Effect of Eplontersen on Cardiac Structure and Function in Patients With Hereditary Transthyretin Amyloidosis.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is associated with polyneuropathy, cardiomyopathy, or both. The effects of eplontersen on cardiac structure and function were assessed. METHODS AND RESULTS: NEURO-TTRansform was an open-label trial involving 144 adults with ATTRv polyneuropathy (49 patients [34%] with cardiomyopathy) receiving eplontersen throughout and compared with a historical placebo group (n = 60; 30 patients [50%] with cardiomyopathy) from the NEURO-TTR trial at week 65. Treatment effect (eplontersen vs placebo), presented as mean difference (95% confidence interval) was analyzed after adjusting for age, sex, region, baseline value, ATTRv disease stage, previous ATTRv treatment, and V30M transthyretin variant. There were notable differences at baseline between the eplontersen group and historical placebo. In the cardiomyopathy subgroup, 65 weeks of eplontersen treatment was associated with improvement from baseline relative to placebo in left ventricular ejection fraction of 4.3% (95% confidence interval 1.40-21.01; P = .049) and stroke volume 10.64 mL (95% confidence interval 3.99-17.29; P = .002) while the remainder of echocardiographic parameters remained stable. CONCLUSIONS: Eplontersen was associated with stable or improved measures of cardiac structure and function vs historical placebo in patients with ATTRv polyneuropathy and cardiomyopathy. Further investigation into eplontersen's effect on transthyretin amyloid cardiomyopathy is being conducted in the CARDIO-TTRansform trial.

Longitudinal association of epicardial and thoracic adipose tissues with coronary and cardiac characteristics in psoriasis.

Background: s: Psoriasis is a disease of systemic inflammation associated with increased cardiometabolic risk. Epicardial adipose tissue (EAT) and thoracic adipose tissue (TAT) are contributing factors for atherosclerosis and cardiac dysfunction. We strove to assess the longitudinal impact of the EAT and TAT on coronary and cardiac characteristics in psoriasis. Methods: The study consisted of 301 patients with baseline coronary computed tomography angiography (CTA), of which 139 had four-year follow up scans. EAT and TAT volumes from non-contrast computed tomography scans were quantified by an automated segmentation framework. Coronary plaque characteristics and left ventricular (LV) mass were quantified by CTA. Results: When stratified by baseline EAT and TAT volume quartiles, a stepwise significant increase in cardiometabolic parameters was observed. EAT and TAT volumes associated with fibro-fatty burden (FFB) (TAT: ρ = 0.394, P < 0.001; EAT: ρ = 0.459, P < 0.001) in adjusted models. Only EAT had a significant four-year time-dependent association with FFB in fully adjusted models (ß = 0.307 P = 0.003), whereas only TAT volume associated with myocardial injury in fully adjusted models (TAT: OR = 1.57 95 % CI = (1.00-2.60); EAT: OR = 1.46 95 % CI = (0.91-2.45). Higher quartiles of EAT and TAT had increased LV mass and developed strong correlation (TAT: ρ = 0.370, P < 0.001; EAT: ρ = 0.512, P < 0.001). Conclusions: Our study is the first to explore how both EAT and TAT volumes associate with increased cardiometabolic risk profile in an inflamed psoriasis cohorts and highlight the need for further studies on its use as a potential prognostic tool for high-risk coronary plaques and cardiac dysfunction.

DeepHeartCT: A fully automatic artificial intelligence hybrid framework based on convolutional neural network and multi-atlas segmentation for multi-structure cardiac computed tomography angiography image segmentation.

