OBJECTIVES:Machine-learning-based clinical risk prediction models are increasingly used to support decision-making in healthcare. While class-imbalance correction techniques are commonly applied to address rare outcomes, their impact on probabilistic calibration remains insufficiently understood. This study evaluated the effect of widely used resampling strategies on both discrimination and calibration across real-world clinical prediction tasks. MATERIALS AND METHODS:Ten clinical datasets spanning diverse medical domains and including over 600 000 patients were analyzed. Multiple machine-learning model families were evaluated. Models were trained on original data and using 3 1:1 class-imbalance correction strategies (synthetic minority oversampling technique, random undersampling, and random oversampling). Performance was assessed on held-out data using discrimination and calibration metrics. RESULTS:Resampling had no positive impact on predictive performance. Changes in area under the receiver operating characteristic curve (ROC-AUC) and precision-recall AUC were small and inconsistent (ROC-AUC: -0.002 to -0.01; PR-AUC: -0.10 to -0.03), with no method showing systematic improvement. In contrast, calibration was consistently degraded. Resampled models showed higher Brier scores (increase 0.029-0.080) and marked deviations in calibration intercept and slope, indicating distorted predicted risks despite preserved ranking performance. DISCUSSION:Across diverse clinical datasets, resampling primarily altered the implicit class prior learned during training, leading to miscalibration when models were evaluated. The consistent dissociation between discrimination and calibration highlights that rank-based metrics alone are insufficient for evaluating clinical utility. Gains from imbalance correction can typically be reproduced by threshold adjustment without distorting predicted probabilities. CONCLUSION:Common 1:1 class-imbalance correction techniques do not improve discrimination and may substantially degrade calibration, limiting their suitability for clinical risk prediction where accurate probabilities are essential.

Excess adiposity is a major risk factor for hypertension and heart disease. Brown fat is associated with protection from cardiovascular pathology, but whether this relationship is causal remains unknown. In this work, we investigate the role of mouse beige fat, as a model of human inducible brown fat, in adipocyte-vascular cross-talk. Using adipocyte-specific Prdm16 knockout mice with a loss of beige adipocyte identity, we discovered marked remodeling of perivascular adipose tissue, increased vascular reactivity, and elevated blood pressure. We show that the circulating enzyme QSOX1 is derepressed in Prdm16-deficient adipocytes, and deletion of Qsox1 in Prdm16 conditional knockout mice prevented vascular fibrosis and normalized vascular reactivity. These results demonstrate a key role for beige adipocytes in blood pressure regulation and identify QSOX1 as an important mediator of adipocyte-vascular cross-talk.

OBJECTIVES:In addition to medical considerations, economic factors are increasingly influencing hospital planning. While guidelines suggest ICU room design and layout likely affect outcomes, data supporting current recommendations are scarce. The aim of this study was to investigate the association of shared rooms vs. single rooms, high vs. low visibility, and distances of nurses' and doctors' charting areas to patients' rooms with mortality and length of stay in a large, mixed-discipline cohort. DESIGN:Retrospective observational cohort study. SETTING:Four ICUs at the University Medical Center Mannheim, Germany. PATIENTS:Critically ill adults with ICU admission between January 2019 and May 2022 for at least 24 hours. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Associations of the index variables with in-hospital mortality and ICU length of stay were assessed by multivariate regression, adjusting for biological sex, Simplified Acute Physiology Score II, need for vasopressors, need for ventilation, and medical vs. surgical admission. Five thousand two hundred ninety-three patient stays with a mortality rate of 18% and a mean length of stay of 6.3 ± 9.2 days in survivors were eligible for this analysis. In the overall cohort, none of the index variables showed associations with mortality. Patients admitted to single rooms showed a mean length of stay increase by 0.81 days (95% CI, 0.04-1.57 d; p = 0.039) compared with shared rooms with up to three beds. CONCLUSIONS:In this mixed cohort of medical and surgical ICUs, neither single rooms compared with shared rooms, high-visibility rooms compared with low-visibility rooms, nor distances to nurses' or doctors' charting areas were associated with mortality. The observed increase in length of stay associated with single room admission highlights the need to balance privacy and infection control benefits with potential implications for ICU capacity and operational efficiency.

