Development Of Resistant Hypertension Research Articles

Is Renal Denervation Effective in Treating Resistant Hypertension?

Resistant hypertension is diagnosed in patients whose blood pressure target is unmet despite the use of three or more antihypertensive medications. Systemic sympathetic hyperactivation is associated with the development of resistant hypertension. As the kidney is largely pervasive of the sympathetic nervous system renal denervation procedure was developed to control blood pressure by attenuating the renal and systemic sympathetic hyperactivity. Renal denervation is a minimally invasive procedure that uses radiofrequency or ultrasound energy waves to reduce the activity of the renal artery nerves. Previous clinical trials have shown conflicting results regarding the efficacy of the procedure. Symplicity HTN-1 and -2 trials showed effective blood pressure lowering results in the renal denervation group with a good safety profile. However, the Symplicity HTN-3 trial showed no difference in blood pressure lowering effect between the renal denervation and control Sham procedure groups. Notwithstanding, some recent clinical trials with Sham control and meta-analysis showed clinical benefits of renal denervation. Other clinical benefits of renal denervation include glucose control, cardiovascular protective effect, reduction of obstructive sleep apnea, and neuralgia control. A subset of patients with satisfactory blood pressure control response to the procedure may experience improved glucose control due to the overall reduced sympathetic activity and insulin resistance. Sympathetic activity control after renal denervation has cardioprotective effects, especially for those with arrhythmia and left ventricular hypertrophy. Also, renal denervation could be helpful in renalorigin pain control. Renal denervation is an effective, safe, non-invasive procedure with many clinical benefits beyond blood pressure control. Further development in the procedure technique and selection of target patients are needed for wider clinical use of renal denervation in resistant hypertension.

Relationship between the hemodynamic profile and resistant hypertension in pregnant patients with hypertensive crisis

ABSTRACTObjectiveReducing maternal morbidity and mortality has been a challenge for low and middle-income countries, especially in the setting of hypertensive disorders of pregnancy. Improved strategies for treating obstetric patients with resistant hypertension are needed. We sought to explore whether hemodynamic parameters may be used to identify patients that develop resistant hypertension in pregnancy.MethodsRetrospective cohort study among pregnant patients with gestational hypertension or preeclampsia that experienced severe blood pressure elevations. Hemodynamic variables were evaluated, including cardiac output (CO), and total peripheral resistance (TPR). The primary endpoint was resistant hypertension. An exploratory logistic regression was performed to evaluate the association between the hemodynamic profile and the development of resistant hypertension. Adverse maternal and fetal outcomes were additionally described according to the presence of resistant hypertension.ResultsFifty-seven patients with severe pregnancy hypertension were included, of whom 34 developed resistant hypertension (59.7%). The resistant hypertension group, in comparison to those without resistant hypertension, presented with a hypodynamic profile characterized by reduced CO < 5 L/min (41.2% vs. 8.7%, p: 0.007), and increased TPR > 1400 dyn-s/cm5 (64.7% vs. 39.1%, p: 0.057). Logistic regression analysis revealed an association between a hypodynamic profile and resistant hypertension (OR 3.252, 95% CI 1.079–9.804; p = 0.035). Newborns of the resistant hypertension group had more frequent low birth weight (<2500 g), low Apgar scores, ICU admissions, and acute respiratory distress syndrome.ConclusionPatients experiencing hypertensive crisis during pregnancy and exhibiting a hypodynamic profile (TPR ≥1400 dyn·s/cm5 and CO ≤ 5 L/min) developed higher rates of resistant hypertension.

Role of brain natriuretic peptide in the pathogenesis of resistant hypertension

Modern medicine has successfully used the N-terminal pro-brain natriuretic peptide (NT-proBNP) as a biomarker for many cardiovascular diseases (CVDs). According to a number of studies, NT-proBNP may also play a role in the development of resistant hypertension (RH), but the existing work addresses this issue only indirectly. In turn, RH causes serious damage to the economic and social spheres, worsening the quality of life of patients. Thus, the complexity of verification and treatment of RH, the inconsistency of the described associations of NT-proBNP and RH makes this topic more relevant than ever.

