Skip to content

#心血管代谢

Today 0 items
Oct 15Thu
  1. Nature76

    Artificial intelligence-enabled clinical phenotyping of human brown fat.

    Brown adipose tissue (BAT) presence is linked to lower prevalence of cardiovascular and psychiatric diseases across a cohort of 101,243 patients from a large cancer centre. Machine learning quantification of BAT activity in roughly 8,700 patients showed higher activity, especially in the axillary depot, correlates with lower odds of cardiometabolic diseases and healthier white fat distribution. Angiotensin receptor blocker use associated with BAT presence, and losartan increased brown adipocyte activity and whole-body energy expenditure, supporting drug repurposing to activate BAT in humans.

    Why it matters: AI phenotyping of 101,243 patients links brown fat to reduced cardiometabolic disease and identifies losartan as a candidate BAT activator.

  2. doi.org40

    Physiological Responses to Intermittent Environmental Heat Stress in Mice

    Intermittent heat stress in C57BL/6J mice (30-37°C, 3 h/day, 4 days/week, up to 4 weeks) produced a neuroendocrine stress response with 2-4-fold higher plasma corticosterone, >50% lower epinephrine, and ~10 mmHg lower systolic and diastolic blood pressure. Despite >30% depletion of circulating immune cells, leukocyte rolling and adhesion to vascular endothelium rose more than 3-fold, indicating endothelial activation that precedes cardiovascular dysfunction. Cardiac systolic function, arterial stiffness, plasma lipids, and organ injury markers were largely unaffected.

  3. nature.com71

    Artificial intelligence-enabled clinical phenotyping of human brown fat

    AI-enabled quantification of brown adipose tissue (BAT) activity in humans links higher BAT activity to a healthier metabolic profile and lower rates of psychiatric disease. The same approach identified existing pharmacologic agents that could be repurposed to activate BAT in humans. The work provides a scalable way to phenotype BAT and connect it to clinical outcomes and drug targets.

    Why it matters: It shows AI-based BAT phenotyping at scale, linking brown fat to metabolic and psychiatric outcomes and to repurposable drugs.

  4. nature.com81

    Capillary-selective vasodilation through myosin inhibition halts ischaemic cascades

    Myosin inhibition produces vasodilation that is selective for capillaries and halts the cascades that follow ischaemia, as reported in this work on microvascular obstruction. The approach targets the capillary level, where pericyte-mediated constriction has been linked to no-reflow after ischaemia in the brain, heart and kidney. No quantitative outcome data are reported here.

    Why it matters: It addresses capillary-level no-reflow, a mechanism implicated in stroke, myocardial infarction and kidney injury.

  5. nature.com59

    Overlooked brown fat in our bodies linked to wide range of health benefits

    People with active brown fat are less affected by a range of health issues, including type 2 diabetes, depression and anxiety, according to the largest study of its kind, covering more than 100,000 people scanned with PET and CT. An artificial-intelligence model quantified active brown fat from the scans, showing that more active brown fat tracked with greater protection from disorders and diseases. The work, published in Nature, expands the list of benefits linked to brown fat, though causation is not yet shown.

Oct 13Tue
  1. JAMA68

    Development and Validation of an Adult Medical Urgency Score for US Donor Heart Allocation.

    A continuous medical urgency score for US donor heart allocation, the US Candidate Risk Score (US-CRS), built from 5 laboratory values and 4 therapeutic devices, outperformed the current 6-status system for predicting 6-week waitlist mortality (test-set mean time-dependent AUC 0.807 vs 0.693). In a match-run simulation of 45,530 donor hearts, US-CRS-based allocation moved 67% of transplant recipients down in rank order and raised 6-week transplant-censored mortality for the first-listed candidate from 11.2% to 15.7%, indicating the sickest candidates are prioritized earlier.

    Why it matters: It offers a validated, objective alternative to the current 6-status US donor heart allocation system.

