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Resistant hypertension is blood pressure (BP) that is persistently above target in spite of the maximally tolerated usage of at least three anti-hypertensives simultaneously. The sympathetic nervous system is instrumental in blood pressure (BP) regulation. Renal (sympathetic) denervation involves using ablative energy to disrupt the sympathetic nerves in renal arteries. This systematic review examines the efficacy of this treatment modality. Abiding by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we conducted an extensive literature search in five databases, Cochrane Library, Google Scholar, PubMed, PubMed Central (PMC), and ScienceDirect, to retrieve studies that are free, open access, and published in English done within the past four years. Nineteen articles passed critical appraisal. These articles were randomized controlled trials (RCT), a case report, a cross-sectional study, a cohort study, and previous reviews. Renal denervation (RDN) was generally superior to sham control in patients with resistant hypertension for reducing various systolic blood pressure (SBP) measures, including 24-hour ambulatory, daytime, and nighttime SBP. The efficacy was highest in patients whose baseline SBP was higher. BP reduction was sustained for years post-procedure. The procedure had a good safety profile with no severe complications. Future studies should compare the efficacy of different types of renal denervation, such as ethanol ablation versus radiofrequency ablation, and renal denervation against other procedure-based treatment modalities, such as carotid baroreceptor stimulation and transcranial direct current stimulation.
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Hypertension is the most prevalent modifiable risk factor associated with cardiovascular mortality. The World Health Organization (WHO) estimates that hypertension directly or indirectly causes the death of at least nine million people globally every year. The number of people living with hypertension (blood pressure (BP) of ≥140 mmHg systolic or ≥90 mmHg diastolic or on medication) doubled between 1990 and 2019, from 650 million to 1.3 billion. Despite a plethora of antihypertensive drugs widely available, a sizable part of the antihypertensive population stays uncontrolled. The unmet need of controlling BP in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. Several device-based approaches have been introduced to lower BP, and most of these strategies aim to modulate autonomic nervous system activity. Importantly, when considering a device-based treatment, each patient's underlying pathophysiology is considered, and the procedural risks are weighed against the cardiovascular risk attributed to the elevated BP. In November 2023, the FDA approved two renal denervation (RDN) devices. This manuscript discusses current interventional devices and procedures recently approved (RDN) and others in the clinical testing stage for arterial hypertension intervention or management. As we list below, all others have shown promising results and are being evaluated on a larger clinical trial. The new device-based classes are as follows: catheter-based RDN, baroreflex amplification, arteriovenous (AV) malformation, carotid body (CB) ablation, pacemaker-based cardiac neuromodulation, electro-acupuncture, and deep brain stimulation. Baroreflex amplification uses peripheral neuromodulation, while AV malformation leverages AV anastomosis. CB ablation modulates chemoreceptors, and pacemaker-based neuromodulation adjusts atrioventricular intervals. Electro-acupuncture proves potential, and deep brain stimulation offers central nervous system intervention.
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BACKGROUND: Hypertension (HTN) remains a significant public health concern and the primary modifiable risk factor for cardiovascular disease, which is the leading cause of death in the United States. We applied our validated HTN computable phenotypes within the All of Us Research Program to uncover prevalence and characteristics of HTN and apparent treatment-resistant hypertension (aTRH) in United States. METHODS: Within the All of Us Researcher Workbench, we built a retrospective cohort (January 1, 2008-July 1, 2023), identifying all adults with available age data, at least one blood pressure (BP) measurement, prescribed at least one antihypertensive medication, and with at least one SNOMED "Essential hypertension" diagnosis code. RESULTS: We identified 99 461 participants with HTN who met the eligibility criteria. Following the application of our computable phenotypes, an overall population of 81 462 were further categorized to aTRH (14.4%), stable-controlled HTN (SCH) (39.5%), and Other HTN (46.1%). Compared to participants with SCH, participants with aTRH were older, more likely to be of Black or African American race, had higher levels of social deprivation, and a heightened prevalence of comorbidities such as hyperlipidemia and diabetes. Heart failure, chronic kidney disease, and diabetes were the comorbidities most strongly associated with aTRH. ß-blockers were the most prescribed antihypertensive medication. At index date, the overall BP control rate was 62%. DISCUSSION AND CONCLUSION: All of Us provides a unique opportunity to characterize HTN in the United States. Consistent findings from this study with our prior research highlight the interoperability of our computable phenotypes.
