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JNC-7: THE EXPRESS REPORT

This issue of "CARDIONET" exclusively focuses on the much awaited report of JNC-7 guidelines for hypertension. JNC-7 made its debut presentation on May 14, 2003 at the American Society of Hypertension (ASH) annual Scientific Session. The presentation of the new guidelines brought forth both praise and criticism from the pre-eminent international audience assembled for the ASH Scientific Session. This issue covers the main features as well as a critical appraisal of the JNC-7 guidelines.
 

The Main Features of JNC-7 Guidelines

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) provides guidelines for increasing awareness, prevention, treatment, and control of hypertension. The JNC (which consists of a coalition of 39 major professional, public, and voluntary organizations and seven federal agencies) released its last report in 1997.

The new guidelines for the prevention and treatment of hypertension include recommendations for a more aggressive approach for detection and control of hypertension, an approach that the guideline authors say will reduce the number of heart attacks and strokes, and save lives, according to an article in the May issue of JAMA. But, the authors add that patient motivation to adhere to effective therapies is critical to successfully achieving blood pressure goals.

New BP Classification
In contrast with the classification provided in the JNC-6 report, a new category designated 'prehypertension' has been added and stages II and III hypertension have been combined.

"Before JNC-7, most patients with blood pressure figures ranging from 120-129 at the systolic, to 80-90 at the diastolic, were considered to have normal blood pressure. But these people are now considered to be pre-hypertensive," said Dr. Claude Lenfant, director of the NHLBI. He noted once a person's blood pressure climbs above 115/75, the risk of heart disease and stroke continue. Moreover, he said, that risk doubles for every 20/10-point rise in blood pressure. The new classification of BP is highlighted in Table 1.

Although the panel did not recommend treating patients in "pre-hypertension" disease category with drugs, members said that without lifestyle changes that include eating healthy foods and getting more exercise, these people are almost certain to develop hypertension (Table 1).
 

"The World Health Organization has estimated that high blood pressure causes 1 in every 8 deaths worldwide, making hypertension the third leading killer in the world. In fact, recent data from the Framingham Heart Study suggest that individuals, who are normotensive at 55 years of age, have a 90% lifetime risk for developing hypertension. Also, for individuals aged 40-70 years, each increment of 20 mm Hg in systolic BP or 10 mm Hg in diastolic BP doubles the risk of CVD across the entire BP range from 115/75 to 185/115 mm Hg."
 

New goal of therapy: "SBP"
The ultimate public health goal of antihypertensive therapy is the reduction of cardiovascular and renal morbidity and mortality. Since most persons with hypertension, especially those aged ³ 50 years, will reach the DBP goal once SBP is at goal, the primary focus should be on achieving the SBP goal. Treating SBP and DBP to targets that are <140/90 mm Hg is associated with a decrease in CVD complications. In patients with hypertension and diabetes or renal disease, the BP goal is <130/80 mm Hg.

Pharmacotherapy
Firstline therapy: The treatment suggestions outlined by the committee for patients indicate a first-line use of inexpensive but effective diuretics. Thiazide-type diuretics should be used as initial therapy for most patients with hypertension, either alone or in combination with one of the other classes (ACE inhibitors, ARBs, b-blockers, CCBs) demonstrated to be beneficial in randomized controlled trials. If a drug is not tolerated or is contraindicated, then one of the other classes proven to reduce cardiovascular events should be used instead. Compelling indications, like coexisting CHD or heart failure, requiring the use of other antihypertensive drugs as initial therapy are discussed later.
 

Combination therapy: Addition of a second drug from a different class should be initiated when use of a single drug in adequate doses fails to achieve the BP goal. However, when BP is more than 20/10 mm Hg above goal, consideration should be given to initiating therapy with 2 drugs, either as separate prescriptions or in fixed-dose combinations.

The JNC committee urged doctors to use other classes of drugs in combination with diuretics to get a patient's blood pressure under control. The initiation of drug therapy with more than one agent may increase the likelihood of achieving the BP goal in a more timely fashion. However, caution should be advised in those at risk for orthostatic hypotension (in diabetes, autonomic dysfunction and older persons).
 

