GPR75: A Newly Identified Receptor for Targeted Intervention in the Treatment of Obesity and Metabolic Syndrome.

Metabolic syndrome increases the risk of stroke, cardiovascular disease, and diabetes. The morbidity and mortality associated with this constellation of risk factors are equally alarming when considering the economic and global significance that this epidemic has on an institutional and patient level. Despite several current treatments available, there needs to be a continuous effort to explore more specific and effective druggable entities for preventative and therapeutic interventions. Within this context, the G-protein coupled receptor, GPR75, is an attractive pharmacological target. GPR75 and its association with its ligand, 20-hydroxyeicosatetraenoic acid, have been shown to promote hypertension, inflammation, obesity, and insulin resistance. This review will help shed light on this novel signaling pathway and offer a perspective on a promising new direction of targeting different aspects of the metabolic syndrome involving GPR75. Gene targeting of GPR75 is more effective than current pharmacologic therapies without the known side effects.

The Interplay of Microbiome Dysbiosis and Cardiovascular Disease.

The intricate ecosystem of the mammalian gut, which hosts a diverse microbiome, plays a vital role in various physiological functions. Trillions of bacteria within the gut contribute to host metabolism, immune modulation, energy homeostasis, and more. Emerging research highlights the gut microbiota's significant impact on cardiovascular diseases (CVDs), with intestinal dysbiosis identified as a risk factor for conditions such as obesity and diabetes, both linked to atherosclerosis. Chronic inflammation, pivotal in atherosclerosis, is influenced by the gut microbiome, where microbial signals, such as lipopolysaccharides, can translocate from the gut to trigger inflammatory responses. Diet has major effects on the gut microbiota, with the Western diet, rich in saturated fats, contributing to dysbiosis and elevated cardiovascular risks. Probiotics and prebiotics offer therapeutic potential in CVD management. Probiotics, or live microorganisms, exhibit antioxidant, anti-inflammatory, and cholesterol-lowering effects. Probiotics are most effective when given with prebiotics, with the former acting on the latter as substrate. Understanding the dynamic interplay between diet, gut microbiota, and CVD provides insights into preventive and therapeutic strategies.

Titin: The Missing Link in Cardiac Physiology.

Titin, an extraordinary protein known for its colossal size and multifaceted roles, is a cornerstone in the structural and functional dynamics of striated muscle tissues, including the heart and skeletal muscles. Its sheer enormity, with a molecular weight exceeding 3000 kDa, is paralleled only by the immense influence it exerts on muscle physiology. This review will delve into the remarkable structural organization of Titin and the genetics of this molecule, including the common mutations resulting in various cardiomyopathies. We will delve deeper into its role in dilated cardiomyopathy, familial restrictive cardiomyopathy, hypertrophic cardiomyopathy, and left ventricular noncompaction cardiomyopathy. This review culminates by discussing the prospects of therapeutic strategies targeting Titin. While these interventions remain primarily theoretical, the possibilities are intriguing. Patients with Titin truncation mutations present unique challenges, but innovative approaches like gene therapy or preemptive treatments with drugs such as angiotensin-converting enzyme inhibitors or beta-blockers offer hope. This multi-pronged approach highlights the significance of understanding Titin's multifaceted role and its potential as a target for future therapeutic interventions.

Neutrophil-to-lymphocyte ratio and prognosis in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

OBJECTIVE: The purpose of this study was to characterize Acute Coronary Syndrome (ACS)-associated inflammation by investigating correlates of the neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of inflammation, and its relation to 1-year mortality in a cohort of patients undergoing percutaneous coronary intervention (PCI) for ACS at a single institution. METHODS: We performed a single-institution, retrospective, observational study of all-comer ACS patients who underwent PCI and were discharged home before the COVID-19 pandemic between September 23, 2011 and July 31, 2017 for who outcomes data were available. RESULTS: NLRhigh group tended to be older, white patients, less likely to smoke, more likely to have a history of heart failure and cardiac arrest, higher creatinine values, lower LVEF, and higher CK-MB (a surrogate for infarct size). Linear regression model demonstrated a strong correlation between increasing NLR and white race (B = 1.103, p = 0.001, hemoglobin (B = -0.30, p < 0.001), peak CK-MB (B = 0.004, p = 0.02), LVEF (B = -0.048, p < 0.001), and serum creatinine (B = 0.47, p = 0.03). There were a total of 87 deaths at one year. NLR > 3.4 was associated with worse one-year survival post-PCI (91.4 % vs. 95.4 %, log-rank p < 0.004), which was confirmed on multivariate analysis. CONCLUSION: Our data confirm the independent prognostic significance of inflammation to mortality after ACS and may provide some insight into the putative benefits of inflammation modulation.

