Association of low muscle mass and obesity with increased all-cause and cardiovascular disease mortality in US adults.

BACKGROUND: Sarcopenic obesity, defined as the coexistence of low muscle mass and high adiposity, is associated with cardiovascular disease (CVD) and mortality. However, to what extent sarcopenia contributes to these risks independently or in conjunction with other cardiovascular risk factors remains unclear. This study aimed to investigate the association of low muscle mass, central obesity (COB), metabolic abnormalities, and their combinations with CVD and mortality risk. METHODS: This cross-sectional analysis used data from the National Health and Nutrition Examination Survey 1999-2006 and 2011-2018. Participants aged >20 years and with reported whole-body dual X-ray absorptiometry data were included. Participants were divided into eight groups based on low muscle mass, metabolic abnormalities, and COB status. RESULTS: The mean age of participants was 55 years, and 50.4% of participants were male. Low muscle mass was observed in 2472 (14.6%) out of 16 839 participants. Among the eight groups, the metabolically unhealthy COB group with low muscle mass had the highest hazard ratio (HR) for all-cause mortality (HR, 2.00; 95% CI, 1.56-2.56; P < 0.001), whereas the metabolically healthy COB group with low muscle mass had the highest HR for CVD mortality (HR, 3.18; 95% CI, 1.53-6.65; P = 0.001). The mediation analysis showed that low muscle mass directly increased the risk of both all-cause mortality (HR, 1.56; 95% CI, 1.35-1.79; P < 0.001) and CVD mortality (HR, 1.80; 95% CI, 1.40-2.31; P < 0.001). Additionally, subgroup analysis revealed that low muscle mass significantly increased the risk of all-cause and CVD mortality in participants without a prior CVD history and those with diabetes mellitus. CONCLUSIONS: Low muscle mass is an independent risk factor for all-cause and CVD mortality, especially in individuals with metabolic abnormalities and COB.

Integrative analysis of mitochondrial metabolic reprogramming in early-stage colon and liver cancer.

Gastrointestinal malignancies, including colon adenocarcinoma (COAD) and liver hepatocellular carcinoma (LIHC), remain leading causes of cancer-related deaths worldwide. To better understand the underlying mechanisms of these cancers and identify potential therapeutic targets, we analyzed publicly accessible Cancer Genome Atlas datasets of COAD and LIHC. Our analysis revealed that differentially expressed genes (DEGs) during early tumorigenesis were associated with cell cycle regulation. Additionally, genes related to lipid metabolism were significantly enriched in both COAD and LIHC, suggesting a crucial role for dysregulated lipid metabolism in their development and progression. We also identified a subset of DEGs associated with mitochondrial function and structure, including upregulated genes involved in mitochondrial protein import and respiratory complex assembly. Further, we identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) as a crucial regulator of cancer cell metabolism. Using a genome-scale metabolic model, we demonstrated that HMGCS2 suppression increased glycolysis, lipid biosynthesis, and elongation while decreasing fatty acid oxidation in colon cancer cells. Our study highlights the potential contribution of dysregulated lipid metabolism, including ketogenesis, to COAD and LIHC development and progression and identifies potential therapeutic targets for these malignancies.

Integrative Evaluation of the Clinical Significance Underlying Protein Arginine Methyltransferases in Hepatocellular Carcinoma.

HCC is a major contributor to cancer-related mortality worldwide. Curative treatments are available for a minority of patients diagnosed at early stages; however, only a few multikinase inhibitors are available and are marginally effective in advanced cases, highlighting the need for novel therapeutic targets. One potential target is the protein arginine methyltransferase, which catalyzes various forms of arginine methylation and is often overexpressed in various cancers. However, the diverse expression patterns and clinical values of PRMTs in HCC remain unclear. In the present study, we evaluated the transcriptional expression of PRMTs in HCC cohorts using publicly available datasets. Our results revealed a significant association between PRMTs and prognosis in HCC patients with diverse clinical characteristics and backgrounds. This highlights the promising potential of PRMTs as prognostic biomarkers in patients with HCC. In particular, single-cell RNA (scRNA) sequencing analysis coupled with another human cohort study highlighted the pivotal role of PRMT1 in HCC progression, particularly in the context of Tex. Translating these findings into specific therapeutic decisions may address the unmet therapeutic needs of patients with HCC.

