Long-term Blood Pressure Control Research Articles

Emerging RNAi Therapies to Treat Hypertension.

Hypertension (HTN), often dubbed the "silent killer," poses a significant global health challenge, affecting over 1.3 billion individuals. Despite advances in treatment, effective long-term blood pressure (BP) control remains elusive, necessitating novel therapeutic approaches. Poor control of BP remains a leading cause of cardiovascular morbidity and mortality worldwide and is becoming an even larger global health problem due to the aging population, rising rates of obesity, poorer dietary patterns and overall cardiometabolic health, and suboptimal rates of patient adherence and optimal BP control. Ribonucleic acid interference (RNAi) technology, which leverages the body's natural gene-silencing mechanism, has emerged as a promising strategy for several diseases and has recently been tested for its antihypertensive effects. We systematically reviewed peer-reviewed articles from databases including PubMed, EMBASE, and Scopus for studies examining RNAi's role in managing HTN, focusing on mechanisms, clinical utility, and safety profile. Key early-phase trials of some RNAi-leading candidate drugs are detailed. Also highlighted are challenges such as target specificity, delivery mechanisms, durability of effect, and immunogenicity. We conclude by summarizing how RNAi has a significant potential role in HTN therapy due to their unique benefits, such as long-term duration of action, infrequent dosing, and lack of major side effects.

Current approach to resistant hypertension

Resistant hypertension is the inability to achieve target blood pressure (<130/80 mmHg) despite using the maximum tolerated doses of three antihypertensive drugs, including a diuretic, or the need for four or more medications. It is linked to aging, obesity, obstructive sleep apnea, and chronic kidney disease, with contributing factors such as high sodium intake and sympathetic nervous system overactivity. Treatment includes optimizing diuretic use, with spironolactone proving highly effective. Lifestyle modifications, including sodium reduction and exercise, are critical. Emerging therapies like renal denervation offer promising long-term blood pressure control.

Immediate-Release versus Extended-Release Tacrolimus: Comparing Blood Pressure Control in Kidney Transplant Recipients – A Retrospective Cohort Study

Background: Hypertension (HTN) is a common side effect of tacrolimus (Tac), the first-line antirejection medication for kidney transplant recipients. The impact of immediate-release tacrolimus (Tac IR) dosed twice daily versus extended-release tacrolimus (Tac ER) dosed once daily on long-term blood pressure control in kidney transplant recipients remains understudied. This study aims to compare the use of Tac IR versus Tac ER in kidney transplant recipients and evaluate the effects of the different formulations on systolic blood pressure (SBP), diastolic blood pressure (DBP), and HTN crisis. Methods: This retrospective cohort study at a single institution collected baseline characteristics, time-varying exposure to Tac IR versus Tac ER, SBP, DBP, HTN crisis, and confounders at each posttransplant visit. A marginal structural linear mixed-effects model was employed to analyze the longitudinal blood pressure control in kidney transplant recipients receiving Tac IR and Tac ER. Results: The final analysis included 654 patients, with mean ages of 52.0 years for Tac IR and 50.3 years for Tac ER. Males constituted 56.7% in Tac IR and 55.0% in Tac ER. Notably, the black population had 2.44 times higher odds of receiving Tac ER after adjusting for the rest of the baseline characteristics. No difference was found between longitudinal SBP (p = 0.386, 95% CI: −1.00, 2.57) or DBP (p = 0.797, 95% CI: −1.38, 1.06). Conclusion: Our study indicates that posttransplant patients taking Tac ER exhibit no difference in chronic SBP and DBP controls compared to Tac IR.