Risk factors for cardiogenic shock in thyroid storm: a retrospective and case-series study.

Aim: Thyroid storm (TS) occurs in 10% of thyrotoxicosis patients and 1% of TS patients experience cardiogenic shock (CS), which is associated with poor prognosis. Methods: This is a single institution, retrospective study in which 56 patients with TS were evaluated. Results: BMI (p = 0.002), history of heart failure (OR 8.33 [1.91, 36.28]; p = 0.004), pro-BNP elevation (p = 0.04), chest x-ray showing interstitial edema (OR 3.33 [1.48, 7.52]; p = 0.01) and Burch-Wartofsky score (62.5 vs 40; p = 0.004) showed association with CS. CS patients had increased length of stay (16.5 vs 4 days; p = 0.01) and higher in-hospital mortality (OR 24.5 [2.90, 207.29]; p < 0.001). Conclusion: These risk factors are useful to risk stratify TS patients on admission, institute therapy in a timely manner and decrease mortality.

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review.

Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21's associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis. This emerging pharmaceutical compound has shown promise in treating liver fibrosis and inflammation linked to nonalcoholic steatohepatitis. The ENTRIGUE trial, a phase 2 clinical trial of PGZ, has demonstrated a 57% reduction in triglyceride level compared to placebo; a 45% reduction in liver hepatic steatosis; improved insulin sensitivity; reductions in nonhigh-density lipoprotein-cholesterol; and reductions in apolipoprotein B-100.

Cardiovascular Manifestations of Hemochromatosis: A Review of Pathophysiology, Mechanisms, and Treatment Options.

Hemochromatosis is a genetic disorder characterized by excessive absorption and accumulation of iron in the body. It is one of the most common inherited disorders. The excess iron deposition can cause damage to various organs, including the liver, heart, pancreas, and joints. If left untreated, hemochromatosis can lead to serious complications such as cirrhosis, diabetes, heart failure, and increased risk of certain cancers. Iron overload in hemochromatosis significantly affects the cardiovascular system, leading to morbidity and mortality. This article reviews the current literature describing the pathogenesis and various cardiovascular manifestations of hemochromatosis, including dilated cardiomyopathy, conduction abnormalities, heart failure, cardiac fibrosis, myocardial infarction, and valvular heart disease. This article aims to provide a detailed understanding of the cardiovascular manifestations associated with hemochromatosis and their underlying mechanisms through a review of current literature in publicly available databases.

The Relationship of Duffy Gene Polymorphism, High Sensitivity C-Reactive Protein, and Long-term Outcomes.

Background: Black adults have higher incidence of all-cause death and worse cardiovascular outcomes when compared to other populations. The Duffy chemokine receptor is not expressed in a large majority of Black adults and the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and long-term cardiovascular outcomes in Black members of two contemporary, longitudinal cohort studies (the Jackson Heart Study and Multi-Ethnic Study of Atherosclerosis). Data on 4,307 Black participants (2,942 Duffy null and 1,365 Duffy receptor positive, as defined using Single Nucleotide Polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was not independently associated with elevated levels of serum hs-CRP levels once conditioning for known CRP locus alleles in linkage disequilibrium with the Duffy gene. Duffy null status was not found to be independently associated with higher incidence of all-cause mortality or secondary outcomes after adjusting for possible confounders in Black participants. Conclusions: These findings suggest that increased levels of hs-CRP found in Duffy null individuals is due to co-inheritance of CRP alleles known to influence circulating levels hs-CRP and that Duffy null status was not associated with worse adverse outcomes over the follow-up period in this cohort of well-balanced Black participants.

