Increased Blood Pressure Levels Research Articles

#1682 Myocardial remodeling in Wistar rats with renal dysfunction treated with a high-salt ration

Abstract Background and Aims High food intake of NaCl is the traditional factor of increase in blood pressure (BP) and cardiovascular risks also hurts kidneys. The purpose of the paper is to evaluate the morphological changes in the myocardium of normotensive Wistar rats with an early stage of renal dysfunction treated with a diet with increased concentration of salt for a long time. Method 30 Wistar rats (age 2.5-3 months) were studied and divided into three groups of 10 each. In the first, control, sham-operated (SO) rats, receiving standard diet (0.34% NaCl), in the second, rats subjected to resection of ¾ of the kidney parenchyma, receiving a standard diet (NE group), in the third, rats subjected to ¾ NE and those receiving a high-sodium diet (4% NaCl, high-salt diet, HSD). The feeds differed only in the %NaCl content. The ¾ NE model was created in two stages with an interval of 7 days. 20 mg/kg Zoletil 100 and 0.05 ml of Xylazine were used as anesthesia. At the first stage, the poles of the left kidney (1/2 part of the kidney) were removed, at the second stage, the right kidney was completely removed. The duration of the experiment was 4 months. At the end of the experiment, systolic BP at the tail was measured in awake rats using the cuff method (ELEMA electromanometer, Sweden). After removal from the experiment, blood was collected from the rats for biochemical analysis, and the LVMI was calculated as the ratio of LV mass to the body weight of the animal (mg/g). Myocardial fragments were placed in formalin, and sections 1.5–2 µm thick were prepared from paraffin blocks. The preparations were stained with Hematoxylin and Eosin and Masson's trichrome and used for histological analysis. The statistical significance of intergroup differences was determined using the Mann–Whitney test and Student's t test. Results During the observation period, BP in the SO group of animals did not change: initially - 120 [120;125] mm Hg, after 4 months - 120 [120;125] mmHg, p = 0.527. In the group with NE on a standard diet, an increase in BP was noted - from 120 [120; 125] mmHg up to 135.0 [132.5;137.5] mmHg, p = 0.011. In the group with NE + HSD, the increase in BP levels was more pronounced - up to 140[140;148] mmHg, (p = 0.001, relative to the SO group). The serum urea level in the SO group was 4.7 [4.5;5.4] mmol/l, creatinine −32.5 [29.0;36.0] µmol/l, in the NE group - 10.0 [9.1;10.9] mmol/l, (p = 0.0001, relative to the SO group) and 69.0[64.0;74.0] µmol/l, (p = 0.0001), in the NE+ HSD group – 10.7 [9.8;11.0] mmol/l, (p = 0.0001) and 64.5[46.3;69.5] µmol/l, (p = 0.001), respectively. Thus, the groups of rats with early-stage kidney dysfunction, although they had higher levels of urea and creatinine in the blood serum relative to the SO group, did not differ significantly from each other in these indicators. LVMI increased in rats with NE on a standard diet (LR −2.07±0.05 mg/g, NE −2.14 ± 0.06 mg/g, p = 0.1591). Consumption of a high-salt diet aggravated the growth of myocardial mass in rats with NE (NE + HSD - 2.41 ± 0.14 mg/g, p = 0.0084 and p = 0.0372, respectively). At the histological level, the increase in LV myocardial mass in rats with NE was characterized by hypertrophy of cardiomyocytes and the formation of interstitial fibrosis. The changes were more pronounced in the group with NE + HSD. The diameter of cardiomyocytes in rats of the SO group was 12.9 ± 0.4 µm, in animals with NE on standard diet - 14.5 ± 0.6 µm, in rats with NE + HSD - 15.5 ± 1.6 µm (p<0 .01 and p < 0.02, relative to the SO group). The area of interstitial fibrosis also increased in rats with NE (10.5 ± 2.6%, in the SO group - 0.6 ± 0.2%, p = 0.0000) and was slightly higher in the NE + HSD group (13.6 ± 2.8%, p = 0.0000, relative to the SO group). In rats with NE, both on a standard diet and with HSD, at this stage of the formation of kidney pathology, the thickness of the nutrimyocardial arteries did not differ significantly from the SO indicator rats. Conclusion Long-term salt intake with increased salt addition in Wistar rats in the initial stages of renal dysfunction does not affect the level of urea and creatinine in the blood serum, but promotes an increase in BP and myocardial remodeling, constantly progressing in the progression of cardiomyocyte hypertrophy and interstitial fibrosis.

Hypertension as predictive factor for bevacizumab-containing first-line therapy in metastatic breast and colorectal cancer in BRECOL (GEICAM/2011-04) study.