LY6D is crucial for lipid accumulation and inflammation in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a serious metabolic disorder characterized by excess fat accumulation in the liver. Over the past decade, NAFLD prevalence and incidence have risen globally. There are currently no effective licensed drugs for its treatment. Thus, further study is required to identify new targets for NAFLD prevention and treatment. In this study, we fed C57BL6/J mice one of three diets, a standard chow diet, high-sucrose diet, or high-fat diet, and then characterized them. The mice fed a high-sucrose diet had more severely compacted macrovesicular and microvesicular lipid droplets than those in the other groups. Mouse liver transcriptome analysis identified lymphocyte antigen 6 family member D (Ly6d) as a key regulator of hepatic steatosis and the inflammatory response. Data from the Genotype-Tissue Expression project database showed that individuals with high liver Ly6d expression had more severe NAFLD histology than those with low liver Ly6d expression. In AML12 mouse hepatocytes, Ly6d overexpression increased lipid accumulation, while Ly6d knockdown decreased lipid accumulation. Inhibition of Ly6d ameliorated hepatic steatosis in a diet-induced NAFLD mouse model. Western blot analysis showed that Ly6d phosphorylated and activated ATP citrate lyase, which is a key enzyme in de novo lipogenesis. In addition, RNA- and ATAC-sequencing analyses revealed that Ly6d drives NAFLD progression by causing genetic and epigenetic changes. In conclusion, Ly6d is responsible for the regulation of lipid metabolism, and inhibiting Ly6d can prevent diet-induced steatosis in the liver. These findings highlight Ly6d as a novel therapeutic target for NAFLD.

Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer.

Introduction: Regarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC). Methods: A review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0). Results: Among 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth's bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration. Conclusions: Given the incidence and favorable outcome of BM in patients with suspected early-stage NSCLC, selective screening with brain MRI may be considered, especially in patients with high-risk features.

Obesity and novel management of inflammatory bowel disease.

Obesity is prevalent within the inflammatory bowel disease (IBD) population, particularly in newly developed countries. Several epidemiological studies have suggested that 15%-40% of IBD patients are obese, and there is a potential role of obesity in the pathogenesis of IBD. The dysfunction of mesenteric fat worsens the inflammatory course of Crohn's disease and may induce formation of strictures or fistulas. Furthermore, obesity may affect the disease course or treatment response of IBD. Given the increasing data supporting the pathophysiologic and epidemiologic relationship between obesity and IBD, obesity control is being suggested as a novel management for IBD. Therefore, this review aimed to describe the influence of obesity on the outcomes of IBD treatment and to present the current status of pharmacologic or surgical anti-obesity treatments in IBD patients.

Smoking and passive smoking increases mortality through mediation effect of cadmium exposure in the United States.

Cigarette smoking is one of the leading causes of preventable and premature death worldwide. Even worse, many people are generally exposed to passive smoking, which leads to several respiratory diseases and related mortalities. Considering, more than 7000 compounds are included in cigarettes, their combustion results intoxicants that have deleterious effects on health. However, there is a lack of research analyzing the effects of smoking and passive smoking on all-cause and disease-specific mortality through its chemical compounds including heavy metals. Thus, this study aimed to evaluate the effect of smoking and passive smoking on all-cause and disease-specific mortality mediated by cadmium, one of the representative smoking-related heavy metals using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 in the United States. We found that current smoking and passive smoking was related to increased risk of all-cause, CVD-related, and cancer-related mortality. Notably, passive smoking showed a synergistic effect with smoking status on the risk of mortality. In particular, current smokers with passive smoking had the highest risk of all-cause and disease-specific deaths. In addition, the accumulation of cadmium in the blood due to smoking and passive smoking mediates the increased risk of all-cause mortality. Further studies are needed to monitor and treat cadmium toxicity to improve smoking-related mortality rates.

Combined Therapy of Low-Dose Angiotensin Receptor-Neprilysin Inhibitor and Sodium-Glucose Cotransporter-2 Inhibitor Prevents Doxorubicin-Induced Cardiac Dysfunction in Rodent Model with Minimal Adverse Effects.

Although cancer-therapy-related cardiac dysfunction (CTRCD) is a critical issue in clinical practice, there is a glaring lack of evidence regarding cardiotoxicity management. To determine an effective and suitable dosage of treatment using angiotensin receptor-neprilysin inhibitors (ARNI) with sodium-glucose cotransporter 2 inhibitors (SGLT2i), we adopted a clinically relevant rodent model with doxorubicin, which would mimic cardiac dysfunction in CTRCD patients. After the oral administration of drugs (vehicle, SGLT2i, ARNI, Low-ARNI/SGLT2i, ARNI/SGLT2i), several physiologic parameters, including hemodynamic change, cardiac function, and histopathology, were evaluated. Bulk RNA-sequencing was performed to obtain insights into the molecular basis of a mouse heart response to Low-ARNI/SGLT2i treatment. For the first time, we report that the addition of low-dose ARNI with SGLT2i resulted in greater benefits than ARNI, SGLT2i alone or ARNI/SGLT2i combination in survival rate, cardiac function, hemodynamic change, and kidney function against doxorubicin-induced cardiotoxicity through peroxisome proliferator-activated receptor signaling pathway. Low-dose ARNI with SGLT2i combination treatment would be practically beneficial for improving cardiac functions against doxorubicin-induced heart failure with minimal adverse effects. Our findings suggest the Low-ARNI/SGLT2i combination as a feasible novel strategy in managing CTRCD patients.

