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Bioscience Reports Jul 2023The mortality of heart failure after acute myocardial infarction (AMI) remains high. The aim of the present study was to analyze hub genes and immune infiltration in...
The mortality of heart failure after acute myocardial infarction (AMI) remains high. The aim of the present study was to analyze hub genes and immune infiltration in patients with AMI and heart failure (HF). The study utilized five publicly available gene expression datasets from peripheral blood in patients with AMI who either developed or did not develop HF. The unbiased patterns of 24 immune cell were estimated by xCell algorithm. Single-cell RNA sequencing data were used to examine the immune cell infiltration in heart failure patients. Hub genes were validated by quantitative reverse transcription-PCR (RT-qPCR). In comparison with the coronary heart disease (CHD) group, immune infiltration analysis of AMI patients showed that macrophages M1, macrophages, monocytes, natural killer (NK) cells, and NKT cells were the five most highly activated cell types. Five common immune-related genes (S100A12, AQP9, CSF3R, S100A9, and CD14) were identified as hub genes associated with AMI. Using RT-qPCR, we confirmed FOS, DUSP1, CXCL8, and NFKBIA as the potential biomarkers to identify AMI patients at risk of HF. The study identified several transcripts that differentiate between AMI and CHD, and between HF and non-HF patients. These findings could improve our understanding of the immune response in AMI and HF, and allow for early identification of AMI patients at risk of HF.
Topics: Humans; Heart Failure; Myocardial Infarction; Risk Assessment; Monocytes; Biomarkers
PubMed: 37334672
DOI: 10.1042/BSR20222552 -
Neurology Jun 2023Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic...
BACKGROUND AND OBJECTIVES
Female patients tend to have greater disability and worse long-term outcomes after stroke than male patients. To date, the biological basis of sex difference in ischemic stroke remains unclear. We aimed to (1) assess sex differences in clinical manifestation and outcomes of acute ischemic stroke and (2) investigate whether the sex disparity is due to different infarct locations or different impacts of infarct in the same location.
METHODS
This MRI-based multicenter study included 6,464 consecutive patients with acute ischemic stroke (<7 days) from 11 centers in South Korea (May 2011-January 2013). Multivariable statistical and brain mapping methods were used to analyze clinical and imaging data collected prospectively: admission NIH Stroke Scale (NIHSS) score, early neurologic deterioration (END) within 3 weeks, modified Rankin Scale (mRS) score at 3 months, and culprit cerebrovascular lesion (symptomatic large artery steno-occlusion and cerebral infarction) locations.
RESULTS
The mean (SD) age was 67.5 (12.6) years, and 2,641 (40.9%) were female patients. Percentage infarct volumes on diffusion-weighted MRI did not differ between female patients and male patients (median 0.14% vs 0.14%, = 0.35). However, female patients showed higher stroke severity (NIHSS score, median 4 vs 3, < 0.001) and had more frequent END (adjusted difference 3.5%; = 0.002) than male patients. Female patients had more frequent striatocapsular lesions (43.6% vs 39.8%, = 0.001) and less frequent cerebrocortical (48.2% vs. 50.7% in patients older than 52 years, = 0.06) and cerebellar (9.1% vs. 11.1%, = 0.009) lesions than male patients, which aligned with angiographic findings: female patients had more prevalent symptomatic steno-occlusion of the middle cerebral artery (MCA) (31.1% vs 25.3%; < 0.001) compared with male patients, who had more frequent symptomatic steno-occlusion of the extracranial internal carotid artery (14.2% vs 9.3%; < 0.001) and vertebral artery (6.5% vs 4.7%; = 0.001). Cortical infarcts in female patients, specifically left-sided parieto-occipital regions, were associated with higher NIHSS scores than expected for similar infarct volumes in male patients. Consequently, female patients had a higher likelihood of unfavorable functional outcome (mRS score >2) than male patients (adjusted absolute difference 4.5%; 95% CI 2.0-7.0; < 0.001).
DISCUSSION
Female patients have more frequent MCA disease and striatocapsular motor pathway involvement with acute ischemic stroke, along with left parieto-occipital cortical infarcts showing greater severity for equivalent infarct volumes than in male patients. This leads to more severe initial neurologic symptoms, higher susceptibility to neurologic worsening, and less 3-month functional independence, when compared with male patients.
