Changes In BP Research Articles

#5699 IS GFR DECLINE INDUCED BY SGLT-2 INHIBITOR OF CLINICAL IMPORTANCE?

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcome and with nephroprotection independent of diabetes status. However, the use of SGLT2i often cause an initial decline in estimated glomerular filtration rate (eGFR). This study addresses the question whether there is a relationship between vascular improvement and GFR dipping. Method We measured GFR (mGFR) and calculated GFR (eGFR) in 65 patients with T2D at baseline and after 12 weeks of treatment with either a combination of Empagliflozin (E) + Linagliptin (L) (n = 34) or Metformin (M) + Insulin (I) (n = 31). mGFR was measured using the gold standard clearance technique by infusion of inulin. In addition, pulse wave velocity (PWV) was obtained at office and under ambulatory conditions. We splitted the study cohort according to the median change of mGFR after 12 weeks and compared the baseline characteristics. Results mGFR and eGFR decreased significantly with E+L and with M+I (Ott C et. al. Cardiovasc Diabetol. 2021). However, no correlation was noticed between the change of mGFR and change of eGFR for either treatment cohorts (E+L: p = 0.404; M+I: p = 0.460). We found a significant decrease in office PWV in the E+L group only (8.2±1.6 to 7.8±1.5, p = 0.028) without any change in 24-h PWV. The change of office PWV correlated with the change of mGFR (p = 0.009) in E+L group only and remained significant after adjustment for the change of office systolic BP (p = 0.018). In addition, we observed a correlation between the change of high sensitive C reactive protein (hsCRP) and change in mGFR (p = 0.031). We identified patients with higher albumin excretion (p = 0.044), higher fasting plasma glucose (p = 0.014) and high hsCRP (p = 0.057) to have a greater decline in mGFR with E+L. Conclusion First, eGFR may not be an appropriate parameter to assess the true change in renal function after receiving E+L in a single patient. Second, after E+L medication a high decrease in mGFR goes in parallel with vascular improvement and less inflammation thereby reflecting the pleiotropic pharmacologic effects of SGLT 2 inhibitors.

#4949 COMBINED ORAL DIURETICS: A BETTER ALTERNATIVE FOR NEPHROTIC EDEMA THAN INTRAVENOUS FUROSEMIDE?

Abstract Background and Aims Edema is a serious complication of nephrotic syndrome and is the main reason why patients usually address to a doctor. There is no guideline on managing nephrotic edema. Besides non pharmacological interventions such as sodium and water restrictions, most doctors would choose high doses of intravenous furosemide as the first option, but still many patients fail to properly decrease their volume overload, as they become diuretic resistant. Amiloride, an ENaC mediated diuretic, is an optimistic management option, especially when used with other diuretics. The aim of the present study was to assess the non inferiority of the combined oral diuretics furosemide and the fixed combination of hydrochlorothiazide/amiloride diuretics with intravenous furosemide in diuretic resistant nephrotic edema. Method We conducted a prospective randomized trial in 22 patients with diuretic resistant nephrotic edema. Based on a computer-generated randomization we assigned patients to receive either intravenous furosemide (40 mg bolus and then continuous administration of 5 mg/h) or oral furosemide (40 mg/day) and hydrochlorothiazide/amiloride (50/5 mg/day). Clinical and laboratory measurements were performed daily, for five days (body weight, urinary output, blood pressure and hydration status by bioimpedance twice, creatinine, urea, albumin, hematocrit, Na, K, Ca, Mg, bicarbonate, pH). The primary outcome was weight and hydration status change from baseline to day 5. Secondary outcomes were safety outcomes (low blood pressure, severe dyselectrolytemia, acute kidney injury or aggravated hypervolemia). Results The patients were equally distributed between the two groups. Mean age was 47,77±15,97 (54,5% females and 45,5% males). Half of the patients had membranous nephropathy (45,5%), followed by minimal change disease (22,7%) and lupus nephritis (9,1%). 86,4% of patients had their first episode of nephrotic edema. The mean weight decrease was of significantly larger magnitude in the combined oral diuretics group compared with the intravenous furosemide group (-7,97±2,83 [SD] vs -4,5±2,6 [SD] kg; p = 0,018). Although the increase in 24-hour urine sodium excretion was higher in combined oral diuretics as compared to intravenous furosemide group, this increment was not statistically significant different (26,79±33,48 [SD] vs 16,04±42,81 mmol/24 h [SD]; p = 0,5). Mean values for changes in systolic and diastolic BP, 24-hour urine volume, hydration status measured by bioimpedance were not significantly different between the two groups. A total of 5 patients could not be followed through, 4 in the intravenous furosemide (two patients experienced low blood, one patient had no response to iv furosemide and one patient suffered from insomnia due to iv pump) and one patient in the oral combination of diuretics group had severe hyperkalemia (>6,5 mmol/l). Conclusion Combined oral diuretics with furosemide, amiloride and hydrochlorothiazide is more effective and safer than intravenous furosemide for the treatment of refractory nephrotic edema. These results make amiloride a promising diuretic and further trials with larger sample sizes and longer follow-up are needed in this regard.

