AVC incidence/progression. In exploratory assessments, inverse associations for HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL with AVC incidence/progression were more pronounced for older, male, and White participants. ApoC3-containing HDL-C only showed a positive association with AVC in these subgroups. Conclusions: In a multiethnic population, HDL-C, HDL-P, large HDL-P, and apoC3-lacking HDL-C were inversely associated with long-term incidence and progression of AVC. Further investigation of HDL composition and mechanisms could be useful in understanding pathways that slow AVC.

Background and hypothesisThe recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner.MethodsFrom the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model.ResultsThe 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis.ConclusionsThis study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.

Machine learning (ML) models of risk prediction with coronary artery calcium (CAC) and CAC characteristics exhibit high performance, but are not inherently interpretable.To determine the direction and magnitude of impact of CAC characteristics on 10-year all-cause mortality (ACM) with explainable ML.We analyzed asymptomatic subjects in the CAC consortium. We trained ML models on 80% and tested on 20% of the data with XGBoost, using clinical characteristics ​+ ​CAC (ML 1) and additional CAC characteristics of CAC density and number of calcified vessels (ML 2). We applied SHAP, an explainable ML tool, to explore the relationship of CAC and CAC characteristics with 10-year all-cause and CV mortality.2376 deaths occurred among 63,215 patients [68% male, median age 54 (IQR 47-61), CAC 3 (IQR 0-94.3)]. ML2 was similar to ML1 to predict all-cause mortality (Area Under the Curve (AUC) 0.819 vs 0.821, p ​= ​0.23), but superior for CV mortality (0.847 vs 0.845, p ​= ​0.03). Low CAC density increased mortality impact, particularly ≤0.75. Very low CAC density ≤0.75 was present in only 4.3% of the patients with measurable density, and 75% occurred in CAC1-100. The number of diseased vessels did not increase mortality overall when simultaneously accounting for CAC and CAC density.CAC density contributes to mortality risk primarily when it is very low ≤0.75, which is primarily observed in CAC 1-100. CAC and CAC density are more important for mortality prediction than the number of diseased vessels, and improve prediction of CV but not all-cause mortality. Explainable ML techniques are useful to describe granular relationships in otherwise opaque prediction models.

This review summarizes the framework behind global guidelines of coronary artery calcium (CAC) in atherosclerotic cardiovascular disease risk assessment, for applications in both the clinical setting and preventive therapy. By comparing similarities and differences in recommendations, this review identifies most notable common features for the application of CAC presented by different cardiovascular societies across the world. Guidelines included from North America are as follows: 1) the 2019 American College of Cardiology/American Heart Association Guideline on the Primary Prevention of Cardiovascular Disease; and 2) the 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for Prevention of Adult Cardiovascular Disease. The authors also included European guidelines: 1) the 2019 European Society for Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias; and 2) the 2016 National Institute for Health and Care Excellence Clinical Guidelines. In this comparison, the authors also discuss: 1) the Cardiac Society of Australia and New Zealand Guidelines on CAC; 2) the Chinese Society of Cardiology Guidelines; and 3) the Japanese Atherosclerosis Society Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases. Last, they include statements made by specialty societies including the National Lipid Association, Society of Cardiovascular Computed Tomography, and U.S. Preventive Services Task Force. Utilizing an in-depth review of clinical evidence, these guidelines emphasize the importance of CAC in the primary and secondary prevention of atherosclerotic cardiovascular disease. International guidelines all empower a dynamic clinician-patient relationship and advocate for individualized discussions regarding disease management and pharmacotherapy treatment. Some differences in precise coronary artery calcium score intervals, risk cut points, treatment thresholds, and stratifiers of specific patient subgroups do exist. However, international guidelines employ more similarities than differences from both a clinical and functional perspective. Understanding the parallels among international coronary artery calcium guidelines is essential for clinicians to correctly adjudicate personalized statin and aspirin therapy and further medical management.

