Baseline Blood Pressure Research Articles

A decade of aging in healthy older adults: longitudinal findings on cerebrovascular and cognitive health

Research suggests an association between cerebrovascular health and cognitive decline, but previous work is limited by its cross-sectional nature or short (< 1–2 years) follow-up. Our aim was to examine, across 10 years of follow-up in healthy older adults, changes in cerebrovascular health and their relationship with subjective memory complaints as an early marker of cognitive decline. Between 2008 and 2010, twenty-eight healthy older adults (69 ± 4 years) underwent baseline blood pressure and transcranial Doppler measurements to assess middle cerebral artery blood velocity (MCAv), cerebrovascular resistance index (CVRi), and measures of cerebral autoregulation (CA). After 9–12 years of follow-up, these measurements were repeated, and presence of memory complaints was evaluated. Linear mixed-model analyses explored effects of aging on cerebrovascular parameters and whether memory complaints were associated with cerebrovascular changes. Across a median follow-up of 10.9 years, no changes in MCAv, CVRi, or CA were found. At baseline, these parameters were not different between subjects with (n = 15) versus without (n = 13) memory complaints. During follow-up, subjects with memory complaints showed larger decreases in MCAv (− 10% versus + 9%, P = 0.041) and increases in CVRi (+ 26% versus − 9%, P = 0.029) compared to other peers without memory complaints, but no distinct changes in CA parameters (P > 0.05). Although a decade of aging does not lead to deterioration in cerebral blood flow or autoregulation, our findings suggest that reductions in cerebral blood flow and increases in cerebrovascular resistance are associated with early subjective cognitive decline.

Blood pressure dynamics during home blood pressure monitoring with a digital blood pressure coach-a prospective analysis of individual user data.

Self-monitoring of blood pressure at home is a better predictor of prognosis and recommended in hypertension guidelines. However, the influence of baseline blood pressure category and measurement schedule on BP values during a period of home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application. We analysed temporal BP changes and performed BP classification tracking in users with self-reported hypertension performing HBPM with a digital and interactive blood pressure coach. Of 3175 users who enrolled in HBPM, 74.1% completed the first measurement period. Overall, mean systolic BP dropped significantly after the first day, but stratification by BP category demonstrated that initial category influenced BP course. BP classification tracking revealed that time to reach final BP category was dependent on baseline category, with users in categories high normal and grade 1 hypertension requiring more days to decrease BP class volatility and to reach their definitive BP class. This was driven by an intense switching between directly neighbouring categories until the middle phase of the HBPM period, while more distant class switching occurred less often and only early on. Overall, >90% of users maintained their category by day 5. Omitting the first day from analysis lead to therapeutically relevant reclassification in 3.8% of users. Users who completed at least two HBPM periods (n = 864) showed a mean SBP/DBP decrease of 2.6/1.6 mmHg, which improved hypertension control from 55.6% to 68.1%. The optimal length of HBPM period depends on BP category. HBPM with a digital coach is associated with a reduction in average BP and improvement in BP control.

Appropriate screening interval to detect the development of chronic metabolic diseases

AimsWe conducted a cohort study to determine the screening intervals of metabolic disorders. MethodParticipants without diabetes mellitus (DM), hypertension (HTN), dyslipidemia, and abdominal obesity who underwent health examinations (2005–2019) in Korea were included. Participants were grouped according to baseline fasting glucose, LDL-C level, blood pressure (BP), and waist circumference (WC). The time to develop metabolic disorders and the percentile of survival time was assessed in each group. ResultThe median follow-up duration was 4.94 years (n=222,413; mean age 37.13 ± 7.49 years). After 8.32(95 %CI 8.22–8.41), 3.01(2.89–3.31), and 1.11(1.03–1.25) years, 10 % of participants developed DM in fasting glucose levels of 100–110, 110–120, and 120–125 mg/dL, respectively. After 8.40(8.33–8.45), 6.33(6.20–6.47), and 1.99(1.97–2.00) years, 10 % developed HTN in BP 120/70, 120/70–130/80, and 130/80–140/90 mmHg, respectively. After 5.99(5.94–6.04), 2.84(2.77–2.90), and 1.36(1.30–1.44) years, 10 % developed dyslipidemia in LDL-C 100–120, 120–140, and 140–160 mg/dL, respectively. After 4.62(4.41–4.80) and 1.67(1.64–1.69) years, 10 % developed abdominal obesity in baseline WC < 80(Women;W)/85(Men;M) and < 85(W)/90(M) cm, respectively. ConclusionIn adults aged 30–40, the screening interval of metabolic disorders should be individualized based on the baseline metabolic derangement. An individual with borderline values may need an annual screening.