ASSOCIATIONS OF INTER-ARM BLOOD PRESSURE DIFFERENCE WITH TREATMENT RESPONSE IN NEWLY TREATED HYPERTENSION

Objective: Inter-arm differences (IAD) in systolic blood pressure (SBP) predict future cardiovascular mortality and morbidity. IAD varies between measures and gets smaller with repeated measures. The relationship of IAD to response to antihypertensive treatment is unknown. We set out to examine associations of IAD with BP treatment response over 18 weeks in treatment-naïve adults with moderate to severe hypertension. Design and method: We previously reported that nurse-led accelerated stepwise management of treatment-naïve grade II/III hypertension is feasible, safe and effective, achieving control of SBP to < 140 mmHg for 76% after 18 weeks. Using this cohort, univariable associations of IAD (mean of 8 simultaneous BP measurements) with vascular and clinical indices, and with BP change on treatment, were examined with mixed-effects linear regression models. Candidate univariable indices (p<0.2) entered multivariable modelling. Regression modelling of change in IAD was undertaken. All analyses adjusted for age, sex and entry SBP. Results: For 52 participants (mean age 59; 42% female), mean (standard deviation: SD) entry SBP was 171 (13.9) mmHg falling, after protocol-led treatment intensification, to 131 (10.7) mmHg at 18 weeks; mean systolic IAD was 4.5 (4.2) mmHg at entry and 3.9 (4.3) mmHg at 18 weeks (p = 0.28). In final adjusted models, IAD at entry was associated with handedness, height, body mass index, smoking and absence of pedal pulses. Greater reduction of SBP from entry to 18 weeks was associated with lower entry IAD, greater SD of daytime ambulatory BP, smoking history and handedness. Adjusted change in IAD over 18 weeks was correlated with falls in SBP (Adjusted R2 = 0.56). Conclusions: These data associate greater systolic IAD with reduced response to intensive BP lowering, and correlate reduction in IAD with change in BP. Slower BP target achievement can carry prognostic implications, suggesting one possible mechanism whereby IAD might predict future mortality.

THE SYNERGISTIC EFFECTS OF PROINFLAMMATORY CYTOKINES ON CARDIOVASCULAR FUNCTION AND SYMPATHETIC OUTFLOW IN RAT

Objective: Inflammation has been implicated in the pathophysiology of cardiovascular dysfunction and neurohumoral activation in cardiovascular diseases. Our previous work has demonstrated that proinflammatory cytokines (PICs) in cardiovascular/autonomic brain regions contribute significantly to the sympathetic excitation and cardiac dysfunction in heart failure and hypertension. Notably, the chronic inflammatory conditions in these disease settings are caused by numerous inflammatory cytokines and chemokines. Given that the elevated levels of a single effector cytokine in the pathophysiological condition are insufficient to cause a significant change in hemodynamic and sympathetic responses, how PIC-driven neuroinflammation promotes sympathetic activation remains unclear. This work sought to determine whether PICs in the brain have a synergistic action to exaggerate their inflammatory effects on hemodynamic and sympathetic responses in rats. Design and method: Blood pressure (BP, mmHg), heart rate (HR, beats/min) and renal sympathetic nerve activity (RSNA, % change) were continuously recorded for 4-5 hours in urethane anesthetized male Sprague Dawley rats. The inflammatory cytokines tumor necrosis factor-↑ (TNF-↑), interleukin (IL)-1↓, IL-6 and vehicle were injected intracerebroventricularly (ICV). Results: We found that while ICV injection of TNF-↑, IL-1↓ or IL-6 alone at a low dose (10 ng, respectively) did not induce significant changes in BP, HR and RSNA, the combined injection of all three cytokines at the same dose (10 ng) elicited a substantial (*p<0.05) increase in BP (18.2 ± 2.1*), HR (62 ± 7*) and RSNA (94.5 ± 5.2 %*), that began within 15-20 mins. These responses peaked at 2-3 hours after ICV injection and remained elevated for the rest of the recording period. Additionally, ICV injection of TNF-↑, IL-1↓ or IL-6 alone at a high dose (50 ng, respectively), produced a dramatic and long-lasting increase in BP, HR and RSNA, that closely resembles the time course and response pattern induced by ICV injection of all three cytokines concurrently at the low dose (10 ng). Conclusions: These data suggest a synergistically excitatory action of PICs in the brain on sympathetic outflow. Interventions that simultaneously target multiple cytokines may have an extended anti-inflammatory effect of reducing sympathetic excitation in hypertension and heart failure.

