Elevated Blood Pressure Research Articles

Exploring side effects of corticosteroids in myasthenia gravis: Unveiling alternatives for safer treatment

Myasthenia Gravis (MG) is a chronic organ-specific autoimmune disease that weakens voluntary muscles by affecting neuromuscular junctions. The formation of antibodies against acetylcholine receptors is the most prevalent cause. The incidence and prevalence rates of (MG) are increasing exponentially (1). In addition to symptomatic medication, corticosteroids continue to be the first-line treatment for MG due to their affordability, ease of access, and efficacy (2). Although corticosteroids are frequently prescribed, they are not without drawbacks. Long-term corticosteroid use can result in various side effects, including osteoporosis, weight gain, acne, elevated blood pressure, mood fluctuations, and a cushingoid appearance. It has also been linked to rare complications such as gastric and esophageal irritation, compressive fractures, and aseptic femoral head fracture (3). Given the hazards associated with long-term corticosteroid use in treating MG, researchers and healthcare professionals should investigate alternative MG treatments. By doing so, new and safer treatment options can be identified, which could contribute to improved treatment and substantially enhance the quality of life for MG-affected populations. Numerous nonsteroidal medications, including mycophenolate mofetil, methotrexate, and azathioprine, have demonstrated success in clinical trials for kidney transplantation, rheumatoid arthritis, and myasthenia gravis, respectively. To confirm the efficacy of these pharmaceuticals in the treatment of MG, urgent research and trials based on in vitro and animal models are required. Based on well-designed clinical trials, these also require human testing (4). The tapering of prednisone is an alternative option. Prednisone tapering is still a problem in the therapeutic management of patients with generalized MG because, although it is a useful treatment, it has a number of adverse effects that make it necessary to find the lowest possible effective dose as quickly as feasible. Rituximab and azathioprine enable quick tapering. It is necessary to evaluate and contrast the corticosteroid-sparing effect of novel treatments with that of azathioprine and rituximab. Given their impact on MG status, it's possible that these novel therapies will make it possible to drastically cut back on corticosteroids or possibly stop taking them entirely(5) The abnormal immune responses in MG can be managed and resolved with the new drugs that specifically target them. These agents include chimeric antigen receptor T [CART-T] cell therapy, autologous stem cell transplantation, B cell depleting agents (anti-CD 19 and 20, and B cell activating factor [BAFF] inhibitors), proteosome inhibitors, terminal complement C5 inhibitors, Fc receptor inhibitors, T cells, and cytokine-based therapies (subcutaneous immunoglobulin [SCIG]). ---Continue

RANKL, but Not R-Spondins, Is Involved in Vascular Smooth Muscle Cell Calcification through LGR4 Interaction.

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.

Exploring Acute Kidney Injury Following Aortic Dissection: A Comprehensive Review of Machine Learning Models for Predicting Risk, Management Strategies, Complications, and Racial and Gender Disparities.

Both types of aortic dissection (AD), Stanford type A and type B, can result in complications such as acute kidney injury (AKI) and aortic rupture. Renal complications in AD arise from compromised renal perfusion affecting the renal arteries. Understanding the intricate connection between AD and AKI is crucial for navigating the complexities of tailored treatment and formulating specific management plans. Concerning machine learning models, in patients with type A aortic dissection, factors such as decreased platelet count on admission, increased D-dimer level, longer cardiopulmonary bypass duration, elevated white blood cell levels, the need for blood transfusion, longer aortic clamp time, extended surgery duration, advanced age, and an elevated body mass index were positively associated with the development of AKI. For the risk of AKI after type B aortic dissection, elevated Nt-pro brain natriuretic peptide, prolonged activated partial thromboplastin time, elevated admission systolic blood pressure, and a higher contrast agent requirement during operative repair were found to predict the risk. Male gender was associated with a higher risk of AKI, and nonwhite race was linked to a higher risk of AKI, a greater likelihood of requiring more urgent procedures, and lower levels of insurance coverage. The treatment of AKI following AD requires a multifaceted approach. Identifying and addressing the underlying cause, such as low blood pressure, renal artery involvement, or medication-induced injury, is crucial for effective management and preventing further kidney damage. Maintaining proper fluid balance is essential for improving renal perfusion, but careful monitoring is necessary to avoid complications. The evolving landscape of research, particularly in biomarkers and AI programs, reveals a promising role in predicting the risk for and managing AKI post-AD.