Serotonin in the regulation of systemic energy metabolism.

Serotonin is a well-known neurotransmitter that is synthesized from the amino acid, tryptophan. To date, more than 14 different serotonin receptors have been discovered; they exist universally in our body and enable diverse biological functions in different organs. Central serotonin regulates mood and behavior, and impacts the systemic energy balance by decreasing appetite. A number of drugs that modulate central serotonin function (e.g., fenfluramine, sibutramine and lorcaserin) were approved and used as anti-obesity drugs, but then later withdrawn due to adverse cardiovascular and carcinogenic effects. Over the past decade, the role of peripheral serotonin in regulating systemic energy metabolism has been extensively explored using tissue-specific knockout animal models. By inhibiting the action of serotonin in liver and adipose tissues, hepatic steatosis was improved and lipid accumulation was mitigated, respectively. Recent findings show that modulation of the serotonergic system is a promising therapeutic target for metabolic diseases. This review summarizes the role of serotonin in regulating energy metabolism in different organs, and discusses the potential of serotonin modulation for treating metabolic diseases.

A Systems Biology Approach to Investigating the Interaction between Serotonin Synthesis by Tryptophan Hydroxylase and the Metabolic Homeostasis.

Obesity has become a global public health and economic problem. Obesity is a major risk factor for a number of complications, such as type 2 diabetes, cardiovascular disease, fatty liver disease, and cancer. Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic monoamine that plays various roles in metabolic homeostasis. It is well known that central 5-HT regulates appetite and mood. Several 5-HT receptor agonists and selective serotonin receptor uptake inhibitors (SSRIs) have shown beneficial effects on appetite and mood control in clinics. Although several genetic polymorphisms related to 5-HT synthesis and its receptors are strongly associated with obesity, there is little evidence of the role of peripheral 5-HT in human metabolism. In this study, we performed a systemic analysis of transcriptome data from the Genotype-Tissue Expression (GTEX) database. We investigated the expression of 5-HT and tryptophan hydroxylase (TPH), the rate-limiting enzyme of 5-HT biosynthesis, in the human brain and peripheral tissues. We also performed differential gene expression analysis and predicted changes in metabolites by comparing gene expressions of tissues with high TPH expression to the gene expressions of tissues with low TPH expression. Our analyses provide strong evidence that serotonin plays an important role in the regulation of metabolic homeostasis in humans.

NAD+ boosting reduces age-associated amyloidosis and restores mitochondrial homeostasis in muscle.

Aging is characterized by loss of proteostasis and mitochondrial homeostasis. Here, we provide bioinformatic evidence of dysregulation of mitochondrial and proteostasis pathways in muscle aging and diseases. Moreover, we show accumulation of amyloid-like deposits and mitochondrial dysfunction during natural aging in the body wall muscle of C. elegans, in human primary myotubes, and in mouse skeletal muscle, partially phenocopying inclusion body myositis (IBM). Importantly, NAD+ homeostasis is critical to control age-associated muscle amyloidosis. Treatment of either aged N2 worms, a nematode model of amyloid-beta muscle proteotoxicity, human aged myotubes, or old mice with the NAD+ boosters nicotinamide riboside (NR) and olaparib (AZD) increases mitochondrial function and muscle homeostasis while attenuating amyloid accumulation. Hence, our data reveal that age-related amyloidosis is a contributing factor to mitochondrial dysfunction and that both are features of the aging muscle that can be ameliorated by NAD+ metabolism-enhancing approaches, warranting further clinical studies.

Combination Immunotherapy Using Oncolytic Virus for the Treatment of Advanced Solid Tumors.

