Similar Systolic Blood Pressure Research Articles

Nighttime blood pressure reductions after radiofrequency renal denervation through 24 months in patients with uncontrolled hypertension: pooled analysis from the SPYRAL HTN trials

Abstract Introduction Studies have shown that elevated nighttime and early morning systolic blood pressure (SBP) are associated with the highest risk for cardiovascular (CV) events. Radiofrequency renal denervation (RF RDN) is an interventional therapy to reduce BP in patients with uncontrolled hypertension (HTN). Although sustained, durable reductions in office and 24-h ambulatory systolic BP (SBP) after RDN have been observed, whether the therapy produces similar, durable nighttime and early morning SBP reductions requires further evaluation. Objective To assess whether RF RDN significantly reduces nighttime SBP through long-term follow-up, in addition to other times of the day. Methods We pooled data from patients with uncontrolled HTN undergoing RF RDN using the latest-generation Symplicity SpyralTM multi-electrode catheter from the published SPYRAL HTN-OFF and -ON MED clinical trials. Office and 24-h ambulatory SBP were evaluated from baseline through 24 months. We also assessed BP changes during specific, diurnal time ranges including nighttime (1am-6am), early morning (7am-9am), and daytime (9am-9pm). The number of antihypertensive drugs and drug burden (determined by number of classes and prescribed dosage) from urine and plasma drug testing were tabulated from baseline through 24 months. Results Outcomes from 388 patients undergoing RF RDN were pooled for this analysis. Patients were on average 54±10yrs old, 26.8% female, mean BMI was 31.3±6.0, 45.1% with >10yrs diagnosis of hypertension, 7.7% with type 2 diabetes, 9.8% with obstructive sleep apnea, 47.7% with a history of smoking. The baseline nighttime SBP was 139±11mmHg, morning SBP was 154±15mmHg, and daytime SBP was 156±9mmHg. At baseline, 92.5% of patients had nocturnal hypertension (BP ≥120/70 mmHg) and took 1.0±1.2 antihypertensive drugs. 12 months after RF RDN, 30.6% of patients no longer had nocturnal hypertension (p<0.0001). The mean nighttime SBP change at 12 months was -10.8±15.4mmHg, morning changed was -12.8±20.4mmHg, and daytime changed was -12.2±13.6mmHg (Figure). The mean 24-h ambulatory SBP change at 12 months was -11.9±12.4mmHg, and the office SBP change was -17.7±15.4mmHg . Patients took 1.8±1.1 antihypertensive drugs at 12 months. Results from 24 months, not currently available, will also be presented for the first time. Conclusions In this pooled cohort of RDN patients with uncontrolled hypertension, nocturnal hypertension was highly prevalent. Clinically meaningful reductions at 12 months throughout the 24-hr circadian cycle, including at nighttime and early morning SBP, are consistent with the "always on" effect of RDN. Results from 24 months will also be presented for the first time at ESC. As an adjunctive therapy to pharmacotherapy, RDN may help to reduce CV risk by lowering nighttime and morning SBP.

Comparing the cardiorespiratory safety of parenteral olanzapine and benzodiazepines to parenteral haloperidol/droperidol and benzodiazepines in emergency department patients

IntroductionThis study sought to assess the cardiorespiratory safety of parenteral olanzapine and benzodiazepine combination treatment compared to parenteral droperidol or haloperidol and benzodiazepine combination treatment. Materials and methodsThis was a retrospective chart review conducted in adult emergency department patients who received intramuscular (IM) or intravenous (IV) droperidol, haloperidol, or olanzapine within one hour of IM or IV benzodiazepine. Patients were stratified into groups based on whether they received either olanzapine in combination with a benzodiazepine (n = 48) or droperidol or haloperidol in combination with a benzodiazepine (n = 48). ResultsPatients in each group had a decrease in their systolic blood pressure (SBP) after IM/IV olanzapine and IM/IV droperidol or haloperidol when used in combination with an IM/IV benzodiazepine ((Olanzapine + benzodiazepine (mmHg), median (IQR): Pre-SBP: 132 (117–151) vs. Post-SBP: 117 (99–131), p < 0.01) (Droperidol or haloperidol + benzodiazepine (mmHg), median (IQR): Pre-SBP: 138 (122–149) vs. Post-SBP: 106 (98–127), p < 0.01)). Both groups had similar percent SBP decreases post-combination treatment (Olanzapine + benzodiazepine (15.6 %) vs. Droperidol or haloperidol + benzodiazepine (15.2 %); p = 0.55). We did not observe any statistically significant between group differences for hypotension (Olanzapine + benzodiazepine: 1/48, 2.1 % vs. Droperidol or haloperidol + benzodiazepine: 3/48, 6.3 %; p = 0.62)), escalation in oxygen requirements (Olanzapine + benzodiazepine: 7/48, 14.6 %) vs. Droperidol or haloperidol + benzodiazepine: 5/48, 10.4 %; p = 0.76)), or intubation due to cardiorespiratory depression (Olanzapine + benzodiazepine: 0/0, 0 % vs. Droperidol or haloperidol + benzodiazepine: 0/0, 0 %; p = 1.00)). ConclusionThis study found decreases in SBP after administering parenteral olanzapine and parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine. The percent change in SBP and the frequency of hypotensive episodes post-combination treatment were not different between groups. There were also no differences between groups in need of increased oxygen requirements post-combination treatment or need for intubation due to cardiorespiratory depression. This study suggests parenteral olanzapine in combination with a parenteral benzodiazepine may have comparable cardiorespiratory safety versus parenteral droperidol or haloperidol in combination with a parenteral benzodiazepine when treating agitation in the adult ED.

