Evaluation and Management of Resistant Hypertension: Core Curriculum 2024.

Resistant hypertension is defined as blood pressure above goal despite confirmed adherence to 3 first-line antihypertensive agents or when blood pressure is controlled with 4 or more medications at maximal or maximally tolerated doses. In addition to meeting these criteria, identifying patients with true resistant hypertension requires both accurate in-office blood pressure measurement as well as excluding white coat effects through out-of-office blood pressure measurements. Patients with resistant hypertension are at higher risk for adverse cardiovascular events and are more likely to have a potentially treatable secondary cause contributing to their hypertension. Effective treatment of resistant hypertension includes ongoing lifestyle modifications and collaboration with patients to detect and address barriers to optimal medication adherence. Pharmacologic treatment should prioritize optimizing first-line, once daily, longer acting medications followed by the stepwise addition of second-, third-, and fourth-line agents as tolerated. Physicians should systematically evaluate for and address any underlying secondary causes. A coordinated, multidisciplinary team approach including clinicians with experience in treating resistant hypertension is essential. New treatment options, including both pharmacologic and device-based therapies, have recently been approved, and more are in the pipeline; their optimal role in the management of resistant hypertension is an area of ongoing research.

Predictive Factors of Apparent Treatment Resistant Hypertension Among Patients With Hypertension Identified Using Electronic Health Records.

BACKGROUND: Early identification of a patient with resistant hypertension (RH) enables quickly intensified treatment, short-interval follow-up, or perhaps case management to bring his or her blood pressure under control and reduce the risk of complications. OBJECTIVE: To identify predictors of RH among individuals with newly diagnosed hypertension (HTN), while comparing different prediction models and techniques for managing missing covariates using electronic health records data. DESIGN: Risk prediction study in a retrospective cohort. PARTICIPANTS: Adult patients with incident HTN treated in any of the primary care clinics of one health system between April 2013 and December 2016. MAIN MEASURES: Predicted risk of RH at the time of HTN identification and candidate predictors for variable selection in future model development. KEY RESULTS: Among 26,953 individuals with incident HTN, 613 (2.3%) met criteria for RH after 4.7 months (interquartile range, 1.2-11.3). Variables selected by the least absolute shrinkage and selection operator (LASSO), included baseline systolic blood pressure (SBP) and its missing indicator (a dummy variable created if baseline SBP is absent), use of antihypertensive medication at the time of cohort entry, body mass index, and atherosclerosis risk. The random forest technique achieved the highest area under the curve (AUC) of 0.893 (95% CI, 0.881-0.904) and the best calibration with a calibration slope of 1.01. Complete case analysis is not a valuable option (AUC = 0.625). CONCLUSIONS: Machine learning techniques and traditional logistic regression exhibited comparable levels of predictive performance after handling the missingness. We suggest that the variables identified by this study may be good candidates for clinical prediction models to alert clinicians to the need for short-interval follow up and more intensive early therapy for HTN.

Resistant Hypertension: Disease Burden and Emerging Treatment Options.

PURPOSE OF REVIEW: To define resistant hypertension (RHT), review its pathophysiology and disease burden, identify barriers to effective hypertension management, and to highlight emerging treatment options. RECENT FINDINGS: RHT is defined as uncontrolled blood pressure (BP) ≥ 130/80 mm Hg despite concurrent prescription of ≥ 3 or ≥ 4 antihypertensive drugs in different classes or controlled BP despite prescription of ≥ to 4 drugs, at maximally tolerated doses, including a diuretic. BP is regulated by a complex interplay between the renin-angiotensin-aldosterone system, the sympathetic nervous system, the endothelin system, natriuretic peptides, the arterial vasculature, and the immune system; disruption of any of these can increase BP. RHT is disproportionately manifest in African Americans, older patients, and those with diabetes and/or chronic kidney disease (CKD). Amongst drug-treated hypertensives, only one-quarter have been treated intensively enough (prescribed > 2 drugs) to be considered for this diagnosis. New treatment strategies aimed at novel therapeutic targets include inhibition of sodium-glucose cotransporter 2, aminopeptidase A, aldosterone synthesis, phosphodiesterase 5, xanthine oxidase, and dopamine beta-hydroxylase, as well as soluble guanylate cyclase stimulation, nonsteroidal mineralocorticoid receptor antagonism, and dual endothelin receptor antagonism. The burden of RHT remains high. Better use of currently approved therapies and integrating emerging therapies are welcome additions to the therapeutic armamentarium for addressing needs in high-risk aTRH patients.

