Large animal models to study effectiveness of therapy devices in the treatment of heart failure with preserved ejection fraction (HFpEF).

Our understanding of the complex pathophysiology of Heart failure with preserved ejection fraction (HFpEF) is limited by the lack of a robust in vivo model. Existing in-vivo models attempt to reproduce the four main phenotypes of HFpEF; ageing, obesity, diabetes mellitus and hypertension. To date, there is no in vivo model that represents all the haemodynamic characteristics of HFpEF, and only a few have proven to be reliable for the preclinical evaluation of potentially new therapeutic targets. HFpEF accounts for 50% of all the heart failure cases and its incidence is on the rise, posing a huge economic burden on the health system. Patients with HFpEF have limited therapeutic options available. The inadequate effectiveness of current pharmaceutical therapeutics for HFpEF has prompted the development of device-based treatments that target the hemodynamic changes to reduce the symptoms of HFpEF. However, despite the potential of device-based solutions to treat HFpEF, most of these therapies are still in the developmental stage and a relevant HFpEF in vivo model will surely expedite their development process. This review article outlines the major limitations of the current large in-vivo models in use while discussing how these designs have helped in the development of therapy devices for the treatment of HFpEF.

Association of the triglyceride-glucose index with all-cause and cardiovascular mortality in patients with cardiometabolic syndrome: a national cohort study.

OBJECTIVE: This study aimed to evaluate the association of triglyceride-glucose (TyG) index with all-cause and cardiovascular mortality risk among patients with cardiometabolic syndrome (CMS). METHODS: We performed a cohort study of 5754 individuals with CMS from the 2001-2018 National Health and Nutrition Examination Survey. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models assessed the associations between TyG index and mortality . Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: Over a median follow-up of 107 months, 1201 all-cause deaths occurred, including 398 cardiovascular disease-related deaths. The multivariate Cox proportional hazards regression model showed a positive association between the TyG index and all-cause and cardiovascular mortality. Each one-unit increase in the TyG index was associated with a 16% risk increase in all-cause mortality (HR: 1.16, 95% CI 1.03, 1.31, P = 0.017) and a 39% risk increase in cardiovascular mortality (HR: 1.39, 95% CI 1.14, 1.71, P = 0.001) after adjusting for confounders. The restricted cubic splines revealed a U-shaped association between the TyG index and all-cause (P for nonlinear < 0.001) and cardiovascular mortality (P for nonlinear = 0.044), identifying threshold values (all-cause mortality: 9.104; cardiovascular mortality: 8.758). A TyG index below these thresholds displayed a negative association with all-cause mortality (HR: 0.58, 95% CI 0.38, 0.90, P = 0.015) but not with cardiovascular mortality (HR: 0.39, 95% CI 0.12, 1.27, P = 0.119). Conversely, a TyG index exceeding these thresholds was positively associated with all-cause and cardiovascular mortality (HR: 1.35, 95% CI 1.17, 1.55, P < 0.001; HR: 1.54, 95% CI 1.25, 1.90, P < 0.001, respectively). Notably, a higher TyG index (≥ threshold values) was significantly associated with increased mortality only among individuals aged under 55 compared to those with a lower TyG index (< threshold values). CONCLUSIONS: The TyG index demonstrated a U-shaped correlation with all-cause and cardiovascular mortality in individuals with CMS. The thresholds of 9.104 and 8.758 for all-cause and cardiovascular mortality, respectively, may be used as intervention targets to reduce the risk of premature death and cardiovascular disease.

Exploring the role of oral microbiome dysbiosis in cardiometabolic syndrome and smoking.

Oral microbiome research has gained significant interest in recent years due to its potential impact on overall health. Smoking has been identified as a significant modulator of the oral microbiome composition, leading to dysbiosis and possible health consequences. Research has primarily focused on the association between smoking and oral microbiome, as well as smoking's association with cardiometabolic syndrome (CMS). This narrative review presents an overview of the recent findings and current knowledge on the oral microbiome and its role in CMS, including the effects of smoking and ethnicity. We discussed the development and composition of the oral microbiome and the association of periodontitis with diabetes and cardiovascular diseases. Furthermore, we highlighted the correlations between oral microbiome and CMS factors, such as diabetes, hypertension, dyslipidemia, and obesity. There is a need for further research in this area to better understand the mechanisms underlying the impact of smoking on oral microbiome dysbiosis and the development of CMS. Interestingly, geographic location and ethnicity have been shown to impact the oral microbiome profiles across populations. This knowledge will help develop personalized disease prevention and treatment approaches considering individual differences in oral microbiome composition. Understanding the complex interplay between oral microbiome, smoking, and CMS is essential for developing effective prevention and treatment strategies for a wide range of diseases.

