2007：AHA： 缺血性心脏病的高血压控制建议

ISSN: 1524-4563 Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0194-911X. Online 72514 Hypertension is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/HYPERTENSIONAHA.107.183885 2007;50;e28-e55 Hypertension O’Gara and Suzanne Oparil Gore, Joseph L. Izzo, Jr, Norman M. Kaplan, Christopher M. O’Connor, Patrick T. Clive Rosendorff, Henry R. Black, Christopher P. Cannon, Bernard J. Gersh, Joel Clinical Cardiology and Epidemiology and Prevention Association Council for High Blood Pressure Research and the Councils on Ischemic Heart Disease: A Scientific Statement From the American Heart REPRINT Treatment of Hypertension in the Prevention and Management of http://hyper.ahajournals.org/cgi/content/full/50/2/e28 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/reprints Reprints: Information about reprints can be found online at journalpermissions@lww.com 410-528-8550. E-mail: Fax:Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters http://hyper.ahajournals.org/subscriptions/ Subscriptions: Information about subscribing to Hypertension is online at by on April 12, 2009 hyper.ahajournals.orgDownloaded from REPRINT Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease A Scientific Statement From the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention Clive Rosendorff, MD, PhD, FAHA, Chair; Henry R. Black, MD; Christopher P. Cannon, MD, FAHA; Bernard J. Gersh, MB ChB, DPhil, FAHA; Joel Gore, MD, FAHA; Joseph L. Izzo, Jr, MD; Norman M. Kaplan, MD; Christopher M. O’Connor, MD, FAHA; Patrick T. O’Gara, MD, FAHA; Suzanne Oparil, MD, FAHA Epidemiological studies have established a strong associ-ation between hypertension and coronary artery disease (CAD). Hypertension is a major independent risk factor for the development of CAD, stroke, and renal failure. The optimal choice of antihypertensive agents remains controver- sial, and there are only partial answers to important questions in the treatment of hypertension in the prevention and management of ischemic heart disease (IHD), such as: ● What are the appropriate systolic blood pressure (SBP) and diastolic blood pressure (DBP) targets in patients at high risk of developing CAD or in those with established CAD? ● Are the beneficial effects of treatment simply a function of blood pressure (BP) lowering, or do particular classes of drugs have uniquely protective actions in addition to lowering BP? ● Are there antihypertensive drugs that have shown particular efficacy in the primary and secondary prevention of IHD? ● Which antihypertensive drugs should be used in patients who have established CAD with stable or unstable angina pectoris, in those with non–ST-elevation myocardial in- farction (NSTEMI), and in those with ST-elevation myo- cardial infarction (STEMI)? This scientific statement summarizes the published data relating to the treatment of hypertension in the context of CAD prevention and management and attempts, on the basis of the best available evidence, to develop recommendations that will be appropriate for both BP reduction and the management of CAD in its various manifestations. Where data are meager or lacking, the writing group has proposed consensus recommendations, with all of the reservations that that term implies and with the hope that large gaps in our knowledge base will be filled in the near future by data from well-designed prospective clinical trials. All of the discussion and recommendations refer to adults. The writing committee has not addressed hypertension or IHD in the pediatric age group. Also, there is no discussion of the different modes of assessing BP, including 24-hour ambulatory BP monitoring. These were the subject of an American Heart Association (AHA) scientific statement in 2005.1 A classification of recommendation and level of evidence have been assigned to each recommendation, according to the AHA format as follows: Classification of Recommendations: Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective. Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on April 9, 2007. A single reprint is available by calling 800-242-8721 (US only) or writing the American Heart Association, Public Information, 7272 Greenville Ave, Dallas, TX 75231-4596. Ask for reprint No. 71-0412. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. This statement was previously published in the May 29, 2007, issue of Circulation (Circulation. 