Performance of the left ventricular myocardium in patients with a negative test result during exercise stress echocardiography

Aim. To determine the possibility of identifying patients with significant coronary artery disease (CAD) by evaluation of the left ventricular (LV) myocardial work indicators by constructing pressure-strain loops despite a negative test result during exercise stress echocardiography. Materials and methods. The study included 79 patients with suspected or previously confirmed CAD, of which 47 (59%) men, who had a negative test result during exercise stress echocardiography on the treadmill. Global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were evaluated using the technique of constructing pressure-strain loops at rest and at peak exercise. Results. With similar systolic blood pressure and LV ejection fraction at peak exercise between the control group and the group of patients with single-vessel CAD, there was revealed significant difference in GWI, GCW and GWE at peak exercise. In patients with multi-vessel CAD, GWI and GCW also significantly differed from the control group at peak exercise. Conclusion. The evaluation of LV myocardial work indicators may be recommended for a more accurate diagnosis of CAD in negative or unreliable test results during exercise stress echocardiography.

A Role of T-Lymphocyte β-Arrestins in Hypertension

The adaptive immune system and T-cells play a central role in the development of essential hypertension. The renin-angiotensin system regulates blood pressure (BP) through multiple mechanisms including effects on the immune system. Among several G-protein coupled receptors (GPCR) that regulate T-cell function, it has been hypothesized that specific T-cell populations use the angiotensin receptor (AT1R) to modulate immune responses in hypertension. Selective ablation of AT1R in T-cells paradoxically increases hypertensive end-organ damage (EOD). While AT1R typically induces the classical G protein signaling, recent studies have uncovered an alternative protective signaling-cascade at this receptor via β-Arrestin ( ARRB) proteins. Thus, we hypothesized that ARRB in T-lymphocytes mediates an anti-hypertensive and anti-inflammatory role in response to angiotensin II (ANG II) thereby decreasing EOD in hypertension. Transgenic mice with T-lymphocyte-specific knock outs of the Arrb1 gene were developed using a CD4-Cre x Arrb1-Flox system. Hypertensive conditions were modeled with a 3-pronged approach designed to induce kidney damage consisting of unilateral nephrectomy (UNX), maintenance on a 4% salt diet, and a continuous infusion of ANG II (1,000 ng/kg/min). Age and sex-matched Cre negative x Arrb1-Flox littermates were used as controls. BP was measured at baseline before and after UNX, and for the following three weeks using radiotelemetry. Inflammation was assessed using quantitative PCR (q-PCR). Preliminary data suggest that loss of T-cell specific Arrb1 is protective against ANG II-induced hypertension. At baseline CD4Arrb1-null and CD4Arrb1-WT mice had similar systolic BP (123.0±2.9 mmHg and 119.6±2.3 mmHg, respectively, n=5-7). However, CD4Arrb1-null mice exhibited an attenuated response to ANG II infusion after three weeks (162.5±11.8 mmHg vs 187.0±5.9 mmHg n=3-5; p = 0.03). After 15 days of ANG II, mice were placed in metabolic cages and urine was collected. In a 24-hour period, CD4Arrb1-null mice excreted significantly more sodium (1.98±0.07 mg/24hrs vs 1.66±0.03 mg/24hrs, n=3-4; p = 0.01). Tissue collected from the renal cortex following three weeks of ANG II infusion was analyzed for inflammatory cytokines using q-PCR. Gene expression was normalized to 18s expression in CD4Arrb1-WT mice under sham experimental conditions. Expression of tumor necrosis factor α (TNF-α) transcripts was attenuated in CD4Arrb1-null mice when compared to CD4Arrb1-WT (1.62±0.24-fold increase vs 0.67±0.07-fold decrease, respectively, n=3-4; p=0.006). Contrary to our hypothesis, these preliminary data suggest that T-cell Arrb1 does not protect against hypertensive or inflammatory responses to ANG II. However, these studies highlight the role of β-arrestin-1 proteins endogenous to T-lymphocytes in the modulation of the hypertensive response to ANG II. Supported by grants from the AHA and NIH. 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.

Increases of renal sodium transporters before and after the occurrence of the hypertension in spontaneously hypertensive rats

