24-h Mean Arterial Pressure Research Articles

Phenotyping Kidney Function in Young Adults With High Blood Pressure: The African-PREDICT Study.

Biomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross-sectional assessment, twenty-four-hour (24-h) blood pressure measurements of 1055 participants (mean age=24.6years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin-to-creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24-h systolic blood pressure (SBP) (β=0.14; p=0.042), 24-h diastolic blood pressure (DBP) (β=0.14; p=0.040), and 24-h mean arterial pressure (MAP) (β=0.16; p=0.020) associated positively with uA1M/Cr in the hypertensive group, while 24-h MAP positively associated with uACR (β=0.17; p=0.017). In exploratory factor analysis, positive associations of 24-h DBP and 24-h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24-h DBP: β=0.18; p=0.026, 24-h MAP: β=0.17; p=0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults. Trial Registration: ClinicalTrials.gov identifier: NCT03292094.

Mediating effects of BMI on the association between DNA methylation regions and 24-h blood pressure in African Americans.

DNA methylation is an important epigenetic mechanism that may influence blood pressure (BP) regulation and hypertension risk. Obesity, a major lifestyle factor associated with hypertension, may interact with DNA methylation to affect BP. However, the indirect effect of DNA methylation on 24-h BP measurements mediated by obesity-related phenotypes such as BMI has not been investigated. Causal mediation analysis was applied to examine the mediating role of BMI in the relation between DNA methylation and 24-h BP phenotypes, including SBP, DBP and mean arterial blood pressure (MAP), in 281 African American participants. Analysis of 38 215 DNA methylation regions, derived from 1 549 368 CpG sites across the genome, identified up to 138 methylation regions that were significantly associated with 24-h BP measurements through BMI mediation. Among them, 38 (19.2%) methylation regions were concurrently associated with SBP, DBP and MAP. Genes associated with BMI-mediated methylation regions are potentially involved in various chronic diseases such as coronary artery disease and renal disease, which are often caused or exacerbated by hypertension. Notably, three genes ( CDH4 , NOTCH1 and COLGALT1 ) showed both direct associations with 24-h BP measurements and indirect associations through BMI after adjusting for age and sex covariates. Our findings suggest that DNA methylation may contribute to the regulation of 24-h BP in African Americans both directly and indirectly through BMI mediation.

Differential Role for the Clock Gene, BMAL1, on Kidney Function in Male versus Female Rats

Many activities of modern life, such as social visits with friends at night, long working hours, jet lag, and shift work cause circadian rhythm disturbances, which increase the risk of renal decline and eventual disease. Chronic kidney disease (CKD) is defined by decreases in glomerular filtration rate (GFR) which is higher during the daytime and lower at night in healthy individuals. Prior studies indicate that processes critical for maintaining blood pressure ( e.g. autoregulation) contribute to this time-of-day-dependence mediated by a molecular timekeeping mechanism known as the molecular circadian clock that resides in all tissues including the kidney. We hypothesized that loss of the molecular clock would impair normal kidney physiology through misalignment of functional rhythms with normal environmental patterns associated with day and night. We used a rat model of circadian disruption to interrogate our hypothesis. Male and female brain and muscle ARNT-like protein 1 knockout (BMAL1 KO) and littermate control (CON) rats aged 12-14 weeks underwent GFR measurements using FITC-labeled sinistrin clearance at two times of the day corresponding to the dark (active) and light (inactive) periods. Following GFR measurements, rats were placed in metabolic cages with food to record water intake and urine excretion over 12h active and inactive periods. Implantable telemeters were used for 24h measurement of systolic and diastolic blood pressure, locomotor activity and body temperature. Autoregulatory behavior was assessed using the isolated juxtamedullary nephron preparation to determine afferent arteriole diameter responses to changes in perfusion pressure. Diurnal measurements of GFR revealed that male BMAL1 KO rats had a significantly lower GFR in the active period as compared to CON males (1.87±0.37 vs 2.55±0.47 ml/min/100g; 2-way ANOVA, p<0.05; n=8-9). As a result, there was no diurnal variation in the KO males as seen in the CON males (Δ GFR 0.63±0.24 vs 0.04±0.21 ml/min/100g/12h CON vs KO respectively) (Sidak post-hoc, p<0.05; n=8-9) in parallel with a lack of diurnal variation in urine volume and Na excretion. Both male (n=8) and female (n=6-9) BMAL1 KO rats also displayed a significantly lower 24h mean arterial pressure (Males; 103±1 vs 107±1 mmHg, p<0.05; Females; 110±1 vs 100±2 mmHg, p<0.05) compared to CON with diurnal variation and autoregulatory reactivity preserved. Male BMAL1 KO rats consumed significantly more water compared to CON (n=5-9, 22.5±5.4 vs 14.7±4.0 mL/12h, p<0.05) concomitant with increased urine excretion (n=5-9, 13.3±6 vs 4.2±0.8 mL/12h, p<0.05) and reduced urine osmolality (n=5-7, 967±398 vs 2140±811 mmol/kg, p<0.05) regardless of time of day. Taken together these data suggest that BMAL1 is necessary for maintaining renal functional rhythms and urine concentrating ability in a sex-dependent manner. R01 DK134562 P01 HL158500. 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.