P012 THE EFFECT OF AGE AND LONG-TERM BLOOD PRESSURE CONTROL ON DIASTOLIC CARDIAC FUNCTION IN MASTERS ATHELETES

Background & Objectives: Arterial hypertension and age underlie the risk for diastolic dysfunction and heart failure with preserved ejection fraction. Blood pressure control and physical exercise are known to ameliorate age related cardiac adaptation. Therefore, we assessed diastolic function including left atrial (LA) strains in Masters Athletes as a model for healthy ageing. Methods: At the World Masters Athletics Championships 2022 in Tampere, Finland 108 Masters Athletes partook in this field-study. Baseline data included body measures, blood pressure, age, sex and sport disciplines. Transthoracic echocardiography was performed analogous to clinical standards. Additionally, LA reservoir strain (LA-Sr) and conduit strain (LA-Scd) were assessed by speckle tracking. Results: Complete data were acquired in 108 (42, 39% female) athletes with a mean age of 62±12 (35-91) years and a body-mass-index of 23,8±2,8 kg/m2. Mean systolic blood pressure was 125±16mmHg, one third (n=36) had values ≥130mmHg. 29 performed endurance, 79 resistance disciplines. LA strain was not influenced by sport discipline nor blood pressure, neither in dichotomization for clinical thresholds nor in linear correlation. Female athletes showed higher LA reservoir and conduit strain (LA-Sr: 29.1±5.3% versus 27±5.5%, p=0.046; LA-Scd: 16.6±6% versus 13.9±5.4%, p=0,018). With increasing age, body-mass-index and left-ventricular-mass-index, LA reservoir and conduit strains declined significantly, independent of blood pressure. In Masters Athletes that did not meet echocardiographic criteria of diastolic dysfunction we found significantly higher LA reservoir and conduit strains than in those with 2 criteria met (LA-Sr 29.8±5.2% versus 25.4±6.6%, p=0.007; LA-Scd -17.3±6% versus -13.4±6.5%, p=0.030). Conclusion: In the specialized cohort of Masters Athletes LA reservoir and conduit strain showed the same dependency from age, body-mass-index and left-ventricular-mass-index as other parameters of diastolic function with higher values in females. Furthermore, impaired diastolic function was associated with decreased LA strain. Therefore, assessment of LA strain seems beneficial beyond classical echocardiographic measurements in determining diastolic function in the elderly. Surprisingly, long-term blood pressure control by physical exercise had no effect on LA strains.

Torsemide in the Management of Essential Hypertension.

Torsemide, a loop diuretic, is increasingly recognized for its role in managing essential hypertension. Its mechanism of action involves inhibiting the reabsorption of sodium and chloride ions in the ascending loop of Henle in the kidneys. By doing so, torsemide promotes diuresis, which refers to increased urine production, and subsequently lowers blood pressure. Studies have shown that torsemide is comparably effective to other antihypertensive agents in lowering blood pressure, with the added benefit of potentially improving renal function. However, while torsemide shows promise in hypertensive management, further research is necessary to fully understand its long-term effects and to establish optimal dosing strategies. Future research should focus on clarifying its role in long-term blood pressure control and refining its use in clinical practice to maximize efficacy and minimize adverse effects.

Purinergic Receptor Antagonists: A Complementary Treatment for Hypertension.

The treatment of hypertension has improved in the last century; attention has been directed to restoring several altered pathophysiological mechanisms. However, regardless of the current treatments, it is difficult to control blood pressure. Uncontrolled hypertension is responsible for several cardiovascular complications, such as chronic renal failure, which is frequently observed in hypertensive patients. Therefore, new approaches that may improve the control of arterial blood pressure should be considered to prevent serious cardiovascular disorders. The contribution of purinergic receptors has been acknowledged in the pathophysiology of hypertension; this review describes the participation of these receptors in the alteration of kidney function in hypertension. Elevated interstitial ATP concentrations are essential for the activation of renal purinergic receptors; this becomes a fundamental pathway that leads to the development and maintenance of hypertension. High ATP levels modify essential mechanisms implicated in the long-term control of blood pressure, such as pressure natriuresis, the autoregulation of the glomerular filtration rate and renal blood flow, and tubuloglomerular feedback responses. Any alteration in these mechanisms decreases sodium excretion. ATP stimulates the release of vasoactive substances, causes renal function to decline, and induces tubulointerstitial damage. At the same time, a deleterious interaction involving angiotensin II and purinergic receptors leads to the deterioration of renal function.

Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management: The POP-HT Randomized Clinical Trial

(Abstracted from JAMA 2023;330:1991–1999 Worldwide, about 10% of pregnancies are affected by an abnormal rise in maternal blood pressure (BP). Individuals whose BP remains high 6 weeks after birth are more likely to have higher BP 5 to 10 years later.