Retrospective data suggest an association between bevacizumab efficacy and the incidence of arterial hypertension (AHT). Additionally, epigenetic mechanisms have been related to AHT. This prospective observational study conducted by GEICAM Spanish Breast Cancer Research Group included metastatic breast (MBC) or colorectal (mCRC) cancer patients treated with bevacizumab-containing chemotherapy as first-line treatment. Blood pressure (BP) levels were measured (conventional and 24-h Holter monitoring) at baseline and up to cycle 3. Primary endpoint assessed BP levels increase as predictive factor for progression-free survival (PFS). Germline DNA methylation profile was explored in pre-treatment blood samples; principal component analysis was used to define an epigenetic predictive score for increased BP levels. From Oct-2012 to Jul-2016, 143 (78 MBC and 65 mCRC) patients were included. The incidence of AHT according to guidelines was neither predictive of PFS nor of best overall tumor response (BOR). No statistically significant association was observed with systolic BP nor diastolic BP increment for PFS or BOR. Grade 3 and 4 adverse events were observed in 37 and 5% of patients, respectively. We identified 27 sites which baseline methylation status was significantly associated to BP levels increase secondary to bevacizumab-containing chemotherapy. Neither the frequency of AHT nor the increase of BP levels were predictive of efficacy in MBC and mCRC patients treated with bevacizumab-containing chemotherapy. ClinicalTrials.gov Identifier: NCT01733628.

Pulmonary hypertension and insulin resistance: a mechanistic overview.

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease, characterized by increased blood pressure levels in pulmonary circulation, leading to a restriction in the circulation flow and heart failure. Although the emergence of new PAH therapies has increased survival rates, this disease still has a high mortality and patients that receive diagnosis die within a few years. The pathogenesis of PAH involves multiple pathways, with a complex interaction of local and distant cytokines, hormones, growth factors, and transcription factors, leading to an inflammation that changes the vascular anatomy in PAH patients. These abnormalities involve more than just the lungs, but also other organs, and between these affected organs there are different metabolic dysfunctions implied. Recently, several publications demonstrated in PAH patients a disturbance in glucose metabolism, demonstrated by higher levels of glucose, insulin, and lipids in those patients. It is possible that a common molecular mechanism can have a significant role in this connection. In this regard, this narrative review intends to focus on the recent papers that mainly discuss the molecular determinants between insulin resistance (IR) associated PAH, which included obesity subclinical inflammation induced IR, PPAR gamma and Adiponectin, BMPR2, mitochondrial dysfunction and endoplasmic reticulum stress. Therefore, the following review will summarize some of the existing data for IR associated PAH, focusing on the better understanding of PAH molecular mechanisms, for the development of new translational therapies.

Arterial stiffness, blood pressure progression and penile vascular disease in males with erectile dysfunction: a closer look at microcirculatory damage

Abstract Background Elevated aortic stiffness may be associated with microvascular remodelling and damage, which may be an important causal contributor to incident cardiovascular disease. Recent evidence supports the independent of age and blood pressure (BP) level predictive value of severe penile arterial insufficiency for adverse cardiovascular events. Purpose Aim of the study is to examine in men with erectile dysfunction the association of increased aortic stiffness with penile vascular damage by taking into account BP level. Methods We measured carotid-femoral pulse wave velocity (PWV) and assessed microvascular (penile vascular damage) changes in four age-matched groups without a history of diabetes and cardiovascular disease; Normal BP (n=137), high-normal BP (n=94), stage I hypertension (n=82) and stage II and III hypertension (n=76). Microvascular damage was examined by measuring penile peak systolic velocity (PSV) with a dynamic penile color Doppler ultrasonography after intracavernous injection of prostaglandin E1. Lower PSV values indicate severe penile vascular disease. Results Carotid-femoral PWV increased and PSV decreased across BP groups (all P<0.001). In regression analysis increased systolic BP (b= -0.185, P<0.01) and PWV (b= -0.170, P<0.05) are significant determinants of low penile PSV after controlling for age, body mass index, cholesterol and smoking. We dichotomized carotid-femoral PWV taking into account the mean value in the whole study population. Figure shows the differences in PSV across the BP groups considering the cut-off PWV value of 8.5m/s (high vs low PWV). Individuals with higher PWV had lower penile PSV in normal BP (P<0.01) and in high normal BP group (P=0.02) after adjusting for age and systolic BP. On the contrary, hypertensive patients already have significant structural damage in the penile arteries and high PWV does not further reduce penile blood flow. Interestingly, figure shows the comparable PSV measurements between individuals with high-normal BP level who had high PWV and patients in stage 1 hypertension group denoting significantly impaired microvascular damage in males with high-normal BP and increased aortic stiffness. The high normal BP group has significantly lower PSV compared to normal BP group independently of PWV value. Conclusion Increased aortic stiffness may promote penile microvascular remodelling and damage in men without increased BP level. Additionally, in men with high-normal BP higher arterial stiffness is associated with comparable penile microvascular damage of men with arterial hypertension. Because aortic stiffening may be preventable, further clinical research on earlier preventive measures that focus on aortic stiffness and microvascular remodelling within individuals with erectile dysfunction who have normal BP is warranted.Aortic stiffness, BP level and PSV