Early vascular aging in acute ischemic stroke: A systematic review and meta-analysis

BackgroundWhile arterial stiffening is a known risk factor for cardiovascular diseases, it remains unclear whether there is an early vascular aging (EVA) in patients who have experienced acute ischemic stroke (AIS). This systematic review and meta-analysis aims to investigate whether patients with AIS exhibit EVA through pulse wave velocity (PWV) measurements shortly after the stroke onset, shedding light on the relationship between arterial stiffness, hypertension, and stroke. MethodsThirteen case-control studies were included, comparing PWV measurements between AIS patients and non-AIS individuals. A meta-analysis was performed to compare PWV levels, age, blood pressure, and the prevalence of different cardiovascular risk factors among 1711 AIS patients and 1551 controls. ResultsDespite AIS patients showing higher PWV compared to controls (mean difference: 1.72 m/s, 95 % CI: 1.05–2.38, p < 0.001; I2 = 88.3 %), their age did not significantly differ (95 % CI: −0.47–0.94, p = 0.519; I2 = 0 %), suggesting EVA in AIS patients. Moreover, AIS patients exhibited elevated systolic and diastolic blood pressure and had higher odds of smoking, hypertension, diabetes, and male gender compared to controls. ConclusionsThis study's findings underscore the presence of EVA in AIS patients, evident through increased PWV measurements shortly after stroke onset. Notably, smoking, hypertension, and diabetes mellitus emerge as substantial factors contributing to accelerated arterial stiffness within this population.

Assessing the impact of annual health screenings in identifying noncommunicable disease risk factors within Qatar’s primary health care corporation Qatari registered population

BackgroundNoncommunicable diseases (NCDs) are a significant global health burden, including in Qatar, where cardiovascular diseases cause mortality. This study examines the outcomes of the annual health checkup implemented by the Primary Health Care Corporation (PHCC) in Qatar in detecting NCDs risk factors among Qataris aged 18+ years.MethodsA cross-sectional study design was implemented to calculate the prevalence of behavioural and metabolic NCDs risk factors among Qataris who underwent annual health checkups between 2017 and 2019. Data on age, gender, tobacco consumption, height, weight, blood pressure, glycated haemoglobin (HbA1c), and cholesterol levels were extracted from electronic medical records.ResultsIn 2019, Qatar experienced an 80% rise in Annual Health checkups attendance compared to 2017. Tobacco use fluctuated between 11.79 and 12.91%, peaking at 35.67% among males in 2018. Qataris with elevated blood pressure dropped from 29.44% in 2017 to 18.52% in 2019. Obesity decreased from 48.32 to 42.29%, more prevalent in females. High HbA1c levels reduced from 13.33 to 8.52%, while pre-diabetic levels rose from 21.1 to 25.52%. High cholesterol ranged from 7.31 to 9.47%. In a regression analysis, males had 2.28 times higher odds of elevated blood pressure and 1.54 times higher odds of high HbA1c, with a 0.68 lower odds of obesity compared to females. Ages 36 and above had 2.61 times higher odds of high cholesterol compared to younger age groups.ConclusionThe annual health screening has shown promising results in detecting and addressing NCDs risk factors among Qataris. The attendance rate has increased over the three-year period, and there has been a decrease in the prevalence of elevated blood pressure, obesity, and high HbA1c levels. However, tobacco consumption and pre-diabetic levels remain significant concerns. These findings can guide the implementation of tailored preventative and curative services to improve the health and well-being of the Qatari population.

Metabolic syndrome and pharmacotherapy outcomes in patients with type 2 diabetes mellitus

BackgroundMetabolic syndrome is a group of metabolic abnormalities that increase predisposition to several diseases including ischemic heart disease and diabetes mellitus. The study aimed to investigate metabolic syndrome among patients with type-2 diabetes mellitus (DM), and its impact on pharmacotherapy outcomes.MethodsAn observational cross-sectional study was performed on 910 patients with type-2 DM between June and December 2023. Fasting blood sugar, triglycerides, high-density lipoproteins (HDL), blood pressure, and abdominal obesity were measured. Metabolic syndrome was identified according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Pharmacotherapy outcomes were assessed according to American Association of Clinical Endocrinologists and American Diabetes Association guidelines using the ability to achieve adequate glycemic control and normal levels of blood pressure and fasting plasma lipoproteins.ResultsIn total, 87.5% of type-2 DM patients had metabolic syndrome; the prevalence increased with age and was higher among females. Metabolic syndrome showed the following distribution of risk factors: insulin resistance (100%), low HDL (95.3%), elevated blood pressure (83%), triglycerides dyslipidemia (80.1%), and abdominal obesity (62.5%). Majority of the patients had either 5 or 4 risk factors of metabolic syndrome. The most common comorbidities were dyslipidemia (97.7%) and hypertension (83%). Treatment outcomes were insufficient where adequate glycemic control was only achieved in 12% of type-2 DM patients, and proper management of comorbid dyslipidemia and hypertension was achieved in 29% and 40.9% of patients, respectively. Adequate blood pressure control was less achieved in patients with metabolic syndrome (34.4%) than those without metabolic syndrome (77.2%). Similarly, dyslipidemia was less controlled in patients with metabolic syndrome (26.9%) than in those without metabolic syndrome (47.3%).ConclusionPharmacotherapy outcomes were inadequate for most patients with type-2 diabetes mellitus. Adopting early preventive and therapeutic interventions for metabolic syndrome is advised to improve treatment outcomes of the comorbid dyslipidemia and hypertension.