Background: Adult spontaneously hypertensive rats (SHR) have increases of renal sodium transporters associated with hypertension. It remains to be determined whether the increases of renal sodium transporters are precede by occurrence of hypertension and reflected by urine exosomal sodium transporters that may serve as non-invasive biomarkers for the effcacy of anti-hypertensive drugs. Methods: 1. Male WKY rats and SHRs were aged of 4, 7 and 10 weeks respectively (n=5/group). 2. Additional 3 sets of 10-week-old rat (n=5/group) were administered by a 7-day intraperitoneal injections of furosemide (NKCC2 inhibitor, 5mg/kg), hydrochlorothiazide (NCC2 inhibitor, 30mg/kg) and amiloride (ENaC inhibitor, 10mg/kg) respectively. 3. The systolic blood pressure (SBP) was measured with a catheter in carotid artery of rats under anesthesia. Tail-cuff methods were used to monitor the drug responses. 4. All rats were rationally fed 0.4% NaCl agar-gelled diet for 7 days. 5. Exosomes were extracted with ultracentrifuge from the urines. Results: SHRs (4 weeks) exhibited similar SBP. The renal NKCC2, the major apical sodium transporters in thick ascending limb, was more than doubled in SHRs (215±14 % of WKY, student t-test, p&lt;0.05, same as below) while the other sodium transporters were normal. However, SHRs had a higher SBP than WKY at ages of 7 (157±10 vs 125±14, mmHg) and 10 weeks (192±8 vs 128±12). There were no differences for the all age groups in heart rate, body weight, urine volume, urine Na+ and Cl− excretion, and serum Cr, K+, Na+, and Cl− concentration between rat strains. At 10-weeks old, renal (161±24) and urine exosomal (159±21, corrected by UCr, same as below) NKCC2 were higher in SHR than WKY. Frusemide normalized SBP on day 1 (day 0: 190±18 vs 138±13; day 1: 149±13 vs 128±16) in SHR; Renal (129±9) and urine-exosomal (137±12) NCC were higher in SHR than WKY. Hydrochlorothiazide normalized SBP in SHR on day 1 (day 0: 206±4 vs 140±9; day 1: 159±11 vs 144±11). Renal (α:134±16; β:137±25) and urine-exosomal (α:153±13; β:158±12) ENaCs were higher in SHR than WKY. Amiloride diminished the difference in SBP between rat strains on day 1 (day 0: 188±18 vs 138±11; day 1: 164±16 vs 147±7). Conclusions: The increase of renal NKCC2 precedes the elevation of SBP in SHRs. Urine exosomal NKCC2, NCC, ENaCs may reflect their renal levels and be indicative of the corresponding inhibitors on the hypertension model. Natural Science Foundation of China 81970605. 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.

Efficacy and safety of a four-drug, quarter-dose treatment for hypertension: the QUARTET USA randomized trial

New approaches are needed to lower blood pressure (BP) given persistently low control rates. QUARTET USA sought to evaluate the effect of four-drug, quarter-dose BP lowering combination in patients with hypertension. QUARTET USA was a randomized (1:1), double-blinded trial conducted in federally qualified health centers among adults with hypertension. Participants received either a quadpill of candesartan 2 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg or candesartan 8 mg for 12 weeks. If BP was >130/>80 mm Hg at 6 weeks in either arm, then participants received open label add-on amlodipine 5 mg. The primary outcome was mean change in systolic blood pressure (SBP) at 12 weeks, controlling for baseline BP. Secondary outcomes included mean change in diastolic blood pressure (DBP), and safety included serious adverse events, relevant adverse drug effects, and electrolyte abnormalities. Among 62 participants randomized between August 2019-May 2022 (n = 32 intervention, n = 30 control), mean (SD) age was 52 (11.5) years, 45% were female, 73% identified as Hispanic, and 18% identified as Black. Baseline mean (SD) SBP was 138.1 (11.2) mmHg, and baseline mean (SD) DBP was 84.3 (10.5) mmHg. In a modified intention-to-treat analysis, there was no significant difference in SBP (−4.8 mm Hg [95% CI: −10.8, 1.3, p = 0.123] and a −4.9 mmHg (95% CI: −8.6, −1.3, p = 0.009) greater mean DBP change in the intervention arm compared with the control arm at 12 weeks. Adverse events did not differ significantly between arms. The quadpill had a similar SBP and greater DBP lowering effect compared with candesartan 8 mg. Trial registration number: NCT03640312.

Inter-arm blood pressure difference in post-stroke patients with hemiparesis.

The aim of this study was to investigate that inter-arm blood pressure (BP) difference (IAD) and reference arm in 420 post-stroke patients with hemiparesis. Synchronous bilateral-arm BP was measured with two automatic BP devices, and the systolic BP difference of ≥10 mm Hg was recorded as increased sIAD. The arm with higher systolic BP (SBP) was assigned as the reference arm. Our results showed that the prevalence of sIAD was 18.1% in the total group. The paretic arms had similar mean SBP levels (133.6±18.4 vs. 133.8±18.4 mm Hg, NS) and DBP (77.8±11.5 vs. 77.2±10.9 mm Hg, NS) as compared with the unaffected arms. The detection rate of hypertension or uncontrolled hypertension on the SBP values of the reference arm was higher than that on the unaffected arm (41.8% vs. 36.3%). It is concluded that in the post-stroke patients with hemiparesis in the rehabilitation period, the prevalence of sIAD ≥10 mmHg was relatively higher, and using the unaffected arm, rather than the unaffected arm, for BP measurement could induce correctly detection of hypertension.