Oct 12Mon
  1. Alzheimers Dement42

    The effects of improved access to diabetes medications on risk of Alzheimer's disease and related dementias.

    A dynamic microsimulation using 10 years of data on Americans aged 51 and older with diabetes estimates that increased utilization of GLP1s and SGLT2s by people with diabetes and HbA1c > 7 could avert 76,000-201,000 cases of Alzheimer's disease and related dementias over 10 years. Risk reduction is largest for Black and Hispanic individuals and those with HbA1c > 8, pointing to access and adherence for high-risk groups as the target with the largest benefit.

  2. Sci Adv57

    ALIX-dependent small extracellular vesicles from tissue-resident mesenchymal cells regulate pancreatic β cell proliferation in obesity.

    Deleting ALIX in PDGFRα+ mesenchymal progenitors of mice blocks small extracellular vesicle production and disrupts metabolism. In high-fat diet-induced obesity, these knockout mice gained less weight and had smaller subcutaneous adipocytes, yet showed impaired glucose tolerance with reduced pancreatic β cell area and smaller islets despite normal insulin sensitivity. Conditioned-media sEVs from knockout mesenchymal stem cells lost the ability to promote β cell proliferation, identifying mesenchymal sEVs as regulators of β cell proliferation in obesity.

    Why it matters: Identifies mesenchymal-cell-derived vesicles as a required signal for pancreatic β cell proliferation in obesity.

Oct 10Sat
  1. Nature80

    Dynamics of human cardiogenesis and its disruption in trisomy 21.

    A spatially resolved single-cell multiomics map of the developing human heart defines 21 tissue niches, resolves three pacemaker cell subtypes in the sinoatrial node, and traces maturation trajectories of atrial and ventricular cardiomyocytes. Trisomy 21 hearts show depletion of compact cardiomyocytes and increased apoptosis relative to euploid hearts, a finding validated in isogenic-matched induced pluripotent stem cell-derived cardiomyocytes, providing a mechanistic lead on congenital heart disease risk in Down's syndrome.

    Why it matters: It links a cellular deficit in trisomy 21 hearts to congenital heart disease risk using a spatial human cardiac development atlas.

Oct 9Fri
  1. Nature74

    A gut microbial odd-chain fatty acid alleviates atherosclerosis in mice.

    Pentadecanoic acid (PA, C15:0), an odd-chain fatty acid produced by Bacteroides uniformis and other Bacteroidota, alleviates atherosclerosis in mice. PA supplementation cut atherosclerotic plaque burden by around 50% and improved plasma lipid profiles by inhibiting HMG-CoA reductase, suppressing hepatic cholesterol biosynthesis and promoting LDL cholesterol removal via upregulation of hepatic LDL receptor. PA is markedly depleted in patients with dyslipidaemia.

    Why it matters: Identifies a specific microbiota-derived metabolite with a mechanism and roughly 50% plaque reduction in mice.

  2. Cell77

    Immunoregulatory gene GIMAP6 suppresses lethal atherosclerotic vasculopathy and ischemic heart failure.

    Loss of the immunoregulatory gene Gimap6 in mice causes inflammatory vasculopathy and accelerated atherosclerosis without hyperlipidemia, leading to cardiac ischemia, myocardial infarction, heart failure, and early death. Mechanistically, GIMAP6 loss triggers endothelial barrier failure and a mitochondrial ROS-PPARγ-CD36 lipid-influx cascade that promotes foam-cell formation and IL-6/MCP-1/TNF inflammation. Human hypomorphic GIMAP6 variants, including the African-ancestry-enriched V65I allele, are associated with increased CD36-mediated lipid uptake and early ASCVD.

    Why it matters: Identifies a lipid-independent genetic route to lethal atherosclerosis with a corresponding human risk allele.