Is it necessary to perform cardiovascular screening in migrant patients?

Migrant patients arriving in Spain often come from countries where there is no universal access to healthcare. Although the prevalence of arterial hypertension (HTN) is lower in West Africa than in Spain, there is a higher prevalence of masked HT due to the absence of health screening. Furthermore, patients with secondary hypertension may not be diagnosed. We present the case of a 36-year-old Senegalese man, with no known pathological history, resident for a year in Spain, who debuted with a hypertensive emergency. At the time of diagnosis, the patient had severe end-organ damage (hypertensive heart disease, hypertensive retinopathy). After the study, he was diagnosed with arterial hypertension secondary to malformation of the renal artery. After performing angioplasty, blood pressure normalized and, at 18 months, target organ damage had reduced. Migrants who arrive in our country must be incorporated into health screening systems to diagnose and treat possible unknown pathologies. In our case, the clue to secondary hypertension was the development of resistant hypertension with target organ damage in a young subject.

¿Es necesario realizar un screening cardiovascular en los pacientes migrantes?

Migrant patients arriving in Spain often come from countries where there is no universal access to healthcare. Although the prevalence of arterial hypertension (HTN) is lower in West Africa than in Spain, there is a higher prevalence of masked HT due to the absence of health screening. Furthermore, patients with secondary hypertension may not be diagnosed. We present the case of a 36-year-old Senegalese man, with no known pathological history, resident for a year in Spain, who debuted with a hypertensive emergency. At the time of diagnosis, the patient had severe end-organ damage (hypertensive heart disease, hypertensive retinopathy). After the study, he was diagnosed with arterial hypertension secondary to malformation of the renal artery. After performing angioplasty, blood pressure normalized and, at 18 months, target organ damage had reduced. Migrants who arrive in our country must be incorporated into health screening systems to diagnose and treat possible unknown pathologies. In our case, the clue to secondary hypertension was the development of resistant hypertension with target organ damage in a young subject.

PP.25.23] FACTORS INFLUENCING RESISTANCE TO DRUG THERAPY IN PATIENTS WITH ESSENTIAL HYPERTENSION

Objective: It is suggested that the development of resistant hypertension (RH) is associated with hyperactivity of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic system. But the precise mechanisms leading to resistance to treatment have not established. Aim: To investigate the relation of RAAS activity and the sympathetic system with low grade inflammation and renal function in patients with RH. Design and method: The study included 51 patients with essential RH. In 21 patients RH was excluded and they formed a control group. Plasma renin activity (PRA) and aldosterone were estimated. Inflammatory marker high sensitive C-reactive protein (hs-CRP) was evaluated by immunoassay. 24-h urinary metanephrines were examined. Glomerular filtration rate (GFR) assessment was based on 24-h endogenous creatinine clearance. Microalbuminuria (MAU) was detected in 24-h urinary samples by turbodimetric method. Blood pressure (BP) was measured at office and by ambulatory BP monitoring. Results: Patients with RH and control group did not differ by age (P > 0.05) and body mass index (P > 0.05). We stated a relationship between aldosterone and average daily SBP and DBP (r = 0, 473, P < 0.05 and r = 0, 550, P < 0.05 respectively). The metanephrins level of patients with RH by 41,2 ± 2,3% (P < 0.05) exceeded it in control group. There was relationship between aldosterone and metanephrins (r = 0,355; P < 0.05). Aldosterone was associated with increasing of creatinine (r = 0,875; P < 0.01), MAU (r = 0,846; P < 0.01) and GFR decreasing (r = −0,480; P < 0.01). The relationships between aldosterone and CRP (r = 0,352; P < 0.05) as well as between metanephrins and CRP (r = 0,468; P < 0.05) and GFR (r = −0,475; P < 0.01) were stated. Conclusions: Aldosterone level and metanephrins of RH patients associated with the deterioration of kidney function and with hs-CRP. The deterioration of kidney function and low-grade inflammation under the activation of RAAS and the sympathetic system may be the basis for the development of RH.