Abstract 13490: Sex Differences in the Association of Multi-Ethnic Genome-Wide Blood Pressure Polygenic Risk Score With Population Systolic Blood Pressure Trajectories

Introduction: Sex differences in the systolic blood pressure (SBP) trajectories have been described previously. However, the contribution of underlying genetic architecture to the sex associated differences in SBP trajectories has not been assessed. Methods: Multiancestry sex-specific SBP polygenic risk scores (SBP-PRS), accumulating 1.1 million variants each, were calculated in the participants of the ARIC, JHS, CARDIA, CHS, MESA, FHS, and JHS who underwent whole genome sequencing under the TransOmics for Precision Medicine Program. Based on the SBP-PRS, the cohort was stratified into low (&lt;20 th centile), intermediate (20 th -80 th centile), and high (&gt;80 th centile) genetic risk of SBP. For individuals on antihypertensive medications, SBP measurements were corrected by adding 15 mmHg. Multivariable adjusted restricted cubic splines were used to depict the non-linear relationship of SBP with age in each sex separately. Bootstrapping using 1000 samples was used to estimate the age and 95% CIs at which the sex-specific SBP trajectories crossed over in each SBP-PRS group. Results: In this study of 21,542 individuals (median age: 56 years; 56.0% females; 35.8% non-White individuals), the non-linear association of SBP with age varied by sex (P interaction : &lt;0.001) and SBP-PRS groups (P interaction : 0.05). On stratifying by SBP-PRS, females had a higher age-related increase in SBP compared with males across the groups (p&lt;0.001 in low, intermediate, and high SBP-PRS groups). The age at which the SBP in females surpassed that of males progressively decreased with increasing genetic risk of SBP [low: 66.7 (66.4-67.0) years, intermediate: 64.3 (64.1-64.6) years, high: 55.8 (54.4-57.1) years; p: &lt;0.001]. In the high SBP-PRS group, the sex-associated differences in SBP trajectories were modest with females and males having nearly similar SBP values in old age. Conclusion: The underlying genetic architecture may contribute to sex difference of SBP trajectories.

MWF RAT AS A NOVEL ANIMAL MODEL OF CARDIORENAL SYNDROME TYPE IV

Objective: Cardiorenal syndrome type 4 (CRS type 4) is characterized by primary chronic kidney disease (CKD) leading to cardiac dysfunction and an increase in cardiovascular events. There is an unmet need for suitable animal models of CRS to further define the pathogenesis and progression of CRS to test new therapeutic strategies. We aim to determine if CKD in aged Munich Wistar Frömter (MWF) rat may translate to cardiovascular alterations of CRS. Design and method: Profibrotic markers and angiotensin receptor (ATR) expression was measured by RT-q-PCR in kidney, aorta and heart from 22 and 45-week-old (aged) male MWF rats (n = 7-10/group). Results: Aged MWF showed higher renal expression of tubular damage markers (Kim-1 and Ngal) and profibrotic factors (Col1A1, Col3A1, TGF-beta) together with lower levels of AT2R. Thoracic aorta also exhibited increased expression of profibrotic CTGF-1 and Col1-A1, as well as a lower AT2R expression. Both age groups were hypertensive with similar systolic and diastolic blood pressure levels. However, aged MWF had an increased PWV and heart weight, together with increased intrinsic arterial stiffness and an outward hypertrophic remodeling in mesenteric arteries. In 45-week-old MWF, levels of cardiac CTGF-1, AT1R and AT2R were higher, whereas TGF-beta expression was lower. No differences were observed for Col1A1 or Col3A1. Conclusions: The presence of renal and vascular fibrosis, hypertension, arterial stiffness and cardiac hypertrophy, together with inflammation, vascular remodeling and early profibrotic cardiac environment, potentially counterregulated by AT2R make aged-MWF rat an useful model for CRS study.

Testosterone effects on autonomic function in women with androgen excess polycystic ovary syndrome

Women with androgen excess-polycystic ovarian syndrome (AE-PCOS) present with increased blood pressure (BP) and impaired cardiovascular autonomic control. We tested the hypothesis that androgens play an obesity-independent role in impaired baroreflex (BR) sensitivity and renin-angiotensin system (RAS) control of BP in women with AE-PCOS. We measured the sympathetic baroreflex (sBR) and cardiovagal baroreflex (cvBR) with the modified Oxford procedure, and integrated baroreflex (iBR) and the RAS response to lower body negative pressure (LBNP) in obese, insulin resistant (IR) women with AE-PCOS (n=9; age=23±4 y; BMI=36.3±6.4 kg/m2) and obese, IR controls (CTL) (n=7; age=29±7 y; BMI=34.9±6.8 kg/m2). Studies were conducted at baseline (BSL), after 4 days of reproductive hormone suppression with a gonadotropin-releasing hormone antagonist (ANT, 250 μg/day), and after 4 days of ANT+testosterone (ANT+T, 5 mg/day). At BSL, AE-PCOS and CTL had similar systolic BP (137±14 vs.133±14 mmHg, respectively) and diastolic BP (76±8 vs.63±12 mmHg, respectively). Resting MSNA burst incidence was lower (10.3±3.1 vs. 14.3±4.4 bursts-1×100 hb, P=0.04), but total MSNA activity was greater in AE-PCOS compared to CTL (249±112 vs. 156±44 bursts/min, respectively, P=0.04). Hormone intervention did not impact resting MSNA or BP in either group. In the AE-PCOS group, sBR gain increased during modified Oxford with ANT suppression of T, but sBR gain was restored to BSL when T was reintroduced (-0.48±0.15, -0.63±0.19, and -0.50±0.15 bursts -1 ·100 hb·mmHg -1 for BSL, ANT and ANT+T, respectively, P=0.01). Hormone interventions did not impact sBR gain in CTL (-0.48±0.06, -0.47±0.10, and -0.46±0.09 bursts -1 ·100 hb·mmHg -1 for BSL, ANT and ANT+T, respectively). iBR gain for AE-PCOS and CTL was similar at BSL (1.4±0.9 vs. 1.0±1.3 FVR unit/mmHg, respectively). In AE-PCOS, T suppression increased iBR gain, which was restored to BSL with ANT+T (4.3±6.5 vs.1.5±0.8 FVR unit/mmHg for ANT and ANT+T respectively, P&lt;0.04), with no effect in CTL (1.9 ± 3.0 vs. 0.7±0.9 FVR unit/mmHg for ANT and ANT+T, respectively). cvBR gain was unaffected by group or treatment. Serum aldosterone was greater in AE-PCOS vs CTL (136.5±60.2 vs. 75.7±41.4 pg/ml, respectively, P&lt;0.04), but unaffected by hormone intervention. Serum angiotensin converting enzyme (S [ACE] ) in AE-PCOS was greater compared to CTL at BSL (101.9±93.4 vs. 38.2 ±14.7 pg/ml, respectively, P&lt;0.04). In AE-PCOS, S [ACE] was reduced by ANT (77.7 ±76.5 and 40.6±10.6 μg/L for ANT vs. ANT+T, respectively, P&lt;0.04), but hormone intervention did not impact CTL (43.4±27.3 and 40.6±1 μg/L for ANT vs. ANT+T, respectively, P&lt;0.04). These data suggest the milieu of AE-PCOS increases susceptibility to T driven autonomic perturbations as T elevation had differential effects in AE-PCOS vs. CTL. Our data indicate a powerful relationship among elevated androgens, autonomic function, and the kidney.NIH HL135089/P20GM 121334 National Institutes of Health, NHLBI HL135089 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.