Advances on the Experimental Research in Resistant Hypertension.

PURPOSE OF REVIEW: Resistant Hypertension (RH) poses a significant public health challenge, contributing to increased mortality, cardiovascular events and organ damage. Both clinical and experimental research are striving for higher standards in a translational manner to integrate new findings and confirm hypotheses. Considering that many are the aspects of RH that are still under investigation, this review aims to shed light on the advances made in experimental research concerning RH. It seeks to underscore the pivotal role of experimental studies in shaping clinical practices and also explore future perspectives. RECENT FINDINGS: It is important to emphasize the significance of experimental models, primarily for advancing our understanding: experimental models have greatly contributed to our comprehension of the underlying mechanisms in RH, including factors like sympathetic activation, endothelial dysfunction and structural vessel abnormalities. Secondly, for assessing treatment approaches: animal models have also played a crucial role in evaluating the potential effectiveness of diverse treatment approaches for RH. These encompass both pharmacological options, involving combinations of established drugs or novel pharmaceuticals, and non-pharmacological alternatives, which include surgical procedures like renal denervation, medical devices like baroreceptor stimulators, and lifestyle modifications. The most lacking component in translational research is the fact that there is no well-established animal model that perfectly replicates RH. Consequently, alternative strategies, including the combination of models, must be considered. What remains clear is that the development of animal models closely mimicking RH holds the promise of providing valuable insights into the essential mechanisms and responses necessary to combat or slow the global progression of RH.

Effect of Continuous Positive Airway Pressure on Blood Pressure in Patients with Resistant Hypertension and Obstructive Sleep Apnea: An Updated Meta-analysis.

PURPOSE OF REVIEW: The effect of continuous positive airway pressure (CPAP) on resistant hypertension in patients at high risk with obstructive sleep apnea (OSA) needs further investigation. We aimed to determine the effect of CPAP on blood pressure in patients with resistant hypertension and OSA. Databases including PubMed, EMBASE, MEDLINE, the Cochrane Library, and CMB were searched. Data were pooled using a random-effects or fixed-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals (CIs). RECENT FINDINGS: A total of 12 trials and 718 participants were included. Compared with control, CPAP significantly reduced 24-h systolic blood pressure (SBP) (WMD: - 5.92 mmHg [ - 8.72, - 3.11]; P＜0.001), 24-h diastolic blood pressure (DBP) (WMD: - 4.44 mmHg [- 6.26 , - 2.62]; P ＜0.001),  daytime SBP (WMD: - 5.76 mmHg [ - 9.16, - 2.36]; P ＜0.001),  daytime DBP (WMD: - 3.92 mmHg [- 5.55, - 2.30];  nighttime SBP (WMD: - 4.87 mmHg [ - 7.96 , - 1.78]; P = 0.002), and nighttime DBP (WMD: - 2.05 mmHg [- 2.99, - 1.11]; P＜0.001) in patients with resistant hypertension and OSA. CPAP improved the blood pressure both in the short (＜3 months) and long term (≥ 3 months). No significant impact on mean heart rate was noted (WMD: -2.76 beats per min [- 7.50, 1.97]; P = 0.25). CPAP treatment was associated with BP reduction in patients with resistant hypertension and OSA.

Consensus Statement on Renal Denervation by the Joint Committee of Japanese Society of Hypertension (JSH), Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT), and the Japanese Circulation Society (JCS).