Abstract 15056: The Activation of Angiotensin II Type1a Receptors in the SFO and PVN is Necessary to Prime Immunity in Salt Sensitive Hypertension

Introduction: Salt sensitive hypertension (HTN) is associated with increased salt intake and elevated activity of the renin-angiotensin system (RAS) in the brain. We have found that DOCA-salt HTN partly depends on a sympathetic-mediated PlGF release in the spleen. Hypothesis: Whether this effect is related to the contribution of RAS signaling in brain nuclei mediating HTN responses is poorly known. We hypothesized that angiotensin type 1a receptors (AT1aR) within the circumventricular organs (CVOs) could mediate DOCA-salt hypertensive responses. Methods: To discriminate between CVOs, we used 3 mouse model with deletion of AT1aR in 3 in brain CVOs. AT1aRfloxed mice were 1) stereotaxically injected with an adenovirus encoding a Cre-recombinase (or GFP as control), directly in the subfornical organ (SFO), or 2) crossed with Sim1Cre+ (and Sim1Cre- as control) mice to delete the gene in the paraventricular nucleus of hypothalamus (PVN) or 3) crossed with Phox2bCre+ (and Phox2bCre- as control) mice to delete the gene in the dorsal motor nucleus of the vagus nerve (DMV). T Results: We implanted mice with pellets of DOCA or placebo, as control, and salt in drinking water for 3 weeks finding that: AT1aRfloxed mice + Virus encoding Cre Recombinase in the SFO and AT1aRfloxed;Sim1Cre+ mice were protected form HTN-DOCA-salt (SFO-SBP mmHg :133±1 vs 106±0,6, ***p>0,0001; PVN-SBP mmHg :144±2 vs 112±2,***p>0,0001 respectively to their controls); whereas AT1aRfloxed;Phox2bCre+ mice had increased blood pressure levels (SBP mmHg :144±1 vs 144±0,7, respectively to control mice). Additionally, deletion of AT1aR in the SFO and PVN attenuated egression of T cells from the spleen and infiltration on target organ with a reduced disruption of renal glomeruli and reduced accumulation of matrix protein in response to DOCA-salt (SFO-Bowman’s size μm 2 1761±150 vs 821±78, respectively, **p<0,001; PVN-Bowman’s size μm 2 3927±212 vs 2805±252, respectively, **p<0,001). Mice KO for AT1aR in the DMV were not protected from organ damage (Bowman’s size μm 2 776 ± 104 vs 1090 ± 94, respectively). Conclusions: ogether, these data indicate that SFO and PVN contribute to blood pressure in the DOCA-salt model of hypertension through AT1aR signaling, while the DMV role was independent from AT1aR.

Non-linear relationship between sleep duration and blood pressure in children with short stature.

Evidence regarding the relationship between sleep duration and blood pressure is controversial. Therefore, the aim of this study was to investigate the relationship between sleep duration and blood pressure in children with short stature. A total of 1,085 participants with short stature were enrolled from the Affiliated Hospital of Jining Medical University in China. The variables involved in this study included sleep duration, anthropometric indicators and biochemical parameters. Sleep duration was evaluated in a face-to-face interview. The average age of the 1,085 selected participants was 10.2 ± 3.5 years old, and approximately 763 (70.32%) of them were male. The results of adjusted linear regression showed that sleep duration was negatively associated with systolic blood pressure z scores (SBP-Z) and diastolic blood pressure z scores (DBP-Z) after adjusting for confounders (β -0.07, 95% CI -0.13, -0.01 P = 0.038; β -0.05, 95% CI -0.10, -0.01 P = 0.035, respectively). A nonlinear relationship was detected between sleep duration and blood pressure, including SBP-Z, DBP-Z and mean arterial pressure z scores (MAP-Z). The inflection point of the nonlinear relationship between sleep duration and SBP-Z is 10 h, and the inflection point of DBP-Z and MAP-Z is 8 h. This study revealed a nonlinear relationship between sleep duration and blood pressure in children with short stature. The findings suggest that the optimal sleep duration in children with short stature was 8-10 h, and sleep durations either too short or too long were associated with increased blood pressure levels.

Unique Gene Expression Signature in Periadrenal Adipose Tissue Identifies a High Blood Pressure Group in Patients With Cushing Syndrome.