Normalizing arterial blood pressure in patients with aortic stenosis does not prevent grading discrepancies between pre-cardiopulmonary bypass transesophageal echocardiography and transthoracic echocardiography.

Aortic stenosis (AS) grading discrepancies exist between pre-cardiopulmonary (pre-CPB) transesophageal echocardiography (TEE) and preoperative transthoracic echocardiography (TTE). Prior studies have not systematically controlled blood pressure. We hypothesized that normalizing arterial blood pressure during pre-CPB TEE for patients undergoing valve replacement for AS would result in equivalent grading measurements when compared to TTE. Single University Hospital. Prospective, Interventional. Thirty-five adult patients underwent procedures for valvular AS between February 2017 and December 2020 at Medical University of South Carolina. Study participants had a TTE within 90 days of their procedure that documented blood pressure, peak velocity (Vp), mean gradient (PGm), aortic valve area (AVA), and dimensionless index (DI). During pre-CPB TEE, if a patient's mean arterial pressure (MAP) fell more than 20% below their baseline blood pressure obtained during TTE, measurements were recorded as "out of range." Phenylephrine was administered to restore MAP to the baseline range and repeat TEE measurements were recorded as "in-range." Differences between imaging modalities and grading parameters were examined using a series of linear mixed models. P values were Bonferroni-adjusted to account for multiple comparisons. Significant discrepancies between TEE and TTE were observed for Vp, PGm, and DI despite blood pressure normalization across all subjects and for out-of-range measures and corrected measures. There were no statistically significant differences between TEE and TTE for AVA. Blood pressure normalization during pre-CPB TEE is not sufficient to avoid AS grading discrepancies with preoperative TTE.

FEATURES OF AMBULATORY BLOOD PRESSURE MONITORING WITH DIFFERENT BLOOD PRESSURE PROFILES IN PATIENTS WITH HYPERTENSION DISEASE OF MIDDLE AND ELDERLY AGE

Background. Insufficient night-time reduction of blood pressure (BP) and night hypertension are associated with an increased risk of death regardless of the average daily BP. The study of daily BP profiles is very relevant in patients with hypertension of different age categories due to the high risk of thrombotic complications.&#x0D; Aim: of the study was to determine the peculiarities of ambulatory blood pressure monitoring (ABPM) indices in middle-aged and elderly hypertensive patients depending on the daily BP profile.&#x0D; Materials and methods. ABPM indicators were determined in 125 patients who were divided into 2 groups. 1st group (n=82) – middle-aged hypertensive patients (45-59 years old); 2nd group (n=43) – elderly hypertensive patients (60-74 years old). In the groups of middle-aged and elderly subjects 2 groups of daily BP profiles were distinguished: "dipper" and "non-dipper".&#x0D; Indices of ABPM were determined using a portable recorder ABPM-04 (company "Meditech", Hungary). Measurements of BP were performed every 15 minutes during the day (from 6 to 22 hours) and every 30 minutes at night (from 22 to 6 hours). We determined the following indices: the average daily systolic BP (SBP) (mm Hg), the average daly diastolic BP (DBP) (mm Hg), the average BP (mm Hg); the maximal daily SBP (mm Hg), the maximal daily DBP (mm Hg). The daily index (DI) was also calculated − the percentage of BP decrease at night compared to daytime BP calculated in % DI of SBP, DI of DBP, DI of average BP.&#x0D; Results. The baseline BP level in the average daily SBP and DBP in middle-aged patients of dipper group was significantly higher by 49,6% and corresponded to 155,9±12,0 mm Hg (p&lt;0,001) and 50,4% and was 97,3±6,1 mm Hg (p&lt;0,01). Similar results are observed in the average BP and the maximal daily SBP and the maximal daily DBP values which were significantly higher than the control group by 21,5% (p&lt;0,05) and equaled 110,0±3,6 mm Hg and 21,3% and amounted to 176,3±23,5 mm Hg (p&lt;0,05) and 23,6% and amounted to 117,0±19,2 mm Hg (p&lt;0,05). The baseline BP level in the average daily and maximal SBP, the average daily DBP and the average BP in patients of non-dipper group was significantly higher by 50,8% (p&lt;0,01) and corresponded to 157,1±12,9 mm Hg and 27,4% and equal to 176,9±24,0 mm Hg (p&lt;0,05), 63,8% and amounted to 106,0±1,0 mm Hg (p&lt;0,05) and 44% and was 124,3±6,8 mm Hg (p&lt;0,05) too. In the surveyed elderly patients only the average daily DBP was significantly different from the corresponding control indicator and was lower by 21,4% (p&lt;0,05) and amounted to 91,5±0,7 mm Hg in dipper and 23,1% (p&lt;0,01) and was 93,5±0,7 mm Hg in non-dipper group.&#x0D; Conclusion. Non-dipper group predominates in the structure of daily BP rhythm in elderly hypertensive patients (62,8% versus 37,2%). The average BP decreases in elderly patients of non-dipper group by 11,1% (p&lt;0,05) reliably to patients of middle age.