Blood pressure in atrial fibrillation and in sinus rhythm during ambulatory blood pressure monitoring: data from the TEMPLAR project

The coexistence of hypertension and atrial fibrillation (AF) is common and accounts for a worse prognosis. Uncertainties exist regarding blood pressure (BP) measurements in AF patients by automated oscillometric devices. The Microlife WatchBP 03 AFIB ambulatory BP monitoring (ABPM) device including an AF algorithm with each measurement was used in 430 subjects aged >65 years referred for ABPM and with assumed paroxysmal AF to perform intra-individual comparisons of BP during both AF-indicated and sinus rhythm. Only subjects with >30% of measurements indicating AF and episodes >30 min for assumed AF and for sinus rhythm were included. Mean age was 78 ± 7 years, 43% were male, 77% hypertensive, and 72% were treated. Compared to sinus rhythm, 24-h mean arterial pressure was similar (87.2 ± 9.5 vs 87.5 ± 10.6 mm Hg, p = 0.47), whereas 24-h systolic BP tended to be lower (123.6 ± 13.9 vs 124.7 ± 16.1 mm Hg, p = 0.05) and night-time diastolic BP higher (64.6 ± 10.9 vs 63.3 ± 10.4 mm Hg, p = 0.01) in assumed AF. Diastolic (not systolic) BP variability was higher in AF (p < 0.001). Results were similar with heart rates <90 and ≥90 bpm. In conclusion, this is the first study to use intra-individual comparisons of averaged BP during an ABPM in assumed paroxysmal AF and sinus rhythm. Our results imply that ABPM is feasible and informative also in patients with AF. We also suggest that an AF detection algorithm offers a new approach to evaluate the reliability of averaged BP values in AF compared to SR during an ABPM.

Effect of 24-h blood pressure dysregulations and reduced ocular perfusion pressure in open-angle glaucoma progression.

Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests (n = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG (P < 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from -2.84 dB [95% confidence interval (CI) -4.12 to -1.57] to -2.16 dB (95% CI -3.46 to -0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP.

Inverse salt sensitivity in normotensive adults: role of demographic factors.

Salt sensitivity and inverse salt sensitivity [ISS; a reduction in blood pressure (BP) on a high sodium diet] are each associated with increased incidence of hypertension. The purpose of this analysis was to determine the prevalence of ISS in normotensive adults and whether ISS is associated with any demographic characteristic(s). Healthy normotensive, nonobese adults [ n = 84; 43 women; age = 37 ± 13 years; baseline mean arterial pressure (MAP) = 89 ± 8 mmHg] participated in a controlled feeding study, consuming 7-day low-sodium (20 mmol sodium/day) and high-sodium (300 mmol sodium/day) diets. Twenty-four-hour ambulatory BP was assessed on the last day of each diet. ISS was defined as a reduction in 24-h MAP more than 5 mmHg, salt sensitivity as an increase in MAP more than 5 mmHg and salt resistance as a change in MAP between -5 and 5 mmHg from low sodium to high sodium. Using this cutoff, 10.7% were ISS, 76.2% salt resistant, and 13.1% salt sensitive. Prevalence of ISS was similar between sexes and age groups ( P > 0.05). However, ISS was more prevalent in those with normal BMI (15.8% ISS) compared with those with overweight BMI (0% ISS; P < 0.01). Interestingly, classification of participants using a salt sensitivity index (ΔMAP/Δ urinary sodium excretion) categorized 21.4% as ISS, 48.8% salt resistant, and 29.8% salt sensitive. Overall, we found that the prevalence of ISS was 10.7% (5 mmHg cutoff) or 21.4% (salt sensitivity index), and that ISS was associated with lower BMI. These results highlight the importance of future work to understand the mechanisms of ISS and to standardize salt sensitivity assessment.