Cushing syndrome (CS) is a rare disease caused by excess cortisol levels with high cardiovascular morbidity and mortality. Hypertension in CS promotes hypercortisolism-associated cardiovascular events. Adipose tissue is a highly plastic tissue with most cell types strongly affected by the excess cortisol exposure. We hypothesized that the molecular and cellular changes of periadrenal adipose tissue in response to cortisol excess impact systemic blood pressure levels in patients with CS. We investigated gene expression signatures in periadrenal adipose tissue from patients with adrenal CS collected during adrenal surgery. During active CS we observed a downregulation of gene programs associated with inflammation in periadrenal adipose tissue. In addition, we observed a clustering of the patients based on tissue gene expression profiles into 2 groups that differed in blood pressure levels (CS low blood pressure and CS high blood pressure). The 2 clusters showed significant differences in gene expression pattens of the renin-angiotensin-aldosterone-system. Renin was the strongest regulated gene compared with control patients and its expression correlated with increased blood pressure observed in our patients with CS. In the CS high blood pressure group, systemic renin plasma levels were suppressed indicative of an abnormal blood pressure associated with periadrenal adipose tissue renin-angiotensin-aldosterone-system activation. Here, we show for the first time a relevant association of the local renin-angiotensin-aldosterone-system and systemic blood pressure levels in patients with CS. Patients from the CS high blood pressure group still had increased blood pressure levels after 6 months in remission, highlighting the importance of local tissue effects on long-term systemic effects observed in CS.

Obesity and hypertension in children and adolescents: a narrative review

One of the major public health problems today is overweight. Obesity is already known to be an important risk factor for several chronic noncommunicable diseases, which are allocated among endocrine-metabolic diseases, cardiovascular diseases, and neoplasms¹. The World Health Organization released in its World Obesity Report 2022 a projection in which it estimates that by 2030 the world will go through an obesity epidemic and Brazil will have 7.7 million obese children, and it also estimates that about 23% of children aged 5 to 9 years and 18% of adolescents aged 10 to 19 years will be affected by this disease. Regarding cardiovascular diseases, arterial hypertension also constitutes one of the most important risk factors that induce these conditions. Currently, with the mandatory measurement of BP starting at three years of age or even earlier in the presence of risk factors for children, there is an increase in blood pressure levels in the pediatric age group, raising a warning sign for global health, since it can be a marker of the onset of target organ damage. Overweight is a significant predictor of high BP in this population, besides obesity being a known important risk factor for the acquisition of cardiovascular diseases.

Correlation Between Body Fat Composition and Blood Pressure Level Among Medical Students in a Tertiary Care Teaching Hospital In Pokhara, Nepal

IntroductionIncrease in body fat is a common finding in young adults due to sedentary lifestyle and unhealthy dietary habits predisposing an individual to increase in blood pressure which is a common cause of cardiovascular morbidity and mortality. This study aimed to determine the association between body fat composition and BP level in young adults.MethodsA cross sectional study was conducted among 350 students of Manipal College of Medical Sciences from January to June, 2020. A structured proforma was used to collect the required information about the subjects and measurement of height, weight, waist and hip circumference, BP was done following standard methods. Body fat percentage was assessed by skinfold thickness.ResultsThe prevalence of were overweight and obesity was found to be 35.14%. Systolic, diastolic and combined hypertension was found in 64.7%, 53.26% and 57.64% respectively, in overweight and obese population. Increase in body fat percentage in boys and increase in waist hip ratio in girls showed no correlation with increase in systolic, diastolic and mean arterial pressure. However, increase in BMI was strongly correlated (p<0.05) with increase in all the measures of blood pressure- systolic, diastolic and mean arterial pressure.ConclusionsBody mass index is a better predictor of increased blood pressure level than body fat percentage and waist hip ratio.

PM2.5 and its respiratory tract depositions on blood pressure, anxiety, depression and health risk assessment: A mechanistic study based on urinary metabolome

Effects of fine particulate matter (PM2.5) and regional respiratory tract depositions on blood pressure (BP), anxiety, depression, health risk and the underlying mechanisms need further investigations. A repeated-measures panel investigation among 40 healthy young adults in Hefei, China was performed to explore the acute impacts of PM2.5 exposure and its deposition doses in 3 regions of respiratory tract over diverse lag times on BP, anxiety, depression, health risk, and the potential mechanisms. We collected PM2.5 concentrations, its deposition doses, BP, the Self-Rating Anxiety Scale (SAS) score and the Self-Rating Depression Scale (SDS) score. An untargeted metabolomics approach was used to detect significant urine metabolites, and the health risk assessment model was used to evaluate the non-carcinogenic risks associated with PM2.5. We applied linear mixed-effects models to assess the relationships of PM2.5 with the aforementioned health indicators We further evaluate the non-carcinogenic risks associated with PM2.5. We found deposited PM2.5 dose in the head accounted for a large proportion. PM2.5 and its three depositions exposures at a specific lag day was significantly related to increased BP levels and higher SAS and SDS scores. Metabolomics analysis showed significant alterations in urinary metabolites (i.e., glucoses, lipids and amino acids) after PM2.5 exposure, simultaneously accompanied by activation of the cAMP signaling pathway. Health risk assessment presented that the risk values for the residents in Hefei were greater than the lower limits of non-cancer risk guidelines. This real-world investigation suggested that acute PM2.5 and its depositions exposures may increase health risks by elevating BP, inducing anxiety and depression, and altering urinary metabolomic profile via activating the cAMP signaling pathway. And the further health risk assessment indicated that there are potential non-carcinogenic risks of PM2.5 via the inhalation route in this area.