Greater resting muscle sympathetic nerve activity reduces cold pressor autonomic reactivity in older women, but not older men.

Previous work demonstrates augmented muscle sympathetic nerve activity (MSNA) responses to the cold pressor test (CPT) in older women. Given its interindividual variability, however, the influence of baseline MSNA on CPT reactivity in older adults remains unknown. Sixty volunteers (60-83y; 30 women) completed testing where MSNA (microneurography), blood pressure (BP), and heart rate (HR) were recorded during baseline and a 2-min CPT (~4°C). Participant data were terciled by baseline MSNA (n=10/group); comparisons were made between the high baseline men (HM) and women (HW), and low baseline men (LM) and women (LW). By design, HM and HW, vs. LM and LW, had greater baseline MSNA burst frequency (37±5 and 38±3 vs. 9±4 and 15±5 bursts/min) and burst incidence (59±14 and 60±8 vs. 16±10 and 23±7 bursts/100hbs; both P<0.001). However, baseline BP and HR were not different between the groups (all P>0.05). During the CPT, there were no differences in the increase in BP and HR (all P>0.05). Conversely, ΔMSNA burst frequency was lower in HW vs. LW (8±9 vs. 22±12 bursts/min; P=0.012) yet was similar in HM vs. LM (17±12 vs. 19±10 bursts/min, P=0.994). Further, ΔMSNA burst incidence was lower in HW vs. LW (9±13 vs. 28±16 bursts/100hbs; P=0.020), with no differences between HM vs. LM (21±17 vs. 31±17 bursts/100hbs; P=0.455). Our findings suggest that heightened baseline activity in older women attenuates the typical CPT-mediated increase in MSNA without changing cardiovascular reactivity. While the underlying mechanisms remain unknown, altered sympathetic recruitment or neurovascular transduction may contribute to these disparate responses.

Perinatal intermittent hypoxia increases early susceptibility to ANG II-induced hypertension in adult male but not in female Sprague-Dawley rats.

Prenatal, perinatal, and adulthood exposure to chronic intermittent hypoxia (IH) increases blood pressure in rodents. Males exposed to chronic IH have higher blood pressure versus females. However, it is unknown if this same-sex difference exists with acute perinatal IH. We tested the hypothesis that acute perinatal IH increases baseline blood pressure and enhances sensitivity to angiotensin II (ANG II)-induced hypertension in male Sprague-Dawley rats. Male and female pups were randomized to control (room air) or IH (10 min of ∼10% O2 for 3 times/day) for the first 8 days of life. IH decreased oxygen saturation, as confirmed via a pulse oximeter. Pups were weaned at postnatal day 21. Blood pressure was measured via telemetry beginning at 14 wk of age and analyzed separately into light and dark phases to assess circadian rhythm. Osmotic minipumps to deliver ANG II were implanted at 15 wk of age. Perinatal IH exposure did not alter baseline blood pressure. One week of ANG II treatment increased blood pressure in light and dark periods in males exposed to IH versus control; there was no effect in females. Blood pressure among the groups was comparable following 2 wk of ANG II infusion. Perinatal IH did not change the circadian rhythm. Following ANG II treatment, indexes of renal injury were measured. Perinatal IH did not alter kidney size, structure, nephron number, or creatinine clearance. These data indicate that acute perinatal IH enhances early ANG II-induced hypertension in males, independent of nephron loss or decreases in body weight or kidney function.NEW & NOTEWORTHY The impact of acute intermittent hypoxia (IH) in early life on blood pressure in adulthood is unknown. This study used a new model exposing female and male rat pups to acute IH in the first 8 days of life, without exposing the dam. Although baseline blood pressure was not altered in adulthood, IH increased susceptibility to angiotensin II hypertension only in males, supporting increased susceptibility of males exposed to IH to a second cardiovascular stressor.