General practice pharmacist-led antipsychotic physical health monitoring: a prospective intervention scoping study.

BACKGROUND: People with severe mental health illness die prematurely, often due to preventable cardiometabolic disease, which can be exacerbated by antipsychotic medicines that are effective for treating mental illness. Literature demonstrates that physical health monitoring, as recommended in guidelines, for people receiving antipsychotics is substandard. Therefore, we aimed to scope the potential of a general practice clinical pharmacist (GPCP)-led multidisciplinary intervention optimising adherence to cardiometabolic monitoring guidelines and delivering polypharmacy reviews. METHOD: Prospective intervention scoping study in three urban general practices; one usual care, two intervention. Patients 18-65 years old prescribed oral antipsychotics were identified from records, and invited for cardiometabolic monitoring and GPCP medication review, from January to December 2022. Interventions and onward referrals were recorded and collated. Anonymised pre- and post-review data were analysed, and actions were graded for clinical importance. RESULTS: In total 1.5% (210/14,159) of patients aged 18-65 years met inclusion criteria; usual care practice (n = 58); and intervention practices (n = 152). From baseline, the usual care practice achieved an absolute 7% increase in the cardiometabolic monitoring care bundle (glucose/glycosylated haemoglobin, lipids, blood pressure plus body mass index) versus 19-58% in the intervention practices. Two-thirds (92/152) of patients participated in medication reviews, requiring pharmacological and/or non-pharmacological clinical actions. The majority of actions were graded as moderate importance. Seven percentage of patients were identified as new pre-diabetic/diabetic and 6% were at high risk of cardiovascular disease requiring statin initiation. CONCLUSION: A pharmacist-led multidisciplinary general practice-based approach may be effective at optimising cardiometabolic monitoring; identifying and treating diabetic and cardiovascular risk factors.

People with severe mental illness die 15­20 years earlier than the general population, many due to preventable and/or treatable heart disease. While antipsychotic medicines are effective for treating mental illness they are associated with potential adverse effects; weight gain, increased blood pressure, blood sugar, and cholesterol. Therefore, guidelines advise regular physical health checks for people with severe mental illness, and those receiving antipsychotics, to reduce avoidable harms and optimise preventative treatments. However, routine monitoring is substandard. This study aimed to explore the potential of a general practice pharmacist-led intervention to optimise physical health monitoring and medication reviews, from January to December 2022. Three practices participated; one providing usual care, and two the pharmacist intervention. The usual care practice achieved a 7% increase in all monitoring parameters (weight, blood pressure, blood sugars plus cholesterol), whereas the pharmacist-led practices achieved a 19­58% increase in monitoring. Two in three patients (92/152) participated in a medication review with the pharmacists that addressed a range of mental and physical health issues. Of the 152 patients in the intervention practices 6% were identified as being at high risk of heart disease requiring preventative medicines, and 7% were identified as having new diabetes and/or pre-diabetes.

Combined Effect of Dietary Acid Load and Cardiometabolic Syndrome on Bone Resorption Marker among Post-Menopausal Women in Malaysia.

