Journal of the American Heart Association最新文献

Background: Low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are risk factors for atherosclerotic cardiovascular disease (ASCVD). However, the extent to which differences in RC levels affect ASCVD risk in populations with varying degrees of LDL-C elevation remains unclear. This study aimed to investigate whether RC can provide additional risk stratification value across different sexes, ages, and elevated LDL-C statuses.

Methods: This study included 12 743 elevated LDL-C participants (LDL-C ≥3.4 mmol/L) and 50 073 age- and sex-matched non-elevated LDL-C controls from the Kailuan Study. Elevated LDL-C participants were categorized by RC levels into <0.5, 0.5 to <1.0, and ≥1.0 mmol/L subgroups. Kaplan-Meier curves and Cox proportional hazards models were used to assess the relationship between RC levels and ASCVD risk across different sexes, ages, and high LDL-C statuses.

Results: During a median follow-up of 12.8 years, 1686 elevated LDL-C participants (13.2%) and 5252 non-elevated LDL-C participants (10.5%) developed ASCVD. In the borderline-high LDL-C group (3.4 ≤ LDL-C < 4.1 mmol/L), those with the lowest RC levels showed no significant risk difference compared with controls (hazard ratio [HR], 1.03 [95% CI, 0.93-1.13]), and this pattern remained consistent across different sexes and ages. In contrast, in the high LDL-C group (LDL-C ≥4.1 mmol/L), even when RC was at the lowest level, ASCVD risk remained significantly higher than that of controls (HR, 1.20 [95% CI, 1.02-1.41]).

Conclusions: In the borderline-high LDL-C population, those with the lowest RC levels showed no significant risk difference compared with controls, and this pattern remained consistent across different sexes and age subgroups. In the high LDL-C population, even when RC was at the lowest level, ASCVD risk remained significantly higher than that of controls.

Background: Neutrophil extracellular traps are released from activated neutrophils and are involved in the pathogenesis of atherosclerotic lesions, atherothrombosis, and myocardial injury. We investigated the prognostic value of circulating neutrophil extracellular trap biomarkers in patients with suspected acute coronary syndrome (ACS).

Methods: A total of 1482 patients admitted with suspected non-ST-segment elevation ACS were included and followed for a median of 4.2 years. The primary end point was a composite of death from any cause, incident myocardial infarction and hospitalization for heart failure. Secondary end points were all-cause mortality, cardiovascular death, incident myocardial infarction, hospitalization for heart failure, and new-onset atrial fibrillation. Admission blood samples were analyzed for the neutrophil extracellular trap biomarkers double-stranded DNA (dsDNA), CitH3 (citrullinated histone H3), and myeloperoxidase-DNA.

Results: A doubling of dsDNA concentration was associated with a hazard ratio (HR) of 3.11 (95% CI, 1.61-5.98, P<0.001) for the primary end point after adjusting for traditional risk factors, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. DsDNA served as a prognostic marker both in patients with (adjusted HR, 5.33 [95% CI, 1.67-17.06], P=0.005) and without ACS (adjusted HR, 2.86 [95% CI, 1.30-6.28], P=0.009). In contrast, CitH3 and myeloperoxidase-DNA showed no significant prognostic value.

Conclusions: In patients with suspected ACS, dsDNA emerged as a long-term prognostic marker for a composite outcome of death, incident myocardial infarction, or heart failure hospitalization, independent of conventional risk factors. DsDNA can independently from established risk factors identify high-risk patients with and without ACS who may benefit from risk reduction.

Background: Genetic risk scores may be useful for analyzing risks for coronary artery disease (CAD). However, comparisons between restricted and genome-wide scores have been underexplored, particularly for individuals at increased risk by one score but not the other. Here, we compared restricted polygenic risk scores with 181 high-confidence genetic variants (PRS₁₈₁) and genome-wide risk scores that encompass 6.6 million single-nucleotide polymorphisms (GRS_6.6M).

Methods: Data were from the RS (Rotterdam Study; n=11 001), MESA (Multi-Ethnic Study of Atherosclerosis; n=2685), and the Sanford Health study (n=25 166). We analyzed score associations with CAD (prevalent and incident), age at onset, and lipid medication use. Combined use of both scores was also examined.

Results: There were robust associations with CAD per SD of the scores for men (PRS₁₈₁: hazard ratio [HR], 1.19 [95% CI, 1.13-1.26]; GRS_6.6M: HR, 1.32 [95% CI, 1.26-1.39]) and women (PRS₁₈₁: HR, 1.24 [95% CI, 1.16-1.32]; GRS_6.6M: HR, 1.32 [95% CI, 1.25-1.40]). PRS₁₈₁ was more strongly associated with early-onset CAD in men (β=-0.93 [95% CI, -1.36 to -0.50]) and women (β=-0.76 [95% CI, -1.31 to -0.21]). Both scores correlated with lipid medication use, but the scores were also associated with CAD among nonusers. Individuals at high risk by both scores had the highest risk and the earliest age at onset.