Dynamic Alterations in Cerebral Hemodynamics Measured by Portable Near-Infrared Spectroscopy in Orthostatic Hypotension and Intolerance.

We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system. Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case-control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system. There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls. Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery.

Dietary magnesium intake is related to larger brain volumes and lower white matter lesions with notable sex differences

PurposeTo examine the association between dietary magnesium (Mg) intake and brain volumes and white matter lesions (WMLs) in middle to early old age.MethodsParticipants (aged 40–73 years) from UK Biobank (n = 6001) were included and stratified by sex. Dietary Mg was measured using an online computerised 24 h recall questionnaire to estimate daily Mg intake. Latent class analysis and hierarchical linear regression models were performed to investigate the association between baseline dietary Mg, Mg trajectories, and brain volumes and WMLs. Associations between baseline Mg, and baseline blood pressure (BP) measures, and baseline Mg, Mg trajectories and BP changes (between baseline and wave 2) were also investigated to assess whether BP mediates the link between Mg intake and brain health. All analyses controlled for health and socio-demographic covariates. Possible interactions between menopausal status and Mg trajectories in predicting brain volumes and WMLs were also investigated.ResultsOn average, higher baseline dietary Mg intake was associated with larger brain volumes (gray matter [GM]: 0.001% [SE = 0.0003]; left hippocampus [LHC]: 0.0013% [SE = 0.0006]; and right hippocampus [RHC]: 0.0023% [SE = 0.0006]) in both men and women. Latent class analysis of Mg intake revealed three classes: “high-decreasing” (men = 3.2%, women = 1.9%), “low-increasing” (men = 1.09%, women = 1.62%), and “stable normal” (men = 95.71%, women = 96.51%). In women, only the “high-decreasing” trajectory was significantly associated with larger brain volumes (GM: 1.17%, [SE = 0.58]; and RHC: 2.79% [SE = 1.11]) compared to the “normal-stable”, the “low-increasing” trajectory was associated with smaller brain volumes (GM: − 1.67%, [SE = 0.30]; white matter [WM]: − 0.85% [SE = 0.42]; LHC: − 2.43% [SE = 0.59]; and RHC: − 1.50% [SE = 0.57]) and larger WMLs (1.6% [SE = 0.53]). Associations between Mg and BP measures were mostly non-significant. Furthermore, the observed neuroprotective effect of higher dietary Mg intake in the “high-decreasing” trajectory appears to be greater in post-menopausal than pre-menopausal women.ConclusionsHigher dietary Mg intake is related to better brain health in the general population, and particularly in women.

Sleeve gastrectomy improved microvascular phenotypes from obesity cohort, detected with optical coherence tomography angiography.

To examine how metabolic status is associated with microvascular phenotype and to identify variables associated with vascular remodeling after bariatric surgery, using noninvasive optical coherence tomography angiography (OCTA). The study included 136 obese subjects scheduled for bariatric surgery and 52 normal-weight controls. Patients with obesity were divided into metabolically healthy obesity (MHO) and metabolic syndrome (MetS) groups according to the diagnosis criteria of the Chinese Diabetes Society. Retinal microvascular parameters were measured by OCTA, including superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel densities. Follow-ups were performed at the baseline and 6months after bariatric surgery. Fovea SCP, average DCP, fovea DCP, parafovea DCP, and perifovea DCP vessel densities were significantly lower in the MetS group, compared to controls (19.91% vs. 22.49%, 51.60% vs. 54.20%, 36.64% vs. 39.14%, 56.24% vs. 57.65% and 52.59% vs. 55.58%, respectively, all p < .05). Parafovea SCP, average DCP, parafovea DCP, and perifovea DCP vessel densities significantly improved in patients with obesity 6months after surgery, compared to baseline (54.21% vs. 52.97%, 54.43% vs. 50.95%, 58.29% vs. 55.54% and 55.76% vs. 51.82%, respectively, all p < .05). Multivariable analyses showed that baseline blood pressure and insulin were independent predictors of vessel density changes 6months after surgery. Retinal microvascular impairment occurred mainly in MetS rather than MHO patients. Retinal microvascular phenotype improved 6months after bariatric surgery and baseline blood pressure and insulin status may be key determinants. OCTA may be a reliable method to evaluate the microvascular complications associated with obesity.

Effectiveness of a Disease Management Program (DMP) in controlling the progression of Chronic Kidney Disease among hypertensives and diabetics.

