REPRINT Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease

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HomeHypertensionVol. 50, No. 2REPRINT Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBREPRINT Treatment of Hypertension in the Prevention and Management of Ischemic Heart DiseaseA 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. IzzoJr, MD, Norman M. Kaplan, MD, Christopher M. O’Connor, MD, FAHA, Patrick T. O’Gara, MD, FAHA and Suzanne Oparil, MD, FAHA Clive RosendorffClive Rosendorff Search for more papers by this author , Henry R. BlackHenry R. Black Search for more papers by this author , Christopher P. CannonChristopher P. Cannon Search for more papers by this author , Bernard J. GershBernard J. Gersh Search for more papers by this author , Joel GoreJoel Gore Search for more papers by this author , Joseph L. IzzoJrJoseph L. IzzoJr Search for more papers by this author , Norman M. KaplanNorman M. Kaplan Search for more papers by this author , Christopher M. O’ConnorChristopher M. O’Connor Search for more papers by this author , Patrick T. O’GaraPatrick T. O’Gara Search for more papers by this author and Suzanne OparilSuzanne Oparil Search for more papers by this author Originally published1 Aug 2007https://doi.org/10.1161/HYPERTENSIONAHA.107.183885Hypertension. 2007;50:e28–e55Epidemiological studies have established a strong association 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 controversial, 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 infarction (NSTEMI), and in those with ST-elevation myocardial 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 2005.1A 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. 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 information 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. TABLE. Summary of Main RecommendationsArea of ConcernBP Target, mm HgLifestyle Modification†Specific Drug IndicationsCommentsUA 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.General CAD prevention<140/90YesAny effective antihypertensive drug or combination‡If SBP ≥160 mm Hg or DBP ≥100 mm Hg, then start with 2 drugsHigh CAD risk*<130/80YesACEI or ARB or CCB or thiazide diuretic or combinationIf SBP ≥160 mm Hg or DBP ≥100 mm Hg, then start with 2 drugsStable angina<130/80Yesβ-Blocker and ACEI or ARBIf β-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 β-blockerA thiazide diuretic can be added for BP controlUA/NSTEMI<130/80Yesβ-Blocker (if patient is hemodynamically stable) and ACEI or ARB§If β-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 β-blockerA thiazide diuretic can be added for BP controlSTEMI<130/80Yesβ-Blocker (if patient is hemodynamically stable) and ACEI or ARB§If β-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 β-blockerA thiazide diuretic can be added for BP controlLVD<120/80YesACEI or ARB and β-blocker and aldosterone antagonist¶and thiazide or loop diuretic and hydralazine/isosorbide dinitrate (blacks)Contraindicated: verapamil, diltiazem, clonidine, moxonidine, α-blockersEpidemiology of Hypertension and CADHypertension 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 contrast, 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 pressure; 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 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 continuous, 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 epidemiological 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.7Effects of TreatmentThe risk of cardiovascular disease in the patient with hypertension 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 cardiovascular 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.10Several studies (HOPE [Heart Outcomes Prevention Evaluation], 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 outcomes 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 “prehypertension” 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 subjects 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. Hypertension 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 InteractionsData from the Framingham Heart Study have provided evidence supportive of an interrelationship between hypertension, 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 insufficiency, 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. Hypertension and abdominal obesity are components of a larger risk factor constellation of cardiovascular risk factors, the “metabolic syndrome,” which also includes a characteristic form of dyslipidemia (high triglycerides and low high-density lipoprotein cholesterol), and an elevated fasting blood glucose level.15Mechanisms of Hypertension and CADThe 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 HemodynamicsIn 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 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 determinants of cardiac structure and function and also influence vascular remodeling and atherosclerosis. When SBP is elevated, there is an increase in both LV output impedance and intramyocardial wall tension, which increase myocardial oxygen demand. The wide pulse pressure and systolic hypertension in older individuals are almost always due to inappropriately high aortic impedance, which results from decreased aortic diameter or increased effective stiffness due to aortic wall thickening or changes in wall composition. Aging is associated with thinning and fragmentation of vascular elastin together with increased collagen deposition; this degenerative process is more pronounced in individuals with sustained systolic hypertension.SBP is not constant within the arterial tree because of structural and functional variation in properties related to wave propagation and wave reflection. Central SBP is particularly influenced by pressure wave reflection, which in turn increases with age and structural changes in arteries. Increased wave reflection leads to central systolic pressure augmentation, which increases