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BACKGROUND: We examined the association of multilevel social determinants of health with incident apparent treatment-resistant hypertension (aTRH). METHODS AND RESULTS: We analyzed data from 2774 White and 2257 Black US adults from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study taking antihypertensive medication without aTRH at baseline to estimate the association of social determinants of health with incident aTRH. Selection of social determinants of health was guided by the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Blood pressure (BP) was measured during study visits, and antihypertensive medication classes were identified through a pill bottle review. Incident aTRH was defined as (1) systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg for those with diabetes or chronic kidney disease while taking ≥3 classes of antihypertensive medication or (2) taking ≥4 classes of antihypertensive medication regardless of BP level, at the follow-up visit. Over a median 9.5 years of follow-up, 15.9% of White and 24.0% of Black adults developed aTRH. A percent of the excess aTRH risk among Black versus White adults was mediated by low education (14.2%), low income (16.0%), not seeing a friend or relative in the past month (8.1%), not having someone to care for them if ill or disabled (7.6%), lack of health insurance (10.6%), living in a disadvantaged neighborhood (18.0%), and living in states with poor public health infrastructure (6.0%). CONCLUSIONS: Part of the association between race and incident aTRH risk was mediated by social determinants of health.
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Antihipertensivos , Negro o Afroamericano , Hipertensión , Determinantes Sociales de la Salud , Población Blanca , Humanos , Determinantes Sociales de la Salud/etnología , Masculino , Estados Unidos/epidemiología , Femenino , Hipertensión/tratamiento farmacológico , Hipertensión/etnología , Hipertensión/epidemiología , Hipertensión/fisiopatología , Persona de Mediana Edad , Antihipertensivos/uso terapéutico , Negro o Afroamericano/estadística & datos numéricos , Población Blanca/estadística & datos numéricos , Anciano , Incidencia , Factores de Riesgo , Presión Sanguínea/efectos de los fármacos , Resistencia a Medicamentos , Disparidades en el Estado de Salud , Escolaridad , Accesibilidad a los Servicios de SaludRESUMEN
In India, around 234 million adults (one in three) suffer from hypertension (HTN). An average of 10% of these cases are likely to be resistant hypertension (RH). This load of 23 million patients is expected to expand further with revisions in diagnostic criteria. The treatment and control rates of hypertension in India average around 30% and 15%, respectively. Pharmacological management involves a stepwise approach starting with optimizing the A-C-D (angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide-like diuretics) triple-drug combination, followed by substitution with a thiazide-like diuretic and use of spironolactone as a next step (fourth drug). The subsequent steps are suggestions based on expert input and must be individualized. These include using a ß-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when target blood pressure (BP) values are not achieved. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are likely to be helpful in managing RH due to their renal and cardiovascular protection as well as mortality benefits. SGLT2i lowers BP independent of the dosage and concomitant anti-hypertensive medications. Patient education and tools to monitor BP and treatment compliance will improve outcomes with these medications. In addition to therapeutic intervention, a preventive approach for RH mandates a need to identify patients at risk and use appropriate preventive and optimal therapy to prevent uncontrolled hypertension in patients with cardiovascular disorders.
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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.
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Hiperaldosteronismo , Hipertensión , Tamizaje Masivo , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/sangre , Femenino , Masculino , Persona de Mediana Edad , Hipertensión/diagnóstico , Tamizaje Masivo/métodos , Tamizaje Masivo/normas , Adulto , Guías de Práctica Clínica como Asunto , Anciano , Registros Electrónicos de SaludRESUMEN
BACKGROUND: Chronic kidney disease (CKD) is a common comorbidity in patients with apparent treatment-resistant hypertension (aTRH). We assessed clinical outcomes, healthcare resource utilization events, and costs in patients with aTRH or difficult-to-control hypertension and stage 3-4 CKD with uncontrolled vs. controlled BP. METHODS: This retrospective cohort study used linked IQVIA Ambulatory EMR-US and IQVIA PharMetrics Plus claims databases. Adult patients had claims for ≥3 antihypertensive medication classes within 30 days between 01/01/2015 and 06/30/2021, 2 office BP measures recorded 1-90 days apart, ≥1 claim with ICD-9/10-CM diagnosis codes for CKD 3/4, and ≥1 year of continuous enrollment. Baseline BP was defined as uncontrolled (≥130/80 mm Hg) or controlled (<130/80 mm Hg) BP. Outcomes included risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure hospitalization), end-stage renal disease (ESRD), healthcare resource utilization events, and costs during follow-up. RESULTS: Of 3,966 patients with stage 3-4 CKD using ≥3 antihypertensive medications, 2,479 had uncontrolled BP and 1,487 had controlled BP. After adjusting for baseline differences, patients with uncontrolled vs. controlled BP had a higher risk of MACE+ (HR [95% CI]: 1.18 [1.03-1.36]), ESRD (1.85 [1.44-2.39]), inpatient hospitalization (rate ratio [95% CI]: 1.35 [1.28-1.43]), and outpatient visits (1.12 [1.11-1.12]) and incurred higher total medical and pharmacy costs (mean difference [95% CI]: $10,055 [$6,741-$13,646] per patient per year). CONCLUSIONS: Patients with aTRH and stage 3-4 CKD and uncontrolled BP despite treatment with ≥3 antihypertensive classes had an increased risk of MACE+ and ESRD and incurred greater healthcare resource utilization and medical expenditures compared with patients taking ≥3 antihypertensive classes with controlled BP.