Insulin-regulated aminopeptidase (IRAP) is required for appropriate dilution of urine after an acute water load

Study Objective: Understand the response to acute water load in mice lacking the insulin-regulated aminopeptidase (IRAP). Hypothesis: IRAP degrades vasopressin in vivo, therefore, mice lacking IRAP would have impaired ability to dilute urine and to excrete water. Methods: Age matched 8–10-week-old IRAP WT and KO male mice were used for all experiments. Immunofluorescence and immunoblotting were performed on kidneys at baseline and after 1-hr acute water load (2ml sterile water/IP). Urine/serum electrolytes and urine osmolality were measured before and after water load. Urine was collected from IRAP WT and KO mice before and after 1-hr administration of OPC 31260 (10mg/kg/IP) and furosemide (2.5mg/ml/IP) for urine osmolality and electrolyte measurements. Results: IRAP is expressed in the glomerulus, thick ascending loop of Henle, distal tubule, connecting and collecting ducts. At baseline, IRAP WT and KO mice have similar systolic blood pressure (122 ± 6.6 vs 128 ± 1.9 mmHg), glomerular filtration rate (251 ± 20 vs 254 ± 16 uL/min), and serum Na + levels (142 ± 1.9 vs 143 ± 2.6 mmol/L), but KO mice have reduced proteinuria (3.3 ± 0.57 vs 4.5 ± 1.6 mg/mg). At baseline, IRAP KO have elevated serum copeptin levels (111 ± 43 vs 53 ± 31 pg/mL) and urine osmolality compared to respective IRAP WT (2506 ± 310 vs 1007 ± 212 mOsm/L). Urine osmolality decreased in IRAP KO after administration of vasopressin type 2 receptor antagonist, OPC 31260 (473 ± 341 vs 2479 ± 215 mOsm/L) and loop diuretic, furosemide (517 ± 96 vs 2750 ± 414 mOsm/L). After an acute water load, IRAP KO have lower serum Na + levels (127 ± 3.8 vs 134 ±3.1 mmol/L) and increased urine osmolality compared to IRAP WT (2741 ± 400 vs 577 ± 274 mOsm/L). Additionally, after an acute water load, IRAP KO mice also have higher protein abundance of the Na + /K + /2Cl - (NKCC2) co-transporter (0.36 ± 0.04 vs 0.20 ± 0.03 AU) and phosphorylation of water channel, AQP2 (0.032 ± 0.005 vs 0.025 ± 0.003 AU). Conclusions: IRAP is required to dilute urine and to increase water excretion in response to an acute water load due to persistent activation of NKCC2 and AQP2. Funding Sources: Harold Amos Medical Faculty Development Award - Robert Wood Johnson Foundation; Vanderbilt Center for Kidney Disease 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.

BLOOD PRESSURE REDUCTION AFTER CATHETER-BASED RENAL DENERVATION IN PATIENTS WITH CARDIOVASCULAR DISEASE IN THE GLOBAL SYMPLICITY REGISTRY

