Secondary Causes Of Resistant Hypertension Research Articles

Abstract P227: Resistant Hypertension In Young Patient- A Case Of Conn’S Syndrome

Abstract: Resistant hypertension (HTN) is defined as elevated blood pressure (BP) while being on three different antihypertensive medications at maximum recommended doses which include diuretics or BP that requires four different antihypertensives. One of the secondary causes of resistant HTN is Conn's Syndrome (CS). CS is mainly due to excessive secretions of aldosterone (aldo), Aldo is a mineralocorticoid hormone that maintains sodium and potassium homeostasis. Excessive secretion can result in hypernatremia and hypokalemia. This is a case of a young patient who presented with resistant hypertension and low potassium. Case: A 47-year-old African American with a known history of HTN presented with a seizure-like episode due to elevated BP and low potassium (K) of 2.6 with a creatinine of 2.2 (baseline creatinine 1.2). He was non-compliant with BP medication hydrochlorothiazide. During hospitalization, BP remained elevated with low K even with K supplementation. BP regimen was broadened to amlodipine, carvedilol, hydralazine, losartan, and spironolactone. Further evaluation showed elevated plasma aldo and low renin with a ratio >30. CT abdomen with contrast confirmed a right adrenal gland adenoma measuring 1.8 cm x 2.0 cm. Ultimately, the patient underwent robot-assisted right adrenalectomy, and adrenal vein sampling (AVS) confirmed CS. The right AVS showed an aldo level >3000 ng/dl and the left adrenal aldo level was 37.6 ng/dl. After successful surgery, BP medicines were cut down to spironolactone. A few months later, BP improved, and all medications were discontinued. Discussion: Aldosterone poses proinflammatory, prothrombotic, and profibrotic changes that in the long-term cause end-organ damage. For these reasons, diagnosing hyperaldosteronism early in young patients is crucial to avoid further complications. Adrenalectomy is a treatment of choice in most cases, many patients could also benefit from pharmacotherapy, especially with newer medications that are not anti-androgenic and nonsteroidal like finerenone. Hyperaldosteronism can be simply diagnosed by checking serum morning aldo level and renin level. Therefore, screening for hyperaldosteronism should be done frequently in young patients with resistant HTN.

Beyond Conventional Control: Insights Into Drug-Resistant Hypertension.

It is believed that 9-18% of patients with hypertension have resistant hypertension, a serious medical disease. The increased cardiovascular risk associated with this illness demands appropriate diagnosis and treatment. It is necessary to conduct an in-depth investigation of the various etiologies, indicators of risk, and multiple disorders of resistant hypertension. This is crucial in order to establish the diagnosis and make the best decisions regarding therapy. Treatment should also take lifestyle changes into account in addition to medicinal and interventional therapy. When there is a suspicion of resistant hypertension, examining the medications used to treat the hypertensive patient after ruling out pseudo hypertension, improper blood pressure monitoring and control, and the white-coat effect are necessary. Resistant hypertension, according to a specific definition, is a condition that cannot be treated with more than two antihypertensive drugs, including a diuretic. An effective multidrug therapy for the treatment of resistant hypertension includes angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, diuretics, long-acting calcium channel blockers, and mineralocorticoid receptor antagonists. However, alternative, cutting-edge treatments, such as renal denervation or baroreflex activation, could develop a brand-new avenue for decreasing blood pressure. These new surgical interventions might prove out to be of immense importance in coming times. Secondary causes of resistant hypertension, such as obstructive sleep apnea, coronary artery diseases, nephropathy, or endocrinal diseases, must be checked out in order to make an accurate diagnosis of this illness. This review article briefly summarizes the epidemiology, risk factors, causes, pathogenesis, diagnosis, and treatment approaches that may help with the long-term management of resistant hypertension.