HOME BLOOD PRESSURE MONITORING WITH A DIGITAL BLOOD PRESSURE COACH. A PROSPECTIVE ANALYSIS OF INDIVIDUAL USER DATA

Objective: The influence of baseline BP category and measurement duration on home blood pressure monitoring (HBPM) are still poorly defined, particularly when used in conjunction with a digital application. Design and method: This is a prospective analysis of real-world user data from a digital BP-coach (Manoa app ) in the period from April 2020 (release of the Manoa app) to November 2021 in Germany. The app was freely available in Germany during this period in all major app stores (iOS, Android). 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. Results: 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%. Conclusions: With a digital HBPM-protocol, five consecutive measurement days are required for a reliable diagnosis and BP categorization. However, especially at therapeutic thresholds, additional measurement days are often required. Excluding day 1 from the protocol resulted in blood pressure reclassifications in 8.4% of all cases, with therapeutic relevance in 3.8% of cases. 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.

Detecting Orthostatic Intolerance in Long COVID in a Clinic Setting.

A likely mechanism of Long COVID (LC) is dysautonomia, manifesting as orthostatic intolerance (OI). In our LC service, all patients underwent a National Aeronautics and Space Administration (NASA) Lean Test (NLT), which can detect OI syndromes of Postural Tachycardia Syndrome (PoTS) or Orthostatic Hypotension (OH) in a clinic setting. Patients also completed the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), a validated LC outcome measure. Our objectives in this retrospective study were (1) to report on the findings of the NLT; and (2) to compare findings from the NLT with LC symptoms reported on the C19-YRS. NLT data, including maximum heart rate increase, blood pressure decrease, number of minutes completed and symptoms experienced during the NLT were extracted retrospectively, together with palpitation and dizziness scores from the C19-YRS. Mann-Witney U tests were used to examine for statistical difference in palpitation or dizziness scores between patients with normal NLT and those with abnormal NLT. Spearman's rank was used to examine the correlation between the degree of postural HR and BP change with C19-YRS symptom severity score. Of the 100 patients with LC recruited, 38 experienced symptoms of OI during the NLT; 13 met the haemodynamic screening criteria for PoTS and 9 for OH. On the C19-YRS, 81 reported dizziness as at least a mild problem, and 68 for palpitations being at least a mild problem. There was no significant statistical difference between reported dizziness or palpitation scores in those with normal NLT and those with abnormal NLT. The correlation between symptom severity score and NLT findings was <0.16 (poor). We have found evidence of OI, both symptomatically and haemodynamically in patients with LC. The severity of palpitations and dizziness reported on the C19-YRS does not appear to correlate with NLT findings. We would recommend using the NLT in all LC patients in a clinic setting, regardless of presenting LC symptoms, due to this inconsistency.

PO-01-078 THE ACUTE PHYSIOLOGIC EFFECTS OF OSTEOPATHIC MANIPULATIVE TREATMENT IN PATIENTS WITH CARDIAC IMPLANTABLE ELECTRONIC DEVICES: A RANDOMIZED CONTROLLED TRIAL

Osteopathic manipulative treatment (OMT) is a procedure used to improve physiologic function and maintain homeostasis. OMT modulates the autonomic nervous system (ANS) and augments heart rate variability (HRV) in healthy subjects. The acute physiologic effects of OMT have been reported in patients with heart failure, but not in those with cardiac implantable electronic devices (CIEDs). To assess the short-term physiologic effects of OMT on heart rate, respiratory rate, arterial blood pressure, and HRV in patients with CIEDs. Cardiac patients with CIEDs at an osteopathic medical center were recruited into a randomized controlled trial (ClinicalTrials.gov ID: NCT0400474) and assigned to either OMT or light touch (control) groups. Short-term physiologic data was recorded pre and post intervention (including one minute HRV via photoplethysmography). HRV was calculated using root mean square of successive RR interval differences (RMSSD). Student’s t-test was used to compare groups; p < 0.05. 20 subjects were enrolled (10 OMT/10 control). Table 1 shows physiologic measurements prior to and post intervention. Changes in HR, RR, BP, and SpO2 were no different between groups before and after intervention; OMT HRV decreased by 12.39 + 34.05 ms, whereas control HRV increased by 19.94 + 18.54 ms (p=0.022). There was a significant decrease in HRV in the OMT group, but no difference in the remaining standard physiologic variables. The difference in HRV is opposite of what would be expected, and could be due to the effects of OMT on the ANS, altered cardiac response in this population, and possibly a decrease in ectopy. Further evaluation of CIED data (arrhythmias, HRV and activity level) may be helpful in determining the long-term effects of OMT on cardiac arrhythmia patients.

