Long-term Cardiovascular Benefits Research Articles

Impact of Laparoscopic Sleeve Gastrectomy on Pulmonary Arterial Stiffness and Right Ventricular Function in Obese Patients.

Pulmonary hypertension (PH) is a serious condition associated with high morbidity and mortality, with obesity identified as a significant risk factor. Pulmonary arterial stiffness (PAS) is an early marker of PH, often preceding clinical symptoms. While laparoscopic sleeve gastrectomy (LSG) has been shown to improve various cardiac parameters in obese patients, its impact on PAS and right ventricular (RV) function in the absence of PH remains unclear. This study investigates the effects of LSG on PAS and RV function in obese patients without pre-existing PH. A cohort of 54 patients with obesity who underwent LSG between January and June 2023 at the University hospital was prospectively studied. Patients were evaluated preoperatively and six months postoperatively using comprehensive echocardiographic assessments. Key parameters measured included tricuspid annular systolic velocity (TAS), tricuspid regurgitation velocity (TRV), pulmonary flow acceleration time (PFAT), pulmonary artery velocity, and PAS. Statistical analyses were conducted using paired t-tests and the Wilcoxon signed-rank test. Significant improvements were observed in several echocardiographic and hemodynamic parameters post-LSG. PAS showed a notable reduction from 2.44 ± 0.68 preoperatively to 1.74 ± 0.32 postoperatively (p < 0.001). Additionally, significant decreases were observed in TRV (2.00 ± 0.30m/sec to 1.79 ± 0.40m/sec, p = 0.025) and systolic pulmonary artery pressure (SPAP) (21.28 ± 4.69mmHg to 18.36 ± 5.28mmHg, p = 0.025). Improvements in RV function were indicated by an increase in tricuspid annular plane systolic excursion (TAPSE) from 17.68 ± 4.17mm preoperatively to 21.18 ± 3.53mm postoperatively (p < 0.001). LSG significantly reduces PAS and improves RV function in obese patients, even in the absence of PH. These findings suggest that LSG may offer protective effects on pulmonary vascular health, highlighting its potential as a therapeutic intervention for reducing PH risk in obese patients. Further research is warranted to explore the long-term cardiovascular benefits of LSG in diverse populations.

Long-Term Cardiovascular Disease Outcomes Following Bariatric Surgery

IntroductionThe long-term cardiovascular benefits of bariatric surgery remain unclear. We aimed to analyze the association between bariatric surgery and cardiovascular disease outcomes. MethodsThe Maryland Health Services Cost Review Commission database (2015-2022) was queried for patients aged 15 to 84 y with obesity. Bariatric surgery patients were matched with nonsurgical patients using propensity score matching. Primary outcomes included all-cause mortality, new-onset heart failure (HF), myocardial infarction (MI), and ischemic stroke. A subgroup analysis of outcomes based on age, sex, diabetes, and smoking status was performed. ResultsA total of 222,700 patients met the inclusion criteria. 104,855 (47.09%) bariatric and 117,845 (52.90%) nonsurgical patients were analyzed. Bariatric surgery was associated with reduced risk of all-cause mortality 12.1 versus 15.7 per 1000 person-years (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.73-0.79, P < 0.001), HF (HR = 0.63, 95% CI = 0.69-0.67, P < 0.001), MI (HR = 0.69, 95% CI = 0.63-0.74, P < 0.001), and stroke (HR = 0.75, 95% CI = 0.69-0.80, P < 0.001). The association between bariatric surgery in the obese population and the improvement in cardiovascular outcomes was significantly pronounced in the pre-existing diabetes mellitus (DM) group compared to the non-DM group in terms of all-cause mortality, HF, and MI (adjusted HR = 0.59, 0.62, 0.59 respectively, P < 0.05). Bariatric surgery was also associated with a statistically significant reduction in all-cause mortality, MI, and stroke in smokers compared to nonsmokers (adjusted HR = 0.61, 0.59, 0.59 respectively, P < 0.05). ConclusionsOur study demonstrates a statistically significant association between bariatric surgery and improvement in long-term cardiovascular outcomes and reduction in all-cause mortality in the obese population following bariatric surgery.

Effects of sodium-dependent glucose transporter 2 inhibitors in patients with type 2 diabetes mellitus and asymptomatic heart failure.

Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have been increasingly used with proven efficacy in patients with heart failure (HF), regardless of diabetes status. Grubić Rotkvić et al recently published an observational study on SGLT2i therapy in patients with type 2 diabetes mellitus and asymptomatic HF. They found that the use of SGLT2i led to reduced cardiac load and improved cardiovascular performance, reinforcing the evolving paradigm that SGLT2i are not merely glucose-lowering agents but are integral to the broader management of cardiovascular risk in patients with type 2 diabetes mellitus. The study by Grubić Rotkvić et al contributes to the growing body of literature supporting the early use of SGLT2i in patients with diabetic cardiomyopathy, offering a potential strategy to mitigate the progression of HF. Future larger studies should be conducted to confirm these findings, and explore the long-term cardiovascular benefits of SGLT2i, particularly in asymptomatic patients at risk of developing HF.