Objective: To evaluate the efficacy of catheter-based renal denervation (RDN) to lower blood pressure (BP) in patients with a history of myocardial infarction or stroke in the Global SYMPLICITY Registry (GSR). Design and method: GSR is a prospective, global, all-comers registry to evaluate the safety and efficacy of catheter-based RDN to lower BP. Patients are enrolled with the intention to receive RDN using either the Symplicity Flex or Symplicity Spyral catheter. Patients are followed at 3, 6, and 12 months, and then annually up to 3 years post-procedure. Office and ambulatory BP are measured at each follow-up and any adverse events are collected. The current post-hoc analysis compares systolic BP (SBP) reduction in patients with and without a history of myocardial infarction as well as with and without history of stroke. Differences in SBP reduction between groups were adjusted for baseline SBP using ANCOVA methods. Results: In March 2021 in GSR, there were 267 patients (10%) with a history of myocardial infarction and 2579 without, and 294 patients with a history of stroke (10%) and 2539 without. Patients with and without a history of myocardial infarction had similar baseline office and ambulatory SBP measurements, whereas patients with a history of stroke had similar office SBP measurements but significantly higher ambulatory SBP (159 ± 22 vs. 154 ± 18, p = 0.005) compared to patients without history of stroke. Office and ambulatory SBP reductions from 6 months to 3 years were similar for patients with and without a history of myocardial infarction after adjusting for differences in baseline SBP (Figure). SBP reductions were also similar for patients with and without a history of stroke except at 6 months for office and ambulatory SBP and at 12 months for ambulatory SBP, when patients with a history of stroke had less BP reduction. Conclusions: Patients with and without a history of stroke or myocardial infarction had similar office and ambulatory SBP reductions after catheter-based RDN, suggesting efficacy of RDN regardless of baseline cardiovascular history.

Blood group and its correlation with cardiovascular risk factors: A community survey

Cardiovascular disease is a leading cause of morbidity and mortality globally. Non-O blood groups have been shown to confer a high risk of coronary heart disease. There is paucity of data on the relationship between blood group and left ventricular hypertrophy, among other cardiovascular risk factors. A community-based study was done to evaluate the blood groups and their associations with conventional cardiovascular risk factors in Ejigbo. Anthropometry, blood pressure and other clinical variables were measured. Blood samples were taken for biochemical analysis for blood group typing, serum cholesterol and triglyceride assay. A 12- lead electrocardiogram was performed. The analysis was done using SPSS version 20 to determine possible relationships between the variables. Two hundred and six cases were recruited and analyzed. The prevalence of the various groups was as follows: A - 23%; B-31.4%; AB-4.4%; O-41.2%; rhesus-positive-92.7% and rhesus-negative-7.3%. Blood group B had similar systolic blood pressure (136.0±23.9 vs 137.3±22.3; p=0.726), higher Sokolow- Lyon voltage sum (3.3±1.1 vs 2.9±0.9; p=0.025) and serum triglycerides [14(21.9%) vs7(8.4%), p=0.021] than those with blood group O. Those with Rhesus Positive status had longer PR interval (169.3±25.4 vs 154.2±19.1; p value=0.055) and QRS duration (83.8±12.8 vs 78.4±7.6; p value=0.043) than those with Rhesus negative blood groups. Binary logistic regression revealed blood group B as an independent determinant of left ventricular hypertrophy( LVH) (OR: 3.028; p=0.012; 95% CI:1.275-7.192). Blood group B is a determinant of LVH. Rhesus positive status is associated with delayed electrical conduction through the myocardium.

Abstract P116: Hypertension Severity As Quantified By Hypertension Daily Dose (HDD) And Blood Pressure And Risk Of Stroke In The REGARDS Study

Background: Hypertension is a modifiable stroke risk factor, but hypertension severity isn't completely captured by blood pressure (BP) alone. Prior studies have shown that among adults with similar systolic BP, those taking a greater number of antihypertensive medications have greater stroke risk. However, count of antihypertension medications does not consider relative dose across classes and incompletely characterizes hypertension medical therapy. The recently described Hypertension Daily Dose (HDD) metric quantifies total dose of BP-lowering medications across multiple classes. The association between HDD and BP with stroke risk is unknown. Objective: Determine stroke risk by HDD and BP levels. Methods: We included Black and White adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study without prevalent stroke at visit 2 (2013-2017; treated as baseline) with follow-up data and full BP assessment. We classified systolic BP using JNC7 groupings and HDD by no BP medications and tertiles among those on BP medications. Cox proportional hazards models estimated hazard ratios (HR) for incident stroke by HDD group and BP group. Results: Of 13,265 participants included (mean age 72 [SD 8.5], 36% Black race, 56% women), 344 incident stroke events occurred during a median follow-up of 5.5 years. The stroke rate was higher among Black than White participants (5.6 vs. 5.0/1000 person-years). Relative to no BP medications and normotension, those with systolic BP ≥140 mm Hg and HDD in tertiles ≥2 had a 2.3x to 3.7x greater risk of incident stroke ( Table ). Those with systolic BP &lt;140 mm Hg had similar stroke risk across HDD groupings. Conclusion: Among Black and White US adults without prevalent stroke, higher HDD was associated with greater risk of incident stroke in those with systolic BP ≥140 mm Hg, possibly reflecting greater disease severity and treatment resistance. These findings support aggressive BP control with antihypertensive medications to lower stroke risk among adults with hypertension.

Th17/Treg imbalance in patients with primary hyperaldosteronism and resistant hypertension.

