Elevated Systolic Blood Pressure Research Articles

Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: a trend analysis study from 1990 to 2021

BackgroundSubarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021.MethodsData on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed.ResultsIn 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 − 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 − 11.95) and 285.62 (95% UI 209.42 − 379.65). The burden associated with SAH primarily affected individuals aged between 50 − 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework.ConclusionsThe burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.

MiPEP31 alleviates Ang II-induced hypertension in mice by occupying Cebpα binding sites in the pri-miR-31 promoter

BackgroundPrevious studies have shown that peptides encoded by noncoding RNAs (ncRNAs) can be used as peptide drugs to alleviate diseases. We found that microRNA-31 (miR-31) is involved in the regulation of hypertension and that the peptide miPEP31, which is encoded by the primary transcript of miR-31 (pri-miR-31), can inhibit miR-31 expression. However, the role and mechanism of miPEP31 in hypertension have not been elucidated.MethodsmiPEP31 expression was determined by western blot analysis. miPEP31-deficient mice (miPEP31−/−) were used, and synthetic miPEP31 was injected into Ang II-induced hypertensive mice. Blood pressure was monitored through the tail-cuff method. Histological staining was used to evaluate renal damage. Regulatory T (Treg) cells were assessed by flow cytometry. Differentially expressed genes were analysed through RNA sequencing. The transcription factors were predicted by JASPAR. Luciferase reporter and electrophoretic mobility shift assays (EMSAs) were used to determine the effect of pri-miR-31 on the promoter activity of miPEP31. Images were taken to track the entry of miPEP31 into the cell.ResultsmiPEP31 is endogenously expressed in target organs and cells related to hypertension. miPEP31 deficiency exacerbated but exogenous miPEP31 administration mitigated the Ang II-induced systolic blood pressure (SBP) elevation, renal impairment and Treg cell decreases in the kidney. Moreover, miPEP31 deletion increased the expression of genes related to Ang II-induced renal fibrosis. miPEP31 inhibited the transcription of miR-31 and promoted Treg differentiation by occupying the Cebpα binding site. The minimal functional domain of miPEP31 was identified and shown to regulate miR-31.ConclusionmiPEP31 was identified as a potential therapeutic peptide for treating hypertension by promoting Treg cell differentiation in vivo. Mechanistically, we found that miPEP31 acted as a transcriptional repressor to specifically inhibit miR-31 transcription by competitively occupying the Cebpα binding site in the pri-miR-31 promoter. Our study highlights the significant therapeutic effect of miPEP31 on hypertension and provides novel insight into the role and mechanism of miPEPs.

Sodium Bicarbonate Treatment and Clinical Outcomes in Chronic Kidney Disease with Metabolic Acidosis: A Meta-Analysis.

In patients with chronic kidney disease (CKD), impaired kidney acid excretion leads to the onset of metabolic acidosis (MA). However, the evidence is not yet conclusive regarding the effects of sodium bicarbonate in treating CKD with MA. Databases with PubMed, Embase, and the Cochrane Library were used to search for randomized controlled trials from the inception until November 11, 2023 to identify randomized controlled trials investigating the effect of sodium bicarbonate in participants with CKD and MA. The primary outcome was the change in estimated glomerular filtration rate (eGFR). Secondary outcomes included hospitalization rates, change in systolic blood pressure (SBP), all-cause mortality, and mid-arm muscle circumference (MAMC). A random-effects model was applied for analysis, and subgroup, sensitivity analyses were also performed. Fourteen RCTs comprising 2,037 patients demonstrated that sodium bicarbonate supplementation significantly improved eGFR (standardized mean difference [SMD]: 0.33, 95% CI: 0.03 to 0.63, P = 0.03). The group receiving sodium bicarbonate had a lower hospitalization rate (odds ratio: 0.37, 95% CI: 0.25 to 0.55, P < 0.001). Higher MAMC was observed with sodium bicarbonate treatment compared with those without (SMD:0.23, 95% CI: 0.08 to 0.38, P = 0.003, I2 < 0.001). However, higher risk of elevated SBP was found with sodium bicarbonate treatment (SMD:0.10, 95% CI: 0.01 to 0.20, P = 0.03). No significant difference in all-cause mortality was noted. In patients with CKD and MA, sodium bicarbonate supplementation may provide potential benefits in preventing the deterioration of kidney function and increasing muscle mass. However, treatment may be associated with higher blood pressure. Due to the risk of bias stemming from the absence of double-blinded designs and inconsistencies in control group definitions across the studies, further research is crucial to verify these findings.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Veno-Arterial Extracorporeal Membrane Oxygenation in the Rat.