Demographic and Metabolic Risk Factors Associated with Development of Diabetic Macular Edema among Persons with Diabetes Mellitus

PurposeDiabetic macular edema (DME), a leading cause of visual impairment, can occur regardless of diabetic retinopathy (DR) stage. Poor metabolic control is hypothesized to contribute to DME development though large-scale studies have yet to identify such an association. This study aims to determine whether measurable markers of dysmetabolism associate with DME development in persons with diabetes. DesignRetrospective cohort study ParticipantsUsing data from the Sight Outcomes Research Collaborative (SOURCE) repository, patients with diabetes mellitus (DM) and no pre-existing DME were identified and followed over time to see what factors associated with DME development. MethodsCox proportional hazard modeling was used to assess the relationship between demographic variables, diabetes type, smoking history, baseline DR status, blood pressure (BP), lipid profile, body mass index (BMI), hemoglobin A1C (HbA1C) and new onset of DME. Main Outcome MeasuredAdjusted Hazard Ratio (HR) of developing DME with 95% confidence intervals. ResultsOf 47,509 eligible patients from 10 SOURCE sites (mean age 63±12 years, 58% female sex, 48% white race), 3633 (7.6%) developed DME in the study period. The mean±standard deviation time to DME was 875±684 days (∼2.4 years) with those with baseline NPDR (HR 3.67 95% [confidence interval (CI]):3.41-3.95) and PDR (HR 5.19 95% [CI]:4.61-5.85) more likely to develop DME. There was no difference in DME risk between type 1 and type 2 patients, however Black race was associated with a 40% increase in DME risk (HR 1.40 95% [CI]:1.30-1.51). Every one unit increase in HbA1C had a 15% increased risk of DME (HR 1.15 95% [CI]:1.13-1.17) and each 10 mmHg increase in systolic blood pressure associated with a 6% increased DME risk (HR 1.06 95% [CI]:1.02-1.09). No association was identified between DME development and BMI, triglyceride levels, or high-density lipoprotein levels. ConclusionsThese findings suggest that in patients with diabetes modifiable risk factors such as elevated HbA1C and blood pressure confer a higher risk for DME development, however other modifiable systemic markers of dysmetabolism such as obesity and dyslipidemia did not. Further work is needed to identify the underlying contributions of race in DME.

#730 Dialysis-induced changes in systolic, diastolic, and pulse pressure in maintenance hemodialysis patients

Abstract Background and Aims Hemodialysis (HD) therapy has a strong impact on cardiovascular function in both the short and long term. In the short term, the dialysis-induced changes in blood volume directly affect the arterial blood pressure (BP), frequently leading to intradialytic hypotension or hypertension, both associated with adverse outcomes. The aim of this study was to investigate the dialysis-induced changes in systolic (SBP), diastolic (DBP), and pulse pressure (PP) in maintenance HD patients and to assess their relationship with pre-HD BP. Methods 197 maintenance HD patients were studied during the middle dialysis session of the week. The mean pre-dialysis fluid overload was 2.0 ± 1.6 L (calculated as the difference between the pre-dialysis body weight and the target weight). All HD sessions lasted approximately 4 h and were performed using mainly low-flux dialyzers. SBP and DBP were measured pre-HD and post-HD using a sphygmomanometer. PP was calculated as SBP minus DBP. The patients were divided into two groups: A) patients with an intradialytic decline in SBP (∆SBP &amp;lt;0), and B) patients with an increase or no change in SBP during HD (∆SBP ≥0). Paired data were compared using the Student's t-test. Correlations between variables were assessed using Spearman's rho (ρ). Results During HD, SBP decreased in 120 (61%) patients (in 20 cases by more than 30 mmHg), remained unchanged in 11 (6%) patients, and increased in 66 (33%) patients (in 13 cases by more than 20 mmHg). DBP decreased in 94 (48%) patients, remained unchanged in 46 (23%) patients, and increased in 57 (29%) patients. In 76 (39%) patients both SBP and DBP decreased, whereas in 33 (17%) patients both SBP and DBP increased. In group A (n = 120), SBP, DBP, and PP decreased by 21 ± 16 mmHg (P &amp;lt; 0.001), 8 ± 11 mmHg (P &amp;lt; 0.001), and 13 ± 14 mm Hg (P &amp;lt; 0.001), respectively. In group B (n = 77), SBP, DBP, and PP increased by 12 ± 10 mmHg (P &amp;lt; 0.001), 4 ± 11 mmHg (P &amp;lt; 0.001), and 8 ± 13 mmHg (P &amp;lt; 0.001), respectively. Pre-HD SBP was 144 ± 23 mmHg in group A and 128 ± 25 mmHg in group B (P &amp;lt; 0.001). Pre-HD DBP was 80 ± 15 mmHg in group A and 68 ± 11 mmHg in group B (P &amp;lt; 0.001). In all patients combined, ∆SBP was similarly correlated with pre-HD SBP and pre-HD DBP (ρ = −0.42 in both cases, P &amp;lt; 0.001), whereas ∆DBP was more strongly correlated with pre-HD DBP (ρ = −0.52, P &amp;lt; 0.001) than with pre-HD SBP (ρ = −0.22, P &amp;lt; 0.01). ∆SBP was correlated with ∆DBP (ρ = 0.55, P &amp;lt; 0.001) and highly correlated with ∆PP (ρ = 0.78, P &amp;lt; 0.001). According to linear regression, SBP tended to increase during HD in patients with pre-HD SBP &amp;lt;118 mmHg (Fig. 1A), whereas DBP tended to increase in patients with pre-HD DBP &amp;lt;68 mmHg (Fig. 1B). Conclusions Patients with dialysis-induced decline in SBP (group A) had a significantly higher pre-HD BP (both SBP and DBP) compared with patients with an increasing or stable SBP (group B). This suggests that a high decline in SBP during HD appears to be more likely in patients with elevated pre-HD BP and that HD appears to have a pressure-normalizing effect in such patients. Similarly, a dialysis-induced increase in SBP or DBP appears to be more likely in patients with low values of pre-HD SBP or DBP, respectively.