G protein-coupled estrogen receptor 1 regulates renal endothelin-1 signaling system in a sex-specific manner.

Demographic studies reveal lower prevalence of hypertension among premenopausal females compared to age-matched males. The kidney plays a central role in the maintenance of sodium (Na+) homeostasis and consequently blood pressure. Renal endothelin-1 (ET-1) is a pro-natriuretic peptide that contributes to sex differences in blood pressure regulation and Na+ homeostasis. We recently showed that activation of renal medullary G protein-coupled estrogen receptor 1 (GPER1) promotes ET-1-dependent natriuresis in female, but not male, rats. We hypothesized that GPER1 upregulates the renal ET-1 signaling system in females, but not males. To test our hypothesis, we determined the effect of GPER1 deletion on ET-1 and its downstream effectors in the renal cortex, outer and inner medulla obtained from 12-16-week-old female and male mice. GPER1 knockout (KO) mice and wildtype (WT) littermates were implanted with telemetry transmitters for blood pressure assessment, and we used metabolic cages to determine urinary Na+ excretion. GPER1 deletion did not significantly affect 24-h mean arterial pressure (MAP) nor urinary Na+ excretion. However, GPER1 deletion decreased urinary ET-1 excretion in females but not males. Of note, female WT mice had greater urinary ET-1 excretion than male WT littermates, whereas no sex differences were observed in GPER1 KO mice. GPER1 deletion increased inner medullary ET-1 peptide content in both sexes but increased outer medullary ET-1 content in females only. Cortical ET-1 content increased in response to GPER1 deletion in both sexes. Furthermore, GPER1 deletion notably increased inner medullary ET receptor A (ETA) and decreased outer medullary ET receptor B (ETB) mRNA expression in male, but not female, mice. We conclude that GPER1 is required for greater ET-1 excretion in females. Our data suggest that GPER1 is an upstream regulator of renal medullary ET-1 production and ET receptor expression in a sex-specific manner. Overall, our study identifies the role of GPER1 as a sex-specific upstream regulator of the renal ET-1 system.

