Risk Factor For Cardiovascular Morbidity Research Articles

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.

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.

Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure.

Hypertension is a principal risk factor for cardiovascular morbidity and mortality, with its severity exacerbated by high sodium intake, particularly in individuals with salt-sensitive blood pressure. However, the mechanisms underlying hypertension and salt sensitivity are only partly understood. Herein, we review potential interactions in hypertension pathophysiology involving the immune system, endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and proteostasis pathways; identify knowledge gaps; and discuss future directions. Recent advancements by our research group and others reveal interactions within and between adaptive and innate immune responses in hypertension pathophysiology. The salt-immune-hypertension axis is further supported by the discovery of the role of dendritic cells in hypertension, marked by isolevuglandin (IsoLG) formation. Alongside these broadened understandings of immune-mediated salt sensitivity, the contributions of T cells to hypertension have been recently challenged by groups whose findings did not support increased resistance of Rag-1-deficient mice to Ang II infusion. Hypertension has also been linked to ER stress and the UPR. Notably, a holistic approach is needed because the UPR engages in crosstalk with autophagy, the ubiquitin proteasome, and other proteostasis pathways, that may all involve hypertension. There is a critical need for studies to establish cause and effect relationships between ER stress and the UPR in hypertension pathophysiology in humans and to determine whether the immune system and ER stress function mainly to exacerbate or initiate hypertension and target organ injury. This review of recent studies proposes new avenues for future research for targeted therapeutic interventions.

Improvement in Echocardiographic Indexes of Systolic Heart Failure Post Kidney Transplantation - a retrospective analysis.

End-stage renal disease (ESRD) is a major risk factor for cardiovascular morbidity and mortality, which can be partially eliminated by kidney transplantation. Systolic heart failure might be considered as contraindication for kidney transplant although some patients demonstrate myocardial recovery post-transplant. We aim to identify and characterize the phenomenon of reverse myocardial remodelling in kidney transplanted patients. The study is a retrospective cohort of patients undergoing kidney transplant between 2016-2019 (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. Data of 293 patients was available for the final analysis. Eighty-one (28%) patients had a LVEF improvement equal or above 5%, whereas 36 (12%) patients had a LVEF improvement 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.

Prescriber decision-making on antithrombotic therapy after endovascular intervention for peripheral artery disease: a protocol for a discrete choice experiment

IntroductionPeripheral artery disease (PAD) is a major risk factor for cardiovascular morbidity and mortality, despite surgical and endovascular treatments. Emerging evidence supports the use of immediate antithrombotic medications after endovascular...

2023 Diabetic Kidney Disease Fact Sheet in Korea.

To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea. We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in patients with diabetes mellitus. The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage. DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.

Blood pressure response to extended-release naltrexone in heroin and prescription opioid users and its implications for cardiovascular morbidity

Background Consuming opioid agonists is a risk factor for cardiovascular disease particularly in intravenous heroin users. The monthly injectable extended-release opioid antagonist, naltrexone (XR-NTX) is an effective treatment for opioid use disorder. The impact of opioid receptor blockade through XR-NTX on blood pressure, a critical risk factor for cardiovascular morbidity, has not yet been characterized. Methods The study evaluated the change in blood pressure during XR-NTX treatment among 14 patients who predominately used intravenous heroin and 24 patients who used prescription oral opioids, all with opioid use disorder. Blood pressure was measured in each patient immediately before the first XR-NTX injection and ∼two weeks after the first injection. The change in diastolic and systolic pressure was compared between the heroin users and the prescription opioids users using analysis of variance. Results XR-NTX treatment was associated with significant decreases in diastolic blood pressure in the heroin group, but not in the prescription opioids group. Systolic blood pressure values in the heroin users showed a decline at trend level only. Conclusions Further research is warranted to replicate our findings and to determine whether XR-NTX effect is relatively specific to blood pressure or generalizes to other components of metabolic syndrome. Distinguishing between heroin and prescription opioid users could shed light on the unique clinical and pharmacological profiles of opioid drugs, particularly regarding their cardiovascular safety. This information can be useful in developing personalized therapeutic strategies based on the route of opioid administration.