This is the first consensus statement of the Joint Committee on Renal Denervation of the Japanese Society of Hypertension (JSH)/Japanese Association of Cardiovascular Intervention and Therapeutics (CVIT)/Japanese Circulation Society (JCS). The consensus is that the indication for renal denervation (RDN) is resistant hypertension or "conditioned" uncontrolled hypertension, with high office and out-of-office blood pressure (BP) readings despite appropriate lifestyle modification and antihypertensive drug therapy. "Conditioned" uncontrolled hypertension is defined as having one of the following: 1) inability to up-titrate antihypertensive medication due to side effects, the presence of complications, or reduced quality of life. This includes patients who are intolerant of antihypertensive drugs; or 2) comorbidity at high cardiovascular risk due to increased sympathetic nerve activity, such as orthostatic hypertension, morning hypertension, nocturnal hypertension, or sleep apnea (unable to use continuous positive airway pressure), atrial fibrillation, ventricular arrythmia, or heart failure. RDN should be performed by the multidisciplinary Hypertension Renal Denervation Treatment (HRT) team, led by specialists in hypertension, cardiovascular intervention and cardiology, in specialized centers validated by JSH, CVIT, and JCS. The HRT team reviews lifestyle modifications and medication, and the patient profile, then determines the presence of an indication of RDN based on shared decision making with each patient. Once approval for real-world clinical use in Japan, however, the joint RDN committee will update the indication and treatment implementation guidance as appropriate (annually if necessary) based on future real-world evidence.

Pressing Update: Aprocitentan for the Treatment of Hypertension.

OBJECTIVE: This article reviews the published data including the pharmacology, efficacy, and safety of aprocitentan, a novel endothelin receptor antagonist developed to treat hypertension in conjunction with additional agents. DATA SOURCES: A literature search was conducted from drug discovery until May 2024 through PubMed, MEDLINE, and National Institutes of Health Clinical Trials Registry utilizing the following search terms: Tryvio, aprocitentan, hypertension, resistant hypertension, endothelin receptor antagonist, and ACT-132577. STUDY SELECTION AND DATA EXTRACTION: All relevant English-language studies, or studies that could be appropriately translated into English, containing the pharmacology, pharmacokinetics, safety, and efficacy of aprocitentan, were selected for review. DATA SYNTHESIS: In the setting of resistant hypertension, aprocitentan has shown significant reductions in blood pressure in both medical office and 24-hour ambulatory settings at 4 weeks with a sustained effect at 40 weeks. Studies evaluating cardiovascular risk reduction have not been conducted at this time. Fluid retention and edema were the most frequent adverse events reported in clinical studies with aprocitentan. As a class, endothelin receptor antagonists may cause fetal harm; aprocitentan should be used with caution to avoid embryo-fetal toxicity. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING DRUGS: Owing to the existent barriers for the treatment of resistant hypertension, aprocitentan presents itself as an effective option when added to traditional antihypertensives. This single-strength, once-daily regimen may serve as an appealing option to both patients and prescribers. CONCLUSION: Aprocitentan is a safe and effective medication for the treatment of hypertension when added to other pharmacological therapies.

Best Practice Alert to Promote Screening for Primary Aldosteronism Among People With Apparent Treatment-Resistant Hypertension.

OBJECTIVE: Guidelines recommend screening all individuals with resistant hypertension for primary aldosteronism (PA) but less than 2% are screened. We aimed to develop a noninterruptive Best Practice Alert (BPA) to assess if its implementation in the electronic health record improved PA screening rates among individuals with apparent treatment-resistant hypertension (aTRH). METHODS: We implemented a noninterruptive BPA on 9/17/2022 at our ambulatory primary care, endocrinology, nephrology, and cardiology clinics. We assessed clinical parameters of people with aTRH before (9/17/2021-9/16/2022) and after (9/17/2022-9/16/2023) the BPA was implemented. The noninterruptive BPA embedded with an order set identified people with aTRH and recommended screening for PA if it was not previously performed. RESULTS: There were 10 944 and 11 463 people with aTRH who attended office visits during the 12 months before and after the BPA implementation, respectively. There were no statistically significant differences in median age (P = .096), sex (P = .577), race (P = .753), and ethnicity (P = .472) between the pre- and post-BPA implementation groups. There was a significant increase in PA screening orders placed (227 [2.1%] vs 476 [4.2%], P < .001) and PA screening labs performed (169 [1.5%] vs 382 [3.3, P < .001) after BPA implementation. PA screening tests were positive in 26% (44/169) and 23% (88/382) of people in the pre- and post-BPA groups, respectively (P = .447). CONCLUSION: Implementation of a real-time electronic health record BPA doubled the screening rate for PA among people with aTRH; however, the overall screening rate was low.