Background: This study aimed to investigate factors associated with bone resorption status and determine the independent and interactive effects of dietary acid load (DAL) and cardiometabolic syndrome (CMS) on bone resorption in post-menopausal women. Methods: Overall, 211 community-dwelling post-menopausal women were recruited from the National Council of Senior Citizens Organization, Malaysia. DAL was estimated using the potential renal acid load from the food frequency questionnaire. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and smoking behaviour was assessed using the Global Adult Tobacco Survey 2011. Serum 25(OH) vitamin D levels were determined using the ADVIA Centaur vitamin D assay and serum C-terminal telopeptides of type I collagen (CTX1) were used as surrogate markers to assess bone resorption. CMS was determined based on the harmonised criteria. Results: Age (ß = -0.145, t = -2.002, P < 0.05) was negatively associated while DAL (ß = 0.142, t = 2.096, P < 0.05) and sleep quality (ß = 0.147, t = 2.162, P < 0.05) were positively associated with CTX1. Height was positively correlated with CTX1 (r = 0.136, P <0.05). Conversely, other variables (CMS traits, CMS, serum 25(OH) vitamin D level, years of menopause, years of education and physical activity) were not significantly associated with CTX1 levels. There was no significant interaction between DAL and CMS on bone resorption. Conclusion: Our findings propose that high DAL, but not CMS, is a potential risk factor for bone resorption. The analysis did not demonstrate the combined effects of DAL and CMS on bone resorption.

The Brain-Heart Axis: Neuroinflammatory Interactions in Cardiovascular Disease.

PURPOSE OF REVIEW: The role of neuroimmune modulation and inflammation in cardiovascular disease has been historically underappreciated. Physiological connections between the heart and brain, termed the heart-brain axis (HBA), are bidirectional, occur through a complex network of autonomic nerves/hormones and cytokines, and play important roles in common disorders. RECENT FINDINGS: At the molecular level, advances in the past two decades reveal complex crosstalk mediated by the sympathetic and parasympathetic nervous systems, the renin-angiotensin aldosterone and hypothalamus-pituitary axes, microRNA, and cytokines. Afferent pathways amplify proinflammatory signals via the hypothalamus and brainstem to the periphery, promoting neurogenic inflammation. At the organ level, while stress-mediated cardiomyopathy is the prototypical disorder of the HBA, cardiac dysfunction can result from a myriad of neurologic insults including stroke and spinal injury. Atrial fibrillation is not necessarily a causative factor for cardioembolic stroke, but a manifestation of an abnormal atrial substrate, which can lead to the development of stroke independent of AF. Central and peripheral neurogenic proinflammatory factors have major roles in the HBA, manifesting as complex bi-directional relationships in common conditions such as stroke, arrhythmia, and cardiomyopathy.

The impact of Ramadan fasting on the metabolic syndrome severity in relation to ethnicity and sex: Results of a systematic review and meta-analysis.

AIMS: The primary goal of this meta-analysis was to examine the changes in various components of metabolic syndrome (MetS) in healthy adults who observed Ramadan fasting (RF) before Ramadan (T1) and at the end of RF (T2). A secondary goal was to assess the impact of RF on MetS severity in various ethnic and sex groups using the MetS z-score. DATA SYNTHESIS: Using PRISMA2020, seven databases were searched for relevant studies published between January 1950 and March 2022. Data extraction involved high-density lipoprotein cholesterol (HDL), triglycerides (TG), fasting blood glucose (FBG), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) for T1 and T2, respectively. The MetS z-score was computed according to international diabetes federation criteria. At T1, the pooled estimates of HDL, TG, FBG, WC, SBP, DBP, and MAP were 1.20 [1.13; 1.27] mmol/L, 1.32 [1.23; 1.42] mmol/L, 4.98 [4.82; 5.15] mmol/L, 87.21 [84.21; 90.21] Cm, 114.22 [101.45; 126.99] mmHg, 76.80 [70.12; 83.47] mmHg, and 89.27 [80.56; 97.98] mmHg, respectively. At T2, the pooled estimates of HDL, TG, FBG, WC, SBP, DBP, and MAP were 1.24 [1.18; 1.31] mmol/L, 1.24 [1.14; 1.34] mmol/L, 4.77 [4.55; 4.99] mmol/L, 85.73 [82.83; 88.64] Cm, 109.48 [97.20; 121.75] mmHg, 74.43 [68.01; 80.85] mmHg, and 86.11 [77.74; 94.48] mmHg, respectively. The MetS z-score showed improvement at T2 for all ethnic groups and both sexes by -0.22 [-0.24; -0.01]. CONCLUSIONS: The current meta-analysis suggests that the RF positively impact the MetS components and the overall MetS z-score. PROSPERO REGISTRATION NUMBER: ID CRD42022329297 OPEN SCIENCE FRAMEWORK IDENTIFIER: DOI 10.17605/OSF.IO/U9H7T.