Serum Phenylacetylglutamine among Potential Risk Factors for Arterial Stiffness Measuring by Carotid-Femoral Pulse Wave Velocity in Patients with Kidney Transplantation.

Phenylacetylglutamine (PAG), a gut microbiota metabolite, is associated with cardiovascular diseases. Arterial stiffness (AS), which is a marker of aging-associated vascular diseases, is an independent risk factor for cardiovascular morbidity and mortality. This study aimed to assess the correlation between serum PAG levels and AS in kidney transplantation (KT) patients, potentially uncovering new insights into the cardiovascular risks in this population. In this study, 100 KT patients were included. Carotid-femoral pulse wave velocity (cfPWV) was measured, and patients with cfPWV > 10 m/s were categorized as the AS group. Serum PAG levels were assessed using liquid chromatography-tandem mass spectrometry. Thirty KT patients (30.0%) exhibited AS, with higher percentages of diabetes mellitus, older age, and elevated levels of systolic blood pressure, serum fasting glucose, and PAG than the control group. After adjusting for factors significantly associated with AS by multivariate logistic regression analysis, serum PAG, age, fasting glucose levels, and systolic blood pressure were independent factors associated with AS. Furthermore, PAG levels had a negative correlation with the estimated glomerular filtration rate and a positive correlation with cfPWV values. Serum PAG levels are positively associated with cfPWV values and are a biomarker of AS in KT patients.

A comparison of electrocardiographic parameters in e-cigarette users, conventional cigarette smokers, and non-smokers

BackgroundSmoking is a major preventable risk factor for cardiovascular morbidity and mortality. Tobacco smoking induces atherosclerosis, ischemic heart diseases, and arrhythmias. The impact of electronic cigarettes on cardiovascular health is still controversial. This study aimed to evaluate the electrocardiographic parameters in chronic electronic cigarette users compared to chronic conventional cigarette smokers and a non-smoker control group of matched age and gender.ResultsThe study involved 105 volunteers with no history of chronic or cardiovascular diseases or cardioactive drug use. Participants were assigned into three study groups, chronic e-cigarette users, conventional cigarette smokers, and non-smokers, each consisting of 35 participants. Demographic data, smoking history, vital signs, and 12-lead electrocardiogram (ECG) were evaluated. Demographic data were insignificantly different among all study groups. The mean heart rate was significantly higher in chronic electronic cigarette users and conventional cigarette smokers compared to non-smokers (p < 0.001).QRS complex duration was significantly shorter in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). Prolonged QT and QTc intervals duration were recorded in e-cigarette users and conventional smokers compared to non-smokers (p < 0.001). All the ventricular repolarization indices (T wave—peak to T-end (Tpe) interval, TPe/QT ratio, and TPe/QTc ratio were significantly prolonged in chronic e-cigarette users, and conventional smokers compared to non-smokers (p < 0.001). Mean systolic, diastolic blood pressure, P wave amplitude and duration, and PR interval were insignificantly different between all groups (P > 0.05).ConclusionsChronic e-cigarette use is associated with higher heart rates, shorter QRS complex, prolonged QT, QTc duration, and prolonged ventricular repolarization indices compared to non-smokers of matched age and gender. Conclusively, e-cigarette use is associated with negative cardiovascular effects like conventional cigarette smoking.