Trajectory of blood pressure levels and weight gain in pregnant women: A group-based approach

Background and objectivesMorbidities associated with increased blood pressure levels during pregnancy represent one of the main causes of maternal mortality. The objective was to identify patterns of systolic blood pressure (SPB) trajectory in pregnant women undergoing prenatal care at the Unified Health System, and associations with weight gain trajectory, demographic, obstetric, anthropometric data, and health related behaviors. Methods and resultsCohort study with pregnant women using the public health services in Brazil. Data were collected through questionnaires and medical records. Trajectory patterns of SBP and weight gain were identified by a group-based trajectory model. For trajectory analysis, 460 women had SBP information available, totaling 2839 measurements, with an average of 6.2 measurements during pregnancy. Three SBP trajectory patterns were identified and classified as “Group 1” (48.0%), with a mean of 103 mmHg (95% CI 102.5–103.7 mmHg), “Group 2” (42.7%) with a mean of 114 mmHg (95% CI 113.7–114.9 mmHg), and “Group 3” (9.1%) with the highest mean SBP value of 130 mmHg (95% CI 128.8–131.5 mmHg). It was observed that regardless of the weight gain trajectory group, women classified in the group with the highest SBP had the highest SBP levels. The probability of being classified in Group 3 was higher among women with higher education, who started pregnancy presenting obesity, and who were using antihypertensive drugs. ConclusionThe probability of belonging to groups with a greater trajectory of SBP during pregnancy was associated with obesity, education, and hypertension under treatment.

Inflammatory and endothelial dysfunction markers in females with metabolic syndrome aged 50–75 years

Introduction: The prevalence of metabolic syndrome (MetS) in Indonesia is 39% and it is higher in females than in males (46% vs. 28%). Features of this syndrome comprise low-grade chronic inflammation and endothelial dysfunction from cardiometabolic abnormalities. High-sensitive C-reactive protein (HsCRP) is a biomarker of cardiovascular disease, whereas ferritin and pentraxin-3 (PTX-3) are markers of chronic inflammation. One of the markers of endothelial dysfunction is an intercellular cell adhesion molecule-1 (ICAM-1). Studies on MetS in women aged 50–70 years and using several markers of inflammation and endothelial dysfunction are rare. The study aimed to determine differences in HsCRP, ferritin, PTX-3, and ICAM-1 level between females with and without MetS aged 50–75 years. Methods: For this cross-sectional study, 160 females aged 50–75 years from South Jakarta were recruited, divided into MetS and non-MetS (control) groups, 80 participants each. Participants that met the inclusion criteria were assessed for vital signs and metabolic parameters (e.g., lipid profile, fasting blood glucose level, and waist circumference [WC]). The groups were compared using an independent t-test for inflammatory (i.e., HsCRP, PTX-3, and ferritin) and endothelial dysfunction (ICAM-1) (p < 0.05) biomarkers. Results: The mean age of the MetS and control groups was 59.6 ± 5.6 and 59.2 ± 5.5 years. MetS criteria included WC of ≥80 cm (95.2%), increased blood pressure level (90.6%); and high-density lipoprotein cholesterol of <50 mg/dL (76.2%). Significant differences were found between the MetS and control groups for ferritin (p = 0.027), PTX-3 (p = 0.045), and ICAM-1 (p = 0.004) but not for HsCRP (p = 0.136). Conclusion: Elevated ferritin, PTX-3 level, and ICAM-1 level are significantly associated with an increased Mets risk in females aged 50–75 years; however, the same is not true for HsCRP.

Increased respiratory modulation of cardiovascular control reflects improved blood pressure regulation in pregnancy.