Background: In India, the number of patients with type II diabetes mellitus in 2006 was 40.9 million and is expected to increase by 2025 to 69.9 million. The occurrence rate of stage 5 CKD was 151 per million population in India. Diabetes Mellitus and hypertension were the usual triggers of Chronic Kidney Disease (CKD). A structured education program helps in the prevention of diabetes and hypertension related complications. Methods: This quasi-experimental study was conducted among 88 participants who had hypertension, diabetes mellitus, or both for five or more years with an objective to find the effect of a Disease Management Program on delaying progression of CKD in patients with hypertension or diabetes mellitus. The baseline data were collected on demographic proforma, serum creatinine, blood pressure, and random blood sugar, and the patients were taught the management of hypertension and diabetes mellitus. In the fourth and the eighth month, blood pressure and blood sugar were reassessed. At one-year blood pressure, blood sugar, and serum creatinine were tested. Baseline and one-year follow-up blood pressure, blood sugar, and estimated Glomerular Filtration Rate were compared. Descriptive statistics and "Wilcoxon signed-rank test" were used to analyze the data. Results: In one year, the mean systolic blood pressure reduced by six mm of Hg and mean blood sugar by 24 mg/dl. The prevalence of CKD stage three and above (&lt; 60 ml/min/m2) was nine (10.22%). The median decline in eGFR was 5 ml/min/m2 (Z= 5.925, P&lt; 0.001). Conclusion: The Disease Management Program led to improvements in blood pressure and diabetes control and median progression of CKD was estimated at five ml/min/m2/year.

Systolic Blood Pressure and Cardiovascular Risk in Normotensive Adults

ObjectiveTo examine the association of systolic blood pressure (SBP) and cardiovascular risk in normotensive adults. Patients and MethodsThis study analyzed data from 7 prospective cohorts between September 29, 1948, and December 31, 2018. Complete information on history of hypertension and baseline blood pressure measurements were required for inclusion. We excluded individuals younger than 18 years old, those with a history of hypertension, and patients with baseline SBP measurements of less than 90 mm Hg or 140 mm Hg or higher. Cox proportional hazards regression and restricted cubic spline models were used to evaluate the hazards of cardiovascular outcomes. ResultsA total of 31,033 participants were included. The mean ± SD age was 45.3±14.8 years, 16,693 of the participants (53.8%) were female, and the mean ± SD SBP was 115.8±11.7. Over a median follow-up of 23.5 years, 7005 cardiovascular events occurred. Compared with those who had SBP levels of 90 to 99 mm Hg, participants with SBP levels of 100 to 109, 110 to 119, 120 to 129, and 130 to 139 mm Hg experienced 23% (hazard ratio [HR], 1.23; 95% CI, 1.07 to 1.42), 53% (HR, 1.53; 95% CI, 1.33 to 1.76), 87% (HR, 1.87; 95% CI, 1.62 to 2.16), and 117% (HR, 2.17; 95% CI, 1.87 to 2.52) increased risks of cardiovascular events, respectively. Compared with follow-up SBP of 90 to 99 mm Hg, the HRs for cardiovascular events were 1.25 (95% CI, 1.02 to 1.54), 1.93 (95% CI, 1.58 to 2.34), 2.55 (95% CI, 2.09 to 3.10), and 3.39 (95% CI, 2.78 to 4.14), respectively, for follow-up SBP levels of 100 to 109, 110 to 119, 120 to 129, and 130 to 139 mm Hg. ConclusionIn adults without hypertension, there is a stepwise increase in risk of cardiovascular events, with increasing SBP starting at levels as low as 90 mm Hg.

Evaluation of vascular risk in patients with migraine with and without aura treated with erenumab: Post hoc analysis of pooled long‐term clinical trial data

To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk. Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene-related peptide pathway in migraine management, particularly in a patient population with pre-existing CV risk factors. Data pooled from four double-blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10-year risk of cardiac, cerebrovascular, and peripheral artery disease as no-risk-factors, low-risk (>0% to ≤10%), moderate-risk (>10% to ≤20%), and high-risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE). There was no apparent difference between placebo- (N=1032) and erenumab-treatment groups (70 mg, N=885; 140 mg, N=504) in clinical worsening of BP category from baseline to Months 1-3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long-term analysis. Erenumab-treated patients with high and moderate 10-year CV risk (N=107) did not experience any ICCAEs during the double-blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low-risk erenumab group (N=273). There were no increases in AEs during the long-term extensions of up to 5 years (N= 2499; 3482 patient-years of exposure to erenumab) with exposure-adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient-years) for no risk factor (N= 1805), low (N= 492), moderate (N= 121), and high (N= 81) 10-year CV risk groups, respectively. Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10-year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.