Risk of resistant hypertension associated with restless legs syndrome and periodic limb movements during sleep: A study on 673 treated hypertensive individuals

Given the limited data available in the literature, the aim of this study was to examine the risk of resistant hypertension (RHT) associated with restless legs syndrome (RLS) and periodic limb movements during sleep (PMLS) in a large sample of treated hypertensive individuals. Demographic and polysomnographic data from 673 treated hypertensive individuals recruited from the research database of the sleep laboratory were analysed. After exclusion of the main causes of pseudo-resistance and secondary hypertension, RHT status was defined by the presence of an uncontrolled hypertension despite treatment with at least three antihypertensive agents (including a diuretic) from different classes in correct combination and at the highest tolerated doses or by the presence of controlled hypertension requiring the use of at least four antihypertensive agents. Logistic regression analyses were conducted to examine the risk of RHT associated with RLS and PMLS in treated hypertensive individuals. After adjustment for major confounding factors associated with RHT, multivariate logistic regression analysis revealed that frequent RLS (≥ 2 episodes/week) combined to PLMS index ≥ 26/hour [OR 2.25 (95% CI 1.37–3.69)] was significant risk factors of RHT in treated hypertensive individuals. In treated hypertensive individuals, frequent RLS combined to PLMS index ≥ 26/hour is associated with higher risk of RHT which suggests that this pathology may be a secondary cause of RHT (such as obstructive sleep apnea syndrome and insomnia with short sleep duration) justifying the establishment of effective treatment in order to avoid the negative consequences associated with the occurrence of resistance to antihypertensive agents.

Risk of resistant hypertension associated with restless legs syndrome and periodic limb movements during sleep: a study on 673 treated hypertensive individuals

ObjectiveGiven the limited data available in the literature, the aim of this study was to examine the risk of resistant hypertension (RHT) associated with restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) in a large sample of treated hypertensive individuals. MethodsDemographic and polysomnographic (PSG) data from 673 treated hypertensive individuals recruited from the research database of the sleep laboratory of Erasme Hospital were analysed. After exclusion of the main causes of pseudo-resistance and secondary hypertension, RHT status was defined by the presence of an uncontrolled hypertension despite treatment with at least three antihypertensive agents (including a diuretic) from different classes in correct combination and at the highest tolerated doses or by the presence of controlled hypertension requiring the use of at least four antihypertensive agents. Logistic regression analyses were conducted to examine the risk of RHT associated with RLS and PLMS in treated hypertensive individuals. ResultsAfter adjustment for major confounding factors associated with RHT, multivariate logistic regression analysis revealed that frequent RLS (≥2 episodes/week) combined with PLMS index ≥26/h [odds ratio (OR) 2.20; 95% confidence interval (CI) 1.35–3.61, p = 0.021] was a significant risk factor of RHT in treated hypertensive individuals. ConclusionIn treated hypertensive individuals, frequent RLS combined with PLMS index ≥26/h is associated with higher risk of RHT which suggests that this pathology may be a secondary cause of RHT (eg, obstructive sleep apnoea syndrome and insomnia with short sleep duration) justifying the establishment of effective treatments in this particular subpopulation.

Resistant Hypertension: Diagnosis and Management.

Resistant hypertension is defined as high blood pressure requiring 3 or more medications for adequate control or controlled blood pressure requiring 4 or more medications. Considering the growing prevalence of hypertension and the strong link with cardiovascular disease, it is vital to understand the causes and treatment of resistant hypertension. This review article starts with an overview of the prevalence and little-known pathophysiology of resistant hypertension. Afterward, we discuss the evaluation and management of suspected secondary resistant hypertension in 2 broad categories: pseudoresistant hypertension and true resistant hypertension. Strategies for the identification and management of pseudoresistant hypertension are addressed. In addition, causes of true resistant hypertension, such as obstructive sleep apnea, primary aldosteronism, and renal artery stenosis, are examined along with their respective treatments. Finally, treatment of resistant hypertension is reviewed including pharmacologic treatments and novel procedural interventions for resistant hypertension. Overall, the review hopes to provide practitioners with a cohesive approach for the diagnosis and treatment of resistant hypertension.