#1713 Blood pressure goals in kidney transplant recipients: an analysis of the collaborative transplant study

Abstract Background and Aims Hypertension is an independent risk factor for cardiovascular disease, the leading cause of death in kidney transplant recipients. Because there is no “one size fits all” approach to blood pressure targets, particularly in the heterogenous group of kidney transplant recipients, identification of subgroup-specific targets, considering factors like age and sex, may be appropriate. However, currently available studies are limited because of sample sizes, and no subgroup analyses have been performed examining the effects of different blood pressure targets on allograft and patient survival. The aim of our study was to investigate the impact of different ACC/AHA blood pressure categories on graft survival and patient mortality and to identify subgroup-specific targets. Method This large-scale retrospective study included 1-year blood pressure data from 62, 556 kidney transplant recipients reported to the Collaborative Transplant Study from 209 centers in 39 countries. Hypertension was categorized according to 2017 ACC/AHA guidelines. The primary outcomes were death-censored graft failure and patient mortality during post-transplant year 1 to 6. Multivariable Cox regression analysis was performed to control for immunologic and nonimmunologic confounders. Results One year after transplantation, 77% of kidney transplant recipients had hypertension. Hypertension stages 1 (130–139/80–89 mmHg), 2a (140–159/90–99 mmHg), and 2b (≥160/≥100 mmHg) were associated with an 8%, 34%, and 102% increased risk of death-censored graft failure, respectively, whereas elevated blood pressure levels (120–129/&amp;lt;80 mmHg) did not significantly increase the risk. Patient mortality was only significantly higher in those with hypertension stage 2b with a Hazard Ratio of 1.21 (95% CI, 1.08–1.36; P &amp;lt; .001). In addition, the impact of hypertension stages on death-censored graft failure varied in different subpopulations (Fig. 1). Female recipients, younger recipients, recipients who received kidneys from donors younger than 60 years, re-transplanted recipients, and recipients with pre-transplant HLA antibodies had a significantly increased risk of death-censored graft failure associated with higher blood pressure levels (Fig. 1). Kidney transplant recipients with hypertension stage 2 continued to have an increased risk of graft failure one year after transplantation, even when they achieved normal blood pressure in the second year. Conclusion This study highlights the importance of treating hypertension early after kidney transplantation to improve long-term graft and patient survival. Attention should be paid to female, younger, and sensitized recipients, who may particularly benefit from optimal blood pressure control.

#3092 Case report: Renal cystic disease caused to heterozygous NEK8 variant in pediatric patient

