Daily Cardiology Research Analysis

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is increasingly acknowledged as a major public health concern due to its complex pathophysiology, which involves neuroinflammation and sympathetic activation. The crosstalk between the heart and hypothalamic microglia in HFpEF, particularly the role of small extracellular vesicles (sEVs), remains insufficiently explored. METHODS AND RESULTS: We constructed an HFpEF model in mice by combining a long-term high-fat diet with the nitric oxide synthase inhibitor l-NAME (N[ω]-nitro-l-arginine methyl ester). These mice exhibited microglial activation and hypothalamic inflammation. Microglial depletion with PLX3397 suppressed sympathetic activity and improved cardiac dysfunction in HFpEF. sEVs derived from the myocardium of HFpEF mice induced a proinflammatory M1 phenotype in microglia, leading to hypothalamic inflammation and sympathetic activation. Intraperitoneal injection of the sEV biogenesis inhibitor GW4869 reversed these changes in HFpEF mice. Similar pathological changes were observed in BV2 microglia treated with sEVs isolated from palmitic acid-treated HL-1 cardiomyocytes. Bioinformatic and RT-qPCR analyses revealed a notable upregulation of miR-200c-3p in sEVs derived from both HFpEF myocardial tissue and palmitic acid-treated HL-1 cardiomyocytes, as well as in microglia. A cardiomyocyte-specific miR-200c-3p sponge inhibited microglial activation, hypothalamic inflammation, and sympathetic activation in HFpEF mice. Conversely, a miR-200c-3p mimic exacerbated proinflammatory responses in BV2 cells, while a miR-200c-3p inhibitor prevented the transition to a proinflammatory phenotype. The antiinflammatory protein DUSP1 (dual-specificity phosphatase 1) was validated as a potential downstream target of miR-200c-3p in microglia. CONCLUSIONS: Our study reveals that HFpEF prompts cardiomyocytes to release sEVs enriched with miR-200c-3p, leading to hypothalamic inflammation and evoking sympathetic outflow, which in turn exacerbates cardiac dysfunction. Focusing on sEV-mediated communication between cardiomyocytes and microglia may offer a new therapeutic approach for HFpEF.

BACKGROUND: Previously developed machine-learning (ML)-based decision support tools for patients presenting with suspected non-ST-segment elevation myocardial infarction (NSTEMI) remain proprietary, limiting public accessibility and clinical adoption. METHODS: To address this limitation, we used two international prospective multicentre diagnostic studies for model derivation and internal validation, and one large prospective European study for external validation, evaluating two open-access ML-based models. The derivation and internal validation cohort comprised 8763 patients (34% women) enrolled across 13 and 12 sites, respectively, in Switzerland, Spain, the Czech Republic, Poland, Belgium, Germany, the UK, Italy and the USA between April 2006 and September 2020, and between August 2011 and June 2013. The external validation cohort included 4882 patients (41% women) from Germany. Patients were excluded if they had a ST-segment elevation myocardial infarction, unclear final diagnosis, renal failure or an absent 12-lead electrocardiogram. A single-high-sensitivity cardiac troponin (hs-cTn) model incorporated information available at emergency department presentation, while a serial-hs-cTn model additionally utilised the second hs-cTn measurement and the time interval between samples. The final diagnosis of NSTEMI was centrally adjudicated by two independent cardiologists in all studies. The diagnostic performance of both models was compared with the European Society of Cardiology (ESC) hs-cTn-0/1 h-algorithm.

IMPORTANCE: The 2026 American Heart Association/American College of Cardiology/multisociety guideline on the management of dyslipidemia issued new recommendations on estimating atherosclerotic cardiovascular disease (ASCVD) risk and on populations eligible for statins for primary prevention. OBJECTIVE: To assess the population health impact of the 2026 guideline on primary prevention statin therapy. DESIGN, SETTING, AND PARTICIPANTS: Nationally representative, cross-sectional sample of nonpregnant adults aged 30 to 79 years without known ASCVD, who participated in the National Health and Nutrition Examination Survey from 2017 to 2023. Data were analyzed from March to May 2026. MAIN OUTCOMES AND MEASURES: Changes in eligibility for primary prevention statin therapy, comparing the 2026 and 2018 lipid guidelines. RESULTS: The weighted sample included 4366 NHANES participants representative of 154.5 million US adults (weighted mean age, 51 years; 52.0% female). Of these, 5.5% (95% CI, 4.7%-6.6%) had untreated low-density lipoprotein cholesterol below 70 mg/dL, 17.8% (95% CI, 16.3%-19.5%) reported currently taking statins, and 8.6% (95% CI, 7.6%-9.8%) met criteria for statin eligibility independent of ASCVD risk estimation based on a low-density lipoprotein cholesterol of 190 mg/dL or greater, diabetes, or chronic kidney disease. The remaining 68.0% of patients (95% CI, 65.9%-70.0%) met guideline criteria for using ASCVD risk estimation to guide statin decisions. In total, an estimated 87.5 million (56.6% [95% CI, 54.2%-58.9%]) nonpregnant US adults aged 30 to 79 years were statin eligible based on the 2026 guideline, including 21.5 million (13.9% [95% CI, 12.5%-15.5%]) who were newly statin eligible. More than 93% of adults aged 70 to 79 years and 85% of adults aged 60 to 69 years are eligible for primary prevention statin therapy compared with 11% of adults aged 30 to 39 years. Newly statin-eligible populations were largely younger and lower risk than populations previously recommended statin therapy (mean estimated 10-year ASCVD risk, 3.1% [95% CI, 2.7%-3.5%] for newly statin-eligible individuals vs 6.1% [95% CI, 5.8%-6.4%] for individuals previously eligible for statin therapy). CONCLUSIONS AND RELEVANCE: The 2026 dyslipidemia guideline substantially expands the US population recommended for primary prevention statin therapy, predominantly in lower-risk individuals.