Abstract P145: Screening Rates for the Diagnostic Workup of Resistant Hypertension

Resistant hypertension is a common clinical condition associated with higher rates of cardiovascular disease, kidney disease, and death. Among individuals with resistant hypertension, secondary causes of hypertension occur in about 20% of cases, but the rates of screening are unknown. We assessed the practice pattern of these guidelines in a major primary and tertiary care academic institution in Northern California. Using the electronic health record, we identified individuals between the years of 2008 and 2014 who were prescribed three separate classes of antihypertensive agents and had follow-up laboratory data within 24 months. We excluded individuals with known causes of secondary hypertension such as hyperaldosteronism, renal artery stenosis, fibromuscular dysplasia, adrenal disease, and end-stage renal disease. We also excluded individuals with diagnosed heart failure, who may have been prescribed selected medications for heart failure instead of hypertension. This cohort of 37,073 individuals with presumed resistant hypertension had a mean age of 58.5 years (SD 15.8), was 51.7% male, and 56.4% Caucasian, 6.3% Black, and 12.4% Asian. Among these individuals, only 520 had a serum aldosterone, and only 447 had both aldosterone and plasma renin activity levels measured. These data infer that the recommended initial screening tests for secondary causes of resistant hypertension - notably primary and secondary hyperaldosteronism - are conducted in only 1.2% of individuals. A detailed chart review of a representative sample of this cohort will be also be conducted. Thus far, these data suggest that there is significant under-screening of reversible causes of resistant hypertension. Furthermore, an electronic implementation strategy to prompt screening for secondary causes may be warranted to reduce blood pressure, optimize use of antihypertensive medications, and lower cardiovascular risk. A similar analysis will be performed in the Veterans Affairs database to evaluate screening rates in health-care delivery systems enriched with African Americans.

PS 14-67 A CURIOUS CASE OF RESISTANT HYPERTENSION

Objective: Renovascular hypertension is an important underdiagnosed secondary cause of resistant hypertension in young. Renal vascular atherosclerosis (90%) and renal fibromuscular dysplasia (FMD) (10%) are two main etiologies. FMD rarely cause clinically significant renal artery stenosis (RAS) and is typically truncal or distal. It's often curable with revascularization, percutaneous renal angioplasty being the treatment of choice. Design and Method: We hereby present a case of renovascular hypertension in young male which turned out to be unifocal FMD not amenable to percutaneous angioplasty. Results: We present a case of resistant hypertension in 34 years old male who was diagnosed with renovascular hypertension due to right RAS. Patient remained hypertensive (maximum BP 210/110 mmHg) despite being on nine antihypertensive medications including diuretics (Table). Computed tomographic angiogram revealed occlusion of right main renal artery (MRA) with reformation through lumbar collaterals. Digital substraction angiography revealed atretic right MRA at its origin while Diethylene Triamine Penta Acetic acid (DTPA) renogram showed a small poorly functional right kidney. As percutaneous interventional revascularization was not possible, autotransplantation of right kidney with in situ revacularization with reversed great saphenous vein graft was planned. Intraoperatively, small calibre right MRA was found which was not amenable to aortorenal bypass. Eventually, patient underwent right nephrectomy. Histopathological examination revealed ischemic nephropathy with fibromuscular dysplasia (Medial fibroplasia) (Figure). Patient recovered completely and doesn’t require antihypertensive drug treatment. Conclusions: FMD is rare cause of ostial unifocal RAS in males but must be ruled out in young hypertensives, even in absence of family history or the classic “string-of-beads” appearance in angiography. This case reiterates the need of multiple imaging modalities for early diagnosis and the usefulness of interventional procedures for prompt treatment of renovascular hypertension. In cases of FMD not amenable to percutaneous angioplasty, nephrectomy may be considered as curative option.