Oncolytic virus (OV) is a new therapeutic strategy for cancer treatment. OVs can selectively infect and destroy cancer cells, and therefore act as an in situ cancer vaccine by releasing tumor-specific antigens. Moreover, they can remodel the tumor microenvironment toward a T cell-inflamed phenotype by stimulating widespread host immune responses against the tumor. Recent evidence suggests several possible applications of OVs against cancer, especially in combination with immune checkpoint inhibitors. In this review, we describe the molecular mechanisms of oncolytic virotherapy and OV-induced immune responses, provide a brief summary of recent preclinical and clinical updates on this rapidly evolving field, and discuss a combinational strategy that is able to overcome the limitations of OV-based monotherapy.

Effect of body shape on the development of cardiovascular disease in individuals with metabolically healthy obesity.

Studies about the effects of metabolically healthy obesity on cardiovascular disease (CVD) have yielded conflicting results. These heterogeneous results could be due to the limited usefulness of BMI in measuring general adiposity, as body mass index (BMI) does not accurately reflect body composition. This study aimed to evaluate the effect of body shape on CVD outcomes across different obesity phenotypes, and to provide an explanation for the heterogeneous effects of metabolically healthy obese (MHO) phenotype on CVD.We analyzed data from the Korean Genome and Epidemiology Study, a population-based cohort study conducted between 2001 and 2012. We divided the participants into 4 groups: metabolically healthy non-obese (MHNO), MHO, metabolically unhealthy non-obese (MUNO), and metabolically unhealthy obese (MUO). To assess body shape, we calculated the z-score of the log-transformed a body shape index (LBSIZ). We computed Pearson correlation coefficients to examine the association of LBSIZ with muscle mass index, percentage of total fat mass (%Total FM), and percentage of abdominal fat mass (%Abdominal FM). We also used Cox proportional hazards regression to evaluate the effect of LBSIZ on CVD events according to the obesity phenotypes.A total of 9460 participants were assessed in this study. The incidence of CVD was 8.53 cases per 1000 person-year. LBSIZ showed strong positive correlation with %Total FM and %Abdominal FM, but negative correlation with muscle mass index. In Cox regression, MHO individuals did not show increased risk of CVD compared with MHNO individuals (hazard ratio [HR], 1.29; 95% confidence interval [CI], 0.96-1.73). However, MHO individuals in the 3rd (HR, 2.40; 95% CI, 1.28-4.51) and 4th (HR, 3.67; 95% CI, 1.99-6.74) quarters of LBSIZ showed significantly higher risk of CVD compared with MHNO individuals in the 1st quarter of LBSIZ. Moreover, LBSIZ showed a linear relationship with CVD among MHO individuals.While the MHO individuals showed similar CVD risk to the MHNO individuals, CVD risk increases with LBSIZ among the MHO individuals. LBSIZ appears to be a useful measure for CVD risk assessment in clinical practice and epidemiologic studies, especially for MHO patients.

Serotonin Regulates De Novo Lipogenesis in Adipose Tissues through Serotonin Receptor 2A.

BACKGROUND: Obesity is defined as excessive fat mass and is a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer. Increasing energy expenditure and regulating adipose tissue metabolism are important targets for the treatment of obesity. Serotonin (5-hydroxytryptophan [5-HT]) is a monoamine metabolite of the essential amino acid tryptophan. Here, we demonstrated that 5-HT in mature adipocytes regulated energy expenditure and lipid metabolism. METHODS: Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme during 5-HT synthesis in non-neural peripheral tissues. We generated adipose tissue-specific Tph1 knockout (Tph1 FKO) mice and adipose tissue-specific serotonin receptor 2A KO (Htr2a FKO) mice and analyzed their phenotypes during high-fat diet (HFD) induced obesity. RESULTS: Tph1 FKO mice fed HFD exhibited reduced lipid accumulation, increased thermogenesis, and resistance to obesity. In addition, Htr2a FKO mice fed HFD showed reduced lipid accumulation in white adipose tissue and resistance to obesity. CONCLUSION: These data suggest that the inhibition of serotonin signaling might be an effective strategy in obesity.

SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1ß release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1ß secretion compared to sulfonylurea accompanied by increased serum ß-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.

The influence of physical activity on risk of cardiovascular disease in people who are obese but metabolically healthy.