Hypertensive pregnancy disorders put the maternal-fetal dyad at risk and are one of the leading causes of morbidity and mortality during pregnancy. Multiple efforts have been made to understand the physiological mechanisms behind changes in blood pressure. Still, to date, no study has focused on analyzing the dynamics of the interactions between the systems involved in blood pressure control. In this work, we aim to address this question by evaluating the phase coherence between different signals using wavelet phase coherence. Electrocardiogram, continuous blood pressure, electrocardiogram-derived respiration, and muscle sympathetic nerve activity signals were obtained from ten normotensive pregnant women, ten normotensive non-pregnant women, and ten pregnant women with preeclampsia during rest and cold pressor test. At rest, normotensive pregnant women showed higher phase coherence in the high-frequency band (0.15-0.4Hz) between muscle sympathetic nerve activity and the RR interval, blood pressure, and respiration compared to non-pregnant normotensive women. Although normotensive pregnant women showed no phase coherence differences with respect to hypertensive pregnant women at rest, higher phase coherence between the same pairs of variables was found during the cold pressor test. These results suggest that, in addition to the increased sympathetic tone of normotensive pregnant women widely described in the existing literature, there is an increase in cardiac parasympathetic modulation and respiratory-driven modulation of muscle sympathetic nerve activity and blood pressure that could compensate sympathetic increase and make blood pressure control more efficient to maintain it in normal ranges. Moreover, blunted modulation could prevent its buffer effect and produce an increase in blood pressure levels, as observed in the hypertensive women in this study. This initial exploration of cardiorespiratory coupling in pregnancy opens the opportunity to follow up on more in-depth analyses and determine causal influences.

Abstract 56: DNA Methylation of Birthweight-Blood Pressure Genes and Changes of Blood Pressures in Response to Weight-Loss Diets

Introduction: DNA methylation (DNAm) may play a critical role in bridging prenatal adverse events and cardiometabolic disorders including hypertension in later life. Hypothesis: DNAm levels of genes related to both birthweight and blood pressure were associated with changes in blood pressures in response to dietary weight-loss interventions. Methods: We included 672 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss dietary intervention study. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm levels as the average methylation level within 500 bp of LINC00319 (cg01820192), ATP2B1 (cg00508575), and LMNA (cg12593793). Generalized linear regression models were used to assess the association between the regional DNAm and 2-year blood pressure changes. Trajectory analysis was used to identify subgroups that shared a similar underlying trajectory of 2-year blood pressure changes. Results: We found that the regional DNAm at LINC00319, but not the other genes, showed different associations with 2-year changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) among participants assigned low- or high-fat diets (P for interaction < 0.05 for all, Figure ). In response to low-fat diet, per standard deviation higher regional DNAm at LINC00319 was associated with greater reductions in both 2-year changes in SBP (β: -1.481; standard error [SE]: 0.632; P = 0.020) and DBP (β: -1.096; SE: 0.413; P = 0.009). Three trajectories of changes in SBP and DBP were identified, and participants with higher baseline regional DNAm at LINC00319 were less likely to have stable or increased blood pressure levels. Conclusions: Our findings indicate that higher regional DNAm level at LINC00319 was significantly associated with greater long-term reduction in blood pressure in response to a low-fat diet, suggesting people with higher regional DNAm levels benefited more from eating a low-fat weight-loss diet.

S-07-6: NEUTROPHIL EXTRACELLULAR TRAPS AS MEDIATORS OF ENDOTHELIAL DAMAGE IN HYPERTENSION AND DIABETES

Objective: Endothelial dysfunction (ED) plays a key role in the pathogenesis of hypertension and diabetes, yet its molecular determinants are poorly understood. Concomitant hypertension and diabetes can synergistically increase damage to the vasculature, with increasing evidence suggesting that resulting immune dysregulation may contribute to endothelial injury. Neutrophil extracellular traps (NETs), networks of chromatin and protein-containing extracellular fibers released to fight infection, are generated from neutrophils following activation of the citrullinating enzyme peptidylarginine deiminase 4 (PAD4). PAD4 has been shown to be upregulated in atherosclerosis, vasculitis, and various inflammatory autoimmune diseases, leading to NET-induced endothelial injury. Whether NETs could contribute to hypertension- and diabetes-induced ED has not been established. The objective of the present study is to investigate the impact of hypertension and diabetes on PAD4 activity and the contribution of NETs to resulting vascular injury. Design and Methods: Promyelocytic HL-60 cells were differentiated to neutrophil-like cells and treated with angiotensin II (10−7 M) and/or high glucose (25 mM) for 24 hours, with or without subsequent NET-inducing PMA stimulation (500 nM). NETs were isolated from the culture medium by differential centrifugation and assessed by Western blot analysis of citrullinated histone H3 (citH3, a primary NET component). Isolated NETs were used to treat Human Umbilical Vein Endothelial Cells (HUVECs) at 0.5–500 ng/ml for 24 hours, after which cell viability (XTT cell assay) and proliferation (BrdU assay) were measured. We also assessed NETosis in mice expressing human renin in the liver (TTRhRen) intercrossed with OVE26 diabetic mice [i.e. hypertensive-diabetic, HD mice], compared with wild-type (WT) FVBN/J mice. We examined kidney levels of citH3, neutrophil elastase (NE), and PAD4 expression by immunohistochemistry. Results: Treatment with high glucose, but not angiotensin II, increased citH3 levels in neutrophil-like cells. NETs isolated from PMA-stimulated cells decreased HUVEC viability by ∼2-fold at 5 ng/ml (P = < 0.0001), and dose dependently decreased proliferation from 0.5–500 ng/ml, with a ∼80% decrease at 500 ng/ml. In HD mice, we observed a significant increase in kidney levels of citH3 (P < 0.0001), NE (P < 0.0001), and PAD4 (P < 0.0001), which was associated with the presence of albuminuria and increased blood pressure levels. Conclusion: These results suggest that NETs are upregulated in hypertension and diabetes and may contribute to endothelial damage and microvascular injury.

