24-hr Systolic Blood Pressure Research Articles

Effect of Salt Substitution on Ambulatory Blood Pressure, Kidney Function and Inflammation in Middle-Aged and Elderly Hypertensive Patients.

Low-sodium (LS) salt substitution is recognized for its potential to reduce blood pressure (BP), but most research relies on office BP measurement (OBPM). There is a lack of data on salt substitution's effect on target organs, such as the kidney as measured by the urine albumin-to-creatinine ratio (UACR), and its impact on inflammatory cytokines, particularly high-sensitivity C-reactive protein (hs-CRP). To evaluate the effect of LS salt substitution on ambulatory BP measurement (ABPM), kidney function, and inflammation in middle-aged and elderly hypertensive patients. In this 12-month prospective, multi-center, randomized, double-blind study, 352 hypertensive patients were randomly assigned to the normal salt (NS) group (n = 176) or the LS group (n = 176) at a 1:1 ratio. ABPM, fasting blood, and morning first spot urine samples were obtained at baseline and the endpoint. Of the 352 patients, 322 completed all follow-up surveys, and 301 underwent ABPM. In the LS roup, significant reductions were observed in 24-hr systolic BP (-2.3 mmHg), 24-hr diastolic BP (-1.5 mmHg), daytime systolic BP (-2.6 mmHg), daytime diastolic BP (-1 mmHg), and nighttime systolic BP (-0.1 mmHg) compared to the NS group (all p 0.05). However, the change in nighttime diastolic BP was not statistically significant (-0.3 vs. 1.1 mmHg, p = 0.063). Additionally, the LS group showed a more substantial decrease in UACR (-2.05 vs. -7.40 µg/mg, p = 0.004) and hs-CRP (-0.06 vs. -0.24 mg/L, p = 0.048) compared to NS. LS salt substitution significantly decreased ABPM, suggesting a notable impact on hypertension. Furthermore, it demonstrated a protective impact on kidney function, as evidenced by changes in UACR. Additionally, LS salt substitution appeared to reduce inflammation, indicated by the decrease in hs-CRP levels. The study was registered in the Chinese clinical trial registry (registration number: ChiCTR1800019727).

Effect of Aging and Hypertension on Ambulatory Blood Pressure, Arterial Stiffness, and Wave Reflection in Mid-life Adults

Introduction: Age-associated increases in blood pressure are partly due to increased arterial stiffness and wave reflection. How these vascular changes during aging contribute to daily fluctuations in blood pressure and hypertension remain to be elucidated. Therefore, the purpose of this study is to compare ambulatory blood pressure, arterial stiffness, and wave reflection between young healthy adults, mid-life adults without hypertension, and mid-life adults with hypertension. Methods: Twenty-five young (age: 26 ± 4 yr and body mass index [BMI]: 23.9 ± 2.5 kg/m2) and 31 mid-life adults (age: 57 ± 4 yr and BMI: 25.4 ± 2.6 kg/m2), free of obesity and major clinical diseases and non-smokers, were included. Hypertension was defined by the current use of anti-hypertension medications or offce seated blood pressure (BP) ≥ 130/80 mmHg. Young adults with hypertension were excluded. Twenty-four-hour ambulatory BP monitoring (Oscar 2™, SunTech Medical®) and assessment of aortic arterial stiffness and wave reflection (SphygmoCor XCEL, AtCor Medical) were performed in all participants. Results: Daytime, nighttime, and 24-hr systolic BP was similar between young adults (YA) and mid-life adults without hypertension (MA; n=12; P>0.9 vs. YA), while mid-life adults with hypertension (MAHTN; n=19) had higher offce, 24-hr, daytime, and nighttime systolic and diastolic BP compared to YA and MA (p<0.01 vs. YA and MA). Compared to YA, MA had higher nighttime diastolic BP (P=0.02). Aortic arterial stiffness, measured by carotid-to-femoral pulse wave velocity, was the highest in MAHTN (p<0.001 vs. YA and P=0<0.01 vs. MA), followed by MA (p<0.01 vs. YA) and YA. Aortic wave reflection, measured by augmentation index and reflection magnitude, was higher in MA and MAHTN compared to YA but was similar between MA and MAHTN (p<0.001 for MA vs. YA; p<0.001 for MAHTN vs. YA; and P>0.9 for MA vs. MAHTN). Conclusions: Our findings indicate that 1) mid-life adults with hypertension had higher ambulatory BP and arterial stiffness than mid-life adults without hypertension and young adults; 2) despite normal offce blood pressure, mid-life adults without hypertension had higher nighttime diastolic BP and arterial stiffness than young adults; and 3) regardless of hypertension, mid-life adults had higher wave reflection than young adults. These findings suggest that 1) vascular aging may present prior to the diagnosis of hypertension based on offce BP; 2) arterial stiffness, rather than wave reflection, may contribute to the development of hypertension during aging; and 3) compared to offce BP, ambulatory BP may be a more sensitive marker of age-associated increases in blood pressure. NIAAA K99/R00 AA028537 to CLH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Effect of Dietary Sodium and Potassium Consumption on Intestinal Permeability and its Relation to Blood Pressure, and Endothelial Function: A Pilot Study