ObjectiveTo evaluate whether early variability in mean corpuscular volume (MCV) during the first five days of intensive care unit stay is associated with in-hospital mortality in critically ill patients.MethodsWe retrospectively studied all adult patients treated on intensive care units (ICU) at the University Medical Center Mannheim between 2018 and 2022 with more than one MCV measurement within the first five days, including at least one on the day of admission. The primary endpoint was in-hospital mortality. MCV variation, expressed as the coefficient of variation (CV), was analyzed using generalized additive models, multivariable logistic and Cox regression.ResultsAmong 5,327 patients (median age 66 years, 38.9% female, mortality 28.3%), median MCV variation was 1.86% (IQR 1.15-2.74%). Patients with high variation (CV >2.5%) showed higher mortality rates (34.7% vs. 20.1%, p<0.0001). In a baseline-adjusted model, this association remained significant (OR 1.65, 95% CI 1.46-1.87, p<0.001). By contrast, baseline MCV at admission showed a univariat association with mortality but was not independently associated with mortality after multivariate adjustment (OR 1.02, 95% CI 0.98-1.06, p=0.31). Determinants of high variation (>2.5%) included elevated CRP, transfusion volume, respiratory disease, and fluid balance disturbances. In a second, severity-adjusted model including lactate, mean arterial pressure, and fluid balance, the previously observed association between high MCV variation and mortality was no longer significant (adjusted OR 1.16, p = 0.57, CI: 0.84-1.59).ConclusionsEarly variation in MCV during the initial five days after ICU admission is associated with in-hospital mortality in unadjusted analyses. However, this relationship is not independent of established clinical severity markers, suggesting that MCV variability reflects disease severity. Nonetheless, MCV variation may serve as a readily accessible adjunctive marker of physiological instability in critically ill patients, meriting further investigation.

Accurate short-term mortality prediction is essential for optimizing ICU management and improving patient outcomes. Many existing models rely on static data and do not reflect the dynamic progression of critical illness. This study aimed to develop and validate an interpretable machine learning algorithm that enables dynamic 48-hour mortality prediction throughout the ICU stay. We conducted a retrospective cohort study using electronic health records of 9,786 ICU patients treated between 2018 and 2022 at a German university hospital. A machine learning model was developed to predict 48-hour mortality, updated every 24 hours during the ICU stay. We trained and evaluated a Light Gradient-Boosting Machine using nested cross-validation and assessed performance via area under the receiver operating characteristic curve. External validation was performed on the MIMIC-IV database. Feature importance was analyzed using SHAP values. Here, we show that the Light Gradient-Boosting Machine algorithm (LGBM-48h) achieves AUROCs of 0.909 (95

Background Cardiogenic shock (CS) is a critical condition associated with high mortality rates, making prompt diagnosis essential for timely interventions that may improve patient outcomes. The Society for Cardiovascular Angiography and Interventions (SCAI) SHOCK Stage Classification is a validated tool for assessing CS and predicting patient outcomes. Here, we evaluated how different parameter definitions affect SCAI stage adjudication, hypothesizing that variations may influence stage determination and the overall assessment of CS.Methods All patients diagnosed with CS or conditions leading to CS at the University Medical Center Mannheim, Germany, from January 2018 to June 2022 were included in the study. SCAI SHOCK stages were assigned retrospectively on the basis of 4 previously published studies. The distribution of SCAI SHOCK stages, outcomes, classification concordance, and predictive performance were assessed.Results From January 2018 to June 2022, we identified 1303 patients on the basis of International Classification of Diseases, Tenth Revision (ICD-10) codes. Of these, 1281 patients (98.2%) were classified into SCAI SHOCK stages according to all 4 classification frameworks. While the assignment of SCAI SHOCK stages and associated mortality rates varied among the frameworks, Kendall's W indicated moderate to strong overall classification agreement (W=0.70). There was no significant difference in predictive performance for in-hospital death.Conclusions Our study demonstrates a moderate to strong concordance and comparable prognostic performance across different SCAI SHOCK Stage Classification frameworks in evaluating patients with CS. Despite differences in stage assignments, all frameworks effectively stratified patients by clinical severity. Comparable stage assignment in retrospective studies requires further standardization of the SCAI SHOCK Stage Classification system.