Cardiac computed tomography angiography (CTA) is an emerging imaging modality for assessing coronary artery as well as various cardiovascular structures. Recently, deep learning (DL) methods have been successfully applied to many applications of medical image analysis including cardiac CTA structure segmentation. However, DL requires a large amounts of data and high-quality labels for training which can be burdensome to obtain due to its labor-intensive nature. In this study, we aim to develop a fully automatic artificial intelligence (AI) system, named DeepHeartCT, for accurate and rapid cardiac CTA segmentation based on DL. The proposed system was trained using a large clinical dataset with computer-generated labels to segment various cardiovascular structures including left and right ventricles (LV, RV), left and right atria (LA, RA), and LV myocardium (LVM). This new system was trained directly using high-quality computer labels generated from our previously developed multi-atlas based AI system. In addition, a reverse ranking strategy was proposed to assess the segmentation quality in the absence of manual reference labels. This strategy allowed the new framework to assemble optimal computer-generated labels from a large dataset for effective training of a deep convolutional neural network (CNN). A large clinical cardiac CTA studies (n = 1,064) were used to train and validate our framework. The trained model was then tested on another independent dataset with manual labels (n = 60). The Dice score, Hausdorff distance and mean surface distance were used to quantify the segmentation accuracy. The proposed DeepHeartCT framework yields a high median Dice score of 0.90 [interquartile range (IQR), 0.90-0.91], a low median Hausdorff distance of 7 mm (IQR, 4-15 mm) and a low mean surface distance of 0.80 mm (IQR, 0.57-1.29 mm) across all segmented structures. An additional experiment was conducted to evaluate the proposed DL-based AI framework trained with a small vs. large dataset. The results show our framework also performed well when trained on a small optimal training dataset (n = 110) with a significantly reduced training time. These results demonstrated that the proposed DeepHeartCT framework provides accurate and rapid cardiac CTA segmentation that can be readily generalized for handling large-scale medical imaging applications.

Coronary flow abnormalities in chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Coronary vasomotion abnormalities have been described in small studies but not studied systematically. We aimed to review the present literature and analyze it to improve our understanding of chronic kidney disease (CKD) related-coronary microvascular dysfunction. OBJECTIVE: Coronary flow reserve (CFR) is a well-known measure of coronary vasomotion. We aimed to assess the difference in CFR among participants with and without CKD. METHODS: PubMed, Embase, and Cochrane CENTRAL were systematically reviewed to identify studies that compared CFR in participants with and without CKD. We estimated standardized mean differences in mean CFR reported in these studies. We performed subgroup analyses according to imaging modality, and the presence of significant epicardial coronary artery disease. RESULTS: In 14 observational studies with 5966 and 1410 patients with and without CKD, the mean estimated glomerular filtration rate (eGFR) was 29 ± 04 and 87 ± 25 ml/min/1.73 m2 , respectively. Mean CFR was consistently lower in patients with CKD in all studies and the cumulative mean difference was statistically significant (2.1 ± .3 vs. 2.7 ± .5, standardized mean difference -.8, 95% CI -1.1, -.6, p < .05). The lower mean CFR was driven by both significantly higher mean resting flow velocity (.58 cm/s, 95% CI .17, .98) and lower mean stress flow velocity (-.94 cm/s, 95% CI -1.75, -.13) in studies with CKD. This difference remained significant across diagnostic modalities and even in absence of epicardial coronary artery disease. In meta-regression, there was a significant positive relationship between mean eGFR and mean CFR (p < .05). CONCLUSION: Patients with CKD have a significantly lower CFR versus those without CKD, even in absence of epicardial coronary artery disease. There is a linear association between eGFR and CFR. Future studies are required to understand the mechanisms and therapeutic implications of these findings. KEY POINTS: In this meta-analysis of observational studies, there was a significant reduction in coronary flow reserve in studies with chronic kidney disease versus those without. This difference was seen even in absence of epicardial coronary artery disease. In meta-regression, a lower estimate glomerular filtration rate was a significant predictor of lower coronary flow reserve. Coronary microvascular dysfunction, rather than atherosclerosis-related epicardial disease may underly increase cardiovascular risk in a patient with chronic kidney disease.

Association of S100A8/A9 with Lipid-Rich Necrotic Core and Treatment with Biologic Therapy in Patients with Psoriasis: Results from an Observational Cohort Study.