Nicholas B Tiller,1 April Kinninger,2 Asghar Abbasi,1 Richard Casaburi,1 Harry B Rossiter,1 Matthew J Budoff,2 Alessandra Adami3 1Institute of Respiratory Medicine and Exercise Physiology, Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA; 2Division of Cardiology, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA; 3Department of Kinesiology, University of Rhode Island, Kingston, RI, USACorrespondence: Harry B Rossiter, Institute of Respiratory Medicine and Exercise Physiology, Division of Respiratory and Critical Care Physiology and Medicine, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, 1124 W. Carson Street, CDCRC Building, Torrance, CA, 90502, USA, Tel +1 310-222-8200, Email hrossiter@lundquist.orgIntroduction: Severe chronic obstructive pulmonary disease (COPD) is partly characterized by diminished skeletal muscle oxidative capacity and concurrent dyslipidemia. It is unknown whether such metabolic derangements increase the risk of cardiovascular disease. This study explored associations among physical activity (PA), muscle oxidative capacity, and coronary artery calcium (CAC) in COPDGene participants.Methods: Data from current and former smokers with COPD (n = 75) and normal spirometry (n = 70) were retrospectively analyzed. Physical activity was measured for seven days using triaxial accelerometry (steps/day and vector magnitude units [VMU]) along with the aggregate of self-reported PA amount and PA difficulty using the PROactive D-PPAC instrument. Muscle oxidative capacity (k) was assessed via near-infrared spectroscopy, and CAC was assessed via chest computerized tomography.Results: Relative to controls, COPD patients exhibited higher CAC (median [IQR], 31 [0– 431] vs 264 [40– 799] HU; p = 0.003), lower k (mean ± SD = 1.66 ± 0.48 vs 1.25 ± 0.37 min− 1; p < 0.001), and lower D-PPAC total score (65.2 ± 9.9 vs 58.8 ± 13.2; p = 0.003). Multivariate analysis—adjusting for age, sex, race, diabetes, disease severity, hyperlipidemia, smoking status, and hypertension—revealed a significant negative association between CAC and D-PPAC total score (β, − 0.05; p = 0.013), driven primarily by D-PPAC difficulty score (β, − 0.03; p = 0.026). A 1 unit increase in D-PPAC total score was associated with a 5% lower CAC (p = 0.013). There was no association between CAC and either k, steps/day, VMU, or D-PPAC amount.Conclusion: Patients with COPD and concomitantly elevated CAC exhibit greater perceptions of difficulty when performing daily activities. This may have implications for exercise adherence and risk of overall physical decline.Keywords: coronary artery calcium, COPD, muscle, oxidative capacity, physical activity, respiratory

Prevalence and severity of coronary artery disease (CAD) in symptomatic patients with zero coronary artery calcium score (CACS) are unclear, particularly in regard to the diabetic population, which represents, per se, a subgroup at increased cardiovascular risk. The aim of this study was to investigate the prevalence and severity of CAD by coronary computed tomography angiography (CCTA) in a symptomatic diabetic cohort with zero CACS.All consecutive symptomatic diabetics referred for CAD suspicion were included in this study. All subjects underwent a noncontrast coronary artery calcium scan followed by CCTA. CACS was quantified using the Agatston method. CAD was defined as a total plaque score (TPS) greater than zero. Obstructive and severe obstructive CAD were defined respectively as luminal stenosis50% and70% in at least one coronary segment.We identified 1722 symptomatic diabetics (mean age 62.5 ± 12.9 years, 62% men). One hundred and eleven subjects had zero CACS and TPS0 (mean age was 49.5 ± 14.8, 58% women, 56% Hispanics). Sixty-five patients (58.5%) had one-vessel disease, followed by 30 (27%) with two-vessel disease and 14 (12.6%) with ≥ three-vessel disease. Obstructive CAD was found in 11 subjects and, among these, three were categorized as severe obstructive CAD.In symptomatic diabetic patients with zero CACS, CAD, including obstructive disease, can still occur and is predominant in middle-aged adults, women and Hispanics. In symptomatic diabetics CCTA is a critical step for accurate risk stratification even when CACS would have placed some of these individuals in a lower-risk category.

Adverse cardiovascular events are a significant cause of mortality in end-stage renal disease (ESRD) patients. High-risk plaque anatomy may be a significant contributor. However, their atherosclerotic phenotypes have not been described. We sought to define atherosclerotic plaque characteristics (APC) in dialysis patients using artificial-intelligence augmented CCTA.We retrospectively analyzed ESRD patients referred for CCTA using an FDA approved artificial-intelligence augmented-CCTA program (Cleerly). Coronary lesions were evaluated for APCs by CCTA. APCs included percent atheroma volume(PAV), low-density non-calcified-plaque (LD-NCP), non-calcified-plaque (NCP), calcified-plaque (CP), length, and high-risk-plaque (HRP), defined by LD-NCP and positive arterial remodeling1.10 (PR).79 ESRD patients were enrolled, mean age 65.3 years, 32.9% female. Disease distribution was non-obstructive (65.8%), 1-vessel disease (21.5%), 2-vessel disease (7.6%), and 3-vessel disease (5.1%). Mean total plaque volume (TPV) was 810.0 mmOur study provides novel insight into ESRD plaque phenotypes and demonstrates that artificial-intelligence augmented CCTA analysis is feasible for CAD characterization despite severe calcification. We demonstrate elevated plaque burden and stenosis caused by predominantly non-calcified-plaque. Furthermore, the quantity of calcified-plaques increased with age, with men exhibiting increased number of 2-feature plaques and higher plaque volumes. Artificial-intelligence augmented CCTA analysis of APCs may be a promising metric for cardiac risk stratification and warrants further prospective investigation.