OP.7D.08] SEVERE RESISTANT HYPERTENSION EXHIBITS THE GREATEST CARDIOVASCULAR RISK AMONG TREATED UNCONTROLLED HYPERTENSIVES

Objective: Data regarding the prognosis of resistant hypertension (RHT) with respect to its severity is limited. We investigated the cardiovascular risk of severe RHT among patients with treated uncontrolled hypertension. Design and method: In a prospective observational study, 1700 hypertensive patients (aged 57±12 years, 50% males) with office blood pressure (BP) >or = 140 and/or 90mmHg despite antihypertensive treatment, were followed for a mean period of 3.6±1.8 years. At baseline, clinical data were collected and patients underwent echocardiographic measurements, routine blood testing and additional workup for exclusion of secondary causes of RHT. Three groups were identified depending on presence of RHT (office-based uncontrolled hypertension under at least 3 drugs including a diuretic) and levels of office systolic BP: 1,187 patients (70%) without RHT, 313 (18%) with not-severe RHT (systolic BP < 160mmHg) and 200 (12%) with severe RHT (systolic BP >or = 160mmHg). Endpoint of interest was cardiovascular morbidity set as the composite of coronary heart disease and stroke. Results: During follow-up, 58 events were recorded (9.5 cases per 1,000 person-years). Incidence rates of cardiovascular events were 7.1 cases per 1,000 person-years in the group without RHT, 12.4 cases per 1,000 person-years in the group with not-severe RHT and 18 cases per 1,000 person-years in the severe RHT group. Unadjusted analysis showed that compared to uncontrolled patients without RHT, patients with not-severe RHT exhibited a similar risk but patients with severe RHT had a significantly higher risk by 2.5 times (CI: 1.28–4.73, p = 0.007) for the composite cardiovascular outcome. Multivariate cox regression revealed that even after adjusting for a series of established risk factors, severe RHT remained as an independent predictor of the cardiovascular outcome, (OR:2.57, CI:1.27–5.19, p = 0.008). Conclusions: Among treated yet uncontrolled hypertensive patients, severe RHT exhibits a significantly higher cardiovascular risk indicating the need for prompt management.

Resistant Hypertension.

Resistant hypertension is a severe medical condition which is estimated to appear in 9-18% of hypertensive patients. Due to higher cardiovascular risk, this disorder requires special diagnosis and treatment. The heterogeneous etiology, risk factors and comorbidities of resistant hypertension stand in need of sophisticated evaluation to confirm the diagnosis and select the best therapeutic options, which should consider lifestyle modifications as well as pharmacological and interventional treatment. After having excluded pseudohypertension, inappropriate blood pressure measurement and control as well as the white coat effect, suspicion of resistant hypertension requires an analysis of drugs which the hypertensive patient is treated with. According to one definition - ineffective treatment with 3 or more antihypertensive drugs including diuretics makes it possible to diagnose resistant hypertension. A multidrug therapy including angiotensin - converting enzyme inhibitors, angiotensin II receptor blockers, beta blockers, diuretics, long-acting calcium channel blockers and mineralocorticoid receptor antagonists has been demonstrated to be effective in resistant hypertension treatment. Nevertheless, optional, innovative therapies, e.g. a renal denervation or baroreflex activation, may create a novel pathway of blood pressure lowering procedures. The right diagnosis of this disease needs to eliminate the secondary causes of resistant hypertension e.g. obstructive sleep apnea, atherosclerosis and renal or hormonal disorders. This paper briefly summarizes the identification of the causes of resistant hypertension and therapeutic strategies, which may contribute to the proper diagnosis and an improvement of the long term management of resistant hypertension.

An overlooked cause of resistant hypertension: upper airway resistance syndrome - preliminary results