The short and long-term efficacy of nurse-led interventions for improving blood pressure control in people with hypertension in primary care settings: a systematic review and meta-analysis

BackgroundPrevious systematic reviews suggest that nurse-led interventions improve short-term blood pressure (BP) control for people with hypertension. However, the long-term effects, adverse events, and appropriate target BP level are unclear. This study aimed to evaluate the long-term efficacy and safety of nurse-led interventions.MethodsWe conducted a systematic review and meta-analysis. We searched the Cochrane Central Register of Controlled Trials, PubMed, and CINAHL, as well as three Japanese article databases, as relevant randomized controlled trials from the oldest possible to March 2021. This search was conducted on 17 April 2021. We did an update search on 17 October 2023. We included studies on adults aged 18 years or older with hypertension. The treatments of interest were community-based nurse-led BP control interventions in addition to primary physician-provided care as usual. The comparator was usual care only. Primary outcomes were long-term achievement of BP control goals and serious adverse events (range: 27 weeks to 3 years). Secondary outcomes were short-term achievement of BP control goals and serious adverse events (range: 4 to 26 weeks), change of systolic and diastolic BP from baseline, medication adherence, incidence of hypertensive complications, and total mortality.ResultsWe included 35 studies. Nurse-led interventions improved long-term BP control (RR 1.10, 95%CI 1.03 to 1.18). However, no significant differences were found in the short-term effects of nurse-led intervention compared to usual care about BP targets. Little information on serious adverse events was available. There was no difference in mortality at both terms between the two groups. Establishing the appropriate target BP from the extant trials was impossible.ConclusionsNurse-led interventions may be more effective than usual care for achieving BP control at long-term follow-up. It is important to continue lifestyle modification for people with hypertension. We must pay attention to adverse events, and more studies examining appropriate BP targets are needed. Nurse-led care represents an important complement to primary physician-led usual care.

Mechanisms of inflammation modulation by different immune cells in hypertensive nephropathy.

Hypertensive nephropathy (HTN) is the second leading cause of end-stage renal disease (ESRD) and a chronic inflammatory disease. Persistent hypertension leads to lesions of intrarenal arterioles and arterioles, luminal stenosis, secondary ischemic renal parenchymal damage, and glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Studying the pathogenesis of hypertensive nephropathy is a prerequisite for diagnosis and treatment. The main cause of HTN is poor long-term blood pressure control, but kidney damage is often accompanied by the occurrence of immune inflammation. Some studies have found that the activation of innate immunity, inflammation and acquired immunity is closely related to the pathogenesis of HTN, which can cause damage and dysfunction of target organs. There are more articles on the mechanism of diabetic nephropathy, while there are fewer studies related to immunity in hypertensive nephropathy. This article reviews the mechanisms by which several different immune cells and inflammatory cytokines regulate blood pressure and renal damage in HTN. It mainly focuses on immune cells, cytokines, and chemokines and inhibitors. However, further comprehensive and large-scale studies are needed to determine the role of these markers and provide effective protocols for clinical intervention and treatment.

Predicting chronic responses to calcium channel blockade with a virtual population of African Americans with hypertensive chronic kidney disease.

Chronic kidney disease (CKD) is associated with the progressive loss of functional nephrons and hypertension (HTN). Clinical studies demonstrate calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN. However, there are few long-term clinical studies that determine the impact of CCBs in patients with hypertensive CKD. African Americans (AA) have a higher prevalence of CKD and a faster progression to total kidney failure as compared to the white population but the mechanisms are poorly understood. Both clinical evidence (the African American Study of Kidney Disease and Hypertension, or AASK trial) and experimental studies have demonstrated that CCB may expose glomerular capillaries to high systemic pressures and exacerbate CKD progression. Therefore, using a large physiological model, we set out to replicate the AASK trial findings, predict renal hemodynamic responses and the role of the renin-angiotensin system during CCB antihypertensive therapy in a virtual population, and hypothesize mechanisms underlying those findings. Our current mathematical model, HumMod, is comprised of integrated systems that play an integral role in long-term blood pressure (BP) control such as neural, endocrine, circulatory, and renal systems. Parameters (n=341) that control these systems were randomly varied and resulted in 1400 unique models that we define as a virtual population. We calibrated these models to individual patient level data from the AASK trial: BP and glomerular filtration rate (GFR) before and after 3 years of amlodipine (10 mg/day). After calibration, the new virtual population (n=165) was associated with statistically similar BP and GFR before and after CCB. Baseline factors such as elevated single nephron GFR and low tubuloglomerular feedback were correlated with greater declines in renal function and increased glomerulosclerosis after 3 years of CCB. Blocking the renin-angiotensin system (RAS) in the virtual population decreased glomerular pressure, limited glomerular damage, and further decreased BP (-14 ± 8 mmHg) as compared to CCB alone (-11 ± 9 mmHg). Our simulations echo the potential risk of CCB monotherapy in AA CKD patients and support blockade of the renin angiotensin system as a valuable tool in renal disease treatment when combined with CCB therapy.