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Antihipertensivos , Presión Sanguínea , Resistencia a Medicamentos , Hipertensión , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Antihipertensivos/uso terapéutico , Antihipertensivos/economía , Estudios Retrospectivos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Hipertensión/epidemiología , Hipertensión/economía , Hipertensión/diagnóstico , Insuficiencia Renal Crónica/fisiopatología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/economía , Insuficiencia Renal Crónica/complicaciones , Anciano , Presión Sanguínea/efectos de los fármacos , Resultado del Tratamiento , Adulto , Factores de Tiempo , Costos de la Atención en Salud , Bases de Datos Factuales , Costos de los MedicamentosRESUMEN
BACKGROUND: Few reports have focused on the association between apparent treatment-resistant hypertension (aTRH) and cardiovascular (CV) mortality in peritoneal dialysis (PD) population, thus we conducted this retrospective cohort to explore it. METHODS: This was a retrospective cohort study conducted from January 2011 to January 2020 with PD patients in 4 Chinese dialysis centers. aTRH was defined according to the American College of Cardiology and American Heart Association guidelines. aTRH duration was calculated as the total number of months when patients met the diagnostic criteria in the first PD year. The primary outcome was CV mortality, and the secondary outcomes were CV events, all-cause mortality, combined endpoint (all-cause mortality and transferred to hemodialysis [HD]), and PD withdrawal (all-cause mortality, transferred to HD, and kidney transplantation). Cox proportional hazards models were used to assess the association. RESULTS: A total of 1,422 patients were finally included in the analysis. During a median follow-up period of 26 months, 83 (5.8%) PD patients incurred CV mortality. The prevalence of aTRH was 24.1%, 19.9%, and 24.6% at 0, 3, and 12 months after PD initiation, respectively. Overall, aTRH duration in the first PD year positively associated with CV mortality (per 3 months increment, adjusted hazards ratio [HR], 1.29; 95% confidence interval 1.10, 1.53; Pâ =â 0.002). After categorized, those with aTRH duration more than 6 months presented the highest adjusted HR of 2.92. Similar results were found for secondary outcomes, except for the CV event. CONCLUSIONS: Longer aTRH duration in the first PD year is associated with higher CV mortality and worse long-term clinical outcomes. Larger studies are warranted to confirm these findings. CLINICAL TRIALS REGISTRATION: There is no clinical trial registration for this retrospective study.
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Enfermedades Cardiovasculares , Hipertensión , Diálisis Peritoneal , Humanos , Diálisis Peritoneal/mortalidad , Diálisis Peritoneal/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Hipertensión/mortalidad , Anciano , Factores de Tiempo , Enfermedades Cardiovasculares/mortalidad , Adulto , China/epidemiología , Antihipertensivos/uso terapéutico , Medición de Riesgo , Resistencia a Medicamentos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Presión Sanguínea , Factores de Riesgo , Resultado del Tratamiento , Prevalencia , Causas de MuerteRESUMEN
INTRODUCTION: Hypertension, a global health concern, poses a significant risk for other cardiovascular diseases. While lifestyle modifications and interventions like the Dietary Approaches to Stop Hypertension (DASH) diet offer some respite, their maintenance can be challenging. Recently, the spotlight has turned toward the renin-angiotensin-aldosterone system, a crucial player in the pathophysiology of hypertension. Contrary to other drugs, Baxdrostat, an innovative aldosterone synthase inhibitor (ASI), targets aldosterone synthesis, mitigating negative systemic effects. AREAS COVERED: Baxdrostat showcases rapid absorption, high oral bioavailability, and significant selectivity for aldosterone synthase which presents a proactive approach to hypertension management by reducing aldosterone levels. Early trials have demonstrated its potential in lowering blood pressure in resistant hypertension cases. Current clinical trials are also exploring its application in primary aldosteronism and chronic kidney disease, with preliminary findings indicating its promise as a novel antihypertensive agent. This article encapsulates the current state of knowledge regarding Baxdrostat, encompassing its uses, ongoing clinical trials, and potential future clinical applications. EXPERT OPINION: Future research endeavors will play a pivotal role in unveiling the effectiveness and safety profile of this novel medication. Thus, positioning the baxdrostat as a valuable addition to the armamentarium of antihypertensive agents, especially for patients with complex, multifactorial hypertensive conditions.