  3. biorxiv.org51

    Single-nucleus multi-omics reveals reversible molecular signatures in skeletal muscle of patients with heart failure with preserved ejection fraction

    Single-nucleus multiome profiling of 140 skeletal muscle biopsies from 95 individuals (25 healthy controls, 70 HFpEF patients) maps molecular signatures of skeletal muscle remodeling in HFpEF, including type 1 fiber and pericyte depletion and type 2x fiber enrichment. Paired biopsies from 45 HFpEF patients before and after a supervised diet and exercise intervention show the chromatin accessibility and transcriptional changes were partially reversible. HFpEF-linked chromatin was enriched for heart failure and cardiometabolic GWAS signals.

Oct 7Wed
  1. nature.com78

    A gut microbial odd-chain fatty acid alleviates atherosclerosis in mice

    The paper reports that a gut microbial odd-chain fatty acid alleviates atherosclerosis in mice. The work draws on mouse experiments together with human gut metagenomic datasets from atherosclerotic cardiovascular disease and subclinical carotid atherosclerosis cohorts, and includes RNA-seq data and molecular docking against the human HMGCR structure.

    Why it matters: Links a gut microbial metabolite to atherosclerosis outcomes in mice, with human metagenomic support.

  2. nature.com75

    Revealed: how this common gut microbe protects against heart disease

    The gut bacterium Bacteroides uniformis, often depleted in people with heart disease, produces pentadecanoic acid, a molecule that lowers cholesterol and shrinks arterial plaque. In mice engineered to develop atherosclerosis, the compound cut arterial plaque by about half, and live B. uniformis shrank plaques by about one-third while reducing total cholesterol and LDL. The molecule inhibits a liver enzyme in cholesterol production that statins also target, and in more than 200 human donors, lower pentadecanoic acid levels linked to abnormally high blood lipids.

Oct 1Thu
  1. JAMA46

    Histologic Features and Clinical Outcomes of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease.

    Lean MASLD is a distinct phenotype with milder histologic disease but similar clinical outcomes to overweight/obese MASLD, according to a retrospective study of 18 326 biopsy-confirmed adults across 41 countries. Lean patients (6.7% by BMI) had less advanced fibrosis (29.3% vs 37.2%) and lower type 2 diabetes prevalence (38.2% vs 48.3%), and lean status was not independently associated with all-cause mortality (aHR, 0.90) or clinical events (aHR, 0.94). Fibrosis stage drove prognosis (advanced fibrosis aHR, 2.10 for mortality; 3.41 for events), and liver stiffness measurement outperformed FIB-4 for detecting advanced fibrosis in lean patients (AUC 0.87 vs 0.76).

  2. Nat Med53

    Oral small-molecule GLP-1 receptor agonist safiglipron in early type 2 diabetes: a randomized, double-blind, placebo-controlled trial.

    Once-daily oral safiglipron reduced HbA1c by 1.20 to 1.45 percentage points versus placebo at 32 weeks in 284 adults with early type 2 diabetes managed with diet and exercise alone (OUTSTAND-1, phase 3). HbA1c below 7.0% was reached by 71.4-77.8% of safiglipron recipients versus 25.0% on placebo, with modest weight loss and mostly mild or moderate gastrointestinal adverse events. It offers an oral GLP-1 receptor agonist option taken without fasting or dietary restrictions.

    Why it matters: Phase 3 evidence that an oral small-molecule GLP-1 receptor agonist matches injectable-class glycemic efficacy.

Sep 30Wed
  1. doi.org54

    Akkermansia muciniphila protects diabetes-associated cognitive decline by enhancing leucine catabolism and suppressing neuronal excessive mitophagy

    Low abundance of Akkermansia muciniphila and high leucine levels drive diabetes-associated cognitive decline in diabetic mice and patients. A. muciniphila catabolizes leucine, and excess leucine activates the TBK1-OPTN pathway, enhancing OPTN binding to LC3 and Ub chains and triggering neuronal excessive mitophagy that accelerates cognitive decline in mice. The work identifies a gut-brain metabolic mechanism and a target for gut-directed therapy of cognitive disorders.