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock.

Associations between PM 2.5 and its chemical constituents and blood pressure: a cross-sectional study.

To investigate the associations between PM 2.5 and its chemical constituents with blood pressure (BP), assess effects across BP quantiles, and identify the key constituent elevating BP. A total of 36 792 adults were included in the cross-sectional study, representing 25 districts/counties of southeast China. Quantile regression models were applied to estimate the associations of PM 2.5 and its chemical constituents (ammonium [NH 4+ ], nitrate [NO 3- ], sulfate [SO 42- ], black carbon [BC], organic matter [OM]) with systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean artery pressure (MAP). A weighted quantile sum (WQS) index was used to estimate the relative importance of each PM 2.5 chemical constituent to the joint effect on BP. The adverse effects of each interquartile range (IQR) increase in PM 2.5 , NH 4+ , NO 3- , SO 42- , and BC on BP were found to be greater with elevated BP, especially when SBP exceeded 133 mmHg and DBP exceeded 82 mmHg. Each IQR increase in all five PM 2.5 chemical constituents was associated with elevated SBP ( β [95% CI]: 0.90 [0.75, 1.05]), DBP ( β : 0.44 [0.34, 0.53]), and MAP ( β : 0.57 [0.45, 0.69]), NH 4+ (for SBP: weight = 99.43%; for DBP: 12.78%; for MAP: 60.73%) and BC (for DBP: 87.06%; for MAP: 39.07%) predominantly influencing these effects. The joint effect of PM 2.5 chemical constituents on risks for elevated SBP and DBP exhibited an upward trend from the 70 th quantile (SBP exceeded 133 mmHg, DBP exceeded 82 mmHg). Long-term exposure to PM 2.5 and its chemical constituents was associated with increased risk for elevated BP, with NH 4+ and BC being the main contributors, and such associations were significantly stronger at 70th to 90th quantiles (SBP exceeded 133 mmHg, DBP exceeded 82 mmHg).

Effect of the Blood Pressure and Antihypertensive Drugs on Cerebral Small Vessel Disease: A Mendelian Randomization Study.

Previous studies yielded conflicting results about the influence of blood pressure (BP) and antihypertensive treatment on cerebral small vessel disease. Here, we conducted a Mendelian randomization study to investigate the effect of BP and antihypertensive drugs on cerebral small vessel disease. We extracted single-nucleotide polymorphisms for systolic BP and diastolic BP from a genome-wide association study (N=757 601) and screened single-nucleotide polymorphisms associated with calcium channel blockers, thiazides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-blockers from public resources as instrumental variables. Then, we chose the genome-wide association study of white matter hyperintensity (WMH; N=18 381), cerebral microbleed (3556 cases, 22 306 controls), white matter perivascular space (9317 cases, 29 281 controls), basal ganglia perivascular space (BGPVS; 8950 cases, 29 953 controls), hippocampal perivascular space (HIPPVS; 9163 cases, 29 708 controls), and lacunar stroke (6030 cases, 248 929 controls) as outcome data sets. Subsequently, we conducted a 2-sample Mendelian randomization analysis. We found that elevated systolic BP significantly increases the risk of BGPVS (odds ratio [OR], 1.05 [95% CI, 1.04-1.07]; P=1.72×10-12), HIPPVS (OR, 1.04 [95% CI, 1.02-1.05]; P=2.71×10-7), and lacunar stroke (OR, 1.41 [95% CI, 1.30-1.54]; P=4.97×10-15). There was suggestive evidence indicating that elevated systolic BP is associated with higher WMH volume (β=0.061 [95% CI, 0.018-0.105]; P=5.58×10-3) and leads to an increased risk of cerebral microbleed (OR, 1.16 [95% CI, 1.04-1.29]; P=7.17×10-3). Elevated diastolic BP was significantly associated with higher WMH volume (β=0.087 [95% CI, 0.049-0.124]; P=5.23×10-6) and significantly increased the risk of BGPVS (OR, 1.05 [95% CI, 1.04-1.06]; P=1.20×10-16), HIPPVS (OR, 1.03 [95% CI, 1.02-1.04]; P=2.96×10-6), and lacunar stroke (OR, 1.31 [95% CI, 1.21-1.41]; P=2.67×10-12). The use of calcium channel blocker to lower BP was significantly associated with lower WMH volume (β=-0.287 [95% CI, -0.408 to -0.165]; P=4.05×10-6) and significantly reduced the risk of BGPVS (OR, 0.85 [95% CI, 0.81-0.89]; P=8.41×10-19) and HIPPVS (OR, 0.88 [95% CI, 0.85-0.92]; P=6.72×10-9). Our findings contribute to a better understanding of the pathogenesis of cerebral small vessel disease. Additionally, the utilization of calcium channel blockers to decrease BP can effectively reduce the likelihood of WMH, BGPVS, and HIPPVS. These findings offer valuable insights for the management and prevention of cerebral small vessel disease.