The metabolic outcomes of metabolically healthy obesity (MHO) remain controversial. The aim of the present study was to determine the effect of physical activity on the cardiovascular disease (CVD) outcomes of MHO. The study included participants who were followed for 10 years and recruited from the Korean Genome and Epidemiology Study (KoGES), a population-based cohort study. Participants with previously recorded CVDs or cancer, or who had received steroids or anticoagulants at baseline were excluded. A total of 8144 participants (3,942 men and 4,202 women) fulfilled inclusion criteria. In a multivariate Cox regression model adjusted for age and sex, MHO participants were not at elevated risk of CVD compared with their metabolically healthy non-obese (MHNO) counterparts (HR, 1.28; 95% CI, 0.96-1.71), although both the non-obese (HR, 1.50; 95% CI, 1.19-1.90) and obese (HR, 1.85; 95% CI, 1.48-2.30) participants with metabolic abnormalities were at elevated risk. However, in the subgroup analysis by physical activity, physically inactive MHO participants had a significantly higher HR for CVD events compared to active MHNO participants (HR, 1.54; 95% CI, 1.03-2.30), while active MHO participants were not at elevated risk (HR, 1.15; 95% CI, 0.70-1.89). Physically inactive MHO participants had significantly increased risk of CVD compared to physically active MHNO participants whereas physically active MHO participants did not.

Percutaneous cardiopulmonary support-supported percutaneous coronary intervention: a single center experience.

BACKGROUND AND OBJECTIVES: Percutaneous cardiopulmonary support (PCPS) has proven to be a valuable technique in high-risk coronary patients undergoing percutaneous coronary intervention (PCI). However, there have been few studies on PCI associated with PCPS in Korea. We summarized our experience with PCPS-supported PCI. SUBJECTS AND METHODS: We retrospectively reviewed 19 patients with PCPS-supported PCI between August 2005 and June 2009. PCPS was used as an elective procedure for 10 patients with at least two of the following conditions: left-ventricular ejection fraction <35%, target vessel(s) supplying more than 50% of the viable myocardium, high risk surgical patients, and patients who refused coronary bypass surgery. In the remaining 9 patients PCPS was used as an emergency procedure, to stabilize and even resuscitate patients with acute myocardial infarction and cardiogenic shock, in order to attempt urgent PCI. RESULTS: Among the 19 patients who were treated with PCPS-supported PCI, 11 (57.9%) survived and 8 (42.1%) patients did not. ST elevation myocardial infarction with cardiogenic shock was more prevalent in the non-survivors than in the survivors (75% vs. 27.3%, p=0.04). The elective PCPS-supported PCI was practiced more frequently in the survivors than in the non-survivors (72.7% vs. 25%, p=0.04). In the analysis of the event-free survival curve between elective and emergency procedures, there was a significant difference in the survival rate (p=0.025). Among the survivors there were more patients with multi-vessel disease, but a lower Thrombolysis in Myocardial Infarction grade in the culprit lesions was detected in the non-survivors, before PCI. Although we studied high-risk patients, there was no procedure-related mortality. CONCLUSION: Our experience suggests that PCPS may be helpful in high risk patients treated with PCI, especially in elective cases. More aggressive and larger scale studies of PCPS should follow.

Gender-based differences in the management and prognosis of acute coronary syndrome in Korea.

PURPOSE: Gender-based differences exist in the characteristics, management, and prognosis of acute coronary syndrome (ACS). However, their impact on prognosis remains unclear. We aimed to identify factors causing these differences in Koreans. MATERIALS AND METHODS: We examined 6,636 ACS patients (66.2% males) visiting 72 Korean hospitals between April-2007 and December-2008. Gender-based differences in clinical demographics, therapy, and outcomes were analyzed over 6 months. RESULTS: Women were older than men [mean (standard deviation, SD) age, 67.6 (9.8) vs. 60.6 (11.2) years; p<0.001]; had higher rates of hypertension, diabetes mellitus, and lack of exercise (p<0.001 for all); and lower rates of obesity, familial history of cardiovascular disease (CVD), and smoking (p<0.05 for all). Atypical symptoms were more common in women (20.5% vs. 15.1% in men, p<0.001), whereas myocardial infarction with ST-segment elevation was less common (17.1% vs. 27.8%, p<0.001). Mean (SD) time lapse from symptom onset to arrival at hospital was longer in women [11.44 (18.19) vs. 8.26 (14.89) hours in men, p<0.001], as was the duration of hospitalization [7.58 (7.61) vs. 7.04 (7.72) days, p=0.007]. Fewer women underwent revascularization procedures, including thrombolytic therapy, balloon angioplasty, stent implantation, and coronary artery bypass grafting (79.4% vs. 83.3% men, p<0.001). No significant differences were observed in CVD-related death, recurrent ACS, stroke, refractory angina, or rehospitalization for angina. CONCLUSION: Female ACS patients were older than male subjects and had more atypical presentation. They arrived at the hospital later than men and had longer hospital stays, but less often required revascularization therapy. However, no gender-based differences were noted in ACS-related mortality and morbidity.