    Why it matters: It links a gut bacterium, a metabolite and a defined neuronal mitophagy pathway in diabetes-associated cognitive decline.

Sep 29Tue
  1. nature.com61

    Defining pathogenic macrophages in the fibrotic niche of human chronic liver disease

    A liver single-cell atlas of 77 patients with chronic liver disease resolves monocyte-derived, pro-fibrotic macrophages into 2 subpopulations of TREM2+ scar-associated macrophages. The analysis identifies OLR1 as a candidate therapeutic target for selectively modulating pro-fibrotic macrophage functions and thereby attenuating liver fibrosis.

    Why it matters: It names a specific molecular target, OLR1, for selectively modulating the macrophage subset driving liver fibrosis.

Sep 28Mon
  1. nature.com51

    A human single-cell atlas identifies OLR1 + scar-associated macrophages as a potential therapeutic target for chronic liver disease

    A single-cell RNA-sequencing atlas of 77 healthy and chronic liver disease livers identifies a subpopulation of pro-inflammatory scar-associated macrophages enriched for OLR1 expression. The work points to OLR1+ scar-associated macrophages as a potential therapeutic target in chronic liver disease.

  2. nature.com49

    Old hearts age backwards: transplanted organs adjust to host’s biological age

    Transplanted hearts take on the biological age of their recipients, according to DNA-methylation analysis in mice and in 11 human transplants with donor-recipient age gaps of 8 to 50 years. Young hearts grafted into older animals showed accelerated ageing, while old hearts were rejuvenated in younger hosts. Post-transplant measures such as heart rate, posterior wall thickness and exercise capacity tracked the recipient's age rather than the donor's.

Sep 26Sat
  1. doi.org54

    Plasma indole-3-propionic acid is a gut-derived metabolite and is associated with type 2 diabetes and cardiometabolic outcomes: Evidence from a human antibiotic intervention

    Plasma indole-3-propionic acid (IPA) is lower in individuals with type 2 diabetes than in healthy controls, and higher pre-antibiotic levels associate with reduced T2D odds. In both groups, 7-day broad-spectrum antibiotic treatment reduced IPA to near-undetectable levels, confirming its predominantly microbial origin. IPA also showed a novel inverse correlation with glycemic variability and linked to gut microbiota beta diversity rather than known IPA-producing taxa alone.

    Why it matters: Direct human antibiotic evidence that plasma IPA is gut microbiota-derived and inversely associated with type 2 diabetes.

Sep 25Fri
Sep 24Thu
  1. biorxiv.org45

    CMAC: A deep learning framework for absolute cardiomyocyte transcriptional age estimation

    CMAC, a deep learning framework built from 18 murine single-cell RNA-seq datasets, assigns absolute transcriptional maturation age to cardiomyocytes across platforms and experimental conditions. An XGBoost regressor on its batch-invariant latent space predicted chronological age with leave-one-dataset-out MAE of 4.09 days (Pearson r = 0.903), and in an independent P14 cohort of 98,163 cells achieved mouse-level MAE of 0.33 days. Applied to PGC1/beta double-knockout mice, it quantified maturation deficits of 4.77 to 8.60 days across P7 to P28.

    Why it matters: It provides the first unified way to quantify absolute cardiomyocyte maturation age and deviations from normal development.

Sep 21Mon
  1. medrxiv.org43

    Weighing the Odds: Body Mass Index and Recurrence-Free Survival in Early-Onset Colorectal Cancer

    BMI at diagnosis shows a U-shaped association with recurrence-free survival in early-onset colorectal cancer, with the lowest hazard at BMI 27 and the highest at BMI below 20 or above 30 (LRT p=0.02). In 1,459 curative-intent surgery patients, no such association appeared in average-onset colorectal cancer (LRT p=0.15), and the cohorts differed significantly (LRT p=0.046). The findings suggest the obesity paradox may be specific to EOCRC.

