Normotensive Subjects Research Articles

Association of soluble E-selectin and morning blood pressure surge in patients with essential hypertension

Background: Elevated soluble E-selectin which reflects a state of endothelial activation with subsequent vasoconstriction may elevate morning blood pressure (BP) surge. This study aimed to analyze soluble E-selectin serum concentrations in patients with essential hypertension against normotensive healthy individuals and to find a role of such molecule in the phenomenon of morning BP surge. Material and methods: In this case-control study, a 24-hour ambulatory blood pressure monitoring with recording of morning BP surge and serum soluble E-selectin levels were measured for a total of 90 patients (60 patients with essential hypertension and 30 normotensive subjects as a control). Results: Hypertensive patients had higher body mass index in comparison to control subjects (30.7 ± 2.3 kg/m 2 vs. 27 ± 3.2 kg/m 2 , p < 0.001). Serum uric acid levels were higher in hypertensive patients than control subjects (7.26 ± 2.60 mg/dL vs. 5.92 ± 1.15 mg/dL, p = 0.028). Hypertensive patients had higher left ventricular mass index (LVMI) (110.5 ± 19.2 g/m2 vs. 99.8 ± 9.5 g/m 2 , p = 0.001). Patients with essential hypertension have higher level of soluble E-selectin than normotensive participants (180.6 ± 96.1 vs . 75.9 ± 31.5 ng/mL, p < 0.001). Soluble E-selectin was positively correlated with morning BP surge (r = 0.696, p ≤ 0.001). Conclusion: Patients with essential hypertension have higher level of soluble E-selectin than normotensive. Soluble E-selectin was positively correlated with morning BP surge.

A study on maternal and fetal cell free DNA (cffDNA) for predicting the adverse pregnancy outcomes

This gender-independent detection of cell-free fetal DNA in maternal plasma using RASSF1A/beta-actin has curtained off a new dimension regarding its utility to predict the adverse pregnancy outcomes. Recent efforts have been directed at developing sequences from cell-free fetal DNA (cffDNA) as markers for pregnancy outcomes. The utility of cffDNA using the methylation-dependent DSCR3 and RASSF1A markers along with total cell-free DNA (cf-DNA) in maternal serum by HYP2 marker are useful in predicting adverse pregnancy outcomes. Indigenously developed low-cost method of the gender-independent sequence markers from cffDNA was investigated and evaluated with the standardized commercial kits as predictive markers for adverse pregnancy outcomes. In the present study, we have tested whether the elevated amount of cffDNA in maternal plasma is associated with adverse pregnancy outcomes and development of new marker by the low-cost method to predict adverse pregnancy outcomes. 210 pregnant women within the age group of 20 – 30 years attending for routine antenatal checkups after 20 weeks with fulfilling the diagnostic criteria of adverse pregnancy outcomes were included in our study. Age-matched pregnant women without adverse pregnancy outcomes were included as controls (n=210). Identification of cell-free fetal DNA (cffDNA) in maternal plasma by using in-house methods (Guanidium isothiocyanate) was found comparable with commercial kit and its content (GE/ µl) in adverse pregnancy outcomes subjects were significantly higher than the normotensive subjects. Our results indicated that indigenously developed method for detection of gender-independent cffDNA can be applicable for screening test of adverse pregnancy outcome.

Differential influences of serum vitamin C on blood pressure based on age and sex in normotensive individuals.

Hypertension is among the most prevalent chronic diseases with diverse etiology, affecting over 1 billion people globally. In numerous studies, vitamin C inversely correlated with blood pressure and was suspected to have antihypertensive properties. Currently, there is conflicting evidence regarding the relationship between vitamin C and blood pressure, with most studies being conducted on hypertensive subjects. The principal objective of this project was to investigate the relationship between vitamin C and blood pressure in normotensive adult subjects. A total of 2,533 individuals aged 20 years and above were enrolled in the present study from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Outcome variables were systolic blood pressure (SBP) and diastolic blood pressure (DBP). Serum vitamin C was regarded as an independent variable. EmpowerStats software and R (version 3.4.3) were used to examine the association between vitamin C and SBP or DBP. Vitamin C was reversely correlated with both SBP (β = -0.02, 95% CI: -0.03 to -0.00, p = 0.0306) and DBP (β = -0.02, 95% CI: -0.04 to -0.01, p = <0.0011) after adjusting all covariates. This reverse relationship may be affected by a number of factors, including a person's gender, age, race, and ethnicity. A U-shaped association between vitamin C and SBP in females and an inverted one between vitamin C and DBP in males were detected, respectively. We further calculated the inflection points at 90.3 μmol/L for females and 40 μmol/L for males. It is somewhat surprising that a reverse U-shaped distribution between vitamin C and SBP and DBP in people over 50 was detected, and the point of inflection of vitamin C were all located at 40 μmol/L. Vitamin C was negatively correlated with both SBP and DBP in this cross-sectional analysis. However, a U-shaped relationship and an inverted one were also observed in certain people, which implied that, though vitamin C is considered a vital antioxidant, maintaining vitamin C at appropriate levels may be beneficial according to different populations.