Evaluation of a Best-Practice Advisory for Primary Aldosteronism Screening

Primary aldosteronism (PA) is a common cause of secondary hypertension and an independent risk factor for cardiovascular morbidity and mortality. Fewer than 2% to 4% of patients at risk are evaluated for PA. To develop and evaluate an electronic health record best-practice advisory (BPA) that assists with PA screening. This prospective quality improvement study was conducted at academic center outpatient clinics. Data analysis was performed between February and June 2023 and included adults with hypertension and at least 1 of the following: 4 or more current antihypertensive medications; hypokalemia; age younger than 35 years; or adrenal nodule(s). Patients previously tested for PA were excluded. A noninterruptive BPA was developed to trigger for PA screening candidates seen in outpatient setting by clinicians who treat hypertension. The BPA included an order set for PA screening and a link to results interpretation guidance. (1) The number of PA screening candidates identified by the BPA between October 1, 2021, and December 31, 2022; (2) the rates of PA screening; and (3) the BPA use patterns, stratified by physician specialty were assessed. Over 15 months, the BPA identified 14 603 unique candidates (mean [SD] age, 65.5 [16.9] years; 7300 women [49.9%]; 371 [2.5%] Asian, 2383 [16.3%] Black, and 11 225 [76.9%] White individuals) for PA screening, including 7028 (48.1%) with treatment-resistant hypertension, 6351 (43.5%) with hypokalemia, 1537 (10.5%) younger than 35 years, and 445 (3.1%) with adrenal nodule(s). In total, 2040 patients (14.0%) received orders for PA screening. Of these, 1439 patients (70.5%) completed the recommended screening within the system, and 250 (17.4%) had positive screening results. Most screening orders were placed by internists (40.0%) and family medicine physicians (28.1%). Family practitioners (80.3%) and internists (68.9%) placed most orders via the embedded order set, while specialists placed most orders (83.0%-95.4%) outside the BPA. Patients who received screening were younger and included more women and Black patients than those not screened. The likelihood of screening was higher among patients with obesity and dyslipidemia and lower in those with chronic kidney disease and established cardiovascular complications. The study results suggest that noninterruptive BPAs are potentially promising PA screening-assistance tools, particularly among primary care physicians. Combined with artificial intelligence algorithms that optimize the detection yield, refined BPAs may contribute to personalized hypertension care.

Differences in carotid to femoral pulse wave velocity and carotid intima media thickness between vegetarian and omnivorous diets in healthy subjects: a systematic review and meta-analysis.

Background: Arterial stiffness and atherosclerosis are known risk factors for cardiovascular morbidity and mortality. Vegetarian diets have been associated with cardiovascular benefits, including improvements in metabolic parameters. However, the impact of a vegetarian diet on cardiovascular parameters, specifically arterial stiffness and atherosclerosis, in healthy individuals remains unclear. Thus, this study aims to analyze differences in arterial stiffness and atherosclerosis between vegetarian and omnivorous diets in healthy subjects. Methods: A systematic review and meta-analysis were conducted following established guidelines. PubMed, Scopus, Web of Science, and Cochrane Library databases were searched for studies examining the association between vegetarian and omnivorous diets with arterial stiffness and atherosclerosis. Cross-sectional studies reporting carotid to femoral pulse wave velocity (cf-PWv) as a measure of arterial stiffness and carotid intima media thickness (c-IMT) as a measure of atherosclerosis were included. Data were synthesized using random effects models, and sensitivity analyses, meta-regressions, and assessment of publication bias were performed. Results: Ten studies were included in the systematic review, and seven studies were included in the meta-analysis. The pooled analysis demonstrated that individuals following a vegetarian diet had differences in the levels of arterial stiffness (cf-PWv) compared to those following an omnivorous diet (MD: -0.43 m s-1; 95% CI: -0.63, -0.23). Similarly, atherosclerosis (c-IMT) was found to be different in individuals adhering to a vegetarian dietary pattern (MD = -29.86 mm; 95% CI: -58.41, -1.32). Conclusions: Our findings suggest that a vegetarian diet is associated with improved arterial stiffness and reduced atherosclerosis in healthy individuals. These results support the inclusion of a well-balanced vegetarian dietary pattern in the prevention and management of cardiovascular diseases. However, further research is needed to explore the effects of a vegetarian diet on arterial health in diverse populations and to assess long-term cardiovascular outcomes.