High sodium (HS) diets can reduce endothelial function (EF) and increase blood pressure (BP) while high potassium (HK) diets are shown to counter this effect. Furthermore, HS diets have also been shown to lead to gut dysbiosis, which is related to increased intestinal permeability (IP). However, the effect of HS diets on IP and whether the addition of HK can attenuate potential HS-induced changes to IP is unknown. Hypotheses: We hypothesized IP would increase on a HS diet and be mitigated by HK and that a higher IP would be related to elevations in BP and lower EF. Methods: Eleven healthy participants (5W/6M, age 32±8 yrs, BMI 23±1, BP 105±6/66±7 mmHg) consumed three 10-day diets of differing sodium and potassium content in randomized order: low sodium (LS)/low potassium (LK) (50mmol/65mmol), HS/LK (300mmol/65mmol), and HS/HK (300mmol/120mmol). On day 9 of each intervention, they collected their urine and wore an ambulatory BP monitor for 24-hr. On day 10, brachial artery flow-mediated dilation (FMD) was measured. Blood was collected and lipopolysaccharide-binding protein (LBP), a biomarker of IP and bacterial translocation, was measured by ELISA. Mixed design ANOVAs assessed sex differences in LBP, FMD, and BPs between diets. Simple linear regressions assessed relations between variables. Results: Twenty-four-hr urinary sodium excretion was higher on both HS diets compared to LS/LK diet (both p<0.01) and 24-hr urinary potassium excretion was higher on HS/HK compared to LS/LK and HS/LK diets (both p<0.01). LBP was different between diets (p<0.01), and there was a significant diet*sex interaction (p=0.02) where men had increased LBP compared to women on the HS/LK and HS/HK diets (both p<0.01). FMD was not different between diets (p=0.13) although men had a lower FMD compared to women after each diet (sex: p<0.01). Twenty-four-hr mean arterial pressure (MAP) was different between diets (p=0.047) as men demonstrated higher 24-hr MAP on the HS/LK diet compared to LS/LK diet (p=0.03) and lower MAP on the HS/HK diet compared to HS/LK diet (p=0.01). LBP was inversely related to FMD (r=-0.82, p<.01) and positively related to MAP (r=0.72, p<.01), 24-hr systolic BP (r=0.66, p=0.03), and 24-hr diastolic BP (r=0.66, p=0.03) on the HS/LK diet for all participants, but not the LS/LK or HS/HK diets. Conclusions: These pilot data suggest that HS diets may increase IP in men, and, in the context of a HS/LK diet, greater IP is associated with lower FMD and higher BP in all participants. NIH R01 HL145055. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of nocturnal blood pressure dipping on recurrence of atrial fibrillation after pulmonary vein isolation.

Lack of the typical nocturnal blood pressure (BP) fall, i.e non-dipper, has been known as a cardiovascular risk. However, the influence of non-dipper on atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) has been unclear. We investigated the clinical impact of non-dipping as evaluated by 24-hour ambulatory BP monitoring on the long-term outcome of AF recurrence post-PVI in 76 AF patients with a history of increased BP. The PVI procedure was successful in all 76 patients (mean age, 66±9years; antihypertensive medication, 89%; non-paroxysmal AF, 24%). Twenty patients had AF recurrence during a median follow-up of 1138 days. There was no difference in BP levels between the AF recurrence and non-recurrence groups (average 24 h systolic BP:126 ± 17 vs.125 ± 14 mmHg; P = 0.84). On the other hand, the patients with non-dipper had a higher AF recurrence than those with dipper (38.9% vs.15.0%; P = 0.018). In Cox hazard analysis adjusted by age, non-paroxysmal AF and average 24-hr systolic BP level, the non-dipper was an independent predictor of AF recurrence (HR 2.78 [95%CI:1.05-7.34], P = 0.039). Non-dipper patients had a larger left atrial (LA) volume index than the dipper patients (45.9 ± 17.3 vs.38.3 ± 10.2 ml/m2, P = 0.037). Among the 58 patients who underwent high-density voltage mapping in LA, 11 patients had a low-voltage area (LVA) defined as an area with a bipolar voltage < 0.5 mV. However, there was no association of LVA with non-dipper or dipper (22.2% vs.16.1%, P = 0.555). Non-dipper is an independent predictor of AF recurrence post-PVI. Management of abnormal diurnal BP variation post-PVI may be important.

A systematic review and meta-analysis of all sham and placebo controlled trials for resistant hypertension

IntroductionThere is a lack of consensus regarding the best add on therapy for treatment of resistant hypertension (RH). This is likely secondary to a paucity of data on the comparative effectiveness of proposed therapies for RH. MethodsPlacebo-controlled and sham-controlled randomized clinical trials testing therapies for the treatment of RH were included in this meta-analysis. Therapies with two or more studies were included as subgroups in this meta-analysis. The primary outcomes being tested were 24-hr systolic blood pressure (SBP) and office SBP. ResultsEight studies were identified that tested mineralocorticoid receptor antagonist (MRA) including 1,414 participants. The raw mean difference (RMD) between MRA and placebo control was statistically significant for 24-hour SBP (-10.56 mmHg; 95% confidence interval (CI) -12.82 to -8.30), 24-hour diastolic (DBP) (-5.48 mmHg; 95% CI -8.48 to -2.58), office SBP (-11.97 mmHg; 95% CI -16.41 to -7.54), and office DBP (-4.14 mmHg; 95% CI -5.62 to -2.65). Six studies were identified that tested renal denervation (RD) including 989 participants. The RMD between RD and sham control was not statistically significant for 24-hour SBP (-1.84 mmHg; 95% CI -3.92 to 0.24), 24-hour DBP (-0.66 mmHg; 95% CI -1.85 to 0.54), office SBP (-1.57 mmHg; 95% CI -6.04 to 2.89), and office DBP (-1.49 mmHg; 95% CI -3.52 to 0.55). Four studies were identified that tested endothelin receptor antagonists (ERA) including 1,193 participants. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-7.02 mmHg; 95% CI -9.15 to -4.90, 24-hr diastolic (DBP) (-6.22 mmHg; 95% CI -7.61 to -4.82), office SBP (-5.84 mmHg; 95% CI -10.08 to -1.60), and office DBP (-3.73 mmHg; 95% CI -5.87 to -1.59). DiscussionMRA lowers BP in patients with RH more than RD, which seems to have little to no effect in RH. ERAs lead to a statistically significant reduction in BP but the confidence in efficacy is limited due to the low number of studies and differences in trial population. Individual factors and their impact on treatment response in RH should be investigated in future research.