Topics: Humans; Female; Male; Aged; Sex Characteristics; Ischemic Stroke; Treatment Outcome; Stroke; Cerebral Infarction; Brain Ischemia; Retrospective Studies
PubMed: 37094993
DOI: 10.1212/WNL.0000000000207346 -
Atherosclerosis Aug 2023Elevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both...
BACKGROUND AND AIMS
Elevated remnant cholesterol and low-grade inflammation each cause atherosclerotic cardiovascular disease (ASCVD); however, it is unknown whether joint elevation of both factors confers the highest risk. We tested the hypothesis that dual elevated remnant cholesterol and low-grade inflammation marked by elevated C-reactive protein is associated with the highest risk of myocardial infarction, ASCVD, and all-cause mortality.
METHODS
The Copenhagen General Population Study randomly recruited white Danish individuals aged 20-100 years in 2003-2015 and followed them for a median 9.5 years. ASCVD was cardiovascular mortality, myocardial infarction, stroke, and coronary revascularization.
RESULTS
In 103,221 individuals, we observed 2,454 (2.4%) myocardial infarctions, 5,437 (5.3%) ASCVD events, and 10,521 (10.2%) deaths. The hazard ratios increased with each of stepwise higher remnant cholesterol and stepwise higher C-reactive protein. In individuals with the highest tertile of both remnant cholesterol and C-reactive protein compared to individuals with the lowest tertile of both, the multivariable adjusted hazard ratios were 2.2 (95%CI:1.9-2.7) for myocardial infarction, 1.9 (1.7-2.2) for ASCVD, and 1.4 (1.3-1.5) for all-cause mortality. Corresponding values for only the highest tertile of remnant cholesterol were 1.6 (1.5-1.8), 1.4 (1.3-1.5), and 1.1 (1.0-1.1), and those for only the highest tertile of C-reactive protein were 1.7 (1.5-1.8), 1.6 (1.5-1.7), and 1.3 (1.3-1.4), respectively. There was no statistical evidence for interaction between elevated remnant cholesterol and elevated C-reactive protein on risk of myocardial infarction (p = 0.10), ASCVD (p = 0.40), or all-cause mortality (p = 0.74).
CONCLUSIONS
Dual elevated remnant cholesterol and C-reactive protein confers the highest risk of myocardial infarction, ASCVD, and all-cause mortality, that is, compared to either of these two factors individually.
Topics: Humans; C-Reactive Protein; Cardiovascular Diseases; Risk Factors; Myocardial Infarction; Atherosclerosis; Cholesterol; Hypercholesterolemia; Inflammation
PubMed: 37217436
DOI: 10.1016/j.atherosclerosis.2023.05.010 -
Molecular Immunology May 2024Myocardial ischemia-reperfusion injury (MIRI) is a complex process that occurs when blood flow is restored after myocardium infarction (MI) with exacerbated tissue... (Review)
Review
Myocardial ischemia-reperfusion injury (MIRI) is a complex process that occurs when blood flow is restored after myocardium infarction (MI) with exacerbated tissue damage. Macrophages, essential cell type of the immune response, play an important role in MIRI. Macrophage subpopulations, namely M1 and M2, are distinguished by distinct phenotypes and functions. In MIRI, macrophages infiltrate in infarcted area, shaping the inflammatory response and influencing tissue healing. Resident cardiac macrophages interact with monocyte-derived macrophages in MIRI, and influence injury progression. Key factors including chemokines, cytokines, and toll-like receptors modulate macrophage behavior in MIRI. This review aims to address recent findings on the classification and the roles of macrophages in the myocardium, spanning from MI to subsequent MIRI, and highlights various signaling pathways implicated in macrophage polarization underlining the complexity of MIRI. This article will shed light on developing advanced therapeutic strategies for MIRI management.