Monitoring of serum potassium and creatinine should be done at least 1 to 2 times per year. Co-morbidities, such as HF, associated diseases, such as diabetes, and the need for laboratory tests influence the frequency of visits. Other cardiovascular risk factors should be treated to their respective goals, and tobacco avoidance should be promoted vigorously. Low-dose aspirin therapy should be considered only when BP is controlled, because the risk of hemorrhagic stroke is increased in patients with uncontrolled hypertension.

The algorithm for treatment of hypertension is shown in Figure 1.
 

BP: blood pressure; ACE: angiotensin-converting enzyme; ARB: angiotensin-receptor blocker; and CCB: calcium channel blocker
 

Compelling Indications
A patient with hypertension and certain co-morbidities requires special attention by the clinician.

1. Ischemic Heart disease

2. Heart Failure
Primary preventive measures are tight BP and cholesterol control in high-risk individuals

3. Diabetic Hypertension

• Combinations of 2 or more drugs are usually needed to achieve the target BP goal of less than 130/80 mm Hg.
  
   

• Thiazide diuretics, b-blockers, ACE inhibitors, ARBs, and CCBs are beneficial in reducing CVD and stroke incidence in patients with diabetes. The ACE inhibitor - or ARB based treatments favourably affect the progression of diabetic nephropathy and reduce albuminuria, and ARBs have been shown to reduce progression to macroalbuminuria.

  4. Chronic kidney disease
   

• The therapeutic goal is to slow deterioration of renal function, prevent CVD and aggressively manage BP which is often achieved with 3 or more drugs to reach target BP values of < 130/80 mm Hg.
   

• The ACE inhibitors and ARBs have demonstrated favourable effects on the progression of diabetic and nondiabetic renal disease.
   

• A limited increase in serum creatinine of as much as 35% above baseline with ACE inhibitors or ARBs is acceptable and not a reason to withhold treatment unless hyperkalemia develops.
   

• With advanced renal disease (serum creatinine of 2.5 to 3.0 mg/dL), increasing doses of loop diuretics are usually needed in combination with other drug classes.

  5. Cerebrovascular disease
   

• During acute stroke, control of BP should be at intermediate levels (approx. 160/100 mm Hg) until the condition has stabilized or improved.
   

• Recurrent stroke rates are lowered by the combination of an ACE inhibitor and thiazide type diuretic

  6. Other special situations

A Critique of JNC-7

New Blood Pressure Classification Questioned
 

• Leading off the critique, Jay N Cohn, MD (University of Minnesota Medical School, Minneapolis) commented on the major step that JNC-7 appears to have taken, away from the previous consensus, on how to classify hypertension. He expressed that this new category "prehypertension" will simply create anxiety in the general population. He pointed out that not all people in the new class are at risk for subsequent development of high blood pressure or for cardiovascular morbid events, which should be the focus of therapeutic efforts. As a result, a potential problem has been introduced, with physicians now having to deal with almost 50% of the overall population. Dr. Aran V. Chobanian, MD (Chairperson of JNC-7 executive committee) replied that the term "prehypertension" was selected after considerable discussion since it was deemed to be a more "action-oriented" term than "high normal," based partly on focus group investigations with doctors who said that the term "prediabetic" or "precancerous" resulted in patient responses, but the term "high normal" was ignored.
  
   

• A question that drew more applause was the issue of how to tell patients with blood pressure of 120/80 mmHg, who had previously considered themselves healthy, that they are now "prehypertensive." It was believed that patients will interpret this to mean that they now have hypertension. Dr. Chobanian agreed that the JNC-7 report has made physicians' lives "more complicated," admitting that the new concept will involve a lot of education and take a few years to get the public to understand that prehypertension is something they should do something about, he predicted. He believes that this is an opportunity to affect the lifelong risk for hypertension. However, he further noted that JNC-7 does not recommend drugs, but healthier lifestyles that are healthier for many other reasons, and he also confirmed that for individuals who are in the prehypertension category, JNC-7 sets no goal as to how low their blood pressure should be reduced.