2007;115:2761–2788), and an erratum will be published in the July 31, 2007, issue of Circulation. Those changes have been incorporated into this version of the statement. When this document is cited, the American Heart Association would appreciate the following citation format: Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL Jr, Kaplan NM, O’Connor CM, O’Gara PT, Oparil S. Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation. 2007;115:2761–2788. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://www.americanheart.org/presenter.jhtml?identifier�3023366. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml? identifier�4431. A link to the “Permission Request Form” appears on the right side of the page. (Hypertension. 2007;50:e28-e55.) © 2007 American Heart Association, Inc. Hypertension is available at http://www.hypertensionaha.org DOI: 10.1161/HYPERTENSIONAHA.107.183885 e28 AHA Scientific Statement by on April 12, 2009 hyper.ahajournals.orgDownloaded from Class IIb: Usefulness/efficacy is less well established by evidence/opinion. Class III: Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful. Level of Evidence: Level of Evidence A: Data derived from multiple randomized clinical trials or meta-analyses. Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies. Level of Evidence C: Only consensus opinion of experts, case studies, or standard of care. The general design of the scientific statement is based on the concept that each of the clinical sections refers to a particular subset of patients, so that each section should provide a “stand-alone” description of the recommendations and their justification, independent of the other sections. This should make it easier for practitioners to extract the informa- tion relevant to any particular patient, without needing to cross-reference, and we hope it will thereby increase the utility of the document. With this organization, there may be some repetition of information from one section to the next, but we have tried to keep that to a minimum. A summary of the main recommendations is presented in the Table. Epidemiology of Hypertension and CAD Hypertension is a major independent risk factor for CAD, stroke, and renal failure. The latest version of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure2 recommendations has defined “hypertension” as a BP of �140/90 mm Hg. At this cutoff value, at least 65 million adult Americans, or nearly one fourth of the adult population of the United States, have hypertension. Another one fourth of the population is in the “prehypertension” range, defined as an SBP of 120 to 139 mm Hg or a DBP of 80 to 89 mm Hg. There is a strong but complex association of BP and age. Until about 50 years of age, SBP and DBP rise in tandem. After age 50 years, SBP continues to rise steadily, whereas DBP tends to fall. The prevalence of systolic hypertension is thus directly proportional to the age of the population, and more than half of Americans over age 65 years have isolated systolic or combined systolic-diastolic hypertension. In con- trast, the prevalence of diastolic hypertension diminishes, and fewer than 10% of individuals over the age of 65 years have diastolic hypertension. The Framingham Heart Study has estimated the 20-year risk of developing hypertension as �90% for men and women not yet hypertensive by middle age (55 to 65 years of age).3 There is also an enhanced risk for cardiovascular events associated with increased pulse pres- sure; this is discussed more fully in the section on “Primary Prevention of CAD in Hypertension: Observational Studies.” There is a change with age in the relative importance of SBP and DBP as risk indicators. Below age 50 years, DBP is the major predictor of IHD risk, whereas above age 60, SBP is more important.4 Because the prevalence of hypertension increases with age, adequate control of both SBP and pulse TABLE. Summary of Main Recommendations Area of Concern BP Target, mm Hg Lifestyle Modification† Specific Drug Indications Comments General CAD prevention �140/90 Yes Any effective antihypertensive drug or combination‡ If SBP �160 mm Hg or DBP �100 mm Hg, then start with 2 drugs High CAD risk* �130/80 Yes ACEI or ARB or CCB or thiazide diuretic or combination If SBP �160 mm Hg or DBP �100 mm Hg, then start with 2 drugs Stable angina �130/80 Yes �-Blocker and ACEI or ARB If �-blocker contraindicated, or if side effects occur, can substitute diltiazem or verapamil (but not if bradycardia or LVD is