Topics: Humans; Myocardial Reperfusion Injury; Myocardium; Macrophages; Myocardial Infarction; Signal Transduction
PubMed: 38447462
DOI: 10.1016/j.molimm.2024.02.007 -
Revista Da Sociedade Brasileira de... 2023
Topics: Humans; Splenic Infarction; Malaria, Falciparum; Plasmodium falciparum
PubMed: 37792838
DOI: 10.1590/0037-8682-0330-2023 -
Cardiovascular Research Dec 2023The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a transforming growth factor-β superfamily member that shares 90% homology with...
AIMS
The heart rejuvenating effects of circulating growth differentiation factor 11 (GDF11), a transforming growth factor-β superfamily member that shares 90% homology with myostatin (MSTN), remains controversial. Here, we aimed to probe the role of GDF11 in acute myocardial infarction (MI), a frequent cause of heart failure and premature death during ageing.
METHODS AND RESULTS
In contrast to endogenous Mstn, myocardial Gdf11 declined during the course of ageing and was particularly reduced following ischaemia/reperfusion (I/R) injury, suggesting a therapeutic potential of GDF11 signalling in MI. Unexpectedly, boosting systemic Gdf11 by recombinant GDF11 delivery (0.1 mg/kg body weight over 30 days) prior to myocardial I/R augmented myocardial infarct size in C57BL/6 mice irrespective of their age, predominantly by accelerating pro-apoptotic signalling. While intrinsic cardioprotective signalling pathways remained unaffected by high circulating GDF11, targeted transcriptomics and immunomapping studies focusing on GDF11-associated downstream targets revealed attenuated Nkx2-5 expression confined to CD105-expressing cells, with pro-apoptotic activity, as assessed by caspase-3 levels, being particularly pronounced in adjacent cells, suggesting an indirect effect. By harnessing a highly specific and validated liquid chromatography-tandem mass spectrometry-based assay, we show that in prospectively recruited patients with MI circulating GDF11 but not MSTN levels incline with age. Moreover, GDF11 levels were particularly elevated in those at high risk for adverse outcomes following the acute event, with circulating GDF11 emerging as an independent predictor of myocardial infarct size, as estimated by standardized peak creatine kinase-MB levels.
CONCLUSION
Our data challenge the initially reported heart rejuvenating effects of circulating GDF11 and suggest that high levels of systemic GDF11 exacerbate myocardial injury in mice and humans alike. Persistently high GDF11 levels during ageing may contribute to the age-dependent loss of cardioprotective mechanisms and thus poor outcomes of elderly patients following acute MI.
Topics: Aged; Animals; Humans; Mice; Aging; Bone Morphogenetic Proteins; Growth Differentiation Factors; Heart; Heart Injuries; Mice, Inbred C57BL; Myocardial Infarction
PubMed: 37742057
DOI: 10.1093/cvr/cvad153 -
JAMA Network Open Aug 2023The COVID-19 pandemic disrupted usual care for emergent conditions, such as acute myocardial infarction (AMI). Understanding whether Black and Hispanic individuals...
IMPORTANCE
The COVID-19 pandemic disrupted usual care for emergent conditions, such as acute myocardial infarction (AMI). Understanding whether Black and Hispanic individuals experiencing AMI had greater increases in poor outcomes compared with White individuals during the pandemic has important equity implications.
OBJECTIVE
To investigate whether the COVID-19 pandemic was associated with increased disparities in treatment and outcomes among Medicare patients hospitalized with AMI.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used Medicare data for patients hospitalized with AMI between January 2016 and November 2020. Patients were categorized as Hispanic, non-Hispanic Black, and non-Hispanic White. The association between race and ethnicity and outcomes as a function of the proportion of hospitalized patients with COVID-19 was evaluated using interrupted time series. Data were analyzed from October 2022 to June 2023.
EXPOSURE
The main exposure was a hospital's proportion of hospitalized patients with COVID-19 on a weekly basis as a proxy for care disruption during the pandemic.
MAIN OUTCOMES AND MEASURES
Revascularization, 30-day mortality, 30-day readmission, and nonhome discharges.