Some observational studies have observed a lower, rather than higher, mortality rate in association with hypercholesterolemia during follow-up of patients after cardiac stress testing. We aim to assess the relationship of hypercholesterolemia and other CAD risk factors to mortality across a wide spectrum of patients referred for various cardiac tests.We identified four cardiac cohorts: 64,357 patients undergoing coronary artery calcium (CAC) scanning, 10,814 patients undergoing coronary CT angiography (CCTA), 31,411 patients without known CAD undergoing stress/rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and 5051 patients with known CAD undergoing stress/rest SPECT-MPI. Each cohort was followed for all-cause mortality using risk-adjusted Cox models. We pooled the hazard ratios between cohorts with a random effects model. Baseline risk varied markedly among cohorts, from an annualized mortality rate of 0.31%/year in CAC patients to 3.63%/year among SPECT-MPI patients with known CAD. Hypertension, diabetes, and smoking were each associated with increased mortality in each patient cohort (pooled hazard ratio[95% CI]: 1.38[1.33-1.44], 1.88[1.76-2.00], and 1.67[1.48-1.86], respectively). By contrast, hypercholesterolemia was associated with decreased rather than increased mortality (pooled hazard ratio[95% CI]: 0.71[0.58-0.84]). Analysis of serum lipids among 7744 patients undergoing CAC or CCTA scanning revealed an inverse relationship between LDL cholesterol and mortality.Among a broad spectrum of patients referred for a variety of cardiac tests and ranging from low to high clinical risk, hypercholesterolemia was not associated with increased mortality risk. Our findings suggest that hypercholesterolemia may be sensitive to confounding by other clinical factors and post-test treatment changes in patient populations.

Objective Excessive cholesterol accumulation in macrophages is the pivotal step underlying atherosclerotic plaque formation. We here explore factors in the serum of patients with RA, and mechanisms through which they interact with and influence cholesterol loading capacity (CLC) of macrophages. Methods In a cross-sectional observational cohort of 104 patients with RA, CLC was measured as intracellular cholesterol content in human THP-1–derived macrophages after incubation with patient serum. Low-density lipoprotein (LDL) oxidation was measured in terms of oxidized phospholipids on apoB100-containing particles (oxPL-apoB100). Antibodies against oxidized LDL (anti-oxLDL), proprotein convertase subtilisin/Kexin type-9 (PCSK9) and high-sensitivity CRP were also quantified. All analyses adjusted for atherosclerotic cardiovascular disease (ASCVD) risk score, obesity, total LDL, statin use, age at diagnosis, and anti-oxLDL IgM. Results OxPL-apoB100, anti-oxLDL IgG and PCSK9 were positively associated with CLC (all P Conclusion Oxidized LDL can directly influence CLC in dual-seropositive RA patients. Two additional and independent pathways—via anti-oxLDL IgG and PCSK9—may mediate the effects of oxPL-apoB100 on CLC, depending on CRP and seropositivity status. If externally validated, these findings may have clinical implications for cardiovascular risk prevention.

Background and aimsWe aimed to identify predictors of change in direct measures of coronary artery calcium (CAC) volume and density in South Asian participants.MethodsWe used data from participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study with prevalent CAC and direct measures of CAC by serial computed tomography (CT) exams (2010-2013, 2016-2018). We examined the distribution of incident CAC volume and peak density, as well as progression and identified risk factors for progression of change in volume and density in multivariable models.ResultsThe study cohort consisted of 102 participants with incident CAC and 285 with CAC progression. CAC volume and density were highest, and incident CAC was most common in the left anterior descending artery (LAD). The greatest progression in volume was in the right coronary artery and the greatest change in density was in the left main. In linear regression models for CAC progression adjusted for baseline density, volume, risk factors, smoking (β +190.1, p=0.02), baseline volume (β +0.24 per mm3, p&nbsp

Publisher Copyright: © 2022 The Authors Background: Despite a potential role of hemoglobin in atherosclerosis, data on coronary plaque volume changes (PVC) related to serum hemoglobin levels are limited. Objectives: The authors sought to evaluate coronary atherosclerotic plaque burden changes related to serum hemoglobin levels using serial coronary computed tomographic angiography (CCTA). Methods: A total of 830 subjects (age 61 ± 10 years, 51.9% male) who underwent serial CCTA were analyzed. The median interscan period was 3.2 (IQR: 2.5-4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were stratified into 4 groups based on the quartile of baseline hemoglobin levels. Annualized total PVC (mm3/year) was defined as total PVC divided by the interscan period. Results: Baseline total plaque volume (mm3) was not different among all groups (group I [lowest]: 34.1 [IQR: 0.0-127.4] vs group II: 28.8 [IQR: 0.0-123.0] vs group III: 49.9 [IQR: 5.6-135.0] vs group IV [highest]: 34.3 [IQR: 0.0-130.7]; P = 0.235). During follow-up, serum hemoglobin level changes (Δ hemoglobin; per 1 g/dL) was related to annualized total PVC (β = −0.114) in overall participants (P < 0.05). After adjusting for age, sex, traditional risk factors, baseline hemoglobin and creatinine levels, baseline total plaque volume, and the use of aspirin, beta-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and statin, Δ hemoglobin significantly affected annualized total PVC in only the composite of groups I and II (β = −2.401; P = 0.004). Conclusions: Serial CCTA findings suggest that Δ hemoglobin has an independent effect on coronary atherosclerosis. This effect might be influenced by baseline hemoglobin levels. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411) publishersversion published