Independent Effects of Blood Pressure on Intraocular Pressure and Retinal Ganglion Cell Degeneration: A Mendelian Randomization Study.

To investigate the causal effect of elevated blood pressure on primary open-angle glaucoma (POAG) and POAG endophenotypes. Two-sample Mendelian randomization (MR) was performed to investigate the causal effect of elevated systolic blood pressure (SBP) (N = 757,601) and diastolic blood pressure (DBP) (N = 757,601) on intraocular pressure (IOP) (N = 139,555), macular retinal nerve fiber layer (mRNFL) thickness (N = 33,129), ganglion cell complex (GCC) thickness (N = 33,129), vertical cup-to-disc ratio (VCDR) (N = 111,724), and POAG liability (Ncases = 16,677, Ncontrols = 199,580). The primary analysis was conducted using the inverse-variance weighted approach. Sensitivity analyses were performed to investigate robustness to horizontal pleiotropy, winner's curse, and collider bias. Multivariable MR was performed to investigate whether any effect of blood pressure on retinal ganglion cell degeneration was mediated through increased IOP. Increased genetically predicted SBP and DBP associated with an increase in IOP (0.17 mm Hg [95% CI = 0.11 to 0.24] per 10 mm Hg higher SBP, P = 5.18 × 10-7, and 0.17 mm Hg [95% CI = 0.05 to 0.28 mm Hg] per 10 mm Hg higher DBP, P = 0.004). Increased genetically predicted SBP associated with a thinner GCC (0.04µm [95% CI = -0.07 to -0.01µm], P = 0.018) and a thinner mRNFL (0.04µm [95% CI = -0.07 to -0.01µm], P = 0.004), an effect that arises independently of IOP according to our mediation analysis. Neither SBP nor DBP associated with VCDR or POAG liability. These findings support a causal effect of elevated blood pressure on retinal ganglion cell degeneration that does not require intermediary changes in IOP. Targeted blood pressure control may help preserve vision by lowering IOP and, independently, by preventing retinal ganglion cell degeneration, including in individuals with a normal IOP.

Association between Systolic Blood Pressure Variability and Incident Aortic Stenosis.

Background: This study investigated the potential link between blood pressure variability (BPV) and the incidence of aortic stenosis (AS) using Korean National Health Insurance Service data from 2002 to 2019. Methods: We collected annual systolic blood pressure variability (SBPV) measurements consisting of three consecutive blood pressure readings each year over three years. The obtained SBPV data was divided into five quantiles, with the highest quintile representing a high fluctuation of blood pressure. Results: Analyzing 9,341,629 individuals with a mean age of 40.7 years, the study found 3981 new AS diagnoses during an average 8.66-year follow-up. Independent predictors for AS included higher blood pressure levels and elevated systolic blood pressure variability (SBPV). The hazard ratios (HR) for different SBPV quintiles compared to the reference (1st quintile) were as follows: 2nd quintile HR 1.09 (p = 0.18), 3rd quintile HR 1.13 (p = 0.04), 4th quintile HR 1.13 (p = 0.04), and 5th quintile HR 1.39 (p < 0.001). Conclusion: Our findings suggest that both hypertension and high fluctuations in SBP during consecutive visits are associated with an increased risk of incident AS. These results emphasize the importance of blood pressure management and stability in the prevention of AS.