Obstructive Sleep Apnea Among Gravidas With Chronic Hypertension Compared to Matched Controls: A Prospective Cohort Study.

Previous studies of obstructive sleep apnea (OSA) risk in gravidas with chronic hypertension (cHTN) did not control for obesity as a risk factor for OSA. We therefore performed this study to evaluate whether OSA is more prevalent among gravidas with cHTN compared to normotensive gravidas matched for body mass index (BMI) and gestational age (primary outcome). We also assessed whether OSA is more severe when comorbid with cHTN in pregnancy (secondary outcome). This was a single-center, prospective cohort study. Adult gravidas at 10-20 weeks of gestation, with and without cHTN, were enrolled and BMI matched. All subjects answered OSA screening questionnaires and underwent a home sleep test when they were between 10 and 20 weeks of gestation. Pregnancy outcomes were followed for all subjects. We performed univariable and multivariable logistic regression to model the relationship between cHTN status and OSA. A total of 100 pregnant subjects (50 with cHTN and 50 normotensive) completed a home sleep test of 2 hours or more. There were no differences in demographic variables between the 2 groups, except that gravidas with cHTN were significantly older than normotensive subjects (mean ± standard deviation [SD] 34 ± 4 vs 30 ± 6 years; P < .001). OSA was more prevalent (64% vs 38%; P = .009; odds ratio [95% confidence interval (CI)] 2.90 [1.30-6.65]; P = .01) and more severe in gravidas with cHTN (moderate or severe OSA 59% vs 21%; P = .009). After controlling for age, we found no overall association between cHTN on OSA risk (adjusted odds ratio [95% CI] 2.22 [0.92-5.40]; P = .076). However, among gravidas older than 25 years of age, cHTN was associated with higher odds of OSA (adjusted odds ratio [95% CI], 2.64 [1.06-6.71], P = .038). cHTN and age are important risk factors for OSA in gravidas. Gravidas with cHTN should be screened for OSA in early pregnancy. Future studies may validate screening tools that include cHTN and age, and investigate the role of OSA therapy in blood pressure control.

Abstract 13889: Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Noncalcified Coronary Plaque and Coronary Artery Calcium Score in Subjects With Coronary Artery Disease According to Hypertension Status

Introduction: Higher amounts of noncalcified plaque and higher coronary artery calcium (CAC) scores are associated with increased cardiovascular events and mortality. The effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on noncalcified coronary plaque and more advanced calcified plaque as measured by the CAC score according to hypertensive (HTN) status is unknown. Methods: A total of 242 subjects with coronary artery disease (CAD) on statin were randomized to 3.36 g of EPA+DHA or none (control) for 30 months. Coronary plaque composition and CAC scores were measured with computed tomographic coronary angiography at baseline and 30-month follow-up. Results: Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3) and median [IQR] triglyceride (TG): 117.5 mg/dL [81.3,166.8]. Despite a significantly higher CAC score at baseline in HTN subjects, both HTN and normotensive (NTN) subjects had similar CAC progression over 30 months with no difference between EPA+DHA and control groups (Figure B). NTN subjects on EPA+DHA had a 20.7% reduction in TG level and 36.6% lower neutrophil count, a marker of inflammation, and lack of progression of noncalcified plaque compared to control who had progression (median % change: -7.6 vs 13.2 mm 3 /mm, P=0.008) (Figure A). In contrast, HTN subjects on EPA+DHA and control had progression of noncalcified coronary plaque with no significant difference between the two groups (Figure A) Conclusions: EPA+DHA prevented progression of noncalcified plaque in NTN subjects but not HTN subjects with no effect on more advanced plaque which has calcified in the setting of low LDL-C and TG levels. The benefit of EPA+DHA in CAD patients on statin therapy appears limited to noncalcified coronary plaque in NTN subjects. Whether this benefit is related to more favorable effects on inflammation based on blood pressure status should be examined further.