PS-C12-3: OPEN-ANGLE GLAUCOMATOUS OPTIC DAMAGE IN RELATION TO SYSTEMIC AND OCULAR PERFUSION PRESSURE

Objective: Glaucoma is the leading cause of irreversible blindness worldwide. One of the pivotal physiopathological mechanisms involved is reduced ocular perfusion pressure (OPP) at the optic nerve head, which depends on the mean arterial pressure (MAP) and intraocular pressure levels. The interplay association of variability and dips in the 24-h MAP with OPP in relation to glaucoma progression remains undocumented. Therefore, we conducted a retrospective longitudinal study to investigate variability and dips in the 24-h MAP and OPP in relation to the progression of open-angle glaucoma damage. Methods: A total of 265 patients with normal-tension glaucoma (NTG; n = 155) and primary open-angle glaucoma (POAG; n = 110) followed at the University Hospital Leuven with longitudinal visual field tests (n = 7000 measures, including both eyes) who underwent ambulatory blood pressure monitoring were studied. The main outcome was longitudinal changes in the mean deviation (MD), expressed in decibels (dB), which was retrieved from visual field tests. The intraocular pressure (IOP) was measured with applanation tonometry. MAP variability independent of the mean (VIMmap) was computed and the five lowest dips in MAP readings were further analyzed. OPP was the difference between 2/3 of the 24-h MAP minus 24-h intraocular pressure levels. Statistics methods included mixed models. Results: The mean age was 64.0y (53% were women). The IOP during eight years of follow-up was 11.3 mmHg. All IOP measures were higher in POAG than NTG (P &lt; 0.046). POAG patients had lower OPP than NTG (P &lt; 0.045). In adjusted mixed models, higher 24-h VIMmap was associated with longitudinal changes in MD in POAG (-2.07 dB changes, P &lt; 0.001). The longitudinal changes in MD associated with dip measures ranged from -2.84 dB (95% confidence interval [CI], -4.12, -1.57; P &lt; 0.001) to -2.16 dB (95% CI, -3.46,-0.85; P = 0.001) in POAG. Lower 24-h MAP combined with high variability and extreme dips in MAP resulted in worse progression of MD (P = 0.009). Reduced OPP was associated with -2.51 to -2.00 dB changes in the MD (P &lt; 0.001) in POAG. Progression in MD was worse in patients experiencing reduced OPP along with high variability and dips in MAP. Conclusions: Progression of open-angle glaucoma damage is associated with high variability and dips in MAP, and reduced OPP. This progression exacerbates if the lower OPP occurs along with extreme dips in the MAP. 24-h ambulatory blood pressure and intraocular pressure should be implemented in the follow-up of glaucoma patients experiencing progression of the disease despite the intraocular pressure remaining normal.

Time-varying parameters of glycemic control and glycation in relation to arterial stiffness in patients with type 1 diabetes.

A substantial proportion of type 1 diabetes (T1D) patients free from known cardiovascular disease (CVD) show premature arterial stiffening, with age, blood pressure, and HbA1c-as gold standard of glycemic control-as main predictors. However, the relationship of arterial stiffness with other time-varying parameters of glycemic control and glycation has been far less explored. This study investigated the relationship of arterial stiffness with several short- and long-term parameters of glycemic control and glycation in patients with T1D, such as advanced glycation end-products (AGEs) and continuous glucose monitoring (CGM)-derived parameters. Cross-sectional study at a tertiary care centre including 54 patients with T1D free from known CVD. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (cf-PWV). Current level and 10-year history of HbA1c were evaluated, and skin AGEs, urinary AGEs, and serum soluble AGE-receptor (sRAGE) concentrations. CGM for 7days was used to determine time in range, time in hyper- and hypoglycemia, and glycemic variability. Cf-PWV was associated with current HbA1c (rs = + 0.28), mean 10-years HbA1c (rs = + 0.36), skin AGEs (rs = + 0.40) and the skin AGEs-to-sRAGE ratio (rs = + 0.40), but not with urinary AGE or serum sRAGE concentrations; and not with any of the CGM-parameters. Multiple linear regression for cf-PWV showed that the model with the best fit included age, T1D duration, 24-h mean arterial pressure and mean 10-years HbA1c (adjusted R2 = 0.645, p < 0.001). Longer-term glycemic exposure as reflected by current and mean 10-years HbA1c is a key predictor of arterial stiffness in patients with T1D, while no relationship was found with any of the short-term CGM parameters. Our findings stress the importance of early and sustained good glycemic control to prevent premature CVD in patients with T1D and suggest that HbA1c should continue to be used in the risk assessment for diabetic complications. The role of skin glycation, as a biomarker for vascular aging, in the risk assessment for CVD is an interesting avenue for further research.