Place of imidazoline receptor agonists in the treatment of arterial hypertension

The review is devoted to one of the most controversial issues of modern antihypertensive therapy — the role of new generation sympatholytics — selective I1-imidazoline receptor agonists (AIRs). In modern European recommendations, AIR (moxonidine rilmenidine), along with other centrally acting drugs (reserpine, alpha-methyldopa, clonidine), are mainly intended for additional therapy in rare cases of resistant hypertension, when other treatment options have been ineffective. Nevertheless, AIR invariably finds its place in Russian recommendations for the treatment of arterial hypertension (AH). This class of drugs is recommended for patients with AH in combination with metabolic syndrome and obesity. It is noted that an important property of AIR is its positive effect on carbohydrate and lipid metabolism. This information is based on an analysis of Russian and foreign studies, which convincingly indicate that this class of drugs not only provides adequate and long-term blood pressure control, but also has the above-mentioned positive metabolic effects. At the same time, AIRs are much less likely to cause side effects characteristic of older generation centrally acting drugs. Thus, AIRs have become firmly established in clinical practice in Russia for the treatment of patients with AH in certain clinical situations.

Multivariable risk model for postpartum re-presentation with hypertension: development phase

ObjectivesPostpartum hypertension is one of the leading causes of re-presentation to hospital postpartum and is associated with adverse long-term cardiovascular risk. Postpartum blood pressure monitoring and management interventions have been...

Long-Term Blood Pressure Control After Hypertensive Pregnancy Following Physician-Optimized Self-Management

Pregnancy hypertension results in adverse cardiac remodeling and higher incidence of hypertension and cardiovascular diseases in later life. To evaluate whether an intervention designed to achieve better blood pressure control in the postnatal period is associated with lower blood pressure than usual outpatient care during the first 9 months postpartum. Randomized, open-label, blinded, end point trial set in a single hospital in the UK. Eligible participants were aged 18 years or older, following pregnancy complicated by preeclampsia or gestational hypertension, requiring antihypertensive medication postnatally when discharged. The first enrollment occurred on February 21, 2020, and the last follow-up, November 2, 2021. The follow-up period was approximately 9 months. Participants were randomly assigned 1:1 to self-monitoring along with physician-optimized antihypertensive titration or usual postnatal care. The primary outcome was 24-hour mean diastolic blood pressure at 9 months postpartum, adjusted for baseline postnatal blood pressure. Two hundred twenty participants were randomly assigned to either the intervention group (n = 112) or the control group (n = 108). The mean (SD) age of participants was 32.6 (5.0) years, 40% had gestational hypertension, and 60% had preeclampsia. Two hundred participants (91%) were included in the primary analysis. The 24-hour mean (SD) diastolic blood pressure, measured at 249 (16) days postpartum, was 5.8 mm Hg lower in the intervention group (71.2 [5.6] mm Hg) than in the control group (76.6 [5.7] mm Hg). The between-group difference was -5.80 mm Hg (95% CI, -7.40 to -4.20; P < .001). Similarly, the 24-hour mean (SD) systolic blood pressure was 6.5 mm Hg lower in the intervention group (114.0 [7.7] mm Hg) than in the control group (120.3 [9.1] mm Hg). The between-group difference was -6.51 mm Hg (95% CI, -8.80 to -4.22; P < .001). In this single-center trial, self-monitoring and physician-guided titration of antihypertensive medications was associated with lower blood pressure during the first 9 months postpartum than usual postnatal outpatient care in the UK. ClinicalTrials.gov Identifier: NCT04273854.

RENAL DENERVATION REDUCES RETINAL ARTERIAL REMODELING IN PATIENTS WITH TREATMENT RESISTANT HYPERTENSION AND TYPE 2 DIABETES MELLITUS