Atherosclerosis, a major contributor to cardiovascular morbidity and mortality, is characterized by chronic inflammation of the arterial wall. This inflammatory process is initiated and maintained by both innate and adaptive immunity. Dendritic cells (DCs), which are antigen-presenting cells, play a crucial role in the development of atherosclerosis and consist of various subtypes with distinct functional abilities. Following the recognition and binding of antigens, DCs become potent activators of cellular responses, bridging the innate and adaptive immune systems. The modulation of specific DC subpopulations can have either pro-atherogenic or atheroprotective effects, highlighting the dual pro-inflammatory or tolerogenic roles of DCs. In this work, we provide a comprehensive overview of the evolving roles of DCs and their subtypes in the promotion or limitation of atherosclerosis development. Additionally, we explore antigen pulsing and pharmacological approaches to modulate the function of DCs in the context of atherosclerosis.

Sepsis-associated coagulopathy increases risk of mortality. Impairment of the anticoagulant protein C (PC) pathway may contribute to the thrombotic phenotype in coronavirus disease 2019 (COVID-19) sepsis. This study assessed the functionality of this pathway in COVID-19 and non-COVID sepsis by measuring its key enzymes, thrombin and activated PC (APC). The study population included 30 patients with COVID-19, 47 patients with non-COVID sepsis, and 40 healthy controls. In healthy controls, coagulation activation and subsequent APC formation was induced by 15 µg/kg recombinant activated factor VII one hour before blood sampling. APC and thrombin in plasma were measured using oligonucleotide-based enzyme capture assays. The indirect thrombin markers prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) were also measured. Compared with stimulated healthy controls, median thrombin, F1+2, and TAT levels were higher in patients with COVID-19 (up to 6-fold, p < 2 × 10−6) and non-COVID sepsis (up to 4.7-fold, p < 0.010). APC levels were 2.4-fold higher in patients with COVID-19 (7.44 pmol/L, p = 0.011) and 3.4-fold higher in non-COVID sepsis patients (10.45 pmol/L, p = 2 × 10−4) than in controls (3.08 pmol/L). Thrombin markers and APC showed correlation in both COVID-19 (r = 0.364–0.661) and non-COVID sepsis patients (r = 0.535–0.711). After adjustment for PC levels, median APC/thrombin, APC/F1+2, and APC/TAT ratios were 2-fold (p = 0.036), 6-fold (p = 3 × 10−7) and 3-fold (p = 8 × 10−4) lower in the COVID-19 group than in the non-COVID sepsis group, and the latter two were also lower in the COVID-19 group than in stimulated healthy controls. In conclusion, it was found that a comparatively lower anticoagulant APC response in COVID-19 patients as compared to non-COVID sepsis patients, potentially linked to endothelial dysfunction, contributes to the prothrombotic phenotype of COVID-19 sepsis.

BACKGROUND:Cardiogenic shock (CS) is characterized by high mortality and requires accurate prognostic tools to predict outcomes and guide treatment. The Society for Cardiovascular Angiography and Interventions (SCAI) shock classification indicates shock severity and can be used for outcome prediction. OBJECTIVE:Here, we compare the prognostic performance of SCAI shock classification determined on admission and during intensive care unit (ICU) stay. METHODS:We included all patients with CS or conditions associated with developing CS based on ICD codes. SCAI shock stages were determined on admission and during the first 5 days of ICU stay. Receiver operating curves were used to compare the prognostic performance of SCAI stages on admission, SCAI stages during ICU stay and CS evolution (absent, resolved, persistent and new onset) for in-hospital mortality. RESULTS:Between 01/2018 and 06/2022, 1303 patients were identified and 862 patients were included. On admission, 50.6 % patients had SCAI shock stage A, 3.9 % SCAI shock stage B, 17.7 % SCAI shock stage C, 7.0 % SCAI shock stage D and 20.8 % SCAI shock stage E. Shock stage distribution changed dynamically during ICU stay. Compared to SCAI stage on admission (AUC 0.80; 95 % CI 0.77-0.83), highest achieved SCAI stage during ICU (AUC 0.86, 95 % CI 0.83-0.89, p < 0.0001) and shock evolution (AUC 0.87, 95 % CI 0.85-0.90, p < 0.0001) yielded better prognostic performance. CONCLUSIONS:SCAI shock stages changed dynamically during ICU stay, and prognostic performance can be improved by considering highest achieved SCAI shock stage as well as the evolution of CS compared to SCAI shock stage on admission.