Sex Differences in the Diastolic Blood Pressure Response to Orthostasis in Obstructive Sleep Apnea

Hypertension is commonly observed with obstructive sleep apnea (OSA), partly due to dysregulation of sympathetic activity. As OSA is considered male-dominant, potential sex differences in the sympathetic regulation of BP have yet to be explored. Hemodynamic responses to an orthostatic challenge have implications for cardiovascular risk and are sympathetically-modulated. Therefore, we tested the hypothesis that females with OSA have differential BP and HR responses to orthostasis relative to males with OSA. 160 individuals not taking antihypertensive medications completed an overnight polysomnography to identify OSA (apnea-hypopnea index ≥5 events/hr). Orthostatic responses were quantified as the changes (Δ) in BP and HR (assessed via brachial cuff) from rest (10min supine) to 60sec post-standing. Females with (n=17, 42±14yrs, 30.7±6.0kg/m2) and without (n=43, 39±12yrs, 27.6±5.7kg/m2) OSA were compared to males with (n=60, 45±11yrs, 31.4±3.8kg/m2) and without (n=40, 39±13yrs, 27.4±3.1kg/m2) OSA using a one-way ANOVA. There were no between-group differences in age (p&gt;0.05 for post-hoc comparisons) and BMI was lower in both females, and males, without OSA relative to males with OSA (p&lt;0.05 for both). ΔSBP did not differ between females with (1±8mmHg) and without (2±8mmHg) OSA nor between males with (4±8mmHg) and without OSA (5±12mmHg, ANOVA p=0.37). Females with OSA had a blunted ΔDBP relative to females without OSA (5±7 vs. 10±6mmHg, p&lt;0.05), whereas males with and without OSA demonstrated similar responses (9±8 vs. 10±6mmHg, p=0.95). ΔHR did not differ between females with (8±8beats/min) and without OSA (9±11beats/min) nor between males with (13±10beats/min) and without OSA (12±10beats/min, ANOVA p=0.06). ΔDBP was not associated with the apnea-hypopnea index (Spearman's r=-0.19, p=0.47; Spearman’s r=0.23, p=0.08) nor nadir SpO2 (Spearman's r=0.27, p=0.29; Spearman’s r=0.06, p=0.64) in females or males with OSA. These data suggest that OSA influences the DBP response to orthostasis in females to a greater extent than males. As DBP is associated with sympathetic activation, this finding could indicate greater sympathetic dysregulation in females, relative to males, with OSA. This work was supported by the National Institutes of Health T32-HL007111 (JMB), HL134808 (NC), HL065176 (PS and VKS), and HL134885 (VKS). 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 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.

Associations of Urine Biomarkers of Kidney Tubule Health With Incident Hypertension and Longitudinal Blood Pressure Change in Middle-Aged Adults: The CARDIA Study.

Urine biomarkers of kidney tubule injury associate with incident hypertension in older adults with comorbidities, but less is known about these associations in younger adults. In 1170 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults; mean age, 45 years; 40% Black people; 56% women) without hypertension, cardiovascular disease, or kidney disease at baseline, we examined associations of urine MCP-1 (monocyte chemoattractant protein-1), α1m (alpha-1-microglobulin), KIM-1 (kidney injury molecule-1), EGF (epidermal growth factor), IL (interleukin)-18, YKL-40 (chitinase-3-like protein 1), and UMOD (uromodulin) with incident hypertension (onset of systolic blood pressure [BP] ≥130 mm Hg or diastolic BP ≥80 mm Hg or initiation of hypertension medications) and longitudinal BP change in models adjusted for hypertension risk factors, estimated glomerular filtration rate, and albuminuria. After a median 9.9 (interquartile range, 5.9-10.2) years, 376 participants developed incident hypertension. In demographic-adjusted analyses, higher tertiles of EGF associated with lower risk of incident hypertension in both Black and White participants. After multivariable adjustment, the risk of incident hypertension remained lower in tertile 2 (hazard ratio, 0.70 [95% CI, 0.50-0.97]) and tertile 3 (hazard ratio, 0.58 [0.39-0.85]) of EGF versus tertile 1. In fully adjusted models, participants in EGF tertile 3 had smaller 10-year increases in systolic (-3.4 [95% CI, -6.1 to -0.7] mm Hg) and diastolic BP (-2.6 [95% CI, -4.6 to -0.6] mm Hg) than tertile 1. Other biomarkers showed inconsistent associations with incident hypertension and BP change. In middle-aged adults without hypertension, cardiovascular disease, or kidney disease, higher urine EGF associated with lower risk of incident hypertension and lower 10-year BP elevations.

OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study

OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. Does OSA in adults associate with the composition and functional potential of the human gut microbiota? We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.

Effect of Sodium Bicarbonate on Systolic Blood Pressure in CKD: A Systematic Review and Meta-Analysis.

Individuals with CKD are at a higher risk of cardiovascular morbidity and mortality. Acidosis is positively correlated with CKD progression and elevated systolic BP. Sodium bicarbonate is an efficacious treatment of acidosis, although this may also increase systolic BP. In this systematic review and meta-analysis, we summarize the evidence evaluating systolic BP and antihypertensive medication change (which may indicate systolic BP change) in response to sodium bicarbonate therapy in individuals with CKD. Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) trials registry databases were searched for randomized control trials where sodium bicarbonate was compared with placebo/usual care in CKD stage G1-5 non-dialysis-dependent populations. Random effects meta-analyses were used to evaluate changes in systolic BP and BP-modifying drugs after sodium bicarbonate intervention. Fourteen randomized control trials (2110 individuals, median follow-up 27 [interquartile range 97] weeks, mean age 60 [SD 10] years, mean systolic BP 136 [SD 17] mm Hg, mean eGFR 38 [SD 10] ml/min, mean serum bicarbonate 22 [SD 4] mmol/L) were eligible for inclusion. Meta-analysis suggested that sodium bicarbonate did not influence systolic BP in individuals with CKD stage G1-5. Results were consistent when stratifying by dose of sodium bicarbonate or duration of intervention. Similarly, there was no significant increase in the use of antihypertensive medication or diuretics in individuals taking sodium bicarbonate, whereas there was a greater decrease in antihypertensive medication use in individuals taking sodium bicarbonate compared with controls. Our results suggest, with moderate certainty, that sodium bicarbonate supplementation does not adversely affect systolic BP in CKD or negatively influence antihypertensive medication requirements.

Joint modeling of longitudinal changes of blood pressure and time to remission of hypertensive patients receiving treatment: Bayesian approach.

Hypertension is a widespread condition when the blood's force on the artery walls is extremely high to develop adverse health effects. This paper aimed to jointly model the longitudinal change of blood pressures (systolic and diastolic) and time to the first remission of hypertensive outpatients receiving treatment. A retrospective study design was used to collect appropriate data on longitudinal changes in blood pressure and time-to-event from the medical charts of 301 hypertensive outpatients under follow-up at Felege Hiwot referral hospital, Ethiopia. The data exploration was done using summary statistics measures, individual profile plots, Kaplan-Meier plots, and log-rank tests. To get wide-ranging information about the progression, joint multivariate models were employed. A total of 301 hypertensive patients who take treatment was taken from Felege Hiwot referral hospital recorded between Sep. 2018 to Feb. 2021. Of this 153 (50.8%) were male, and 124 (49.2%) were residents from rural areas. About 83(27.6%), 58 (19.3%), 82 (27.2%), and 25 (8.3%) have a history of diabetes mellitus, cardiovascular disease, stroke, and HIV respectively. The median time of hypertensive patients to have first remission time was 11 months. The hazard of the patient's first remission time for males was 0.63 times less likely than the hazard for females. The time to attain the first remission for patients who had a history of diabetes mellitus was 46% lower than for those who had no history of diabetes mellitus. Blood pressure dynamics significantly affect the time to the first remission of hypertensive outpatients receiving treatment. The patients who had a good follow-up, lower BUN, lower serum calcium, lower serum sodium, lower hemoglobin, and take the treatment enalapril showed an opportunity in decreasing their blood pressure. This compels patients to experience the first remission early. Besides, age, patient's history of diabetes, patient's history of cardiovascular disease, and treatment type were the joint determinant factors for the longitudinal change of BP and the first remission time. The Bayesian joint model approach provides specific dynamic predictions, wide-ranging information about the disease transitions, and better knowledge of disease etiology.