Back Up at the Pump? I Have a Gut Feeling About This: A Review of the Gastrointestinal Manifestations From Congestive Heart Failure.

Heart failure, which is a clinical syndrome characterized by the heart's inability to maintain adequate cardiac output, is known to affect various organ systems in the body due to its ischemic nature and activation of the systemic immune response, but the resultant complications specifically on the gastrointestinal tract and the liver are not well discussed and poorly understood. Gastrointestinal-related phenomena are common symptoms experienced in patients with heart failure and frequently found to increase morbidity and mortality in these populations. The relationship between the gastrointestinal tract and heart failure are strongly linked and influence each other much so that the bidirectional association of the two is oftentimes referred to as cardiointestinal syndrome. Manifestations include gastrointestinal prodrome, bacterial translocation and protein-losing gastroenteropathy by gut wall edema, cardiac cachexia, hepatic insult and injury, and ischemic colitis. More attention is needed from a cardiology perspective to recognize these common presenting gastrointestinal phenomena that affect much of our patient population with heart failure. In this overview, we describe the association between heart failure and the gastrointestinal tract, the pathophysiology, lab findings, clinical manifestations and complications, and the management involved.

The Critical Role of the Adipocytokine NOV in Obstructive Sleep Apnea Induced Cardiometabolic Dysfunction: A Review.

Obstructive sleep apnea (OSA) is highly prevalent and associated with oxidative stress, chronic inflammation, and adverse cardiovascular consequences. The comorbid condition of obesity remains epidemic. Both obesity and OSA are highly comorbid in patients with cardiovascular disease including atrial fibrillation, resistant hypertension, congestive heart failure, and coronary artery disease. Patients with these preexisting cardiovascular conditions should be screened for OSA with a low threshold to treat, even if OSA severity is mild. Nephroblastoma overexpressed (NOV/CCN3) protein has been identified in multiple chronic inflammatory states, most notably in obesity and more recently in OSA, even in the absence of obesity. As such, NOV may represent an important biomarker for oxidative stress in OSA and may lead to a deeper understanding of the relationship between OSA and its clinical sequelae.

Silencing the Adipocytokine NOV: A Novel Approach to Reversing Oxidative Stress-Induced Cardiometabolic Dysfunction.

OBJECTIVE: NOV/CCN3 is an adipocytokine recently linked to obesity, insulin resistance, and cardiometabolic dysfunction. NOV is manufactured and secreted from adipose tissue, with blood levels highly correlated with BMI. NOV levels are increased in obesity and a myriad of inflammatory diseases. Elevated NOV levels cause oxidative stress by increasing free radicals, decreasing antioxidants, and decreasing heme oxygenase (HO-1) levels, resulting in decreased vascular function. Silencing NOV in NOV knockout mice improved insulin sensitivity. We wanted to study how suppressing NOV expression in an obese animal model affected pathways and processes related to obesity, inflammation, and cardiometabolic function. This is the first study to investigate the interaction of adipose tissue-specific NOV/CCN3 and cardiometabolic function. METHODS: We constructed a lentivirus containing the adiponectin-promoter-driven shNOV to examine the effect of NOV inhibition (shNOV) in adipose tissue on the heart of mice fed a high-fat diet. Mice were randomly divided into three groups (five per group): (1) lean (normal diet), (2) high-fat diet (HFD)+ sham virus, and (3) HFD + shNOV lentivirus. Blood pressure, tissue inflammation, and oxygen consumption were measured. Metabolic and mitochondrial markers were studied in fat and heart tissues. RESULTS: Mice fed an HFD developed adipocyte hypertrophy, fibrosis, inflammation, and decreased mitochondrial respiration. Inhibiting NOV expression in the adipose tissue of obese mice by shNOV increased mitochondrial markers for biogenesis (PGC-1α, the nuclear co-activator of HO-1) and functional integrity (FIS1) and insulin signaling (AKT). The upregulation of metabolic and mitochondrial markers was also evident in the hearts of the shNOV mice with the activation of mitophagy. Using RNA arrays, we identified a subgroup of genes that highly correlated with increased adipocyte mitochondrial autophagy in shNOV-treated mice. A heat map analysis in obese mice confirmed that the suppression of NOV overrides the genetic susceptibility of adiposity and the associated detrimental metabolic changes and correlates with the restoration of anti-inflammatory, thermogenic, and mitochondrial genes. CONCLUSION: Our novel findings demonstrate that inhibiting NOV expression improves adipose tissue function in a positive way in cardiometabolic function by inducing mitophagy and improving mitochondrial function by the upregulation of PGC-1α, the insulin sensitivity signaling protein. Inhibiting NOV expression increases PGC-1, a key component of cardiac bioenergetics, as well as key signaling components of metabolic change, resulting in improved glucose tolerance, improved mitochondrial function, and decreased inflammation. These metabolic changes resulted in increased oxygen consumption, decreased adipocyte size, and improved cardiac metabolism and vascular function at the structural level. The crosstalk of the adipose tissue-specific deletion of NOV/CCN3 improved cardiovascular function, representing a novel therapeutic strategy for obesity-related cardiometabolic dysfunction.