Introduction Endothelial dysfunction has been shown to play a role in severe COVID-19, the pathophysiology of which may be attributed to a myriad of factors including unmitigated immune and inflammatory response, viral-induced injury to the endothelium, end-stage organ failure, and coagulopathy. In addition, severe COVID-19 is most often seen in patients with multiple comorbidities, which themselves are often associated with endothelial dysfunction (such as myocardial and renal failure, as well as thrombotic disorders). However, the literature is still emerging on this topic and there appears to be no consensus on the extent to which endothelial dysfunction plays a role in severe COVID-19.

Although brown fat is strongly associated with a constellation of cardiometabolic benefits in animal models and humans, it has also been tied to cancer cachexia. In humans, cancer-associated cachexia increases mortality, raising the possibility that brown fat in this context may be associated with increased cancer death. However, the effect of brown fat on cancer-associated cachexia and survival in humans remains unclear. Here, we retrospectively identify patients with and without brown fat on fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET) scans obtained as part of routine cancer care and assemble a cohort to address these questions. We did not find an association between brown fat status and cachexia. Furthermore, we did not observe an association between brown fat and increased mortality in patients with cachexia. Our analyses controlled for confounding factors including age at cancer diagnosis, sex, body mass index, cancer site, cancer stage, outdoor temperature, comorbid conditions (heart failure, type 2 diabetes mellitus, coronary artery disease, hypertension, dyslipidemia, cerebrovascular disease), and β-blocker use. Taken together, our results suggest that brown fat is not linked to cancer-associated cachexia and does not worsen overall survival in patients with cachexia.NEW & NOTEWORTHY This study finds that brown fat is not linked to cancer-associated cachexia. Moreover, this work shows that brown fat does not worsen overall survival in patients with cachexia.

Brown adipose tissue (BAT) regulates metabolic physiology. However, nearly all mechanistic studies of BAT protein function occur in a single inbred mouse strain, which has limited the understanding of generalizable mechanisms of BAT regulation over physiology. Here, we perform deep quantitative proteomics of BAT across a cohort of 163 genetically defined diversity outbred mice, a model that parallels the genetic and phenotypic variation found in humans. We leverage this diversity to define the functional architecture of the outbred BAT proteome, comprising 10,479 proteins. We assign co-operative functions to 2,578 proteins, enabling systematic discovery of regulators of BAT. We also identify 638 proteins that correlate with protection from, or sensitivity to, at least one parameter of metabolic disease. We use these findings to uncover SFXN5, LETMD1, and ATP1A2 as modulators of BAT thermogenesis or adiposity, and provide OPABAT as a resource for understanding the conserved mechanisms of BAT regulation over metabolic physiology.

Although arteries and atherosclerotic plaques are three-dimensional structures, the evaluation of plaque size and morphology in preclinical models of atherosclerosis is typically performed in two dimensions by histological analysis. Here, we describe a method to visualize arteries and atherosclerotic plaques in three dimensions. This method combines AdipoClear, a procedure that achieves whole tissue immunolabeling and clearing, and light-sheet fluorescence microscopy, which generates a three-dimensional reconstruction of vessel architecture including atherosclerotic lesions if present. This approach reveals the volume, geometry, acellular component and surface of atherosclerotic plaques as well as the spatial position of the lesion in relation to the affected artery.

Purpose: Previous studies have shown positive effects of intensive low-density lipoprotein (LDL)-lowering therapy on atheroma volume using invasive intravascular ultrasound. This study describes the changes in coronary plaque composition on coronary computed tomography angiography in patients treated with proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. Materials and Methods: In this prospective study, coronary plaques were analyzed using third-generation dual-source computed tomography before and after 1 year of PCSK9-inhibitor treatment. Plaque markers included total plaque volume (TPV), calcified plaque volume (CPV), noncalcified plaque volume (NCPV), lumen volume and vessel volume (VV), minimal luminal area (MLA), minimal lumen diameter (MLD), corrected coronary opacification, eccentricity, remodeling index, and functional plaque parameters. Primary endpoint was defined as change in TPV; the secondary endpoint was TPV or CPV regression or nominal change in plaque parameters. Results: We analyzed 74 coronary plaques in 23 patients (60±9 y, 65% male). After 1 year of PCSK9-inhibitor treatment, LDL was reduced from 148 to 66 mg/dL (P<0.0001). Significant changes were found for VV (196 to 215 mm3, P=0.0340), MLA (3.1 to 2.6 mm2, P=0.0413), and MLD (1.7 to 1.4 mm, P=0.0048). TPV, CPV, NCPV, lumen volume, and functional plaque parameters did not change significantly (P>0.05). Conclusions: Coronary artery plaque analysis by coronary computed tomography angiography highlights that LDL lowering therapy affects plaque composition. The primary endpoint of TPV change was not reached; however, VV, MLA, and MLD changed significantly.