Investigations of Laser-Assisted Renal Denervation for Treatment of Resistant Hypertension.

BACKGROUND AND OBJECTIVES: Renal denervation (RDN) is an emerging surgical treatment for resistant hypertension. However, the current RDN using radiofrequency can cause undesirable thermal damage to the medial and luminal layers due to direct contact between the arterial lumen and energy source. The aim of this study is to evaluate the feasibility of the new laser-assisted RDN by exploring the potential treatment conditions. METHODS: For ex vivo testing, six different treatment conditions (10 and 20 W applied for delivery of 300, 450, and 600 J) were tested on the porcine liver and renal artery (RA) by using a continuous wave 1064 nm laser wavelength. The ablated area in the liver tissue was measured to estimate the extent of the coagulated area. Histological evaluation was performed on the treated RA tissues to confirm the extent of thermal nerve damage. RESULTS: The ablated depth, length, and area in the liver tissue increased with laser power and total energy. According to the histological results, 20 W groups yielded more significant damage to the RA nerves than 10 W groups at the total energy of 300 J (0.0 ± 0.0 mm for 10 W vs. 2.9 ± 1.0 mm for 20 W), 450 J (1.9 ± 0.6 mm for 10 W vs. 6.8 ± 1.5 mm for 20 W), and 600 J (2.9 ± 0.4 mm for 10 W vs. 7.3 ± 0.8 mm for 20 W). The treated RA exhibited insignificant medial injury in depth (medial thinning ≤ 25%), and no difference in the medial thinning was found among the six groups (p = 0.4). CONCLUSION: The current study demonstrated that the 1064 nm laser at 20 W with delivery of 450 J could effectively damage the RA nerves with no or minimal injury to the surrounding tissue. The proposed laser-assisted RDN may enhance physiological effects with insignificant complications in in vivo situations. Further in vivo studies will be conducted to validate the current findings by evaluating the extent of blood pressure reduction and norepinephrine changes after the laser-assisted RDN on a large animal model.

Echocardiographic findings following renal sympathetic denervation for treatment resistant hypertension, the ReShape CV-risk study.

OBJECTIVE: The aim of this study was to describe and compare echocardiographic findings before renal sympathetic denervation (RDN) and 6 and 24 months after the procedure. MATERIALS AND METHODS: Patients with treatment resistant hypertension (TRH) were included in this non-randomised intervention study. RDN was performed by a single experienced operator using the Symplicity Catheter System. Echocardiographic measurements were performed at baseline, and after 6 and 24 months. RESULTS: The cohort consisted of 21 patients with TRH, with a mean systolic office blood pressure (BP) of 163 mmHg and mean diastolic BP 109 mmHg. Mixed model analysis showed no significant change in left ventricular (LV) mass index (LVMI) or left atrium volume index (LAVI) after the RDN procedure. Higher LVMI at baseline was significantly associated with greater reduction in LVMI (p < 0.001). Relative wall thickness (RWT) increased over time (0.48 mm after two years) regardless of change in BP. There was a small but significant reduction in LV end-diastolic (LVIDd) and end-systolic (LVIDs) diameters after RDN, with a mean reduction of 2.6 and 2.4 mm, respectively, after two years. Progression to concentric hypertrophy was observed only in in patients who did not achieve normal BP values, despite BP reduction after RDN. CONCLUSION: There was no reduction of LV mass after RDN. We found a small statistically significant reduction in LVIDd and LVIDs, which together with increase in RWT can indicate progression towards concentric hypertrophy. BP reduction after RDN on its own does not reverse concentric remodelling if target BP is not achieved.

