Resistant Hypertension
2011; Lippincott Williams & Wilkins; Volume: 57; Issue: 6 Linguagem: Finlandês
10.1161/hypertensionaha.111.171520
ISSN1524-4563
AutoresMustafa I. Ahmed, David A. Calhoun,
Tópico(s)Hormonal Regulation and Hypertension
ResumoHomeHypertensionVol. 57, No. 6Resistant Hypertension Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBResistant HypertensionBad and Getting Worse Mustafa I. Ahmed and David A. Calhoun Mustafa I. AhmedMustafa I. Ahmed From the Vascular Biology and Hypertension Program, Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL. and David A. CalhounDavid A. Calhoun From the Vascular Biology and Hypertension Program, Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, AL. Originally published18 Apr 2011https://doi.org/10.1161/HYPERTENSIONAHA.111.171520Hypertension. 2011;57:1045–1046Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 See related article, pp 1076–1080Resistant hypertension (RHTN) is most simply defined as high blood pressure (BP) requiring ≥4 antihypertensive medications, whether controlled or uncontrolled.1 The true prevalence of RHNT is unknown and is likely to remain so, because determining an accurate estimation of prevalence would require a large prospective study of a diverse hypertensive cohort in which subjects' medications are force titrated if the BP remains above goal, adherence is closely monitored, and ambulatory BP monitoring is done to exclude white-coat RHTN. Given the cost and logistical challenges, such a study has not been done and is not likely to ever be done.In the absence of a definitive study, clinical trials have been largely relied on to serve as surrogate opportunities to estimate the prevalence of RHTN. In that regard, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is probably the most relevant in that it included a large and diverse cohort, and, per protocol, subjects were to have continued escalation of their treatment regimen as long as the BP remained elevated.2 At the end of the 5-year treatment period, uncontrolled hypertension was common in ALLHAT, with 34% of subjects never having achieved BP control and with 27% of subjects receiving ≥3 antihypertensive medications.3 These data, as well as control rates from other clinical trials, have been interpreted to suggest a prevalence of RHTN of 20% to 30% of general hypertensive cohorts.1The problem, of course, is that ALLHAT and other clinical trials were not designed to determine the prevalence of RHTN. On one hand, enrollment criteria would have often resulted in underestimating the prevalence of RHTN by excluding subjects at highest risk of having RHTN, such as the patients with chronic kidney disease, the very elderly, the very obese, and, in the case of ALLHAT, patients with a known history of RHTN (ie, needing >2 medications to achieve a BP of 140/90 mm Hg on ≥3 medications, and the remaining 30% were controlled with BP <140/90 mm Hg on ≥4 medications. Based on these figures and current estimates of there being 68-million hypertensive adult Americans, ≈6.1 million Americans have RHTN. Consistent with other reports, Persell4 found that, compared with patients with controlled hypertension, subjects with RHTN were more likely obese, older, black, and more likely to have diabetes mellitus and chronic kidney disease. Increased cardiovascular risk was reflected in greater rates of coronary heart disease, heart failure, and stroke.The 9% rate likely represents the current best estimate of the prevalence of RHTN in the United States. In specifically relating lack of BP control to the number of antihypertensive medications being used, Persell4 has overcome a limitation of previous estimates that simply inferred treatment resistance from treated but still uncontrolled hypertension. What is still not fully accounted for is to what degree poor adherence is contributing to the apparent treatment resistance. The NHANES surveyors did report having observed prescription containers for ≈90% of the reported BP medications, suggesting at least that almost all of the prescribed medications were available to subjects at some point in time. It does not, however, confirm taking the medication on a reliable basis. Studies of small numbers of subjects that document BP control in subjects who had been