INFLUENCE OF STRESS ON VITAL SIGNS AMONG THE ORAL SURGEON DURING COMPLICATED DENTAL EXTRACTIONS AND REMOVAL OF IMPACTED TOOTH- AN OBSERVATIONAL STUDY

Dentistry is identied as a stressful profession since it involves more physical work in addition to the routine surgical stress. Different studies pointed out that long-term consequence of these stressors make negative impacts on the professionals. There are many stress related studies available in the dental specialty but very few studies are focused about vital changes. Here we study the basic vital changes that happen among the oral surgeon during the minor surgical procedure. The aim of this study is to evaluate the blood pressure, pulse rate and respiratory rate uctuations among the oral surgeon during complicated dental extraction and removal of impacted tooth. The vital changes comparison were appreciated by calculating the difference in recorded values at three chronological points, 5 minutes before the dental procedure, intra operatively and immediately at the end of the procedure. The results showed there were greater changes in BP and pulse rate during complicated dental extraction and removal of impacted tooth and there was no signicant differences in the respiratory rate. In order to maintain the normal vitals it is suggested to follow the proper diagnosis and treatment plan before the procedure.

S-36-2: SOCIAL FRAMEWORK TO PROMOTE SALT REDUCTION AND HEALTHY DIETS WITHIN HYPERTENSION AND STROKE PREVENTION

Beyond the physiological effects of sodium and potassium strong evidence from animal, clinical and epidemiological studies, has implicated excess dietary sodium and low potassium intake as major factors associated with the development of hypertension and increase in stroke risk. Daily salt intake of 5–6 g 85–100 mmol was recommended for the general population i.e. 2.0–2.4 g Na along with K intake to at least 90 mmol d 3.51 g perd. Randomized trials demonstrate that salt reduction and potassium increase in diet lowers blood pressure and reduces the risk of brain damage and cardiovascular disease. Population studies showed that 15 percent reduction of salt intake from 9.5 g/day was associated with a 40 percent reduction of stroke and CHD mortality. Potassium lowers BP via multiple mechanisms, by acting directly on the vasculature and by triggering a signalling cascade mediated by endothelium and also reduces salt-sensitivity. A meta-analysis of 21 RCTs reported that increasing potassium intake lowers BP 3.5/2.0 mm Hg and the risk of stroke. Eating more than 11 g of salt /day was associated with 2.5 times more likely to have a stroke than those who got less than 4.5 g /day. Switching from regular salt to a salt substitute reduced the risk for stroke, major CV events and death in a large trial of adults in rural China with a history of stroke or high risk for stroke. High salt intake reduces resting cerebral blood flow and induces endothelial dysfunction in mice and impairs vasodilatory responses of cerebral vessels. Gut-brain relation links dietary salt to cognitive impairment though a gut-initiated adaptative immune response damaging brain function via increase in circulating IL-17. A high potassium diet reduces cerebral infact size and improves vascular function independently of BP changes. Thus high salt and low potassium intake interfere in multtiple brain vascular strutural complex processes including fluid homeostasis and inflammatory mechanisms, immune responses and gut-microbiome-brain axis.

PS-C24-1: EFFECTS OF ANGIOTENSIN RECEPTOR-NEPRILYSIN INHIBITOR ON CAROTID ARTERIAL IMT AND ELASTIC MODULUS, BAPWV IN HYPERTENSIVE PATIENTS WITH HEART FAILURE

Objective: Sacubitril/valsartan is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT1) receptor. Effects of Sacubitril/valsartan on carotid arterial IMT and elastic modulus, baPWV in hypertensive patients with heart failure Methods: Thirty-three hypertensive patients with chronic heart failure (mean age 79 years, male 15) were assigned to receive Sacubitril/valsartan (gradual increase depending on the condition) of Sacubitril/valsartan added to existing drug therapies (average number of antihypertensive agents 3) or switched from ARB or ACE inhibitor for 6 months. Changes in home BP, BNP, NT-proBNP, hANP, estimated glomerular filtration rate (eGFR), baPWV and central blood pressure (cSBP) were evaluated. EΘ was obtained by the phased-tracking method (Kanai, Circulation 2003). At four locations of bilateral common carotid arteries, IMT and Etheta; were measured simultaneously. Results: The basal values before Sacubitril/valsartan administration of Body weight(BW), BNP, NT-proBNP, hANP, EF, serum K, eGFR, home early morning blood pressure, home early morning heart rate, baPWV, cSBP, IMT, EΘ were 63 ± 16 kg and 310 ± 237 pg /,mL, 1981 ± 237 pg / mL, 475 ± 514 pg / mL, 51 ± 14%, 4.2 ± 0.4 mEq / L, 46 ± 14 ml / min / 1.73 m2, 141 ± 8/75 ± 11 mmHg, 76 ± 14 bpm, 1526 ± 245 cm / sec, 137 ± 13 mmHg, 0.84 ± 0.12 mm, and 301 ± 141 kPa respectively. ARNI s reduced BW (-4%), BNP (-32%), NT-proBNP (-38%), home early morning blood pressure-17 / -10mmHg, and baPWV (-4%) significantly (p &lt; 0.05). In addition, EF (+ 5%) and hANP were significantly increased, and serum K and eGFR were unchanged. On the other hand, IMT (-5%) in carotid echo decreased, and EΘ decreased significantly. Conclusions: Sacubitril/valsartan was effective for BP control improved cardiac function and arterial stiffness in hypertensive patients with chronic heart failure. EΘ is a good surrogate marker for the early detection of vascular remodeling such as improvement of endothelial dysfunction prior to changes in IMT.