Nutritional Practices, Quality of Life and, Health Status of Elderly in Rural Communities in Owo Local Government Area, Ondo State, Nigeria

The study investigates the nutrition practices, health status, and quality of life of elderly individuals in Owo, Ondo State, Nigeria. It involves a descriptive cross-sectional design with 346 elderly participants aged 60-90, systematically sampled from six rural communities. Data were collected via structured, interviewer-administered questionnaires on demographics, medical and lifestyle histories, daily activities, health-seeking behaviors, food consumption, and nutritional care practices. Nutritional status and high blood pressure were assessed using anthropometric indices and a digital sphygmomanometer. Key findings indicate that 37.6% of participants were aged 60-64. Significant differences were noted between sexes in socio-demographic variables. Alcohol consumption, tobacco sniffing, and cigarette smoking were reported by 15.3%, 11.0%, and 4.6% respectively. Additionally, 23.1% were on hypertensive drugs and 20.1% were confirmed diabetics. Meal frequency varied, with 16.5% eating less than three times daily and 59.2% eating three times daily. Lunch (58.0%) and breakfast (36.6%) were the most skipped meals, and 15% ate outside the home. Dietary diversity scores revealed 66.5% with medium and 27.5% with good diversity. Significant gender differences were observed in dietary diversity and consumption patterns of cereals, roots, tubers, and fruits. Nutritional care practices and daily living activities scores showed 90.2% and 80.6% with fair practices and good activity scores, respectively, while 46.2% demonstrated good health-seeking behavior. Common health complaints included body and joint pain. Central obesity rates were 33.8% (WC), 30.3% (WHtR), and 30.6% (WHR). Elevated systolic and diastolic blood pressure were found in 36.7% and 23% of participants, respectively. Only 31.2% reported a good quality of life. Significant positive correlations were found between nutritional status, quality of life, nutritional care practices, and functionality. Malnutrition, poor quality of life, and inadequate care practices among the elderly in rural areas highlight a public health challenge requiring targeted interventions.

Progression of diabetic retinopathy in women with pregestational diabetes during pregnancy and postpartum.

Diabetic retinopathy (DR) may worsen during pregnancy, but its course in the postpartum remains poorly understood. Understanding the natural history of DR during and after pregnancy can help determine when sight-threatening DR treatment should be administered. A prospective longitudinal cohort study recruited pregnant women with pre-existing type 1 (T1D) or type 2 diabetes from two tertiary Diabetes Antenatal Clinics in Melbourne, Australia. Eye examination results in early pregnancy, late pregnancy, and up to 12-months postpartum were compared to determine DR changes. Two-field fundus photographs and optical coherence tomography scans were used to assess DR severity. Overall, 105 (61.4%) women had at least two eye examinations during the observation period. Mean age was 33.5 years (range 19-51); 54 women (51.4%) had T1D; 63% had HbA1c <7% in early pregnancy. DR progression rate was 23.8% (95% CI 16.4-32.6). Having T1D (RR 4.96, 95% CI 1.83-13.46), pre-existing DR in either eye (RR 4.54, 95% CI 2.39-8.61), and elevated systolic blood pressure (adjusted RR 2.49, 95% CI 1.10-5.66) were associated with increased risk of progression. Sight-threatening progression was observed in 9.5% of women. Among the 19 eyes with progression during pregnancy, 15 eyes remained stable, three eyes progressed, and only one eye regressed in the postpartum. Nearly 1 in 4 women had DR progression from conception through to 12-months postpartum; almost half of these developing sight-threatening disease. DR progression occurring during pregnancy was found to predominantly remain unchanged, or worsen, after delivery, with very few eyes spontaneously improving postpartum.