VASCULAR AGE IN ADOLESCENTS WITH PRIMARY HYPERTENSION

Objective: There is evidence that children with primary hypertension (PH) are more mature than their normotensive peers in terms of bone and the immune system age. The aim of our study was to evaluate vascular age and its relationship with hypertension-mediated organ damage (HMOD) in adolescents with PH. Design and method: We assessed 362 children [90 girls; 15.5 (13.9;16.8) years] referred for work-up of office hypertension and 64 normotensive (NT) subjects [12 girls; 14.5 (13.8;15.6) years] not different in terms of age, body mass (BM) and BMI. We analyzed age- and height-related pulse wave velocity (PWV); the expected vascular age (based on measured PWV) was obtained from pooled pediatric and adult PWV norms and the difference (VascAgeDiff) between the vascular and chronological age was calculated. In all patients we obtained ambulatory blood pressure monitoring (ABPM) and HMOD: left ventricular mass index (LVMi), carotid intima-media thickness (cIMT) and pulse wave analysis (PWA) parameters: stroke volume (SV), cardiac output (CO), aortic BP (AoBP), total peripheral resistance (TPR). Results: Based on office, ABPM and AoBP, patients were classified into white coat hypertension (WCH) - 166 patients, ambulatory prehypertension (AmbPreHT) – 32; spurious hypertension (sHT – isolated systolic hypertension and normal AoBP) – 55; true hypertension (tHT – elevated office, ambulatory and AoBP) – 99. VascAgeDiff progressively increased from NT through sHT, WCH, AmbPreHT to tHT (3.5; 6.2; 7.2; 10.0; 10.7 years; p &lt; 0.01). VascAgeDiff correlated (univariate analysis) significantly with weight, BMI z-score, office systolic (SBP) and diastolic blood pressure (DBP), AoBP, 24-h mean arterial pressure, 24-h DBP, CO, serum uric acid and LDL cholesterol level (p &lt; 0.05). Multivariate regression analysis including above mentioned parameters revealed that significant predictors of VascAgeDiff were: weight, SBP, DBP, AoBP, CO and serum LDL cholesterol (p &lt; 0.05). Conclusions: Out study suggests early vascular aging in adolescents with PH, even at mildly increased BP levels (WCH, prehypertension). Vascular changes were associated with increased weight, DBP, AoBP, CO and LDL cholesterol.

OPEN-ANGLE GLAUCOMATOUS OPTIC NEUROPATHY IS RELATED TO DIPS RATHER THAN INCREASES IN THE MEAN ARTERIAL PRESSURE OVER 24-H

Objective: Mean arterial pressure (MAP) drives ocular perfusion. Excessive 24-h MAP variability relates to glaucoma, however, whether this is due to dips or increases in the blood pressure (BP) is undocumented. We investigated the association of open-angle glaucoma (OAG) in relation to the five largest MAP dips/increases over 24-h, henceforth called dips/blips. Design and method: In the Maracaibo Aging Study (MAS), 93 participants aged 40y or older (women, 87.1%; mean age, 61.9y) underwent baseline ophthalmological and 24-h ambulatory BP monitoring assessments. OAG was the presence of optic nerve damage and visual field defects. Statistical methods included logistic regression and the generalized R2 statistic. For replication, 48 OAG cases at the Leuven Glaucoma Clinic were matched with 48 controls recruited from Flemish population. Results: In MAS, 26 had OAG. OAG compared to non-OAG participants experienced longer and deeper dips (116.5 vs. 102.7 minutes; to 60.3 vs. 66.6 mmHg; 21.0 vs. 18.0 mmHg absolute or 0.79 vs. 0.81 relative dips compared to the preceding reading). The adjusted odds ratios associated with dip measures ranged from 2.25 (95% confidence interval [CI], 1.31–4.85; P = 0.009) to 3.39 (95% CI, 1.36 8.46; P = 0.008). On top of covariables and 24 MAP level/variability, the dip measures increased the model performance (P values below 0.025). Blips did not associate with OAG. The case-control study replicated the MAS observations. Conclusions: Dips rather than increases in the 24-h MAP level were associated with increased risk for OAG. An ophthalmological examination combined with 24-h BP monitoring might be precautious steps required in normotensive and hypertensive patients at risk of OAG.

Sphinganine is associated with 24-h MAP in the non-sleepy with OSA.

