Racial and Ethnic Differences in Risk Factors and Outcomes in Adults With Acute Myocardial Infarction.

Introduction Understanding racial/ethnic differences in patients with acute myocardial infarction (AMI) lays the foundation for more equitable health care. This study evaluated racial/ethnic differences in risk factors, treatment, and outcomes in patients with AMI. Methods This retrospective study included patients aged 18-50 years hospitalized for AMI between 2006 and 2016. Cox regression models were used to evaluate the association of race/ethnicity with all-cause mortality. Results Among 1753 patients hospitalized for type 1 AMI (median age 44 years, 85% male), 35.8% self-identified as White, 9.4% non-Hispanic Black, 37.6% Hispanic, 14.5% Asian, and 2.6% as other. Compared to White patients, Black patients were more likely to have hypertension (53.1% vs 32.2%, p < 0.001) and Hispanic patients were more likely to have diabetes (28.2% vs 15.5%, p < 0.001) and obesity (23.9% vs 17.7%, p = 0.008). There were no substantial differences in revascularization rates or initial medical treatment. However, adherence to statin therapy was lower among Black and Hispanic patients (50.3% and 58.6% for Black and Hispanic vs 67.4% and 72.3% for White and Asian patients, respectively). Over a median follow-up of 7.5 years, Black patients had higher all-cause mortality (unadjusted hazard ratio = 1.88, 95% confidence interval = 1.09-3.24) compared to White patients, but this difference was no longer significant after adjustments (adjusted hazard ratio = 1.32, 95% confidence interval = 0.74-2.36). Discussion and Conclusion There are racial/ethnic differences in risk factors and medication adherence patterns in adults with AMI. To achieve equitable care, programs with tailored intervention addressing needs of different groups should be developed.

Acute myocardial infarction in young adults with chronic kidney disease.

OBJECTIVE: The goal of this study was to evaluate the prevalence of chronic kidney disease (CKD) in young patients with acute myocardial infarction (AMI) and to report their characteristics and clinical outcomes. BACKGROUND: Underlying renal dysfunction is a risk factor for poor cardiovascular outcomes in older patients. The implication of CKD in young patients with AMI is not well studied. METHODS: This is a retrospective population-based cohort study of patients aged 18-50 who presented with AMI between 2006 and 2016. Medical records were reviewed to confirm diagnosis and to identify treatment and long-term outcomes. Cox regression models were used to evaluate the association of CKD with mortality. RESULTS: Among 1753 young patients with type 1 AMI (median age 45 years, 85.3% male), CKD was present in 112 (6.8%) patients. A higher proportion of CKD patients had concomitant hypertension, hyperlipidemia, diabetes, and obesity. Use of statin and P2Y12 inhibitors post-AMI was lower in CKD patients. Over a median follow-up of 7.2 years, CKD was associated with higher all-cause mortality [hazard ratio (HR), 9.3; 95% CI, 6.3-13.8]. This association persisted after adjusting for demographics, comorbidities, and treatment (adjusted HR, 3.6; 95% CI, 2.2-6.0). CONCLUSION: Presence of CKD was associated with 3.6-fold higher mortality over a median follow-up of 7.2 years. A lower proportion of CKD patients were treated with statin therapy and P2Y12 inhibitors. These findings highlight the need for intensive risk factor modification and optimal use of guideline-directed medical therapies in this high-risk population.

Cardiorespiratory Fitness and Mortality in Patients Aged 60 to 90 Years.

Chronological age alone does not fully reflect a patient's prognosis. We sought to assess the association of cardiorespiratory fitness (quantified by METs) with all-cause mortality among patients aged 60 to 90 years. This retrospective study included patients who underwent exercise treadmill testing at an integrated healthcare system from 2011 to 2019. Patients were categorized into age groups: 60 to <70 years, 70 to <80 years, and 80 to 90 years; and cardiorespiratory fitness level: low (<5 METs), moderate (5 to 10 METs), and high fitness (>10 METs). Mean follow-up was 3.5 years. A total of 40,520 patients were included (mean age 67.7 ± 4.7 years, 48.6% women). Of whom, 27,021 were 60 to <70 years old (66.7%); 12,638 70 to <80 years old (31.2%); and 1,861 80 to 90 years old (4.6%). There were 3,494 patients categorized as low (8.6%), 21,863 as moderate (54%), and 15,163 as high fitness (37.4%). Low fitness level was independently associated with lower survival (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.15 to 2.24). Using age 60 to 70 group with high fitness level as reference, the age 80 to 90 group with high fitness level had better survival than their younger counterparts with low fitness level (age 80 to 90 years high fitness level: HR 2.9, 95% CI 1.2 to 7.2; age 60 to 70 years low fitness level: HR 4.3, 95% CI 3.1 to 5.9; age 70 to 80 years low fitness level: HR 6.8, 95% CI 5.2 to 8.9) on adjusted analysis. In conclusion, higher cardiorespiratory fitness is associated with better survival. Patients >80 years old with high fitness level have comparable or even better survival than their younger counterparts with submoderate fitness levels. Chronological age alone should not be the only factor when considering prognosis.