The effects of Silymarin on the features of cardiometabolic syndrome in adults: A systematic review and meta-analysis.

Some medicinal herbs and their effective components showed positive effects on the features of the cardiometabolic syndrome (CMS). The aim of the present systematic review and meta-analysis is to examine the effects of silymarin on the components of CMS in adults. Four electronic databases including PubMed/Medline, Scopus, Web of Science, and Embase were systematically searched up to December 31, 2020 to identify all eligible clinical trials. A random-effect model using DerSimonian and Laird method was used to estimate the pooled weighted mean differences (WMDs) and the 95% confidence intervals (95%CIs). Finally, 11 clinical trials met the eligibility criteria. Our results demonstrated that silymarin significantly reduced the levels of fasting blood glucose (WMD: -17.96 mg/dL, 95% CI: -32.91, -3.02;I2 : 82.4%, p < 0.001), hemoglobin A1C (WMD: -1.25%, 95% CI: -2.34, 0.16; I2 : 92.9%, p Ë‚ 0.001), total cholesterol (WMD: -17.46 mg/dL, 95% CI: -30.98, -3.95; I2  = 62.9%, p = 0.006), triglyceride (WMD: -25.70 mg/dL, 95% CI: -47.23, -4.17; I2 :54.3%, p = 0.025), low-density lipoprotein-cholesterol (WMD: -10.53, 95% CI: -19.12, -1.94; I2: 37.5%, p = 0.119) and increased high-density lipoprotein- cholesterol (WMD: 3.36 mg/dL, 95% CI: 0.88, 5.84; I2 : 37.4%, p = 0.120) compared to placebo. However, its effects on BMI were not statistically significant. Silymarin can be an effective complementary therapy to improve most features of CMS. However, due to high heterogeneity and limited clinical trials in some parameters, further high-quality clinical trials are needed to confirm its efficacy.

Multi-Bioactivity of Protein Digests and Peptides from Oat (Avena sativa L.) Kernels in the Prevention of the Cardiometabolic Syndrome.

The aim of this study was to characterize the digests and peptides derived from oat kernel proteins in terms of their major enzyme inhibitory activities related to the prevention of cardiometabolic syndrome. It also entailed the characteristics of antioxidant bioactivity of the analyzed material. The study was carried out using coupled in silico and in vitro methods. The additional goal was to investigate whether identified peptides can pervade Caco-2 cells. Based on the results of bioinformatic analysis, it was found that the selected oat proteins may be a potential source of 107 peptides with DPP-IV and/or ACE inhibitory and/or antioxidant activity. The duodenal digest of oat kernels revealed multiple activities. It inhibited the activities of the following enzymes: DPP-IV (IC50 = 0.51 vs. 10.82 mg/mL of the intact protein), α-glucosidase (IC50 = 1.55 vs. 25.20 mg/mL), and ACE (IC50 = 0.82 vs. 34.52 mg/mL). The DPPH• scavenging activity was 35.7% vs. 7.93% that of the intact protein. After in silico digestion of oat proteins, 24 peptides were selected for identification using LC-Q-TOF-MS/MS. Among them, 13 sequences were successfully identified. One of them, i.e., VW peptide, exhibited triple activities, i.e., DPP-IV and ACE inhibitory and DPPH• scavenging activity. The multifunctional peptides: PW, TF, VF, and VW, were identified in the basolateral samples after transport experiments. Both in silico and in vitro analyses demonstrated that oat kernel proteins were the abundant sources of bioactive digests and peptides to be used in a diet for patients suffering from cardiometabolic syndrome.

Preventing Diabetes and Atherosclerosis in the Cardiometabolic Syndrome.