Rho-kinase inhibition reduces systolic blood pressure and forearm vascular resistance in healthy older adults: a double-blind, randomized, placebo-controlled pilot study.

Rho-kinase has been implicated in the development of hypertension in preclinical studies and may contribute to age-related blood pressure elevation. This study tested the hypothesis that Rho-kinase contributes to elevated systolic blood pressure (SBP) in healthy older adults. Young (18-30 years, 6F/6M) and older (60-80 years, 7F/6M) adults were enrolled in a double-blind, placebo-controlled crossover study using intravenous fasudil infusion to inhibit Rho-kinase. Fasudil lowered SBP in older adults compared to placebo (saline) (2-h post-infusion: 125 ± 4 vs. 133 ± 4 mmHg, P < 0.05), whereas fasudil had no impact on SBP in young adults. Immediately following fasudil infusion, there was a transient reduction in mean arterial pressure (MAP) in young adults that was no longer evident 1-h post-infusion. In older adults, MAP remained lower throughout the fasudil visit compared to placebo (2-h post-infusion: 93 ± 3 vs. 100 ± 3 mmHg, P < 0.05) such that age-related differences in SBP and MAP were abolished. Aortic stiffness (carotid-femoral pulse wave velocity) was not altered by fasudil when central MAP was included as a covariate in analyses. Fasudil reduced forearm vascular resistance in older (2-h post-infusion: 3.3 ± 0.4 vs. 4.8 ± 0.6 mmHg/ml/min, P < 0.05) but not young (4.0 ± 0.6 vs. 3.8 ± 0.5 mmHg/ml/min) adults, which was accompanied by an increase in brachial artery diameter only in older adults. Brachial artery flow-mediated dilation was not affected by fasudil in either group. These findings indicate that Rho-kinase inhibition reduces SBP in healthy older but not young adults, which is associated with a concomitant reduction in forearm vascular resistance.

Particulate matter, polycyclic aromatic hydrocarbons and metals, platelet parameters and blood pressure alteration: Multi-pollutants study among population

Epidemiological findings have determined the linkage of fine particulate matter (PM2.5) and the morbidity of hypertension. However, the mode of action and specific contribution of PM2.5 component in the blood pressure elevation remain unclear. Platelets are critical for vascular homeostasis and thrombosis, which may be involved in the increase of blood pressure. Among 240 high-PM2.5 exposed, 318 low-PM2.5 exposed workers in a coking plant and 210 workers in the oxygen plant and cold-rolling mill enrolled in present study, both internal and external exposure characteristics were obtained, and we performed linear regression, adaptive elastic net regression, quantile g-computation and mediation analyses to analyze the relationship between urine metabolites of polycyclic aromatic hydrocarbons (PAHs) and metals fractions with platelets indices and blood pressure indicators. We found that PM2.5 exposure leads to increased systolic blood pressure (SBP) and pulse pressure (PP). Specifically, for every 10 μg/m3 increase in PM2.5, there was a 0.09 mmHg rise in PP. Additionally, one IQR increase in urinary 1-hydroxypyrene (1.06 μmol/mol creatinine) was associated with a 3.43 % elevation in PP. Similarly, an IQR increment of urine cobalt (2.31 μmol/mol creatinine) was associated with a separate 1.77 % and 4.71 % elevation of SBP and PP. Notably, platelet-to-lymphocyte ratio (PLR) played a mediating role in the elevation of SBP and PP induced by cobalt. Our multi-pollutants results showed that PAHs and cobalt were deleterious contributors to the elevated blood pressure. These findings deepen our understanding of the cardiovascular effects associated with PM2.5 constituents, highlighting the importance of increased vigilance in monitoring and controlling the harmful components in PM2.5.