Inflammation plays a pivotal role in blood pressure regulation. Data on experimental models of hypertension and hypertensive patients reflect the imbalance between T regulatory (Treg) and Th17 effector cells (Th17). The aim of this study was to quantify peripheral blood Treg lymphocytes and Th17 subsets in individuals with primary hyperaldosteronism (PHA) and resistant hypertension (RHT) presenting with elevated blood pressure levels and augmented cardiovascular risk when compared with normotensive controls (CTRL). Twenty CTRL participants, 21 patients with PHA, and 20 patients with RHT were enrolled. Plasma renin and angiotensin II, serum aldosterone concentration, ambulatory blood pressure monitoring (ABPM), echocardiography, clinical data, and phenotype of peripheral blood cells were assessed. There were no statistically significant differences in terms of age and sex between the groups. Similar systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in ABPM were observed in individuals with PHA and RHT. PHA patients had lower angiotensin II and 4‑fold higher aldosterone concentrations than CTRL patients. Both, PHA and RHT were associated with cardiac hypertrophy and coronary artery disease. RHT patients presented a significantly higher CD4+IL‑17A+ T cell number when compared with PHA and CTRL ones. The number of CD4+CD25+FOXP3+ T cells did not differ between patients with secondary hypertension and normotensive controls. Finally, positive correlations between the data on 24 h SBP and the content of CD4+IL‑17A+ and CD4+CD25+FOXP3+ in the PHA were found. Elevated 24 h SBP in PHA was associated with the increased numbers of CD4+IL‑17 and CD4+CD25+FOXP3+ T cells.

Abstract 13411: Vasodilatory Capacity With Regadenoson Myocardial Perfusion Imaging In Patients With End Stage Liver Disease

Introduction: The sensitivity and specificity of myocardial perfusion imaging in end stage liver disease (ESLD) patients ranges between 35-37% and 63-88%, respectively. Despite high levels of endogenous catecholamines and angiotensin, ESLD induced arterial vasodilation may exhaust the vasodilatory capacity of common pharmacologic stress agents. Reduced heart rate (HR) response to vasodilator stress test has been associated with increased major adverse cardiac events (MACE) in pre-transplant end stage renal disease patients but there is limited data in ESLD. We hypothesize that the hemodynamic response, measured as a change in HR and systolic blood pressure (SBP), during regadenoson stress test will be more robust when associated with low level exercise. Method: Forty-five subjects with ESLD referred for pre-transplant risk stratification were assigned to 1 of 3 groups: regadenoson alone or associated with low level treadmill or bicycle maneuver. Regadenoson was injected 2 minutes after low level exercise in the treadmill and bicycle groups. Myocardial perfusion images and hemodynamic changes were performed and interpreted as part of the standard clinical protocol. Results: There were 21 subjects in the regadenoson alone group, 10 in the low level treadmill group, and 14 in the bicycle maneuver group. There were no perfusion abnormalities in any of the groups and LVEF were greater than 50%. There was a statistically significant difference in HR response between the 3 groups (p = 0.015), but not in percentage SBP change between the 3 groups (p = 0.4). Pairwise comparison of regadenoson alone vs. low level treadmill percentage HR change showed statistical significance (p = 0.011). There was no MACE at 6-month follow-up. Conclusions: Low level exercise achieved a higher HR response than the other groups with a similar SBP response. The increased HR response may represent a more physiologic assessment of the true vasodilatory capacity remaining in ESLD patients.

Paradoxical increase in ambulatory systolic blood pressure in coarctation of aorta as compared to idiopathic hypertension

Abstract Background The relationship between office vs ambulatory blood pressure (BP) indices is well-studied in patients with idiopathic hypertension, and based on these data, it is known that average 24-hour ambulatory BP is typically lower than office BP. However, emerging data show that office systolic BP (SBP) underestimates arterial afterload in patients with coarctation of aorta (COA), and minimal increase in stroke volume during low intensity exercise results in exaggerated rise in SBP as compared to those with idiopathic hypertension. We hypothesized that COA patients will have higher ambulatory SBP and a higher prevalence of masked hypertension compared to patients with idiopathic hypertension. Methods Case-control study of 118 COA patients and 118 patients with idiopathic hypertension matched by age, sex, body mass index and office SBP. Results Although both groups had similar office SBP (132±17 mmHg) by design, the COA group had paradoxical increases in 24-hour ambulatory SBP (135±14 vs 126±13, p&amp;lt;0.001) and daytime ambulatory SBP (142±16 vs 130±13, p&amp;lt;0.001), and less nocturnal dipping (−3±5 vs −9±4, p&amp;lt;0.001). The COA group also had a higher prevalence of masked hypertension (36 [31%] vs 14 [12%], p&amp;lt;0.001), and worse arterial function indices. Conclusion These findings underscore the potential limitations of relying on office SBP for screening/monitoring of hypertension in COA and potential pitfalls in extrapolating idiopathic hypertension guidelines recommendations to the treatment of COA. It also provides rationale for further studies to determine if pharmacologic BP interventions guided by ambulatory BP data will improve clinical outcomes in the COA population. Funding Acknowledgement Type of funding sources: None.