PURPOSE OF REVIEW: Cardiometabolic syndrome is characterized by abdominal adiposity, insulin resistance, hypertension, and dyslipidemia. There is a growing burden of cardiometabolic disease in many parts of the world. This review highlights the critical preventive and therapeutic measures that need to be implemented to reduce the impact of cardiometabolic syndrome on cardiovascular health. RECENT FINDINGS: Recent cardiovascular outcome trials demonstrated that newer glucose-lowering medications reduce cardiovascular and renal events in patients with type 2 diabetes mellitus (T2DM). These medications should be considered in patients with T2DM and atherosclerotic cardiovascular disease (ASCVD). These novel drugs may also play a role in primary prevention of cardiovascular disease (CVD) and renal disease in high-risk patients without T2DM. To manage dyslipidemia associated with cardiometabolic syndrome, in addition to lifestyle interventions and statin therapy, ezetimibe, and proprotein convertase subtilisin/Kexin type 9 (PCSK9), inhibitors can be used to reduce the risk of major adverse cardiovascular outcomes (MACE) especially in patients with T2DM and coronary artery disease (CAD). The residual risk of MACE in such a high-risk population can be further mitigated by treatment with an omega-3 fatty acid such as icosapent ethyl. Lifestyle modifications and the use of proven pharmacological therapies are essential for the prevention and progression of diabetes and ASCVD in those with the cardiometabolic syndrome.

The vicious cycle: a history of obesity and COVID-19.

Recently, we face a surge in the fast-forward Coronavirus Disease 2019 (COVID-19) pandemic with nearly 170 million confirmed cases and almost 3.5 million confirmed deaths at the end of May 2021. Obesity, also known as the pandemic of the 21st century, has been evolving as an adverse prognostic marker. Obesity is associated with a higher risk of being SARS-CoV-2-positive (46%), as well as hospitalization (113%) and death (48%) due to COVID-19. It is especially true for subjects with morbid obesity. Also, observational studies suggest that in the case of COVID-19, no favorable "obesity paradox" is observed. Therefore, it is postulated to introduce a new entity, i.e., coronavirus disease-related cardiometabolic syndrome (CIRCS). In theory, it applies to all stages of COVID-19, i.e., prevention, acute proceedings (from COVID-19 diagnosis to resolution or three months), and long-term outcomes. Consequently, lifestyle changes, glycemic control, and regulation of the renin-angiotensin-aldosterone pathway have crucial implications for preventing and managing subjects with COVID-19. Finally, it is crucial to use cardioprotective drugs such as angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and statins. Nevertheless, there is the need to conduct prospective studies and registries better to evaluate the issue of obesity in COVID-19 patients.

[A new hypothesis on vascular calcification: the exhausting buffer syndrome (EBS)].

Here we propose that the Western world lifestyle disrupts phosphate metabolism and homeostasis due to caloric or acidic hyperphagia. Psychic factors such as social defeat due to stressed social coexistence characterized by reduced activity and chronic hypoventilation (hypercapnia) also play a role. At least two mechanisms mediate the harmful vascular effects of phosphates with intracellular acidosis being a feature in both of them. First, insufficient lifestyle and adjacent diet together with the psychosomatic mechanism of social defeat (mainly through chronic hypercapnic acidosis) lead to insulin resistance characterized by the classical Cardiometabolic Syndrome. Secondly, overload with fixed acids caused by renal insufficiency or acidic diet (due to intracellular metabolic acidosis) leads to our here proposed Exhausting Buffer Syndrome (EBS) which tends to elevate serum inorganic phosphate levels. These two mechanisms overlap and are regulated through genetically determined processes that drive the disruption of phosphate metabolism and lead to vascular calcification. To have a lower intake of calories and less acidic foods combined with low-grade hypocapnia, might be one of several solutions. (Neuropsychopharmacol Hung 2021; 23(1): 215-220)

Gut microbiome of a porcine model of metabolic syndrome and HF-pEF.