Therapeutic Potential of Sodium-glucose Co-transporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists for Patients with Acute Coronary Syndrome: A Review of Clinical Evidence.

Atherosclerotic Cardiovascular Disease (ASCVD) is still one of the leading causes of death globally, with Coronary Artery Disease (CAD) being the most prevalent form of ASCVD. Patients with type 2 Diabetes Mellitus (DM) experience an increased risk for ASCVD during the disease course, with CAD being the most common cause of death among affected individuals, resulting in shorter life expectancy and increased morbidity among survivors. Recently, 2 novel classes of anti-diabetic drugs, namely Sodium-Glucose Co-Transporter- 2 (SGLT-2) inhibitors and Glucagon-Like Peptide-1 (GLP-1) receptor agonists, have shown impressive cardio-renal benefits for patients with type 2 DM, while they might decrease cardio-renal risk even in the absence of baseline DM. However, there is no evidence to date regarding their safety and efficacy in the setting of an acute coronary syndrome (ACS) event, regardless of concomitant DM. This study aims to provide a detailed, updated presentation of currently available clinical evidence concerning the potential role of SGLT-2 inhibitors and GLP-1 receptor agonists in the setting of an ACS, and to highlight whether those drug classes could be utilized as adjuncts to standard-of-care treatment in this specific patient population, along with a presentation of the potential short- and long-term cardiovascular benefits.

Examining the Impact of Ertugliflozin on Cardiovascular Outcomes in Patients with Diabetes and Metabolic Syndrome: A Systematic Review of Clinical Trials.

Cardiovascular diseases (CVDs) constitute a significant cause of morbidity and mortality globally, particularly among individuals with type 2 diabetes mellitus (T2DM). Ertugliflozin, a Sodium-Glucose Co-transporter-2 (SGLT2) inhibitor, is hypothesized to confer cardiovascular protection; however, long-term follow-up studies are necessary to support the hypothesis. This systematic review was conducted to evaluate the cardiovascular effects of ertugliflozin in diabetic versus non-diabetic cohorts, focusing on major adverse cardiovascular events (MACEs), hospitalizations for heart failure, and cardiovascular mortality. Adhering to PRISMA guidelines, the review encompassed studies indexed in PubMed, Scopus, and Web of Science up to March 2024. Eligibility was restricted to studies involving T2DM patients undergoing ertugliflozin treatment with reported outcomes relevant to cardiovascular health. Out of 767 initially identified articles, 6 met the inclusion criteria. Data concerning hazard ratios (HR) and confidence intervals (CI) were extracted to compare the effects of ertugliflozin with those of a placebo or other standard therapies. The collective sample size across these studies was 8246 participants. Ertugliflozin was associated with a significant reduction in hospitalizations for heart failure relative to a placebo (HR 0.70, 95% CI 0.54-0.90, p < 0.05). Furthermore, when combined with metformin, ertugliflozin potentially reduced MACEs (HR 0.92, 95% CI 0.79-1.07), although this finding did not reach statistical significance. Importantly, for patients with pre-existing heart failure, ertugliflozin significantly decreased the exacerbations of heart failure (HR 0.53, 95% CI 0.33-0.84, p < 0.01). Overall, ertugliflozin markedly reduces hospitalizations due to heart failure in T2DM patients and may improve additional cardiovascular outcomes. These results endorse the integration of ertugliflozin into therapeutic protocols for T2DM patients at elevated cardiovascular risk and substantiate its efficacy among SGLT2 inhibitors. Continued investigations are recommended to delineate its long-term cardiovascular benefits in diverse patient populations, including the potential impact on arrhythmias.

Clinically-relevant reductions in oxygen partial pressure as possible contributor to cardiovascular benefits of sauna practice

The practice of sauna has been found to have both acute and long-term cardiovascular benefits, which are generally postulated to be a result of thermoregulatory physiological adaptations. Another element of sauna conditions which has been overlooked is that the extremely high absolute water content of air at sauna temperature, even at low relative humidity, results in significantly decreased partial pressure of oxygen. Using the Arden-Buck equation for water-carrying capacity of air along with the barometric formula, it is shown in this hypothesis that typical sauna conditions have an oxygen partial pressure reduction that may be equivalent to significant elevations above sea level. This effect may also be enhanced by lower air density further reducing available oxygen relative to respiratory volume.This paper presents the hypothesis that altitude adaptation may be a contributing factor in the cardiovascular benefits of sauna treatments, suggesting that sauna should be considered as an alternative in instances where intermittent hypoxic training is indicated but not available, and that clinical research into sauna treatment is merited for conditions in which intermittent hypoxic training is known to have applications. The hypothesis could be investigated through pulse oximetry of subjects under sauna conditions and by tracking blood markers of altitude adaptation compared to a control group using steam rooms.