Referral Pathway for Hypertension with High Cardiovascular Risk: A Review

Hypertension is considered as a common and powerful contributor to all the major cardiovascular diseases (CVDs), including coronary disease, stroke, peripheral artery disease, renal disease, and heart failure. Results from the Framingham study indicated that high blood pressure (BP), even within what is regarded as the non-hypertensive range, imposes an increased risk of CVD. The median BP at which cardiovascular sequelae appeared in the Framingham study was 130/80 mmHg. Epidemiological data have shown that the risk of CVD rises with increasing BP levels, starting at ≥115/75 mmHg in a strong, independent, graded, and continuous manner. Early and aggressive BP lowering is mandatory as it can contribute to long-term CV risk reduction. According to the Framingham study data, 31% of strokes occur in patients with normal or high normal hypertension. Clinical trial data suggest that antihypertensive therapies, particularly those that block the renin-angiotensin-aldosterone system (RAAS), can reduce CVD risks at least partly independently of BP lowering, although a major controversy involves this question. An optimal strategy to reduce CV risk may include lifestyle modifications, promoting adherence to early and aggressive target level achievement, appropriate drug choice, and especially global risk reduction.

S-05-4: ENVIRONMENTAL POLLUTANTS AND BLOOD PRESSURE

Pollution via air, land and water was estimated to cause over nine million deaths globally in 2019. The vast majority of these deaths and associated economic losses occur in LMICs. It is estimated that almost seven million of these annual deaths are due to air pollution, which is increasing, due to an increase in outdoor sources whilst there has been a global decrease in household air pollution since 2000. Of deaths caused by air pollution, it is estimated that approximately half are caused by cardiovascular disease (CVD) with about one third due to coronary heart disease and one fifth due to stroke. One of the mechanisms whereby air pollution impacts adversely on CVD health is via raised blood pressure (BP). Lead pollution which is thought to cause almost one million deaths per year globally is also linked to increased BP levels and thereby to adverse CV outcomes. This presentation will focus on air pollution and BP, since air pollution from combined indoor and outdoor sources is the major contributor to pollution-induced mortality. Air pollution is cause by a mixture of particles or particulate matter (PM) and gaseous compounds which consist of nitrogen oxides. The PM which consists of solid and liquid particles is classified by its aerodynamic diameter across a wide range and those with a diameter < 2.5pm (PM2.5) are commonly used to evaluate this form of pollution. Short and longer-term exposures to elevated outdoor PM2.5 have been shown to be associated with higher BP and incident and prevalent hypertension. The mechanisms involved are thought to include damage to the vascular endothelium, via inflammatory and pro-oxidative reactions. Few high-quality data linking different parameters of air pollution and effects on BP are available from around the world, particularly those areas worst affected by pollution. Using the May Measurement Month (MMM) database, associations between BP and pollution are under investigation in retrospective and prospective studies. In the retrospective studies data collected on the bespoke MMM app from 29 countries in MMM18 and MMM19 allow linkage between longitudinal and latitudinal coordinates of where BP was screened and PM2.5 pollution, based on data collected from ground monitors, satellite observations, meteorological data and land use. In prospective studies from MMM21 data arising from 12 cities in the Philippines, Vietnam, Thailand and Indonesia, BP results and PM2.5 levels are in progress using linear mixed models to evaluate cross-sectional associations at the individual and screen-site levels.