Excessive daytime sleepiness is a debilitating symptom of obstructive sleep apnea (OSA) linked to cardiovascular disease, and metabolomic mechanisms underlying this relationship remain unknown. We examine whether metabolites from inflammatory and oxidative stress-related pathways that were identifiedin our prior work could be involved in connecting the two phenomena. This study included 57 sleepy (Epworth Sleepiness Scale (ESS) ≥ 10) and 37 non-sleepy (ESS < 10) participants newly diagnosed and untreated for OSA that completed an overnight in-lab or at home sleep study who were recruited from the Emory Mechanisms of Sleepiness Symptoms Study (EMOSS). Differences in fasting blood samples of metabolites were explored in participants with sleepiness versus those without and multiple linear regression models were utilized to examine the association between metabolites and mean arterial pressure (MAP). The 24-h MAP was higher in sleepy 92.8mmHg (8.4) as compared to non-sleepy 88.8mmHg (8.1) individuals (P = 0.03). Although targeted metabolites were not significantly associated with MAP, when we stratified by sleepiness group, we found that sphinganine is significantly associated with MAP (Estimate = 8.7, SE = 3.7, P = 0.045) in non-sleepy patients when controlling for age, BMI, smoking status, and apnea-hypopnea index (AHI). This is the first study to evaluate the relationship of inflammation and oxidative stress related metabolites in sleepy versus non-sleepy participants with newly diagnosed OSA and their association with 24-h MAP. Our study suggests that Sphinganine is associated with 24 hourMAP in the non-sleepy participants with OSA.

Therapeutic Phlebotomy in Patients with Grade 1 Hypertension: A Randomized-Controlled Trial.

Aim: Study aim was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. Methods: In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. Primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed. Results: Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs. Conclusions: Study results showed that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.

Normal-tension glaucomatous optic neuropathy is related to blood pressure variability in the Maracaibo Aging Study.

Hypoperfusion of the optic nerve might be involved in the pathogenesis of normal-tension glaucomatous optic neuropathy (GON). Mean arterial pressure (MAP) drives ocular perfusion, but no previous studies have addressed the risk of GON in relation to blood pressure (BP) variability, independent of BP level. In a cross-sectional study, 93 residents of Maracaibo, Venezuela, underwent optical coherence tomography, visual field assessments and 24-h ambulatory BP monitoring between 2011 and 2016. We investigated the association of normal-tension GON with or without visual field defects with reading-to reading variability of 24-h MAP, as captured by variability independent of the MAP level (VIMmap). Odds ratios (ORs) were adjusted for 24-h MAP level and for a propensity score of up to five risk factors. Among the 93 participants (87.1% women; mean age, 61.9 years), 26 had open-angle normal-tension GON at both eyes; 14 had visual field defects; and 19 did not have visual field defects. The OR ratios for normal-tension GON, expressed per 1-SD increment in VIMmap (2 mm Hg), were 2.17 (95% confidence interval, 1.33-3.53) unadjusted; 2.20 (1.35-3.61) adjusted for 24-h MAP level only; 1.93 (1.10-3.41) with additional adjustment for age, educational attainment, high-density lipoprotein (HDL) cholesterol and office hypertension; and 1.95 (1.10-3.45) in models including intraocular pressure. We confirmed our a priori hypothesis that BP variability, most likely operating via hypoperfusion of the optic nerve, is associated with normal-tension GON. 24-H ambulatory BP monitoring might therefore help stratify the risk of normal-tension GON.

ADDITIVE BLOOD-PRESSURE LOWERING EFFECT OF AEROBIC TRAINING ON ANTIHYPERTENSIVE MEDICATION IN METABOLIC SYNDROME INDIVIDUALS