Higher levels of vigorous physical activity are associated with enhanced nocturnal blood pressure dipping

Introduction: Nocturnal blood pressure (BP) dipping determined from 24-hour ambulatory blood pressure monitoring (ABPM) is associated with reduced cardiovascular disease (CVD) risk. Physical activity lowers the risk of CVD related, in part, to preserved endothelial function and lower aortic stiffness, however the relation between physical activity and nocturnal dipping remains unclear. The objective of our cross-sectional retrospective analysis was to assess the relation between physical activity and nocturnal BP dipping, and whether this relation was confounded by measures of vascular function. We hypothesized that higher levels of physical activity would be associated with greater nocturnal BP dipping. Methods: Healthy adults (n=172, age 19 to 65 years, 55% female) had 24-hour ABPM measured. BP recordings were taken every 30 min during the daytime and every 60 min during the nighttime. Nocturnal “dippers” had a 10-20% difference between their mean daytime and nighttime systolic BP and “non-dippers/inverse dippers” had &lt;10% difference. The modifiable activity questionnaire was used to assess physical activity levels via self-reported days/week with greater than 30 min of moderate activity (3.0-6.0 METs) and vigorous activity (&gt;6.0 METs). Endothelial function (brachial artery flow-mediated dilation, FMD), and aortic stiffness (carotid-femoral pulse wave velocity, cfPWV) were also assessed. Results: Nocturnal BP dippers performed more days/week of moderate and vigorous physical activity compared to non-dippers (P=0.007 and P=0.008, respectively). Both moderate (B=0.386, P=0.042) and vigorous physical activity (B=0.604, P=0.002) were associated with nocturnal BP dipping in univariate linear regression analyses. However, only vigorous activity (B=0.926, P=0.001) remained associated with nocturnal BP dipping after adjustment for age, BMI, 24-hr systolic BP and diastolic BP, brachial FMD and cfPWV. Conclusion: Vigorous physical activity may attenuate CVD risk in part from enhanced nocturnal BP dipping. Future studies should investigate additional mechanisms by which vigorous physical activity may enhance nocturnal BP dipping. This study was supported by grants from the National Institutes of Health (AG063790; HL014388, HL07121; AG043722). Dr. Pierce is supported by the Russell B. Day and Florence D. Day Endowed Chair in Liberal Arts and Sciences, University of Iowa. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

PS-C25-3: THE EFFECT OF MOUNTAINEERING ON THE ASSOCIATION BETWEEN BLOOD PRESSURE AND PHYSICAL ACTIVITY. THE MOUNT FUJI STUDY

Objective: It has not been fully investigated whether the response of blood pressure (BP) to activity at high altitudes differs from that at low altitudes or how temperature is involved in these differences. We hypothesized the BP response to activity during mountaineering would be increased compared to that in daily living, and conducted this study to compare physiological BP response to accelerometer measurements during mountaineering and daily living. Design and method: In 15 healthy people (mean age 33 ± 6 years), a new multi-sensor ambulatory BP monitoring (ABPM) device equipped with barometer, thermometer, and accelerometer was used to measure blood pressure responses to activity during a trip to Mt. Fuji and during daily life at low altitudes on another day. Associations between physical activity (log-transformed 5-min average values of accelerometer just before each ambulatory BP) and the corresponding BP were obtained from 843 and 676 readings during the Mt. Fuji trip and daily living, respectively. Result: All ambulatory systolic BP (SBP) parameters were significantly higher during the Mt. Fuji trip than during daily living at low altitudes (all p &lt; 0.01). There were significant positive correlations between physical activity and corresponding BPs in both mountaineering and daily living (all P &lt; 0.01), and there was an interaction between BPs and physical activity according to the two conditions (P &lt; 0.01). On Mt. Fuji, multivariate regression analysis showed that increased physical activity and lower temperature were associated with increased 24-hr SBP and diastolic BP (DBP) (all P &lt; 0.05). The goodness-of-fit values of the association between activity and 24-hr SBP or DBP were improved by adding temperature to the model of both 24-hr SBP and DBP. However, these associations were not found in the daily living model. Conclusions: BP response to activity was more pronounced during mountaineering than daily living. Lower temperature compounded the BP response to activity in the mountains but not in daily living.

S-42-4: ISOLATED NOCTURNAL HYPERTENSION IN PATIENTS LIVING WITH HUMAN INMUNODEFICIENCY VIRUS (HIV)

