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      Benefits from Treatment and Control of Patients with Resistant Hypertension

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          Abstract

          Resistant hypertension is commonly found in everyday clinical practice. However, the risks of resistant hypertension, as well as the benefits of treatment and control of blood pressure in patients with resistant hypertension remain vaguely clarified. Data from small clinical studies and observational cohorts suggest that patients with resistant hypertension are at increased cardiovascular risk, while control of blood pressure offers substantial benefits. It has to be noted however that data from appropriate large randomized studies are missing, and resistant hypertension remains remarkably understudied. Resistant hypertension has attracted significant scientific interest lately, as new therapeutic modalities become available. The interventional management of resistant hypertension either by carotid baroreceptor stimulation or renal sympathetic denervation is currently under investigation with promising preliminary results. This review presents available evidence regarding the benefits of treatment and control of blood pressure in patients with resistant hypertension and offers a critical evaluation of existing data in this field.

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          Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.

          Henry Krum, Markus P. Schlaich, Rob Whitbourn … (2009)
          Renal sympathetic hyperactivity is associated with hypertension and its progression, chronic kidney disease, and heart failure. We did a proof-of-principle trial of therapeutic renal sympathetic denervation in patients with resistant hypertension (ie, systolic blood pressure >/=160 mm Hg on three or more antihypertensive medications, including a diuretic) to assess safety and blood-pressure reduction effectiveness. We enrolled 50 patients at five Australian and European centres; 5 patients were excluded for anatomical reasons (mainly on the basis of dual renal artery systems). Patients received percutaneous radiofrequency catheter-based treatment between June, 2007, and November, 2008, with subsequent follow-up to 1 year. We assessed the effectiveness of renal sympathetic denervation with renal noradrenaline spillover in a subgroup of patients. Primary endpoints were office blood pressure and safety data before and at 1, 3, 6, 9, and 12 months after procedure. Renal angiography was done before, immediately after, and 14-30 days after procedure, and magnetic resonance angiogram 6 months after procedure. We assessed blood-pressure lowering effectiveness by repeated measures ANOVA. This study is registered in Australia and Europe with ClinicalTrials.gov, numbers NCT 00483808 and NCT 00664638. In treated patients, baseline mean office blood pressure was 177/101 mm Hg (SD 20/15), (mean 4.7 antihypertensive medications); estimated glomerular filtration rate was 81 mL/min/1.73m(2) (SD 23); and mean reduction in renal noradrenaline spillover was 47% (95% CI 28-65%). Office blood pressures after procedure were reduced by -14/-10, -21/-10, -22/-11, -24/-11, and -27/-17 mm Hg at 1, 3, 6, 9, and 12 months, respectively. In the five non-treated patients, mean rise in office blood pressure was +3/-2, +2/+3, +14/+9, and +26/+17 mm Hg at 1, 3, 6, and 9 months, respectively. One intraprocedural renal artery dissection occurred before radiofrequency energy delivery, without further sequelae. There were no other renovascular complications. Catheter-based renal denervation causes substantial and sustained blood-pressure reduction, without serious adverse events, in patients with resistant hypertension. Prospective randomised clinical trials are needed to investigate the usefulness of this procedure in the management of this condition.
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            Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