Abstract Background and Aims Polycystic kidney diseases (PKDs) are the most prevalent inherited kidney disease [1]. They are caused by pathogenic variants in genes encoding for proteins with roles in the functioning of primary cilium, a sensory organelle at the cell surface of almost all cells regulating key signaling pathways. Therefore, they are also classified as Ciliopathy and can occur with isolated renal involvement with/without systemic manifestations. As 1 of the family of “Never in Mitosis A–related kinases” (NEK), NEK8 is a regulator of Hippo pathway that controls cell growth, regulate the renal tubule epithelial cell cytoskeletal structure, and is involved in ciliary biogenesis/function. Biallelic NEK8 mutations are reported as causing a syndromic ciliopathy with multiorgan developmental defects, referred to as renal-hepatic-pancreatic dysplasia [1]. A recent paper [1] analyzed a total of 21 patients from 12 families with heterozygous NEK8 variants and cystic kidney disease and proposed a dominant negative effect for specific heterozygous variants in the NEK8 kinase domain as a new cause of PKD. Method We describe a case report of PKD associated with NEK8 heterozygous mutation. Results 8 years old female patient accessed to Emergency Department with first evidence of isolated macro-hematuria. Previous medical history was unremarkable. The girl was afebrile, in good clinical condition, with elevated blood pressure values (120/82 mmHg) at the physical examination. The laboratory tests showed normal blood count with hemoglobin 11.7 g/dl, serum creatinine 0.42 mg/dl, no inflammatory markers. Urinalysis revealed proteinuria (100 mg/dL), hemoglobinuria, active urinary sediment with microhematuria (3557 red blood cell/microliter) and leukocyturia (535 white blood cells/microliter). An abdominal ultrasound study observed kidneys of increased size (longitudinal diameter of approximately 14 cm) with presence of multiple cystic formations with a maximum diameter of 2 cm and lost cortico-medullary differentiation; other organs were normal. Ultrasound findings were confirmed with MRI. The macrohematuria resolved quickly, however we recorded the persistence of positive urinary sediment. No other concomitant clinical manifestations were recorded and the cardiological evaluation was normal. Suspecting a cystic renal disease, we proposed a genetic analysis by whole exome sequencing (WES): an heterozygous NEK8 variant (c.133C&amp;gt;T, p. Arg45Trp) was found. Due to persistent proteinuria and hypertension we suggested to initiate RAAS inhibitor treatment. Conclusion The patient's clinical history and onset of disease agree with the data described in the literature for the NEK8 variant c.133C&amp;gt;T, p. Arg45Trp. In literature all patients had an early onset of PKD. Enlarged kidney were present in 79%, followed by hypertension in 67% of cases; no patients had liver involvement, as in our patient. Kidney failure occurred before adulthood in non-mosaic case. The absence of a phenotype with systemic involvement, doesn't exclude the possible subsequent appearance of extra-renal manifestations. Therefore, it is necessary to set up a multidisciplinary follow-up, including cardiological evaluation and radiological study of brain structure. An early nephroprotective therapy and behavioral strategy must be established to prevent disease progression. Thus, it is suggested to include NEK8 in the genetic analysis when PKD is suspected.

#2961 Association of polygenic risk scores for blood pressure with incidence of hypertension and chronic kidney disease

Abstract Background and Aims Genetic risk for elevated blood pressure (BP) has been associated with a higher risk of hypertension and cardiovascular disease. However, the generalizability of previous findings has been limited due to a lack of studies among Asian populations. This study aimed to investigate whether genetic risk for BP predicts the incidence of hypertension and chronic kidney disease (CKD) in Asian populations. Method We performed genome-wide association studies for systolic and diastolic BP (SBP and DBP, respectively) using data from the Korean Genome and Epidemiology Study (KoGES). We then meta-analyzed these results with summary statistics from Biobank Japan to construct polygenic risk scores (PRSs) and examined the association between BP PRSs and incident hypertension or CKD. This study included participants without hypertension, cardiovascular disease, or CKD at baseline (n=4349, median age 48.5 years, 48.8% men). Participants were categorized into four groups based on their PRS percentile (&amp;lt;5, 5–50, 50–95, &amp;gt;95). Results As the PRS percentile increases, the median SBP and DBP at baseline also increase. Compared to the lowest SBP PRS percentile, higher PRS percentile was associated with increased risk of hypertension (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.22–1.83 for PRS percentile 5–50, HR 1.94, 95% CI 1.58–2.38 for PRS percentile 50–95, and HR 2.35, 95% CI 1.80–3.07 for PRS percentile &amp;gt;95). Elevated DBP PRS was also associated with higher risk of hypertension (HR 1.27, 95% CI 1.04–1.54 for PRS percentile 5–50, HR 1.72, 95% CI 1.41–2.09 for PRS percentile 50-95, and HR 2.09, 95% CI 1.60–2.72 for PRS percentile &amp;gt;95). The highest PRS percentile for SBP and DBP was associated with earlier onsets of hypertension by median 11 and 9 years, respectively, compared to the lowest PRS percentile for SBP and DBP. However, both SBP and DBP RPSs were not associated with incident CKD. Conclusion Genetic risk for elevated BP was associated with a higher risk of incident hypertension and earlier onset of hypertension in the Asian population. However, there was no association between PRS for elevated BP and the incidence of CKD.