Abstract 15824: Microvascular Endothelial Kir2.1 Channels Play Important Role in Flow-Induced Dilation During Hypertension in Humans

Hypertension is associated with decreased endothelial function through reduced contributions of NO. Our recent study discovered that flow-induced generation of NO in resistance arteries of mice and humans, and flow-induced vasodilation (FIV), a hallmark of the endothelial response to flow, critically depend on endothelial inwardly-rectifying K+ channels (Kir2.1). The goal of this study was to establish whether these channels contribute to the impairment of endothelial function in peripheral resistance arteries of humans with hypertension. We measured microvascular function in vessels extracted from subcutaneous fat biopsies isolated from 28 subjects: normotensive (n=19; 30.6±4.4yo; systolic blood pressure-SBP: 115.2±5.7mmHg; diastolic blood pressure-DBP: 75.3±11.3mmHg) and hypertensive (n=9; 50±5.2yo; SBP: 147.1±6.1 mmHg; DBP: 93.1±16.8mmHg). Consistent with previous studies, we find that FIV is impaired in hypertensive subjects as demonstrated by a significant reduction in dilation when compared to the normotensive group. Furthermore, our data suggest that the impairment of FIV in this cohort can be partially attributed to a Kir-dependent vasodilation. Specifically, we show that blocking Kir channels with a specific inhibitor, ML133, or functionally downregulating with endothelial-specific adenoviral vector containing dominant-negative Kir2.1 (dnKir2.1) result in significant decrease in FIV in normotensive subjects and smaller effect in hypertensive patients. The Kir2.1-dependent vasodilation was negatively correlated to both SBP and DBP indicating that Kir contribution reduces as blood pressure increases. In addition, we show that exposing normotensive vessels to acute high pressure, which is known to impair FIV, results in loss of Kir channel contribution, as high-pressure impairs vasodilation in normotensive vessels but no effect is seen when these vessels were incubated with dnKir2.1. Overexpressing WTKir2.1 in endothelium resulted in some improvement in vasodilation in arteries from all participants, with a greater recovery in hypertensive patients. Our data suggest that hypertension-induced suppression of Kir2.1 is an important mechanism underlying endothelial dysfunction in hypertension.

Abstract 11938: Novel Approach for Optimal Assessment of Cardiovascular Risk of Blood Pressure in Asymptomatic Subjects Utilizing Mild Exercise Stress Test Protocol

Background: BP risk class assessment has been relying on resting BP (rBP) measurements by healthcare providers. Often, this measurement does not correlate with 24-hour ambulatory BP monitoring nor with at-home measurements. Purpose: To assess whether abnormal rise in BP post-mild exercise protocol (PMEP), which resembles most of the activities subjects are under all day, will be more physiologic and informative for risk stratification, beyond the rBP measurements. Methods: We screened 2,924 subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System, also known as the Rasmussen Risk Score, which consists of 10 tests: 7 vascular and 3 cardiac (published previously). The vascular tests include rBP, BP PMEP (2.4 mi/hr and 7% elevation for 3 minutes), small (C2) artery stiffness, and CIMT. Out of the total subjects, 1094 (37%) were asymptomatic and on no medications. These were divided into four BP classes according to the current ACC/AHA guidelines. Results: In the table, normotension with an abnormal rise in BP PMEP has significant cardiovascular structural and functional abnormalities (CVSFA) than those without. Also noted, the higher the BP class, the higher the CVSFA with and without an abnormal rise in BP PMEP. Conclusions: Abnormal rise in BP PMEP in normotensive subjects is associated with significant CVSFA. This may represent a “masked hypertension” cohort. These findings mandate early diagnosis, follow-up, and optimal treatment. Additionally, an abnormal rise in BP PMEP in other classes is more pronounced with stepwise increases in BP class. Hence, we advocate for PMEP for BP classification and treatment. Early detect to protect.

Gut-Immune-Kidney Axis: Influence of Dietary Protein in Salt-Sensitive Hypertension.

Humans with salt-sensitive hypertension demonstrate increased morbidity, increased mortality, and renal end-organ damage when compared with normotensive subjects or those with salt-resistant hypertension. Substantial evidence from humans and animals has also demonstrated the role of dietary components other than salt to modulate hypertension. Evidence presented in this review provides support for the view that immunity and inflammation serve to amplify the development of salt-sensitive hypertension and leads to malignant disease accompanied by end-organ damage. Interestingly, salt-sensitive disease is modulated by changes in dietary protein intake, which also influences immune mechanisms. Together, the evidence presented in this review from animal and human studies indicates that changes in dietary protein source have profound effects on the gut microbiota, microbiota-derived metabolites, DNA methylation, gene expression, immune cell activation, the production of cytokines and other factors, and the development of salt-sensitive hypertension and related disease phenotypes.

Prevalence of hs-CRP among Indians with hypertension.