Increase in blood pressure in patients with metastatic kidney cancer treated with combination checkpoint inhibitor and vascular endothelial growth factor receptor tyrosine kinase inhibitor therapy.

e24128 Background: The combination therapy of an immune checkpoint inhibitor (ICI) with a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) is considered a first line treatment option for patients with metastatic clear cell renal cell carcinoma (ccRCC). TKI-induced hypertension is a well-known potential side effect with VEGFR-TKIs however little is known about the real-world increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with and without underlying hypertension treated with this combination therapy. Methods: A retrospective study was performed that included patients with metastatic ccRCC who were treated at the University of Florida Health Cancer Center between June 2019 and September 2022 who received treatment with the combination of an ICI and VEGFR-TKI. The data collected included history of hypertension, patients use of anti-hypertensive therapy at baseline, SBP and DBP prior to initiation of therapy and at approximately one month after initiation of treatment. Results: We identified a total of 29 patients who met the inclusion criteria for our study. The median age was 68 years old (IQR 61-72) while 25 patients (86%) were male and 4 (14%) were females. There were 27 patients (93%) who were treated with axitinib with pembrolizumab, while 1 (3%) was treated with cabozantinib with nivolumab, and 1 (3%) was treated with lenvatinib with pembrolizumab. Out of the 29 patients, 11 (38%) did not have hypertension prior to therapy while 18 (62%) did have baseline hypertension and were receiving at least one anti-hypertensive treatment. In those patients without baseline hypertension, the median baseline SBP was 113 and the median SBP after one month of treatment was 144 (p = 0.01). Conversely, those patients with baseline hypertension, the median baseline SBP was 122 and median SBP after one month of treatment was 148 (p = 0.003). In those without hypertension at baseline, the mean SBP increase after one month was 27.3% while in those with baseline hypertension the mean increase in SBP of 17.0%. Conclusions: Our study demonstrates that in a real-world population of patients with metastatic ccRCC there is a statistically significant elevation of both SBP and DBP when treated with the combination of an ICI and VEGFR-TKI and that in those patients without baseline hypertension and not on anti-hypertensive therapy at baseline, there is a more pronounced increase in blood pressure. This data should reinforce the need to have close monitoring of SBP and DBP during therapy, regardless of whether the patient has underlying hypertension or not, and may help guide anti-hypertensive therapy during kidney cancer treatment.

Sex differences in clinical risk factors in obese ischemic stroke patients with a history of smoking

Clinical risk factors associated obesity and smoking, as well as their combined effect, are not fully understood. This study aims to determine sex differences in risk factors in a population of acute ischemic stroke (AIS) patients who are obese and with a history of previous or current smoking.MethodsA retrospective analysis of risk factors in male and female AIS patients with baseline data of obesity and current or previous history of smoking, smoking, and obesity alone was determined. The primary predictor and outcome are risk factors associated with male and female AIS patients. Baseline risk factors were analyzed using a multivariate regression analysis to determine specific risk factors linked with the combined effect of obesity and current or previous history of smoking’’.ResultsMale obese AIS patients who are current or previous smokers were more likely to be older patients(OR = 1.024, 95% CI, 1.022–1.047, P = 0.033) that present with coronary artery disease (OR = 1.806, 95% CI, 1.028–3.174, P = 0.040), a history of alcohol use (OR = 2.873, 95% CI, 1.349–6.166, P = 0.006), elevated serum creatinine (OR = 4.724, 95% CI, 2.171–10.281, P < 0.001) and systolic blood pressure (OR = 1.029, 95% CI, 1.011–1.047, P < 0.002). Females were more associated with depression (OR = 0.432, 95% CI, 0.244–0.764, P = 0.004), previous TIA (OR = 0.319, 95% CI, 0.142–0.714, P < 0.005), and higher levels of HDL (OR = 0.938, 95% CI, 0.915–0.962, P < 0.001).ConclusionOur results reveal sex differences in risk factors in obese AIS patients with a current or past history of smoking. This finding emphasizes the need to develop management strategies to improve the care of obese AIS patients who are either current or former smokers.