Striatin Gene Variants Are Associated With Salt Sensitivity of Blood Pressure by Mechanisms That Differ in Women and Men.

Salt sensitivity of blood pressure (SSBP) is a substantial risk factor for cardiovascular morbidity and mortality. Striatin (STRN) is critical for estrogen and aldosterone nongenomic signaling. However, the role of biological sex on the SSBP phenotype associated with STRN gene variants remains unexplored. Data from 1306 subjects participating in the Hypertensive Pathotype (HyperPATH) Consortium were used to identify STRN gene single-nucleotide variants associated with SSBP. Haploblock analysis revealed a novel diplotype in the upstream regulatory region of STRN (rs888083 and rs6744560), with 31% of subjects being homozygous for the risk diplotype. Individuals homozygous for the risk diplotype had significantly greater SSBP than nonrisk diplotypes (P<0.009). While a significant genotype/SSBP association was present in both sexes, their potential mechanisms differed. Women, but not men homozygous risk diplotypes, had significantly greater aldosterone levels than nonrisk diplotypes (5.8±0.4 versus 3.2±0.7 ng/dl; P=0.01; liberal Na+ diet, adjusted). Men, but not women, homozygous risk diplotypes, had significantly reduced renal plasma flow response to Angiotensin II than nonrisk diplotypes (delta 95.2±5.2 versus 122.9±10.2 mL/min per 1.73 m2; P=0.01; liberal Na+ diet, adjusted). The single-nucleotide variants composing the risk diplotype were associated with lower STRN mRNA expression in human tissues (in silico). In women, the primary driver of SSBP is increased aldosterone, while in men, it is reduced renal plasma flow responses. Thus, despite a common hypertensive phenotype (SSBP) in both sexes, the specific treatment approaches might differ to increase therapeutic gain and mitigate adverse effects. These genetic- and sex-based observational results require confirmation in a prospective clinical study.

The correlation between Plasma Fibrinogen Levels and Glycemic Status in type 2 Diabetes Mellitus

Abstract Introduction/Objective Background: Fibrinogen is considered a well-known contributor to the progression of atherosclerotic lesions and a predictor of cardiovascular events. Patients with diabetes mellitus (DM) have higher levels of fibrinogen, which may raise their thromboembolic risk for cardiovascular disease (CVD). Plasma fibrinogen is an indicator of inflammation, and endothelial dysfunction has been described as an independent risk factor for cardiovascular morbidity in type-2 diabetes mellitus (T2DM) patients. Poor glycemic control has been reported to be associated with hyperfibrinogenemia. Aim This study aims to estimate the levels of fibrinogen in patients with type-2 diabetes mellitus and determine its correlation with glycated hemoglobin levels. Methods/Case Report Subjects and methods: It is a cross-sectional analytic study conducted in the Benghazi Diabetic Clinic, Libya. Patients who were diagnosed with type 2 diabetes mellitus, either newly detected or already on diet or treatments, were included in the study during the period between May 2022 to December 2022. A total of 231 adult subjects were selected, with ages ranging from 20-80 years. Random blood sugar levels were assessed. Plasma fibrinogen levels (mg/dl) were estimated by the "Clauss method" and glycosylated hemoglobin (%) by the "immunoturbidimetric method." Patients were categorized into three groups depending upon the HbA1c values, i.e., into &amp;lt;5.7% (good control), 5.7-6.5% (fair control), and &amp;gt;6.5% (poor control). Results (if a Case Study enter NA) Result: Out of 231 subjects, (40.6%) were males and (59.4%) were females, with a mean±SD of age was (47.03±15.54) years. There was a significant positive correlation between fibrinogen and HbA1c in the fair control group (r=0.424, p=0.003) and the poor control group (r=0.369, P=0.000). Moreover, the difference between fibrinogen and age in the good control group was significant (p&amp;gt;0.05), whereas no significance was recognized in other groups. Conclusions Plasma fibrinogen levels are elevated in type 2 DM, and this elevation was associated with poor glycemic control; increased HbA1c levels. The other parameters which correlated with plasma fibrinogen levels were age. Lowering plasma fibrinogen levels could be an integral approach to cardiovascular complications reduction in type-2 DM.