Clinical variables for predicting type-1 and type-2 non-ST segment elevation myocardial infarction in those presenting with ischemic symptoms.

Introduction: The accuracy of detecting myocardial infarction (MI) has greatly improved with the advent of more sensitive assays, and this has led to etiologic subtyping. Distinguishing between type 1 and type 2 non-ST-segment elevation myocardial infarction (NSTEMI) early in the clinical course allows for the most appropriate advanced diagnostic procedures and most efficacious treatments. The purpose of this study was to investigate the predictive effect of demographic and clinical variables on predicting NSTEMI subtypes in patients presenting with ischemic symptoms. Material and methods: We performed a single institution retrospective cohort study of patients who presented to the emergency department (ED) with ischemic signs and symptoms consistent with non-ST-segment myocardial infarction, for whom results of coronary angiography were available. We analyzed demographic, laboratory, echocardiography and angiography data to determine predictors of NSTEMI sub-types. Results: Five hundred and forty-six patients were enrolled; 426 patients were found on coronary angiography to have type 1 acute MI (T1AMI), whereas 120 patients had type 2 acute MI (T2AMI). Age (OR per year = 1.03 (1.00, 1.05), p = 0.03), prior MI (OR = 3.50 (1.68, 7.22), p = 0.001), L/H > 2.0 (OR = 1.55 (1.12, 2.13), p = 0.007), percentage change in troponin I > 25% (OR = 2.54 (1.38, 4.69), p = 0.003), and regional wall motion abnormalities (RWMA) (OR = 3.53 (1.46, 8.54), p = 0.004) were independent predictors of T1AMI, whereas sex, race, body mass index, hypertension, end-stage renal disease (ESRD), heart failure, family history (FH) of coronary artery disease (CAD), HbA1c, and left ventricular ejection fraction (LVEF) were not. Conclusions: Key clinical variables such as age, prior MI, L/H ratio, percentage change in troponin I, and presence of RWMA on echocardiogram may be utilized as significant predictors of T1AMI in patients presenting with ischemic symptoms to the ED.

Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion.

