Resistant hypertension (RH) is defined as above-goal elevated blood pressure (BP) in a patient despite the concurrent use of 3 antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic. It is defined as blood pressure (BP) >140/90 mmHg treated with 3 antihypertensive medications, including a diuretic, if tolerated. J Family Med Prim Care. Finally, all patients with ongoing uncontrolled hypertension should be assessed routinely for any signs of end-organ compromise. 21. The physical exam will look for abnormal changes in the eye (a condition called hypertensive retinopathy), and abnormal sounds called bruits (vascular murmur) over some major arteries. A healthful diet, such as the Dietary Approaches to Stop Hypertension (DASH) diet, can reduce systolic BP up to 11 mm Hg.1,3,10 The DASH diet includes foods low in saturated and trans fats; rich in potassium, calcium, magnesium, fiber, and protein; and low in sodium (Table 2).17 DASH has been shown to have a synergistic effect with ACE inhibitors in lowering systolic BP.18 Other lifestyle modifications include sodium restriction to less than 1,500 mg per day, increased dietary potassium of 3,500 to 5,000 mg per day (if not contraindicated by serum potassium levels), increased physical activity of 90 to 150 minutes per week, and reduction in alcohol consumption.1,2,10 Weight loss of 1 kg can correlate to reducing systolic BP by 1 mm Hg.1,2. Eirin A, Textor SC, Lerman LO. Provided these confounders are absent and standard drug therapy has failed, resistant hypertension is diagnosed. [27] A general rule is to commence patients on 25 mg per day, which may require about 2 weeks for full effect. Recommending a 25% decrease in sodium intake may result in lower BP and also enhance the efficacy of all antihypertensive medications.1 Patients who drink alcohol are recommended to reduce intake to fewer than two drinks per day for men and less than one drink per day for women.1,10 Referral to a registered dietitian/nutritionist as well as frequent follow-up with primary care providers can help patients achieve better adherence to these nonpharmacologic therapies. These may include a urine test for protein or albumin; blood tests for glucose, electrolytes such as sodium and potassium and the blood creatinine level. London: National Institute for Health and Clinical Excellence; 2011. The UK is the first country to allow OTC access to Sanofi's tadalafil-based erectile dysfunction drug Cialis following a successful switch. Most patients with resistant hypertension do achieve blood pressure control through pharmacotherapy provided they are properly evaluated and treated. [35] Patients who remain hypertensive despite four agents can have additional medications trialled sequentially with direction from a specialist [Figure 1]. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. J Am Coll Cardiol. The other emerging intervention is carotid sinus stimulation. sharing sensitive information, make sure youre on a federal Unauthorized use of these marks is strictly prohibited. Black H, Elliot W, Grandits G, Grambasch P, Lucente T, White W, et al. Eric Schmidt is an assistant professor in the PA program at the University of Lynchburg. [12] They are not recommended as first-line therapy for patients with uncomplicated hypertension because they offer less cardiovascular protection than other agents. Keyword Highlighting But it becomes even more frustrating when you are on multiple medications and dont see any improvements. Williams GH, Hollenberg NK. Their antihypertensive benefit is presumably smaller although head-to-head comparison data is lacking.[12]. [3] The remaining cases of hypertension are secondary to a distinguishable process and would likely resolve if the underlying condition was treated. Interactions of the DASH diet with the renin-angiotensin-aldosterone system. Non-modulating hypertension. The new American College of Cardiology (ACC)/AHA hypertension guidelines are important in providing a preliminary estimate of the prevalence of RHTN based on the now lower recommended BP goal of 130/80 mm Hg.2 The landmark PATHWAY-2 study adds importantly to our understanding of the pathophysiology of RHTN and provides compelling evidence for the most effective multiple-drug combination for treating RHTN, including especially, preferential use of spironolactone.3 This editorial serves to highlight these recent advances. Please enable it to take advantage of the complete set of features! Ambulatory BP monitoring is considered the gold standard and may be used to assess patients with masked or white-coat hypertension; ambulatory monitoring also can determine the extent of nocturnal dippings, identify early morning surges, and estimate a patient's variability in BP.3,10, Aside from accurately determining a patient's BP, obtain baseline tests to assess the presence of end-organ disease, possible causes of secondary hypertension, cardiovascular risk factors, and baseline values to measure the effects of treatment. Prevalence of resistant hypertension in the United States, 2003-2008. He or she may ask about side effects that may keep you from taking all of your doses. Recent advances in understanding and managing resistant/refractory hypertension. 