Abstract P394: Initial Antihypertensive Prescribing in Relation to Blood Pressure Among Medicaid and Medicare Recipients

Introduction: Early treatment for hypertension (HTN) portends better outcomes. However, few real-world studies have assessed initial antiHTN regimens and how they differ by baseline blood pressure (BP). We sought to compare initial treatment patterns, stratified by BP, between Medicaid and Medicare recipients. Methods: We performed a cross-sectional study of adults with newly-treated HTN in the One Florida+ Consortium(2012-2020) who had linked claims-EHR data from the treatment initiation visit. Eligible patients were Floridians with Medicaid or Medicare aged ≥18 years, with diagnosed HTN, who filled ≥1 first-line antiHTN class with no evidence of anti HTN fills during the year prior (in which continuous insurance enrollment was required). Baseline BP was categorized per current HTN guidelines, and logistic regression was used to estimate age-adjusted odds of combination vs. monotherapy, per 10 mmHg increase in systolic BP (SBP) or diastolic BP (DBP). Results: We included 2,902 patients (47% Medicaid, 53% Medicare); mean age was 44 (Medicaid) and 67 yrs(Medicare); 60% (64% and 56%, respectively) were women and 42% (57% and 29%, respectively) were Black. Initial antiHTN classes were similar comparing cohorts: ACEI, ARB and thiazide initiation varied little by BP category, in contrast to CCBs and β-blockers (Figure, panels A-B). In age-adjusted analyses, use of initial combination therapy was 40% more likely (OR, 1.40; 95% CI, 1.11, 1.76) among Medicare recipients and inversely related to BP category (panels C-D) among Medicare patients, in which each 10mmHg greater SBP (OR, 0.93; 95% CI, 0.88, 0.97) and DBP (OR 0.82; 95% CI, 0.75, 0.90) had lower odds of combination therapy. Among Medicaid recipients, only SBP associated with combination therapy (OR1.11; 95% CI, 1.03, 1.20). Conclusions: We observed similar initial class patterns among Medicaid &amp; Medicare recipients across baseline BP, but differential use of combination therapy was less likely at higher baseline BP in Medicare recipients, which contrasts current guidance.

Abstract P502: Blood Pressure Variability and Neurodegenerative Biomarkers: The Multidomain Alzheimer Preventive Trial

Background: Increased Blood Pressure (BP) Variability (BPV) may represent an alteration in physiological homeostatic patterns, typical of late life, and has been associated with cerebrovascular disease, cognitive impairment and dementia, including Alzheimer’s disease. Accumulation of Brain beta amyloid (Aβ) and neurofilament light chain (NFL) release are typical biomarkers of neurodegeneration, whose assessment requires neuroimaging and cerebrospinal fluid (CFS) measurements, thus limiting their use in large-scale screening of the aging populations. Nevertheless, plasma Aβ42/40 ratio is associated with CSF Aβ42/40 ratio, similarly plasma NFL levels correlate with NFL in CFS. Furthermore, blood progranulin (PGL) is also considered a neurodegenerative biomarker, since deficiency exerts pleiotropic effects on the development, maintenance, stress response, and ageing of neural circuit. Objective: We aimed to explore the association of visit-to-visit BPV with blood concentrations of neurodegenerative biomarkers in a population of older adults. Methods: Participants were selected among community-dwelling participants aged ≥70 years from the Multidomain Alzheimer Preventive Trial (MAPT) Study. Plasma blood sample was collected 12 months after enrolment and BP was assessed every six months from enrollment (0, 6, 12 months). Systolic BPV (SBPV) and diastolic BPV (DBPV) were determined through several indicators considering BP change over time, the order of measurements and formulas independent of mean BP levels. Multivariable linear regressions were used to assess the association between visit-to-visit BPV and either PGL, Aβ42/40 and NFL. Results: The study population consisted of 470 participants (mean age 75.7 ± 4.5 years; female, 59.7%). Visit-to-visit BPV (all indicators, both systolic and diastolic) was not associated with blood levels of neurodegenerative biomarkers after adjustment for demographics, BMI, MAPT randomization group, education, baseline BP, antihypertensive drugs, diabetes mellitus, ischemic heart disease, atrial fibrillation, stroke: per 1-SD increase in systolic BPV (coefficient of variation %): Aβ42/40: adjusted β (SE) = -0.07 (0.04), p=0.13 and NFL: adjusted β (SE) = -0.06 (0.04), p=0.19. Conclusion: Neither systolic nor diastolic visit-to-visit BPV were associated with neurodegenerative blood biomarkers (Aβ42/40, NFL, and PGL) in a population of older adults. Further studies with longer-term assessment of BPV are needed.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Association between blood pressure during 12-28 weeks gestation and pre-eclampsia: predictive value of blood pressure trajectories constructed by latent class growth modeling