Recent studies suggest that PGC1-α plays a crucial role in mitochondrial and vascular function, yet the physiological significance of PGC1α and HO expression in adipose tissues in the context of obesity-linked vascular dysfunction remains unclear. We studied three groups of six-week-old C57BL/6J male mice: (1) mice fed a normal chow diet; (2) mice fed a high-fat diet (H.F.D.) for 28 weeks, and (3) mice fed a high-fat diet (H.F.D.) for 28 weeks, treated with adipose-specific overexpression of PGC-1α (transgenic-adipocyte-PGC-1α) at week 20, and continued on H.F.D. for weeks 20-28. R.N.A. arrays examined 88 genes involved in adipocyte proliferation and maturation. Blood pressure, tissue fibrosis, fasting glucose, and oxygen consumption were measured, as well as liver steatosis, and the expression levels of metabolic and mitochondrial markers. Obese mice exhibited a marked reduction of PGC1α and developed adipocyte hypertrophy, fibrosis, hepatic steatosis, and decreased mitochondrial respiration. Mice with adipose-specific overexpression of PGC1-α exhibited improvement in HO-1, mitochondrial biogenesis and respiration, with a decrease in fasting glucose, reduced blood pressure and fibrosis, and increased oxygen consumption. PGC-1α led to the upregulated expression of processes associated with the browning of fat tissue, including UCP1, FGF21, and pAMPK signaling, with a reduction in inflammatory adipokines, NOV/CCN3 expression, and TGFß. These changes required HO-1 expression. The R.N.A. array analysis identified subgroups of genes positively correlated with contributions to the browning of adipose tissue, all dependent on HO-1. Our observations reveal a positive impact of adipose-PGC1-α on distal organ systems, with beneficial effects on HO-1 levels, reversing obesity-linked cardiometabolic disturbances.

Relation of Left Ventricular Hypertrophy Subtype to Long-Term Mortality in Those With Subclinical Cardiovascular Disease (from the Multiethnic Study of Atherosclerosis [MESA]).

The clinical and biochemical profile of differing Left ventricular hypertrophy phenotypes and its effect on long-term outcomes is ill-defined. The study investigated the differences in risk profiles and prognostic effect of concentric (CH) and eccentric hypertrophy (EH) on long-term adverse outcomes in a contemporary, ethnically diverse cohort. We analyzed follow-up data over 15 years from the Multiethnic Study of Atherosclerosis study. A total of 4,979 participants with cardiac magnetic resonance performed at baseline enrollment were included. Descriptive statistics, Kaplan-Meier curves, and regression models were applied. Independent variables associated with CH were black and Hispanic race/ethnicity, systolic blood pressure, and metabolic syndrome. Independent variables associated with EH were systolic blood pressure and urine creatinine, whereas serum creatinine had an inverse association. The primary end point of all-cause death (n = 1,137, 22.8%) occurred in 21.7%, 47.4%, and 56.6% of participants with no, CH, or EH, respectively (p- < 0.001). Age (hazard ratio [HR] per year = 1.10 [1.09 to 1.11], p <0.001), male gender (HR = 1.48 [1.29 to 1.69], p <0.001), black race (HR = 1.17 [1.005 to 1.36], p = 0.04), fasting glucose (HR = 1.005 [1.003 to 1.007], p <0.001), baseline creatinine (HR per mg/100 ml = 1.29 [1.15 to 1.46], p <0.001), left ventricular ejection fraction (HR per 1% = 0.98 [0.98 to 0.99], p = 0.005), IL-6 (HR per pg/ml = 1.17 [1.12 to 1.22], p <0.001), CH (HR = 1.84 [1.41 to 2.41], p <0.001), and EH (HR = 2.58 [1.77 to 3.76], p <0.001) were significant predictors of all-cause mortality. In conclusion, CH and EH are 2 distinct clinical phenotypes of left ventricular hypertrophy with differing gender and racial predisposition, both of which are associated with worse long-term adverse outcomes.

Cancer and cardiovascular-related perceived risk in a diverse cancer center catchment area.

PURPOSE: Despite cancer and cardiovascular disease (CVD) sharing several modifiable risk factors, few unified prevention efforts exist. We sought to determine the association between risk perception for cancer and CVD and engagement in healthy behaviors. METHODS: Between May 2019 and August 2020, we conducted a cross-sectional survey of adults ≥ 40 years residing in Brooklyn neighborhoods with high cancer mortality. We considered one's perceived risk of cancer and CVD compared to age counterparts as the primary exposures. The primary study outcome was a weighted health behavior score (wHBS) composed of 5 domains: physical activity, no obesity, no smoking, low alcohol intake, and healthy diet. Modified Poisson regression models with robust error variance were used to assess associations between perceived risk for cancer and CVD and the wHBS, separately. RESULTS: We surveyed 2448 adults (mean [SD] age, 61.4 [12.9] years); 61% female, 30% Non-Hispanic White, and 70% racial/ethnic minorities. Compared to their age counterparts nearly one-third of participants perceived themselves to be at higher CVD or cancer risk. Perceiving higher CVD risk was associated with an 8% lower likelihood of engaging in healthy behaviors (RR 0.92; 95% CI 0.86-0.99). Perceiving greater cancer risk was associated with a 14% lower likelihood of engaging in healthy behaviors (RR 0.86; 95% CI 0.79-0.95). The association between cancer risk and wHBS attenuated but remained significant (aRR 0.90; 95% CI 0.82-0.98) after adjustment. CONCLUSION: Identifying high-risk subgroups and intervening on shared risk behaviors could have the greatest long-term impact on reducing CVD and cancer morbidity and mortality.