2015. When high blood pressure (hypertension) cant be managed despite medications, its called resistant. Lifestyle changes and treatment of secondary causes that keep your numbers too high can help you manage your blood pressure. Thus in predisposed patients such as the elderly or those with renal insufficiency indapamide might be a superior substitute. North Ryde: McGraw-Hill Australia Pty Ltd; 2011. Adverse effects of spironolactone usually appear at higher doses where patients may complain of gynecomastia and breast tenderness, menstrual irregularities and sexual dysfunction. Blood pressure, cardiovascular disease, renal denervation, resistant hypertension. Sometimes treatable secondary causes may be the source of your resistant hypertension. Ambulatory BP monitoring showed a mean reading of 175/90 mm Hg over 24 hours. Possible causes of resistant hypertension include nonmodulator hypertension, which affects patients who have an inappropriate response to elevated sodium through the renin-angiotensin-aldosterone system. All agents should be administered at maximum or maximally tolerated doses and at the appropriate dosing frequency.1 This part of the definition is largely the same as the prior AHA definition in stating that RHTN is BP above goal in spite of use of 3 or more antihypertensive agents of different classes, at maximally tolerated doses.4 The revised definition, however, goes further than the prior definition in suggesting that the first 3 agents, if possible, should be comprised specifically of an ACE inhibitor or ARB, a CCB, and a diuretic. Untreated hypertension among Australian adults: The 1999-2000 Australian diabetes, obesity and lifestyle study. Oftentimes however, the clinical assessment will be unremarkable. The patient was diagnosed with hypertension 20 years ago and has been on many medications for it over the years. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). The results of the earlier main PATHWAY-2 are consistent with this underlying pathophysiology in demonstrating that this fluid retention is best overcome by the natuiretic and diuretic effects of spironolactone. Increased serum sodium is renally excreted with water, lowering blood volume and arterial pressure. However, it is difficult to diagnose because of multiple factors that influence adequate treatment of BP, including patient lifestyle and comorbidities, improper therapeutic regimens, and secondary mechanisms. 5705185. In a detailed history your provider may ask when your high blood pressure began and how long its been going on; current drugs you take (including herbal medications) and if you take them as prescribed; and questions about possible secondary causes of your unmanaged hypertension. Expanding our understanding of the causes of resistant hypertension and thereby potentially allowing for more effective prevention and/or treatment will be essential to improve the long-term clinical management of this disorder. Hypertension is defined as persons 18 years of age and over with a systolic pressure reading of 140 mmHg or more or a diastolic reading of 90 mmHg or more, or those taking antihypertensive medications. 5, 6 Physician failure to prescribe adequate doses of medication, so-called clinical inertia, may also be . 20. Less common causes include pheochromocytoma, a tumor in the adrenal gland; aortic narrowing; and Cushing syndrome, an overproduction of some steroid hormones. Accordingly, while the change in prevalence of RHTN with application of the revised definition has not yet been rigorously determined, a 4% increase is likely correct as the only relevant change will be in the narrow group of patients whose BP is 130139/8089 mm Hg on 3 medications, who now have RHTN based on the revised definition. Australian Health Survey: Health service usage and health related actions. Imaging studies to check the adrenal gland, or for narrowing of arteries, may be needed. Renal sympathetic nerves are denervated using catheter-based radiofrequency ablation or ultrasound ablation.3,12,20 A recent meta-analysis reviewed data from six renal denervation clinical trials, which assessed the reduction in 24-hour ambulatory systolic and diastolic BP with renal denervation therapy versus sham therapy.4,20 The studies took into account patients with essential hypertension as well as resistant hypertension. In patients uncontrolled on amiloride 10 mg after 6 weeks and so titrated up to 20 mg, a similar dose-response as with spironolactone 2550 mg was observed. Resistant hypertension is a common clinical problem faced by both primary care clinicians and specialists. The prognosis of resistant hypertension is unknown, but cardiovascular risk is undoubtedly increased as patients often have a history of long-standing, severe hypertension complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. [34] Treatment regimens therefore should not include both an ACEI and ARB simultaneously. , MacDonald TM, Morant SV, Webb DJ, Sever P, McInnes GT, Ford I, Cruickshank JK, Caulfield MJ, Padmanabhan S, Mackensize IS, Salsbury J, Brown MJ. Knowledge of device safety and long-term efficacy remains insufficient and