Population pharmacokinetics of the dual endothelin receptor antagonist aprocitentan in subjects with or without essential or resistant hypertension.

Aprocitentan is a novel, potent, dual endothelin receptor antagonist that recently demonstrated efficacy in the treatment of difficult-to-treat (resistant) hypertension. The aim of this study was to develop a population pharmacokinetic (PK) model describing aprocitentan plasma concentration over time, to investigate relationships between subject-specific factors (covariates) and model parameters, and to quantify the influence of the identified covariates on the exposure to aprocitentan via model-based simulations, enabling judgment about the clinical relevance of the covariates.PK data from 902 subjects in ten Phase 1, one Phase 2, and one Phase 3 study were pooled to develop a joint population PK model. The concentration-time course of aprocitentan was described by a two-compartment model with absorption lag time, first-order absorption and elimination, and reduced relative bioavailability following very high doses of 300 and 600 mg.The population PK model described the observed data well. Volume and clearance parameters were associated with body weight. Renal function as reflected by estimated glomerular filtration rate (eGFR), hepatic impairment, and sex were identified as relevant covariates on clearance.The subject-specific characteristics of body weight, eGFR, hepatic impairment, and sex were shown to influence exposure parameters area under the concentration-time curve and maximum concentration in steady state to a limited extent, i.e., not more than 25% different from a reference subject, and therefore do not warrant dose adjustments.

Tackling the Disproportionate Burden of Resistant Hypertension in US Black Adults.

PURPOSE OF REVIEW: Elevated blood pressure is the leading modifiable risk factor for cardiovascular morbidity and mortality in the US. Older individuals, Black adults, and those with comorbidities such as chronic kidney disease, have higher levels of uncontrolled and resistant hypertension. This review focuses on resistant hypertension, specifically in the US Black population, including potential benefits and limitations of current and investigational agents to address the disparate toll. RECENT FINDINGS: There is a necessity to implement public health measures, including early screening, detection, and evidence-based hypertension treatment with lifestyle, approved and investigational agents. The evidence highlights the importance of implementing feasible and cost-effective public health measures to advocate for early screening, detection, and appropriate treatment of hypertension. A team-based approach involving physicians, advanced practice nurses, physician assistants, pharmacists, social workers, and clinic staff to implement proven approaches and the delivery of care within trusted community settings may mitigate existing disparities.

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

Blood pressure targets, medication consideration and unique concerns in elderly hypertension IV: Focus on frailty, orthostatic hypotension, and resistant hypertension.

Hypertension increases the risk of cardiovascular disease in the elderly. Although treating hypertension can reduce the risk of cardiovascular disease and its related mortality, it is also challenging because these patients could have frailty, orthostatic hypotension (OH) and resistant hypertension (RHTN), which makes them more susceptible to treatment-related adverse events. Identifying such patients and tailoring the choice of drugs and blood pressure targets is crucial to balance the harms and benefits. The Clinical Frailty Scale is recommended to assess elderly patients with hypertension and frailty. For very frail patients, unnecessary medications should be deprescribed to avoid adverse events. Hypertension and OH frequently co-occur in the elderly, and recognizing and managing OH is essential to prevent falls and adverse events. The management of blood pressure in elderly patients with frailty, OH, and RHTN is complex, requiring the patients, their family and caregivers to be involved in decision-making to ensure that treatment plans are well-informed and aligned with the patient's needs.

Resistant hypertension in dialysis.