Objective: In hypertensive individuals with metabolic syndrome (MetS), antihypertensive medications (AHM) are prescribed in conjunction with lifestyle advice (i.e., exercise) to reduce blood pressure (BP). However, if the combination of both treatments results in better BP control remains unknown. The objective of this study was to analyze the separated and combined effects of AHM and exercise training on ambulatory blood pressure (ABP). Design and method: Thirty-six hypertensive individuals with MetS under long-term prescription with AHM targeting the renin-angiotensin-aldosterone system (RAAS) were recruited. Before and after a 4-month aerobic interval training their AHM prescription was withdrawn during 3 days (i.e., PLAC trials) and 24-h ABP compared to when individuals held their habitual dose of medication (i.e., AHM trial) using a double-blind, randomized design. Plasma renin activity (PRA) and aldosterone concentration were measured to confirm withdrawal effects on RAAS. Urine albumin and creatinine ratio (UACR) was measured to assess kidney function. Results: Before the intervention AHM reduced 24-h mean arterial pressure (MAP) by -5 ± 5 mmHg (P &lt; 0.001, Figure 1). After 4-months of aerobic training AHM reduced MAP an additional -3 ± 5 mmHg (92 ± 9 to 89 ± 8 mmHg; P = 0.014). However, BP lowering effect was not observed when AHM was withdrawn after training (97 ± 8 vs 96 ± 8 mmHg; P = 507). AHM increased PRA before and after training (P &lt; 0.005) whilst had no effect on plasma aldosterone concentration (P = 1.000). Aerobic training did not significantly reduced RAAS hormones or the UACR. Conclusions: Aerobic training and AHM in conjunction reduce BP to a higher extent than each treatment in isolation. These findings support the combination of habitual AHM with exercise training with the goal to reduce BP in hypertensive MetS individuals.

Effects of antihypertensive medication and high‐intensity interval training in hypertensive metabolic syndrome individuals

Pharmacological and non-pharmacological therapies are simultaneously prescribed when treating hypertensive individuals with elevated cardiovascular risk (ie, metabolic syndrome individuals). However, it is unknown if the interactions between antihypertensive medication (AHM) and lifestyle interventions (ie, exercise training) may result in a better ambulatory blood pressure (ABP) control. To test this hypothesis, 36 hypertensive individuals with metabolic syndrome (MetS) under long-term prescription with AHM targeting the renin-angiotensin-aldosterone system (RAAS) were recruited. Before and after 4months of high-intensity interval training (HIIT), participants completed two trials in a double-blind, randomized order: (a) placebo trial consisting of AHM withdrawal for 3days and (b) AHM trial where individuals held their habitual dose of AHM. In each trial, 24-h mean arterial pressure (MAP) was monitored and considered the primary study outcome. Secondary outcomes included plasma renin activity (PRA) and aldosterone concentration to confirm withdrawal effects on RAAS, along with the analysis of urine albumin-to-creatinine ratio (UACR) to assess kidney function. The results showed main effects from AHM and HIIT reducing 24-h MAP (-5.7mmHg, p<0.001 and -2.3mmHg, p=0.007, respectively). However, there was not interaction between AHM and HIIT on 24-h MAP (p=0.240). There was a main effect of AHM increasing PRA (p<0.001) but no effect on plasma aldosterone concentration (p= 0.368). HIIT did not significantly improve RAAS hormones or the UACR. In conclusion, AHM and HIIT have independent and additive effects in lowering ABP. These findings support the combination of habitual AHM with exercise training with the goal to reduce ABP in hypertensive MetS individuals.

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study.

Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile. Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (β = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (β = 0.13 [95%CI 0.06-0.19]; p = 0.0003). Children on HD had a significant and sustained increase in BP over 1year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.

Vascular Inflammation and Cardiovascular Burden in Metastatic Breast Cancer Female Patients Receiving Hormonal Treatment and CDK 4/6 Inhibitors or Everolimus

Background: Chemotherapy regimens for breast cancer treatment can promote vascular dysfunction and lead to high cardiovascular risk.Purpose: To investigate the cardiovascular burden and vascular inflammation in metastatic breast cancer patients receiving CDK 4/6 inhibitors or everolimus in addition to standard hormonal treatment.Methods: 22 consecutive female patients with metastatic breast cancer were enrolled. Relative wall thickness (RWT) and left ventricle mass (LVM) measurements by transthoracic echocardiography were obtained followed by 24-h ambulatory blood pressure monitoring, and 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Uptake of the radiotracer in the aortic wall was estimated as tissue-to-background ratio (TBR). Each patient was assessed for the aforementioned parameters before the initiation and after 6 months of treatment.Results: At follow up, patients assigned to CDK 4/6 treatment demonstrated increased 24-h systolic blood pressure (SBP) (p = 0.004), daytime SBP (p = 0.004) and night time SBP (p = 0.012) (Group effect). The 24-h mean arterial pressure measurements were also higher in CDK 4/6 population, in comparison to everolimus that displayed firm values (Group effect- p = 0.035, Interaction effect-p = 0.023). Additionally, 24 h diastolic blood pressure recordings in CDK 4/6 therapy were higher opposed to everolimus that remained consistent (Interaction effect- p = 0.010). In CDK 4/6 group, TBR aorta also increased significantly, whereas TBR values in everolimus remained stable (Interaction effect-p = 0.049). Both therapeutic regimens displayed statistically significant damaging effect to RWT and LVM.Conclusion: CDK 4/6 inhibitors and hormonal treatment can lead to increased vascular inflammation, and higher blood pressure compared to the combination of everolimus and hormonal treatment. Moreover, both treatment strategies promoted left ventricle remodeling.