Objective: Renal denervation has been shown to be a safe and effective method to lower blood pressure (BP) in patients with uncontrolled treatment resistant hypertension (TRH). Patients with TRH and T2DM typically show hypertrophic arteriolar remodeling, which is associated with the development of early target end-organ damage. By using the retinal vasculature as a mirror of vascular remodeling in the systemic circulation, arteriolar remodeling can be non-invasively assessed with Scanning Laser Doppler Flowmetry (SLDF). In this analysis we assessed the impact of RDN on retinal arteriolar remodeling in patients with TRH and T2DM. Design and method: Retinal arteriolar remodeling was assessed using SLDF together with office and 24-hour ambulatory BP before and 6 as well as 12 months after renal denervation in 22 patients with TRH and T2DM. All patients participated in the investigator initiated study program “Renal Denervation in Treatment Resistant Hypertension” (NCT01687725). SLDF allows confocal measurement of the retinal arteriolar parameters, such as outer (OD) and inner (ID) diameter. Based on ID and OD the following parameters of arteriolar remodeling are derived: retinal arteriolar wall thickness (WT), wall-to-lumen ratio (WLR), and retinal arteriolar crosssectional area (CA). Results: Retinal arteriolar parameters were analysed in 18 male and 4 female patients with 6.5 antihypertensive medications on average. There was a significant reduction of systolic and diastolic 24-hour ambulatory as well office BP 6 as well as 12 months after RDN (table 1). In 77.3% of the patients number of antihypertensive medications was reduced. We found a reduction of hypertrophic retinal arteriolar remodeling and also a reduction of WLR 12 months after RDN (table 1). Of note, no significant changes of retinal arteriolar remodeling were found 6 months after RDN. Conclusions: In very high-risk patients with TRH and T2DM endovascular RDN reduced retinal arteriolar remodeling and retinal wall-to-lumen ratio, a prognostic marker of further end-organ damage. Whereas BP-changes already occurred 6 months after RDN, changes in retinal arteriolar remodelling were observed 12 months after RDN. We conclude that after RDN reversal of arteriolar remodeling happens slowly and requires long-term effective BP control.

Interventions for reducing blood pressure in prehypertension: A meta-analysis.

We aimed to address which interventions best control blood pressure (BP) and delay disease progression in prehypertension and to give recommendations for the best option following a quality rating. A Bayesian network meta-analysis was used to assess the effect of the intervention on BP reduction, delaying hypertension progression and final outcome, with subgroup analyses for time and ethnicity. Recommendations for interventions were finally based on cumulative ranking probabilities and CINeMA. From 22,559 relevant articles, 101 eligible randomized controlled trial articles (20,176 prehypertensive subjects) were included and 30 pharmacological and non-pharmacological interventions were evaluated. Moderate-quality evidence demonstrated that angiotensin II receptor blockers, aerobic exercise (AE), and dietary approaches to stop hypertension (DASH) lowered systolic blood pressure (SBP). For lowering diastolic blood pressure (DBP), AE combined with resistance exercise (RE) or AE alone provided high quality evidence, with calcium channel blockers, lifestyle modification (LSM) combined with drug providing moderate quality evidence. LSM produced the best BP lowering effect at 12 months and beyond of intervention. In Asians, TCD bubble was moderate quality evidence for lowering SBP and RE may have had a BP lowering effect in Caucasians. No recommendation can be given for delaying the progression of hypertension and reducing mortality outcomes because of low to very low quality of evidence. AE combined RE are preferentially recommended for BP control in prehypertension, followed by DASH. Long-term BP control is preferred to LSM. Asians and Caucasians add TCD bubble and RE to this list as potentially effective interventions. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022356302, identifier: CRD42022356302.

Predictive value of gut microbiota in long-term blood pressure control: a cross-sectional study

ObjectivesTo investigate the prediction of long-term blood pressure control using the intestinal flora of patients with hypertension.MethodsA total of 125 patients with primary grade-2 hypertension who attended the cardiovascular department of Hebei Province Hospital of Chinese Medicine between April 2021 and April 2022 were enrolled; these included 65 patients with substandard long-term blood pressure control (the uncontrolled group) and 60 patients with standard long-term blood pressure control (the controlled group). General clinical data and data on morning stools and diet were recorded for all the enrolled patients. The 16 s rDNA sequencing of faecal intestinal flora was also performed to analyse the differences in intestinal flora between the two groups of patients and to investigate the relationship between blood pressure compliance and the presence of flora.ResultsThe intestinal flora of the two groups of patients differed in terms of the Firmicutes–Bacteroidetes ratio (F/B), α-diversity analysis (Chao1, ACE and Shannon) results and β-diversity analysis results. At the genus level, the number of Streptococcus and Paraprevotella in patients in the uncontrolled group was greater than that of the controlled group, and the level of Akkermansia and Bifidobacterium was lower than that in the controlled group. A logistic regression analysis of the difference factors found differences in ACE, F/B, Streptococcus, Paraprevotella and Akkermansia in the two groups; these differences remained after correcting for age, gender and body mass index. The receiver operating characteristic curves revealed the following: ACE (area under the curve [AUC] = 85.282), Streptococcus (AUC = 82.705), Akkermansia (AUC = 77.333), Paraprevotella (AUC = 66.154) and F/B (AUC = 60.436).ConclusionsThere were significant differences in the intestinal flora of the patients in the controlled blood group compared with that of the uncontrolled group. Therefore, the ACE, genus levels of Streptococcus and Akkermansia could provide some prediction of late blood pressure compliance or non-compliance in patients with hypertension.