Psoriasis is a systemic inflammatory disease with an increased risk of atherosclerotic events and premature cardiovascular disease. S100A7, A8/A9, and A12 are protein complexes that are produced by activated neutrophils, monocytes, and keratinocytes in psoriasis. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature previously found to be associated with cardiovascular risk factors and psoriasis severity. LRNC can decrease with biologic therapy, but how this occurs remains unknown. We investigated the relationship between S100 proteins, LRNC, and biologic therapy in psoriasis. S100A8/A9 associated with LRNC in fully adjusted models (ß = 0.27, P = 0.009; n = 125 patients with psoriasis with available coronary computed tomography angiography scans; LRNC analyses; and serum S100A7, S100A8, S100A9, S100A12, and S100A8/A9 levels). At 1 year, in patients receiving biologic therapy (36 of 73 patients had 1-year coronary computed tomography angiography scans available), a 79% reduction in S100A8/A9 levels (‒172 [‒291.7 to 26.4] vs. ‒29.9 [‒137.9 to 50.5]; P = 0.04) and a 0.6 mm2 reduction in average LRNC area (0.04 [‒0.48 to 0.77] vs. ‒0.56 [‒1.8 to 0.13]; P = 0.02) were noted. These results highlight the potential role of S100A8/A9 in the development of high-risk coronary plaque in psoriasis.

Inflammation, coronary plaque progression, and statin use: A secondary analysis of the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study.

BACKGROUND: Statin treatment is a potent lipid-lowering therapy associated with decreased cardiovascular risk and mortality. Recent studies including the PARADIGM trial have demonstrated the impact of statins on promoting calcified coronary plaque. HYPOTHESIS: The degree of systemic inflammation impacts the amount of increase in coronary plaque calcification over 2 years of statin treatment. METHODS: A subgroup of 142 participants was analyzed from the Risk Stratification with Image Guidance of HMG CoA Reductase Inhibitor Therapy (RIGHT) study (NCT01212900), who were on statin treatment and underwent cardiac computed tomography angiography (CCTA) at baseline and 2-year follow-up. This cohort was stratified by baseline median levels of high-sensitivity hs-CRP and analyzed with linear regressions using Stata-17 (StataCorp). RESULTS: In the high versus low hs-CRP group, patients with higher baseline median hs-CRP had increased BMI (median [IQR]; 29 [27-31] vs. 27 [24-28]; p < .001), hypertension (59% vs. 41%; p = .03), and LDL-C levels (97 [77-113] vs. 87 [75-97] mg/dl; p = .01). After 2 years of statin treatment, the high hs-CRP group had significant increase in dense-calcified coronary burden versus the low hs-CRP group (1.27 vs. 0.32 mm2 [100×]; p = .02), beyond adjustment (ß = .2; p = .03). CONCLUSIONS: Statin treatment over 2 years associated with a significant increase in coronary calcification in patients with higher systemic inflammation, as measured by hs-CRP. These findings suggest that systemic inflammation plays a role in coronary calcification and further studies should be performed to better elucidate these findings.

Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis: The Microvascular Disease in Aortic Stenosis (MIDAS) Study.

Importance: Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS). Objective: To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR). Design, Setting, and Participants: In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days. Exposures: MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging. Main Outcomes and Measures: LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity. Results: There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (ß,-0.31; P = .03; ß, 0.41; P = .002, respectively). Stress MBF was associated with hs-cTnT (unadjusted ß, -0.48; P = .005) and log NT-pro BNP (unadjusted ß, -0.37; P = .045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P = .008; 0.62 vs 0.46; P = .02; and -13.47 vs -17.11; P = .006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P = .008). Conclusions and Relevance: In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.

Low coronary flow relative to myocardial mass predicts heart failure in symptomatic hypertensive patients with no obstructive coronary artery disease.