Tachycardia-induced metabolic rewiring as a driver of contractile dysfunction.

Prolonged tachycardia-a risk factor for cardiovascular morbidity and mortality-can induce cardiomyopathy in the absence of structural disease in the heart. Here, by leveraging human patient data, a canine model of tachycardia and engineered heart tissue generated from human induced pluripotent stem cells, we show that metabolic rewiring during tachycardia drives contractile dysfunction by promoting tissue hypoxia, elevated glucose utilization and the suppression of oxidative phosphorylation. Mechanistically, a metabolic shift towards anaerobic glycolysis disrupts the redox balance of nicotinamide adenine dinucleotide (NAD), resulting in increased global protein acetylation (and in particular the acetylation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase), a molecular signature of heart failure. Restoration of NAD redox by NAD+ supplementation reduced sarcoplasmic/endoplasmic reticulum Ca2+-ATPase acetylation and accelerated the functional recovery of the engineered heart tissue after tachycardia. Understanding how metabolic rewiring drives tachycardia-induced cardiomyopathy opens up opportunities for therapeutic intervention.

Metabolic disorders predict future impairment of kidney function in the Japanese general population

Abstract Background/Introduction Metabolic syndrome (MetS) which is defined as accumulation of visceral fat followed by a cluster of metabolic disorders is one of the most important risk factors of cardiovascular morbidity and mortality. Although the close relationship between kidney dysfunction and cardiovascular events have also been reported, the association of kidney dysfunction with MetS remains unidentified. Purpose The present study investigated whether MetS or its components predict future deterioration of kidney function in the general population. Methods Consecutive 14917 subjects with normal estimated glomerular filtration rate (eGFR; ≥60mL/min/1.73m²) who visited our hospital for a physical check-up from 2008 to 2018 (male=8876, 51.3±12.4 year-old) were enrolled and followed up until 2019 for 1847 days (median) with the endpoint being the development of impaired kidney function (eGFR&amp;lt;60mL/min/1.73m²). Metabolic syndrome was defined based on the Japanese diagnostic criteria (2005; waist circumference ≥85 cm for males and ≥90 cm for females and ≥2 of the following three criteria: (1) triglyceride≥150 mg/dL and/or high-density lipoprotein cholesterol &amp;lt; 40 mg/dL; (2) systolic blood pressure≥130 mmHg and/or diastolic blood pressure ≥85 mmHg; and (3) fasting plasma glucose ≥110 mg/dL). Participants who had medication for each metabolic disorder were considered to meet each criterion. Results During the follow-up, 2150 subjects (25.9 per 1000 person-year) developed impaired kidney function. The incidence was more frequent in subjects with (39.3 per 1000 person-year) than without MetS (24.2 per 1000 person-year, p&amp;lt;0.001). Moreover, each component of MetS showed a significant impact on the incident impaired kidney function (obesity 23.0 vs. 31.2, lipid 23.3 vs. 34.2, blood pressure 19.9 vs. 35.9, glucose 24.8 vs. 35.2 per 1000 person-year) and the incidence was increased with increasing the number of metabolic disorders in individuals at baseline (0, 1, 2 and ≥3 factor(s); 17.3, 26.9, 32.9 and 39.7 per 1000 person-year, respectively). Non-adjusted hazard ratio (HR) (95% confidence interval [CI]) of MetS for the new onset of impaired kidney function was 1.619 (1.447-1.810). In multivariate Cox hazard analysis adjusted for sex, age, pulse rate, serum creatinine, uric acid, hemoglobin, current smoking and frequent alcohol consumption, MetS was an independent predictor of the development of impaired kidney function (HR=1.312, 95%CI [1.167-1.475]). Similar results were obtained in sub-analysis using subjects without any medications (n=11963) (data not shown). Conclusions Metabolic syndrome and its components are important predictors for the development of impaired kidney function in the general population. Prediction of the deterioration of kidney function may lead to effective prevention of chronic kidney disease and relating cardiovascular disease.