Metabolic syndrome (MetS) is a composite of cardiometabolic risk factors, including obesity, dyslipidemia, hypertension, and insulin resistance, with a range of secondary sequelae such as nonalcoholic fatty liver disease and diastolic heart failure. This syndrome has been identified as one of the greatest global health challenges of the 21st century. Herein, we examine whether a porcine model of diet- and mineralocorticoid-induced MetS closely mimics the cardiovascular, metabolic, gut microbiota, and functional metataxonomic phenotype observed in human studies. Landrace pigs with deoxycorticosterone acetate-induced hypertension fed a diet high in fat, salt, and sugar over 12 wk were assessed for hyperlipidemia, hyperinsulinemia, and immunohistologic, echocardiographic, and hemodynamic parameters, as well as assessed for microbiome phenotype and function through 16S rRNA metataxonomic and metabolomic analysis, respectively. All MetS animals developed obesity, hyperlipidemia, insulin resistance, hypertension, fatty liver, structural cardiovascular changes including left ventricular hypertrophy and left atrial enlargement, and increased circulating saturated fatty acid levels, all in keeping with the human phenotype. A reduction in α-diversity and specific microbiota changes at phylum, family, and genus levels were also observed in this model. Specifically, this porcine model of MetS displayed increased abundances of proinflammatory bacteria coupled with increased circulating tumor necrosis factor-α and increased secondary bile acid-producing bacteria, which substantially impacted fibroblast growth factor-19 expression. Finally, a significant decrease in enteroprotective bacteria and a reduction in short-chain fatty acid-producing bacteria were also noted. Together, these data suggest that diet and mineralocorticoid-mediated development of biochemical and cardiovascular stigmata of metabolic syndrome in pigs leads to temporal gut microbiome changes that mimic key gut microbial population signatures in human cardiometabolic disease.NEW & NOTEWORTHY This study extends a prior porcine model of cardiometabolic syndrome to include systemic inflammation, fatty liver, and insulin sensitivity. Gut microbiome changes during evolution of porcine cardiometabolic disease recapitulate those in human subjects with alterations in gut taxa associated with proinflammatory bacteria, bile acid, and fatty acid pathways. This clinical scale model may facilitate design of future interventional trials to test causal relationships between gut dysbiosis and cardiometabolic syndrome at a systemic and organ level.

Changes in Dietary Intake of Major Nutrients and Food Sources among Costa Rican Adolescents in the Last 20 Years.

BACKGROUND: Adolescence offers a window of opportunity to prevent adult obesity and noncommunicable disease risk factors. With the rising prevalence of adolescent obesity over the last 20 y, identifying any changes in dietary risk factors is crucial. OBJECTIVES: We aimed to assess the dietary intake of major nutrients and their food sources in Costa Rican adolescents from 1996 to 2017. METHODS: Means from 3-d food records from adolescents (ages 13-18 y) living in San José (the province with the highest concentration of adolescents in Costa Rica) were obtained in 1996 (n = 276), 2006 (n = 133), and 2017 (n = 818). Differences in consumption of major nutrients and selected food groups by sex and survey period were tested using age- and area-adjusted ANOVAs. RESULTS: In 2017, adolescents consumed significantly (P < 0.05) less saturated and trans fats [saturated: -3.2% of total energy (TE); trans: -1.4% TE], vegetables (-24 g/d), beans (-42 g/d), and white rice (22 g/d) than in 1996. The 2017 adolescents also reported significantly higher consumption of unsaturated fatty acids (MUFAs: up from 8.2% to 15.3% TE; PUFAs: up from 5.5% to 9.5% TE; P < 0.05), sugary drinks (+134 g/d), pastries/desserts (+55 g/d), other refined starchy foods (+36 g/d), and snacks/fast foods (+26 g/d) than their 1996 counterparts. In 1996 and 2006, the main source of calories was white rice, whereas in 2017, it was sugary drinks (12% TE and 15% TE, respectively; P < 0.05). The intake ratio of beans to white rice was significantly higher in 1996 (1:1.6) than in 2017 (1:3.5). CONCLUSIONS: The changes in the intake of major nutrients and food sources of Costa Rican adolescents present new public health challenges for cardiometabolic risk prevention. Costa Rica should prioritize the design of comprehensive strategies that target added sugar intake while simultaneously increasing access to and promotion of healthful items.

Effects and outcomes of cardiac surgery in patients with cardiometabolic syndrome.