Coarctation of aorta is associated with left ventricular stiffness, left atrial dysfunction and pulmonary hypertension

Brachial systolic blood pressure (BP) is the most commonly used metric for monitoring hypertension. However, recent studies suggest that brachial systolic BP underestimates left ventricle (LV) systolic load in patients with coarctation of aorta (COA). Since brachial systolic BP is used as a surrogate of arterial afterload in clinical practice, it is important to determine how well it correlates with LV remodeling and stiffness in patients with COA as compared to patients with idiopathic hypertension. This is cross-sectional study of COA patients with hypertension (COA group) and adults with idiopathic hypertension (control group). Both groups were matched 1:1 based on age, sex, BMI and systolic BP. We hypothesized that the COA group will have higher LV systolic and diastolic stiffness, and more advanced left atrial remodeling and pulmonary hypertension. We assessed LV systolic stiffness using end-systolic elastance, and diastolic stiffness using LV stiffness constant and chamber capacitance (LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg) RESULTS: There were 112 patients in each group. Although both groups had similar systolic BP, the COA group had a higher end-systolic elastance (2.37 ± 0.74 vs 2.11 ± 0.54 mm Hg/mL, P= .008), higher LV stiffness constant (6.91 ± 0.81 vs 5.93 ± 0.79, P= .006) and lower LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg (58 ± 9 vs 67 ± 11 mL/m2, P< .001). Additionally, the COA group had more advanced left atrial remodeling and higher pulmonary artery pressures which is corroborating evidence of high LV filling pressure. COA patients have more LV stiffness and abnormal hemodynamics compared to non-COA patients with similar systolic BP, suggesting that systolic BP may underestimate LV systolic load in this population. Further studies are required to determine whether the observed LV stiffness and dysfunction translates to more cardiovascular events during follow-up, and whether adopting a stricter systolic BP target in clinical practice or changing threshold for COA intervention will lead to less LV stiffness and better clinical outcomes.

Combined spinal epidural anesthesia in obese parturients undergoing cesarean surgery

There is asignificant increase in number of obese pregnant women worldwide. Obese parturients undergoing cesarean section have a higher risk for hypotension and require higher doses of vasopressors following spinal anesthesia compared to nonobese parturients. This study aimed to compare the maternal hemodynamic changes when combined spinal-epidural anesthesia (CSEA) is induced in the left lateral decubitus and sitting positions in obese pregnant women undergoing elective cesarean section. In this study, pregnant women with full-term gestation diagnosed as obese undergoing elective cesarean section were included. Two groups were formed: the CSEA was performed in left lateral position in groupI (n = 50) and in sitting position in groupII (n = 50). At the end of the CSEA procedure, patients were placed in the supine position. When the sensory block reached at the upper level of T6 dermatome, surgery was initiated. Hemodynamic, anesthetic and neonatal parameters were recorded. In all patients, CSEA was successful and sufficient anesthesia was provided for surgery. Time to reach T6 dermatome sensory level in groupII was found to be longer than groupI (P = 0.011). At 20 min after spinal injection, the maximum sensory block level was similar in both groups. There were no significant differences between groups in terms of sensory block time and the time to requiring postoperative supplemental analgesics. There were no significant differences in terms of the volume of intravenous fluid administered, ephedrine and atropine requirements between groups. Both groups had similar systolic blood pressure, heart rate and oxygen saturation values during surgery and postoperatively. While both groups had similar diastolic blood pressure (DBP) values during surgery and at the 1st postoperative hour, groupII had lower DBP values at the 2nd postoperative hour compared with groupI (P = 0.04). Left lateral decubitus and sitting positions during performance of CSEA lead to similar maternal hemodynamic changes in obese pregnant women undergoing cesarean section.

The Impact of Perioperative Blood Pressure on Hematoma Development After Panniculectomy.

Hematoma affects 10% to 13% of patients undergoing panniculectomy. Although elevated perioperative blood pressure has been associated with hematoma after rhytidectomy, this has not been established for panniculectomy. We sought to determine the impact of perioperative blood pressure on hematoma development in patients undergoing panniculectomy. A retrospective review was performed on patients undergoing isolated panniculectomy procedures. Blood pressure parameters recorded included systolic blood pressures (SBPs), diastolic blood pressures (DBPs), and mean arterial pressure. The mean, peak, and trough blood pressure values were recorded. Preoperative, intraoperative, and postoperative blood pressures were recorded, and differences between phases were calculated. Univariate and multivariate logistic regressions were performed. One hundred forty-three patients were identified, which included 84% (n = 120) women and 17% (n = 23) men. A history of hypertension was present in 55% (n = 79) of patients, of which 91% (n = 72) were medically controlled. Preoperative antiplatelet or anticoagulation was used in 21% (n = 31) of patients. Seven patients (5%) developed a hematoma, of which 5 required operative drainage. Development of hematoma was not associated with patient, surgical, or postoperative pain variables. There was an association between hematoma and elevated postoperative blood pressures on univariate and multivariate analyses. The mean peak SBP in the hematoma group was 160 mm Hg in comparison to 141 mm Hg in the nonhematoma group. For each 10-mm Hg increase in postoperative peak SBP, the odds of a hematoma increased by 2.8 times. When comparing phases of care, hematoma patients had similar intraoperative and postoperative peak SBP, but their postoperative SBP was 19 mm Hg higher than preoperative baseline. Conversely, nonhematoma patients had a postoperative blood pressure that was similar to their preoperative baseline and 20 mm Hg lower than their intraoperative values. Hematoma is associated with elevated postoperative blood pressures. A postoperative mean peak SBP of 160 mm Hg was associated with hematoma, and for each 10 mm Hg, the risk of hematomsa increased by 2.8 times. The risk of hematoma may be reduced by strict postoperative blood pressure control. We recommend a postoperative peak SBP goal of 140 mm Hg or less, with a value equal to or less than their preoperative baseline and 20 mm Hg lower than their intraoperative pressure.