Objective: To explore the associations between blood pressure trajectories during pregnancy and risk of future pre-eclampsia in a large cohort enrolling pregnant women at gestational age of ~12 weeks from community hospitals in Tianjin. Latent class growth modeling (LCGM) was used to model the blood pressure trajectories. Methods: This was a large prospective cohort study. The study enrolled pregnant women of ~12 weeks of gestation in 19 community hospitals in Tianjin from November 1, 2016 to May 30, 2018. We obtained related information during 5 antepartum examinations before gestational week 28, i.e., week 12, week 16, week 20, week 24 and week 28. LCGM was used to model longitudinal systolic (SBP) and diastolic blood pressure (DBP) trajectories. For the association study, the predictors were set as SBP and DBP trajectory membership (built separately), the outcome was defined as the occurrence of preeclampsia after 28 weeks of gestation. Results: A total of 5 809 cases with known pregnant outcomes were documented. After excluding 249 cases per exclusion criteria, 5 560 cases with singleton pregnancy were included for final analysis. There were 128 cases preeclampsia and 106 cases gestational hypertension in this cohort. Univariate logistic regression and multivariate logistic regression showed the higher baseline SBP level and DBP level were related with increased risk of preeclampsia. Four distinctive SBP trajectories and DBP trajectories from 12 weeks to 28 weeks of gestation were identified by LCGM. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for SBP latent classification trajectory_ 4 was 4.023 (95%CI: 2.368 to 6.835, P<0.001), and the OR for SBP latent classification trajectory_3 was 1.854 (95%CI: 1.223 to 2.811, P=0.004). Logistic regression showed that: using the DBP latent classification trajectory_1 as the reference group, the OR for DBP latent classification trajectory_4 was 4.100 (95%CI: 2.571 to 6.538, P<0.001), and 2.632 (95%CI: 1.570 to 4.414, P<0.001) for DBP latent classification trajectory_2. After controlling for potential confounders (baseline BMI, being primipara or not, white blood cell counts, hemoglobin level, platelet counts and alanine aminotransferase level), the OR for DBP_traj_4 was 2.527 (95%CI: 1.534 to 4.162, P<0.001), and the OR for DBP_traj_3 was 1.297 (95%CI: 0.790 to 2.128, P=0.303), and 2.238 (95%CI: 1.328 to 3.772, P=0.002) for DBP_traj_2. Therefore, BP trajectories from 12 weeks to 28 weeks identified by LCGM served as novel risk factors that independently associated with the occurrence of preeclampsia. Receiver operating characteristic (ROC) curve analysis showed incremental diagnostic performance by combing baseline blood pressure levels with blood pressure trajectories. Conclusion: By applying LCGM, we for the first time identified distinctive BP trajectories from gestational week 12 to 28, which can independently predict the development of preeclampsia after 28 weeks of gestation.

Angiotensin deficient FVB/N mice are normotensive.

All previous rodent models lacking the peptide hormone angiotensin II (Ang II) were hypotensive. A mixed background strain with global deletion of the angiotensinogen gene was backcrossed to the FVB/N background (Agt-KO), a strain preferred for transgenic generation. Surprisingly, the resulting line turned out to be normotensive. Therefore, this study aimed to understand the unique blood pressure regulation of FVB/N mice without angiotensin peptides. Acute and chronic recordings of blood pressure (BP) in freely-moving adult mice were performed to establish baseline BP. The pressure responses to sympatholytic and sympathomimetic as well as a nitric oxide inhibitor and donor compounds were used to quantify the neurogenic tone and endothelial function. The role of the renal nerves on baseline BP maintenance was tested by renal denervation. Finally, further phenotyping was done by gene expression analysis, histology and measurement of metabolites in plasma, urine and tissues. Baseline BP in adult FVB/N Agt-KO was unexpectedly unaltered. As compensatory mechanisms Agt-KO presented an increased sympathetic nerve activity and reduced endothelial nitric oxide production. However, FVB/N Agt-KO exhibited the renal morphological and physiological alterations previously found in mice lacking the production of Ang II including polyuria and hydronephrosis. The hypotensive effect of bilateral renal denervation was blunted in Agt-KO compared to wildtype FVB/N mice. We describe a germline Agt-KO line that challenges all previous knowledge on BP regulation in mice with deletion of the classical RAS. This line may represent a model of drug-resistant hypertension because it lacks hypotension.