The prevalence of hypertension in the early twentieth century varied in India, ranging from 2-15% in Urban India and 2-8% in Rural India. In the inter heart and inter stroke study, hypertension accounted for 17.9% and 34.6% of population attributable risk for coronary artery disease and stroke respectively. CRP appears in serum in response to a variety of inflammatory stimuli .Raised level of hs-CRP is seen with increasing with age, during an infection, inflammation, coronary artery diseases, obesity, sepsis, smoking and vasculitis. CRP is also a factor in the development of atherosclerotic plaque. Although CRP was believed to be a marker of vascular inflammation, recent research indicates that it plays an active role in atherogenesis. So in this study we measured serum hs- CRP in patients with essential hypertension and correlated with blood pressure. The study consists of 50 patients with essential hypertension with antihypertensive medications. in the age group of 40 to 60 years of both sexes and 25 normotensive subjects with no history of cardiovascular, neoplastic, hepatic, renal, infectious or auto immune disease. IHEC clearance and informed consent were obtained. hs-CRP was measured by ELISA kit. Our study showed significantly elevated serum hs-CRP level in hypertensive subjects in comparison with control subjects. To find out the relationship between physiological and biochemical parameters with CRP Pearson correlation coefficient has been applied. The level of significance has been fixed as 5% (p<0.05). SPSS15 software has been used for calculation. Our study showed significantly elevated serum hs-CRP level in hypertensive subjects in comparison with control subjects. But there is no correlation of hs-CRP level with both systolic and diastolic pressure. Several studies have shown inflammatory markers such as CRP as an independent determinant of endothelium dependent vascular function among patient with coronary heart disease (CHD) in patients with hypertension. There was no significant correlation was observed between levels of hs-CRP and systolic and diastolic blood pressure in this study but there was a significant elevation hs-CRP level was observed in hypertensive patients.

Association between the triglyceride-glucose (TyG) index and increased blood pressure in normotensive subjects: a population-based study

BackgroundInsulin resistance (IR) is an important contributor to the development of hypertension (HTN), and the triglyceride-glucose (TyG) index has been proposed as a simple, reliable marker of IR. This study investigated the association between the TyG index and blood pressure (BP) elevation in a large general population.MethodsThe study enrolled 15,721 adults with no history of cardiometabolic diseases from the 2016–2019 Korea National Health and Nutrition Examination Survey. Participants were classified into quartiles based on the TyG index and BP was categorized as normal BP, elevated BP, pre-HTN, and HTN. The associations of the TyG index with BP categories were assessed using multivariate multinomial logistic regression models with normal BP as the reference group.ResultsThe mean systolic/diastolic BP and prevalence of HTN increased with the TyG index (P for trend < 0.001). The continuous TyG index had a strong dose-response relationship with increased odds of elevated BP, pre-HTN, and HTN. Compared with the lowest TyG index quartile, the highest TyG index quartile was significantly associated with higher odds of having elevated BP (odds ratio [OR], 1.52; 95% confidence interval [CI], 1.24–1.87; P for trend < 0.001), pre-HTN (OR, 2.22; 95% CI, 1.95–2.53; P for trend < 0.001), and HTN (OR, 4.24; 95% CI, 3.49–5.16; P for trend < 0.001).ConclusionWe found that a higher TyG index was positively associated with the risk of increased BP in normal healthy individuals. This study suggests that the TyG index might serve as a potential predictor of HTN. However, further studies with larger sample sizes and various target populations in longitudinal designs are needed.

A cross-sectional study to correlate antioxidant enzymes, oxidative stress and inflammation with prevalence of hypertension

AimsHypertension a multifactorial consequence of environmental factors, life style and genetics is the well-recognized risk factor contributing to coronary heart diseases. The antioxidant imbalance, excessive reactive oxygen species (ROS) leads to oxidative stress which is pivotal in progression of hypertension. The present study aims to understand the complex interaction between oxidative stress, inflammation and antioxidant system which is crucial to maintain cellular homeostasis which further can exaggerate hypertension pathophysiology. Materials and methodsThe metabolic profile of hypertensive and normotensive subjects from Malwa region, Punjab was compared by estimating lipid profile, cardiac, hepatic and renal markers. The oxidative stress markers (protein carbonyls and lipid peroxidation), inflammatory markers (Nitric oxide, Myeloperoxidase and advanced oxygen protein products), and antioxidant enzymes (Superoxide Dismutase, Catalase, and Total Antioxidant Capacity) were analyzed. Key findingsIt is observed that the metabolic markers are altered in hypertensive subjects which further these subjects showed increased oxidative, inflammatory profile and compromised antioxidant status when compared with normotensive subjects. Co-relation analysis validated the involvement of inflammation and oxidative stress in impaired endothelial function and vital organ damage. Significance of studyThese markers may act as early indicators of hypertension which usually do not show any physical symptoms, thus can be diagnosed and treated at the earliest. The current study suggests that disturbed homeostasis, a consequence of altered interaction between antioxidant system and inflammatory events raises the oxidative stress levels which eventually leads to hypertension and associated complications. These indicators can serve as early indicators of future chronic complications of hypertension.

Rate and risk factors of metabolic components and component combinations according to hypertension status in Tibetans in a cross-sectional study.