Association between nut consumption and metabolic syndrome in Korean adults: results from the Korean Genome and Epidemiology Study–Health Examinees

BackgroundThe epidemiological evidence regarding nut consumption and metabolic diseases focuses on Western populations. Nut consumption among Koreans is relatively low, and the prevalence of metabolic syndrome is rapidly increasing, highlighting the need for more focused studies in this population. This cross-sectional study aimed to investigate the relationship between nut consumption and metabolic syndrome in Korean adults.MethodsA total of 112,501 adults (39,481 men and 73,020 women) aged 40–79 years were selected from baseline data of the Korean Genome and Epidemiology Study–Health Examinees. Nut consumption was assessed using a validated semi-quantitative food frequency questionnaire and categorized as non-consumers, &amp;lt;1 serving/week, ≥1 to &amp;lt;2 servings/week, or ≥2 servings/week (15 g per serving). Metabolic syndrome and its components were defined according to the Korean Society of CardioMetabolic Syndrome criteria. Associations between nut consumption and metabolic syndrome and its components were examined using multiple logistic regression with adjustments for potential confounders.ResultsIn the study population, the prevalence of metabolic syndrome was 21.4% (26.9% in men and 18.4% in women), and the mean nut intake was 0.8 serving/week (0.7 serving/week in men and 0.8 serving/week in women). After adjusting for confounders, higher nut consumption was associated with a lower odds ratio (OR) of metabolic syndrome in individuals consuming ≥2 servings/week compared with non-consumers [OR = 0.85, 95% confidence interval (CI) = 0.80–0.91, p for trend &amp;lt;0.001]. Specifically, in men, this level of consumption was associated with a 14% reduction in the OR of metabolic syndrome (OR = 0.86, 95% CI = 0.77–0.95, p for trend = 0.028). In women, a similar reduction of 14% was observed (OR = 0.86, 95% CI = 0.80–0.93, p for trend &amp;lt;0.001). Among the metabolic syndrome components, nut consumption was inversely associated with abdominal obesity, low high-density lipoprotein-cholesterol, and elevated triglycerides in men and women, whereas no associations were observed for elevated blood pressure or elevated fasting blood glucose.ConclusionOur findings suggest that higher nut consumption is inversely associated with metabolic syndrome and its components in Korean adults. Further studies are needed to examine the longitudinal association between nut consumption and metabolic diseases in this population.

Immunological insights into hypertension: unraveling triggers and potential therapeutic avenues.

Hypertension remains the leading cause of morbidity and mortality worldwide. Despite its prevalence, the development of novel antihypertensive therapies has only recently accelerated, with novel agents not yet commercialized, leaving a substantial proportion of individuals resistant to existing treatments. The intricate pathophysiology of hypertension is now understood to involve chronic low-grade inflammation, which places the immune system in the spotlight as a potential target for new therapeutics. This review explores the factors that initiate and sustain an immune response in hypertension, offering insights into potential targets for new treatments. Several factors contribute to immune activation in hypertension, including diet and damage-associated molecular pattern (DAMP) generation. Diets rich in fat or sodium can promote inflammation by inducing intestinal barrier dysfunction and triggering salt-sensitive receptors in T cells and dendritic cells. DAMPs, such as extracellular adenosine triphosphate and heat-shock protein 70, are released during episodes of increased blood pressure, contributing to immune cell activation and inflammation. Unconventional innate-like γδ T cells contribute to initiating and maintaining an immune response through their potential involvement in antigen presentation and regulating cytokine-mediated responses. Immunologic memory, sustained through the formation of effector memory T cells after exposure to hypertensive insults, likely contributes to maintaining an immune response in hypertension. When exposed to hypertensive insults, these memory cells are rapidly activated and contribute to elevated blood pressure and end-organ damage. Evidence from human hypertension, although limited, supports the relevance of distinct immune pathways in hypertension, and highlights the potential of targeted immune interventions in human hypertension. Diet and acute bouts of high blood pressure result in the release of dietary triggers, neoantigens, and damage-associated molecular patterns (DAMPs), which promote immune system activation. Elements such as lipopolysaccharides (LPS), sodium, heat-shock protein (HSP)70, extracellular adenosine triphosphate (eATP), and growth arrest-specific 6 (GAS6) promote activation of innate immune cells such as dendritic cells (DCs) and monocytes (Mo) through their respective receptors (toll-like receptor [TLR]4, amiloride-sensitive epithelial sodium channel [ENaC], TLR2/4, P2X7 receptor [P2RX7], and Axl) leading to costimulatory molecule expression and interleukin (IL)-1β and IL-23 production. The neoantigens HSP70 and isolevuglandins (IsoLGs) are presented to T cells by DCs and possibly γδ T cells, triggering T cell activation, IL-17 and interferon (IFN)-γ production, and the formation of T effector memory (TEM) cells in the kidney, perivascular adipose tissue, bone marrow, and spleen. Exposure of TEM cells to their cognate antigen or previous activating stimuli causes these cells rapid expansion and activation. Cumulatively, this inflammatory state contributes to hypertension and end-organ damage. The figure was created using images from smart.servier.com and is licensed under a Creative Commons Attribution 4.0 license (CC BY 4.0).

Nimbidiol protects from renal injury by alleviating redox imbalance in diabetic mice.