  Comprehensive Risk Assessment Preferred
   

• Dr. Cohn continued his critique by stating his preference for a more comprehensive assessment of vascular health, including measurements such as arterial elasticity, funduscopic examination, and microalbuminuria. In this reply, Dr. Chobanian emphasized that the committee had aimed at making JNC-7 a "simple and straightforward" guide for clinicians, not for hypertension specialists.
   

• Professor Michael O'Rourke, MD, DSc (St Vincent's Hospital, Australia), noted that JNC-7 has moved towards measures of arterial pressure rather than measures of risk. Dr. Chobanian replied that measurements of cardiovascular risk were related to the other major risk factors, such as cholesterol, diabetes, and smoking, and the use of surrogate markers of risk was not included in the recommendations.
   

• Several questioners commented on the absence of left ventricular hypertrophy (LVH) as a compelling indication in JNC-7. Dr. Chobanian replied saying that even though LVH is an important factor, the data were not strong enough to make it a compelling indication.

  Drug Recommendations Challenged
   

• Professor Graham A McGregor, MD (St George's Hospital Medical School, London, UK), noted that simply restricting salt intake doubles the efficacy of an ACE inhibitor or an ARB, and most physicians would opt for an ARB and then add a thiazide-type diuretic. While admitting that eventually most patients will probably end up on both drugs, he nevertheless believes that if they restrict salt, many patients can be controlled on an ACE inhibitor and an ARB and it would be illogical to add a diuretic. He also added that the rate of impotence caused by first-line therapy with diuretics is unacceptable. Dr. Chobanian responded by making 2 points: first, a low salt diet is very difficult to follow, and second, if an individual develops impotence on any agent, there is no reason not to switch to another drug, considering how many "wonderful" drugs are available.
   

• Several delegates suggested that larger numbers of patients would respond to monotherapy if they were simply tried on different drugs. It was feared that when clinicians see the guidelines, they will start the patients on a diuretic and then add another drug, whereas many patients could be adequately controlled on monotherapy, simply by switching to a different drug. Another concern with diuretics was the possible side effects with lifelong treatment. Dr. Chobanian confirmed that JNC-7 does not advocate substitution of any particular class of drug (e.g., diuretics) to find one with a better effect over another. The emphasis from the practical standpoint is to combine therapy to get blood pressure levels down and keep them down, he said. He pointed out that wherever side effects occurred, those drugs should not be used.

   

  The "Two Basic Types" Theory of Hypertension Was Ignored
  
  Over the past 25 years during which JNC reports have been produced, science has leaped forward but JNC has leaped nowhere, Dr. Laragh declared, adding that the latest recommendations are little different from the first JNC report, published in 1977 after it was discovered that blood pressure could be lowered with diuretic-based therapy. Since that time, JNC has repeatedly recommended the use of diuretics. In JNC-5, ACE inhibitors and beta-blockers were added as first-line therapy, but although the recommendations were based on evidence from clinical trials, these 2 classes of agents were removed in JNC-6 and
  JNC-7, respectively, he noted.
  
  Dr. Laragh proposes that 2 causes of hypertension be recognized: salt and increased plasma renin. According to Dr. Laragh, salt accounts for 30% to 35% of the incidence of hypertension, so many patients only need a desalting drug such as chlorthalidone or hydrochlorothiazide (HCTZ), or spironolactone, which Dr. Laragh prefers as a safer alternative and which is also inexpensive. The other 50% to 60% of people with high blood pressure have hypertension caused by high plasma renin (plasma renin activity [PRA] > 0.65 ng/ml/h).
  
  According to Dr. Laragh, the only reason to treat high blood pressure is not to correct the blood pressure levels per se, but rather to avoid the future occurrence of MI, stroke, renal failure, or heart failure, and the only drugs that are known to protect against these are the anti-renin system drugs, i.e., ACE inhibitors, ARBs, and beta-blockers. All of these agents lower or block renin and all give measurable and immediate protection from MI, stroke, heart and kidney failure.
  
  As a result of this simple dichotomous analysis of hypertension, patients in whom diuretics like chlorthalidone, HCTZ, or spironolactone are not effective should be switched to an antirenin drug. Renin testing (which is available in the US) can be used to more quickly identify whether a patient has salt (low-renin) hypertension or high-renin hypertension. Thus, two thirds of all hypertension can be corrected with monotherapy, according to Dr. Laragh. This can be done because it involves using a drug mechanistically, which is only possible to do with the correct drug. However, there can be no such certainty when patients are given 3 drugs. Around 63% of patients in ALLHAT took 3 drugs to control their blood pressure, whereas, according to Dr. Laragh, 65% of his patients are controlled with 1 drug.