To estimate the prevalence of metabolic syndrome (MS) and metabolic components and their associated factors and component combinations according to hypertension status in Tibetans living at high altitude. Multistage sampling of 1473 participants (799 hypertensive patients and 674 normotensive subjects). MS prevalence and the number of metabolic components ≥ 3 were significantly higher in the hypertensive than normotensives. In hypertensive patients, the most common component was central obesity and it combined with: high blood pressure, in those with 2 risk factors, plus fasting hyperglycemia, in those with 3 risk factors, and high triglyceride, in those with 4 risk factors. In normotensive subjects, the most common single component was low high-density-lipoprotein cholesterol, and most component combination included central obesity and hyperglycemia in those with 2 risk factors, plus high blood pressure in those with 3 risk factors, and high triglycerides in those with 4 risk factors. Body mass index and female both were associated with increased possibilities of MS in hypertensive and normotensive participants. Low incoming, and high educational levels were associated with an elevated probability of MS in normotensive Tibetans also. The priority of prevention from cardiovascular diseases by targeting metabolic components in the hypertensive was different from normotensives. Different MS components had various lifestyle and socioeconomic factors.

The association of plasma sortilin with essential hypertension and subclinical carotid atherosclerosis: A cross-sectional study.

BackgroundSortilin, a protein that regulates glucose and lipid metabolism, has recently been linked to cardiovascular diseases (CVDs) such as coronary heart disease and carotid artery stenosis. In this study, we measured circulating sortilin concentrations in essential hypertensive (EH) patients, and evaluated the association between sortilin, hypertension, and subclinical carotid atherosclerosis in hypertensive individuals.MethodsThis cross-sectional study included 336 individuals, including 186 newly diagnosed EH patients and 150 age-and-sex-matched normotensive healthy subjects (NT). Plasma sortilin and adiponectin (ADI) levels were measured using ELISA kits. In the EH group, high-resolution B-mode ultrasound was used to detect the existence of subclinical carotid atherosclerosis (subAS), which was defined as having a carotid intima–media thickness (cIMT) ≥ 1.0 mm and/or plaque on the carotid artery without any clinical manifestations.ResultsOur findings showed that plasma sortilin concentrations ranged from 3.34–11.34 ng/ml for all subjects. Sortilin levels were significantly higher in the EH group than in the NT group (8.10 ± 1.82 ng/ml vs. 6.37 ± 1.52 ng/ml, P < 0.001) and were further upregulated in the EH with subclinical carotid atherosclerosis (EH + subAS) group compared to the EH without subclinical carotid atherosclerosis (EH-subAS) group (8.42 ± 1.75 ng/ml vs. 7.79 ± 1.84 ng/ml, P < 0.05). In correlation analysis, sortilin was positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), white blood cell (WBC), endothelin-1 (ET-1), high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and cIMT (all P < 0.05) and negatively associated with NO and ADI (P < 0.001). Multiple linear regression analysis revealed that SBP, LDL-C, and ET-1 were independently associated with plasma sortilin levels. Increased sortilin levels were independently associated with the risk of EH (OR: 1.86, 95%CI: 1.56–2.20, P < 0.001) and EH + subAS (OR: 1.33, 95%CI: 1.07–1.66, P = 0.011), after adjustment for multiple risk factors. Restricted spline curve showed that elevated sortilin levels increase the odds of having EH.ConclusionElevated sortilin levels are associated with an increased risk of essential hypertension and subclinical carotid atherosclerosis in hypertensive patients.

Isolated diastolic hypertension is not a benign situation regarding hypertension mediated organ damage in patients with first diagnosed and never treated essential hypertension

Abstract Background Isolated diastolic hypertension (IDH) usually remains untreated as it is considered benign compared to isolated systolic or combined systolic/diastolic hypertension. Hypertension mediated organ damage (HMOD) needs to be assessed in each individual hypertensive patient in order to estimate cardiovascular risk. We aimed to investigate the HMOD differences between first diagnosed and never treated patients with IDH compared to normotensive subjects. Methods From 550 first diagnosed and never-treated hypertensive and non-diabetic patients, we studied 81 patients with IDH (mean age = 49±9, 63% males, 26% smokers) and 53 normotensives (mean age = 51±13, 30% males, 28% smokers). Office and ambulatory blood pressure monitoring (24h ABPM), CV risk factors [smoking, obesity (BMI), hyperlipidemia and HMOD [aortic stiffness (PWV), left ventricular diastolic dysfunction (EEa), cardiac mass (LVMI) and cardiac hypertrophy (LVH), coronary arteries microcirculation (CFR), carotid intima-media thickness (cIMT) were estimated in each hypertensive patient as well as normotensive subject. Results IDH patients had similar age, BMI, lipid profile, central systolic BP and smoking habit, and increased systolic (139±12 vs. 133±18, p=0.03), diastolic (89±9 vs. 84±9 mmHg, p=0.02) and mean office BP (106±9 vs. 82±9 mmHg, p&amp;lt;0.001) as well as 24h systolic (125±3 vs. 119±6 mmHg, p&amp;lt;0.001) and diastolic ABPM (84±4 vs. 73±4 mmHg, p&amp;lt;0.001) compared to normotensives. Regarding HMOD, IDH patients had LVH in 7/81 (9%). Increased LVMI (79±18 vs. 69±18 g/m2, p=0.01) and IMT (0.9±0.2 vs. 0.8±0.1 mm, p=0.01) but similar PWV, E/Ea and CFR were found compared to normotensives. In multiple regression analysis (age and weight were used as independent variables), LVMI was independently related to office systolic (Beta=0.26, p=0.02) and diastolic BP (Beta=0.28, p=0.01) as well as central diastolic BP (r=0.38, p=0.04) while no relationship was found between LVMI and 24h ABPM. Conclusions The presence of HMOD in IDH in first diagnosed and never treated patients with arterial hypertension underscores the need for antihypertensive treatment (life style changes and medication). As HMOD may regress with successful antihypertensive treatment, there is still time for physicians to reduce future CV events in those patients. Funding Acknowledgement Type of funding sources: None.