Chronic hyperglycemia-induced oxidative stress plays a crucial role in the development of diabetic nephropathy (DN). Moreover, adverse extracellular matrix (ECM) accumulation elevates renal resistive index leading to progressive worsening of the pathology in DN. Nimbidiol is an alpha-glucosidase inhibitor, isolated from the medicinal plant, 'neem' (Azadirachta indica) and reported as a promising anti-diabetic compound. Previously, a myriad of studies demonstrated an anti-oxidative property of a broad-spectrum neem-extracts in various diseases including diabetes. Our recent study has shown that Nimbidiol protects diabetic mice from fibrotic renal dysfunction in part by mitigating adverse ECM accumulation. However, the precise mechanism remains poorly understood. The present study aimed to investigate whether Nimbidiol ameliorates renal injury by reducing oxidative stress in type-1 diabetes. To test the hypothesis, wild-type (C57BL/6J) and diabetic Akita (C57BL/6-Ins2Akita/J) mice aged 10-14weeks were used to treat with saline or Nimbidiol (400μgkg-1 day-1) for 8weeks. Diabetic mice showed elevated blood pressure, increased renal resistive index, and decreased renal vasculature compared to wild-type control. In diabetic kidney, reactive oxygen species and the expression levels of 4HNE, p22phox, Nox4, and ROMO1 were increased while GSH: GSSG, and the expression levels of SOD-1, SOD-2, and catalase were decreased. Further, eNOS, ACE2, Sirt1 and IL-10 were found to be downregulated while iNOS and IL-17 were upregulated in diabetic kidney. The changes were accompanied by elevated expression of the renal injury markers viz., lipocalin-2 and KIM-1 in diabetic kidney. Moreover, an upregulation of p-NF-κB and a downregulation of IkBα were observed in diabetic kidney compared to the control. Nimbidiol ameliorated these pathological changes in diabetic mice. Altogether, the data of our study suggest that oxidative stress largely contributes to the diabetic renal injury, and Nimbidiol mitigates redox imbalance and thereby protects kidney in part by inhibiting NF-κB signaling pathway in type-1 diabetes.

Correlation between vitamin D levels and blood pressure in elderly hypertensive patients with osteoporosis.

The association between vitamin D and blood pressure in elderly patients with hypertension complicated by osteoporosis remains unclear. The objective of this study is to explore whether vitamin D deficiency contributes to elevated blood pressure in elderly individuals with both hypertension and osteoporosis. This study represents a single-center retrospective observational investigation carried out at the Zhongshan Hospital Affiliated to Xiamen University. Ambulatory blood pressure, bone density, vitamin D levels, and additional laboratory parameters were collected upon admission. The association between vitamin D and ambulatory blood pressure outcomes was assessed using Spearman correlation tests and partial correlation analyses. The relationship between vitamin D and changes in blood pressure was analyzed through Generalized Additive Models, and threshold analysis was conducted to explore potential thresholds. 139 patients with newly diagnosed osteoporosis were consecutively included (mean age 73 years, 84.9% female). There is a negative correlation between 25-(OH) D3 and 24 h mean systolic blood pressure (mSBP), diurnal mSBP, nocturnal mSBP, maximum SBP, respectively. The results of the generalized additive model analysis show that there is a nonlinear relationship between 25-(OH) D3 and 24 h mSBP, diurnal mSBP, nocturnal mSBP, respectively. After determining the critical point of 25-(OH) D3 as 42 nmol/L, a segmented linear regression model was used to calculate the effect size and 95% confidence interval on both sides of the critical point. When 25-(OH) D3 is ≤42 nmol/L, it significantly negatively correlates with 24 h, diurnal, and nocturnal mean SBP. Conversely, when 25-(OH) D3 exceeds 42 nmol/L, there is no statistically significant association with 24 h, diurnal, or nocturnal mSBP. There was a significant negative correlation between vitamin D levels and blood pressure levels in elderly patients with hypertension and osteoporosis.

Racial differences in baroreflex function: Implications for the cardiovascular conundrum

Study objectiveAfrican Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. DesignParticipants completed a 5-minute baseline period where resting cardiac metrics were assessed. SettingLaboratory. Participants130 college-aged individuals (54 women, 57 AAs). Main outcome measuresBaroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. Results and conclusionsResults showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

Impact of Sacubitril/ Valsartan on quality of life and ejection fraction of heart failure patients with and without chronic kidney disease.