PS-BPP04-9: THE RXPATH RANDOMIZED TRIAL OF THE HYPERTENSION CANADA PROFESSIONAL CERTIFICATION PROGRAM: A NOVEL IMPLEMENTATION STRATEGY FOR HYPERTENSION GUIDELINES

The uptake of clinical practice guidelines into practice is poor for many chronic conditions, including hypertension. We designed a guidelines-based educational program for primary care clinicians, the Hypertension Canada Professional Certification Program (HC-PCP, www.hypertension.ca/professional-certification-program). It consists of four online modules, an online prospective patient registry, and expert evaluations of the blood pressure measurement technique and case management by the learner. We then evaluated its impact on patient level outcomes. Objective: The objective of RxPATH was to determine the effect of the HC-PCP for pharmacists on systolic blood pressure reduction in patients with poorly controlled hypertension. Design and Methods: Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy). Setting: Community pharmacies in Alberta, Canada Population: Pharmacists with prescriptive authority volunteered to participate. We enrolled patients with poorly controlled hypertension (BP &gt; 140/90mmHg or &gt; 130/80mmHg in those with diabetes), identified by their pharmacist. Intervention: Pharmacists were enrolled in the HC-PCP. They then provided this care to their patients with poorly controlled hypertension. Control: Pharmacists were given a copy of the Hypertension Canada Guidelines and provided usual care to their patients prior to undertaking the HC-PCP. Outcomes: The primary outcome was difference in change in systolic blood pressure between intervention and control groups at 3 months. We also evaluated patient satisfaction using the Consultant Satisfaction Questionnaire (CSQ). Results: We enrolled 890 patients from 61 pharmacies (104 pharmacists). Mean age was 61.6 (SD 14.1) years, 46% were female, 35.5% had diabetes, and mean baseline BP was 152.4 (SD 13.8)/87.0 (SD 10.6)mmHg. Change in systolic BP was 9.9 (SD 16.5) for the intervention group, compared to 9.9 (SD 16.2) mmHg in the control group, p = 0.29. Patient satisfaction using the CSQ was high at 76 (of 90 maximum). Conclusions: Most educational programs do not get evaluated at the patient level. RxPATH demonstrated that the HC-PCP intervention did not result in a greater reduction in systolic BP compared to control. While both groups did have clinically meaningful reductions in BP, possible reasons for lack of a difference with the intervention include: COVID-19 staffing/workload issues in pharmacies, selection bias for pharmacists interested in hypertension/contamination of usual care group, and short follow-up duration. Feedback on the HC-PCP from pharmacists was positive, patient satisfaction was high, and we plan to make this program widely available to primary care providers.

Biomarkers of mitochondrial dysfunction and inflammaging in older adults and blood pressure variability.

Most physiopathological mechanisms underlying blood pressure variability (BPV) are implicated in aging. Vascular aging is associated with chronic low-grade inflammation occurring in late life, known as "inflammaging" and the hallmark "mitochondrial dysfunction" due to age-related stress. We aimed to determine whether plasma levels of the pleiotropic stress-related mitokine growth/differentiation factor 15 (GDF-15) and two inflammatory biomarkers, interleukin 6 (IL-6) and tumor necrosis factor receptor 1 (TNFR-1), are associated with visit-to-visit BPV in a population of community-dwelling older adults. The study population consisted of 1096 community-dwelling participants [median age 75 (72-78) years; 699 females, 63.7%] aged ≥ 70years from the MAPT study. Plasma blood sample was collected 12months after enrolment and BP was assessed up to seven times over a 4-year period. Systolic (SBPV) and diastolic BPV (DBPV) were determined through several indicators taking into account BP change over time, the order of measurements and formulas independent of mean BP levels. Higher values of GDF-15 were significantly associated with increased SBPV (all indicators) after adjustment for relevant covariates [adjusted 1-SD increase in GDF-15: β (SE) = 0.07 (0.04), p < 0.044, for coefficient of variation%]. GDF-15 levels were not associated with DBPV. No significant associations were found between IL-6 and BPV, whereas TNFR1 was only partially related to DBPV. Unlike inflammation biomarkers, higher GDF-15 levels were associated with greater SBPV. Our findings support the age-related process of mitochondrial dysfunction underlying BP instability, suggesting that BPV might be a potential marker of aging.