RESULTS
A total of 1 319 273 admissions for AMI (579 817 females [44.0%]; 122 972 Black [9.3%], 117 668 Hispanic [8.9%], and 1 078 633 White [81.8%]; mean [SD] age, 77 [8.4] years) were included. For patients with non-ST segment elevation MI (NSTEMI) overall, the adjusted odds of mortality and nonhome discharges increased by 51% (adjusted odds ratio [aOR], 1.51; 95% CI, 1.29-1.76; P < .001) and 32% (aOR, 1.32; 95% CI, 1.15-1.52; P < .001), respectively, and the odds of revascularization decreased by 27% (aOR, 0.73; 95% CI, 0.64-0.83; P < .001) among patients hospitalized during weeks with a high hospital COVID-19 burden (>30%) vs patients hospitalized prior to the pandemic. Black individuals with NSTEMI experienced a clinically insignificant 7% greater increase in the odds of mortality (aOR, 1.07; 95% CI, 1.00-1.15; P = .04) for each 10% increase in the COVID-19 hospital burden but no increases in readmissions or nonhome discharges or reductions in revascularization rates compared with White individuals. There were no differential increases in adverse outcomes among Hispanic compared with White patients with NSTEMI based on hospital COVID-19 burden. Increases in hospital COVID-19 burden were not associated with changes in outcomes or the use of revascularization in STEMI overall or by racial or ethnic group.
CONCLUSIONS AND RELEVANCE
This study found that while hospital COVID-19 burden was associated with worse treatment and outcomes for NSTEMI, race and ethnicity-associated inequities did not increase significantly during the pandemic. These findings suggest the need for additional efforts to mitigate outcomes associated with the COVID-19 pandemic for patients admitted with AMI when the hospital COVID-19 burden is substantially increased.
Topics: United States; Female; Humans; Aged; Non-ST Elevated Myocardial Infarction; Pandemics; COVID-19; Cross-Sectional Studies; Medicare; Myocardial Infarction; Treatment Outcome
PubMed: 37624599
DOI: 10.1001/jamanetworkopen.2023.30327 -
International Journal of Nanomedicine 2023Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted...
PURPOSE
Myocardial ischemia-reperfusion injury after myocardial infarction has always been a difficult problem in clinical practice. Endothelial cells and their secreted extracellular vesicles are closely related to inflammation, thrombosis formation, and other processes after injury. Meanwhile, low-molecular-weight gelators have shown great potential for nasal administration. This study aims to explore the therapeutic effects and significance of endothelial cell-derived extracellular vesicles combined with a hydrogel for nasal administration on myocardial ischemia-reperfusion injury.
METHODS
We chose a gel system composed of a derivative of glutamine amide and benzaldehyde as the extracellular vesicle delivery vehicle. This hydrogel was combined with extracellular vesicles extracted from mouse aortic endothelial cells and administered multiple times intranasally in a mouse model of ischemia-reperfusion injury to the heart. The delivery efficiency of the extracellular vesicle-hydrogel combination was evaluated by flow cytometry and immunofluorescence. Echocardiography, TTC Evan's Blue and Masson's staining were used to assess mouse cardiac function, infarct area, and cardiac fibrosis level. Flow cytometry, ELISA, and immunofluorescence staining were used to investigate changes in mouse inflammatory cells, cytokines, and vascular neogenesis.
RESULTS
The vesicles combined with the hydrogel have good absorption in the nasal cavity. The hydrogel combined with vesicles reduces the levels of pro-inflammatory Ly6C (high) monocytes/macrophages and neutrophils. It can also reduce the formation of microcirculation thrombi in the infarcted area, improve endothelial barrier function, and increase microvascular density in the injured area. As a result, the heart function of mice is improved and the infarct area is reduced.
CONCLUSION
We first demonstrated that the combination of extracellular vesicles and hydrogel has a better absorption efficiency in the nasal cavity, which can improve myocardial ischemia-reperfusion injury by inhibiting inflammatory reactions and protecting endothelial function. Nasal administration of vesicles combined with hydrogel is a potential therapeutic direction.
Topics: Mice; Animals; Myocardial Reperfusion Injury; Endothelial Cells; Administration, Intranasal; Myocardial Infarction; Hydrogels; Extracellular Vesicles
PubMed: 37791323
DOI: 10.2147/IJN.S420301 -
Basic Research in Cardiology Jun 2023Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in...