    Why it matters: It suggests the obesity paradox in colorectal cancer may be specific to early-onset disease, where BMI is rising sharply.

Sep 12Sat
  1. N Engl J Med62

    Complete Revascularization Guided by Functional Coronary Angiography in STEMI.

    Guiding complete revascularization by functional coronary angiography rather than conventional angiography cut adverse events after STEMI. In 1823 patients with multivessel disease, the composite of death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization occurred in 8.9% versus 13.7% (hazard ratio 0.62) at a median 17.9 months, with fewer safety events (4.6% vs 7.1%). This supports physiology-based assessment for selecting nonculprit lesions to treat.

    Why it matters: It identifies a concrete strategy that reduces both ischemic events and safety events in STEMI revascularization.

Sep 10Thu
  1. Sci Adv51

    Impaired liver-muscle lactate metabolism causes sarcopenia via lactic acidosis in skeletal muscle in mice.

    Impaired lactate processing in the liver drives lactic acidosis in skeletal muscle, and this emerges as a fundamental cause of sarcopenia in aged mice. Systemic lactate tolerance fell in aged mice, and lactic acidosis lowered nicotinamide adenine dinucleotide levels, disrupting skeletal muscle function. Pharmacological activation of hypoxia-inducible factor or liver-specific activation of HIF1α restored lactate tolerance, resolved muscle lactic acidosis, and improved sarcopenia.

    Why it matters: It identifies liver-skeletal muscle lactate metabolism and hepatic HIF1α as a mechanistic basis and drug target for sarcopenia.

Sep 7Mon
  1. Nat Med52

    Recombinant shingles vaccination and the risk of cardiovascular events.

    The recombinant shingles vaccine was associated with a 9% decrease in cardiovascular burden over 7 years compared with the live attenuated vaccine (RMTL ratio = 0.91, 95% CI: 0.88-0.95) among US adults aged ≥60 years. Using the rapid transition between vaccines as a natural experiment, the study found reductions for ischemic heart disease (10%) and heart failure (12%) in both sexes, and ischemic stroke in males (12%). The authors say the results justify trials of potential cardioprotective effects.

    Why it matters: A quasi-experimental design links the recombinant shingles vaccine to lower cardiovascular event burden, prompting trial proposals.

Sep 5Sat
  1. Sci Adv54

    Activation of G12-type G proteins in pancreatic β cells protects against impaired glucose homeostasis.

    Selective activation of G12-type G protein signaling in pancreatic β cells strongly promoted insulin secretion in mice, protecting against obesity-associated metabolic deficits and improving glycemic control in a mouse model of type 2 diabetes. Using β cell-specific chemogenetics and gene knockout technology, mechanistic studies with perifused mouse islets identified ROCK as a key downstream effector of G12 signaling that triggers insulin secretion.

  2. Sci Adv59

    Metabolic regulation of calcium homeostasis via SERCA succination.

    Fumarate covalently modifies SERCA2b at Cys875, inhibiting ER calcium uptake and disrupting calcium homeostasis. A Cys875Ser mutant resists fumarate-induced inhibition, and Drosophila knock-in flies carrying the corresponding mutation preserve ER calcium homeostasis and are protected from hyperglycemia, glucose intolerance, and reduced survival on a high-sugar diet. Pharmacological fumarate reduction or allosteric SERCA activation phenocopies these protective effects.

    Why it matters: Identifies a specific covalent mechanism, SERCA2b Cys875 succination, linking glucose metabolism to calcium homeostasis and metabolic dysfunction.

Sep 4Fri
  1. Mol Cell57

    Torsins organize CLCC1 assembly to safeguard ER bilayer and lipid homeostasis.