AIMS: The transition from hypertension to heart failure (HF) remains poorly understood. We hypothesized that insufficient perfusion to match global metabolic demand, reflected by a low ratio of myocardial blood flow to global myocardial mass, may be a HF risk marker. METHODS AND RESULTS: A retrospective cohort (n = 346) of patients with hypertension who underwent clinical positron emission tomography (PET) myocardial perfusion imaging for chest pain and/or dyspnoea at Brigham and Women's Hospital (Boston, MA, USA) were studied. Patients without obstructive coronary artery disease by history or PET perfusion (summed stress score <3), HF, cardiomyopathy, or ejection fraction (EF) <40% were followed for HF hospitalization (primary outcome), all-cause death, and their composite. Myocardial blood flow, left ventricular (LV) mass, volumes, and EF were obtained from PET, and a 'flow/mass ratio' was determined as hyperaemic myocardial blood flow over LV mass indexed to body surface area. A lower flow/mass ratio was independently associated with larger end-diastolic (ß = -0.44, P < 0.001) and end-systolic volume (ß = -0.48, P < 0.001) and lower EF (ß = 0.33, P < 0.001). A flow/mass ratio below the median was associated with an adjusted hazard ratio of 2.47 [95% confidence interval (CI) 1.24-4.93; P = 0.01] for HF hospitalization, 1.95 (95% CI 1.12-3.41; P = 0.02) for death, and 2.20 (95% CI 1.39-3.49; P < 0.001) for the composite. CONCLUSION: An integrated physiological measure of insufficient myocardial perfusion to match global metabolic demand identifies subclinical hypertensive heart disease and elevated risk of HF and death in symptomatic patients with hypertension but without flow-limiting coronary artery disease.

Role of Exercise Treadmill Testing in the Assessment of Coronary Microvascular Disease.

OBJECTIVES: The authors aimed to study the sensitivity and specificity of exercise treadmill testing (ETT) in the diagnosis of coronary microvascular disease (CMD), as well as the prognostic implications of ETT results in patients with CMD. BACKGROUND: ETT is validated to evaluate for flow-limiting coronary artery disease (CAD), however, little is known about its use for evaluating CMD. METHODS: We retrospectively studied 249 consecutive patients between 2006 and 2016 who underwent ETT and positron emission tomography within 12 months. Patients with obstructive CAD or left ventricular systolic dysfunction were excluded. CMD was defined as a coronary flow reserve <2. Patients were followed for the occurrence of a first major adverse event (composite of death or hospitalization for myocardial infarction or heart failure). RESULTS: The sensitivity and specificity of a positive ETT to detect CMD were 34.7% (95% CI: 25.4%-45.0%) and 64.9% (95% CI: 56.7%-72.5%), respectively. The specificity of a positive ETT to detect CMD increased to 86.8% (95% CI: 80.3%-91.7%) when only classifying studies with ischemic electrocardiogram changes that lasted at least 1 minute into recovery as positive, although at a cost of lower sensitivity (15.3%; 95% CI: 8.8%-24.0%). Over a median follow-up of 6.9 years (IQR: 5.1-8.2 years), 30 (12.1%) patients met the composite endpoint, including 13 (13.3%) with CMD (n = 98). In patients with CMD, ETT result was not associated with the composite endpoint (P = 0.076). CONCLUSIONS: Our data suggest limited sensitivity of ETT to detect CMD. However, a positive ETT with ischemic changes that persist at least 1 minute into recovery in the absence of obstructive CAD should raise suspicion for the presence of CMD given a high specificity. Further study is needed with larger patient sample sizes to assess the association between ETT results and outcomes in patients with CMD.

Chronic inflammatory diseases and coronary heart disease: Insights from cardiovascular CT.

Epidemiological and clinical studies have demonstrated a consistent relationship between increased systemic inflammation and increased risk of cardiovascular events. In chronic inflammatory states, traditional risk factors only partially account for the development of coronary artery disease (CAD) but underestimate total cardiovascular risk likely due to the residual risk of inflammation. Computed coronary tomography angiography (CCTA) may aid in risk stratification by noninvasively capturing early CAD, identifying high risk plaque morphology and quantifying plaque at baseline and in response to treatment. In this review, we focus on reviewing studies on subclinical atherosclerosis by CCTA in individuals with chronic inflammatory conditions including rheumatoid arthritis (RA), systemic lupus erythematous (SLE), human immunodeficiency virus (HIV) infection and psoriasis. We start with a brief review on the role of inflammation in atherosclerosis, highlight the utility of using CCTA to delineate vessel wall and plaque characteristics and discuss combining CCTA with laboratory studies and emerging technologies to complement traditional risk stratification in chronic inflammatory states.