Hypertension is the most common finding in chronic kidney disease patients, with prevalence ranging from 60% to 90% depending on the stage and etiology of the disease. It is also a significant independent risk factor for cardiovascular disease, progression to end-stage kidney disease and mortality. According to the current guidelines, resistant hypertension is defined in the general population as uncontrolled blood pressure on three or more antihypertensive drugs in adequate doses or when patients are on four or more antihypertensive drug categories irrespective of the blood pressure control, providing that antihypertensive treatment included diuretics. The currently established definitions of resistant hypertension are not directly applicable to the end-stage kidney disease setting. The diagnosis of true resistant hypertension requires confirmation of adherence to therapy and confirmation of uncontrolled blood pressure values by ambulatory blood pressure measurement or home blood pressure measurement. In addition, the term "apparent treatment-resistant hypertension," defined as an uncontrolled blood pressure on three or more antihypertensive medication classes, or use of four or more medications regardless of blood pressure level was introduced. In this comprehensive review we focused on the definitions of hypertension, and therapeutic targets in patients on renal replacement therapy, including the limitations and biases. We discussed the issue of pathophysiology and assessment of blood pressure in the dialyzed population, management of resistant hypertension as well as available data on prevalence of apparent treatment-resistant hypertension in end-stage kidney disease. To conclude, larger sample-size and even higher quality studies about drug adherence should be conducted in the population of patients with the end-stage kidney disease who are on dialysis. It also should be determined how and when blood pressure should be measured in the group of dialysis patients. Additionally, it should be stated what the target blood pressure values in this group of patients really are. The definition of resistant hypertension in this group should be revisited, and its relationship to both subclinical and clinical endpoints should be established.

Dual Endothelin Antagonism with Aprocitentan as a Novel Therapeutic Approach for Resistant Hypertension.

PURPOSE OF REVIEW: Resistant hypertension (RH) defined as uncontrolled blood pressure despite the use of a combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic at maximally tolerated doses is associated with a substantially increased risk of cardiovascular and renal events. Despite targeting relevant pathophysiological pathways contributing to elevated blood pressure, approximately 10-15% of hypertensive patients remain above recommended blood pressure targets. Further optimization of blood pressure control is particularly challenging in patient populations who frequently present with RH such as elderly and patients with chronic kidney disease, due to the unfavorable safety profile of the recommended fourth-line therapy with mineralocorticoid receptor antagonists. This review explores the potential role of endothelin antagonists as an alternative fourth-line therapy. RECENT FINDINGS: Despite the well-described role of the endothelin pathway in the pathogenesis of hypertension, it is currently not targeted therapeutically. Recently however, main outcome data from the PRECISION study, a randomized placebo-controlled phase 3 trial, in patients with RH on guideline-recommended standardized single-pill background therapy convincingly demonstrated the safety and blood pressure-lowering efficacy of the dual endothelin antagonist Aprocitentan. Findings from the phase 3 PRECISION study could signify a turning point in the utilization of endothelin receptor antagonists as a standard treatment for patients with RH.

Sexual Dimorphic Interplays Between Gut Microbiota and Antihypertensive Drugs.

PURPOSE OF THE REVIEW: The purpose of this study is to review the current literature regarding gut microbiota in blood pressure regulation and its interactions with antihypertensive drugs and to discuss how sex differences in gut microbiota contribute to sexual dimorphism of hypertension and treatment. RECENT FINDINGS: The significance of gut microbiota in blood pressure regulation and hypertension etiology is growingly recognized. Targeting the dysbiotic microbiota is proposed to be a new therapeutic method. Recently, a few studies demonstrated that the gut microbiota is highly involved in the modulation of the efficacy of antihypertensive drugs, suggesting a novel mechanism by which gut microbiota plays a role in treatment-resistant hypertension. Furthermore, studies on sex differences in gut microbiota, etiology of hypertension, and sex bias in prescription of antihypertensive medications have revealed promising avenues in sexual dimorphism-based precision medicine. However, no scientific questions are ever raised on how sex differences in gut microbiota contribute to the sex specific responses of certain classes of antihypertensive drugs. Given the dynamics and complexity among individuals, precision medicine is proposed of great potential. We review current knowledge on the interactions between gut microbiota, hypertension, and antihypertensive drugs with an emphasis on sex as a crucial determinant. We propose that sex differences in gut microbiota be a research focus to advance our understanding of hypertension management.

Association between physical activity and resistant hypertension in treated hypertension patients: analysis of the national health and nutrition examination survey.