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Hiperaldosteronismo , Hipertensión , Humanos , Aldosterona/farmacología , Aldosterona/uso terapéutico , Citocromo P-450 CYP11B2/farmacología , Hiperaldosteronismo/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Sistema Renina-Angiotensina , Antihipertensivos/efectos adversos , Inhibidores Enzimáticos/farmacología , Antagonistas de Receptores de Mineralocorticoides/farmacología , Renina/farmacología , Renina/uso terapéutico , Ensayos Clínicos Fase II como AsuntoRESUMEN
Background and Objectives: Treatment resistant hypertension (trHTN) is a common clinical problem faced by many clinicians. Laparoscopic adrenalectomy effectively trims blood pressure (BP) elevation secondary to various functional adrenal disorders. However, the impact of adrenalectomy on BP within trHTN patients has never been reported. Our present study aims to investigate the effect of adrenalectomy on BP management within trHTN patients, and to explore clinical predictors for postoperative BP normalization. Patients and Methods: In our current study, 117 patients diagnosed with trHTN and performed with unilateral adrenalectomy were consecutively enrolled, demographic and medical information were documented for baseline data collection. BP was measured with a standard electronic sphygmomanometer twice a day. Long-term periodical interview was conducted and 109 (93.2%) enrolled patients were successfully followed-up at an averaged 36.2 months. Results: At follow-up, 27/109 (25%) trHTN patients acquired BP normalization and 68/109 (62%) patients acquired BP improvement. Mean taking anti-hypertensive agents reduced from presurgical 4.24 to present 1.21 (P < 0.01), along with 7.2 mmHg reduction in SBP (P < 0.01). Image macro-adenoma and hypokalemia history were found to be the two strongest predictors for postoperative BP normalization. (χ2= 28.032, P < 0.01). The incidence of adverse postoperative events was quite small. Conclusions: In summary, this current study implicates that adrenalectomy is an efficacious and safe surgical strategy for BP management in trHTN patients. Patients with both unilateral macro-adenoma and hypokalemia are more prone to acquire postoperative BP normalization.
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BACKGROUND: The aim of this study was to assess the prevalence, characteristics, and determinants of apparent treatment-resistant hypertension (aTRH) in an unselected large population of patients with end-stage kidney disease (ESKD) treated with hemodialysis (HD) throughout the country. METHODS: A database of 5879 patients (mean age 65.2 ± 14.2 years, 60% of males receiving hemodialysis) was obtained from the biggest provider of hemodialysis in the country. Hypertension and aTRH were defined using pre- or/and post-dialysis BP values. Patients with and without aTRH (non-aTRH) were compared. RESULTS: Using pre- and post-dialysis criteria, hypertension was diagnosed in 90.7% and 89.1% of subjects, respectively. According to pre- and post-dialysis blood pressure criteria, aTRH incidences were 40.9% and 38.4%, respectively. The hypertensive patients with aTRH versus non-aTRH were younger, had a higher rate of cardiovascular disease, lower dialysis vintage, shorter time on dialysis, higher eKt/V, higher ultrafiltration, higher pre- and post-dialysis BP and HR, and higher use of antihypertensive drugs. Factors that increase the risk of aTRH according to both pre- and post-dialysis BP criteria were age-OR 0.99 [0.98-0.99] and 0.99 [0.98-0.99], the history of CVD 1.26 [1.08-1.46] and 1.30 [1.12-1.51], and diabetes 1.26 [1.08-1.47] and 1.28 [1.09-1.49], adjusted OR with 95% CI. CONCLUSIONS: In the real-life world, as much as 40% of HD patients may have aTRH. In ESKD HD patients, aTRH seems to be multifactorial, influenced by patient-related rather than dialysis-related factors. Various definitions of aTRH preclude easy comparisons between studies.