OBJECTIVE:Upper airway resistance syndrome is a sleep-disordered breathing syndrome that is characterized by repetitive arousals resulting in sympathetic overactivity. We aimed to determine whether upper airway resistance syndrome was associated with poorly controlled hypertension.METHODS:A total of 40 patients with resistant hypertension were enrolled in the study. All of the patients underwent polysomnographic examinations and 24-hour ambulatory blood pressure monitoring to exclude white coat syndrome and to monitor treatment efficiency. Among 14 upper airway resistance syndrome patients, 2 patients had surgically correctable upper airway pathologies, while 12 patients were given positive airway pressure therapy.RESULTS:All patients underwent polysomnographic examinations; 22 patients (55%) were diagnosed with obstructive sleep apnea and 14 patients (35%) were diagnosed with upper airway resistance syndrome, according to American Sleep Disorders Association criteria. The patients with upper airway resistance syndrome were younger and had a lower body mass index compared with other patients, while there were no difference between the blood pressure levels and the number of antihypertensive drugs. The arousal index was positively correlated with systolic blood pressure level (p = 0.034; rs = 0.746), while the Epworth score and AHI were independent of disease severity (p = 0.435, rs = 0.323 and p = 0.819, rs = -0.097, respectively). Eight patients were treated with positive airway pressure treatment and blood pressure control was achieved in all of them, whereas no pressure reduction was observed in four untreated patients.CONCLUSIONS:We conclude that upper airway resistance syndrome is a possible secondary cause of resistant hypertension and that its proper treatment could result in dramatic blood pressure control.

Cardiac function and hypertension in patients with obstructive sleep apnea

Cardiac function and hypertension in patients with obstructive sleep apnea Adriana Bertolami, Carolina Gonzaga, Celso AmodeoSleep Laboratory of Dante Pazzanese Institute of Cardiology, Sao Paulo, BrazilAbstract: Cardiovascular disease is one of the major causes of death worldwide. Among its risk factors, obstructive sleep apnea (OSA) is a common but still underestimated condition. OSA often coexists and interacts with obesity, sharing multiple pathophysiological mechanisms and subsequent cardiovascular risk factors, such as type 2 diabetes, dyslipidemia, systemic inflammation, and in particular hypertension. There is also evidence suggesting an increased risk of arrhythmia, heart failure, renal failure, acute myocardial infarction, stroke, and death. OSA is characterized by recurrent episodes of partial (hypopnea) or complete interruption (apnea) of breathing during sleep due to airway collapse in the pharyngeal region. The main mechanisms linking OSA to impaired cardiovascular function are secondary to hypoxemia and reoxygenation, arousals, and negative intrathoracic pressure. Consequently, the sympathetic nervous and the renin-angiotensin-aldosterone systems may be overestimulated, and blood pressure increased. Resistance to treatment for hypertension represents a growing issue, and given that OSA has been recognized as the major secondary cause of resistant hypertension, clinical investigation for apnea is mandatory in this population. Standard diagnosis includes polysomnography, and treatment for OSA should include control of risk factors for cardiovascular disease, including obesity. So far, continuous positive airway pressure is the treatment of choice for OSA, impacting positively on blood pressure goals; however, the impact on long-term follow-up and on cardiovascular disease should be better assessed.Keywords: obstructive sleep apnea, hypertension, cardiac function

OP-346 An Overlooked Cause of Resistant Hypertension; Upper Airway Resistance Syndrome