Abstract 12276: The Mediating Effects of Insomnia Symptom Severity on the Relationship Between Acculturation Stress and the Prevalence of Hypertension Among Latinx Adults

Introduction: Hypertension (HTN), a well-known risk factor for cardiovascular morbidity and mortality, affects about 44% of Latinxs in the US. Acculturation stress, a type of sociocultural stress, is associated with poor cardiovascular outcomes (i.e., HTN), in this population yet the mechanisms driving this association are understudied. Insomnia symptom severity(ISI) has been associated with increased acculturation stress and increased risk of HTN. So, ISI may drive the positive association between acculturation stress and HTN among Latinxs. We aim to examine the direct and indirect effects of acculturation stress on the prevalence of HTN via ISI among Latinxs. Hypothesis: We hypothesize that increased acculturation stress will be directly and indirectly associated with an increased prevalence of hypertension via increasing ISI. Methods: Using a sample of Latinx adults participating in the Hispanic Community Health Survey/Study of Latinos Baseline and Sueño Ancillary studies (n=1464), we conducted weighted unadjusted and adjusted bias corrected bootstrap tests of mediation. Acculturation stress was measured through the Hispanic Stress Index. ISI was measured through the Insomnia Severity Index. Hypertension was categorized as blood pressure &amp;gt130/80 or antihypertensive medication use. Adjustments for age, sex, nativity status, body mass index, and site were made. Results: Participants were M age=41.99 (SD=12.96). Most were women (53.76%), immigrants (65.44%), and of Mexican heritage (31.80%). Participants had a M ISI=7.38 (SD=6.49). About 39.01% were hypertensive. The total and direct effects of acculturation stress on the prevalence of HTN were statistically significant (PR=1.01, 95% CI: 1.00-1.02; PR=1.01, 95%CI: 1.00-1.02). ISI was a statistically significant mediator in the relationship between increased acculturation stress and increased prevalence of HTN in unadjusted models (Indirect effect=0.002, BCa 95% CI: 0.0002-0.004). Conclusions: Results suggest acculturation stress impacts HTN via increasing ISI among Latinxs. These findings should be replicated using longitudinal designs. If replicated, ISI may be an important target of intervention to mitigate the effects of acculturation stress on HTN among Latinxs.

Abstract 19133: Sodium Induced-RGMa Plays a Role 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 isoleuvoglandins 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. We found that TGFβ1R1 (8837 ± 780.9 vs. 9688 ± 942.5, p =0.350) and TGFβ1R2 (7012 ± 717.0 vs. 7176 ± 633.9, p = 0.059) were being similarly expressed between high or normal salt treatment. Interestingly, RGMa (2253 ± 441.0 vs. 516 ± 84.1, p &lt;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. To further investigate, 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. We found a positive correlation between the changes in pulse pressure and RGMa (r = 0.5154, p = 0.1911). Our data suggest that RGMa mediates Na + -induced inflammation and salt-sensitive hypertension which may reveal a novel therapeutic target.