Introduction: Activation of the plasmatic coagulation system is a major contributor to acute myocardial infarction (AMI). Markers of plasmatic coagulation and thrombin activation are correlated with clinical, laboratory and outcome parameters. In this study, we sought to evaluate if the catalytically active coagulation factors thrombin and activated protein C (APC) can be measured in patients with AMI and whether there are associations with laboratory or clinical parameters. Methods: Thrombin and APC was quantified using oligonucleotide-enzyme-capture assays (OECAs) in 132 patients presenting with AMI immediately before and 24 h after percutaneous coronary intervention (PCI). Results: APC was measured above the lower limit of quantification (LLOQ) in 43 (32.6%) patients before PCI (day 0) and in 55 (41.7%) patients on the following day (day 1). Thrombin was measured in 62 (47.0%) patients on day 0 and 60 (45.5%) on day 1. Both APC and thrombin were correlated with markers of thrombin generation including F1 + 2 and TAT. Additionally, APC values correlated with CK and CK-MB while thrombin correlated with CK and troponin I after PCI. APC levels above a cutoff of 0.141 ng/ml after PCI, but not thrombin, predicted 30 day major adverse cerebrovascular events. Conclusion: Both thrombin and APC were elevated above the LLOQ in a subset of patients with AMI before and after PCI and correlated with surrogate markers of myocardial injury. Our results indicate that enzymatically active APC and thrombin are present in the circulation of patients with AMI.

White fat stores excess energy, whereas brown and beige fat are thermogenic and dissipate energy as heat. Thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, although the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear1,2. Here we retrospectively categorized 134,529 18F-fluorodeoxyglucose positron emission tomography–computed tomography scans from 52,487 patients, by presence or absence of BAT, and used propensity score matching to assemble a study cohort. Scans in the study population were initially conducted for indications related to cancer diagnosis, treatment or surveillance, without previous stimulation. We report that individuals with BAT had lower prevalences of cardiometabolic diseases, and the presence of BAT was independently correlated with lower odds of type 2 diabetes, dyslipidemia, coronary artery disease, cerebrovascular disease, congestive heart failure and hypertension. These findings were supported by improved blood glucose, triglyceride and high-density lipoprotein values. The beneficial effects of BAT were more pronounced in individuals with overweight or obesity, indicating that BAT might play a role in mitigating the deleterious effects of obesity. Taken together, our findings highlight a potential role for BAT in promoting cardiometabolic health. Retrospective analysis of 18F-FDG PET/CT scans from over 50,000 patients reveals correlations between presence of brown adipose tissue and lower odds of having cardiometabolic conditions, such as type 2 diabetes, cardiovascular disease and hypertension.

The association of brown adipose tissue (BAT) and body fat distribution and their combined effects on metabolic health in humans remains unknown. Here, we retrospectively identify individuals with and without BAT on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and assemble a propensity score-matched study cohort to compare body fat distribution and determine its role in mediating the benefits of brown fat. We find that BAT is associated with lower amounts of visceral adipose tissue and higher amounts of subcutaneous adipose tissue, resulting in less central obesity. In addition, BAT is independently associated with lower blood glucose and white blood cell count, improved lipids, lower prevalence of type 2 diabetes mellitus, and decreased liver fat accumulation. These observations are most prominent in individuals with central obesity. Our results support a role of BAT in protection from visceral adiposity and improved metabolic health.