previously uncontrolled with multidrug regimens when those same regimens are administered by clinical staff suggest that such poor adherence is an important cause of apparent treatment resistance.5 Likewise, to what extent white-coat effects are contributing to apparent treatment resistance in the clinic is not considered in the current analysis. Previous studies of patients with RHTN suggest that 20% to 40% of patients with elevated office BP levels may be controlled out of office when recorded by ambulatory monitoring.6Both of the above factors, that is, poor adherence and white-coat effects, if they could have been properly accounted for, would have reduced the observed prevalence of RHTN, suggesting that true RHTN is even less common than 9% of the general hypertensive population. However, countervailing those diminishing effects would have been the large proportion of patients who would have been accurately labeled as having RHTN if their medications had been properly titrated. That is, of the treated subjects whose BP remained uncontrolled, 72% were receiving only 1 or 2 antihypertensive medications. With titration to ≥3 medications, a proportion would have remained uncontrolled and, hence, added to the observed prevalence rate of RHTN. The end result of these competing effects is obviously unknown, but given the large number of uncontrolled hypertensive subjects, it seems reasonable to interpret the 9% prevalence rate as a minimum value. Even worse from a public health prospective, whatever the actual prevalence of RHTN, we can anticipate it increasing as populations worldwide are growing older and are increasingly affected by obesity, diabetes mellitus, and chronic kidney disease, all strong predictors of developing RHTN.The findings of Persell4 also highlight the role that effective drug selection may play in reducing the prevalence of RHTN. In spite of the well-established superiority of chlorthalidone compared with hydrochlorothiazide in reducing BP, the majority of patients with RHTN (55%) were receiving hydrochlorothiazide as their diuretic.7 Also, in spite of consistent recommendations to use loop diuretics in patients with advanced chronic kidney disease, 33% of subjects with a glomerular filtration rate <30 mL/min lacked such treatment. Especially conspicuous was the pronounced lack of use of aldosterone antagonists. A substantial body of literature clearly demonstrates the broad benefit of spironolactone and eplerenone for treating RHTN, and, yet, only 3% of patients with RHTN were receiving these medications. With more appropriate diuretic selection, including more intensive use of aldosterone antagonists, the prevalence of RHTN would have, undoubtedly, been lower. These therapeutic deficiencies emphasize the importance of better educating clinicians on assembling effective multiple-drug combinations or convincing clinicians to more readily refer patients with RHTN to hypertension specialists.DisclosuresNone.FootnotesThe opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.Correspondence to Mustafa I. Ahmed, Vascular Biology and Hypertension Program, University of Alabama at Birmingham, 1530 3rd Ave South, Birmingham, AL 35294-2041. E-mail [email protected]eduReferences1. Calhoun DA, Jones D, Textor S, Goff DC, Murphy TP, Toto RD, White A, Cushman WC, White WB, Sica D, Ferdinand K, Giles TD, Falkner B, Carey RM. American Heart Association scientific statement resistant hypertension: diagnosis, evaluation, and treatment. Hypertension. 2008; 51: 1403– 1419. LinkGoogle Scholar2. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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). JAMA. 2002; 288: 2981– 2997. CrossrefMedlineGoogle Scholar3. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM, for the ALLHAT Collaborative Research Group. Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering and Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens. 2002; 4: 393– 404. CrossrefGoogle Scholar4. Persell SD. Prevalence of resistant hypertension in the United States,2003–2008. Hypertension. 2011; 57; 1076– 1080. LinkGoogle Scholar5. Bunker J, Callister W, Chang C-L, Sever PS. How common is true resistant hypertension. J Human Hypertens. 