present) Can add dihydropyridine CCB (not diltiazem or verapamil) to �-blocker A thiazide diuretic can be added for BP control UA/NSTEMI �130/80 Yes �-Blocker (if patient is hemodynamically stable) and ACEI or ARB§ If �-blocker contraindicated, or if side effects occur, can substitute diltiazem or verapamil (but not if bradycardia or LVD is present) Can add dihydropyridine CCB (not diltiazem or verapamil) to �-blocker A thiazide diuretic can be added for BP control STEMI �130/80 Yes �-Blocker (if patient is hemodynamically stable) and ACEI or ARB§ If �-blocker contraindicated, or if side effects occur, can substitute diltiazem or verapamil (but not if bradycardia or LVD is present) Can add dihydropyridine CCB (not diltiazem or verapamil) to �-blocker A thiazide diuretic can be added for BP control LVD �120/80 Yes ACEI or ARB and �-blocker and aldosterone antagonist¶ and thiazide or loop diuretic and hydralazine/isosorbide dinitrate (blacks) Contraindicated: verapamil, diltiazem, clonidine, moxonidine, �-blockers UA indicates unstable angina; LVD, LV dysfunction; and ACEI, ACE inhibitor. Before making any management decisions, you are strongly urged to read the full text of the relevant section of the scientific statement. *Diabetes mellitus, chronic kidney disease, known CAD or CAD equivalent (carotid artery disease, peripheral arterial disease, abdominal aortic aneurysm), or 10-year Framingham risk score �10% (see Appendix). †Weight loss if appropriate, healthy diet (including sodium restriction), exercise, smoking cessation, and alcohol moderation. ‡Evidence supports ACEI (or ARB), CCB, or thiazide diuretic as first-line therapy. §If anterior MI is present, if hypertension persists, if LV dysfunction or HF is present, or if the patient has diabetes mellitus. ¶If severe HF is present (New York Heart Association class III or IV, or LVEF �40% and clinical HF). See text. Rosendorff et al Treatment of Hypertension in Ischemic Heart Disease e29 by on April 12, 2009 hyper.ahajournals.orgDownloaded from pressure rather than DBP in the elderly has become the dominant public health imperative. However, nearly all of the epidemiological and clinical trial data concerning outcomes have been based on SBP and/or DBP, so there are few if any data on the efficacy of antihypertensive drugs as a function of pulse pressure. Also, at all ages, the relationship between SBP or DBP and IHD mortality is consistent, robust, and contin- uous, with no apparent threshold value. In a meta-analysis of 61 studies that included almost 1 million adults, BP was related to fatal IHD over the BP range of 115/75 to 185/ 115 mm Hg. Overall, each increase in SBP of 20 mm Hg (or 10 mm Hg in DBP) doubles the risk of a fatal coronary event. Absolute risk of these adverse outcomes also increases with age, such that for any given SBP, the risk of fatal CAD was �16-fold higher for persons 80 to 89 years of age than for those 40 to 49 years of age.5 In the Chicago Heart Association Detection Project in Industry, men 18 to 39 years of age at baseline with a BP of 130 to 139/85 to 89 mm Hg or with stage 1 hypertension (140 to 159/90 to 99 mm Hg) accounted for nearly 60% of all excess IHD, overall cardiovascular disease, or all-cause mortality.6 On the basis of these epide- miological data, it can be argued from a public health perspective that many people with BPs previously regarded as normal could benefit from BP reduction if they are at significant risk for future coronary events for other reasons.7 Effects of Treatment The risk of cardiovascular disease in the patient with hyper- tension can be greatly reduced with effective antihypertensive therapy. The major reductions in cardiovascular morbidity and mortality over the past 50 years have been attributed mainly to the increased availability and utilization of various drug treatments for hypertension. Randomized trials have shown that BP lowering produces rapid reductions in cardio- vascular risk8 that are highly consistent with predictions of risk reduction that can be inferred from observational studies. For example, a 10-mm Hg–lower usual SBP (or a 5-mm Hg– lower usual DBP) would predict a 50% to 60% lower risk of stroke death and an approximately 40% to 50% lower risk of death due to CAD or other vascular causes at middle age, benefits that are only slightly less in older people.5 However, there are data to show in very old individuals, those at least 85 years of age, that the