Purpose: The study aimed to compare morphological and anatomic plaque markers derived from coronary computed tomography angiography (cCTA) for the detection of lesion specific ischemia with invasive instantaneous wave free ratio (iFR (R)) as the reference standard. Methods: In our prospective study, we enrolled patients with suspected coronary artery disease (CAD), who had undergone cCTA, using a low-dose third-generation dual-source CT and invasive coronary angiography (ICA) with iFR (R) measurement. Various plaque markers were assessed on cCTA. Discriminatory power of these markers for the detection of ischemia-inducing coronary artery disease was evaluated against invasive iFR (R). Results: Our study cohort included 39 patients (66.6 +/- 12.0 years, 72 % male). Among 54 vessel-specific lesions, 15 lesions (28 %) were characterized as hemodynamically significant by iFR (R) <= 0.89. The area under the curve (AUC) of lesion length/ minimal luminal diameter(4) (LL/MLD4) (0.84) was greater than the AUC of minimal luminal area (MLA) (0.82), MLD (0.81), the degree of luminal diameter stenosis (0.81), corrected coronary opacification (CCO) (0.79), remodeling index (RI) (0.75), and percentage aggregate plaque volume (%APV) (0.72). LL, vessel volume (VV), total plaque volume (TPV), calcified and non-calcified plaque volume (CPV and NCPV) did not reach statistical significance and were unable to discriminate between vessels with and without ischemia-inducing coronary stenosis. Conclusion: LL/MLD4, MLA, MLD, the degree of luminal diameter stenosis, CCO, RI, and %APV derived from cCTA can support the detection of hemodynamically significant coronary stenosis as compared with iFR (R), with LL/MLD4 showing the greatest discriminatory power.

Background: Percutaneous coronary intervention (PCI) represents an important alternative to coronary bypass surgery for the treatment of patients with complex coronary artery disease and high perioperative risk. Protected percutaneous coronary intervention applies temporary percutaneous ventricular assist devices to mitigate potential hemodynamic compromise in high-risk patients. The Impella system is currently the most commonly used device for protected percutaneous coronary intervention and showed improved hemodynamic parameters in earlier trials. Methods: This study was designed as a retrospective, observational multi-center registry conducted in ten hospitals in Germany. We included consecutive patients undergoing protected high-risk percutaneous coronary intervention with Impella support. The primary endpoint was defined as the occurrence of a major adverse cardiac event defined as all-cause mortality, ST-elevation myocardial infarction, or stroke during a postprocedural 180-day follow-up period. Results: In total, 157 patients (80.3% male; mean age 71.8 ± 10.8 years) were included in the present study, and 180-day follow-up was complete for 149 patients (94.9%). At baseline, the patients had a median left ventricular ejection fraction of 39.0% (interquartile range, 25.0–50.0%). The median SYNergy between PCI with TAXUS and Cardiac Surgery-Score I was 33.0 (interquartile range, 24.0–40.5) and the median EuroSCORE II was 7.2% (interquartile range, 3.2-17.1%). During postprocedural follow-up, 34 patients (22.8%) suffered a major adverse cardiac event. All-cause mortality was 18.1% (27 patients). Nine patients (6.0%) sustained a ST-elevation myocardial infarction, while 4 patients (2.7%) had a stroke. Conclusions: Patients undergoing protected high-risk percutaneous coronary intervention with Impella support showed an acceptable 180-day clinical outcome regarding major adverse cardiac event and mortality.

White fat stores excess energy, while brown and beige fat dissipate energy as heat 1 . These thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, though the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear 2, 3, 4 . Here, we categorized 139,224 18 F-FDG PET/CT scans from 53,475 patients by presence or absence of BAT and used propensity score matching to assemble a study cohort. Individuals with BAT showed lower prevalences of cardiometabolic diseases. Additionally, BAT independently correlated with lower odds of type II diabetes, coronary artery disease and congestive heart failure. These findings were supported by improved glucose, triglyceride and high-density lipoprotein values. The effects of BAT were more pronounced in overweight and obesity, indicating that BAT can offset the deleterious effects of obesity. Strikingly, we also found lower rates of hypertension among patients with BAT. Studies in a mouse model with genetic ablation of beige fat demonstrated elevated blood pressure due to increased sensitivity to angiotensin II in peripheral resistance arteries. In addition to highlighting a role for BAT in promoting overall cardiometabolic health, this study reveals a new link between thermogenic adipose tissue and blood pressure regulation.