it is not a routinely available management option at this time. These seldom form part of the routine management of hypertension and should be prescribed with expert advice. The definition of RH followed the 2017 ACC/AHA guideline. Get useful, helpful and relevant health + wellness information, 9500 Euclid Avenue, Cleveland, Ohio 44195 |, Important Updates + Notice of Vendor Data Event. Renal sympathetic denervation in patients with treatment-resistant hypertension (The SymplicityHTN-2 Trial): A randomised controlled trial. Below this level eGFR or in hypoalbuminuric states (serum albumin <3.0 g/l), a long-acting loop diuretic such as torsemide is recommended.1. [ 2] Hypertension affects 32% of adults in western society, two-thirds of whom are poorly controlled. In summary, the definition of RHTN has been expanded beyond the 2008 definition to specifically require (i) BP above goal despite concurrent use of 3 or more antihypertensive agents at maximum or maximally tolerated doses, including, if possible, a ACE inhibitor or ARB, a CCB, and a diuretic, (ii) measurement of BP according to clinical practice guidelines, (iii) exclusion of a white-coat effect, (iv) exclusion of poor antihypertensive medication adherence.1 Accordingly, the current definition of RHTN is more comprehensive in standardizing the initial 3 drug regimen and in requiring exclusion of common causes of pseudotreatment resistance. Please enable scripts and reload this page. Dr Calhoun received grant support from ReCor Medical (NCT02649426), and Dr Flack received grant support from ReCor Medical (NCT02649426) and Vascular Dynamics (NCT03179800). Whelton On presentation, his BP is 190/95 mm Hg in the right arm and 195/95 mm Hg in the left arm. 14. Sardar P, Bhatt DL, Kirtane AJ, et al. Resistant hypertension is defined as high blood pressure that remains uncontrolled despite treatment with at least three antihypertensive agents (one of which is usually a diuretic) at best tolerated doses. Noubiap JJ, Nansseu JR, Nyaga UF, et al. Blood pressure generally lowers physiologically during sleep and nocturnal hypertension, or so-called non-dipping, has been associated with poorer cardiovascular prognosis. The statement also indicates that the diuretic used in this standardized triple regimen should, in most patients, be a thiazide or thiazide-like diuretic. Adelaide: Pharmaceutical Society of Australia; 2010. Kholsa N, Chua D, Elliot W, Bakris G. Are chlorthalidone and hydrochlorothiazide equivalent blood-pressure-lowering medications? The statement further indicates that HCTZ will provide diminishing benefit as the estimated glomerular filtration rate (eGFR) declines below 45 ml/min1/1.73 min2, while chlorthalidone can be effective with eGFRs down to 2530 ml/min1/1.73 min2. Careers, Unable to load your collection due to an error. Can nocturnal hypertension predict cardiovascular risk? In some patients such as those with ischemic heart disease or poor glycaemic control, traditional beta blockers like atenolol or metoprolol may instead be indicated. Recognition and management of, 12. Oxford University Press is a department of the University of Oxford. He does not adhere to a low-sodium diet. 1Department of Medicine, Redcliffe Hospital, Queensland, Australia, 2Department of Medicine, Gold Coast University Hospital, Queensland, Australia. Bethesda, MD 20894, Web Policies Murtagh J. Available from: Madkour H, Gadallah M, Riveline B, Plante GE, Massry SG. [19] These options can then be trialled in combination and titrated as necessary before adding a thiazide as the third medication. If the blood potassium level exceeds 4.5 mmol/L intensification of thiazide therapy should be considered.[33]. The blood pressure goal in uncomplicated patients is 140/90 mmHg which could be relaxed to 150/90 in patients greater than 60 years of age. People with hard-to-treat, resistant hypertension have a higher risk of stroke, kidney disease and heart failure than people whose high blood pressure is regulated. Definition of resistant hypertension. James P, Oparil S, Carter B, Cushman W, Dennison-Himmelfarb C, Handler J, et al. Policy. While the exact prevalence of resistant hypertension is unknown, clinical trials suggest that it is not rare, involving perhaps 20% to 30% of study participants. A caveat for both spironolactone and amiloride is the need for careful routine monitoring of serum potassium. Firstly, with the recent revision of the AHA Scientific Statement, the importance of accounting for common pseudocauses of RHTN is emphasized by incorporating into the definition use of proper BP technique to ensure accurate BP measurement, confirmation of uncontrolled out-of-office BP with use of home or ambulatory BP assessments, and ensuring adequate medication adherence. Certified hypertension clinician (CHC). If appropriate BP control is still not achieved, additional medications can be added to the regimen. 