Hypertension résistante et maladie rénale chronique : épidémiologie et pronostic

The emergence of new effective therapeutic strategies for the treatment of resistant hypertension such as renal sympathetic denervation technique has lead to a renewed interest in the screening and assessment of prognosis of this specific entity which constitutes a subset of uncontrolled hypertension. Its prevalence is unknown, but estimated between 12 and 15 % among hypertensive subjects from the general population. Several factors have been associated with the development of resistant hypertension, four of which are essential: age, diabetes, chronic kidney disease and vascular structural alteration. Excessive salt intake is also a risk factor for poorly controlled hypertension in patients with salt-dependent hypertension, and may participate to the genesis of resistant hypertension. Because of population ageing and increasing prevalence of diabetes, obesity and chronic kidney disease, the prevalence of resistant hypertension is expected to rise. A better understanding of its determinants and associated risks (such as chronic kidney disease) would identify high-risk groups that may benefit from extensive diagnosis work up and more specific treatments.

Predicting the development of resistant hypertension with non-invasive hemodynamic measures

Predicting the development of resistant hypertension with non-invasive hemodynamic measures

Renal Nerve Ablation for Resistant Hypertension

Sympathetic renal denervation, or renal nerve ablation (RNA), has become the new buzz word in hypertension and interventional cardiology. Recent advances in catheter-based approaches have allowed sympathetic fiber interruption through transvascular techniques that are minimally invasive and can be delivered expeditiously and safely. Radiofrequency (RF) energy sources are currently the preferred modalities, but other sources of energy, such as cryoablation, microwave, high-intensity focus ultrasound, and local neurotoxic agent infusion, are under intense investigation. Results thus far have been encouraging and offer promise for the future. The role of the sympathetic nervous system (SNS) in the development of resistant hypertension and cardiovascular disease has long been known, and a great deal of work has been done through the years trying to explore potential interventions to interrupt the sympathetic influence on systemic vasculature and target organs. In this article we attempt an overview of time-dependent interventions on the SNS and examine approaches used in humans and in the many experimental models that offer a better understanding of the role of sympathetic activity in cardiovascular disease. Naturally we focus on methods and techniques addressing sympathetic renal denervation in patients with drug-resistant hypertension, examine the current state of the art, and attempt a look into the future. In 1889, after meticulous experiments on dogs, Bradford1 reported that stimulation of dorsal and splanchnic nerves causes changes in blood pressure (BP) and kidney size measured by plethysmography. Whether BP increased or decreased depended on the anatomic area stimulated, as well as the electric impulse frequency, but outcomes were consistent and reproducible. Neurosurgical treatment of hypertension was independently suggested by researchers in 1923.2 Adson, however, was the first to performed surgical sympathectomy for the treatment of malignant hypertension in 1925.3 During the following years and in the 1930s, Peet in Ann Arbor, Page and …

Clinical profile and management approach of patients diagnosed with resistant hypertension in a tertiary government hospital