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Refractory hypertension is highly prevalent among the hypertensive population, and current clinical management has failed to provide optimal control for these individuals. This subtype of arterial hypertension is defined as a persistently elevated systolic blood pressure reading of 140 mmHg, or higher, despite multiple antihypertensive use at maximally tolerated dosing. These patients have an elevated risk of cardiovascular and renal complications, urging for the need of more effective therapeutic management. Renal sympathetic efferent nerves have been noted to play an important role in volume and blood pressure homeostasis. Before the implementation of oral antihypertensives, the use of surgical lumbar sympathectomy for the reduction of persistent hypertension was considered a life-saving approach. However, individuals were left with debilitating side effects, such as postural hypotension, syncope, and impotence. A new and minimally invasive technique has been proposed, where the kidneys undergo selective denervation in hopes of providing decreased cardiovascular morbidity and mortality for patients with resistant hypertension. Some studies demonstrated promising outcomes with a reduction in blood pressure, a decrease in medication reliance, and a potential long-lasting effect of the procedure with an overall improvement in cardiovascular health. Unfortunately, most of the available data was obtained from observational, uncontrolled studies with short-term follow-up, small sample sizes, and high variability in blood pressure measurement. Therefore, further evidence is needed to determine whether renal denervation provides long-term benefits for blood pressure control and improves outcomes for mortality and cardiovascular events in this patient population.
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Hipertensión , Humanos , Presión Sanguínea , Hipertensión/terapia , Hipertensión/fisiopatología , Ejercicio FísicoRESUMEN
Patients with apparent treatment-resistant hypertension (aTRH) are at increased risk of end-organ damage and cardiovascular events. Little is known about the effects of blood pressure (BP) control in this population. Using a national claims database integrated with electronic medical records, the authors evaluated the relationships between uncontrolled BP (UBP; ≥130/80 mmHg) or controlled BP (CBP; <130/80 mmHg) and risk of major adverse cardiovascular events plus (MACE+; stroke, myocardial infarction, heart failure requiring hospitalization) and end-stage renal disease (ESRD) in adult patients with aTRH (taking ≥3 antihypertensive medication classes concurrently within 30 days between January 1, 2015 and June 30, 2021). MACE+ components were also evaluated separately. Multivariable regression models were used to adjust for baseline differences in demographic and clinical characteristics, and sensitivity analyses using CBP <140/90 mmHg were conducted. Patients with UBP (n = 22 333) were younger and had fewer comorbidities at baseline than those with CBP (n = 11 427). In the primary analysis, which adjusted for these baseline differences, UBP versus CBP patients were at an 8% increased risk of MACE+ (driven by a 31% increased risk of stroke) and a 53% increased risk of ESRD after 2.7 years of follow-up. Greater MACE+ (22%) and ESRD (98%) risk increases with UBP versus CBP were seen in the sensitivity analysis. These real-world data showed an association between suboptimal BP control in patients with aTRH and higher incidence of MACE+ and ESRD linked with UBP despite the use of multidrug regimens. Thus, there remains a need for improved aTRH management.
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Hipertensión , Estudios Retrospectivos , Estudios de Cohortes , Humanos , Masculino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Antihipertensivos/farmacocinética , Antihipertensivos/uso terapéutico , Factores de Riesgo , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Incidencia , Estados Unidos/epidemiología , FemeninoRESUMEN
BACKGROUND: A limited number of studies have been conducted to test the magnitudes of the association between apparent treatment resistant hypertension (aTRH) and risk of cardiovascular disease (CVD). AIM: To investigate the association between aTRH and risk of CVD and examine whether sex and age modify this association. METHODS: We applied an observational analysis study design using data from the United States Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT recruited participants (n = 25516) from 625 primary care settings throughout the United States, Canada, Puerto Rico, and United States Virgin Islands, aged 55 and older with hypertension and at least one additional risk factor for heart disease. aTRH was assessed from the year 2 visit. CVD event was defined as one of the following from the year 2 follow-up visit: Fatal or non-fatal myocardial infarction, coronary revascularization, angina, stroke, heart failure, or peripheral artery disease. Cox proportional hazards regression was used to examine the effect of aTRH on CVD risk. Potential modifications of sex and age on this association were examined on the multiplicative scale by interaction term and additive scale by joint