INTRODUCTION: Cardiometabolic syndrome (CMS) is diabetes mellitus (or insulin resistance) plus any two of the following risk factors: hypertension, obesity, and hyperlipidemia. The correlation of metabolic syndrome with cardiovascular disease and the increase in the prevalence of patients with risk factors have solidified the importance of continued focus on metabolic syndrome. We retrospectively evaluated single-center data to determine if there is an association between CMS and outcomes. METHODS: The local Society of Thoracic Surgeons Adult Cardiac Database was queried for consecutive coronary bypass (CABG) cases from 2002 to 2010. Short and long-term outcomes were compared between groups of patients with CMS and then risk-adjusted using multiple regression models with adjusted odds ratios and hazard ratios. RESULTS: Of 11 021 CABG cases, 3881 (35.2%) had CMS, with an annual prevalence that increased from 32% to 40% during the study. Patients with CMS were more likely to have prior cerebrovascular diseases, strokes, renal insufficiency, and worse New York Heart Association status. Unadjusted postoperative comparisons revealed that patients with CMS had higher rates of stroke, renal failure, dialysis, deep sternal wound infection, and longer intensive care unit and hospital length of stay. Risk-adjusted odds ratios did not reveal a significant impact on short-term outcomes, however, adjusted hazard ratios continued to demonstrate significant decreases in long-term survival in patients with CMS. CONCLUSIONS: Patients with CMS were more likely to present with increased comorbidities. Patients with CMS undergoing CABG were at risk for worse short-term secondary postoperative outcomes and reduced long-term survival. The data supports the need for further investigation for risk reduction surrounding operative revascularization.

Cardiovascular Active Peptides of Marine Origin with ACE Inhibitory Activities: Potential Role as Anti-Hypertensive Drugs and in Prevention of SARS-CoV-2 Infection.

Growing interest in hypertension-one of the main factors characterizing the cardiometabolic syndrome (CMS)-and anti-hypertensive drugs raised from the emergence of a new coronavirus, SARS-CoV-2, responsible for the COVID19 pandemic. The virus SARS-CoV-2 employs the Angiotensin-converting enzyme 2 (ACE2), a component of the RAAS (Renin-Angiotensin-Aldosterone System) system, as a receptor for entry into the cells. Several classes of synthetic drugs are available for hypertension, rarely associated with severe or mild adverse effects. New natural compounds, such as peptides, might be useful to treat some hypertensive patients. The main feature of ACE inhibitory peptides is the location of the hydrophobic residue, usually Proline, at the C-terminus. Some already known bioactive peptides derived from marine resources have potential ACE inhibitory activity and can be considered therapeutic agents to treat hypertension. Peptides isolated from marine vertebrates, invertebrates, seaweeds, or sea microorganisms displayed important biological activities to treat hypertensive patients. Here, we reviewed the anti-hypertensive activities of bioactive molecules isolated/extracted from marine organisms and discussed the associated molecular mechanisms involved. We also examined ACE2 modulation in sight of SARS2-Cov infection prevention.

Ameliorative effect of low-dose spironolactone on obesity and insulin resistance is through replenishment of estrogen in ovariectomized rats.

Women have a lower incidence of cardiovascular diseases (CVD) than men at a similar age but the reverse is the case after menopause, indicating a possible protective effect of estrogen on cardiometabolic function. Although various hormonal therapies have been formulated to combat the CVD risks in postmenopausal state, the beneficial effects have not been consistent. Obesity with insulin resistance (IR) is closely linked to CVD risks while ovariectomized rodents have been shown to mimic a state of obesity and IR. We therefore hypothesized that low-dose spironolactone would ameliorate obesity and IR in estrogen-deprived rats by replenishing estrogen and suppressing elevated glycogen synthase kinase-3 (GSK-3). Ten-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM), spironolactone (SPL; 0.25 mg/kg), and ovariectomized (OVX) rats treated with or without spironolactone daily for 8 weeks. Results showed that estrogen deprivation through ovariectomy caused increased body mass gain and visceral adiposity that are accompanied by increased HOMA-IR, HOMA-ß, 1-hour postload glucose, glucose intolerance, platelet/lymphocyte ratio, plasma insulin, atherogenic dyslipidemia, uric acid, GSK-3, corticosterone, and aldosterone and depressed 17ß-estradiol. However, treatment of OVX rats with spironolactone ameliorated all these effects. Taken together, the results demonstrate that treatment with low-dose spironolactone improves obesity and IR, which appears to involve replenishment of estrogen and suppression of GSK-3 along with circulating mineralocorticoid and glucocorticoid. The findings imply a positive cardiometabolic effect of low-dose spironolactone usage in estrogen-deprived conditions.

Antihypertensive and Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Fish as Potential Cardioprotective Compounds.