Resistant hypertension is blood pressure that remains above target despite treatment with maximum doses of 3 anti-hypertensive drugs which may include a diuretic. The prevalence of resistant hypertension is unknown, and there are no local studies in the Philippines concerning this condition. A retrospective descriptive study was conducted in the Hypertension Clinic of the Section of Hypertension of the Philippine General Hospital (PGH) to describe the approach of management of patients with resistant hypertension which may eventually help in creating local guidelines in the management of this condition. A total of 51 patients were diagnosed with resistant hypertension, and charts were reviewed and analyzed. Majority of the patients were females (31, 60.8%) with a mean age of 56.3 yrs. Their most common presenting symptoms were headache, exertional dyspnea, nape pain, dizziness and easy fatigability. Of the 51 patients, 45% also had diabetes mellitus, 11.8% had dyslipidemia and 7.8% had previous history of pre-eclampsia. Approximately 35% of these patients were smokers. The average BP before referral to the section was 167/94. By this time, most patients will either be on a 4-drug regimen (42.1%) or a 3-drug regimen (36.8%). Physicians often prescribe a 2-drug combination as their initial management of hypertension (42.1%) with the usual combination of a calcium channel blocker and a beta blocker. Twelve patients were started on monotherapy using a beta-blocker or an ACE-inhibitor. Patients had a median number of 6 follow-ups prior to referral to a hypertension specialist. The median number of visits in the Hypertension Clinic prior to control of BP was 3 follow-ups, and the average BP was 119/71. The regimens of the patients with controlled BP are 3-drug combinations (36.4%), 4-drug combination (36.4%) and 5-drug combination (27.3%). Female gender, older age, diabetes and a BP within the range of stage II hypertension may contribute to the development of resistant hypertension in the Philippine population. Early referral to a hypertension specialist may benefit a patient with resistant hypertension, decreasing the number of follow-up visits to control a patient's blood pressure. Four to five drug combinations may be needed to adequately control a patient's blood pressure.

300 THE PREVALENCE OF WHITE-COAT RESISTANT HYPERTENSION (WC-RH) AMONGST PATIENTS REFERRED FOR CATHETHER-BASED RENAL DENERVATION (RDN) PROCEDURE FOR TRUE RESISTANT HYPERTENSION (TRH) AT THE NATIONAL HEART INSTITUTE OF MALAYSIA

Introduction and objectives: There is limited data on prevalence of WC-RH in patients considered eligible for renal denervation (RDN). In Simplicity HTN 1&2 trials, Ambulatory Blood Pressure Monitoring (ABPM) was not used in all patients to assess true resistant hypertension (TRH). The objectives are to determine the prevalence of WC-RH amongst patients referred for RDN and to assess the clinical predictors of WC-RH. Methods: 37 patients were enrolled between August 2011 and January 2012. Inclusion criteria for RDN are those used in Symplicity HTN 1&2. Patient had ≥3 office BP of systolic ≥160 (≥150 for type 2 DM) and adhered to ≥3 antihypertensive drugs. Patients with eGFR of <45 ml/min were excluded. WC-RH is defined as average daytime ABPM ≤135/85. All patients had ABPM assessment. Results: 13 patients (35%) had WC-RH and 24 patients (65%) were classified as TRH. In WC-RH group, the mean±SD age is 64.9±9.5. There are 7(54%) Malay, 3(23%) Chinese and 3(23%) Indian patients. There are 3(23%) smoker, 8(62%) dyslipidaemic and 7(54%) diabetic. The mean±SD systolic ABPM in WC-RH group are 126.7±7.4. The mean±SD age of the TRH group is 64.5±9.7. There were 3(13%) smoker, 18(75%) dyslipidaemia and 14(58%) diabetic. No patient's baseline characteristics are statistically significant as clinical predictors for the diagnosis of WC-RH. Conclusion: More than 1/3 of patients with RH initially considered eligible for RDN procedures have WC-RH. The use of ABPM may avoid mislabelling of patient with TRH thus avoiding unnecessary tests to look for secondary hypertension and expensive invasive procedures. Background: Obesity has been associated with resistant hypertension (RHTN) by high aldosterone and adipocytokines plasma levels. Resistin is a hormone produced by adipocite tissue implicated in endothelial dysfunction and vascular stiffness in hypertensive subjects. However, the role of both aldosterone and resistin in the development of resistant hypertension is not clearly understood. Methods: Office BP, aldosterone and resistin plasma levels (ELISA), endothelial function (brachial flow-mediated dilation, FMD) and vascular stiffness (pulse wave velocity- PWV) were evaluated in 93 RHTN patients. Pearson[Combining Acute Accent]s correlation was used to analyze the association between aldosterone and resistin with the other variables. Results: RHTN patients had (mean±SD): age (58.0±10.8 y.o.), BMI (30.89±4.83 kg/m2), Systolic BP (SBP) (147±17mmHg), Diastolic BP (DBP) (87±11 mmHg), PP (60±15 mmHg), aldosterone levels (119.5±66.8 pg/mL), resistin levels (11.4±5.8 ng/mL), FMD test response (7.8± 1.8%) and pulse wave velocity (PWV= 11.5±1.8 m/s). Aldosterone plasma levels correlated with SBP (p< 0.001; r=0.41), PP (p< 0.001; r=0.35), FMD response (p< 0.05; r= -0.23), but not resistin (p>0,05). Both resistin and aldosterone plasma levels correlated with PWV (p< 0.05; r=0.32; p< 0.001; r= 0.43, respectively). Conclusion: Despite the importance of resistin in endothelial dysfunction in RHTN, aldosterone may surpass the importance of this adipocytokine in resistant hypertension pathophysiology, playing an important role in the mechanisms of antihypertensive therapy resistance.