2011; 25: 137– 140. CrossrefMedlineGoogle Scholar6. Salles GF, Cardoso CRL, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressure in resistant hypertension. Arch Intern Med. 2008; 168: 2340– 2346. CrossrefMedlineGoogle Scholar7. Ernst ME, Carter BL, Goerdt CJ, Steffensmeier JJG, Phillips BB, Zimmerman MB, Bergus GR. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension. 2006; 47: 353– 358. LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Parati G and Ochoa J (2018) White-Coat and Masked Hypertension Hypertension: A Companion to Braunwald's Heart Disease, 10.1016/B978-0-323-42973-3.00012-3, (104-114), . Schmidt C, Öner A, Mann M, Krockenberger K, Abbondanzieri M, Brandewiede B, Brüge A, Hostenkamp G, Kaiser A, Neumeyer H and Ziegler A (2018) A novel integrated care concept (NICC) versus standard care in the treatment of chronic cardiovascular diseases: protocol for the randomized controlled trial CardioCare MV, Trials, 10.1186/s13063-018-2502-1, 19:1, Online publication date: 1-Dec-2018. Li P, Nader M, Arunagiri K and Papademetriou V (2016) Device-Based Therapy for Drug-Resistant Hypertension: An Update, Current Hypertension Reports, 10.1007/s11906-016-0671-4, 18:8, Online publication date: 1-Aug-2016. Parati G, Ochoa J, Lombardi C and Bilo G (2015) White Coat Hypertension: Definition, Terminology and Prevalence White Coat Hypertension, 10.1007/978-3-319-07410-8_1, (1-19), . Gijón-Conde T, Graciani A and Banegas J (2014) Demografía y características clínicas de la hipertensión resistente en 6.292 pacientes en atención primaria, Revista Española de Cardiología, 10.1016/j.recesp.2013.09.029, 67:4, (270-276), Online publication date: 1-Apr-2014. Gijón-Conde T, Graciani A and Banegas J (2014) Resistant Hypertension: Demography and Clinical Characteristics in 6292 Patients in a Primary Health Care Setting, Revista Española de Cardiología (English Edition), 10.1016/j.rec.2013.09.027, 67:4, (270-276), Online publication date: 1-Apr-2014. Jung O and Geiger H (2014) Welche Rolle spielt die Therapieadhärenz?, CardioVasc, 10.1007/s15027-014-0310-4, 14:1, (39-42), Online publication date: 1-Feb-2014. Ghosh S, Kapil V, Fuentes-Calvo I, Bubb K, Pearl V, Milsom A, Khambata R, Maleki-Toyserkani S, Yousuf M, Benjamin N, Webb A, Caulfield M, Hobbs A and Ahluwalia A (2013) Enhanced Vasodilator Activity of Nitrite in Hypertension, Hypertension, 61:5, (1091-1102), Online publication date: 1-May-2013. Jung O, Gechter J, Wunder C, Paulke A, Bartel C, Geiger H and Toennes S (2013) Resistant hypertension? Assessment of adherence by toxicological urine analysis, Journal of Hypertension, 10.1097/HJH.0b013e32835e2286, 31:4, (766-774), Online publication date: 1-Apr-2013. Parati G, Ochoa J and Bilo G (2013) False Versus True Resistant Hypertension Resistant Hypertension, 10.1007/978-88-470-5415-8_6, (59-75), . de la Sierra A (2012) Clinical differences between resistant hypertensive patients and patients treated and controlled with three or less drugs, Journal of Hypertension, 10.1097/HJH.0b013e32835822c4, 30:11, (2242-2243), Online publication date: 1-Nov-2012. Foy A, Ruggiero N and Filippone E (2012) Revascularization in Renal Artery Stenosis, Cardiology in Review, 10.1097/CRD.0b013e31824a72e9, 20:4, (189-193), Online publication date: 1-Jul-2012. Clark D, Guichard J, Calhoun D and Ahmed M (2015) Recent Advancements in the Treatment of Resistant Hypertension, Postgraduate Medicine, 10.3810/pgm.2012.01.2519, 124:1, (67-73), Online publication date: 1-Jan-2012. Brands M and Manhiani M (2012) Sodium-retaining effect of insulin in diabetes, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 10.1152/ajpregu.00390.2012, 303:11, (R1101-R1109), Online publication date: 1-Dec-2012. Liu L and Zhang X (2012) Poor BP Control in the Hypertensive Population: Which Factors are Involved? Special Issues in Hypertension, 10.1007/978-88-470-2601-8_25, (323-330), . Anyfanti P, Gavriilaki E and Douma S (2011) Evaluating the True Prevalence of Resistant Hypertension, Hypertension, 58:4, (e23-e23), Online publication date: 1-Oct-2011. June 2011Vol 57, Issue 6 Advertisement Article InformationMetrics © 2011 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.111.171520PMID: 21502566 Originally publishedApril 18, 2011 PDF download Advertisement SubjectsClinical StudiesEpidemiology
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