Young Trauma-Exposed Women with Low Sleep Effciency have Blunted Sympathetic Baroreflex Sensitivity and Higher Muscle Sympathetic Nerve Activity

Introduction: Poor sleep, a known risk factor for cardiovascular disease (CVD) and one of the American Heart Association’s essential 8th, is common after trauma-exposure. Although premenopausal women are thought to be protected from CVD, trauma exposure might increase their CVD risk. In a recent large epidemiological study examining sleep-related CVD comorbidities, the empirical cut off point for optimal sleep effciency (SE) was set at 83%, distinguishing between good and poor sleep effciency. Studies have suggested an overactive sympathetic nervous system and an impaired baroreflex sensitivity (BRS) as potential mechanisms of increased CVD risk. However, the impact of poor sleep effciency on muscle sympathetic nerve activity (MSNA) and BRS in young trauma-exposed women is unknown. We hypothesized that young trauma-exposed women with poor sleep effciency will present with impaired BRS and increased MSNA at rest. Methods: We collected data on 30 women (18 – 40 years) from diverse backgrounds who had been exposed to trauma. Sleep data was acquired via ActiWatch for 7 days and used to categorize our participants into two groups: good effciency (SE &gt; 83%, n=17) and poor effciency (SE &lt; 83%, n=13), with SE calculated as the percentage of time spent asleep while in bed. Additionally, we collected continuous noninvasive blood pressure (BP), heart rate (HR), and MSNA (burst frequency, incidence, and total activity) during 10 minutes of quiet rest. Sympathetic BRS was determined as the slope of the regression between individual sympathetic bursts and diastolic BP bins (3 mmHg), weighted against the number of cardiac cycles, utilizing an automated program (Ensemble, NZ). Results: There were no significant differences in trauma symptom severity, resting BP and HR between the two groups (p&gt;0.05 for all). However, resting sympathetic BRS was blunted in the poor SE (-0.10±0.88 bursts/100hb/mmHg) compared to the good SE (-1.44±1.58 bursts/100hb/mmHg, p=0.006) group, even after adjusting for age (p=0.009). Likewise, resting total MSNA was higher in the poor SE compared to the good SE after adjusting for age (p=0.028). MSNA burst frequency and burst incidence were comparable between the groups (p&gt;0.05). Conclusion: Our analyses revealed that poor sleep effciency is associated with decreased sympathetic baroreflex sensitivity and higher total muscle sympathetic activity at rest, regardless of age. Blunted sympathetic BRS may contribute to increased sympathetic activity in young women with poor sleep effciency. Future studies testing strategies to improve sleep effciency in this population could provide potential long-term cardiovascular benefits. UL1TR002494 and NIH K01HL161027 No disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

446-P: Antihyperglycemic Medication Initiation after Cardiovascular Hospitalization in Older Adults with Diabetes Increases Hypoglycemia without Improving Survival

Background: The short-term safety and long-term cardiovascular benefits of initiating new antihyperglycemic medications at hospital discharge are unclear, especially for elderly patients with acute cardiovascular disease. This study aimed to determine if initiation of a new diabetes medication is associated with differences in outcomes in this patient population. Methods: This was a population-based cohort study of individuals ≥65 years with diabetes on antihyperglycemic medication who were discharged from a hospitalization for heart failure, acute myocardial infarction, or stroke in Ontario, Canada from April 2011 to March 2019. We categorized individuals based on initiation of a new diabetes medication (initiators) within 30 days of discharge. Primary outcome was a composite of death or cardiovascular hospitalization. Secondary outcome was rate of hypoglycemia. We performed a Cox-regression on a propensity matched cohort. Results: A total of 54,117 individuals were included, with 5,129 (9.5%) initiators and 48,988 (90.5%) non-initiators. Median age was 78 years (IQR 71-84) and 56.7% were male. Matched pair analysis included 4,844 pairs of initiators and non-initiators with standardized differences of ≤0.05 for all baseline variables. Median follow-up was near 2.2 years in both groups. There were no significant differences in the hazard of the composite of death/cardiovascular hospitalization (HR 0.97, 95% CI 0.92-1.02, p=0.18) or the hazard of death (HR 0.98, 95% CI 0.93-1.04, p=0.56). There was a higher risk of hypoglycemia among initiators (113 [2.3%] vs 76 [1.6%]) within one year of follow-up (HR: 1.49, 95% CI 1.12-1.98, p=0.007). Conclusion: Starting a new antihyperglycemic medication in patients with diabetes who are discharged after hospitalization for a cardiovascular event is associated with an increased risk of hypoglycemia but does not reduce mortality or cardiovascular events. Disclosure A.Farahvash: None. A.Sivaswamy: None. H.Abdel-qadir: Other Relationship; AstraZeneca, JAZZ Pharmaceuticals. I.C.Lega: None.

EXERCISE RELATED HYPOTENSIVE EFFECT IN A CARDIAC REHABILITATION PROGRAM AS A POSSIBLE PROGNOSTIC MARKER OF CARDIOVASCULAR RISK

Objective: There are some studies that analyze the correlation between the magnitude of the hypotensive effect after exercise and the long-term cardiovascular benefit. However, this same effect in a cardiac rehabilitation program (CRP) is unknown. The aim was meausuring the benefit of this effect in patients undergoing a cardiac rehabilitation program. Design and method: We analyzed 19 patients who completed a CRP for 3 months (2 weekly sessions of cardiovascular and resistance exercise), in the period between September 2021 and September 2022, after an Acute Coronary Syndrome or hospitalization for Decompensated Heart Failure. In each rehabilitation session, the blood pressure values were evaluated before the beginning of the exercise and after (1st minute and 5th minute of recovery). The effect was compared in two different moments of the program - 1st and 12th session - having defined as main “outcome” a magnitude of higher systolic blood pressure drop in the 12th compared to the 1st session. After completion of the CRP, all patients included in the study were given two validated questionnaires to assess insomnia (“Insomnia Severity Index – ISI”) and the impact of the current illness on quality of life (EQ-5D). Results: Regarding the patients included, the clinical and sociodemographic characteristics are described in table 1. Comparing males and females, using a T-student analysis, there was a statistically significant difference in relation to a greater systolic hypotensive effect in the male group compared to the female group (91.7% vs 40.0%, p &lt; 0.05) – table 2. Regarding the analysis of the impact on quality of life, the total number of patients with improvement in the hypotensive effect of systolic blood pressure showed statistically significant lower values in the questionnaire (EQ5D) – 6.8±1.3 vs 9.0±1.0 (p&lt;0.05) and higher in the score of insomnia 10.7 ± 9.0 vs. 3.9 ± 4.1 - table 2. Conclusions: The systolic hypotensive effect of exercise, observed in the rehabilitation program of the current study, is associated with better rates of insomnia and impact on quality of life. The authors intend to confirm this hypothesis in the longitudinal evaluation of future events.

Long-term effects of lowering postprandial glucose level on cardiovascular outcomes in early-stage diabetic patients with coronary artery disease: 10-year post-trial follow-up analysis of the DIANA study

AimsTo elucidate the long-term cardiovascular benefit of lowering postprandial hyperglycemia (PPG) in early-stage T2DM patients. MethodsThis 10-year post-trial follow-up study included 243 patients from the DIANA (DIAbetes and diffuse coronary Narrowing) study, a multi-center randomized controlled trial which compared the efficacy of one-year life-style and pharmacological (voglibose/nateglinide) intervention lowering PPG on coronary atherosclerosis in 302 early-stage T2DM subjects [impaired glucose tolerance (IGT) or newly-diagnosed T2DM] (UMIN-CTRID#0000107). MACE (all-cause death, non-fatal MI or unplanned coronary revascularization) were compared in (1) three assigned therapies (life-style intervention/vogliose/nateglinide) and (2) patients with and without improvement of PPG (reversion from IGT to NGT or from DM to IGT/NGT on 75 g oral glucose tolerance test). ResultsDuring the 10-year post-trial observational period, voglibose (HR = 1.07, 95%CI: 0.69–1.66, p = 0.74) or nateglinide (HR = 0.99, 95%CI: 0.64–1.55, p = 0.99) did not reduce MACE. Similarly, achieving the improvement of PPG was not associated with a reduction of MACE (HR = 0.78, 95%CI: 0.51–1.18, p = 0.25). However, in IGT subjects (n = 143), this glycemic management significantly reduced the occurrence of MACE (HR = 0.44, 95%CI: 0.23–0.86, p = 0.01), especially unplanned coronary revascularization (HR = 0.46, 95%CI: 0.22–0.94, p = 0.03). ConclusionsThe early improvement of PPG significantly reduced MACE and unplanned coronary revascularization in IGT subjects during the post-trial 10-year period.

β subunits of voltage-gated calcium channels in cardiovascular diseases.

Calcium signaling is required in bodily functions essential for survival, such as muscle contractions and neuronal communications. Of note, the voltage-gated calcium channels (VGCCs) expressed on muscle and neuronal cells, as well as some endocrine cells, are transmembrane protein complexes that allow for the selective entry of calcium ions into the cells. The α1 subunit constitutes the main pore-forming subunit that opens in response to membrane depolarization, and its biophysical functions are regulated by various auxiliary subunits-β, α2δ, and γ subunits. Within the cardiovascular system, the γ-subunit is not expressed and is therefore not discussed in this review. Because the α1 subunit is the pore-forming subunit, it is a prominent druggable target and the focus of many studies investigating potential therapeutic interventions for cardiovascular diseases. While this may be true, it should be noted that the direct inhibition of the α1 subunit may result in limited long-term cardiovascular benefits coupled with undesirable side effects, and that its expression and biophysical properties may depend largely on its auxiliary subunits. Indeed, the α2δ subunit has been reported to be essential for the membrane trafficking and expression of the α1 subunit. Furthermore, the β subunit not only prevents proteasomal degradation of the α1 subunit, but also directly modulates the biophysical properties of the α1 subunit, such as its voltage-dependent activities and open probabilities. More importantly, various isoforms of the β subunit have been found to differentially modulate the α1 subunit, and post-translational modifications of the β subunits further add to this complexity. These data suggest the possibility of the β subunit as a therapeutic target in cardiovascular diseases. However, emerging studies have reported the presence of cardiomyocyte membrane α1 subunit trafficking and expression in a β subunit-independent manner, which would undermine the efficacy of β subunit-targeting drugs. Nevertheless, a better understanding of the auxiliary β subunit would provide a more holistic approach when targeting the calcium channel complexes in treating cardiovascular diseases. Therefore, this review focuses on the post-translational modifications of the β subunit, as well as its role as an auxiliary subunit in modulating the calcium channel complexes.

Diastolic blood pressure and lipid profile in breastfed versus formula-fed infants as early indicators for CVD: a cross-sectional study

BackgroundCardiovascular disease is one of the major causes of death in the world. Low-density lipoprotein cholesterol (LDL-C) is a major cause of cardiovascular disease. Longevity of breastfeeding and exclusiveness have both been proposed as possible moderators of the hazard of future CVD. Dyslipidemia, which includes high levels of triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C), with higher levels of LDL-C, as well as hypertension, obesity, and insulin resistance, accelerates atherosclerotic progression and increases the danger of CVD. The consumption of infant formula has been linked to rapid growth, which raises fat accumulation in late infancy and programmed aberrant vascular biology linked to early CVD.ObjectivesThis study aimed to compare the blood pressure and lipid profiles of breastfed and formula-fed infants in an effort to determine the cause of the differences.ResultsBoth the breastfed and the formula-fed groups showed negligible differences in blood pressure, systolic blood pressure, and blood sugar. Regarding the lipid profile, breastfed newborns had significantly higher levels of Total cholesterol (P <0.001), Triglycerides (P 0.02), HDL-C (P <0.001), LDL-C (P 0.01) and Non-HDL (P <0.001). Newborns who were breastfed had greater levels of non-HDL cholesterol than infants who were fed formula.ConclusionEarly infancy breastfeeding was linked to a higher lipid profile in breastfed infants, suggesting it may have long-term cardiovascular health benefits that should be supported. The molecular mechanism through which breastfeeding regulates lipid metabolism was revealed by further research.

Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study.

IntroductionPatients with chronic hypoparathyroidism are at increased risk of cardiovascular disease. This study evaluated the risk of developing cardiovascular conditions over a period of 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1–84), rhPTH(1–84), compared with a historical control cohort of patients not treated with rhPTH(1–84).MethodsThis retrospective cohort study comprised patients with chronic hypoparathyroidism treated with rhPTH(1–84) in the REPLACE (NCT00732615), RELAY (NCT01268098), and RACE (NCT01297309) clinical trials, and controls selected from the IBM® Explorys electronic medical record database (January 2007–August 2019) who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials. Cardiovascular outcomes were the first diagnosis of cerebrovascular, coronary artery, peripheral vascular disease, or heart failure during the study period.ResultsWe evaluated 113 adult patients with chronic hypoparathyroidism treated with rhPTH(1–84) and 618 control patients who did not receive rhPTH(1–84). Over the 5-year follow-up period, 3.5% of patients (n = 4) in the rhPTH(1–84) cohort had a cardiovascular event compared with 16.3% (n = 101) in the control cohort. Kaplan–Meier analysis demonstrated that patients in the rhPTH(1–84) cohort had lower risk of experiencing a cardiovascular event compared with patients in the control cohort (P = 0.005). Multivariable analyses adjusted for baseline variables showed that patients in the rhPTH(1–84) cohort had 75% lower risk for a cardiovascular event compared with patients in the control cohort (adjusted hazard ratio, 0.25 [95% CI 0.08–0.81]; P = 0.020).ConclusionLong-term treatment with rhPTH(1–84) was associated with a lower risk of incident cardiovascular conditions compared with conventional therapy in patients with chronic hypoparathyroidism. Previous studies demonstrated that mineral homeostasis was maintained with lower use of calcium and active vitamin D when rhPTH(1–84) was added to conventional therapy. Future studies are needed to understand whether improved regulation of mineral homeostasis conferred by rhPTH(1–84) may provide long-term cardiovascular benefits to patients with chronic hypoparathyroidism.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02198-y.

Bioactive spermidine nanoparticles for effective cardiovascular recovery and diabetic therapy

Cardiovascular complications account for more than 80% of type II diabetes (T2D)-related mortality every year. Although glucagon-like peptide 1 receptor agonists (GLP-1RA) can effectively maintain the glycemic level, their efficacy and related cardiovascular benefits are significantly limited owing to their short half-life. Hence, in this study, on the basis of calorie restriction theory, spermidine containing bioactive polymers have been developed to deliver liraglutide with sustained release kinetics. Calorie restrictive and cardiovascular beneficial spermidine (SPM) was conjugated to oxidized dextran to synthesize bioactive SPM-DEX polymer and the SPM-DEX/Liraglutide nanoparticles were successfully prepared using the flash nanocomplexation (FNC) technique via electrostatic polyelectrolyte complexation. Single administration of these sub-100 nm liraglutide nanoparticles efficiently prolonged the hypoglycemic efficacy of liraglutide for more than 4 days. Moreover, through modulating glucose metabolism dysfunction and excessive lipid metabolism, these long-acting liraglutide and SPM containing nanoparticles efficiently maintained a stable blood glucose level (BGL) and body weight in 30 days as biochemical indices, such as HbA1c and triglycerides, were all reduced to the normal range. In addition, by downregulating the Wnt/β-catenin signaling pathway, SPM containing nanoparticles effectively postponed the progression of myocardial fibrosis and systemically improved the systolic function of the cardiac left ventricle. We believe this highly biocompatible, bioactive and calorie restrictive spermidine-containing liraglutide nanoparticles with long-term hypoglycemic efficacy and cardiovascular benefits may hold great clinical potentials.

Hypertension and the kidneys.

Hypertension is a leading risk factor for cardiovascular disease and all-cause mortality globally. Hypertension and chronic kidney disease are closely intertwined conditions as hypertension can lead to deteriorating renal function and progressive chronic kidney disease can contribute to worsening hypertension. In the setting of chronic kidney disease, the pathophysiology of hypertension is complex and involves the interplay of many factors including a reduced number of functioning nephrons, sodium retention and volume expansion, upregulation of the sympathetic nervous system, hormonal factors such as upregulation of the renin-angiotensin-aldosterone system, and endothelial dysfunction. Poorly controlled hypertension can accelerate the progression to end-stage kidney disease. This review discusses the pathophysiological mechanisms that contribute to hypertension, including sympathetic nervous system activity, the renin-angiotensin-aldosterone system and the role of sodium. In the setting of chronic kidney disease, the relationship with hypertension and renovascular disease as a potential cause and target for therapeutic intervention is briefly reviewed. Finally, treatment options, targets and the long-term cardiovascular benefits of optimal blood pressure control are discussed.

Preserved Cardio‐Inotropic Baroreflex Function Following Optimized Hemodynamic Management in High‐Thoracic Spinal Cord Injury

. Chronic high-level spinal cord injury (SCI) results in a complex phenotype of cardiovascular consequences, notably impairments to cardiac contractile function and baroreflex control of blood pressure. Recently, our group has demonstrated that hemodynamic management targeting the heart (i.e. dobutamine, DOB), rather than standard vasopressor treatment (i.e. norepinephrine, NE) improves cord oxygenation and mitigates hemorrhage in a porcine model of acute T2 SCI. Yet, the potential long-term cardiovascular benefits of acute cardio-centric hemodynamic management remain elusive.Assess the chronic changes in hemodynamics and baroreflex function associated with acute DOB administration in animals with T2 SCI.17 Yucatan mini-pigs received a T2 weight-drop contusion SCI, with either DOB (2.5 ug/kg/min, n=6), NE (4.25 ug/kg/min, n=6) or no treatment (CON, n=5) starting at 30 mins until 6 hrs post-SCI. Animals were subsequently recovered and housed for 12 weeks post-SCI. During terminal experiments, animals were instrumented with left ventricular (LV), pulmonary artery and femoral artery catheters to assess LV function, cardiac output (Q) and blood pressure, respectively. Linear regression analyses were used to estimate cardiovagal baroreflex (V-BRx) gain from the relationship of pulse interval vs. systolic blood pressure, and "cardio-inotropic" baroreflex (I-BRx) gain from the relationship of LV contractile function (rate of pressure rise for a given end-diastolic volume) vs. diastolic blood pressure during modified Oxford tests.Data are presented as means±SD. At 12 weeks post-SCI, DOB animals had preserved cardiac output (∆Q=+531±471ml/min) and mean arterial pressure (MAP=81±9mmHg), whereas both Q and MAP were lower in CON animals (∆Q=-385±720ml/min, p=0.44; MAP=65±3mmHg, p<0.0037). In contrast, NE-treated animals had uncharacteristic hypertension as indicated by elevations to MAP (NE=88±11 vs. CON=65±3mmHg, p=0.0029), arterial elastance (NE=3.7±0.4 vs. CON=2.7±0.1mmHg/ml, p=0.016) and total peripheral resistance (NE=50.3±4.3 vs. CON:35.7±10.3mmHg/ml/min, p=0.074). I-BRx function also appeared to be improved in DOB (slope=-0.56±0.33ml/s) vs. CON (slope=-0.04±0.05ml/s, p=0.044), while V-BRx gain did not differ between groups.Cardio-centric management appears to optimize cardiovascular hemodynamics more effectively than vasopressor therapy in chronic high-thoracic SCI. Reduced secondary spinal cord damage with DOB therapy may preserve descending sympathetic pathways to the heart, ultimately improving baroreflex control of blood pressure.

Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Patients With Type 2 Diabetes and Other Risk Factors for Cardiovascular Disease

The cardiovascular outcome in selected populations when sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) are emerging as standard therapy is not clearly understood. It is important to learn the magnitude of cardiovascular benefit using SGLT2-Is across the select subgroups that include both sexes and multiple age and racial and ethnic groups. To evaluate the association between use of SGLT2-Is and cardiovascular benefits in a prespecified group in a larger sample size using data obtained from randomized clinical trials. Search of electronic databases PubMed, Google Scholar, Web of Science, and Cochrane from inception to January 10, 2021, with additional studies identified through conference papers and meeting presentations, ClinicalTrials.gov, and reference lists of published studies. Placebo-controlled randomized clinical trials in which participants had atherosclerotic cardiovascular disease (ASCVD) or risk factors for ASCVD, diabetes, or heart failure and which reported the primary outcome were included in this study. Multicenter observational and nonobservational studies and those with different outcomes of interest were excluded. Medical Subject Heading search terms included SGLT2-I and multiple cardiovascular outcomes in different combinations. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The analysis of all outcomes was performed using a Mantel-Haenszel equation and the random-effects model. Six efficacy outcomes of SGLT2-I use (cardiovascular death and hospitalization for heart failure [HHF] as the primary outcome and major adverse cardiovascular event, HHF, cardiovascular death, acute myocardial infarction, and all-cause mortality as secondary outcomes), were evaluated. Subgroup analysis was performed for the primary outcome of cardiovascular death or HHF. Odds ratios (ORs) and 95% CIs were used to compare 2 interventions. Ten studies with 71 553 participants were included, among whom 39 053 received SGLT2-Is; among studies that reported these data, 28 809 were men and 15 655 were women (mean age, 65.2 [range, 61.9-70.0] years). Race and ethnicity were defined in the original trials and were categorized as Asian, Black, or other (6900 participants) and White (26 646 participants) for the purposes of this analysis (the category "other" was not specified consistently). In terms of age, 16 793 were younger than 65 years and 17 087 were 65 years or older. At a mean follow-up 2.3 (range, 0.8-4.2) years, the SGLT2-I group favored reduction in primary outcome (3165 of 39 053 [8.10%] vs 3756 of 32 500 [11.56%]; OR, 0.67 [95% CI, 0.55-0.80]; P < .001). No difference was noted in the rate of acute myocardial infarction compared with the placebo group (1256 of 26 931 [4.66%] vs 958 of 20 373 [4.70%]; OR, 0.95 [95% CI, 0.87-1.03]; P = .22). Subgroup analysis favored SGLT2-I use for the primary outcome in both sexes, age groups, and racial and ethnic groups. This meta-analysis supports that SGLT2-Is have emerged as an effective class of drugs for improving cardiovascular morbidity and mortality in selected patients. Sodium-glucose cotransporter 2 inhibitors were not associated with reduced risk of acute myocardial infarction. Future long-term prospective studies are warranted to understand the long-term cardiovascular benefits.

Exploring new treatment options for polycystic ovary syndrome: Review of a novel antidiabetic agent SGLT2 inhibitor.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age associated with long-term metabolic and cardiovascular consequences. A plethora of symptoms and their severity differentiate on an individual level, giving the syndrome numerous phenotypes. Due to menstrual cycle abnormalities, women suffer from irregular menstrual bleeding, difficulty in conception, and infertility. Furthermore, the risk of pregnancy complications such as gestational diabetes mellitus, hypertensive disorders of pregnancy, and preterm birth are higher in women with PCOS than in the general population. Often, women with PCOS have comorbidities such as dyslipidemia, obesity, glucose intolerance or diabetes type 2, non-alcoholic fatty liver disease, and metabolic syndrome, which all influence the treatment plan. Historic insulin-sensitizing agents, although good for some of the metabolic derangements, do not offer long-term cardiovascular benefits; therefore, new treatment options are of paramount importance. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors, a new class of antidiabetic agents with beneficial cardiovascular, bodyweight, and antihyperglycemic effects, although not approved for the treatment of PCOS, might be an attractive therapeutic addition in the PCOS armamentarium. Namely, recent studies with SGLT-2 inhibitors showed promising improvements in anthropometric parameters and body composition in patients with PCOS. It is important to further explore the SGLT-2 inhibitors potential as an early therapeutic option because of the PCOS-related risk of metabolic, reproductive, and psychological consequences.

BNP worsens 12 days after alcohol cessation while other cardiovascular risk biomarkers improve: An observational study.

Subjects with alcohol use disorder (AUD) display a high prevalence of cardiovascular risk factors (CRFs), and a high incidence of cardiovascular diseases associated with an earlier mortality. Abstinence has long-term cardiovascular and global health benefits. However, few studies have examined the short-term effect of alcohol cessation on cardiac function and key CRFs. The aim of the study was to assess brain natriuretic peptide (BNP) and other CRFs on admission for alcohol cessation and 12 days later, in inpatients with AUD. A retrospective chart review of inpatients hospitalized for alcohol cessation was conducted. Patients who did not relapse at day 12 were included. We compared, at entry and at day 12, BNP and other CRFs: hemodynamic and electromyographic variables, lipid, homocysteine level, and liver enzymes at entry and at day 12. Wilcoxon, Student tests, and repeated-measures ANOVA were conducted. Fifty-five patients were included (38 males, mean age 50.5 years, alcohol per day 60g-750g, 44 current tobacco smokers). BNP was significantly increased (11.8pg/mL [±16.2] to 35.5pg/mL [±47.6], p<0.001). Repeated-measure ANOVA showed a significant between-subject effect (p=0.024), but no significant interaction between BNP variation and having a BNP at entry >10pg/mL (p=0.092). In contrast, a significant improvement on 8 of 13 other CRFs and liver enzymes measures was observed (p≤0.05). A rapid improvement of several CRFs was confirmed. However, the increase of BNP at day 12 supports its investigation as a possible relevant biomarker of cardiac function in alcohol withdrawal.

Abstract 15491: Effects of Intensive Smoking Cessation Counseling After Acute Coronary Syndrome on 5-year Incidence of Major Adverse Cardiovascular Events and Smoking Abstinence

Introduction: Smoking cessation is recommanded after an acute coronary syndrome (ACS). Long-term cardiovascular benefits of smoking cessation counseling during a hospitalization and shortly after discharge for an ACS remains unknown. We aimed to study the 5-year incidence of major adverse cardiovascular events (MACE, defined as cardiovascular death, myocardial infarction, stroke, unplanned coronary revascularization or hospitalization due to angina) and smoking abstinence after ACS, comparing usual care to an intensive smoking cessation counseling intervention in hospital and after discharge. Methods: We studied 951 smokers from the SPUM-ACS cohort hospitalized for ACS between 2009 and 2014 in a multicenter prospective study with information available at the 5-year follow-up visit on incident MACE. At baseline in 4 study centers, a non-randomized part of smokers with ACS received proactive in-hospital smoking cessation counseling along with several telephone counseling over a 2 months period after discharge. We compared this intensive counseling group to the usual care group, regarding the incidence of MACE at 5 years. We used a multivariate adjusted Cox-proportional hazards model to estimate hazard ratios (HR) and 95% confidence intervals (CI). The secondary outcome was smoking cessation rate 5 years post-ACS. Results: Out of 951 smokers with ACS, 228 (35%) received the intensive in-hospital smoking intervention, of which 186 (82%) accepted to receive counseling after discharge. After multivariable adjustment for age, sex, education and study site, the 5-year risk of a recurrent MACE was comparable between the intensive counseling group and the usual care group, with a multivariable HR of 1.02 (95% CI 0.71-1.46, p=0.92). Among 669 patients alive 5 years post-ACS with known smoking status, 95 (56%) had stopped smoking in the intensive counseling group and 234 (47%) in the usual care group, with a multivariate odds ratio of 0.69 (95% CI 0.47-1.03; p=0.07). Conclusions: In this observational study, an intensive smoking cessation intervention during hospitalization for ACS with post-discharge telephone counseling did not reduce 5-year recurrence of MACE. However, this early intervention may confer a benefit for long-term smoking abstinence.