Do children with solitary or hypofunctioning kidney have the same prevalence for masked hypertension?

Having a low nephronnumber is a well-known risk factor for hypertension. There is an inverse relationship between the filtration surface area and systemic hypertension. A significant percentage of masked hypertension can be detected in children with nephron loss by ambulatory blood pressure monitoring (ABPM). We prospectively investigated ABPM results of children having reduced kidney mass with normal office blood pressures (BPs) and kidney function. Forty-three children with congenital solitary kidney (group 1), 11 children with acquired solitary kidney (group 2), and 76 children with hypofunctioning kidney (group 3) were compared with age, gender, and BMI-matched healthy control group (group 4). The dietary salt intake of 76 patients was evaluated as salt equivalent (g/day). The primary endpoint was change from baseline in mean 24-h ABPM variables and the proportion of patients with masked hypertension when assessed by ABPM. The masked hypertension ratio of all patients was 12.3% when assessed with ABPM. Night hypertension was significantly higher in all patient groups than in the control group (p = 0.01). Diastolic BP loads of groups 1 and 3 were higher than in controls (p = 0.024). Systolic BP loads were higher only in group 1 than in the control group (p = 0.003). The dietary salt equivalent of patients in group 1 correlated positively with 24-h SBP and mean arterial pressure (MAP) values. Patients with excessive dietary salt intake in group 1 had a significantly higher diastolic BP load than those without excessive salt intake in group 1 (p = 0.002). Masked hypertension can be seen in children with a solitary kidney or when one of the kidneys is hypofunctioning. Systolic BP loads are higher in children with congenital solitary kidney, and salt intake correlates with systolic BP profiles especially in those. Our results suggest that being born with a congenital solitary kidney increases predisposition to hypertension and salt sensitivity.

Changes in sleepiness and 24-h blood pressure following 4 months of CPAP treatment are not mediated by ICAM-1.

Continuous positive airway pressure (CPAP) therapy reduces circulating intercellular adhesion molecule 1 (ICAM-1) in adults with obstructive sleep apnea (OSA). ICAM-1 levels may affect the daytime sleepiness and elevated blood pressure associated with OSA. We evaluated the association of changes from baseline in ICAM-1 with changes of objective and subjective measures of sleepiness, as well as 24-h ambulatory blood pressure monitoring (ABPM) measures, following 4 months of CPAP treatment. The study sample included adults with newly diagnosed OSA. Plasma ICAM-1, 24-h ABPM, Epworth Sleepiness Scale (ESS), and psychomotor vigilance task (PVT) were obtained at baseline and following adequate CPAP treatment. The associations between changes in natural log ICAM-1 and changes in the number of lapses on PVT, ESS score, and 24-h mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, anti-hypertensive medications, AHI, and daily hours of CPAP use. Among 140 adults (83% men),mean (± SD) body mass index (BMI) was 31.5± 4.2 kg/m2, and apnea-hyopnea index (AHI) was 36.8± 15.3 events/h.Sleepiness measures, although not ICAM-1 or ABPM measures, improved significantly following CPAP treatment. We observed no statistically significant associations between the change in ICAM-1 and changes in sleepiness, MAP, or other ABPM measures. Changes in ICAM-1 levels were not related to changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Future work should explore whether or notother biomarkers may have a role in mediating these treatment outcomes in adults with OSA.