Introduction: People living with HIV (PLHIV) have higher rates of cardiovascular events compared to the general population; however mechanisms behind this discrepancy are poorly understood. High prevalence of hypertension has been proposed as a mechanism underlying cardiovascular events with contradictory results when office blood pressure (BP) is considered. Ambulatory blood pressure measurements (ABPM) have the advantage to measure BP during sleep, a cause of masked hypertension. Additionally, body weight and electrolytes disturbances are common in PLHIV under antiretroviral and antibiotic therapy. We aim to describe the prevalence of isolated nocturnal hypertension (INH) and it characteristics in PLHIV. Material and methods: A random sample of PLHIV from the provincial HIV program in Cordoba, Argentina, underwent clinical and laboratory examination, and 24 h ABPM. Nocturnal hypertension (NH) was defined as nocturnal systolic BP ≥ 120 mmHg and or nocturnal diastolic BP≥70 mmHg. INH was defined in those patients with NH with daytime systolic and diastolic BP&lt; 135/85 mmHg respectively. Results: PLHIV were included in the study: 60% male, mean age was 44.6 (27–69) years old, 87% were receiving antiretroviral therapy. BMI was 25.8 ± 4.8, mean CD4 count was 404.4 ± 289, cells/ml and 86.2% were virologically suppressed. The prevalence of NH was 48.5% [95%CI:36–60%], the vast majority having INH 29/32 (90%), thus the population prevalence of INH was 43.9% [95%CI:32–55,%]. INH patients have an excess of 10.4 and 8 mmHg in 24 hr systolic BP and diastolic BP respectively compared to no INH patients (both p &lt; 0.001). No differences were found regards age, sex, viral load, CD4+ cells and years of HIV history between patients with and without INH. Multiple linear regression (adj-R2 = 0.27, p &lt; 0.001) adjusted by sex and age determined that BMI (β = 0.79, p = 0.02]), plasma uric acid (β = 0.33, p = 0.01) and plasma potassium (β = -9.5, p = 0.03]) independently predicted nocturnal systolic BP in PLHIV. In a multiple logistic regression model adjusted by age and sex, BMI≥30 was associated with INH (OR 4.04 [95%CI: 1.25–13) Conclusion: INH is highly prevalent in PLHIV conferring an excessive hypertension load that may explain the associated high CVS risk. Obesity, increased uric acid, and low plasma potassium are associated with nocturnal systolic BP. Our work suggests the routine use of ABPM and explore metabolic disturbances in obese PLHIV.

Impact of COVID‐19 on Ambulatory Daytime and Nighttime Blood Pressure in Young Otherwise Healthy Adults

BackgroundCOVID‐19 has been shown to cause impairments in vascular function and elevations in resting sympathetic nerve activity in young otherwise healthy adults. Notably, our laboratory recently reported that persistence of COVID‐19 symptoms beyond the acute phase of the illness (i.e., beyond 4 weeks) was accompanied by macro‐ and micro‐ vascular dysfunction as measured by flow mediated dilation and reactive hyperemia, respectively. Interestingly, despite consistent reports of vascular alterations, no studies have reported changes in resting blood pressure (BP) following COVID‐19. One caveat is that BP has only been measured in the laboratory setting. Indeed, to date, no studies have assessed the effect of COVID‐19 on ambulatory BP, which allows for a complete assessment of daytime and nighttime BP without the potential for well known “white coat” effects on BP. Thus, we aimed to investigate the effect of COVID‐19 on 24‐hr ambulatory BP in young adults diagnosed with COVID‐19 within the preceding 6 months. We hypothesized that ambulatory BP would be greater in individuals who had COVID‐19 compared to controls who never had COVID‐19, and that those with symptoms would have higher BP compared to those who were asymptomatic at the time of testing.MethodsWe studied 21 young healthy adults who had a positive laboratory diagnosis of COVID‐19 (COVID: 23 ± 1 years [Mean ± SE]; 12 ± 1 [range: 4 to 22] weeks since diagnosis; 13 females) and 10 controls (23 ± 1 years, 6 females) who never had COVID‐19. Eleven individuals who had COVID‐19 were asymptomatic at the time of testing while 10 were symptomatic. Ambulatory BP was measured using the Oscar 2 oscillometric monitor (Sun Tech Medical). Participants were instructed to perform normal daily activities but not to perform any exercise during the 24‐hr period. Measurements were obtained every 20 min during daytime and every 30 min during nighttime. Average daytime, nighttime and 24‐hr systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were calculated.ResultsDaytime, nighttime, and 24‐hr BPs were not different between control and COVID subjects (P > 0.05 for all comparisons). Similarly, there were no differences in any of the BP assessments between control, asymptomatic or symptomatic COVID subjects (e.g., daytime SBP: control 122 ± 4; asymptomatic 119 ± 4; symptomatic 125 ± 2 mmHg, P = 0.451). Interestingly, in the COVID group, daytime, nighttime, and 24‐hr SBP, DBP, and MAP were inversely correlated with time since diagnosis (P < 0.05 for all with medium to large effect size). Multiple linear regression showed that after accounting for age, BMI, and physical activity (reported average exercise minutes/week), time since diagnosis was a significant predictor of daytime and 24‐hr SBP, DBP, and MAP (e.g., daytime SBP: P = 0.028, β coefficient = ‐0.697). For nighttime BP, time since diagnosis was a significant predictor only for SBP.ConclusionThese preliminary data suggest that the effect of COVID‐19 on ambulatory BP in young adults may be dependent on the time since diagnosis with higher daytime and nighttime BP present closer to the onset of the infection, which appeared to be independent of symptomology. Longitudinal follow up studies are warranted.

Mice Exposed to Maternal Separation are Resilient to the Loss of Circadian Heart Rate Rhythm in Response to Chronic High Salt Diet

