JNC 7.5

It is now 4 years since the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)1 was published, and many of us are wondering whether and when JNC 8 will appear. In the meantime, a lot has been happening in the world of hypertension, which make some of the recommendations of JNC 7 obsolete. There have been many major clinical trials published, and several new guidelines, both from the United States and overseas. These include a scientific statement from the American Heart Association (AHA) about the treatment of hypertension in high-risk patients,2 the 2007 Guidelines for the Management of Arterial Hypertension, the Task Force of the European Society of Hypertension (ESH) and the European Society of Cardiology,3 the 2007 Canadian Hypertension Education Program recommendations,4,5 and the American Society of Hypertension (ASH) Writing Group (HWG) position paper entitled “Expanding the definition and classification of hypertension.”6 This brief paper will discuss some of the items that might be changed if there were to be a new version of the JNC recommendations. The views expressed are personal. Most people accept the idea that hypertension can still only be diagnosed on the basis of blood pressure (BP) measurement. The situation has become muddied by the suggestion that there is a “syndrome” of hypertension that includes the cluster of risk factors that compose the metabolic syndrome and also changes in the vasculature, which were emphasized by the HWG.6 These other measures may be very helpful in estimating a patient's risk, and hence the need for treatment, but they are not the same as BP itself, and the HWG did not specify what BP levels should be used to define hypertension.6 The benefits of treating hypertension are all based on BP numbers, and we really have no idea what the benefits are from treating vascular changes independently of BP, so we should not lose sight of the main goal. All the recent guidelines, including JNC 7, have recognized the limitations of traditional clinic BP measurement and advocated the wider use of outof office monitoring, but there are no guidelines thus far saying that these measurements should be routine. The closest to date is a statement published by the Canadian Hypertension Education Program in 2005,7 which discussed 3 options for diagnosing hypertension, based on: (1) office BP exclusively, (2) a combination of office BP and ambulatory BP monitoring, and (3) a combination of office BP and home monitoring. While ambulatory BP monitoring remains the most expensive method of BP measurement, and thus is not widely used, the use of home monitoring is growing rapidly, and the existing guidelines such as JNC 7 give only the sketchiest recommendations as to how it should be used in practice. Statements are being prepared both in the United States (endorsed by the AHA and ASH) and the European Society of Hypertension, which will make much stronger and more detailed recommendations for the routine use of home monitoring unless there is a contraindication such as excessive anxiety. Perhaps the most controversial aspect of JNC 7 was the introduction of the label of prehypertension for people who had previously been labeled as having high-normal BP.1 This concept has not been adopted by the 2007 European guidelines, which point out that lumping everyone in the range of 120 to 139/80 to 89 mm Hg in a single group makes little sense for several reasons: (1) the risk associated with the 2 extremes of BP (120/80 vs 139/89 mm Hg) is very different; (2) the term prehypertension may cause unnecessary anxiety; and (3) the recommendation that the condition be treated with lifestyle changes rather than drugs may be inappropriate in many individuals: an older person with a BP of 122/82 mm Hg does not need any intervention, while a high-risk patient with a BP of 138/88 mm Hg may need drug treatment. In place of “prehypertension,” the European guidelines refer to “normal” (120–129/80–84 mm Hg) and “high-normal” (130–139/85–89 mm Hg). My vote would be to use the European nomenclature in any future guidelines. One of the more criticized aspects of JNC 7 was the decision to recommend treatment solely on the basis of BP rather than on risk. This was a step back from JNC VI, which based treatment decisions on a matrix of BP and other risk factors, including target organ damage. The same approach has been adopted by the European guidelines. In both cases, the matrix was determined by data from observational studies such as the Framingham Heart Study in the United States8 and the Systemic Coronary Risk Evaluation (SCORE) project in Europe.9 The rationale for this approach is that 2 patients with the same level of BP may have very different levels of risk. The difference between the “risk-based approach” and JNC 7 can be illustrated by a patient who has a BP of 135/85 mm Hg. According to JNC 7, this patient would be labeled as prehypertensive and lifestyle changes would be advised unless diabetes or kidney disease were present, in which case medications would be prescribed. According to the ESH guidelines,3 if there were no other risk factors, no intervention is recommended; if 1 or 2 other risk factors are present, lifestyle changes are indicated; if there are 3 or more other risk factors or diabetes, drug treatment should be considered; and if there is diabetes, kidney disease, or coronary heart disease, drug treatment should definitely be used. Thus, the ESH guidelines give a much more graded approach to treatment. There is no doubt that the presence of several types of hypertensive target organ damage increases cardiovascular disease risk, but JNC 7 does not say much about this. The most prominently featured measure is urinary microalbumin, which is described as an “optional test” for the majority of patients, but one that should be performed annually in high-risk patients with diabetes and kidney disease.1 There are no specific recommendations for echocardiography. In contrast, the European guidelines make extensive recommendations for the evaluation of many types of target organ damage. A list entitled “recommended tests” includes an echocardiogram, carotid ultrasound, proteinuria, ankle-brachial index, funduscopy, glucose tolerance test if the fasting glucose is >100 mg/dL, and pulse wave velocity measurement. These tests vary in their practicality and cost. Microalbuminuria is recommended for all hypertensive patients, which seems appropriate since there is a large database showing its prognostic importance and because it is so easy to perform.10 The ankle-brachial index is