Conclusions: PRS₁₈₁ and GRS_6.6M appear to identify different subsets of individuals. Use of both scores together may provide better association information on CAD risk and age at onset than each score alone.

Caveolae, 50-100 nm cholesterol-rich plasma membrane invaginations, serve as critical signaling hubs in vascular cells. These structures-scaffolded by caveolin proteins (CAV1, CAV2, CAV3) and regulated by Cavins-orchestrate membrane dynamics, mechanotransduction, and lipid trafficking in endothelial cells, smooth muscle cells, and macrophages. In vascular physiology, caveolae modulate vascular tone, regulate lipoprotein metabolism, and mediate mechanosensation. In pathology, caveolae are implicated in atherosclerosis, pulmonary hypertension, and diabetic vasculopathy. This review synthesizes advances in caveolae biology, highlighting their roles in vascular homeostasis and disease. We propose caveolae-targeted therapies as promising strategies for cardiovascular disorders, contingent on resolving context-dependent signaling complexity.

Background: Heart failure (HF) progresses through stages, from risk factors (stage A) to structural abnormalities, or elevated biomarkers (stage B), to clinical HF (stage C) as depicted by the American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines. Most individuals in stage B never develop clinical HF, highlighting the need for refined preclinical phenotyping. We hypothesized that refined HF stages incorporating cardiorespiratory fitness (CRF) would be differentially associated with HF risk.

Methods: This observational cohort study investigated FHS (Framingham Heart Study) participants who completed submaximal exercise testing (stage 2 of the Bruce protocol). CRF (peak oxygen uptake) was estimated on the basis of stage 2 heart rate, weight, age, sex, treadmill grade, and velocity. We evaluated the association of HF substages (categorized by CRF above versus below the sex-specific median) with incident HF using Cox models adjusted for age and sex.

Results: Among 1683 individuals (55% women, age 58±8 years, estimated CRF 35.4±3.2 mL/kg per min in women and 40.1±4.2 mL/kg per min in men) 522 individuals (31%) were classified as no HF risk factors ("healthy"; stage H), 693 (41%) as stage A, and 468 (28%) as stage B at baseline. Over median follow-up of 20 years, 99 HF events occurred. Stage B participants with low CRF had a >2.5-fold higher HF risk (hazard ratio [HR], 2.75 [95% CI, 1.50-5.07]; P=0.001). Among stage B participants, every 1-SD increase in CRF was associated with lower HF risk (HR, 0.57 [95% CI, 0.43-0.76]; P=0.0001).

Conclusions: Incorporating CRF into HF staging criteria may improve risk assessment and facilitate precision targeting of preventive therapies, especially among individuals classified as stage B.

Studies have established the safety and benefits of exercise training in patients admitted with acute heart failure, yet heterogeneity in exercise delivery patterns exists. Hence, a scoping review was undertaken to map the evidence on early exercise-based interventions (early mobilization with/without exercise training) in patients recovering from acute heart failure (admission to up to 2 weeks post-hospitalization), for geographic distribution, exercise prescription, and exercise initiation time. A systematic search was conducted across 5 databases until September 2024. Studies, including protocols, providing early exercise-based intervention anytime between admission and up to 2 weeks from discharge, in any setting, were included. Data were extracted from 30 included studies, and the obtained evidence was mapped. This study uses the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Extension for Scoping Reviews. The review included 1,54 980 participants with acute heart failure, and 26.6% (8 of 30) of the studies focused on the older adult population. Early exercise-based interventions, ie, early mobilization (n=12), exercise training (n=5), or combined (n=13), were limited to higher- (n=23) and upper-middle-income (n=6) countries and were primarily observational (n=19) in design. The median (Q1-Q3) initiation time to exercise was 3.8 days (2.8-5.5), with a dose of eight sessions (4.7-21). The intensity ranged from very low to moderate intensity, with the duration per session ranging from 10 to 60 minutes. The use of pre-specified, well-developed initiation, monitoring, and termination criteria was not common. Early exercise-based interventions were comprehensive, multi-modal, and of low-moderate intensity, initiated within 4 days of admission.