Early life stress (ELS) is associated with increases in body mass index and systolic blood pressure in adult life, leading to obesity and obesity‐induced hypertension, major risk factors for cardiovascular disease (CVD). Previously, we have shown that Maternal Separation and Early Weaning (MSEW), a model that mimics the effects of ELS in humans, increases blood pressure and sympathetic activation in obese male mice. We have also shown that MSEW males fed a low‐fat diet (LF) displayed increased water intake, urine excretion, potassium excretion, glomerular filtration rate (GFR), and renal cortex NHE3 expression compared to controls. The aim of this study was to further investigate the status of the water and electrolyte homeostasis (WEH) when we challenge mice exposed to MSEW with a chronic high‐salt diet (HS). C57BL/6J mice pups were separated from the dams from postnatal day (PD) 2 to PD 16 and weaned early on PD 17. Control (C) litters remained undisturbed with the dams and were weaned on PD 21. At weaning, mice were placed on a LF (10% Kcal from fat, Research Diets). After 18 weeks, mice were implanted with radiotelemeters to measure systolic blood pressure (SBP) and heart rate (HR). At 20 weeks, a baseline was recorded and then mice were placed on a LF+HS (10% Kcal from fat, 4% NaCl, Research Diets) for 6 weeks. Single mouse metabolic cages were used to measure water intake and urine excretion before and after LF+HS. GFR was measured using a transcutaneous technique. After 6 weeks, control and MSEW mice showed a similar response to LF+HS in water intake (3.84 ± 0.54 vs. 4.56 ± 1.01 ml), urine excretion (1.90 ± 0.93 vs. 2.63 ± 1.18 ml), and GFR (930.98 ± 41.30 vs. 975.97 ± 86.12 ml/min/100g BW). In addition, 6 weeks of LF+HS did not change 24‐hr SBP from baseline in control (125.5 ± 5.85 vs. 129.33 ± 6.0 mmHg) and MSEW mice (117.33 ± 9.55 vs. 126.67 ± 11.98 mmHg). Similarly, HR did not change in control (612.88 ± 19.51 vs. 651.67 ± 17.84 bpm) and MSEW mice (602.25 ± 15.27 vs. 575.83 ± 11.24 bpm). At baseline, both groups show normal circadian rhythm of blood pressure. However, LF+HS control males lack day‐night HR amplitude (day: 655 ± 14.50 vs. night: 647.67 ± 11.17 bpm, p=NS) while MSEW mice preserve this function (day: 557.67 ± 6.97 mmHg vs. night: 594 ± 5.51 bpm, p&lt;0.05). These data indicate that MSEW male mice are resilient to loss of circadian HR rhythm in response to a chronic HS. Ongoing studies of renal sodium transporters expression may provide insights into the potential mechanisms by which MSEW male mice display this resilience.

Predictors of antihypertensive efficiency of renal denervation in patients with resistant hypertension and type 2 diabetes mellitus

Abstract Background Currently, one of the actively studied interventional methods for the treatment of resistant hypertension (RHTN) is renal denervation (RDN). Despite the safety of the procedure and the long-lasting antihypertensive effect, a significant decrease in systolic blood pressure (SBP) ≥10 mmHg is observed only in 60–80% of patients. According to the Global SYMPLICITY Registry (GSR) study, patients with diabetes mellitus could benefit from lower blood pressure after renal denervation due to initially higher sympathetic activity. The indicators associated with the processes of sympathetic hyperactivation include impaired diastolic function and total peripheral resistance (TPR), reflecting the resistance of arterioles (resistive vessels) to blood flow. Purpose To identify predictors of the antihypertensive efficacy of renal denervation in patients with RHTN and type 2 diabetes mellitus (DM) based on the results of a six-month follow-up. Methods The study included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61,4±6,4 years, 14 men, mean 24-hour (24-hr) blood pressure (BP) (systolic/diastolic) 158,6±15,2/79,8±12,7 mmHg, mean HbA1c 7,2±1,2%). The prospective interventional study with renal denervation (NCT02667912 and NCT01499810 at ClinicalTrial.gov) enrolled 30 patients. Office BP and ABPM, diastolic function and TPR assessment were performed in all patients at baseline and 6 months after RDN. 29 patients completed 6-month follow-up. Results RDN led to a significant reduction in systolic and diastolic 24-hr BP (−10.9/−5.7 mmHg, p=0.002/0.003). Depending on the degree of decrease in 24-hr systolic BP, the patients were retrospectively divided into 2 groups: “responders” (persons with a decrease in 24-hr SBP by 10 or more mmHg) and “non-responders” (with a lesser degree of decrease in 24-hr SBP). The proportion of respondents to the intervention was 48.3%. Initially, the group of “responders” differed from the group of “non-responders” by higher average E/e' values (15.1 and 11.9, respectively, p=0.049) and TPR indicators (2.39±0.45 and 1.93±0.35 dyn s cm–5, respectively, p=0.003). These indicators were included in a logistic model to predict the antihypertensive efficacy of renal denervation. The sensitivity was 78.6% (11 correct predictions out of 14 cases), specificity – 80% (12 correct predictions out of 15 cases), (p=0.020). Conclusion Estimation of the total peripheral resistance and the average ratio E/e' allows predicting the antihypertensive efficacy of renal denervation in patients with resistant hypertension and type 2 diabetes mellitus. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Russian Foundation for Basic Research

Abstract P209: Loss Of Rgs2 Specifically In CD4+ T Cells Decreases The Hypertensive Response To Vasopressin

Regulator of G protein Signaling (RGS) family members can modulate multiple cardiovascular hormones and are associated with hypertension and preeclampsia, a hypertensive disorder in pregnancy. We previously observed a 9-fold increase in RGS2 in CD4+ T cells isolated from women with preeclampsia compared to normotensive women. Further, in non-pregnant mice, we showed that loss of RGS2 in CD4+ T cells prevented angiotensin II-induced hypertension (measured via radiotelemetry) and resulted in increased levels of the anti-inflammatory cytokines interleukin 4 and transforming growth factor beta. We hypothesize that modulating RGS2 in CD4+ T cells may be a therapeutic strategy for hypertension. The objective of this study was to determine if loss of RGS2 specifically in CD4+ T cells protects against the development of arginine vasopressin-induced hypertension in mixed background CD4+ RGS2 knockout mice (CD4 RGS2 KO ). To generate mice wherein RGS2 is specifically knocked out in CD4+ T cells, CD4-Cre+ mice (C57BL/6J) were crossed with RGS2 flox/flox mice (B6SJLF1/J). Female 8-12 week old CD4 RGS2 KO or littermate control mice (n=5 per group) from this mixed strain were administered 24 ng/hr vasopressin for 21 days via mini-osmotic pump. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MP), and heart rate (HR) were assessed using a high throughput non-invasive blood pressure system. Prior to vasopressin infusion, KO and CTL mice showed no differences in SBP, DBP, MP, or HR. At 9-13 days of vasopressin-infusion, KO mice had a significantly lower 24-hr SBP [KO 138.7 ±4.7 vs CTL 155.9 ±3.4 mmHg, p&lt;0.05], DBP [KO 106.9 ±4.1 vs CTL 122.8 ±2.9 mmHg, p&lt;0.05], MP [KO 117.2 ±4.3 vs CTL 133.5 ±3.0 mmHg, p&lt;0.05], and HR [KO 378 ±18.7 vs CTL 445 x±12.8 BPM, p&lt;0.05] compared to CTL mice. Here, we demonstrate that in a mixed strain CD4+ RGS2 KO mouse, loss of RGS2 specifically in CD4+ T cells prevented vasopressin-induced hypertension. Therefore, RGS2 expression in CD4+ T cells may play an expanded role in the modulation of hypertension.