also easy to do and gives important prognostic information in older patients.11 It is not mentioned in the JNC 7 guidelines, even though there is a separate section on peripheral vascular disease. Perhaps the most surprising inclusion in this list is carotid ultrasound. The statement is made that “echocardiography and vascular ultrasonography can be considered as recommended tests, particularly in patients in whom organ damage is not detected by routine investigations such as the electrocardiogram, and in the elderly in whom cardiac hypertrophy and arterial disease are frequent.”3 The key measurement here for the carotid ultrasound is intimomedial thickness, and my impression is that few vascular laboratories that perform it in the United States actually perform this measurement reliably. There is also the question as to how much information it provides that is truly independent of the echocardiogram, since vascular and arterial hypertrophy tend to go hand in hand.12 Carotid ultrasound, however, is the only test in this list that can detect atheromatous plaque. A new recommendation published by the AHA2 is that high-risk individuals, defined as those patients with known coronary artery disease (CAD), or with “CAD risk equivalents” (carotid artery disease, peripheral arterial disease, or abdominal aortic aneurysm or a 10-year Framingham risk score >10%) should have their BP lowered to <130/80 mm Hg. While observational trials certainly suggest that risk is lower at very low levels of BP, the evidence from interventional trials supporting this argument is thin. The main support comes from the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) trial,13 which was performed in patients with documented CAD, in which the primary outcome was change in the volume of atheromatous plaque measured by intravascular ultrasound. The main finding was that the patients with the lowest BPs at the end of the trial had the greatest regression of plaque volume. The AHA statement reviewed the possibility of the “J-curve phenomenon” (increased CAD risk at very low pressures), and concluded that it was unproven, but nevertheless advised caution in lowering the diastolic pressure to <60 mm Hg. The trend to recommend lower target BP levels is also apparent in the ESH guidelines, where it is suggested that “Antihypertensive treatment should be more aggressive in diabetics, in whom a target BP of <130/80 mm Hg appears a reasonable one. Similar targets should be adopted in individuals with cerebrovascular disease and can at least be considered in patients with coronary disease.”3 The basis for the recommendation about stroke patients was the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) study,14 which showed that lowering the BP in already normotensive patients reduced the likelihood of recurrent strokes. JNC 7 made a clear recommendation to start all patients who need antihypertensive drugs on a diuretic, a decision that was heavily influenced by the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)15 results. If the diuretic does not control the BP by itself, any of the other major classes of drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers) can be added. Since that time, 2 major findings have been established suggesting that this recommendation needs modifying. The first is the meta-analyses performed using data from older clinical trials in which a β-blocker (almost always atenolol) was compared with placebo or other antihypertensive drugs. The study concluded that β-blockers (particularly atenolol) are somewhat better than placebo at preventing stroke but not for reducing cardiovascular events or mortality and that they are not as good as other antihypertensive drugs for reducing any of the end points.16,17 A more recent analysis18 concluded that there were benefits in young patients but not in the elderly with β-blockers. As a result of these analyses, and the recent results of the ASCOT trial,19 the British Hypertension Society20 has stated that they “are no longer preferred as routine initial therapy for hypertension.” The European guideline says, “Thus β-blockers may still be considered an option for initial and subsequent antihypertensive treatment strategies. Because they favor an increase in weight, have adverse effects on lipid metabolism and increase (compared with other drugs) the incidence of new-onset diabetes, they should not be preferred, however, in hypertensives with multiple metabolic risk factors including the metabolic syndrome…”3 The other finding that has surfaced since JNC 7 is the observation in several of the large outcomes trials, including ALLHAT, that diuretic treatment is associated with an increased risk of new-onset diabetes. In ALLHAT, the rate after 4 years was 11.0% in the diuretic group, 9.3% in the amlodipine group, and 7.8% in the lisinopril group.15 There is also evidence that new-onset diabetes does increase the risk of cardiovascular disease events,21 although it is still disputed whether drug-induced diabetes carries the same risk. Since patients with the metabolic syndrome are at undoubtedly increased risk of developing diabetes, these considerations mean that the old custom of routinely starting hypertensive patients on β-blockers and diuretics is no longer tenable. These considerations indicate that there is a real need to update JNC 7. Its predecessor JNC VI was published in 1997, so there was a 6-year gap between the two. Given how long it takes to prepare a multiauthored document such as the JNC reports, if the same interval is maintained, work should start now. One of the things that we are seeing is that there is no magic to the numbers 140/90 mm Hg. It was always an arbitrary threshold, and it is becoming clear that there are groups of high-risk patients, such as those with known coronary disease or cerebrovascular disease, who may benefit from even lower pressures. Some of the possible revisions, such as a return to the JNC VI concept of treatment based on risk rather than on BP alone, would require vary careful thought, including how the presence of specific types of target organ damage would influence a patient's risk categorization, but there are others, such as new guidelines on the use of β-blockers and diuretics, which should be revised straight away. A brief statement could be made by ASH, which would at least help to fill the vacuum. It is notable that, as in many other aspects of health care, the Canadians are ahead of us and that they have promised to update their recommendations annually.5

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