The term metabolic/cardiometabolic/insulin resistance syndrome could generally be defined as the co-occurrence of several risk factors inclusive of systemic arterial hypertension. Not only that organizations, such as the world health organization (WHO) have identified high blood pressure as one of the main risk factors of the cardiometabolic syndrome, but there is also a link between the occurrence of insulin resistance/impaired glucose tolerance and hypertension that would consequently lead to type-2 diabetes (T2D). Hypertension is medicated by various classes of synthetic drugs; however, severe or mild adverse effects have been repeatedly reported. To avoid and reduce these adverse effects, natural alternatives, such as bioactive peptides derived from different sources have drawn the attention of researchers. Among all types of biologically active peptides inclusive of marine-derived ones, this paper's focus would solely be on fish and fishery by-processes' extracted peptides and products. Isolation and fractionation processes of these products alongside their structural, compositional and digestion stability characteristics have likewise been briefly discussed to better address the structure-activity relationship, expanding the reader's knowledge on research and discovery trend of fish antihypertensive biopeptides. Furthermore, drug-likeness of selected biopeptides was predicted by Lipinski's rules to differentiate a drug-like biopeptide from nondrug-like one.

Deciphering PPARγ activation in cardiometabolic syndrome: studies by in silico and in vivo experimental assessment.

Cardiometabolic syndrome (CMetS) is a consolidation of metabolic disorders characterized by insulin resistance, dyslipidemia and hypertension. Curcumin, a natural bioactive compound, has been shown to possess notable anti-oxidant activity and it has also been included as a super natural herb in the super natural herbs database. Most of the beneficial effects of Curcumin are possibly due to activation of the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ). The present study investigates molecular interactions of curcumin with PPARγ protein through molecular docking and molecular dynamics (MD) simulation studies. Further, effect of curcumin on high fat diet induced CMetS was studied in rats along with western blot for PPARγ and nuclear factor-κB (NF-κB) expressions and histopathological studies. Computational studies presented several significant molecular interactions of curcumin including Ser289, His323, His449 and Tyr473 of PPARγ. The in vivo results further confirmed that curcumin was able to ameliorate the abnormal changes and also, increased PPARγ expressions. The results confirm our hypothesis that activation of PPARγ by curcumin possesses the therapeutic potential to ameliorate the altered levels of metabolic changes in rats in the treatment of CMetS. This is the first report of CMetS treatment by curcumin and study of its underlying mechanism through in silico as well as in vivo experiments.

Oral hormonal therapy with ethinylestradiol-levonorgestrel improves insulin resistance, obesity, and glycogen synthase kinase-3 independent of circulating mineralocorticoid in estrogen-deficient rats.

Estrogen deficiency has been associated with increased incidence of cardiovascular diseases , and recent clinical trials of standard formulations of hormonal therapies have not demonstrated consistent beneficial effects. Estrogen-progestin therapy has been used as exogenous estrogen to normalize depressed estrogen level during menopause. Ovariectomized rodents mimic an estrogen-deficient state in that they develop cardiometabolic dysfunction, including insulin resistance (IR). We therefore hypothesized that hormonal therapy with combined oral contraceptive steroids, ethinylestradiol-levonorgestrel (EEL), improves IR, obesity, and glycogen synthase kinase-3 (GSK-3) through reduction of circulating mineralocorticoid in ovariectomized rats. Twelve-week-old female Wistar rats were divided into 4 groups: sham-operated (SHM) and ovariectomized (OVX) rats were treated with or without EEL (1.0 µg ethinylestradiol and 5.0 µg levonorgestrel) daily for 8 weeks. Results showed that OVX or SHM + EEL treated rats had increased HOMA-IR (homeostatic model assessment of IR), 1 h postload glucose, HOMA-ß, triglycerides (TG), total cholesterol (TC), TC/HDL cholesterol, TG/HDL cholesterol, plasma insulin, GSK-3, corticosterone, and aldosterone. On the other hand, OVX + EEL treatment ameliorated all these effects except that of aldosterone. Taken together, the results demonstrate that oral hormonal replacement with EEL improves IR and pancreatic ß-cell function and suppresses GSK-3 and glucocorticoid independent of circulating aldosterone, suggesting a positive cardiometabolic effect of oral EEL therapy in estrogen-deficient rats.