Effects of Dietary Sodium Reduction on Blood Pressure in Subjects With Resistant Hypertension

Observational studies indicate a significant relation between dietary sodium and level of blood pressure. However, the role of salt sensitivity in the development of resistant hypertension is unknown. The present study examined the effects of dietary salt restriction on office and 24-hour ambulatory blood pressure in subjects with resistant hypertension. Twelve subjects with resistant hypertension entered into a randomized crossover evaluation of low (50 mmol/24 hours x 7 days) and high sodium diets (250 mmol/24 hours x 7 days) separated by a 2-week washout period. Brain natriuretic peptide; plasma renin activity; 24-hour urinary aldosterone, sodium, and potassium; 24-hour ambulatory blood pressure monitoring; aortic pulse wave velocity; and augmentation index were compared between dietary treatment periods. At baseline, subjects were on an average of 3.4+/-0.5 antihypertensive medications with a mean office BP of 145.8+/-10.8/83.9+/-11.2 mm Hg. Mean urinary sodium excretion was 46.1+/-26.8 versus 252.2+/-64.6 mmol/24 hours during low- versus high-salt intake. Low- compared to high-salt diet decreased office systolic and diastolic blood pressure by 22.7 and 9.1 mm Hg, respectively. Plasma renin activity increased whereas brain natriuretic peptide and creatinine clearance decreased during low-salt intake, indicative of intravascular volume reduction. These results indicate that excessive dietary sodium ingestion contributes importantly to resistance to antihypertensive treatment. Strategies to substantially reduce dietary salt intake should be part of the overall treatment of resistant hypertension.

Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension

Essential hypertension is a disease multifactorially triggered by genetic and environmental factors. The contribution of genetic polymorphisms of the renin-angiotensin-aldosterone system and clinical risk factors to the development of resistant hypertension was evaluated in 90 hypertensive patients and in 115 normotensive controls living in Southwestern Brazil. Genotyping for insertion/deletion of angiotensin-converting enzyme, angiotensinogen M235T, angiotensin II type 1 receptor A1166C, aldosterone synthase C344T, and mineralocorticoid receptor A4582C polymorphisms was performed by PCR, with further restriction analysis when required. The influence of genetic polymorphisms on blood pressure variation was assessed by analysis of the odds ratio, while clinical risk factors were evaluated by logistic regression. Our analysis indicated that individuals who carry alleles 235-T, 1166-A, 344-T, or 4582-C had a significant risk of developing resistant hypertension (P < 0.05). Surprisingly, when we tested individuals who carried the presumed risk genotypes A1166C, C344T, and A4582C we found that these genotypes were not associated with resistant hypertension. However, a gradual increase in the risk to develop resistant hypertension was detected when the 235-MT and TT genotypes were combined with one, two or three of the supposedly more vulnerable genotypes - A1166C (AC/AA), C344T (TC/TT) and A4582C (AC/CC). Analysis of clinical parameters indicated that age, body mass index and gender contribute to blood pressure increase (P < 0.05). These results suggest that unfavorable genetic renin-angiotensin-aldosterone system patterns and clinical risk variables may contribute to increasing the risk for the development of resistant hypertension in a sample of the Brazilian population.