Expanding the use of salivary cortisol as a non-invasive outpatient test in the dynamic evaluation of suspected adrenal insufficiency.

Adrenal insufficiency (AI) is potentially life-threatening, and accurate diagnosis is crucial. The first-line diagnostic test, the adrenocorticotrophic hormone (ACTH) stimulation test, measures serum total cortisol. However, this is affected in states of altered albumin or cortisol-binding globulin levels, limiting reliability. Salivary cortisol reflects free bioactive cortisol levels and is a promising alternative. However, few studies are available, and heterogenous methodologies limit applicability. This study prospectively recruited 42 outpatients undergoing evaluation for AI, excluding participants with altered cortisol-binding states. Serum (immunoassay) and salivary (liquid chromatography tandem mass spectrometry) cortisol levels were sampled at baseline, 30 min, and 60 min following 250 µg synacthen administration. AI was defined as a peak serum cortisol level <500 nmol/L in accordance with guidelines. The study recruited 21 (50%) participants with AI and 21 without AI. There were no significant differences in baseline characteristics, blood pressure, or sodium levels between groups. Following synacthen stimulation, serum and salivary cortisol levels showed good correlation at all timepoints (R2 = 0.74, P < 0.001), at peak levels (R2 = 0.72, P < 0.001), and at 60 min (R2 = 0.72, P < 0.001). A salivary cortisol cut-off of 16.0 nmol/L had a sensitivity of 90.5% and a specificity of 76.2% for the diagnosis of AI. This study demonstrates a good correlation between serum and salivary cortisol levels during the 250 µg synacthen test. A peak salivary cortisol cut-off of 16.0 nmol/L can be used for the diagnosis of AI. It is a less invasive alternative to evaluate patients with suspected AI. Its potential utility in the diagnosis of AI in patients with altered cortisol-binding states should be further studied.

Association of Blood Pressure With Rates of Macular Ganglion Cell Complex Thinning in Patients With Glaucoma

There are scarce data on the association of blood pressure measures with subsequent macular structural rates of change in patients with glaucoma. To investigate the association of baseline blood pressure measures with rates of change of the macular ganglion cell complex in patients with central or moderate to advanced glaucoma damage at baseline. This prospective cohort study, conducted from August 2021 to August 2022, used data from patients in the Advanced Glaucoma Progression Study at the University of California, Los Angeles. Participants were between 39 and 80 years of age and had more than 4 macular imaging tests and 2 or more years of follow-up. A diagnosis of glaucoma with either central damage or a visual field mean deviation worse than -6 dB. The main outcome was the association of blood pressure measures with ganglion cell complex rates of change. Macular ganglion cell complex thickness rates of change were estimated with a bayesian hierarchical model. This model included relevant demographic and clinical factors. Blood pressure measures, intraocular pressure, and their interactions were added to the model to assess the association of baseline blood pressure measures with global ganglion cell complex rates of change. The cohort included 105 eyes from 105 participants. The mean (SD) age, 10-2 visual field mean deviation, and follow-up time were 66.9 (8.5) years, -8.3 (5.3) dB, and 3.6 (0.4) years, respectively, and 67 patients (63.8%) were female. The racial and ethnic makeup of the cohort was 15 African American (14.3%), 23 Asian (21.9%), 12 Hispanic (11.4%), and 55 White (52.4%) individuals based on patient self-report. In multivariable analyses, female sex, history of taking blood pressure medications, higher intraocular pressure, thicker central corneal thickness, shorter axial length, higher contrast sensitivity at 12 cycles per degree, and higher baseline 10-2 visual field mean deviation were associated with faster ganglion cell complex thinning. Lower diastolic blood pressure was associated with faster rates of ganglion cell complex thinning at higher intraocular pressures. For intraocular pressures of 8 and of 16 mm Hg (10% and 90% quantiles, respectively), every 10 mm Hg-lower increment of diastolic blood pressure was associated with 0.011 μm/y slower and -0.130 μm/y faster rates of ganglion cell complex thinning, respectively. In this cohort study, a combination of lower diastolic blood pressure and higher intraocular pressure at baseline was associated with faster rates of ganglion cell complex thinning. These findings support consideration of evaluating and addressing diastolic blood pressure as a therapeutic measure in patients with glaucoma if supported by appropriate clinical trials.