ObjectiveUpper airway resistance syndrome is a sleep disordered breathing syndrome characterized by repetetive arousals resulting in sympathetic overactivity. We aimed to determine whether upper airway resistance syndrome is related to resistant hypertension.MethodsFourty patients with resistant hypertension were enrolled in the study. All patients underwent polysomnographic examination. All patients underwent 24 hours ambulatory blood pressure monitoring in order to rule out white coat syndrome and to monitor treatment efficiency.ResultsTwenty-two patients (55%) were diagnosed with obstructive sleep apnoea and 14 patients (35%) were diagnosed with upper airway resistance syndrome according to American Sleep Disorders Association criteria. Upper airway resistance syndrome patients were younger and had a lower BMI when compared to other patients while there were no difference between the blood pressure levels and the number of antihypertensive drugs. Arousal index was determined to be positively correlated with systolic blood pressure level (p=0.034; r=0.746 ) while epword score and apnea-hypopnea index were independent of disease severity (p=0.435, r=0.323 and p=0.819, r= -0.097 respectively). Eight patients were treated with positive airway pressure treatment and blood pressure control was achieved in all whereas no pressure reduction was observed in 4 untreated patients.ConclusionsWe concluded that upper airway resistance syndrome is a possible secondary cause of resistant hypertension and its proper treatment can result in dramatic blood pressure control. ObjectiveUpper airway resistance syndrome is a sleep disordered breathing syndrome characterized by repetetive arousals resulting in sympathetic overactivity. We aimed to determine whether upper airway resistance syndrome is related to resistant hypertension. Upper airway resistance syndrome is a sleep disordered breathing syndrome characterized by repetetive arousals resulting in sympathetic overactivity. We aimed to determine whether upper airway resistance syndrome is related to resistant hypertension. MethodsFourty patients with resistant hypertension were enrolled in the study. All patients underwent polysomnographic examination. All patients underwent 24 hours ambulatory blood pressure monitoring in order to rule out white coat syndrome and to monitor treatment efficiency. Fourty patients with resistant hypertension were enrolled in the study. All patients underwent polysomnographic examination. All patients underwent 24 hours ambulatory blood pressure monitoring in order to rule out white coat syndrome and to monitor treatment efficiency. ResultsTwenty-two patients (55%) were diagnosed with obstructive sleep apnoea and 14 patients (35%) were diagnosed with upper airway resistance syndrome according to American Sleep Disorders Association criteria. Upper airway resistance syndrome patients were younger and had a lower BMI when compared to other patients while there were no difference between the blood pressure levels and the number of antihypertensive drugs. Arousal index was determined to be positively correlated with systolic blood pressure level (p=0.034; r=0.746 ) while epword score and apnea-hypopnea index were independent of disease severity (p=0.435, r=0.323 and p=0.819, r= -0.097 respectively). Eight patients were treated with positive airway pressure treatment and blood pressure control was achieved in all whereas no pressure reduction was observed in 4 untreated patients. Twenty-two patients (55%) were diagnosed with obstructive sleep apnoea and 14 patients (35%) were diagnosed with upper airway resistance syndrome according to American Sleep Disorders Association criteria. Upper airway resistance syndrome patients were younger and had a lower BMI when compared to other patients while there were no difference between the blood pressure levels and the number of antihypertensive drugs. Arousal index was determined to be positively correlated with systolic blood pressure level (p=0.034; r=0.746 ) while epword score and apnea-hypopnea index were independent of disease severity (p=0.435, r=0.323 and p=0.819, r= -0.097 respectively). Eight patients were treated with positive airway pressure treatment and blood pressure control was achieved in all whereas no pressure reduction was observed in 4 untreated patients. ConclusionsWe concluded that upper airway resistance syndrome is a possible secondary cause of resistant hypertension and its proper treatment can result in dramatic blood pressure control. We concluded that upper airway resistance syndrome is a possible secondary cause of resistant hypertension and its proper treatment can result in dramatic blood pressure control.

Dynamic resistant hypertension patterns as predictors of cardiovascular morbidity

Little is known regarding the clinical course and prognosis of resistant hypertension (RHT). We evaluated predictors of persistent RHT and the associated cardiovascular risk. We studied 1911 treated hypertensive patients (aged 59±11 years, 49% men) for a mean period of 3.9 years. At baseline, clinical data were collected and patients underwent echocardiographic measurements, routine blood testing and additional workup for exclusion of secondary causes of RHT (office-based uncontrolled hypertension under at least three drugs including a diuretic or controlled hypertension under four or more drugs). Endpoint of interest was the composite of coronary artery disease and stroke. Four groups were identified depending on presence or absence of RHT at baseline and follow-up: 1153 patients (60%) never having RHT, 189 (10%) with resolved RHT, 204 (11%) with incident RHT and 365 (19%) with persistent RHT. Two-thirds of the patients with RHT at baseline remained resistant at the end of the study. Independent variables associated with both incident and persistent RHT were diabetes mellitus, history of cardiovascular disease, hypertension duration, SBP, left ventricular hypertrophy and glomerular filtration rate. Persistent RHT compared with never-having RHT was associated with a 2.2-fold increased risk for cardiovascular morbidity (95% CI: 1.21-4.05, P = 0.01) after adjustment for risk factors. In treated hypertensive patients, among prospective RHT dynamic patterns, persistent RHT is frequent and independently associated with adverse cardiovascular prognosis.

