Circulation最新文献

Background: The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and cardiovascular-kidney-metabolic syndrome) that contribute to cardiovascular health. The 2026 Heart Disease and Stroke Statistics Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

Methods: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistics Update with review of published literature through the year before writing. The 2026 Statistics Update is the product of a full year's worth of effort in 2025 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes a new chapter on cardiovascular-kidney-metabolic syndrome, as well as an expanded chapter on tobacco and nicotine use and exposure.

Results: Each of the chapters in the Statistics Update focuses on a different topic related to heart disease and stroke statistics.

Conclusions: The Statistics Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Background: As an iron-dependent form of regulated cell death caused by lipid peroxidation, ferroptosis has been implicated in ischemic injury, but the underlying mechanisms in acute myocardial infarction (AMI) remain poorly defined. ALDH2 (acetaldehyde dehydrogenase 2) catalyzes detoxification of lipid aldehydes derived from lipid peroxidation and acetaldehydes from alcohol consumption. The Glu504Lys polymorphism of ALDH2 (rs671, ALDH2*2), affecting ≈40% of East Asians, is associated with increased risk of myocardial infarction (MI). This study aims to investigate the role of ALDH2*2 and ferroptosis in AMI.

Methods: A Chinese cohort of 177 patients with acute heart failure with ALDH2 wild type and ALDH2*2 was enrolled. The MI mouse model of left anterior descending coronary artery ligation was conducted on wild-type and ALDH2*2 mice and mice with cardiomyocyte-specific knockdown of eIF3E (eukaryotic translation initiation factor 3 subunit E) by adeno-associated virus. The lipid peroxidation products were measured by mass spectrometry-based lipidomics and metabolomics in human plasma, mouse serum samples, mouse heart tissues, and primary cardiac myocytes.

Results: Human ALDH2*2 carriers exhibit more severe heart failure after AMI with features of ferroptosis in plasma, as seen through lipidomic analysis, characterized by increased bioactive lipids and decreased antioxidants, such as coenzyme Q10 and BH4 (tetrahydrobiopterin). Similar features were observed in MI mouse models of ALDH2*2, whereas ferroptosis inhibition by Fer-1 significantly improved heart function and reversed ferroptosis markers. Importantly, ALDH2*2 significantly decreased ALDH2 protein levels, whereas ferroptosis-related markers, including TFRC (transferrin receptor) and ACSL4 (acyl-coenzyme A synthetase long-chain family member 4) were notably upregulated in the infarct heart tissues. Mechanistically, ALDH2 physically interacts with the eIF3 complex via the eIF3E factor, which prevents eIF3E-eIF4G1 (eukaryotic initiation factor 4G)-mRNA assembly. The ALDH2*2 variant causes ALDH2 deficiency, disrupting its interaction with the eIF3 complex by releasing the bound eIF3E to assemble an eIF3E-eIF4G1-mRNA ternary complex, thereby driving selective translation of mRNAs (eg, TFRC, ACSL4, and UAP1) containing the GAGGACR (R represents A/G) motif to promote ferroptosis. Consistently, cardiomyocyte-specific eIF3E knockdown restored ALDH2*2 cardiac function by attenuating ferroptosis in MI.

Conclusions: ALDH2*2 aggravates acute heart failure after MI by promoting the selective translation of mRNAs containing the GAGGACR motif, thereby driving cardiomyocyte ferroptosis. Targeting ferroptosis represents a potential therapeutic option for mitigating MI injury, especially for ALDH2*2 carriers.

Background: Current guidelines recommend a stepwise strategy to achieve low-density lipoprotein cholesterol (LDL-C) goals after acute coronary syndrome (ACS). Earlier intensive strategies based on a combination of lipid-lowering therapies (LLTs) could be useful from the onset of ACS. However, the role of bempedoic acid in ACS, particularly when combined with high-intensity statins and ezetimibe, remains uncertain. The aim of ES-BempedACS (Efficacy and Security of Bempedoic Acid in Acute Coronary Syndrome) was to compare the efficacy and safety of triple LLT (high-dose, high-intensity statin+ezetimibe+bempedoic acid) versus standard of care (high-dose, high-intensity statin+ezetimibe) after ACS.

Methods: ES-BempedACS is a multicenter, independent, pragmatic, prospective, randomized, open, blinded end point controlled trial conducted in 12 Spanish hospitals between November 2023 and October 2024. The primary end point was the proportion of patients achieving LDL-C <55 mg/dL (<1.4 mmol/L) at 8 weeks after ACS, comparing triple LLT with standard of care.

Results: A total of 206 patients (59.5±10.9 years of age [mean±SD]; 21.4% women) were randomized within the first 72 hours of ACS to triple LLT or standard therapy of high-intensity statin+ezetimibe (ie, dual LLT). The baseline LDL-C level was 133.6±28.8 mg/dL. After 8 weeks, the LDL-C level was reduced to <55 mg/dL in 59.4% of patients in the triple LLT group compared with 53.1% in the control group (dual LLT; P=0.376). The percentage change in LDL-C level was 57.5±17.8% and 56.9±18.5% in the triple and dual LLT groups, respectively (P=0.823). Triple versus dual LLT showed similar results in reduction of non-high-density lipoprotein cholesterol levels (49.0±25.4 in triple LLT versus 49.1±31.2 in dual LLT; P=0.970) and triglyceride levels (14.9±36.9 in triple LLT versus 16.8±36.0 in dual LLT;) P=0.718), without differences in adverse events.

Conclusions: Both dual and triple LLT after ACS allow for high rates (>50%) of adequate LDL-C control (<55 mg/dL) at 8 weeks. Adding bempedoic acid to statin-ezetimibe therapy in the setting of ACS is safe but failed to improve the percentage of patients achieving the LDL-C goal (<55 mg/dL) at 8 weeks. Larger, randomized studies are needed to confirm our findings.

Registration: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2021-006550-31.