Heme-oxygenase and lipid mediators in obesity and associated cardiometabolic diseases: Therapeutic implications.

Obesity-mediated metabolic syndrome remains the leading cause of death worldwide. Among many potential targets for pharmacological intervention, a promising strategy involves the heme oxygenase (HO) system, specifically its inducible form, HO-1. This review collects and updates much of the current knowledge relevant to pharmacology and clinical medicine concerning HO-1 in metabolic diseases and its effect on lipid metabolism. HO-1 has pleotropic effects that collectively reduce inflammation, while increasing vasodilation and insulin and leptin sensitivity. Recent reports indicate that HO-1 with its antioxidants via the effect of bilirubin increases formation of biologically active lipid metabolites such as epoxyeicosatrienoic acid (EET), omega-3 and other polyunsaturated fatty acids (PUFAs). Similarly, HO-1and bilirubin are potential therapeutic targets in the treatment of fat-induced liver diseases. HO-1-mediated upregulation of EET is capable not only of reversing endothelial dysfunction and hypertension, but also of reversing cardiac remodeling, a hallmark of the metabolic syndrome. This process involves browning of white fat tissue (i.e. formation of healthy adipocytes) and reduced lipotoxicity, which otherwise will be toxic to the heart. More importantly, this review examines the activity of EET in biological systems and a series of pathways that explain its mechanism of action and discusses how these might be exploited for potential therapeutic use. We also discuss the link between cardiac ectopic fat deposition and cardiac function in humans, which is similar to that described in obese mice and is regulated by HO-1-EET-PGC1α signaling, a potent negative regulator of the inflammatory adipokine NOV.

The Association of Nephroblastoma Overexpressed (NOV) and Endothelial Progenitor Cells with Oxidative Stress in Obstructive Sleep Apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent hypoxia, chronic inflammation, and oxidative stress and is associated with cardiometabolic disease. Several biological substrates have been associated with OSA such as nephroblastoma overexpressed (NOV), endothelial progenitor cells (EPC), and circulating endothelial cells (CEC). Few studies have looked at the association of NOV with OSA while the EPC/CEC relationships with OSA are unclear. In this study, we hypothesize that (1) NOV is associated with the severity of OSA independent of BMI, identifying a protein that may play a role in the biogenesis of OSA complications, and (2) EPCs and CECs are also associated with the severity of OSA and are biomarkers of endothelial dysfunction in OSA. METHODS: 61 subjects underwent overnight polysomnography (PSG), clinical evaluation, and blood analysis for NOV, EPC, CEC, interleukin 6 (IL-6), and other potential biomarkers. RESULTS: NOV and EPCs were independently associated with the oxygen desaturation index (ODI) after adjusting for potential confounders including body mass index (BMI), age, and sex (NOV p = 0.032; EPC p = 0.001). EPC was also independently associated with AHI after adjusting for BMI, age, and sex (p = 0.017). IL-6 was independently associated with AHI, but not with ODI. CONCLUSION: NOV and EPC levels correlate with the degree of OSA independent of BMI, indicating that these biomarkers could potentially further elucidate the relationship between OSA patients and their risk of the subsequent development of cardiovascular disease.