Whereas prior experiments in juvenile pigs had reported infarct size reduction by intravenous metoprolol early during myocardial ischaemia, two major clinical trials in patients with reperfused acute myocardial infarction were equivocal. We, therefore, went back and tested the translational robustness of infarct size reduction by metoprolol in minipigs. Using a power analysis-based prospective design, we pretreated 20 anaesthetised adult Göttingen minipigs with 1 mg kg metoprolol or placebo and subjected them to 60-min coronary occlusion and 180-min reperfusion. Primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was a secondary endpoint. There was no significant reduction in infarct size (46 ± 8% of area at risk with metoprolol vs. 42 ± 8% with placebo) or area of no-reflow (19 ± 21% of infarct size with metoprolol vs. 15 ± 23% with placebo). However, the inverse relationship between infarct size and ischaemic regional myocardial blood flow was modestly, but significantly shifted downwards with metoprolol, whereas ischaemic blood flow tended to be reduced by metoprolol. With an additional dose of 1 mg kg metoprolol after 30-min ischaemia in 4 additional pigs, infarct size was also not reduced (54 ± 9% vs. 46 ± 8% in 3 contemporary placebo, n.s.), and area of no-reflow tended to be increased (59 ± 20% vs. 29 ± 12%, n.s.).Infarct size reduction by metoprolol in pigs is not robust, and this result reflects the equivocal clinical trials. The lack of infarct size reduction may be the result of opposite effects of reduced infarct size at any given blood flow and reduced blood flow, possibly through unopposed alpha-adrenergic coronary vasoconstriction.
Topics: Animals; Metoprolol; Myocardial Infarction; Myocardial Ischemia; Myocardium; Swine; Swine, Miniature
PubMed: 37289247
DOI: 10.1007/s00395-023-00993-4 -
Circulation Jul 2023Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant...
BACKGROUND
Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant identification of risk mediators. Therefore, we assessed mediators of the association between socioeconomic status and first recurrent atherosclerotic cardiovascular disease event (rASCVD) after MI.
METHODS
In this cohort study on 1-year survivors of first-ever MI with Swedish universal health coverage ages 18 to 76 years, individual-level data from SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and linked national registries was collected from 2006 through 2020. Exposure was socioeconomic status by disposable income quintile (principal proxy), educational level, and marital status. The primary outcome was rASCVD and secondary outcomes were cardiovascular and all-cause mortality. We initially assessed the incremental attenuation of hazard ratios with 95% CIs in sequential multivariable models adding groups of potential mediators (ie, previous risk factors, acute presentation and infarct severity, initial therapies, and secondary prevention). Thereafter, the proportion of excess rASCVD associated with a low income mediated through nonparticipation in cardiac rehabilitation, suboptimal statin management, a cardiometabolic risk profile, persistent smoking, and blood pressure above target after MI were calculated using causal mediation analysis.
RESULTS
Among 68 775 participants (73.8% men), 7064 rASCVD occurred during a mean 5.7-year follow-up. Income, adjusted for age, sex, and calendar year, was associated with rASCVD (hazard ratio, 1.63 [95% CI, 1.51-1.76] in the lowest versus highest income quintile). Risk attenuated most by adjustment for previous risk factors and by adding secondary prevention variables for a final model (hazard ratio, 1.38 [95% CI, 1.26-1.51]) in the lowest versus highest income quintile. The proportions of the excess 15-year rASCVD risk in the lowest income quintile mediated through nonparticipation in cardiac rehabilitation, cardiometabolic risk profile, persistent smoking, and poor blood pressure control were 3.3% (95% CI 2.1-4.8), 3.9% (95% CI, 2.9-5.5), 15.2% (95% 9.1-25.7), and 1.0% (95% CI 0.6-1.5), respectively. Risk mediation through optimal statin management was negligible.
CONCLUSIONS
Nonparticipation in cardiac rehabilitation, a cardiometabolic risk profile, and persistent smoking mediate income-dependent prognosis after MI. In the absence of randomized trials, this causal inference approach may guide decisions to improve health equity.
Topics: Male; Humans; Female; Cardiovascular Diseases; Cohort Studies; Socioeconomic Disparities in Health; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Atherosclerosis; Risk Factors
PubMed: 37459408
DOI: 10.1161/CIRCULATIONAHA.123.064440