Background: Despite recent advances in pharmacotherapy, heart failure (HF) remains a major cause of hospitalization and death, particularly among aging populations. Sodium-glucose cotransporter 2 inhibitors have reduced hospitalization for HF and cardiovascular death. However, the mechanisms underlying these cardioprotective effects, particularly in the absence of diabetes, remain unclear. Therefore, we aimed to define the cardiac-specific effects of sodium-glucose cotransporter 2 inhibitors and the mechanism by which they improve HF prognoses.

Methods: We investigated the cardioprotective properties of empagliflozin in mouse models of HF induced by transverse aortic constriction. Empagliflozin was administered daily for 2 weeks, starting 2 weeks after transverse aortic constriction, and then cardiac function was evaluated.

Results: Empagliflozin preserved cardiac function and markedly reduced myocardial fibrosis and HF markers. Empagliflozin decreased cardiac C-C chemokine receptor type 2-positive macrophages, suggesting attenuated inflammation. Empagliflozin also reduced C-C motif chemokine ligand 2 expression in cardiac fibroblasts, indicating direct modulation of fibroblast behavior under mechanical stress and inhibited recruitment of proinflammatory macrophages.

Conclusions: We propose a novel antifibrotic mechanism in which empagliflozin acts directly on mechanically stressed cardiac fibroblasts to reduce chemokine signaling and macrophage-mediated inflammation. This mechanosensitive, fibroblast-targeted action might represent a paradigm shift in understanding sodium-glucose cotransporter 2 inhibitor cardioprotection and lead to new therapeutic strategies to mitigate HF progression.

Background: Triptan medications are proposed as an association of cerebral ischemic stroke in patients with migraine, but population-based data on this are lacking.

Methods: A retrospective, observational, cohort study was performed using computerized claims data from a proprietary, insurance-based registry-Marketscan (by Merative). Patients with at least 1 claim related to a migraine diagnosis were included. The primary exposure was initiation of any triptan medication defined by at least 1 prescription fill. The primary end point was time to cerebral ischemic stroke. Secondary end points included time to retinal stroke (central retinal artery occlusion, other retinal artery occlusion), intracranial hemorrhage, and myocardial infarction. The association between triptan initiation and study end points was modeled using a propensity score-overlap weighted Cox model. Adjusted hazard ratios (HR) and corresponding 95% CIs were computed.

Results: In total, 869 092 patients (median age 40.0 years [Q1-Q3, 30.0-50.0]; 77.5% female) met study selection criteria of whom 287 629 initiated a triptan and 581 463 did not. Median follow-up was 2555 days in the entire cohort. Initiation of a triptan was associated with higher hazard of cerebral ischemic stroke (adjusted HR, 2.37 [95% CI, 1.65-3.51]; absolute risk difference of 0.17% per year). Of 4 secondary end points, 2 were associated with triptan use: intracranial hemorrhage (adjusted HR, 2.37 [95% CI, 1.65-3.41]) and myocardial infarction (adjusted HR, 2.06 [95% CI, 1.60-2.66]).

Conclusions: In a population-based cohort study, initiation of a triptan was independently associated with risk of subsequent cerebral ischemic stroke.

Background: Radiomic and transcriptomic analyses have independently identified features linked to mechanical thrombectomy (MT) outcomes. Here, we integrated paired radiomics/transcriptomics of stroke clots to identify neutrophil extracellular trap (NET) enrichment as a predictor of first-pass MT success, assessing the potential to noninvasively detect NET enrichment using prethrombectomy computed tomography imaging.

Methods: We performed radiomic/transcriptomic analyses of 32 stroke clots retrieved by MT. Clots were segmented from pre-MT computed tomography angiography and noncontrast computed tomography scans, and radiomic features (RFs) were extracted using PyRadiomics. Differentially expressed genes were identified between modified first-pass effect (mFPE) success and failure using the criteria of log(fold-change) ≥1.5 and q <0.05. RFs significantly different between mFPE outcomes were identified. A NET enrichment score was computed from expression data, and RFs that differed significantly between low- and high-NET-enriched clots were selected to construct an RF signature predictive of NET enrichment. Immunofluorescence was completed on clots to provide ground truth NET labeling.

Results: A total of 44 differentially expressed genes were identified between mFPE outcomes. NET formation, neutrophil degranulation, and the NET signaling pathway were among the most enriched gene ontologies in the mFPE failure group, with related genes downregulated in the mFPE success group. Forty RFs were significantly different between mFPE outcomes. Of these, 4 were found to be predictive of clot NET enrichment. Immunofluorescence validated that transcriptomic NET signatures accurately reflected NET presence within clot tissues.

Conclusions: NET enrichment in clots is associated with reduced mFPE success. With further validation, RFs extracted from prethrombectomy computed tomography imaging may serve as noninvasive biomarkers of clot NET content to aid in preprocedural MT decision-making.