Sodium-glucose cotransporter 2 inhibition does not improve the acute pressure natriuresis response in rats with type 1 diabetes.

What is the central question of this study? Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular risk in patients with both diabetic and non-diabetic kidney disease: can SGLT2 inhibition improve renal pressure natriuresis (PN), an important mechanism for long-term blood pressure control, which is impaired in type 1 diabetes mellitus (T1DM)? What is the main finding and its importance? The SGLT2 inhibitor dapagliflozin did not enhance the acute in vivo PN response in either healthy or T1DM Sprague-Dawley rats. The data suggest that the mechanism underpinning the clinical benefits of SGLT2 inhibitors on health is unlikely to be due to an enhanced natriuretic response to increased blood pressure. Type 1 diabetes mellitus (T1DM) leads to serious complications including premature cardiovascular and kidney disease. Hypertension contributes importantly to these adverse outcomes. The renal pressure natriuresis (PN) response, a key regulator of blood pressure (BP), is impaired in rats with T1DM as tubular sodium reabsorption fails to down-regulate with increasing BP. We hypothesised that sodium-glucose cotransporter 2 (SGLT2) inhibitors, which reduce cardiovascular risk in kidney disease, would augment the PN response in T1DM rats. Non-diabetic or T1DM (35-50mg/kg streptozotocin i.p.) adult male Sprague-Dawley rats were anaesthetised (thiopental 50mg/kg i.p.) and randomised to receive either dapagliflozin (1mg/kg i.v.) or vehicle. Baseline sodium excretion was measured and then BP was increased by sequential arterial ligations to induce the PN response. In non-diabetic animals, the natriuretic and diuretic responses to increasing BP were not augmented by dapagliflozin. Dapagliflozin induced glycosuria, but this was not influenced by BP. In T1DM rats the PN response was impaired. Dapagliflozin again increased urinary glucose excretion but did not enhance PN. Inhibition of SGLT2 does not enhance the PN response in rats, either with or without T1DM. SGLT2 makes only a minor contribution to tubular sodium reabsorption and does not contribute to the impaired PN response in T1DM.

S-58-3: HOW COULD CONTINUOUS CUFFLESS AUTOMATED BLOOD PRESSURE MEASUREMENT DEVICES CONTRIBUTE TO HYPERTENSION MANAGEMENT?

Evidence that hypertension is the most importat global risk factor for cardiovascular morbidity and mortality, and demonstration of the cardiovascular protection offered by antihypertensive treatment, have been based on upper-arm cuff blood pressure (BP) measurements. This approach is recommended by current hypertension guidelines for BP measurement in clinical practice, as well as for validation of novel BP measuring devices. However, the spot or intermittent BP measurements in static conditions allowed by arm-cuff devices are unable to identify and track the continuous and rapid BP changes characterizing daily life. Moreover, cuff-based BP measurements are exposed to errors related to cuff size, shape and positioning, and cuff inflation may itself induce an alerting response and produce discomfort in the users during daily activities and in particular during sleep, which may modify the measured BP levels. To face these issues, use of continuous recordings techniques, not based on arm-cuff inflation, would be required. This is possible through intra-arterial recordings, which however are not feasible in daily practice because of their invasiveness. An alternative solution is represented by photoplethysmographic volume-clamp method for finger BP monitoring which, however, is difficult to implement in clinical practice because of its cost and complexity. Technological progress is now offering an increasingly large and heterogeneous series of cuffless BP monitors, which estimate BP based on sensors, signal processing and algorithms embedded in wearable devices, smartphones or pocket devices. These cuffless devices might allow for comfortable and continuous BP recordings, detecting rapid BP changes during day and night sleep, thus offering information on both short, mid and long term BP variability. Cuffless devices might also be useful for continuous non invasive BP monitoring in different clinical settings, including ICUs, during anaesthesia, in patients with arrhythmias, hypotension/syncope, and other transient conditions affecting BP levels and variability. Moreover, cuffless BP measurement devices connected to telemonitoring facilities or smartphones apps may improve patients empowerment, adherence to treatment and long-term BP control. In spite of all these potential advantages, however, cuffless BP devices have to face specific accuracy issues, which would need refinement of specific validation protocols aimed at testing the need of individual calibration, the stability of measurements after calibration and the device actual ability to track BP changes before they might be recommended for clinical use.