            (2002)
            Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality, but the optimal first-step therapy is unknown. To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease (CHD) or other cardiovascular disease (CVD) events vs treatment with a diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, active-controlled clinical trial conducted from February 1994 through March 2002. A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers. Participants were randomly assigned to receive chlorthalidone, 12.5 to 25 mg/d (n = 15 255); amlodipine, 2.5 to 10 mg/d (n = 9048); or lisinopril, 10 to 40 mg/d (n = 9054) for planned follow-up of approximately 4 to 8 years. The primary outcome was combined fatal CHD or nonfatal myocardial infarction, analyzed by intent-to-treat. Secondary outcomes were all-cause mortality, stroke, combined CHD (primary outcome, coronary revascularization, or angina with hospitalization), and combined CVD (combined CHD, stroke, treated angina without hospitalization, heart failure [HF], and peripheral arterial disease). Mean follow-up was 4.9 years. The primary outcome occurred in 2956 participants, with no difference between treatments. Compared with chlorthalidone (6-year rate, 11.5%), the relative risks (RRs) were 0.98 (95% CI, 0.90-1.07) for amlodipine (6-year rate, 11.3%) and 0.99 (95% CI, 0.91-1.08) for lisinopril (6-year rate, 11.4%). Likewise, all-cause mortality did not differ between groups. Five-year systolic blood pressures were significantly higher in the amlodipine (0.8 mm Hg, P =.03) and lisinopril (2 mm Hg, P<.001) groups compared with chlorthalidone, and 5-year diastolic blood pressure was significantly lower with amlodipine (0.8 mm Hg, P<.001). For amlodipine vs chlorthalidone, secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine (10.2% vs 7.7%; RR, 1.38; 95% CI, 1.25-1.52). For lisinopril vs chlorthalidone, lisinopril had higher 6-year rates of combined CVD (33.3% vs 30.9%; RR, 1.10; 95% CI, 1.05-1.16); stroke (6.3% vs 5.6%; RR, 1.15; 95% CI, 1.02-1.30); and HF (8.7% vs 7.7%; RR, 1.19; 95% CI, 1.07-1.31). Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy.
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              Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study.

              Stella Douma, Niki Kartali, Panagiota Papaefthimiou … (2008)
              Results of several studies published since 1999 suggest that primary hyperaldosteronism (also known as Conn's syndrome) affects more than 10% of people with hypertension; however, such a high prevalence has also been disputed. Experts generally agree that resistant hypertension has the highest prevalence of primary hyperaldosteronism, on the basis of small studies. We aimed to assess the prevalence of primary hyperaldosteronism in a large group of patients with resistant hypertension. Patients with resistant hypertension (blood pressure >140/90 mm Hg despite a three drug regimen, including a diuretic) who attended our outpatient clinic were assessed for primary hyperaldosteronism. Serum aldosterone and plasma renin activity were determined and their ratio was calculated. Patients with a positive test (ratio >65.16 and aldosterone concentrations >416 pmol/L) underwent salt suppression tests with intravenous saline and fludrocortisone. Diagnosis of primary hyperaldosteronism was further confirmed by the response to treatment with spironolactone. Over 20 years, we studied 1616 patients with resistant hypertension. 338 patients (20.9%) had a ratio of more than 65.16 and aldosterone concentrations of more than 416 pmol/L. On the basis of salt suppression tests, 182 (11.3%) patients had primary hyperaldosteronism, and response to spironolactone treatment further confirmed this diagnosis. Hypokalaemia was seen only in 83 patients with primary hyperaldosteronism (45.6%). Although the prevalence of primary hyperaldosteronism in patients with resistant hypertension was high, it was substantially lower than previously reported. On the basis of this finding, we could assume that the prevalence of primary hyperaldosteronism in the general unselected hypertensive population is much lower than currently reported. Thus, the notion of an epidemic of primary hyperaldosteronism is not supported.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Hypertens
                Journal ID (publisher-id): IJHT
                Title: International Journal of Hypertension
                Publisher: SAGE-Hindawi Access to Research
                ISSN (Electronic): 2090-0392
                Publication date Collection: 2011
                Publication date (Electronic): 22 December 2010
                Volume: 2011
                Electronic Location Identifier: 318549
                Affiliations
                1Veterans Affairs Medical Center, George Washington University, Washington, DC 20422, USA
                2Veterans Affairs Medical Center, Georgetown University, Washington, DC 20422, USA
                32nd Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 49 Konstantinoupoleos Street, 54643 Thessaloniki, Greece
                Author notes

                Academic Editor: A. Gradman

                Article
                DOI: 10.4061/2011/318549
                PMC ID: 3014695
                PubMed ID: 21234402
                SO-VID: 2fbab3fc-13b2-4e2f-9d8d-4e9e2142c7ac
                Copyright © Copyright © 2011 Michael Doumas et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 11 October 2010
                Date accepted : 16 November 2010
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Cardiovascular Medicine
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine

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