Yeni Tanı Dipper ve Non-dipper Hipertansif Hastalarda Strain Analiz Metoduyla Sol Ventrikül Global Sistolik Fonksiyonlarının Değerlendirilmesi

Objective: Non-dipper hypertension has been associated with enhanced target organ damage and adverse cardiovascular outcomes. The effect of dipper and non-dipper status on cardiac target organ damage has not been comprehensively investigated by two-dimensional (2D) strain echocardiography. We aimed to investigate myocardial deformational strain parameters in dipper and non-dipper untreated hypertensive patients. Material and Methods: We included 42 newly diagnosed hypertensive patients without a previous history of cardiovascular disease and coexisting chronic disease. Study population consisted of two groups of patients, 23 dipper patients and 19 non-dipper patients. Global longitudinal strain (GLS), radial strain and circumferential strain analysis were measured by 2D speckle tracking method. Results: The study population included 42 patients (15 male) with a mean age of 54.5±9 years. The assessment of left ventricular (LV) systolic function by GLS showed decreased values in non-dippers compared with dippers (-18.13±2.07 vs. -13.7±1.95; p=0.001). But no significant intergroup differences were observed in circumferential and radial strain. The analysis showed that night-time mean arterial pressure (MAP), nighttime systolic and diastolic blood pressures, 24-hr systolic blood pressure, dipping rate and nocturnal reduction rate of MAP were the parameters that correlated with GLS. Only dipping rate was independently associated with LV GLS. Conclusion: An isolated non-dipper BP was found to cause impaired LV systolic function detected by myocardial strain.

Dental caries-related primary hypertension in children and adolescents: Cross-sectional study.

Hypertension is a growing clinical problem in pediatric population. Also, the cause of hypertension is usually unknown and it may result from systemic inflammation related to tooth decay. To estimate the potential association in cross-sectional study between tooth decay and hypertension in children and adolescents. Study group-65 children diagnosed with primary arterial hypertension; control subjects-44 normotensive children. Blood pressure, dental examination, measurement of salivary cortisol, alpha-amylase, secretory IgA, and lysozyme concentrations were performed in all of the children. Hyper- and normotensive children had similar peripheral blood morphology and serum biochemical parameters, except of uric acid concentration, which was significantly higher in the study group (p=.047). Salivary evening concentrations of cortisol and alpha-amylase were significantly higher in hypertensive children (p=.002 and p=.004, respectively). Although 24-hr systolic blood pressure (SBP), including daytime and nighttime SBP, correlated with "decay," "microalbuminuria," "BMI," and "glomerular filtration rate" (r>.75, r>.7, r<.68, and r<.43, respectively), in multivariate analysis only "decay" was associated with hypertension both in children and in adolescents (p<.0001). Tooth decay in children/adolescents might be regarded as a potent trigger factor of hypertension in individuals in whom all other causes of secondary arterial hypertension have been excluded.

Inflammation and hypertension development: A longitudinal analysis of the African-PREDICT study

BackgroundThe role of inflammation in the development of hypertension remains incompletely understood. While single inflammatory mediators have been shown to associate with changes in blood pressure (ΔBP), the role of clusters of inflammatory mediators has been less comprehensively explored. We therefore determined whether individual or clusters of inflammatory mediators from a large biomarker panel were associated with ΔBP over 4.5 years, in young healthy adults. MethodsWe included 358 adults (white, n = 156; black, n = 202) with detailed information on ambulatory blood pressure (BP) at baseline and follow-up. Baseline blood samples were analysed for 22 inflammatory mediators using multiplexing technology. Principal component analysis was used to study associations between clusters of inflammatory mediators and ΔBP. ResultsIn the total cohort in multivariable-adjusted regression analyses, percentage change in 24hr systolic BP associated positively with Factors 1 (Interferon-gamma, interleukin (IL)-4, IL-7, IL-10, IL-12, IL-17A, IL-21, IL-23, macrophage inflammatory protein (MIP)-1α, MIP-1β, TNF-α, granulocyte-macrophage colony-stimulating factor (GM-CSF)) and 2 (IL-5, IL-6, IL-8, IL-13). Change in daytime systolic BP associated positively with Factors 1, 2 and 3 (C-Reactive protein, IL-1β, IL-2, MIP-3α). Subgroup analysis found these findings were limited to white study participants. Numerous associations were present between individual inflammatory mediators (Interferon-gamma, GM-CSF, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-21, IL-23, MIP-1α and MIP-1β) and ΔBP in the white but not black subgroups. ConclusionWe found independent relationships between numerous inflammatory mediators (individual and clusters) and ΔBP over 4.5 years. The relationship between inflammatory markers and ΔBP was only found in white participants. ClinicalTrials.gov (Identifier: NCT03292094)..