The Critics of ALLHAT also reject JNC-7
 

Researchers Dr. J.H. Laragh, MD (New York Hospital/Cornell University Medical Center, New York), founder of ASH, along with Dr. L.M. Resnick, MD (Weill College of Medicine, New York) and Dr. J. Meltzer, MD (Columbia University of Physicians and Surgeons, New York), who recently challenged the findings of ALLHAT (the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial), have extended their criticisms to the JNC-7. The important points made by them are as follows:
 

• They believe that JNC-7 has been inappropriately based on the ALLHAT results and expressed their opposition to the way the JNC guidelines have been produced.
   

• Dr. Meltzer also criticized the ALLHAT report for basing its conclusion on a secondary endpoint when the trial was originally intended to make recommendations only on the basis of the results of its primary endpoints. Secondary endpoints constitute useful data, but are collected mainly for hypothesis generation and the elucidation of possibilities for further studies, Dr. Meltzer pointed out. Another change in ALLHAT since its rationale and design was published was its appearance as a study of first-step therapy. However, ALLHAT could not be a first-step study because 90% of patients were already on antihypertensive drugs for an unknown number of years before they were entered into the trial. In contrast to most other studies of this nature, there was no washout period in ALLHAT, Dr. Meltzer noted. To call ALLHAT a study of first-step response is post hoc reasoning, he believes.
   

  ALLHAT and JNC-7 Express - Unbelievably Fast?
  
  Dr. Meltzer questioned why both the ALLHAT and JNC-7 reports appeared as "JAMA express," for which the peer-review process time is 24-48 hours and the time for authors' response is 72 hours. In the case of ALLHAT, Dr. Meltzer doubts that the report could have been reviewed within this period of time or that all the many authors could have responded within 72 hours. In the case of JNC-7, he questions the need for an express version of a report that essentially made only 2 changes since JNC-6, creation of the category 'prehypertension' and the recommendation, based on ALLHAT, that most patients should be started on a diuretic.

ANBP2 study contraindicates
ALLHAT findings
The Second Australian Blood Pressure Study (ANBP2, published in NEJM 2003) was a prospective randomized study involving 6083 elderly hypertensives who were treated with a regimen based on either an ACE inhibitor or a diuretic with other antihypertensives added on if required. The results showed a significant 12% reduction in the rate of cardiovascular events or death and a 17% reduction in both cardiovascular events and first cardiovascular events in men (p = 0.02) in the ACE inhibitor group as compared to the diuretic group. Hence this study which suggests that antihypertensive treatment with ACE inhibitors leads to better outcomes than treatment with diuretics, contradicts the
ALLHAT study findings.
 

European and US guidelines differ

The new European Society of Hypertension (ESH)/European Society of Cardiology (ESC) guidelines for the management of arterial hypertension were presented at the ESH meeting at Milan in June 2003. According to the ESH/ESC guidelines, a SBP <120 mm Hg and DBP <80 mmHg is considered 'optimal', whereas, SBP up to 129 mmHg and DBP up to 84 mmHg is normal. They have classified SBP of 130-139 mmHg and DBP of 85-89 mmHg as 'high-normal'. Also, the ESH/ESC guidelines differ in terms of medical treatment. They add that the choice of drugs should be influenced by risk profile, the presence of target organ damage, associated diseases and the patient's previous experience with the drug.
 

Conflict of Interest

The JNC guidelines were originally suggestive and now they are becoming coercive, Dr. Laragh believes. He sees a major conflict of interest in the governmental operation. He claims that physicians are not free to criticize the National Institutes of Health.
 

AS A FINAL POINT

The JNC-7 guidelines have recommended major changes in hypertension management. On the other hand, it has received a fair share of criticism. The final decision rests in the hands of the practising clinician. He alone can discern, on the basis of his clinical experience coupled with the available scientific evidence, as to what would be in the best interests of his patients.