AW-APSH-1: TARGETING WINDOWS OF PLASTICITY TO PREVENT HYPERTENSION.

Failing lifestyle interventions, there are many classes of anti-hypertensive drugs that are highly effective in most patients if taken appropriately. But multiple agents taken daily may be required to achieve target blood pressure (BP). The problem is that the majority of patients are non-compliant: they do not take their drugs continuously, choose to only take some, or stop taking them completely. It is time to focus on interventions that do not require lifelong daily medications, and this requires understanding and treating the causative factors. For decades, it has been understood that the kidney, under the influence of both the renin-angiotensin-aldosterone system and sympathetic nerves, has a dominant role in the long-term control of extracellular fluid volume and BP. The kidney is an important target for the treatment of hypertension. Early postnatal life is a period of remarkable plasticity and is a neglected window of opportunity to prevent disease onset. Our aim is to preserve and protect function of existing nephrons. If born with reduced renal mass (less nephrons), the compensatory response is to increase the filtration rate of each individual nephron so that GFR is maintained. Clinically, the degree of nephron overload is linked to faster age and disease related reduction in renal functional reserve, glomerular damage, albuminuria and hypertension. By targeting the postnatal period of maturation, our aim is to prevent maladaptive compensatory hypertrophy and hyperfiltration to preserve kidney health-span without the need for lifelong drug therapy. Our studies in a large animal model of congenital renal mass reduction demonstrate the long-term therapeutic potential of a brief period of angiotensin converting enzyme inhibition early in life to alter the trajectory of renal and cardiovascular disease.

The Safety and Efficacy of Clonidine in Hemodialysis Patients: A Systematic Review and Meta-Analysis

Background: Clonidine is a frequently prescribed long-term antihypertensive medication in hemodialysis (HD) patients in the USA, but its safety and efficacy has not been clearly established in the HD population. Objective: To evaluate, we conducted a systematic review and meta-analysis on the safety and efficacy of clonidine in HD patients. Methods: Keyword search of “clonidine” and “dialysis” was conducted through April 2021 in PubMed, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov databases. Inclusion criteria were as follows – study design: randomized controlled trials, cohort studies, prospective studies, retrospective studies, or case series; subjects: adult HD patients; main outcome: blood pressure (BP) and safety; language: English; and article type: peer-reviewed publications. Studies that examined the effects of clonidine in populations other than adult HD patients were excluded. Meta-analysis was performed on BP reduction outcomes. Results: Eight studies met the inclusion criteria for the systematic review, including prospective pre-post studies (2), double-blind controlled trial (1), single-blinded placebo-controlled trial (1), crossover open-label clinical trial (1), retrospective analysis (1), and case report series (2). Three studies included in the meta-analysis ranged from 2 to 12 weeks duration, with a collective sample size of 24 (ages 12–77 years). Risk of bias, assessed using the ROBINS-1 tool, was high for all included studies. Significant adverse effects reported included hypotension, light-headedness, drowsiness, dry mouth, rebound hypertension, and contact dermatitis from patch application. Short-term clonidine use was associated with significant improvement in systolic BP (pooled effect: −12.985 mm Hg, 95% CI [−7.878, −18.092], p < 0.001), while changes in diastolic BP were not statistically significant (−11.119 mm Hg, 95% CI [−22.725, 0.487], p = 0.060). No data currently support the long-term efficacy of clonidine in HD patients. This study was unfunded and was developed using PRISMA guidelines and registered on PROSPERO (CRD42018112042). Conclusions: There is no evidence supporting the long-term use of clonidine in the HD population and a significant side-effect profile. There is low-quality evidence demonstrating the efficacy of clonidine in lowering BP in HD patients in short-term use, but significant safety concerns remain. Fluid removal strategies and other antihypertensives should be used over clonidine for long-term BP control in the HD population.