effects and relative excess risk for interaction. RESULTS: Of the total study participants (n = 25516), 5030 experienced a CVD event during a mean of 4.7 years follow-up. aTRH was associated with a 30% increase in risk of CVD compared to non-aTRH [hazards ratio (HR) = 1.3, 95%CI: 1.19-1.42]. Sex and age modified this relationship on both multiplicative and additive scales independently. Stratified by sex, aTRH was associated with a 64% increase in risk of CVD (HR = 1.64, 95%CI: 1.43-1.88) in women, and a 13% increase in risk of CVD (HR = 1.13, 95%CI: 1.01-1.27) in men. Stratified by age, aTRH had a stronger impact on the risk of CVD in participants aged < 65 (HR = 1.53, 95%CI: 1.32-1.77) than it did in those aged ≥ 65 (HR = 1.18, 95%CI: 1.05-1.32). Significant two-way interactions of sex and aTRH, and age and aTRH on risk of CVD were observed (P < 0.05). The observed joint effect of aTRH and ages ≥ 65 years (HR = 1.85, 95%CI: 1.22-2.48) in males was less than what was expected for both additive and multiplicative models (HR = 4.10, 95%CI: 3.63-4.57 and 4.88, 95%CI: 3.66-6.31), although three-way interaction of sex, age, and aTRH on the risk of CVD and coronary heart disease did not reach a statistical significance (P > 0.05). CONCLUSION: aTRH was significantly associated with an increased risk of CVD and this association was modified by both sex and age. Further studies are warranted to test these mechanisms.
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Heart failure (HF) in the elderly is an increasingly large and complex problem in modern society. Notably, the cause of HF with preserved ejection fraction (HFpEF) is multifactorial and its pathophysiology is not fully understood. Among these, hypertension has emerged as a pivotal factor in the pathophysiology and therapeutic targets of HFpEF. Neuronal elements distributed throughout the cardiac autonomic nervous system, from the level of the central autonomic network including the insular cortex to the intrinsic cardiac nervous system, regulate the human cardiovascular system. Specifically, increased sympathetic nervous system activity due to sympatho-vagal imbalance is suggested to be associated the relationship between hypertension and HFpEF. While several new pharmacological therapies, such as sodium-glucose cotransporter 2 inhibitors, have been shown to be effective in HFpEF, neuromodulatory therapies of renal denervation and vagus nerve stimulation (VNS) have received recent attention. The current review explores the pathophysiology of the brain-heart axis that underlies the relationship between hypertension and HFpEF and the rationale for therapeutic neuromodulation of HFpEF by non-invasive transcutaneous VNS.
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Insuficiencia Cardíaca , Hipertensión , Estimulación del Nervio Vago , Humanos , Anciano , Volumen Sistólico/fisiología , Hipertensión/terapia , Corazón , DesnervaciónRESUMEN
Systemic hypertension (HTN) is the hallmark of cardiovascular disease and the forerunner of heart failure. These associations have been established over decades of research on essential HTN. Advancements in the treatment of patients diagnosed with HTN, consisting of alpha- or beta-adrenergic receptor blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide, or aldosterone receptor blockers known as anti-mineralocorticoids, in the presence or absence of low sodium salt diets, often fail to control blood pressure adequately to prevent morbidity and mortality. Low sodium diets have had limited success in controlling HTN because low sodium intake is associated with renin-angiotensin-aldosterone system upregulation. Therefore, upregulating aldosterone secretion, sodium, and water retention which, in turn, moves the blood pressure back toward the range of HTN dictated by the baroreceptor reset value, as a compensatory mechanism, especially in resistant HTN. These impediments to blood pressure control in HTN may have been effectively circumvented by the advent of a new class of drugs known as aldosterone synthase inhibitors, represented by baxdrostat. The mechanism of action of baxdrostat as an aldosterone synthase inhibitor demonstrates the inextricable linkage between sodium and blood pressure regulation. Theoretically, combining a low sodium diet with the activity of this aldosterone synthesis inhibitor should alleviate the adverse effect of renin-angiotensin-aldosterone system upregulation. Aldosterone synthesis inhibition should also decrease the oxidative stress and endothelial dysfunction associated with HTN, causing more endothelial nitric oxide synthesis, release, and vasorelaxation. To the best of our knowledge, this is the first systematic review to summarize evidence-based articles relevant to the use of a novel drug (aldosterone synthase inhibitor) in the treatment of HTN and cardiovascular disease. Making the current database of relevant information on baxdrostat and other aldosterone synthase inhibitors readily available will, no doubt, aid physicians and other medical practitioners in their decision-making about employing aldosterone synthase inhibitors in the treatment of patients.
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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.