Introduction

In 1977 the first Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC I) was published.[1]There were only a limited number of effective antihypertensive drugs available and only a few long-term clinical treatment trials had been completed. Treatment data regarding the relative merits of various anti-hypertensive medications were limited. This committee evaluated treatment results of hypertension and published an algorithm based on available information. This suggested that the "first-step drug should usually be a thiazide diuretic"..."starting with less than a maximal dose." ( Table I ). The report stated that "if a diuretic proved ineffective and therapeutic goal is not achieved, an additional drug should be added as the second step to the therapeutic program." At that time "second step" drugs included reserpine, methyldopa, or propranolol, a blocker. The concept of adding one drug to another if the first was ineffective was labeled "stepped care." The report noted that when a third drug was needed, "hydralazine or clonidine may be added to the regimen." Numerous criticisms of the JNC I report followed. Some of these were based on the choice of diuretics suggested as initial therapy, despite treatment data demonstrating their effectiveness. Members of the committee were criticized for recommending a "cookbook algorithm" approach to treatment. Critics noted that physicians should not be advised to follow a protocol-driven program. Over the next 20-25 years many large-scale randomized, blinded trials were completed and many newer, better tolerated, and more effective medications were introduced -- but the original concept of stepped care (whether it was called "modified or individualized") continued to represent a reasonable approach to treatment. The next four JNC reports also listed diuretics as one of the preferred initial medications ( Table I ).[2-5] But the arguments about stepped care continued. Dr. Irvine Page, one of the pioneers in the treatment of hypertension commented in an editorial in "Modern Medicine" in 1985: We must not get snarled in nonproblems such as whether stepped-care is good or bad. Stepped-care is merely a way of presenting an orderly scenario in what otherwise threatens to join the New Yorkers' Department of Utter Confusion. The JNC VI, in 1997, again suggested the use of diuretics as one of the preferred drugs in uncomplicated hypertension but listed other agents for "compelling indications."[6] Despite the availability of many other effective, well-tolerated antihypertensive drugs, the use of thiazide diuretics had stood the test of time.[7] Recent trials[8,9] have since reconfirmed that thiazide diuretics are as effective in lowering blood pressure and reducing cardiovascular events as any of the other available drugs including the newer medications, i.e., the angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. In addition, numerous studies[10-15] have confirmed that a majority of patients do not respond to monotherapy either with a diuretic, a blocker, a calcium channel blocker, an ACE inhibitor, or the more recently introduced agents (angiotensin receptor blockers [ARBs]). Hence, the need for a stepped-care approach that utilizes more than one medication. In most instances, other than in those patients with stage 1 hypertension (140-160/90-100 mm Hg) with few other risk factors, it has been necessary to use two or three medications to produce goal blood pressure levels and reduce cardiovascular events. The recommendation of blockers as one of the preferred initial therapies over the years has also been criticized, but there are abundant data describing the benefits of these agents either alone or with a diuretic.[16] In general, especially in the elderly, these medications as monotherapy may not be as effective as a diuretic. An "express version" of the JNC 7 has just been published [17]; it recognizes and reemphasizes many of the issues raised in previous reports. It is important to highlight some of its recommendations. An expanded full report will be published in the future and a roundtable discussion highlighting details of the JNC 7 will be published in an upcoming issue of The Journal of Clinical Hypertension.

Some Details of the JNC 7

Definitions of hypertension are updated and modified based on recent analyses of epidemiologic data. Normal blood pressure is now defined as 120/80 mm Hg or below; pre-hypertension as 130-139/85-89; stage 1 as 140-159/90-99 mm Hg; and stage 2 as 160/100 mm Hg. The new designation of pre-hypertension does not imply that individuals with blood pressures at these levels should be labeled as hypertensives or treated with medications; it suggests that some attention should be paid to modifying any cardiovascular risk factors and to nonpharmacologic approaches to keeping or lowering blood pressure to levels as close to the normal range as possible. The JNC 7 report summarizes newer data on the benefits of nonpharmacologic approaches to blood pressure lowering, i.e., weight loss if appropriate, exercise, modification of alcohol intake, and a low-sodium diet, and also includes an update on the low-sodium Dietary Approaches to Stop Hypertension (DASH) diet.[18] A summary table of the possible blood

pressure-lowering effects of each of these interventions is presented in the "express report" ( Table II ). Lifestyle modifications are again recommended for all hypertensive patients.