Blood pressure stratification for predicting liver fibrosis risk in metabolic dysfunction associated fatty liver disease

Introduction and ObjectivesThe optimal blood pressure (BP) range for patients with metabolic dysfunction-associated fatty liver disease (MAFLD) is currently unknown. This study aimed to explore the relationship between stratified BP levels and MAFLD progression. Patients and MethodsThe data of adults who underwent yearly health check-ups were screened to establish both a cross-sectional and a 6-year longitudinal cohort of individuals with MAFLD. BP was classified into the following categories optimal, normal, high-normal, and hypertension. Liver fibrosis was diagnosed with fibrosis-4 (FIB-4) score, nonalcoholic fatty liver disease fibrosis score (NFS), and aspartate aminotransferase-to-platelet ratio index (APRI). ResultsA total of 10,232 individuals were included in the cross-sectional cohort. In the MAFLD population, individuals with liver fibrosis had significantly higher BP levels and hypertension prevalence (P < 0.001) than those without. Furthermore, liver fibrosis score was significantly associated with BP levels (P < 0.001). In the 6-year longitudinal cohort of 3661 individuals with MAFLD without liver fibrosis, the incidence rates of liver fibrosis increased with increasing BP levels as follows optimal=11.20%, normal=13.90%, high-normal=19.50%, hypertension=26.20% (log-rank 22.205; P < 0.001). Cox regression analysis showed that both baseline high-normal BP (hazard ratio [HR], 1.820; P=0.019) and hypertension (HR, 2.656; P < 0.001) were predictive of liver fibrosis. ConclusionsBP stratification may be useful in predicting the progression of MAFLD. Individuals having MAFLD with concurrent hypertension or high-normal BP are at a higher risk of liver fibrosis. These findings may provide a criteria for early intervention of MAFLD to prevent liver fibrosis.

The association of long-term ambient fine particulate matter exposure with blood pressure among Chinese adults

Previous studies indicated that long-term exposure to high level of fine particulate matter (PM2.5) was associated with elevated blood pressure (BP) and hypertension, but most of them were conducted in high-income countries with low PM2.5 level. Therefore, we aimed to evaluate the adverse impacts of long-term exposure to PM2.5 on BP and hypertension in China with high concentration. A total of 99,084 adults aged ≥18 years old were included from three cohorts among the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China. PM2.5 concentrations during 2000–2015 at 1 × 1 km spatial resolution were evaluated using satellite-based spatiotemporal models. Generalized estimating equation was applied to assess the impact of three-year average PM2.5 concentrations on BP level and hypertension. We also examined whether health status and lifestyles modified the effects of PM2.5 on BP and hypertension. Generally, high concentration of PM2.5 was associated with increased BP level and higher risk of hypertension. With each 10 μg/m3 increment in PM2.5 concentration, systolic BP (SBP) and diastolic BP (DBP) increased by 1.67 [95% confidence interval (CI): 1.48, 1.86] mmHg and 0.45 (95% CI: 0.35, 0.56) mmHg, and the prevalence of hypertension increased by 29% [odds ratio (OR): 1.29, 95% CI: 1.26, 1.32]. In comparison with the first quartile of PM2.5 concentration, SBP, DBP and prevalence of hypertension in the fourth quartile were increased by 8.26 (95% CI: 7.73, 8.80) mmHg, 2.85 (95% CI: 2.55, 3.15) mmHg, and 133% (OR: 2.33, 95% CI: 2.21, 2.47), respectively, in the fully adjusted model. However, the relationships of PM2.5 with BP might be non-linear, as BP level started to decline when PM2.5 exceeded 75 μg/m3. In conclusion, long-term PM2.5 exposure could elevate BP level and prevalence of hypertension. People living in high-polluted areas should strengthen their awareness of prevention.

Drugs associated with posterior reversible encephalopathy syndrome, a worldwide signal detection study.

Posterior reversible encephalopathy syndrome (PRES) can occur in a variety of clinical conditions, such as severe hypertension, pregnancy, inflammatory diseases, hematopoietic stem cells or solid organ transplantation. Apart increased blood pressure levels and altered renal function, several drugs have been reported as potential triggering factor. These descriptions are nevertheless limited to case reports or small case series. Systematic analysis of drugs associated with PRES using global pharmacovigilance database is lacking and can be useful. We performed a disproportionality analysis using VigiBase, the World Health Organization pharmacovigilance database, using the information component (IC). The IC compares observed and expected values to find associations between drugs and PRES using disproportionate Bayesian reporting. An IC0.25 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. Here we present an analysis of 3278 cases of PRES reported in VigiBase. These results identified 73 molecules statistically associated with PRES using full database as background with an IC0.25 > 0. Only 34% (N = 25/73) of them had this information written in the summary of product characteristics. The main drug classes involved were antineoplastic and immunomodulating agents and the drugs with the greatest number of cases were tacrolimus, cyclosporin, bevacizumab, methotrexate, and vincristine. An overall mortality of 8.1% (N = 267/3278) was identified in cases of drug-associated PRES. These results will help clinicians identify potential suspected drugs associated with PRES and decide which drug to discontinue and eventually lead to a re-evaluation of drug labels for some molecules.