Arterial compliance and its dynamics in obese adolescents.

Arterial compliance (AC) decrease with aging is accelerated by factors associated with the progression of atherosclerotic process, including obesity. Prevalence of obesity increases not only in adult population but also in children and adolescents. The results of studies characterizing the effect of obesity on AC (often indirectly estimated by pulse wave velocity (PWV)) are contradictory. Considering the limitations of previously applied methods and the need to interpret AC values in the context of potential confounders or during various physiological states, the aim of this study was to compare AC of control and obese adolescents during four different physiological states: supine rest, head-up tilt (HUT), supine recovery and mental arithmetic (MA). AC was assessed by the method based on two-element Windkessel model as the ratio of a time constant t characterizing diastolic blood pressure decay and total peripheral resistance (TPR). In total, fifty healthy and normotensive subjects (40 females, 10 males, age 17.5 years (SD=1.1 years)) were examined - 25 obese and 25 age- and sex-matched control subjects. We observed significantly increased AC values during all phases in obese group. An increase in AC was also preserved after controlling for blood pressure influence. These results were confirmed using PWV based AC estimation. Interestingly, AC decreased similarly during stress phases (HUT, MA) in both groups. Lastly, TPR was decreased throughout the study protocol in obese subjects. In conclusion, AC is increased in young obese subjects consistently during various physiological states. Furthermore, changes of physiological states evoke similar response of AC in both groups indicating preserved autonomic control of elastic arteries. A decreased TPR in obese subjects points towards the influence of different maturation state of the arterial tree and/or changes in vasomotion possibly counterbalancing acceleration of atherosclerosis process.

Interaction analysis of lipid accumulation product and family history of diabetes on impaired fasting glucose and diabetes risk in population with normotension in Eastern China: a community-based cross-sectional survey

BackgroundLipid accumulation product (LAP) is considered to be a new convenient useful indicator to assess the visceral fat. Therefore, we aimed to evaluate the risk factors of impaired fasting glucose (IFG) and diabetes, and explore the possible interacting influences of LAP with other factors on the risk of IFG and diabetes among Chinese normotension adults.MethodsA multistage stratified cluster sampling method was conducted to select urban residents in Bengbu, China. For each eligible participant, data on questionnaire survey, anthropometric measurements and laboratory tests were obtained. The effects of body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR) and LAP for predicting IFG and diabetes were performed by multiple logistic regressions and receiver operating characteristic (ROC) analyses. The interaction effects were evaluated by relative excess risk of interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI).ResultsSix thousand, four hundred sixty-seven normotension subjects (2695 men and 3772 women) were enrolled in our study, the prevalence of IFG and diabetes were 9.37% and 14.33%, respectively. When assessed using ROC curve analysis, LAP exhibited higher diagnostic accuracy for identifying IFG and diabetes than BMI, the area under the AUC curve was 0.650 (95% CI: 0.637 to 0.662). After adjustment for age, sex, educational level and other confounding factors, multivariate logistic regression analyses indicated that subjects with the fourth quartile of LAP were more likely to develop IFG (adjusted OR: 2.735, 95% CI: 1.794–4.170) and diabetes (adjusted OR: 1.815, 95% CI: 1.297–2.541) than those with the first quartile. A significant interaction between LAP and family history of diabetes was observed in participants (RERI = 1.538, 95%CI: 0.167 to 3.612; AP = 0.375, 95%CI: 0.118 to 0.631; SI = 1.980, 95%CI: 1.206 to 3.251). However, a significant interaction between LAP and abdominal obesity was indicated by the value of RERI (1.492, 95%CI: 0.087 to 3.723) and AP (0.413, 95%CI: 0.014 to 0.756), but not the value of SI (1.824, 95%CI: 0.873 to 3.526).ConclusionOur results demonstrated that there might be synergistic effect between LAP and family history of diabetes on the risk of IFG and diabetes.