The effect of cardiac geometry variation according to sex and race on outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

INTRODUCTION: The prevalence and long-term consequences of differences in baseline cardiac geometry (as a result of hypertension) in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are ill-defined. The primary purpose of this study was to clarify whether there were differences among sexual and racial groups in echocardiographic findings reflecting cardiac geometry and adaptation in patients undergoing PCI for ACS and whether this could explain the differences in outcomes seen between these groups. MATERIAL AND METHODS: We analyzed 1-year follow-up data from a single institution, a retrospective, observational study that enrolled 1,153 patients who presented with ACS and were treated with PCI, for whom echocardiographic data were available. RESULTS: Normal, concentric hypertrophy, and eccentric hypertrophy in males vs. females were observed as follows: 29% vs. 19% (p = 0.001), 25% vs. 31% (p = 0.02), and 8% vs. 14% (p = 0.004), respectively. The primary endpoint of all-cause death (n = 89, 7.7%) occurred in 48 (10.5%) females and in 41 (8.2%) males, p = 0.03. Major adverse cardiac events and bleeding (MACE-B - all-cause death, non-fatal myocardial infarction, stroke or hospitalization for bleeding) was higher among women than men (21.6% vs. 13.5%, p = 0.0002). Males with eccentric hypertrophy (EH) had similar MACE-B outcomes as females with EH 1-year post-PCI (29% vs. 32%, respectively, p = 0.77). CONCLUSIONS: Females undergoing PCI for ACS are at higher risk for worse outcomes because they are more likely to express the eccentric hypertrophy phenotype; however, it did not account for the difference in adverse outcomes observed between sexes.

Eccentric hypertrophy predicts adverse events in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

INTRODUCTION: The effect of the type of left ventricular hypertrophy in patients presenting with an acute coronary syndrome (ACS) on long-term outcomes is ill-defined. The purpose of this study was to investigate the prognostic effect of concentric (CH) or eccentric hypertrophy (EH) on adverse outcomes in patients presenting with ACS undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS: We analyzed 1-year follow-up data from a single-institution, retrospective, observational study that enrolled 1,153 patients who presented with ACS and were treated with PCI, for whom echocardiographic data were available. RESULTS: Normal geometry was observed in 718 (62.3%) patients, while 27.2% had CH and 10.5% had EH. The primary endpoint of all-cause death (n = 90, 7.8%) occurred in 6.4%, 8.0%, and 14.9% of patients with no, concentric, or eccentric hypertrophy, respectively (p = 0.005). Major adverse cardiac events (MACE - all-cause death, non-fatal myocardial infarction or stroke or hospitalization for bleeding) occurred in 13.9%, 17.8%, 30.6%, respectively (p < 0.001). Age (HR per year = 1.04 (1.02, 1.05), p < 0.001), female gender (HR = 1.56 (1.12, 2.16), p = 0.008), diabetes (HR = 1.49 (1.07, 2.06), p = 0.02), eccentric hypertrophy (HR = 1.58 (1.006, 2.47), p = 0.047), peak troponin I (HR per 1 ng/ml = 1.004 (1.001, 1.006), p = 0.004) and left ventricular ejection fraction < 50% (HR = 1.57 (1.12, 2.20), p < 0.008) were significant predictors of MACE. CONCLUSIONS: The presence of eccentric hypertrophy in ACS patients undergoing PCI is an independent predictor of adverse outcomes at 1 year.

The pivotal role of heme Oxygenase-1 in reversing the pathophysiology and systemic complications of NAFLD.

The pathogenesis and molecular pathways involved in non-alcoholic fatty liver disease (NAFLD) are reviewed, as well as what is known about mitochondrial dysfunction that leads to heart disease and the progression to steatohepatitis and hepatic fibrosis. We focused our discussion on the role of the antioxidant gene heme oxygenase-1 (HO-1) and its nuclear coactivator, peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α) in the regulation of mitochondrial biogenesis and function and potential therapeutic benefit for cardiac disease, NAFLD as well as the pharmacological effect they have on the chronic inflammatory state of obesity. The result is increased mitochondrial function and the conversion of white adipocyte tissue to beige adipose tissue ("browning of white adipose tissue") that leads to an improvement in signaling pathways and overall liver function. Improved mitochondrial biogenesis and function is essential to preventing the progression of hepatic steatosis to NASH and cirrhosis as well as preventing cardiovascular complications.