Transcatheter therapies for resistant hypertension: Clinical review.

Resistant hypertension (RHTN) is a commonly encountered clinical problem and its management remains a challenging task for healthcare providers. The prevalence of true RHTN has been difficult to assess due to pseudoresistance and secondary hypertension. Atherosclerotic renal artery stenosis (RAS) has been associated as a secondary cause of RHTN. Initial studies had shown that angioplasty and stenting for RAS were a promising therapeutic option when added to optimal medical management. However, recent randomized controlled trials in larger populations have failed to show any such benefit. Sympathetic autonomic nervous system dysfunction is commonly noted in individuals with resistant hypertension. Surgical sympathectomy was the treatment of choice for malignant hypertension and it significantly improved mortality. However, post-surgical complications and the advent of antihypertensive drugs made this approach less desirable and it was eventually abandoned. Increasing prevalence of RHTN in recent decades has led to the emergence of minimally invasive interventions such as transcatheter renal denervation for better control of blood pressure. It is a minimally invasive procedure which uses radiofrequency energy for selective ablation of renal sympathetic nerves located in the adventitia of the renal artery. It is a quick procedure and has a short recovery time. Early studies in small population showed significant reduction in blood pressure. The most recent Symplicity HTN-3 study, which is the largest randomized control trial and the only one to use a sham procedure in controls, failed to show significant BP reduction at 6 mo.

Patterns of exposure to resistant hypertension and cardiovascular morbidity: a 4-year prospective study

Purpose: Even though resistant hypertension (RHT) is a frequent clinical condition, little is known regarding its clinical course and prognosis. We investigated the associated cardiovascular risk of diverse patterns of RHT evolution. Methods: In a prospective observational study, 1911 treated hypertensive patients (aged 59±11 years, 49% males) were followed for a mean period of 3.9±1.7 years. At baseline, clinical data were collected and patients underwent echocardiographic measurements, routine blood testing and additional workup for exclusion of secondary causes of RHT. Four groups were identified depending on presence or absence of RHT (office-based uncontrolled hypertension under at least 3 drugs including a diuretic or controlled hypertension under 4 or more drugs) at baseline and follow-up: 1,153 patients (60%) never having RHT, 189 (10%) with resolved RHT, 204 (11%) with incident RHT and 365 (19%) with persistent RHT. Endpoint of interest was cardiovascular morbidity set as the composite of coronary heart disease and stroke. Results: During follow-up, 65 events occurred (9.7 cases per 1,000 person-years). Incidence rates of cardiovascular events were 6.4 cases per 1,000 person-years in the never having RHT group, 9.1 cases per 1,000 person-years in the resolved RHT group, 13.2 cases per 1,000 person-years in the incident RHT group and 18.1 cases per 1,000 person-years in the persistent RHT group. Unadjusted analysis showed that patients with persistent RHT exhibited a significantly higher risk by 2.5 times (CI:1.42-4.36, p=0.002) for the composite cardiovascular outcome compared with the never having RHT group, while there was a gradually higher risk in patients with resolved and incident RHT that did not reach statistical significance. After adjusting for a series of established risk factors, persistent RHT remained as an independent predictor of the cardiovascular outcome, associated with a more than twofold risk (OR:2.2, CI:1.21-4.05, p=0.01) Conclusions: In treated hypertensive patients, persistence of RHT is frequent and independently associated with adverse cardiovascular prognosis.