Coronary vasomotor dysfunction portends worse outcomes in patients with breast cancer.

BACKGROUND: Impaired MFR in the absence of flow-limiting CAD is associated with adverse events. Cardiovascular disease is an important cause of morbidity and mortality in patients with breast cancer. We sought to test the utility of MFR to predict outcomes in a cohort of patients with breast cancer. METHODS: We retrospectively studied consecutive patients with breast cancer or breast cancer survivors who underwent cardiac stress PET imaging from 2006 to 2017 at Brigham and Women's Hospital. Patients with a history of clinically overt CAD, LVEF < 45%, or abnormal myocardial perfusion were excluded. Subjects were followed from time of PET to the occurrence of a first major adverse cardiovascular event (MACE) and all-cause death. RESULTS: The final cohort included 87 patients (median age 69.0 years, 98.9% female, mean MFR 2.05). Over a median follow-up of 7.6 years after PET, the lowest MFR tertile was associated with higher cumulative incidence of MACE (adjusted subdistribution hazard ratio 4.91; 95% CI 1.68-14.38; p = 0.004) when compared with the highest MFR tertile. CONCLUSIONS: In patients with breast cancer, coronary vasomotor dysfunction was associated with incident cardiovascular events. MFR may have potential as a risk stratification biomarker among patients with/survivors of breast cancer.

Heightened splenic and bone marrow uptake of 18F-FDG PET/CT is associated with systemic inflammation and subclinical atherosclerosis by CCTA in psoriasis: An observational study.

BACKGROUND AND AIMS: Psoriasis is an immune-mediated inflammatory disease with increased risk of myocardial infarction. Preclinical studies in psoriasis models show an association between chronic inflammation and immune cell proliferation in the spleen and bone marrow (BM). We sought to test the hypothesis that splenic and BM 18F-fluorodeoxyglucose (18F-FDG) uptake is heightened in psoriasis and that higher uptake associates with systemic inflammation and subclinical atherosclerotic disease measures in this cohort. METHODS: Multimodality imaging and biomarker assays were performed in 240 participants (210 with psoriasis and 30 healthy). Splenic and BM uptake was obtained using 18F-FDG positron emission tomography/computed tomography (PET/CT). Coronary artery plaque characteristics including non-calcified burden (NCB) and lipid rich necrotic core (LRNC) were quantified using a dedicated software for CT angiography. All analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA). RESULTS: Splenic and BM 18F-FDG uptake was increased in psoriasis (vs. healthy volunteers) and significantly associated with proatherogenic lipids, immune cells and systemic inflammation. Higher splenic 18F-FDG uptake associated with higher total coronary burden (ß = 0.37; p<0.001), NCB (ß = 0.39; p<0.001), and LRNC (ß = 0.32; p<0.001) in fully adjusted models. Similar associations were seen for BM 18F-FDG uptake in adjusted models (ß = 0.38; ß = 0.41; ß = 0.24; respectively, all p<0.001). CONCLUSIONS: Heightened splenic and BM uptake of 18F-FDG is associated with proatherogenic lipids, immune cells, inflammatory markers and coronary artery disease. These findings provide insights into atherogenic mechanisms in psoriasis and suggest that immune cell proliferation in the spleen and BM is associated with subclinical atherosclerosis.

The relationship between systemic inflammation and increased left ventricular mass is partly mediated by noncalcified coronary artery disease burden in psoriasis.

OBJECTIVE: Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB). METHODS: We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA. RESULTS: The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m2.7(3.8), 2nd tertile:25.5 g/m2.7(3.8), 3rd tertile:27.7 g/m2.7(5.5), p<0.001]. Both GlycA (ß=0.24, p = 0.001) and NCB (ß=0.50, p<0.001) associated with LV mass in models adjusted for age, sex, hypertension, hypertension therapy, lipid therapy, biologic therapy for psoriasis, waist:hip ratio, psoriasis disease duration and severity. In multivariable-adjusted mediation analyses, NCB accounted for 32% of the GlycA-LV mass relationship. Finally, over one year, change in NCB independently associated with change in LV mass (ß=0.25, p = 0.002). CONCLUSIONS: Both systemic inflammation and coronary artery NCB were associated with LV mass beyond cardiovascular risk factors in psoriasis. Furthermore, a substantial proportion of the inflammatory-LV mass relationship was mediated by NCB. These findings underscore the possible contribution of early coronary artery disease to the relationship between systemic inflammation and LV mass.