INTRODUCTION: Current guidelines suggest that regular aerobic training might lower blood pressure in hypertensive individuals. However, evidence linking resistant hypertension (RH) with total daily physical activity (PA), including work-, transport-, and recreation-related PA, is limited. Therefore, this study assessed the association between daily PA and RH. METHOD: A cross-sectional study was conducted using data acquired from a nationwide survey in the US (the National Health and Nutrition Examination Survey, NHANES). The weighted prevalence of RH was calculated, and moderate and vigorous daily PA was assessed using the Global Physical Activity Questionnaire (GPAQ). A multivariate logistic regression model determined the association between daily PA and RH. RESULTS: A total of 8,496 treated hypertension patients were identified, including 959 RH cases. The unweighted prevalence of RH among treated hypertension cases was 11.28%, while the weighted prevalence was 9.81%. Participants with RH had a low rate of recommended PA levels (39.83%), and daily PA and RH were significantly associated. PA exhibited significant dose-dependent trends with a low probability of RH (p-trends < 0.05). Additionally, participants with sufficient daily PA had a 14% lower probability of RH than those with insufficient PA [fully adjusted odds ratio (OR) = 0.86; 95% confidence interval (CI) = 0.74-0.99). CONCLUSION: The present study revealed that RH has an incidence of up to 9.81% in treated hypertension patients. Hypertensive patients tended to be physically inactive, and insufficient PA and RH were significantly associated. Sufficient daily PA should be recommended to reduce the RH probability among treated hypertension patients.

Differential effects of renal denervation on skin and muscle sympathetic nerve traffic in resistant and uncontrolled hypertension.

PURPOSE: Renal denervation (RDN) exerts sympathoinhibitory effects. No information is available, however, on whether these effects have a regional or a more generalized behavior. METHODS: In 14 patients with resistant hypertension (RHT, age 58.3 ± 2.2 years, mean ± SEM), we recorded muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively) using the microneurographic technique, before, 1 month, and 3 months after RDN. Measurements included clinic blood pressure (BP), heart rate (HR), 24-h BP and HR, as well as routine laboratory and echocardiographic variables. Ten age-matched RHT patients who did not undergo RDN served as controls. RESULTS: MSNA, but not SSNA, was markedly higher in RHT. RDN caused a significant reduction in MSNA 1 month after RDN, with this reduction increasing after 3 months (from 68.1 ± 2.5 to 64.8 ± 2.4 and 63.1 ± 2.6 bursts/100 heartbeats, P < 0.05). This effect was not accompanied by any significant change in SSNA (from 13.1 ± 0.5 to 13.4 ± 0.6 and 13.3 ± 0.4 bursts/min, P = NS). No quantitative or, in some cases, qualitative relationship was found between BP and the MSNA reduction induced by RDN. No significant changes in various sympathetic markers were detected in the control group who did not undergo RDN and were followed for 3-months observation. CONCLUSIONS: These data provide the first evidence that RDN exerts heterogeneous effects on sympathetic cardiovascular drive, inducing a marked reduction in MSNA but not in SSNA, which appears to be within the normal range in this condition.These effects may depend on the different reflex modulation regulating neuroadrenergic drive in these cardiovascular districts.

Revisiting resistant hypertension: a comprehensive review.

Resistant hypertension (RHT) is typically defined as blood pressure that remains above guideline-directed targets despite the use of three anti-hypertensives, usually including a diuretic, at optimal or maximally tolerated doses. It is generally estimated to affect 10-30% of those diagnosed with hypertension, though the true incidence might be lower after one factor in the prevalence of non-adherence. Risk factors for its development include diabetes, obesity and other adverse lifestyle factors, and a diagnosis of RHT confers a greater risk of adverse cardiovascular outcomes, such as stroke, heart failure and mortality. It is essential to exclude pseudoresistance and secondary hypertension and to ensure non-pharmacologic management is optimised prior to consideration of fourth-line anti-hypertensive agents or advanced interventions, such as device therapies. In this review, we will cover the different definitions of RHT, along with the importance of careful diagnosis and management strategies, and discuss newer agents and research needs.