Background: Vasospastic angina (VSA) is characterized by chest pain at rest with transient ischemic electrocardiographic changes in the ST segment, and a prompt response to nitrates. Vasospastic angina is among the most frequent of the coronary artery diseases in Asia, and coronary computed tomography angiography (CCTA) may become available as a non-invasive diagnosis method. Methods: We prospectively enrolled 100 patients with suspected vasospastic angina at two centers from 2018 to 2020. All patients underwent baseline CCTA without a vasodilator in the early morning followed by catheterized coronary angiography and spasm testing. CCTA with intravenous infusion of nitrate (IV) was repeated within 2 weeks of baseline CCTA. Vasospastic angina as detected by CCTA was defined as significant stenosis (≥50%) with negative remodeling without definite plaques or diffuse small diameter (

Aims To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA). Methods and results We analyzed mild stenosis (25–49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02–3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09–2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07–2.22; P = 0.020). Conclusion In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. Clinical trial registration ClinicalTrials.gov NCT02803411

ImportanceCoronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts.ObjectiveTo evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor–based model.Design, Setting, and ParticipantsTwo observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands.ExposureTraditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score.Main Outcomes and MeasuresModel discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed.ResultsThe median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, −0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2Conclusions and RelevanceIn 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.

Trisomy 13 is a rare chromosomal disorder in which all or a percentage (mosaicism) of cells contain an extra 13th chromosome. Sinus of Valsalva aneurysms are rare, with an incidence of 0.1% to 3.5% of all congenital heart defects. This article reports the case of a patient with trisomy 13 with a new systolic murmur found to have a ruptured sinus of Valsalva aneurysm diagnosed on coronary computed tomography angiography. This is the first case to report sinus of Valsalva aneurysm rupture secondary to Streptococcus viridans endocarditis in a patient with trisomy 13 syndrome and highlights the importance of coronary computed tomography angiography in noninvasive imaging and surgical planning.

BackgroundThe metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease.MethodsWe studied 1,791 MESA participants of an ancillary study on body composition who had adipokine levels measured (leptin, adiponectin, resistin) at either visit 2 or 3. RC was calculated as non-high density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C), measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed effects models were used to assess the cross-sectional and longitudinal associations between adipokines and levels of RC.ResultsMean (SD) age was 64.5±9.6 years and for body mass index (BMI) was 29.9±5.0 kg/m2; 52.0% were women. In fully adjusted models that included BMI, LDL-C and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.4% (12.0, 16.8) lower RC. With each 1-unit increment in leptin and resistin, there was 4.5% (2.3, 6.6) and 5.1% (1.2, 9.2) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5(4-8) years.ConclusionsLower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for BMI and LDL-C.CLINICAL PERSPECTIVEWhat is new?- Among individuals without history of cardiovascular disease, adiponectin is inversely associated with cross-sectional levels of remnant cholesterol, whereas leptin and resistin are directly associated.- Adiponectin had an inverse association with progression of remnant cholesterol levels over time.What are the clinical implications?- Adiponectin levels were not associated with LDL-C levels but with levels of triglyceride-rich lipoproteins, particularly remnant cholesterol.-Incrementing adiponectin via lifestyle modification and/or pharmacological therapies (i.e. GLP-1 agonists) could be a mechanism to reduce remnant cholesterol levels and ultimately cardiovascular risk.

Coronary computed tomographic angiography (CCTA) is becoming the first-line investigation for establishing the presence of coronary artery disease and, with fractional flow reserve (FFRCT), its haemodynamic significance. In patients without significant epicardial obstruction, its role is either to rule out atherosclerosis or to detect subclinical plaque that should be monitored for plaque progression/regression following prevention therapy and provide risk classification. Ischaemic non-obstructive coronary arteries are also expected to be assessed by non-invasive imaging, including CCTA. In patients with significant epicardial obstruction, CCTA can assist in planning revascularisation by determining the disease complexity, vessel size, lesion length and tissue composition of the atherosclerotic plaque, as well as the best fluoroscopic viewing angle; it may also help in selecting adjunctive percutaneous devices (e.g., rotational atherectomy) and in determining the best landing zone for stents or bypass grafts.