Chronic kidney disease (CKD) patients are at high risk of heart failure (HF) and both share similar risk factors, including diabetes and elevated blood Pressure (B.P). Aim of this study was to determine the impact of sacubitril/valsartan on the quality of life (QOL) and ejection fraction (EF) of patients with HF with and without CKD. Single center (Doctors Hospital Lahore), observational study with longitudinal follow up, on 104 HF patients from July 2019 to July 2020. HF was diagnosed on both clinical and echo parameters. New York Heart Association Class II-IV, EF less than or equal to 40% HF with reduced EF and stage three CKD patients were included. Sacubitril/Valsartan was prescribed at a starting daily dose of 50mg and then up titrated to 400mg. Patients were followed up with clinical evaluation, QOL assessment, echocardiography and biochemical profile at one, four, eight and 12 months. Gender, age, and diabetes mellitus between CKD and non-CKD patients were noted to be statistically different, defined as p<0.05. CKD patients' QOL increased from 45.15 to 57.57 from baseline to 12 months (p-value<0.01). Non-CKD patients' QOL increased from 48.07 to 56.25. In CKD patients, EF increased from 27.87% to 29.29% from baseline to 12 months (p-value 0.03) whereas in non-CKD patients EF improved from 29.42% to 31.43%. Sacubitril/ valsartan improves QOL in patients of HF with reduced EF both with and without CKD. Clinical improvement was independent of Left Ventricular EF as measured by QOL. Thus, QOL is a useful tool to assess the drug's beneficial effect.

Effect of Intraoperative Blood Pressure Regulation on Postoperative Hemorrhage After Bariatric Surgery

IntroductionWith a rising number of bariatric procedures, the absolute number of postoperative complications is increasing, too. Postoperative bleeding, particularly along the staple line, is a recognized challenge. Numerous strategies including reinforcement of the staple line (SLR) have been proposed to improve bleeding rates, but no single technique has shown superiority over the others. In our bariatric center, we have implemented intraoperative blood pressure regulation alone, without SLR, to reduce hemorrhagic complications postoperatively.MethodsThis retrospective observational analysis compares the incidence of postoperative bleeding in two groups of consecutive patients (total n = 438 patients), one with and one without intraoperative blood pressure elevation to 150 mmHg systolic without the additional use of staple line reinforcement. This intervention was integrated into our standard bariatric surgical procedure, no randomization or matching was conducted. Significant postoperative bleeding was defined as drop of hemoglobin of more than 2.5 mg/dl in 48 h and one of the following symptoms: lactate ≥ 2 mmol/L, bloody drainage, quantity of drainage more than 200 ml and/or radiological signs.ResultsDefined postoperative bleeding occurred in 33 (7.5%) patients. We observed a decrease in bleeding rates from 10% to 5% (n = 22 vs. n = 11) after introducing intraoperative blood pressure increase (p = 0.034). The rate of revisional surgery for bleeding also decreased from 2.7% to 0.5% (n = 6 vs. n = 1). In multivariate analysis, the intervention with blood pressure elevation showed a significant decrease on bleeding rates (p = 0.038).ConclusionThe use of increased intraoperative blood pressure alone, without staple line reinforcement, appears to be an effective and suitable method for reducing post-bariatric hemorrhagic complications.Graphical

Determining the optimal diagnostic and risk stratification approaches for people with hypertension in two rural populations in Kenya and The Gambia: a study protocol for IHCoR-Africa Work Package 2.

Sub-Saharan Africa (SSA) has one of the highest prevalences of hypertension worldwide. The impact of hypertension is of particular concern in rural SSA, where access to clinics and hospitals is limited. Improvements in the management of people with hypertension in rural SSA could be achieved by sharing diagnosis and care tasks between the clinic and the community. To develop such a community-centred programme we need optimal approaches to identify and risk stratify patients with elevated blood pressure. The aim of the study is to improve the evidence base for diagnosis and risk estimation for a community-centred hypertension programme in two rural settings in SSA. We will conduct a cross-sectional study of 1250 adult participants in Kilifi, Kenya and Kiang West, The Gambia. The study has five objectives which will determine the: (1) accuracy of three blood pressure (BP) measurement methods performed by community health workers in identifying people with hypertension in rural SSA, compared to the reference standard method; (2) relationship between systolic BP and cardiovascular risk factors; (3) prevalence of hypertension-mediated organ damage (HMOD); (4) accuracy of innovative point-of-care (POC) technologies to identify patients with HMOD; and (5) cost-effectiveness of different combinations of BP and HMOD measurements for directing hypertension treatment initiation. This study will determine the accuracy of three methods for community BP measurement and POC technologies for HMOD assessment. Using the optimal methods in this setting it will estimate the prevalence of hypertension and provide the best estimate to date of HMOD prevalence in SSA populations. The cost-effectiveness of decision-making approaches for initiating treatment of hypertension will be modelled. These results will inform the development of a community-centred programme to improve care for hypertensive patients living in rural SSA. Existing community engagement networks will be used to disseminated within the research setting.

Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with βFLI→SBP = 0.081, P < 0.001 versus βSBP→FLI = 0.020, P = 0.031; βFLI→DBP = 0.082, P < 0.001 versus βDBP→FLI = -0.006, P = 0.480 for CEMC, and βFLI→SBP = 0.057, P < 0.001 versus βSBP→FLI = -0.001, P = 0.727; βFLI→DBP = 0.061, P < 0.001, versus βDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.