Abstract 11808: Association Between Weight Gain After Smoking Cessation and Future Hypertension

Introduction: While smoking cessation reduces the risk of ischemic heart disease and stroke, it may be associated with weight gain. However, literature on the association between weight gain after smoking cessation and future hypertension is scarce. Methods: Of the 234,596 individuals who visited our health checkup center, 1085 individuals (mean age 47.5 ± 10.6 years; 1005 men) with previous history of smoking and available data after 5 years of smoking cessation were included. We compared the relationship between weight gain after smoking cessation and future hypertension (changes in blood pressure [BP] from baseline to 5 years, following smoking cessation and prescription rate of antihypertensive drugs. Multiple regression analysis was performed to evaluate changes in systolic and diastolic blood pressures (SBP and DBP) using covariates affecting BP changes from baseline values, such as weight gain, age, baseline weight, sex, and habitual alcohol consumption. Results: Since a median weight gain of 1.7 kg was observed after 1 year of smoking cessation, we divided participants into two groups: high weight gain (547 individuals, ≥1.7 kg) and low weight gain (538 individuals, &lt;1.7 kg). There was no significant difference in the prescription rate of antihypertensive drugs between the two groups (high weight gain vs. low weight gain), at the baseline (10.6% vs. 10.4%; p = 0.92) and 5 years following smoking cessation (25.4% vs. 28.4%, p=0.26). Nevertheless, the changes in SBP (high weight gain vs. low weight gain: 7.9±15.4 vs 3.8±15.4 mmHg, p&lt;0.001) and DBP (high weight gain vs. low weight gain: 4.2±10.5 vs 1.1±10.8 mmHg, p&lt;0.001) from baseline to 5 years following smoking cessation were significantly higher in the high weight gain group. Additionally, multiple regression analysis showed that changes in SBP were influenced by high weight gain (β=-0.13, p&lt;0.001) and age (β=0.06, p&lt;0.05), while changes in DBP were influenced by high weight gain (β=-0.14, p&lt;0.001), age (β=-0.10, p&lt;0.001), and baseline weight (β=-0.10, p&lt;0.01). Conclusions: Our results suggest that weight gain following smoking cessation subsequently leads to hypertension, and weight loss guidance may be useful in such cases.

Abstract 11679: Simple Text-Messaging and Social Support to Increase Hypertension Medication Adherence in Non-Hispanic Black Adults in New Orleans, LA

Introduction: Non-Hispanic Black adults (NHB) have the highest US CVD risk, the leading cause of mortality. Medication nonadherence predicts suboptimal HTN control. Self-measured blood pressure (SMBP) effectively tracks BP changes and medication response. Purpose: This New Orleans, LA predominantly NHB single cohort pilot study examined uncontrolled HTN utilizing bidirectional electronic messaging (BEM) with an interdisciplinary healthcare team assessing medication adherence, quality of life (QOL), and BP, without pharmacotherapeutic change. Methods: Participants were screened from Tulane Cardiology Clinic and community sources. Eligibility criteria included: uncontrolled HTN (BP &gt;130/80 mmHg), low Krousel-Wood (KW) adherence score, and smartphone access. Participants (n=36) were provided validated bluetooth-enabled BP devices synced to smartphones via a cloud-based BP recording app. Demographic information included: age, self-identified race (91.7% NHB), and sex. Pre- and post-study KW adherence scores, CDC Health Related QOL surveys, BMI and BP were obtained. Participants were followed with BEM for 8 weeks with SMBP and daily text reminders. Results: Mean age was 58.7±12.8 years; mean BMI was 34.8±7.8; 63.9% were female; 25.7 % with previous diabetes diagnosis; 72% with obesity. Nonadherence significantly improved with mean KW adherence composite score change from 2.19 to 1.58 (p = 0.0001). Mean baseline SBP/DBP was 142.19/81.19; SBP decreased significantly by mean 10.5±20.0 mmHg (p = 0.0027) with no significant change in DBP. There was a non-significant decline in the average summary index of unhealthy days during the previous 30 days from 9.1 days to 6.8 days, change -2.3 ± 10.7 (p = 0.21). Conclusions: A novel approach combining cloud-based bluetooth SMBP transmission with BEM health communication significantly improved medication adherence and systolic BP in a predominantly NHB urban cohort without modifying existing pharmacotherapy. “Supported in part by U54 GM104940 from the National Institute of General Medical Sciences of NIH, which funds the LA Clinical and Translational Science Center. Content is solely the responsibility of the authors and does not necessarily represent official views of the NIH.”