The preclinical candidate indole-2-carboxamide improves immune responses to Mycobacterium tuberculosis infection in healthy subjects and individuals with type 2 diabetes.

A novel group of agents known as the indole-2-carboxamides (often referred to as indoleamides) have been shown to demonstrate high antimycobacterial activity. Studies have demonstrated that the best indoleamides possess desirable ADME/Tox properties, with less adverse effects and increased efficacy against both MDR-TB (multi-drug resistant TB) and XDR-TB (extensively drug-resistant TB). The primary mechanism of killing Mycobacterium tuberculosis (Mtb) by indoleamides is by disrupting the function of the essential mycolic acid transporter MmpL3 protein (Mycobacterial membrane protein Large 3). Therefore, targeting this essential mycobacterial transporter by small molecules opens new possibility for the development of novel and effective anti-TB agents. In the present study, we characterized the effects of indoleamides in altering the viability of Mtb in an in vitro granuloma model using immune cells derived from healthy subjects and those with type 2 diabetes mellitus (T2DM). Our results indicate that treatment with the best indoleamide 3 resulted in a significant reduction in the viability of Mtb in both THP-1 macrophages as well as in granulomas derived from healthy individuals and subjects with T2DM. Graphical Abstract.

Glutathione as a Marker for Human Disease.

Glutathione (GSH), often referred to as "the master antioxidant," participates not only in antioxidant defense systems, but many metabolic processes, and therefore its role cannot be overstated. GSH deficiency causes cellular risk for oxidative damage and thus as expected, GSH imbalance is observed in a wide range of pathological conditions including tuberculosis (TB), HIV, diabetes, cancer, and aging. Consequently, it is not surprising that GSH has attracted the attention of biological researchers and pharmacologists alike as a possible target for medical intervention. Here, we discuss the role GSH plays amongst these pathological conditions to illuminate how it can be used as a marker for human disease.

Characterizing the Effects of Glutathione as an Immunoadjuvant in the Treatment of Tuberculosis.

Mycobacterium tuberculosis is the etiological agent that is responsible for causing tuberculosis (TB), which continues to affect millions of people worldwide, and the rate of resistance of M. tuberculosis to antibiotics is ever increasing. We tested the synergistic effects of N-acetyl cysteine (NAC; the precursor molecule for the synthesis of glutathione [GSH]) and individual first-line antibiotics typically given for the treatment of TB, such as isoniazid (INH), rifampin (RIF), ethambutol (EMB), and pyrazinamide (PZA), to improve the ability of macrophages to control intracellular M. tuberculosis infection. GSH, a pleiotropic antioxidant molecule, has previously been shown to display both antimycobacterial and immune-enhancing effects. Our results indicate that there was not only an increase in beneficial immunomodulatory effects but also a greater reduction in the intracellular viability of M. tuberculosis when macrophages were treated with the combination of antibiotics (INH, RIF, EMB, or PZA) and NAC.

Effects of ReadiSorb L-GSH in Altering Granulomatous Responses against Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (M. tb), a rod-shaped acid-fast bacterium, is the causative agent of tuberculosis (TB). TB remains one of the leading causes of morbidity and mortality worldwide. Additionally, approximately one-third of the world's population has latent tuberculosis infection (LTBI) as a result of the body's primary mechanism of defense against M. tb infection, the formation of a granuloma. A granuloma is the aggregation of immune cells that encapsulate the bacteria to keep them localized to prevent further infection and thus the bacteria become quiescent. However, if an individual becomes immunocompromised, they become more susceptible to M. tb, which may lead to bacterial reactivation and an active infection, because the host is no longer able to generate adequate immune responses. In this study, we examined liposomal glutathione's (L-GSH) effectiveness in promoting the formation of solid, stable granulomas. We assessed this ability by generating in vitro human granulomas constructed from peripheral blood mononuclear cells (PBMCs) that were derived from healthy subjects and testing their granulomatous effector responses against both M. bovis bacille Calmette-Guérin (BCG) and the highly virulent Erdman strain of M. tb. Additionally, we measured the survival and immune characteristics of the Erdman strain of M. tb in THP-1 originated macrophages as well as in vitro granulomas generated from individuals from type 2 diabetes (T2DM). Our results demonstrate that L-GSH treatment can decrease the intracellular survival of both BCG and virulent M. tb, as well as downregulate the levels of overexpressed proinflammatory cytokines delegated from the granulomas derived from not only healthy subjects but also individuals with T2DM.