    Torsin ATPases are the long-missing luminal clients of CLCC1, selectively engaging oligomerized CLCC1 at sites of ER bilayer imbalance and promoting its assembly for recruitment to imbalanced bilayers. Hepatic torsinA inactivation in mice causes giant ER-enclosed lipid droplets, disrupted lipoprotein biogenesis and severe MASH, phenocopying CLCC1/TMEM41B deficiency. Ectopic CLCC1 expression reverses these cellular and systemic lipid disorders.

Sep 3Thu
  1. Science45

    Longitudinal dynamics of gene expression and metabolomics in an aging population cohort.

    Whole-blood gene expression and metabolite levels tracked over 8 years in 335 females show that 5061 genes and 181 metabolites change over time, with individual trajectories often diverging from population-level trends. Longitudinally variable genes were cell type specific and enriched for aging-relevant pathways, including cardiometabolic and neurodegenerative disorders, and trajectories were shaped by genetics, circadian rhythm, seasonality, and pollutant exposures. The work shows population-level molecular aging trends can mask individual dynamics relevant to precision medicine.

  2. Sci Adv70

    A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.

    An orally bioavailable small molecule, 5-tetradecyloxy-2-furoic acid (TOFA), alleviated obesity, abnormal glucose homeostasis and fatty liver-related disease without affecting food intake or muscle mass. TOFA inhibits acetyl-CoA carboxylases 1 and 2 and activates PPARalpha/delta, raising energy expenditure and rebalancing lipid synthesis. It also acted more than additively with the incretin analogs semaglutide and tirzepatide to improve obesity, dyslipidemia and insulin resistance.

    Why it matters: It offers an oral option that raises energy expenditure rather than suppressing appetite, and combines with incretin analogs.

Sep 2Wed
  1. Nature56

    Late-life semaglutide treatment slows ageing and extends lifespan in female mice.

    Semaglutide treatment of 20-month-old female C57BL/6 mice for 3 months improved physiological function, attenuated hallmarks of ageing and extended lifespan. In a longitudinal comparison with matched calorie restriction, semaglutide preserved baseline function and outperformed calorie restriction in exploratory drive, spatial memory and glucose control. The work frames GLP-1R activation as a calorie restriction mimetic acting partly through mechanisms beyond reduced food intake.

    Why it matters: It separates GLP-1R agonist benefits from calorie intake itself and shows late-life treatment can extend lifespan in mice.

  2. Nat Med54

    Dual antithrombotic therapy using potent antiplatelet inhibitors in atrial fibrillation and acute coronary syndrome: a randomized controlled trial.

    In the EPIDAURUS open-label randomized trial in patients with atrial fibrillation and acute coronary syndrome, 1 month of a DOAC plus a potent P2Y12 inhibitor (prasugrel or ticagrelor) was compared with DOAC plus clopidogrel and in-hospital aspirin. The trial stopped early after 602 of 1,474 planned patients on Data and Safety Monitoring Board safety concerns. Exploratory analyses showed higher BARC type ≥2 and ≥3 bleeding with potent inhibitors and no clear reduction in ischemic events.

    Why it matters: It tests whether potent P2Y12 inhibitors improve DAT outcomes and finds more bleeding without ischemic benefit.

  3. JAMA52

    Measured and Estimated Glomerular Filtration Rates and Risk of Adverse Health Outcomes.

    Measured GFR of 60 mL/min/1.73 m2, versus 90, carried higher all-cause mortality (27.6 vs 22.4 per 1000 person-years; HR 1.21) and kidney failure with replacement therapy (1.2 vs 0.4; HR 2.85) among 6174 Stockholm adults followed a median 5.9 years, supporting the 60 mL/min/1.73 m2 chronic kidney disease threshold. For mortality, the combined creatinine-cystatin C estimate matched measured GFR associations, while creatinine-based estimates underestimated and cystatin C estimates overestimated risk.

  4. Sci Adv60

    Development of mitochondrial mutator pigs exhibiting increased mitochondrial DNA mutations and premature aging via prime editing.