Recommendations for Specific Therapy: JNC 7

Based on evidence from numerous controlled clinical trials, including the recently reported Anti-hypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT),[9] the JNC 7 has recommended that "thiazide diuretics be used as initial drug therapy for most patients with hypertension" (Figure 1). The report recognizes that many patients will require a second or third drug; in any multidrug treatment program a diuretic should be one of the medications used. "Addition of a second drug from a different class should be initiated when the use of a single drug in adequate doses fails to achieve goal blood pressure." Emphasis is placed on the use of two or more medications in many situations -- either as separate drugs or in fixed-dose combinations.

Figure 1. Algorithm for treatment of hypertension, from the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7)[17] BP=blood pressure; ACE=angiotensinconverting enzyme; ARB=angiotensin receptor blocker; CCB=calcium channel blocker; SBP/DBP=systolic/diastolic blood pressure; *see Table 6 of the JNC 7 report Reproduced with permission from JNC 7. JAMA. 2003;289:25602572.[17]

(Enlarge Image)

JNC 7 suggests that in patients with stage 2 hypertension (blood pressures 160/100 mm Hg) "consideration should be given to initiating therapy with two agents, one of which should be a diuretic, i.e., a blocker and a diuretic, an ACE inhibitor, an ARB or calcium channel blocker, and a diuretic. In addition, multiple drugs as initial therapy may be indicated in patients with stage 1 hypertension if they have diabetes, or if there is evidence of renal disease or coronary heart disease. This new report also recognizes compelling reasons for the use of specific medications. For example, in patients with angina or postmyocardial infarction a blocker, or in some instances an ACE inhibitor, should be the drugs of choice (usually along with a diuretic if the patient has hypertension and goal blood pressures are not reached with the blocker alone). In heart failure and hypertension the use of an ACE inhibitor or ARB or a blocker along with a diuretic is clearly indicated. In some cases, the use of an aldosterone antagonist may be necessary to control symptoms. In patients with diabetic nephropathy, an ACE inhibitor or an ARB is the medication of choice, but it is often necessary in these patients to use a diuretic to achieve goal blood pressure. The report notes that the use of an ACE inhibitor or an ARB in a treatment program compared with a regimen that does not include these agents may reduce the occurrence of new-onset diabetes. The JNC 7 report bases its conclusions on more data than were available for any of the other JNC reports; however, some of the conclusions are similar, i.e., a thiazide diuretic should remain a preferred initial therapy in a majority of patients. Other drugs should be considered if there are contraindications or intolerance to the diuretic. Other medications should be added if goal blood pressure is not achieved. As noted, emphasis is placed on multidrug therapy as possible first-step treatment. This is an effective way to treat many hypertensives. In addition, despite some arguments to the contrary, abundant data have demonstrated that when a specific algorithm or treatment plan is followed, results are better than when some guidance is not provided.

Blood Pressure Treatment Goals

Trial results have indicated that even patients with less severe degrees of hypertension (stage 1) (140-159/90-99 mm Hg) -- even without comorbidities -- should be treated. Goal levels in specific subgroups of patients, e.g., diabetics, patients with renal disease, etc., should be set at levels lower than previously recommended (<130/80 mm Hg). If followed by a majority of physicians, the JNC 7 treatment recommendations should help to reduce the number of "resistant" hypertensives in the United States and should result in increasing numbers of patients with controlled blood pressure. Present levels of control at 30%-35% can be increased significantly if lifestyle modifications and medication are used appropriately. The JNC 7 updates information on compliance-adherence of physicians and patients. This initial publication of the JNC 7 in JAMA represents an executive summary or express version. It is short and succinct and will be more helpful to family practitioners than previous JNC reports that were, in many cases, too long and detailed. The longer version of the JNC 7 will be published in the future. This will provide physicians and health care professionals who are interested with more details of the trials and studies on which the committee's report is based. The medical community should be reassured that those of us who participated in the writing of this

report were guided by evidence and while some individuals may not agree with all of the JNC 7's conclusions, the report reflects scientifically validated information.

References
1. Joint National Committee. Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. A cooperative study. JAMA. 1977;237: 255-261. 2. