Risk Factor For Cardiovascular Morbidity Research Articles

Effects of Continuous Positive Airway Pressure Treatment on Vascular Function in a Real-Life Cohort of Elderly Patients with Obstructive Sleep Apnoea Syndrome

Background: Obstructive sleep apnoea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality and has a detrimental effect on vascular function, in particular on arterial stiffness and endothelial function. Continuous positive airway pressure (CPAP) is the gold-standard therapy for OSAS and its effects on arterial stiffness and endothelial function have been demonstrated in non-elderly patients. Objectives: The objective of this study was to evaluate the effect of one year of CPAP treatment on arterial stiffness, through assessment of carotid–femoral pulse wave velocity (cf-PWV), and on endothelial function, through the reactive hyperaemia index (RHi), in a real-life cohort of elderly patients with moderate-to-severe OSAS and several comorbidities. Methods: In this nonrandomised prospective study, we enrolled 469 consecutive elderly patients affected by moderate-to-severe OSAS distributed in two groups: CPAP-treated (n = 225) and untreated patients (n = 244). Results: At one-year follow-up, in the treated group emerged an important improvement in poligraphics (AHI, ODI, TC90, mean SpO2%), laboratory (HOMA index, eGFR, hs-CRP) and vascular function parameters: cf-PWV. The stepwise multivariate linear regression demonstrated a significant correlation between the delta of the polygraph parameters and the delta of PWV and RHi. Conclusions: Our study confirmed the favourable effects of CPAP therapy in a cohort of elderly patients affected by OSAS and several comorbidities on sleep respiratory parameters and vascular function; early diagnosis and treatment with CPAP might be beneficial to delay or prevent the occurrence of cardiovascular events in these groups of patients.

Mood instability and cardiovascular modification in cardiovascular disease outpatients. The ABC study on heart disease

Abstract Introduction Mood instability (MI) is a condition characterized by unpredicted frequent fluctuations in a person's emotional state. It is a common personality trait observed in the general population, and it has been reported to be associated with a range of adverse health outcomes, and may also serve as an additional risk factor for cardiovascular morbidity. Purpose To assess mood instability and its effects on cardiovascular function among CVD outpatients. Methods Consecutive patients who were presented to the cardiac outpatient clinic in the last 5 years were recruited and divided into 2 groups according to the presence or absence of MI symptoms based on the patient’s self-assessment psycho-emotion questionnaire. Cardiovascular functions were assessed and compared between both groups. Results A total of 415 patients were included in this preliminary analysis. Patients' mean age was 66±18 years, and 57% were males. Coronary artery diseases were registered in 93(22%) patients. 137 (33%) patients suffered mood instability symptoms, and they shared most demographic and clinical characteristics with patients who did not suffer from MI. However, males were more frequent among patients with no MI symptoms. Interestingly, we observed a significant difference in systolic blood pressure values (SBP) between both groups, (SBP= 150±23 Vs 145±21 mmHg, p= 0.02, for patients with and without MI, respectively). Yet, no difference was observed in diastolic blood pressure (DBP) values (80±12 Vs 79±11 mmHg for patients with and without MI, respectively, p<0.19). Patients with MI symptoms had also a higher heart rate (HR) (77±15 bpm) than patients without symptoms (72±13 bpm, p=0.0003). Using multivariable linear regression models, mood instability (β±SE= 4.3±2.2, p<0.049) and age (β±SE= 0.4±0.05, p<0.0001) were independent predictors for higher SBP values. Mood instability was also independently associated with a higher heart rate (β±SE= 5.1±1.4, p=0.001). Results Kept true even stronger with repeated BP and HR measurements. Conclusion Our results showed that mood instability is associated with a significant increase in systolic blood pressure and heart rate values in cardiac outpatients.

2024 Latin American Society of Hypertension guidelines on the management of arterial hypertension and related comorbidities in Latin America.

Hypertension is responsible for more than two million deaths due to cardiovascular disease annually in Latin America (LATAM), of which one million occurs before 70 years of age. Hypertension is the main risk factor for cardiovascular morbidity and mortality, affecting between 20 and 40% of LATAM adults. Since the publication of the 2017 LASH hypertension guidelines, reports from different LATAM countries have confirmed the burden of hypertension on cardiovascular disease events and mortality in the region. Many studies in the region have reported and emphasized the dramatically insufficient blood pressure control. The extremely low rates of awareness, treatment, and control of hypertension, particularly in patients with metabolic disorders, is a recognized severe problem in LATAM. Earlier implementation of antihypertensive interventions and management of all cardiovascular risk factors is the recognized best strategy to improve the natural history of cardiovascular disease in LATAM. The 2024 LASH guidelines have been developed by a large group of experts from internal medicine, cardiology, nephrology, endocrinology, general medicine, geriatrics, pharmacology, and epidemiology of different countries of LATAM and Europe. A careful search for novel studies on hypertension and related diseases in LATAM, together with the new evidence that emerged since the 2017 LASH guidelines, support all statements and recommendations. This update aims to provide clear, concise, accessible, and useful recommendations for health professionals to improve awareness, treatment, and control of hypertension and associated cardiovascular risk factors in the region.

Twelve hot questions in the management of hypertension in patients aged 80+ years and their answers with the help of the 2023 European Society of Hypertension Guidelines.

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality, and highly prevalent in older age, underscoring the importance of its appropriate management. The population is ageing at an increasing rate, with those aged 80+ years being the fastest growing population characterized by high heterogeneity in terms of functionality and autonomy. The prevalence of hypertension rises with increasing age, due to a significant increase in SBP largely as a result of age-related stiffening of the aorta and other large arteries, affecting almost 80% of those aged 80+ years. Appropriate management of blood pressure in this population is a priority for clinicians. Frailty is a condition characterized by marked vulnerability to adverse health outcomes and is common among older adults including those with hypertension. Hypertension increases frailty level and at the same time, individuals with increasing frailty present with more drug-related adverse effects meaning they are less tolerant to blood pressure lowering by medication. Thus, frailty is a factor that should be integrated when treating hypertension in this population. The European Society of Hypertension 2023 Guidelines on the management of Hypertension are the first international guidelines to integrate the concept of adapting blood pressure management in older adults according to their frailty/functionality level, and to propose practical tools for the application of this concept in the daily practice of physicians and other healthcare professionals. The present article prepared by the European Society of Hypertension Working Group on Hypertension in Older Adults aims to further address some important aspects mentioned concisely in the 2023 European Society of Hypertension guidelines, in order to help physicians and other healthcare professionals including those practicing in primary care. To this end, this study discusses 12 'hot questions' which are answered with the help of the 2023 European Society of Hypertension Guidelines. We hope the present article and Working Group's actions will contribute to understanding and applying the ideal management of hypertension in this most vulnerable population.

Abstract 49: Activator protein 1 (AP-1) Complex in Antigen Presenting Cells contributes to Salt-Sensitive Blood Pressure in Humans

Salt-sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality. The exact mechanism by which salt intake increases blood pressure is complex and not fully understood. We previously found that sodium entry into antigen-presenting cells (APCs) via the epithelial sodium channel (ENaC) activates proinflammatory cytokines to activate T cells and modulate salt-sensitive hypertension. The activator protein 1 (AP-1) transcriptional factors (FOS/JUN) have been implicated in activating the pro-inflammatory pathway, but its role in SSBP is unknown. We hypothesized that high salt activates the AP-1 signaling pathway and inflammation in APCs and contributes to SSBP. Our bulk RNA-sequencing data in human monocytes, demonstrated that high salt increases the expression of the AP-1 gene family, FOS (2,378.1 ± 480.7 vs 6,494.0 ± 945.5, p= 0.0009), and JUN (7,313.9 ± 984.9 vs11,370.0 ± 1,286.3, p= 0.0015) compared to normal salt-treated monocytes. In additional experiments, we enrolled patients with hypertension and phenotype them for SSBP using an established inpatient protocol of salt-loading/depletion and performed single-cell transcriptomic analyses on peripheral blood mononuclear cells (PBMCs). We observed expression of the e FOS (r= 0.5041, p= 0.0464) and JUN (r= 0.7083, p= 0.0021) genes changes in concert with blood pressure in salt-sensitive (SS) but not in salt-resistant (SR) patients. To confirm whether genes expression translates to protein expression, we cultured total splenocytes from salt-sensitive SV/129 mice for 24 hours in either normal (150 mM) or high salt media (190 mM) and performed flow cytometry. Compared to normal salt, high salt-induced a significant increase in the expression of FOS-JUN genes in monocytes of the spleen. We also adoptively transferred PBMCs from salt-sensitive (SS) and salt-resistant (SR) hypertensive individuals into immunodeficient NSG mice, treated with the high salt diet for three weeks and performed flow cytometry on immune cells of the kidney, aorta, and spleen. We found that immune cells from SS people demonstrated a higher propensity to infiltrate mouse tissues with increased expression of FOS-JUN genes than immune cells from SR people. These preliminary findings disclose the role of the AP-1 gene family in salt-sensitive hypertension and may provide a potential therapeutic target for the treatment and diagnosis of SSBP.

P155 WHAT ARE THE SEX DIFFERENCES IN THE USE OF SINGLE-PILL COMBINATIONS IN THE TREATMENT OF ARTERIAL HYPERTENSION? RESULTS FROM HOME BLOOD PRESSURE MONITORING IN SLOVAKIA IN 2022

Arterial hypertension (AH) is the leading risk factor for cardiovascular morbidity and mortality for both, men and women. Aim of the trial: To evaluate the share of single-pill combinations (SPC) according to the gender of doctors and their patients. To evaluate the efficacy of the AH treatment with HBPM and education. Patients and Methods: This project was conducted from April to June 2022 at 178 general physician practices. We have enrolled consecutive adult patients willing to complete a questionnaire and take office BP and HBPM measurements. Results: 4375 pts with AH were enrolled (2089 women, 51,8%), mean age 61,1 ± 19,1 years. The mean office BP was higher in male (136,7 ± 10,9/ 81,9 ± 7,2 mmHg), vs female patients (135±7,2/ 80,2 ± 6,2 mmHg). Mean blood pressure at home (HBP) was also higher in males (134,1± 7,2/ 81,1± 6,3 mmHg). There were 72% (129) of female doctors, participating in the trial. The widest use of SPC was when male doctors treated male patients (70,7%). The lowest use of SPC was when female doctors treated female patients (52,1%). 44,6% of patients were treated with double SPC and 14,3% with triple. Dual SPC was the most preferred treatment when male patients were treated by male doctors (52,3%). Triple SPC strategy was used mostly when female doctors were giving care to male patients (16,8%). More patients reached optimal BP at home when treated by a male doctor (68%). Conclusion: Appropriate education of patients and their engagement via HBPM, led to 67% BP control. The preference for SPC by male doctors led to significantly better BP control at home, regardless of the gender of patients. By systematic rationalization of pharmacotherapy according to the 2023 ESH Guidelines, using SPC has the potential to improve adherence and increase the BP control rate in Slovakia to fulfill the initiative Charter 70/2023.

Abstract P179: The Role of Sodium Induced-RGMa in Salt-Sensitive Hypertension

Salt sensitivity of blood pressure, characterized by blood pressure fluctuations that mirror dietary sodium (Na) intake, is an independent risk factor for cardiovascular morbidity and mortality in people with and without hypertension. We previously found that elevated Na uptake via the amiloride-sensitive epithelial sodium channel (ENaC) in antigen-presenting cells leads to the upregulation of isolevuglandins and proinflammatory cytokines ultimately leading to T cell activation and salt-sensitive hypertension. In addition, we also showed that SMAD3 activation plays a role in inflammation and salt-sensitive hypertension. In previous studies, RGMa has been shown to be upstream of SMAD3. Furthermore, previous studies have also shown that knockdown of RGMa leads to reduced levels of TGFβ1-induced SMAD3 phosphorylation. The exact mechanism by which elevated extracellular Na leads to increased blood pressure remains unknown. We hypothesized that RGMa complexes with TGFβ1R1 to promote SMAD3 phosphorylation ultimately contributing to inflammation in salt-sensitive hypertension. To test our hypothesis, we isolated monocytes from human participants (N =11) and treated them with either high (190 mMol/L) or normal (150 mMol/L) Na in vitro for 72 hours and subsequently performed bulk RNA sequencing. In additional experiments, we performed an in vivo high Na treatment by utilizing a rigorous salt-loading/depletion protocol on human participants (N = 9) and conducted single-cell transcriptomic analyses. Our bulk RNA sequencing analyses revealed there was no difference in expression of TGFβ1R1 (8837 ± 780.9 vs. 9688 ± 942.5, p =0.350) and TGFβ1R2 (7012 ± 717.0 vs. 7176 ± 633.9, p = 0.059). Interestingly, RGMa (2253 ± 441.0 vs. 516 ± 84.1, p <0.001) and TGFβ1 (5118 ± 353.9 vs. 9067 ± 826.4, p = 0.073) were significantly upregulated in human monocytes after high Na treatment compared to normal salt. However, single-cell transcriptomic analyses found no correlation between the changes in pulse pressure and RGMa (r = 0.5154, p = 0.1911). Our data suggest that RGMa mediates Na-induced inflammation but may not play a role in salt-sensitive hypertension.

Renal Denervation for the Treatment of Hypertension: A Scientific Statement From the American Heart Association.

Hypertension is a leading risk factor for cardiovascular morbidity and mortality. Despite the widespread availability of both pharmacological and lifestyle therapeutic options, blood pressure control rates across the globe are worsening. In fact, only 23% of individuals with high blood pressure in the United States achieve treatment goals. In 2023, the US Food and Drug Administration approved renal denervation, a catheter-based procedure that ablates the renal sympathetic nerves, as an adjunctive treatment for patients in whom lifestyle modifications and antihypertensive medications do not adequately control blood pressure. This approval followed the publication of multiple randomized clinical studies using rigorous trial designs, all incorporating renal angiogram as the sham control. Most but not all of the new generation of trials reached their primary end point, demonstrating modest efficacy of renal denervation in lowering blood pressure across a spectrum of hypertension, from mild to truly resistant. Individual patient responses vary, and further research is needed to identify those who may benefit most. The initial safety profile appears favorable, and multiple ongoing studies are assessing longer-term efficacy and safety. Multidisciplinary teams that include hypertension specialists and adequately trained proceduralists are crucial to ensure that referrals are made appropriately with full consideration of the potential risks and benefits. Incorporating patient preferences and engaging in shared decision-making conversations will help patients make the best decisions given their individual circumstances. Although further research is clearly needed, renal denervation presents a novel treatment strategy for patients with uncontrolled blood pressure.

Abstract Mo060: SPEG mediates increased atrial fibrillation incidence in chronic kidney disease

Introduction: Chronic kidney disease (CKD) is a major public health problem. CKD is a risk factor of cardiovascular morbidity and mortality due to the increased incidence of atrial fibrillation (AF). AF onset is known to be the consequence of cardiomyocyte intracellular calcium (Ca 2+ ) mishandling where increased ryanodine receptor type 2 (RyR2) activity causes triggered activity. RyR2 activity is regulated by phosphorylation of serine 2367 (S2367) by the ‘striated muscle preferentially expressed protein’ (SPEG). Reduced RyR2 phosphorylation at S2367 increases the risk of AF. We hypothesized that changes in atrial SPEG underly the increased risk of AF in CKD patients. Methods: The experimental 5/6 nephrectomy model was used to mimic CKD disease in mice. AF inducibility was determined using intracardiac programmed electric stimulation. Echocardiography was used to analyze cardiac structure. RYR2 phosphorylation and SPEG levels were measured by western blotting. Intracellular Ca2+ dynamics were assessed by confocal microscopy. Results: CKD mice showed increased serum phosphate (14.1±1.4 vs 9.3±0.4mg/dL; p<0.01), creatinine (0.4±0.1 vs 0.8±0.3 mg/dL; p<0.001) and urea (30.5±1.1 vs 20.9±0.4 mg/dL; p<0.001). AF incidence was 4-fold higher in CKD respect sham mice (60 vs 14.2%; p<0.05). CKD mice showed longer P waves (14.3±0.4 vs 12.5±0.3; p<0.01) and greater increase of left atrial size than Sham mice (35.0±7.5 vs 13.9±4.6; p<0.05). Ejection fraction was reduced in CKD mice after 6 weeks of CKD progression (57.9±0.6 vs 61.7±0.8%; p<0.001) while no changes were observed in Sham mice. SPEG levels were decreased in atria from CKD mice compared to sham (0.64±0.11 vs 1.19±0.13; p<0.05). RyR2 phosphorylation at S2367 was reduced in CKD mice atria (0.66±0.16 vs 1.25±0.26 in sham; p=0.098). Atrial cardiomyocytes from CKD mice exhibited altered Ca 2+ handling, with decreased SERCA activity (p<0.05), increased spark-mediated diastolic Ca 2+ leak (p<0.01) and increased NCX activity (p<0.05). Finally, CKD-induced AF onset was prevented in a mice with a mutation that mimics RYR2 phosphorylation at SPEG site (S2367D mice) Conclusion: This study shows for the first time that SPEG levels are decreased in atria from CKD mice what induces increased RyR2 activity leading to increased AF incidence. By conserving RYR2 phosphorylation at Ser2367, CKD-induced AF was prevented. Thus, we propose SPEG as a possible therapeutic target to reduce the increased incidence of AF in CKD patients.

Coronary Artery Disease in Patients on Dialysis: Impact of Traditional Risk Factors.

Background and Objectives: End-stage kidney disease (ESKD) is a major risk factor for cardiovascular morbidity and mortality. This study aims to evaluate the contribution of traditional risk factors to the development of coronary artery disease (CAD) in patients on dialysis. Materials and Methods: In this study, 54 patients on dialysis with angina symptoms or a positive exercise stress test underwent coronary angiography. Lesions with obstruction >70% lumen diameter of the coronary artery were considered significant. Traditional risk factors included hypertension, diabetes, smoking, dyslipidemia, age, gender, and time spent on dialysis. Results: Out of 54 participants, 41 (75.92%) were men and 13 (24.07%) women. CAD was present in 34 (62.96%) patients, and 20 (37.03%) patients were without CAD. The average age of the participants was 66.51 years. In the group with CAD, the average age was 69.52 years with an average time spent on dialysis of 2.73 years. In the group without CAD, the average age was 61.40 years with a time spent on dialysis of 2.35 years. Hypertension was present in 92.59% of all participants and 97.05% of those with CAD. Diabetes was present in 41.17 patients with CAD and 40% of those without CAD. Dyslipidemia was present in 76.47 participants with CAD and in 40% of those without CAD. Smoking was noticed in 35.29% of the participants with CAD and 57.14% of those without CAD. Besides hypertension, significant predictors for the development of CAD in patients on dialysis were dyslipidemia (OR 3.698, Cl 1.005-13.608, p = 0.049) and age (OR 1.056, Cl 1.004-1.110, p = 0.033). Conclusions: Among the traditional risk factors, hypertension, dyslipidemia, and age are the predictors for the development of CAD in patients on dialysis. Further large randomized clinical studies are needed to clarify the role of traditional risk factors for CAD in patients with ESKD.

Assessment of the impact of resting heart rate on the risk of major adverse cardiovascular events after ischemic stroke: a retrospective observational study

BackgroundAlthough elevated heart rate is a risk factor for cardiovascular morbidity and mortality in healthy people, the association between resting heart rate and major cardiovascular risk in patients after acute ischemic stroke remains debated. This study evaluated the association between heart rate and major adverse cardiovascular events after ischemic stroke.MethodsWe conducted a retrospective cohort study analyzing data from the Chang Gung Research Database for 21,655 patients with recent ischemic stroke enrolled between January 1, 2010, and September 30, 2018. Initial in-hospital heart rates were averaged and categorized into 10–beats per minute (bpm) increments. The primary outcome was the composite of hospitalization for recurrent ischemic stroke, myocardial infarction, or all-cause mortality. Secondary outcomes were hospitalization for recurrent ischemic stroke, myocardial infarction, and heart failure. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, using the heart rate < 60 bpm subgroup as the reference.ResultsAfter a median follow-up of 3.2 years, the adjusted hazard ratios for the primary outcome were 1.13 (95% CI: 1.01 to 1.26) for heart rate 60–69 bpm, 1.35 (95% CI: 1.22 to 1.50) for heart rate 70–79 bpm, 1.64 (95% CI: 1.47 to 1.83) for heart rate 80–89 bpm, and 2.08 (95% CI: 1.85 to 2.34) for heart rate ≥ 90 bpm compared with the reference group. Heart rate ≥ 70 bpm was associated with increased risk of all secondary outcomes compared with the reference group except heart failure. ConclusionsHeart rate is a simple measurement with important prognostic implications. In patients with ischemic stroke, initial in-hospital heart rate was associated with major adverse cardiovascular events.

The Critical Role of Community Pharmacists in Blood Pressure Monitoring.

Arterial hypertension is the most important modifiable risk factor for cardiovascular morbidity and mortality. In some countries, pharmacists' patient-centered approach has become a common practice, and their role in supporting the management of cardiovascular disease has been successfully developed for years. In particular, recent findings have confirmed benefits of pharmacist-provided hypertension care. Current guidelines emphasize the need for regular BP measurements in subjects age 40 years and older, who are at increased risk of hypertension. A panel of experts in cardiology, hypertensiology, family medicine, and pharmacy presented a narrative review of implementing community pharmacy blood pressure (CPBP) measurements into Polish pharmacy practice to assist pharmacists in CPBP readings. The paper focuses on basic aspects of management of untreated patients with elevated blood pressure levels, as well as management of individuals diagnosed with hypertension, who should follow their primary care physicians' recommendations for anti-hypertensive therapy. The article also includes a few important aspects related to CPBP measurement, such as equipment and techniques. Development of ready-made schemes of procedures for patients with different results of blood pressure measurement could ensure a uniform standard of services provided by pharmacists. This gives an opportunity to provide such patients with medical care and initiate treatment, and facilitates effective maintenance of BP in hypertensive subjects. This article reviews the role of pharmacists in Poland in screening for hypertension by taking blood pressure measurements.

Association between the Serum Soluble Urokinase Plasminogen Activator Receptor and Peripheral Arterial Stiffness According to the Cardio-Ankle Vascular Index in Patients Undergoing Kidney Transplantation.

High soluble urokinase plasminogen activator receptor (suPAR) levels are correlated with cardiovascular (CV) disease. Arterial stiffness is associated with aging-related vascular diseases and is an independent risk factor for CV morbidity and mortality. It can be measured by the cardio-ankle vascular index (CAVI). We evaluated the association between serum suPAR levels and arterial stiffness according to the CAVI in kidney transplantation (KT) recipients. In this study, 82 patients undergoing KT were enrolled. Serum suPAR levels were analyzed using an enzyme immunoassay. The CAVI was measured using a plethysmograph waveform device, and patients with a CAVI of 9.0 were assigned to the peripheral arterial stiffness (PAS) group. Twenty KT patients (24.4%) had PAS, were of older age (p = 0.042), and had higher serum triglyceride (p = 0.023) and suPAR levels (p 0.001) than the normal group. After adjusting for factors significantly associated with PAS by multivariate logistic regression analysis, serum suPAR levels (odds ratio [OR] 1.072, 95% confidence interval (CI) 1.023-1.123; p = 0.004) were independently associated with PAS in KT patients. The logarithmically transformed suPAR level (log-suPAR) was also positively correlated with the left or right CAVI values (all p 0.001) from the results of the Spearman correlation analysis in KT patients. Serum suPAR levels are positively associated with left or right CAVI values and are independently associated with PAS in KT patients.

Myeloid Cell Glucocorticoid, Not Mineralocorticoid Receptor Signaling, Contributes to Salt-Sensitive Hypertension in Humans via Cortisol.

Salt sensitivity of blood pressure (SSBP) is an independent risk factor for cardiovascular morbidity and mortality, yet the etiology is poorly understood. We previously found that serum/glucocorticoid-regulated kinase 1 (SGK1) and epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel (ENaC)-dependent sodium entry into monocyte-derived antigen-presenting cells (APCs) and activation of NADPH oxidase, leading to the formation of isolevuglandins (IsoLGs) in SSBP. Whereas aldosterone via the mineralocorticoid receptor (MR) activates SGK1 leading to hypertension, our past findings indicate that levels of plasma aldosterone do not correlate with SSBP, and there is little to no MR expression in APCs. Thus, we hypothesized that cortisol acting via the glucocorticoid receptor (GR), not the MR in APCs mediates SGK1 actions to induce SSBP. We performed cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) analysis on peripheral blood mononuclear cells of humans rigorously phenotyped for SSBP using an inpatient salt loading/depletion protocol to determine expression of MR, GR, and SGK1 in immune cells. In additional experiments, we performed bulk transcriptomic analysis on isolated human monocytes following in vitro treatment with high salt from a separate cohort. We then measured urine and plasma cortisol, cortisone, renin, and aldosterone. Subsequently, we measured the association of these hormones with changes in systolic, diastolic, mean arterial pressure and pulse pressure as well as immune cell activation via IsoLG formation. We found that myeloid APCs predominantly express the GR and SGK1 with no expression of the MR. Expression of the GR in APCs increased after salt loading and decreased with salt depletion in salt-sensitive but not salt-resistant people and was associated with increased expression of SGK1. Moreover, we found that plasma and urine cortisol/cortisone but not aldosterone/renin correlated with SSBP and APCs activation via IsoLGs. We also found that cortisol negatively correlates with EETs. Our findings suggest that renal cortisol signaling via the GR but not the MR in APCs contributes to SSBP via cortisol. Urine and plasma cortisol may provide an important currently unavailable feasible diagnostic tool for SSBP. Moreover, cortisol-GR-SGK1-ENaC signaling pathway may provide treatment options for SSBP.

Childhood asthma was associated with the presence of cardio-cerebrovascular diseases in US middle-aged and elderly

BackgroundAsthma and cardio-cerebrovascular diseases (CVDs) share a common etiology of chronic systemic inflammation. Our manuscript was to investigate the association between childhood asthma and CVDs in middle-aged and elderly. MethodsA total of 12,070 US middle-aged and elder were enrolled in the National Health and Nutrition Examination Survey. Childhood asthma was defined as a previous diagnosis of asthma at <18 years of age. Associations between childhood asthma and overall and cause-specific CVDs were evaluated using multivariable logistic regression models and subgroup analyses, including coronary artery disease (CAD), angina, and stroke. ResultsThe prevalence of CVDs, including CAD (p = 0.031) and angina (p < 0.001), was significantly higher in patients with asthma (p = 0.008). Asthma was independently associated with a higher risk of CVDs (odds ratio [OR]:1.50, 95 % confidence interval [CI]: 1.22–1.84, p < 0.001), CAD (OR: 1.55, 95 %CI: 1.17–2.02, p = 0.002), and angina (OR: 1.93, 95 %CI: 1.42–2.58, p < 0.001) while not related to stroke (p = 0.233). Subgroup analysis suggested that the association was consistent across sex, race, and the presence of obesity, chronic obstructive pulmonary disease, and diabetes. ConclusionsChildhood asthma was significantly associated with the presence of cardiocerebrovascular diseases, including CAD and angina in middle-aged and elderly. These findings underscore the importance of addressing childhood asthma as a potential risk factor for cardiovascular morbidity in middle-aged and elderly populations.

Antigen Presenting Cell activator protein 1 (AP-1) complex contributes to Salt-sensitive Blood Pressure

Salt-sensitivity of blood pressure (SSBP) affects 50% of the hypertensive and 25% of the normotensive population and is a major independent risk factor for cardiovascular morbidity and mortality. We previously found that SSBP is associated with activation of the NLRP3 inflammasome in antigen presenting cells (APCs) via increased oxidated stress and isolevuglandin (IsoLG) formation, but the underlying mechanisms are unknown. The activator protein 1 (AP-1) (FOS/JUN) has been implicated in activation of the NLRP3 inflammasome but its role in SSBP is not known. We hypothesized that AP-1 transcription factor in APCs senses elevated sodium and contributes to SSBP. We further hypothesize that antioxidant flavonoid, diosmetin prevents AP-1 activation and SSBP. Using bulk RNA-sequencing in human monocytes, we found elevated sodium increases expression of the AP-1 gene family when compared to normal sodium concentration, including cFOS (2378.18 ± 480.7 vs 6494.09 ± 945.55, p= 0.0009), FOSB (53.63 ± 17. 55 vs 131.06 ± 10.30, p= 0.397), cJUN (7313.90 ± 984.93 vs 11370.09 ± 1286.35, p= 0.2563) JUNB (4218.4.36 ± 199.17 vs 570.45 ± 200.91, p= 0.0445) and JUND (3309. 63 ± 270.64 vs 8057.90 ± 1043.05, p= 0.00006). In additional experiments, we enrolled people with hypertension and phenotype them for SSBP using an established in-patient protocol of salt-loading/depletion and performed single-cell transcriptomic analyses in vivo on peripheral blood mononuclear cells (PBMCs). We found that expression of the FOSB and JUNB genes are more sensitive in concert with blood pressure in salt-sensitive (SS) but not salt-resistant (SR) humans. Moreover, diosmetin attenuated high salt-induced hypertension, 123.5 ± 4.1 vs 146.8 ± 2.5 mm Hg in controls, **p&lt; 0.01). In addition, diosmetin also reduced high salt-induced inflammation including APC production of IsoLG-protein adducts, IL-1β, and NLRP3 inflammasome expression. These findings reveal a role for immune cell AP-1 (FOS/JUN) signaling in salt-sensitive hypertension and diosmetin may provide a potential therapeutic target for treatment of SSBP. 1R01HL144941-01A1. 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.

48-HOUR AMBULATORY BLOOD PRESSURE MEASUREMENT AND VOLUME STATUS IN CHRONIC HEMODIALYSIS PATIENTS

Objective: Both arterial hypertension and fluid overload present prevalent risk factors for cardiovascular morbidity and mortality in end-stage kidney disease patients. Bioelectrical impedance analysis (BIA) is a promising method to assess hypervolemia in hemodialysis (HD) patients. A consensus on how to correctly assess blood pressure (BP) values in HD patients remains to be reached. Ambulatory BP measurement (ABPM) has been found to closely correlate with end-organ damage and cardiovascular risk. Less is known about the significance of 48-hour ABPM and its correlation with overhydration in HD patients. Design and method: 88 randomly selected chronic HD patients completed a 48-hour ABPM and BIA using a body composition monitor before the midweek HD session. Statistical analysis was performed using commercially available SPSS® (version 29.0; Chicago, IL, USA). Descriptive statistics and Pearson's parametric correlation test were performed. P-values of less than 0.05 were considered statistically significant. Results: Included patients were male in 61.4%, with a mean age of 63.7±13.1 years and median dialysis vintage of 47 (95% CI (48.4, 75.6)) months. 21 (23.9%) patients had a dipping pattern, 62 (70.5%) were overhydrated for more than 1 L, and 50% of those patients for more than 2.5 L. Patients’ antihypertensive therapy and their 48-hour ABPM are presented in Tables 1 and 2, respectively. We found a statistically significant and positive correlation between the average 48-hour systolic BP, day-time systolic BP, night-time diastolic BP and overhydration assessed by BIA (r=0.217; p=0.044; r=0.225, p=0.036; r=0.224, p=0.038, respectively) (Table 2). Conclusions: Increased average 48-hour systolic BP, day-time systolic BP and night-time diastolic BP directly correlate with overhydration measured by BIA in chronic HD patients.

Effect of home-based heat therapy on 24-h blood pressure and cutaneous microvascular function in post-menopausal women with hypertension

Hypertension is a leading risk factor for cardiovascular morbidity and mortality and is often accompanied by microvascular dysfunction. Despite a clear effcacy in men, standard antihypertensive medications are less effective in post-menopausal women. Consequently, adjuvant therapies are needed to improve blood pressure control and microvascular function in post-menopausal women. Heat therapy may fill this therapeutic gap as it has been shown to reduce blood pressure and improve microvascular function in healthy and certain clinical populations. Therefore, the purpose of this study was to test the hypothesis that 8 weeks of home-based heat therapy would improve 24-h blood pressure and cutaneous nitric oxide-dependent vasodilation in post-menopausal women with hypertension. Post-menopausal women (69 ± 5 y) with hypertension were randomized to 8 weeks of sham ( N = 15) or heat therapy ( N = 13). Participants immersed their lower legs ~33 cm into a circulated and temperature-controlled (sham: 35 °C; heat therapy: 42 °C) water bath 4 days per week, and 45 min per session. Blood pressure and cutaneous microvascular function and were assessed before (pre) and after (post) the 8-week intervention. Mean arterial blood pressure was measured across 24-h using an ambulatory monitor. To assess microvascular function, an intradermal microdialysis probe was inserted in the anterior aspect of the lower leg at a site directly exposed to water (immersed) and at another site not directly exposed (non-immersed). Red blood cell flux was measured (laser doppler flowmetry) during cutaneous hyperemia induced by 39 °C local heating. N(G)-nitro-L-arginine methyl ester (L-NAME; 20mM) was then infused in each probe until a nadir in red blood cell flux was achieved. Cutaneous vascular conductance was calculated as red blood cell flux divided by mean arterial pressure and normalized to maximal vasodilation (42 °C heating + 56 mM sodium nitroprusside; CVC%max). Nitric oxide-dependent dilation was calculated as the difference between CVC%max measured during the 39 °C plateau and the L-NAME nadir. Mean arterial blood pressure did not differ across time or between groups (sham: pre, 96 ± 5 mmHg vs. post, 96 ± 6 mmHg; heat therapy: pre, 97 ± 4 mmHg vs. 99 ± 7 mmHg; P = 0.5 for interaction). Cutaneous vasodilation induced by local heating did not differ across time for either group (sham: pre, 60 ± 19 CVC%max vs. post, 64 ± 12 CVC%max; heat therapy: pre, 68 ± 15 CVC%max vs. post, 63 ± 13 CVC%max) or between immersed and non-immersed sites ( P = 0.9 for interaction). Similarly, nitric oxide-dependent vasodilation did not differ across time or between sites for either group ( P = 1.0 for interaction). Taken together, 8 weeks of home-based heat therapy does not improve blood pressure or cutaneous microvascular function in post-menopausal women with hypertension. This work was supported by grants from the National Institutes of Health (T32 AG020494; R01AG059314; F32HL167556) and the American Heart Association (TPA958179). 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.

Pattern of Arrhythmia among Diabetes Mellitus Patients in South-South, Nigeria: 24-Hour Ambulatory ECG (Holter ECG) Study

Background: Diabetes is known to be an independent risk factor for cardiovascular morbidity and mortality, commonly associated with rhythm disorders like atrial fibrillation (AF) and ventricular arrhythmias (VA), Diabetes Mellitus (DM) patients have silent myocardial infarctions (MI) with conduction abnormalities like ectopics and others. Regular 12 lead ECGs may not capture subtle conduction abnormalities unlike Holter ECGs which takes longer time to record heart rhythms. The study aims to determine the occurrence and pattern of cardiac arrhythmias in Diabetes Mellitus. Methods: A total of 33 diabetic subjects with age ranged from 18 years and above presented to Goodheart Medical Consultants hospital for 24-hour ambulatory ECG (Holter ECG) using Schiller type (MT-101) Holter ECG machine. Results: In this study, the population consisted of 54.5% men and 45.5% women with a mean age of 63.4 ±14.41, the most common age group was 61–80 years with 42.4%. The two most common forms of arrhythmias for Holter ECGs in this study were supraventricular ectopics 36.4% and ventricular ectopics 33.3%. Conclusion: Supraventricular ectopics is the most common arrhythmia observed among the diabetic subjects in Southern Nigeria and was notably observed more in diabetic male subjects than females. This arrhythmia exposes them to risk of stroke and mortality. Diabetes-related arrhythmias may be a sign of other underlying illnesses.

Improvement in Echocardiographic Indexes of Systolic Heart Failure Post-Kidney Transplantation: A Retrospective Analysis

Introduction: End-stage renal disease is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered contraindication for kidney transplant, although some patients demonstrate myocardial recovery post-transplant. We aimed to identify and characterize the phenomenon of reverse myocardial remodeling in kidney transplanted patients. Methods: The study is a retrospective cohort of patients undergoing kidney transplants between 2016 and 2019 (n = 604) at Rabin Medical Center. Patients were assessed according to availability of two echocardiographic examinations: pre- and post-kidney transplant. The change in estimated ejection fraction (EF) and possible predictors of myocardial recovery were examined. Results: Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal to or above 5%, whereas 36 (12%) patients had a LVEF improvement of 10% or more post-transplantation. Twenty-five patients (8.5%) had moderate or severe systolic heart failure with LVEF reduced to 40% or less at baseline. 13 of them (52%) had a LVEF improvement of ≥5%, and 10 patients (40%) had an improvement of ≥10% in their EF. Cox regression analyses identified female gender as the only independent variable associated with LVEF improvement of at least 10%. Conclusion: Renal transplantation might lead to improved LV systolic function in some patients.