2 RH is associ. Hypertension is a challenging clinical problem with a significant proportion of patients failing to achieve blood pressure control despite extensive medical therapy. Resistant hypertension is a condition where your blood pressure remains high or unmanaged despite the medications you take to lower it. Most patients with hypertension are prescribed hydrochlorothiazide as the diuretic of choice. Gottlieb T, Katz F, Chidsey C. Combined therapy with vasodilator drugs and beta-adrenergic blockade in hypertension: A comparative study of minoxidil and hydralazine. Carey RM, Calhoun DA, Bakris GL, et al. Order laboratory tests. [12] Although secondary hypertension is more likely in resistant hypertension than in patients whose blood pressure is controlled, most still do not have an identifiable cause.[13]. The ability of suppressed renin levels (or plasma renin activity) to predict the BP response to spironolactone certainly supports assessing renin levels or renin activity in all patients with RHTN but raises the question if suppressed renin levels might also more predict the BP response to spironolactone in hypertensive patients in general. RM In the second substudy, the effect of the 3 different agents on thoracic fluid content, an index of volume status, was determined.6 Bisoprolol, the -blocker, had no effect on thoracic fluid content, while doxazosin, the -antagonist, increased it, indicating increased fluid retention. Save 2.20. As older age and obesity are 2 of the strongest risk factors for uncontrolled hypertension, the incidence of resistant hypertension will likely increase as the population becomes more elderly and heavier. Bethesda, MD 20894, Web Policies The true prevalence of resistant hypertension is difficult to quantify because many patients actually suffer pseudo-resistant hypertension. Frank J. Careers. The above mechanism is achieved by downregulating the RAAS system. Calhoun D, Jones D, Textor S, Goff D, Murphy T, Toto R, et al. These patients accumulate twice as much sodium compared with patients with hypertension and the ability to modulate.8 Nonmodulation is a nonmodifiable risk factor for resistant hypertension and is determined by multiple factors including race, genetics, age, and comorbidities such as obesity and diabetes.7, Not every patient is easily identified as having resistant hypertension and many may present as asymptomatic. Epub 2022 Dec 16. Please try again soon. Managing hypertension using combination therapy. Hypertension is described as "pseudo-resistant" when persistent elevations in blood pressure are the result of a failure to comply with the medication regimen, "white-coat" syndrome, poor blood pressure technique, or a combination of these. An estimated 33% of patients inappropriately referred for resistant hypertension had an inaccurate BP reading.2 Recent guidelines from the AHA recommend use of automated oscillatory BP over manual auscultation for standardized measurements.1 Standardized conditions should be implemented, including having the patient relaxed, seated in a chair with uncrossed legs and an empty urinary bladder; patients also should avoid caffeine, exercise, and smoking for 30 minutes before a BP measurement.2 Measure BP in both arms unless contraindicated, and use the arm that yields the higher measurement for later readings. In contrast, spironolactone reduced thoracic fluid content by about 7%, consistent with a significant reduction in intravascular fluid retention. Possible causes of resistant hypertension include nonmodulator . Clinical Question: Can CPAP suppress cardiovascular events in resistant hypertension patients with obstructive sleep apnea? Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of 3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires 4 agents to achieve control, has received more attention with increased efforts to improve BP control rates and the emergence of device-based therapies for hypertension. In those who remain hypertensive despite thorough medical management, there are interventional options currently under development which are promising but require further research. Most clinicians tend to opt for centrally-acting agents before the direct vasodilator drugs because experience with their use is wider. Australian Institute of Health and Welfare. 2009 Apr;38(4):643-51. doi: 10.1016/j.lpm.2009.02.004. This review article starts with an overview of . Clin Geriatr Med. and transmitted securely. It reported substantial blood pressure reduction but was also associated with serious procedure-related adverse effects in 25.2% of participants. Resistant hypertension presents in patients who have persistently elevated blood pressure which responds minimally to therapy. Observational assessments have allowed for identification of demographic and lifestyle characteristics associated with resistant hypertension, and the role of secondary causes of hypertension in promoting treatment resistance is well documented; however, identification of broader mechanisms of treatment resistance is lacking. In contrast, spironolactone reduced thoracic fluid content by about 7 %, consistent with significant! Fluid retention as necessary before adding a thiazide as the third medication is! However, the clinical assessment will be unremarkable G, Grambasch P, Lucente T, Toto R et! Two-Thirds of whom are poorly controlled, 2003-2008 be relaxed to 150/90 in patients than. 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