Leisure-Time Physical Activity Has a More Favourable Impact on Carotid Artery Stiffness Than Vigorous Physical Activity in Hypertensive Human Beings.

Aim. To assess the effect of leisure time versus vigorous long-term dynamic physical activity (PA) on carotid stiffness in normotensive versus hypertensive subjects. Methods. The study was conducted on 120 leisure-time exercisers and 120 competitive athletes. One hundred and twenty sedentary subjects served as controls. In addition, participants were classified according to whether their systolic blood pressure was ≥130 mmHg (hypertensives, n = 120) or normal (normotensives, n = 240) according to the ACC/AHA 2017 definition. Carotid artery stiffness was assessed with an echo-tracking ultrasound system, using the pressure-strain elastic modulus (EP) and one-point pulse wave velocity (PWVβ) as parameters of stiffness. Results. The effect of the two levels of PA differed in the normotensives and the hypertensives. Among the normotensives, there was an ongoing, graded reduction in EP and PWVβ from the sedentary subjects to the athletes. By contrast, among the hypertensives, the lowest levels of EP and PWVβ were found among the leisure-time PA participants. EP and PWVβ did not differ between the hypertensive sedentary subjects and the athletes. A significant interaction was found between PA and BP status on EP (p = 0.03) and a borderline interaction on PWVβ (p = 0.06). In multiple regression analyses, PA was a negative predictor of EP (p = 0.001) and PWVβ (p = 0.0001). The strength of the association was weakened after the inclusion of heart rate in the models (p = 0.04 and 0.007, respectively). Conclusions. These data indicate that in people with hypertension, leisure-time PA has beneficial effects on carotid artery stiffness, whereas high-intensity chronic PA provides no benefit to vascular functions.

Abstract 030: Aldosterone Promotes Nanoscale Colocalization Of Epithelial Sodium Channel Subunit Alpha And Sodium Calcium Exchanger In Neuro2a Cells

We previously reported that hypertensive patients have a higher concentration of sodium ([Na + ]) in their cerebrospinal fluid (CSF) compared with normotensive subjects but no difference in plasma [Na + ] was observed, suggesting the potential importance of CSF [Na + ] in hypertension. Epithelial sodium channels (ENaC) in the brain have been shown to be up regulated in salt-induced hypertension (SH). However, the molecular mechanisms of how brain ENaC contributes to SH development are not yet understood. We hypothesize that ENaC forms a nanoscale colocalization with the sodium-calcium exchanger (NCX) that mediates downstream signaling pathways leading to SH. To test our hypothesis, using self-labeling proteins we generated SNAP-ENaC-α and Halo-NCX1 constructs, enabling high-resolution imaging of surface expressed proteins. Expression of ENaC-α-SNAP and NCX1.5-Halo was confirmed by western blot showing an increase in expression (fold change) of ENaC-α (7.6 ± 1.7 vs. 1 ± 0.3, p&lt;0.02) and NCX1.5 (10.1 ± 0.8 vs. 1 ± 0.4, p&lt;0.0006) in transfected Neuro2A cells compared with controls. Transfected cells were treated with vehicle or aldosterone (100 nM) for 2 hours (n=15 cells from 3 repeat experiments/group) and imaged using ground-state depletion super-resolution microscopy. Data were analyzed using object-based analysis (OBA). Aldosterone treatment increased the density of individual ENaC-α clusters on the cell surface (12.4 ± 1.3 vs. 6.9 ± 1.08 clusters/μm 2 , p&lt;0.002), supporting the functional role of aldosterone on increasing ENaC-α surface abundance. Importantly, the frequency (3.1 ± 0.34% vs 1.7 ± 0.22% colocalized /total clusters, p&lt;0.001) and the density (0.5 ± 0.1 vs 0.2 ± 0.04 clusters/μm 2 of cell surface, p&lt;0.009) of colocalized (&lt; 40nm) ENaC-α and NCX 1.5 clusters were significantly increased in aldosterone treated cells. In sum, these data show aldosterone increases the number of ENaC-α channels on the cell surface and promotes its nanoscale colocalization with NCX, providing evidence for a functional role of ENaC-α and NCX1 coupling. Nanoscale colocalization of ENaC and NCX is potentially significant in SH, and future studies will focus on elucidating the functional importance and mechanisms.