association between high BP and mortality is weaker9 and that lowering BP in patients older than 80 years reduces stroke but not nonstroke (including coronary) deaths.10 Several studies (HOPE [Heart Outcomes Prevention Eval- uation], SAVE [Survival And Ventricular Enlargement], and EUROPA [EUropean trial on Reduction Of cardiac events with Perindopril in stable coronary Artery disease]; see below) have shown a beneficial effect of angiotensin- converting enzyme (ACE) inhibitors on cardiovascular out- comes in individuals, some hypertensive and some not but all with established cardiovascular disease or with high risk for the development of cardiovascular disease. However, we do not yet have any outcome studies of treatment of “prehyper- tension” in individuals with BPs in the range of 130 to 139/80 to 89 mm Hg. The only prospective clinical trial of BP reduction in individuals with “normal” BPs is the TROPHY (TRial Of Preventing HYpertension) study,11 in which sub- jects with an SBP of 130 to 139 mm Hg or a DBP of 85 to 89 mm Hg were randomized to be treated for 2 years with either the angiotensin receptor blocker (ARB) candesartan or placebo and followed up for an additional 2 years. Hyperten- sion developed in significantly more participants in the placebo group (two thirds of this cohort at 4 years) than in the candesartan group, with a relative risk reduction of 66.3% at 2 years and 15.6% at 4 years. However, the study was not designed or powered to assess cardiovascular outcomes. Risk Factor Interactions Data from the Framingham Heart Study have provided evidence supportive of an interrelationship between hyper- tension, dyslipidemia, glucose intolerance, cigarette smoking, and left ventricular (LV) hypertrophy.12 These 5 primary risk factors are the most important reversible determinants of cardiovascular risk and appear to operate independently of one another, although it appears that the risk increases in a multiplicative rather than simply additive fashion. This has led to the idea that the threshold at which a patient should be treated for hypertension, as well as the goal to which he/she should be treated, is lowered in those at high risk for cardiovascular disease by virtue of the presence of other risk factors. In the guidelines developed by the National Kidney Foundation,13 this principle has been followed for patients with albuminuria and even modest chronic renal insuffi- ciency, for which the BP threshold for the institution of antihypertensive therapy is 130/80 mm Hg. The American Diabetes Association,14 the National Kidney Foundation,13 and the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure2 all agree that the BP goal of treatment in individuals with diabetes mellitus or with chronic kidney disease should be �130/ 80 mm Hg, a lower goal than that recommended for other hypertensive patients (�140/90 mm Hg). There is also a correlation between hypertension and body mass, and both are strongly correlated with CAD. Hyperten- sion and abdominal obesity are components of a larger risk factor constellation of cardiovascular risk factors, the “met- abolic syndrome,” which also includes a characteristic form of dyslipidemia (high triglycerides and low high-density lipoprotein cholesterol), and an elevated fasting blood glu- cose level.15 Mechanisms of Hypertension and CAD The diffuse arteriosclerosis of hypertension, the more patchy atherosclerotic lesions of epicardial CAD, and the remodeling of medium and small coronary arteries may all have common pathophysiological mechanisms. Prevention and reversal of these processes are major goals of therapy for hypertension, CAD, and ischemic heart failure (HF). Physical Forces and Hemodynamics In hypertension, there is both an increased myocardial oxygen demand and a diminished coronary blood flow or, at least, a diminished coronary flow reserve. The increased demand is due to the increased LV output impedance, which raises intramyocardial wall tension, as well as to LV hypertrophy if e30 Hypertension August 2007 by on April 12, 2009 hyper.ahajournals.orgDownloaded from present. The diminished coronary flow reserve is a complex function of the plaque-related occlusive CAD, remodeling of medium and small coronary arteries, and, if the diastolic pressure is low enough, a decrease in coronary perfusion pressure. Physical forces (pressure and flow) are the primary deter- minants of cardiac structure and function and also influence v