Sleep duration, baseline cardiovascular risk, inflammation and incident cardiovascular mortality in ambulatory U.S. Adults: National health and nutrition examination survey.

INTRODUCTION: The interplay between sleep duration and inflammation on the baseline and incident cardiovascular (CV) risk is unknown. We sought to evaluate the association between sleep duration, C-reactive protein (CRP), baseline CV risk, and incident CV mortality. METHODS: We used data from the National Health and Nutrition Examination Survey 2005-2010 linked with the cause of death data from the National Center for Health Statistics for adults aged ≥18 years. The associations between self-reported sleep duration and CRP, 10-year atherosclerotic CV disease risk score (ASCVD) and CV mortality were assessed using Linear, Poisson and Cox proportional hazard modeling as appropriate. RESULTS: There were 17,635 eligible participants with a median age of 46 years (interquartile range [IQR] 31, 63). Among them, 51.3% were women and 46.9% were non-Hispanic Whites. Over a median follow-up of 7.5 years (IQR 6.0, 9.1), 350 CV deaths occurred at an incident rate of 2.7 per 1000-person years (IQR 2.4, 3.0). We observed a U-shaped associations between sleep duration and incident CV mortality rate (P-trend=0.011), sleep duration and 10-year ASCVD risk (P-trend <0.001), as well as sleep duration and CRP (P-trend <0.001). A self-reported sleep duration of 6-7 hours appeared most optimal. We observed that those participants who reported <6 or >7 hours of sleep had higher risk of CV death attributable to inflammation after accounting for confounders. CONCLUSIONS: There was a U-shaped relationship of incident CV mortality, 10-year ASCVD risk, and CRP with sleep duration. These findings suggest an interplay between sleep duration, inflammation, and CV risk.

Abdominal subcutaneous adipose tissue negatively associates with subclinical coronary artery disease in men with psoriasis.

OBJECTIVE: Understand the relationship between abdominal subcutaneous adipose tissue (ASAT) and coronary atherosclerosis defined as noncalcified and lipid-rich necrotic core burden in psoriasis. METHODS: We performed a cross-sectional study of 232 participants (92 women) with psoriasis and without known cardiovascular disease. Participants underwent coronary computed tomography angiography to characterize coronary atherosclerosis burden and low dose abdominal computed tomography to quantify subcutaneous and visceral adipose tissue. Fat depot volumes were first adjusted for each participant's BMI (ASATadjBMI). RESULTS: In women, there was a positive correlation between ASATadjBMI and systemic inflammation as assessed by hs-C-reactive protein (r=0.30; p=.004) and GlycA (r=0.29; p=.007) as well as total cholesterol (r=0.24; p=.02) and low-density lipoprotein cholesterol (r=0.22; p=.04). In men, ASATadjBMI correlated with hs-C-reactive protein (r=0.18; p=.04) and insulin resistance (r=0.17; p=.04). In models fully adjusted for traditional cardiovascular risk factors, ASATadjBMI negatively associated with noncalcified and lipid-rich necrotic core burden in men (ß= -0.17; p=.03, ß= -0.20; p=.03, respectively), but not women (ß= -0.06; p=.57, ß= 0.09; p=.49, respectively) with psoriasis. CONCLUSIONS: For a given BMI, ASAT negatively associated with coronary atherosclerosis burden in male participants with psoriasis. The observed sex-specific effects warrant further study of ASAT in states of chronic inflammation.

Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification.

OBJECTIVE: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease. METHODS: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/µL [to convert to cells ×109/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment-including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein-for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality. RESULTS: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score. CONCLUSION: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.