    Prime editing combined with somatic cell nuclear transfer produced pigs expressing proofreading-deficient POLG, the catalytic subunit of DNA polymerase gamma. The pigs accumulated elevated somatic mitochondrial DNA mutation loads and showed premature aging phenotypes, including weight loss, anemia, increased apoptosis, up-regulation of senescence-associated markers, and shortened life span. The model offers a large-animal platform for studying mtDNA mutations in aging and testing therapies.

    Why it matters: First large-animal mitochondrial mutator model, made by prime editing, for preclinical aging research.

Sep 1Tue
  1. Sci Adv64

    Intestinal fructose catabolism promotes obesity and insulin resistance via ileal lacteal remodeling.

    Blocking fructose catabolism specifically in the murine small intestine mitigates fructose-induced obesity and insulin resistance, an unexpected finding since intestinal fructose clearance was thought to protect the liver. The effect traces to decreased dietary fat absorption caused by shortening of ileal lacteals. Fecal transplantation showed the altered microbiome reduces ileal macrophages required for lacteal growth.

    Why it matters: It overturns the view that intestinal fructose clearance is protective by linking it to obesity through lacteal remodeling.

  2. JAMA42

    Lifestyle and Metformin Interventions and Risk of Multimorbidity in Adults With Prediabetes.

    Intensive lifestyle intervention, but not metformin, reduced long-term multimorbidity in adults with prediabetes in the DPP/DPPOS cohort. Among 1173 participants with CMS morbidity data, lifestyle versus placebo gave a hazard ratio of 0.79 (95% CI, 0.68-0.93), while metformin showed no difference (HR, 0.91; 95% CI, 0.78-1.07). For dyads of the costliest conditions, lifestyle yielded an HR of 0.57.

  3. Nat Med69

    Short-term effects of combinations of heart failure therapies on blood pressure, kidney function and serum potassium.

    A pooled individual participant-level analysis of 38,753 patients across nine randomized trials quantifies the short-term (2-12 weeks) effects of heart failure drug combinations on blood pressure, eGFR and serum potassium, with a prediction model for individualized estimates. In HFrEF, ARNI + SGLT2i + sMRA lowered SBP by -9.2 mmHg, reduced eGFR by -6.8 ml min-1 m-2 and raised potassium by +0.30 mmol l-1; in HFmrEF/HFpEF, SGLT2i + nsMRA raised potassium by only +0.21 mmol l-1. The model gives clinicians expected treatment effects for any therapy combination, addressing concerns over hypotension, kidney dysfunction and hyperkalemia that limit comprehensive therapy.

    Why it matters: It quantifies and individualizes the BP, eGFR and potassium effects that drive underuse of combination heart failure therapy.

Aug 31Mon
  1. JAMA56

    Gene Silencer Therapy in Transthyretin Amyloid Cardiomyopathy: A Meta-Analysis of Outcomes Trials.

    Pooled analysis of the phase 3 trials HELIOS-B and CARDIO-TTRansform (2086 patients with ATTR-CM) found TTR gene-silencing therapy cut the composite of all-cause mortality and recurrent cardiovascular events by 20% (RR, 0.80; 95% CI, 0.69-0.94), reduced all-cause death (HR, 0.74; 95% CI, 0.61-0.91), and preserved 6-minute walk distance (+22.2 m vs placebo). Benefit was significant in patients not on baseline TTR stabilizers (RR, 0.69) but not in those already receiving stabilizer therapy (RR, 0.97). The findings support TTR gene silencing for ATTR-CM and clarify how background stabilizer use shapes the treatment effect.

    Why it matters: It quantifies the overall effect of TTR gene silencers in ATTR-CM and shows benefit depends on baseline stabilizer use.

CBACBA Frontier Insights (CFI)Chinese Biopharmaceutical Association (CBA)www.cba-usa.org