LV pressure load and cardiac work. These in turn may cause angina pectoris and LV hypertrophy.Systolic HypertensionIn persons who have elevated or high-normal BP at an early age, the increased vascular wall tension leads to thinning, fragmentation, and fracture of elastin fibers, as well as increased collagen deposition in arteries, which results in decreased compliance of these vessels. In addition to these structural abnormalities, endothelial dysfunction, which develops over time as a consequence of both aging and hypertension, contributes functionally to increased arterial rigidity in elderly persons with a widened pulse pressure and subsequent isolated systolic hypertension.16 Increased arterial stiffness, with related increases in pulse wave velocity and reflection, leads to augmentation of central SBP and afterload, and also decreased DBP, which has the potential to compromise coronary perfusion pressure. Augmentation of central aortic SBP, as seen in aging and in the presence of hypertension and/or arterial disease, greatly increases cardiac work and pressure-related cardiac pathology, including both CAD and LV hypertrophy, because it is the pressure against which the LV must eject blood into the systemic circulation.Oxidative StressOxidative stress is a critical feature in both hypertension and atherogenesis.17,18 Excessive generation of reactive oxygen species can damage endothelial or muscular cells and lead to acute and chronic changes in structure and function. For example, injured endothelium loses its vasodilator capacity and contributes to thrombosis and occlusion. Reactive oxygen species stimulate release of chemotactic cytokines and adhesion molecules on the luminal surface of the injured endothelium, thereby promoting adhesion of circulating leukocytes to the vessel wall. This low-grade, self-perpetuating vascular inflammatory process underlies the ongoing atherosclerotic process and contributes to continuing recruitment of leukocytes from the circulation into the subendothelial space. Inflammatory mediators also activate medial smooth muscle cells, causing them to proliferate and migrate into the subintimal space. In the presence of dyslipidemia, monocytes within the vessel wall incorporate oxidized low-density lipoprotein cholesterol and become lipid-laden macrophages, the core of the atherosclerotic plaque. In established lesions, resident macrophages secrete metalloproteinase and cathepsins, which may destabilize the fibrous cap of the plaque, result in plaque rupture, and release tissue factor to cause thrombosis, coronary occlusion, and acute myocardial infarction.These processes may also contribute to the microcirculatory structural abnormalities seen in chronic hypertension. In vascular tissue, the principal effectors of oxidative injury are the NAD(P)H oxidases, which are activated by mechanical forces (eg, hypertension), hormones (particularly angiotensin II), oxidized cholesterol, and cytokines.19 When cells are activated, these oxidases facilitate superoxide anion (·O2−) generation. ·O2− readily reacts with nitric oxide to form peroxynitrite (ONOO−), a particularly toxic metabolite that also shortens the half-life of endothelium-derived nitric oxide. Reactive oxygen species such as hydrogen peroxide and ONOO− rapidly oxidize lipids, which makes them more atherogenic, and produce phenotypic changes such as vascular smooth muscle cell proliferation, adhesion molecule expression, and premature senescence in vascular cells.20 Several NAD(P)H oxidase isoforms expressed in endothelial and vascular smooth muscle cells appear to be upregulated in the setting of atherosclerosis and arterial injury.21Humoral and Metabolic FactorsMany of the mechanisms of the initiation and maintenance of hypertension are also those that mediate damage to target organs, including the coronary vessels and the myocardium. These mechanisms include increased sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS) activity; deficiencies in release and/or activity of vasodilators, for example, nitric oxide, prostacyclin, and the natriuretic peptides; structural and functional abnormalities in conductance and resistance arteries, particularly endothelial dysfunction; and increased expression of growth factors and inflammatory cytokines in the arterial tree.17 The corollary of this idea is that antihypertensive drugs may exert at least some of their beneficial effects on the vasculature by actions that are independent of BP lowering alone. This is controversial and will be discussed more fully in later sections.Angiotensin II elevates BP and promotes target-organ damage, including atherosclerosis, by a large variety of mechanisms. There are direct effects of angiotensin II on constriction and remodeling of resistance vessels, aldosterone synthesis and release, enhancement of sympathetic outflow from the brain, and facilitation of catecholamine release from the adrenals and peripheral sympathetic nerve terminals.18,22,23 Aldosterone may mimic or potentiate the vasotoxic properties of angiotensin II and norepinephrine.24 Angiotensin II promotes cardiac and vascular smooth muscle cell hypertrophy directly via activation of the angiotensin II type 1 (AT1) receptor and indirectly by stimulating expression of a number of growth factors and cytokines, for example, platelet-derived growth factor, basic fibroblast growth factor, insulin-like growth factor-1, and transforming growth factor-β and their receptors, as well as monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1. Finally, there is a link between RAAS activation and fibrinolysis. Angiotensin II induces the formation of plasminogen activator inhibitor-1 via an AT1 receptor–dependent effect on endothelial cells, whereas ACE downregulates tissue plasminogen activator production by degrading bradykinin, a potent stimulator of endothelial tissue plasminogen activator expression.25,26ACE inhibitors and ARBs