Resistant hypertension—complex mix of secondary causes and comorbidities

Resistant hypertension—complex mix of secondary causes and comorbidities

Resistant Hypertension: Underlying Causes and Treatment

Resistant hypertension (RH) is defined as failure to achieve goal blood pressure while receiving a 3 drug regimen at optimal doses that includes a diuretic. The exact prevalence of resistant hypertension is unknown which may vary from 5% to 50%. Patient or clinician-related factors contributing to resistant hypertension include patient's non-adherence to antihypertensive therapy, White-coat effect and pseudo-hypertension and life style factors (Obesity, alcohol, smoking, dietary sodium etc). Several drugs may induce pre-existing hypertension where non-steroidal anti-inflammatory drugs are usually the most common due to their frequent use; whereas oral contraceptives, sympathomimetics (decongestants, anorectics), adrenal steroids and antineoplastic drugs targeting the vascular endothelial growth factor (VEGF) pathway has a good deal of contribution to resistant hypertension. Most common secondary causes of resistant hypertension are obstructive sleep apnea, renal artery stenosis, renal parenchymal disease, and primary aldosteronism while some uncommon causes such as pheochromocytoma, Cushing's disease, thyroid and parathyroid dysfunction; and aortic coarctation also contribute to resistant hypertension. Both pharmacological and non-pharmacological treatments are available for the management of resistant hypertension. This article reviews the prevalence, symptoms, causes and treatment of resistant hypertension.

Common Secondary Causes of Resistant Hypertension and Rational for Treatment

Resistant hypertension is defined as uncontrolled blood pressure despite the use of three antihypertensive drugs, including a diuretic, in optimal doses. Treatment resistance can be attributed to poor adherence to antihypertensive drugs, excessive salt intake, physician inertia, inappropriate or inadequate medication, and secondary hypertension. Drug-induced hypertension, obstructive sleep apnoea, primary aldosteronism, and chronic kidney disease represent the most common secondary causes of resistant hypertension. Several drugs can induce or exacerbate pre-existing hypertension, with non-steroidal anti-inflammatory drugs being the most common due to their wide use. Obstructive sleep apnoea and primary aldosteronism are frequently encountered in patients with resistant hypertension and require expert management. Hypertension is commonly found in patients with chronic kidney disease and is frequently resistant to treatment, while the management of renovascular hypertension remains controversial. A step-by-step approach of patients with resistant hypertension is proposed at the end of this review paper.

Difficult-to-Treat or Resistant Hypertension: Etiology, Pathophysiology, and Innovative Therapies

Despite the many therapeutic options available today for the treatment of hypertension, a sizable number of patients still remain resistant to treatment. The prevalence of resistant hypertension in the general population under optimal conditions is about 3–5%. Although several factors and conditions can be identified and corrected a percentage of hypertensive patients remain with unacceptably high blood pressure levels. The high prevalence of hypertension in the general population renders this small percentage significant, in terms of actual patient numbers. This special issue of the journal expoars a whole spectrum of topics related to resistant hypertension: several articles address pathophysiolog and secondary causes of resistant hypertension and modern approaches to therapy. Of interest is the referance to the newer interventional approaches, that is, Baroreceptor stimulation therapy and catheter based sympathetic renal denervation.

Clinical approach in treatment of resistant hypertension.

Resistant hypertension, defined as failure to achieve target blood pressure despite the use of optimal or maximum doses of at least 3 agents, one of which is a diuretic, or requiring 4 or more medications to achieve blood pressure goal, is likely to affect up to 20% of all patients with hypertension. Apparent resistant hypertension may be caused by medication nonadherence, substances that either interfere with antihypertensive mediations or cause blood pressure elevation, and under- or inappropriate medication treatment. Certain patient characteristics are associated with the presence of resistant hypertension and include chronic kidney disease, diabetes, obesity, and presence of end-organ damage (microalbuminuria, retinopathy, left-ventricular hypertrophy). Secondary causes of resistant hypertension are not uncommon and include obstructive sleep apnea, chronic kidney disease, primary aldosteronism, renal artery stenosis, pheochromocytoma, and Cushing's disease. Initial medication management usually includes adding or increasing the dose of a diuretic, which is effective in lowering the blood pressure of a large number of patients with resistant hypertension. Additional management options include maximizing lifestyle modification, combination therapy of antihypertensive agents depending on individual patient characteristics, adding less-commonly used fourth- or fifth-line antihypertensive agents, and referral to a hypertension specialist.