Isolated systolic hypertension in young adults and its relationship with ambulatory blood pressure measurements

Introduction: The definition of Isolated Systolic Hypertension (ISH) is accepted by guidelines, which adopt a blood pressure (BP) cutoff point of 140/90 mmHg, with elevated Systolic Blood Pressure (SBP) and normal diastolic blood pressure (DBP) in the clinic. This phenotype represents the most common form of Hypertension (HT) in young individuals. The prognosis of ISH differs according to various explanatory mechanisms. Some associations of this phenotype with Ambulatory Blood Pressure Monitoring (ABPM) have been described, but little emphasis has been placed on its association with nocturnal BP values. To the best of our knowledge, there is no epidemiological data on young patients establishing this relationship in Latin America. Objective: To describe the characteristics of ISH in our population of young patients and analyze its relationship with different ABPM phenotypes. Materials and methods: Consecutive adult individuals between 16 and 40 years of age, without antihypertensive treatment, were evaluated in a cross-sectional study. They were referred for ABPM to a tertiary hospital between July 2013 and August 2022. Each individual underwent an initial interview, three BP measurements using current standards with OMROM HEM 705 devices, and subsequent ABPM with Spacelabs 90207. A general description of the sample was provided, and an analysis was conducted based on different patient phenotypes determined by clinic BP measurements in relation to various ABPM phenotypes. Results: A total of 395 individuals (69% women, 29 ± 6.5 years) were finally evaluated. The frequencies according to clinic phenotypes were as follows: Normotensive = 77%, ISH = 6%, HT = 17%. Among the ISH group, 29.2% had white coat hypertension (WCH). The Kappa agreement was 31% for clinic phenotypes vs. ABPM. Among ISH patients, 37% had at least one elevated period (daytime or nighttime), and 12.5% had elevated BP only during the nighttime.

The Acute Coronary Syndrome Risk in Medically Managed Subjects with Type 2 Diabetes Mellitus - Is the ASCVD Risk Score Failing Here?

Type 2 Diabetics have elevated risk for acute coronary syndrome (ACS). The current management algorithm focuses on atherosclerotic cardiovascular (ASCVD) risk score to stratify this risk. However, in medically managed subjects, this algorithm may not be accurate. This study compares the ASCVD risk score in an Indian population with T2DM under medical supervision and the actual incidence of ACS. It also compared the ASCVD risk scores in cases with T2DM who developed ACS to controls and tried to estimate whether the ASCVD risk score is different in the two subsets, evaluating the utility of the ASCVD risk score in predicting ACS. This is an electronic medical record (EMR) based case-control study. Only records of subjects with T2DM where details of age, sex, body mass index, blood pressure, duration of diabetes, family history of ACS, lipid profile, renal and liver function tests were included. The incidence of ACS was calculated in the selected records, and the records of subjects with ACS were compared with age and sex-matched subjects without ACS. Data are summarized as median and interquartile range (IQR). Wilcoxon rank-sum test was used for checking differences in continuous variables and Pearson's Chi-squared test for categorical data. Univariate and multivariate logistic regression analyses were used to check the effect of ASCVD scores and other variables on the occurrence of ACS.Statistical data analyses were performed using JASP, version 0.16.4 (JASP Team [2022]) for MS Windows. Of the 1226 EMRs included in the analysis, 207 had ACS. The actual incidence of ACS was 16.85% in 6 years, higher than the mean predicted 10-year incidence of 14.56 percent (p <0.05). The cases were age and sex-matched with controls and the ASCVD incidence was estimated in the two groups. The mean ASCVD score in the cases was 14.565 ± 8.709 (Min: 1.5, Max: 38.3) and controls 13.114 ± 8.247 (Min: 1.4, Max: 45). The chance of development of ACS increases with elevated systolic blood pressure (per mmHg rise OR: 1.04, 95% CI: 1.03, 1.06; p <0.001), positive family history (OR: 5.70, 95% CI: 3.41, 9.77; p <0.001), statin use (OR: 2.26, 95% CI: 1.46, 3.52; p <0.001), and longer duration of diabetes (for every year increase OR: 1.19, 95% CI: 1.13, 1.25; p <0.001). The ASCVD risk score underestimates the ACS risk in subjects with T2DM under medical supervision and may not differ in those who developed and did not develop ACS. We also conclude that factors like a negative family history (30% less risk), longer duration of diabetes, and higher SBP are relevant in those who developed ACS.

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.

#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD

Abstract Background and Aims Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD. Method We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP &amp;lt; 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score &amp;gt;0; Uncontrolled BP, SBP &amp;gt;140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT. Results During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P &amp;lt; 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66). Conclusion Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.