have been shown to limit oxidative reactions in the vasculature by blocking the activation of NAD(P)H oxidase, which supports the concept that these RAAS blockers may have important vasoprotective effects beyond BP lowering.27 Furthermore, there is evidence of interaction between the RAAS and dyslipidemia, wherein hypercholesterolemia upregulates the RAAS, particularly vascular AT1 receptor density and functional responsiveness, and systemic angiotensin II peptide synthesis,28,29 whereas the RAAS stimulates the accumulation of low-density lipoprotein cholesterol in the arterial wall.30CalciumCalcium ions (Ca2+) are major intracellular mediators of vascular smooth muscle cell contraction, as well as of inotropic and chronotropic functions of the heart. Ca2+ enters vascular smooth muscle cells, cardiomyocytes, and pacemaker cells via voltage-dependent L- and T-type calcium channels.31 In vascular smooth muscle, the voltage-gated L-type (long-acting, slowly activating) channel allows entry of sufficient Ca2+ for initiation of contraction by calcium-induced intracellular Ca2+ release from the sarcoplasmic reticulum. In addition to these acute regulatory functions, increased intracellular Ca2+ has atherosclerosis-promoting effects.32The dihydropyridine calcium channel blockers (CCBs) bind to a common site on the α1-subunit of the L-type channel. The dihydropyridine CCBs are highly selective for arterial/arteriolar tissues, including the coronary arteries, where they cause vasodilation. The nondihydropyridine CCBs, including the phenylalkylamines (verapamil-like) and benzothiazepines (diltiazem-like), bind to different sites on the α1-subunit and are less selective for vascular smooth muscle; they have negative chronotropic and dromotropic effects on sinoatrial and atrioventricular nodal conducting tissue and negative inotropic effects on cardiomyocytes. The nondihydropyridine CCBs have greater effects on the atrioventricular node than on the sinoatrial node and may predispose to high-degree atrioventricular block when administered to patients with preexisting atrioventricular nodal disease or when given with other agents, for example, β-blockers, that depress the atrioventricular node. Both dihydropyridine CCBs and nondihydropyridine CCBs are indicated for the treatment of hypertension and angina pectoris. The antianginal effects of CCBs result from afterload reduction, that is, their ability to decrease SBP, as well as coronary vasodilation, and in the case of nondihydropyridine CCBs, heart rate slowing. CCBs are particularly effective in treating angina due to coronary spasm, for example, Prinzmetal’s variant or cold-induced angina.33Primary Prevention of CAD in HypertensionPrimary Versus Secondary PreventionIHD can be prevented or reversed when aggressive targets are achieved for major cardiovascular disease risk factors.2,34 The distinction between primary and secondary prevention is arbitrary, because the major therapeutic objective in any individual is to retard or reverse the underlying atherosclerotic disease process. Furthermore, existing therapies are the same for primary or secondary cardiac protection. The effectiveness of any therapy is judged by the degree of reduction in the surrogate end point (BP) and the ability of the chosen regimen to reduce clinical end points (eg, myocardial infarction [MI]).BP and Treatment GoalsThe overall goal of therapy is to reduce excess morbidity and unnecessary deaths. In the case of hypertension, dyslipidemia, and diabetes mellitus, surrogate end points (BP, cholesterol, and blood glucose) have been established as diagnostic markers, and discrete values of these markers have been established as therapeutic targets. The current consensus target for BP is <140/90 mm Hg in general and <130/80 mm Hg in individuals with diabetes mellitus or chronic kidney disease.2,13,14 Recently, it has been found that treatment of prehypertension (BP 120 to 139/80 to 89 mm Hg) reduces the incidence of subsequent hypertension.11 An analysis of the 274 patients with CAD who completed the intravascular ultrasound substudy of the CAMELOT (Comparison of AMlodipine versus Enalapril to Limit Occurrences of Thrombosis) trial35 showed that those subjects with a “normal” BP according to the definition given in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure2 (<120/80 mm Hg) had a mean decrease of atheroma volume of 4.6 mm3; “prehypertensive” (120 to 139/80 to 89 mm Hg) subjects had no significant change; and “hypertensive” (≥140/90 mm Hg) subjects had a mean increase in atheroma volume of 12.0 mm3. There is, therefore, a very powerful historical trend for lower BP goals, especially in those with target-organ damage. There remains, however, controversy about specific BP treatment goals for individuals with nascent or overt CAD. On the one hand, it can be argued from pathophysiological principles that very low SBP values (ie, <120 mm Hg) may be appropriate to reduce myocardial workload.2,36 At the same time, there is a concern that excessive lowering of DBP may impair coronary perfusion.At present, there are no clinical trials specifically designed to answer the question of what the most appropriate BP target(s) should be in individuals with latent or overt CAD. Judgments and recommendations must be based on the analysis of large epidemiological studies, such as the data in 986 000 individuals followed up for a median of 12.7 years in the Prospective Studies Collaboration, in which there was a strong log-linear association between BP and cardiovascular disease risk. Over the range of 115/75 to 185/115 mm Hg, each 20-mm Hg elevation in SBP (or 10-mm Hg elevation in DBP) roughly doubled the risk of dying of IHD or stroke.5 Although epidemiological correlations cannot be used as proof of the value of treatment, they are useful in establishing expectations for reasonable treatment strategies. However, on the basis of this huge cohort and prospec