Antihypertensive Effect Of Amlodipine In Co-Administration With Omeprazole In Patients With Hypertension And Acid-Related Disorders: Cytochrome P450-Associated Aspects.

BackgroundCYP2C19 and CYP3A are the main enzymes involved in omeprazole metabolism, while CYP3A is the principal enzyme family for amlodipine biotransformation. Concomitant use of these drugs in patients with hypertension and acid-related disorders (ARD) might lead to drug–drug interaction.PurposeThe aim of the study was to find if adding omeprazole for treating ARD to amlodipine long-term therapy of hypertension influenced blood pressure of CYP2C19 polymorphism carriers.Patients and methodsFifty-one patients diagnosed with hypertension and ARD were enrolled in the study. Evaluation of antihypertensive therapy was performed by office (OBPM) and ambulatory (ABPM) blood pressure monitoring. Peripheral venous blood was collected for DNA extraction and real-time polymerase chain reaction was performed for CYP2C19*2G681A (rs4244285), CYP2C19*3G636A (rs4986893) and CYP2C19*17C−806T (rs12248560) polymorphisms analysis.ResultsOf 51 patients there were 21 extensive metabolizers (EMs), 18 ultrarapid metabolizers (UMs) and 12 intermediate metabolizers (IMs). The results of OBPM showed that antihypertensive effect was significantly more pronounced in IMs compared to EMs or UMs and the average group value in the following parameters: average office systolic blood pressure (BP), dynamics of the average office systolic BP. According to dynamics of diastolic BP, the antihypertensive effect was also significantly higher in IMs than in UMs and the average group value. The results of ABPM revealed that there was a significantly more pronounced antihypertensive effect in IMs compared to all other analyzed groups according to the dynamics of both daytime systolic and 24 hr diastolic BP. The average daytime diastolic BP and its dynamics, the average 24 hr systolic BP and its dynamics were higher in IMs compared to EMs and UMs.ConclusionAdding omeprazole to long-term amlodipine therapy in patients with hypertension and ARD may lead to a significantly more pronounced antihypertensive effect in patients genotyped CYP2C19 IMs.

Physical Activity Modulates Blood Pressure Regulation During Controlled Low and High Salt Diets

PURPOSE: Increased blood pressure (BP) reactivity and variability are predictive of future cardiovascular events. Excess dietary salt exaggerates neurally-mediated BP reactivity, and BP variability in salt-resistant rodents. Regular physical activity (PA) blunts BP reactivity in rodents. However, the interaction of salt and PA on neurovascular regulation has not been investigated in humans. Therefore, we sought to test the hypothesis that high habitual PA mitigates high dietary salt-induced increases in BP reactivity and BP variability in healthy, young adults. METHODS: Nine participants (5F/4M, 27±2 yrs, BMI: 23.3±0.9 kg/m2) completed randomized, controlled 10-day diets of low (2.6 g/day), and high (18 g/day) salt. Beat-to-beat laboratory BP was measured via photoplethysmography on day 10 of each diet. BP reactivity was assessed as ΔBP (mmHg) during the final minute of a 2-min hand grip exercise at 40% maximal voluntary contraction compared to a preceding baseline. Average real variability (ARV) index was used to assess BP variability derived from 24-hour ambulatory BP monitoring. Habitual PA was assessed via accelerometry (Actigraph GT3X). Differences in high vs. low salt BP reactivity (ΔBP reactivity) and ambulatory BP variability (ΔBP ARV) were correlated against PA. Twenty four-hour urinary sodium excretion was measured. RESULTS: There were no differences in 24-hr mean arterial BP on the high vs. low salt diet (82.9±2.1 vs. 79.8±2.4 mmHg; p > 0.10). Urinary Na+ excretion increased on the high vs. low salt diet (256.9±20.5 vs. 39.5±11.2 mmol/24 hours; p < 0.05). There was a trend for the high salt diet to augment systolic (p = 0.08), but not diastolic BP reactivity during hand grip exercise. Habitual PA was inversely correlated to Δ systolic BP reactivity (r = -0.74, p = 0.03), and there was a trend for an inverse correlation with Δ diastolic BP reactivity (r = -0.68, p = 0.06) during hand grip exercise. There was a trend for higher 24-hr systolic BP ARV on the high salt diet (10.6±0.8 vs. 8.9±0.6 mmHg; p = 0.09), but there was no correlation between PA with Δ systolic BP ARV (r = -0.29, p = 0.48) on the high vs. low salt diet. CONCLUSION: These preliminary data suggest that high habitual physical activity may offset some of the adverse neurovascular effects of high dietary salt in young, healthy, salt-resistant humans.

Abstract 042: Evidence of Angiotensin II (AngII)-dependent Obesity-induced Hypertension in Female Mice Exposed to Postnatal Neglect