Abstract 19164: The Role of Klf6 in Hypertensive Inflammation

Salt-sensitivity of blood pressure (SSBP) is a major risk factor for cardiovascular morbidity and mortality in people with or without hypertension. We previously found that oxidative lipid protein modification via NADPH oxidase in antigen presenting cells (APCs) contributes to SSBP but the underlying mechanisms are not known. HIF1α, which codes glycolytic enzymes in APCs enhances expression of Kruppel like factor 6 (KLF6), promoting expression of PDGFB which binds to the PDGFB receptor to activate NADPH oxidase, leading to increased oxidative stress and activation of mTOR. We hypothesize that HIF2α contributes to SSBP through activating NADPH oxidase by enhancing KLF6. To test this 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. We found that elevated sodium increases expression of HIFα (16437 ± 1810 vs. 42233 ± 6282, p = 2.28E-05) and KLF6 (9058 ± 584.3 vs. 12817 ± 1108, p = 0.6768). Interestingly, while the PDGFB receptor was upregulated by elevated sodium ( 21.18 ± 4.600 vs. 566.3 ± 205.3, p = 3.91E-13), the ligand PDGFB was downregulated (1249 ± 215.9 vs. 610.5 ± 118.2, p = 6.11E-04). In additional experiments, we performed single cell transcriptomic analysis in on immune cells of people phenotyped for SSBP. We found that in monocytes, as salt goes up with blood pressure so does the expression of KLF6 (r = 0.3773, p = 0.3561), PDGFB (r = 0.5604, p = 0.1485), and PDGFB receptor (r = 0.4436, p = 0.2709). Our data demonstrate the HIF1α-KLF6 pathway contributes to inflammation and SSBP.

The Antioxidative Effects of Flavones in Hypertensive Disease.

Hypertension is the leading remediable risk factor for cardiovascular morbidity and mortality in the United States. Excess dietary salt consumption, which is a catalyst of hypertension, initiates an inflammatory cascade via activation of antigen-presenting cells (APCs). This pro-inflammatory response is driven primarily by sodium ions (Na+) transporting into APCs by the epithelial sodium channel (ENaC) and subsequent NADPH oxidase activation, leading to high levels of oxidative stress. Oxidative stress, a well-known catalyst for hypertension-related illness development, disturbs redox homeostasis, which ultimately promotes lipid peroxidation, isolevuglandin production and an inflammatory response. Natural medicinal compounds derived from organic materials that are characterized by their anti-inflammatory, anti-oxidative, and anti-mutagenic properties have recently gained traction amongst the pharmacology community due to their therapeutic effects. Flavonoids, a natural phenolic compound, have these therapeutic benefits and can potentially serve as anti-hypertensives. Flavones are a type of flavonoid that have increased anti-inflammatory effects that may allow them to act as therapeutic agents for hypertension, including diosmetin, which is able to induce significant arterial vasodilation in several different animal models. This review will focus on the activity of flavones to illuminate potential preventative and potential therapeutic mechanisms against hypertension.

ASSOCIATION BETWEEN VITAMIN D LEVEL AND ESSENTIAL HYPERTENSION

Introduction: There is relationship between vitamin D deficiency and hypertension (HTN). The mechanism causing the development of HTN, the Renin Aldosterone Angiotensin System, was discovered to be strongly inhibited by vitamin D. This study was piloted to assess the role of vitamin D deficiency in the development of essential hypertension (EH). Methods: A total of 50 patients with EH and 50 healthy participants participated in this study. Every participant was subjected to clinical history, physical examination, and other necessary blood testing, electrocardiography, and echocardiography. Results: There was a significant decrease in vitamin D in hypertensive group (20.25±3.28 ng/mL) than normotensive group (38.33±6.89 ng/mL). Vitamin D level was moderately negative correlated with systolic blood pressure (BP) (r – 0.43, p – 0.001), strong negative correlation with diastolic BP (r – 0.76, p&lt;0.001), strong negative correlation with intimal thickness (r – 0.67, p&lt;0.001), and moderate negative correlation with ventricular mass (r – 0.48, p&lt;0.001). Intimal thickness and ventricular mass were significantly higher in patients with EH with low vitamin D than those with normal vitamin D levels. Conclusion: There is a strong inverse relationship between serum vitamin D and HTN. Vitamin D deficiency levels are considered an additional risk factor for cardiovascular morbidity and mortality.