Abstract 070: ONE UP-REGULATED NOVEL MICRORNA AND 4 DOWN-REGULATED MRNA TARGETS WERE IDENTIFIED IN PERIPHERAL BLOOD MONONUCLEAR CELLS OF HYPERTENSIVE PATIENTS WITH METABOLIC SYNDROME

Introduction: Hypertension is associated with target organ damage such as kidney injury. The immune system plays a role in hypertension and target organ damage. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs are crucial post-transcriptional regulators of immune cell development and function. Hypothesis: MicroRNAs play a role in the activation of immune cells in hypertension with target organ damage in humans. Methods: Normotensive subjects (NTN) and patients with hypertension (HTN) associated or not with at least 2 other features of the metabolic syndrome (MetS) or chronic kidney disease (CKD) were studied (n=15-16). PBMCs were isolated from blood, RNA extracted, small and total RNA sequencing (RNA-seq) using an Illumina HiSeq-2500 and data were analyzed using a systems biology approach. Differentially expressed (DE) microRNAs and mRNAs were identified with fold change (FC) &gt;2 and &gt;1.5, respectively, and P &lt;0.005. DE miRNAs with RNA-seq count number (CN) &gt;500, and predicted targets by TargetScan with CN&gt;300 were validated by reverse transcription-quantitative PCR (RT-qPCR) in PBMCs. Results: RNA-seq identified DE microRNAs and mRNAs in HTN (22 and 19), MetS (57 and 401) and CKD (6 and 26) compared to NTN. RT-qPCR validated a novel miRNA (miR-pl-86 [2-fold up]) and 4 predicted mRNA targets (WD repeat domain 89 [ WDR89 , 51% down], Dmx like 1 [ DMXL1 , 52% down], zinc finger protein 600 [ ZNF600 , 63% down] and NOC3 like DNA replication regulator [ NOC3L , 61% down]) in MetS vs NTN ( P &lt;0.05). RNA-seq results were correlated with RT-qPCR data for miR-pl-86 (R 2 =0.37, P &lt;5.5E-07, n=56) , WDR89 (R 2 =0.29, P &lt;1.4E-05, n=57) , DMXL1 (R 2 =0.33, P &lt;2.7E-06, n=57) , ZNF600 (R 2 =0.25, P &lt;7.9E-05, n=57) , and NOC3L (R 2 =0.27, P &lt;3.5E-05, n=57). Conclusion: This study identified one up-regulated novel microRNA and 4 down-regulated mRNA targets in PBMCs of patients with HTN and MetS.

423.6: Salt Sensitivity in Living Kidney Donors: A New Cardiovascular Risk Factor?

Introduction: Kidney transplantation with living donor (LKD) is associated with longer graft and patient survival compared with deceased donor organs. Until recently, it was believed that the long-term risk of end-stage renal disease (ESRD), cardiovascular events (CVE) or death in LKD is similar to or even smaller than the general population. Normotensive salt-sensitive (Ss) subjects over 25 years old have a mortality similar to that of hypertensive subjects, while salt-resistant (Sr) normotensive subjects have a longer survival. Objective: To compare, in healthy subjects that we have studied to be a LKD, the levels of 24 hour mean ambulatory blood pressure monitoring (24 hs mABPM), kidney function and left ventricular mass index (LVMI) between Ss and Sr, before and a year after donation. Methods: Data from 42 LKD were included. There were 34 (82%) women, with a mean age of 49 (11) years (range 26 to 66 years). None had a history of kidney disease, diabetes, CVE or hypertension. The subjects were placed on a high-salt diet containing 250 mmol Na for 7 days and on a low-salt diet containing 30 mmol Na during the following 7 days. Compliance with the diet was assessed twice a week by measurement of 24-hour urinary Na excretion (NaUE). On the last day of both the high and low-salt periods, 24-hour ABPM was performed with an automated, noninvasive device. Salt-sensitivity (SS) was defined by a significant decrease (P<0.05) of 24 hs mABPM from high to low salt intake. Trans-thoracic m-mode echocardiograms were performed on the last day of the first period. LV mass was calculated according to the Penn convention and corrected for body surface area to produce the LVMI. Data with normal and nonparametric distribution were expressed as mean and standard deviation (SD) or median and interquartile range (ICR), Student t test and Wilcoxon test were used respectively, P values < 0.05 were considered to be statistically significant. Results: SS was found in 13 of the 42 living kidney donors (31%). The Ss group were older than Sr 53 (10) vs 47 (10) years, but it was not statistically significant (p=0.08). Pre-donation, with high-salt diet the 24 hs mABPM was significantly greater in Ss than in Sr, without any differences in creatinine clearence (CrCl), 24 hs NaUE and 24 hs potassium urinary (KUE) excretion. On the other hand with low-salt diet we did not find any significant differences in 24 hs mABPM, CrCl, NaUE and KUE between groups. LVMI was significantly greater in Ss than in Sr donors. One year after donation we found the same statistically differences in 24 hs mABPM with high-salt diet and no differences with the low-salt diet. Again LVMI was significantly greater in Ss than in Sr donors. The increase of LVMI after donation was significant only in Ss donors (23,2 vs 4,5 g/m2). Conclusion: Ss healthy LKD showed a greater LVMI than Sr ones and a greater increment one year after donation. The study of SS could be included to make kidney transplantation with living donor organs safer.