Previously, we have shown that female mice subjected to maternal separation with early weaning (MSEW), a model of postnatal neglect, display exacerbated diet-induced obesity and high blood pressure (BP) compared with control mice. Female MSEW mice show activated renin-angiotensin system components, including increased plasma renin activity and adipose tissue-derived angiotensinogen secretion. The goal of this study was to test whether augmented obesity-induced hypertension in female MSEW mice is AngII-dependent. Mouse MSEW was achieved by repeated, daily separations from the dam and 4-day early weaning. Normally reared controls (C) were weaned at postnatal day 21. Each experimental group of female weanlings was comprised of 6 mice each and derived from 3 different litters, that were placed on high fat diet (HFD, 60% kcal from fat). After 18 weeks, mice were implanted with radiotelemetry for BP measurement. At week 20, average 24-hr systolic blood pressure (SBP) was 134±2 mmHg in MSEW mice and 126±2 in C (P&lt;0.05). No significant changes in mean arterial pressure, diastolic blood pressure or heart rate were observed between groups. Next, we also determined the BP sensitivity to the acute administration of AngII (1, 10 and 50 ug/kg, s.c.). AngII-induced BP changes, assessed by BP area under the curve, were similar between MSEW and C mice at all doses (50 ug/kg dose:145±10 vs. 132±15 mmHgx30 min, respectively). Chronic enalapril treatment (2.5 mg/kg/day, drinking water, 7 days) was conducted to block endogenous AngII synthesis. Enalapril reduced SBP 15±2 mmHg in MSEW mice but only 6±1 mmHg in C mice (p&lt;0.05). The BP response to acute AngII doses increased similarly in MSEW and C enalapril-treated mice, (50 ug/kg dose: 200±13 vs. 207±22 mmHgx30 min, respectively). In addition, BP and HR responses to acute injections (i.p) of mecamylamine (5 mg/kg), propranolol (5 mg/kg) or atropine (1 mg/kg) were similar between untreated MSEW and C mice, suggesting that exacerbated BP in female MSEW mice is independent of sympathetic or parasympathetic dysfunction. Taken together, these data provide evidence that increased BP in female MSEW mice results from elevated circulating AngII rather than enhanced AngII sensitivity or sympathetic nerve activity.

Abstract P149: Bilateral Renal Denervation Attenuates Hypertension in Male Rats Deficient of Functional Endothelin B Receptors but Does Not Affect Salt-Sensitivity

Independent studies of renal sympathetic nerves and the endothelin (ET) system have demonstrated important contributions of each in the progression of hypertension. Very few studies, however, have investigated the interaction between the ET system and renal nerves in relation to blood pressure control and electrolyte homeostasis. Although endothelin B (ETB) receptors in the renal medulla promote natriuresis, ETB receptors on sympathetic neurons are thought to increase neuronal activity. We hypothesized that renal denervation reduces blood pressure in a salt-sensitive, hypertensive model of ET dysfunction, the ETB-deficient (ETB-def) rat, which lacks functional ETB receptors in all tissues except neurons. After bilateral renal sympathetic denervation (Dnx) or sham operation of ETB-def and transgenic control (TG) rats, baseline blood pressure was recorded via telemetry for 5 days on a normal salt (0.49% NaCl) diet followed by a high salt (4.0%) diet. At baseline, ETB-def Dnx rats had a lower 24-hr systolic blood pressure (SBP) (152.6 ± 3.6 mmHg) relative to ETB-def sham (167.8 ± 2.6 mmHg; p &lt; 0.005; n = 7/group). Denervation did not significantly affect TG rats relative to sham on normal salt (138.8 ± 2.5 vs. 144.7 ± 0.5 mmHg respectively; p = 0.53; n = 6/group). Following 10 days of high salt diet, ETB-def sham rats had an increased 24-hr SBP (+10.59 ± 2.8 mmHg relative to baseline; p &lt; 0.005). There was a similar increase in SBP in ETB-def Dnx rats (+10.03 ± 2.3 mmHg relative to baseline; p &lt; 0.005), although the ETB-def Dnx group remained lower than ETB-def sham. High salt had no effect on TG sham or Dnx animals (-2.2 ± 1.3 and -0.6 ± 2.8 mmHg relative to baseline). Preliminary evidence from a subset of the animals in this experiment indicated a dramatically reduced inner medullary ET-1 content in ETB-def sham rats vs. TG sham (97.9 ± 15.4 vs. 327.0 ± 25.4 ng/mg total protein; p &lt; 0.005; n = 3-4/group) in both ETB-def and TG groups, Dnx tended to increase inner medullary ET-1 content (181.8 ± 75.8 and 402.7 ± 19.6 ng/mg total protein respectively). We conclude that in a model of ET dysfunction, the renal nerves are integral mediators of hypertension during normal salt diet, but do not mediate the increase in pressure following high salt diet in this model of salt-sensitive hypertension.

PS 02-59 NON-DIPPING-TYPE BLOOD PRESSURE VARIATIONS IN YOUNG KAZAKHS DERIVED FROM INCREASED SYMPATHETIC ACTIVITY IN THE MORNING

Objective: Many cases of non-dipping-type blood pressure variations and hypertension have been documented amongst elderly and middle-aged Kazakhs. The purpose of this study was to discover whether there are also large numbers of non-dippers among young Kazakhs and to compare the blood pressure variations seen in these individuals with those observed in age-matched dipping-type Kazakhs. Design and Method: We performed ambulatory blood pressure monitoring and defined non-dippers as individuals that exhibited a nighttime systolic blood pressure (SBP) reduction of Results: Dippers and non-dippers accounted for 73% and 27% of the subjects, respectively. The physiological characteristics of the dippers and non-dippers did not differ, nor did their 24-hr SBP values. However, daytime SBP was lower and nighttime SBP was higher in the non-dippers than the dippers (non-dippers vs. dippers: daytime SBP: 117 ± 5 vs. 123 ± 10 mmHg, P = 0.022; nighttime SBP: 109 ± 7 vs. 97 ± 7 mmHg, P = 0.005). MEM analysis of the non-dippers detected SBP variations with a 24-hr frequency periodicity, a very weak power spectral density (PSD), and an ultradian periodicity. The HRV analysis revealed that the low frequency/high frequency ratio was lower in the non-dippers than in the dippers during the morning. Conclusions: Young non-dipping Kazakhs exhibited SBP variations with a 24-hr frequency periodicity, a very weak PSD, and an ultradian periodicity. Furthermore, the non-dippers displayed less sympathetic nerve activity during the morning than the dippers.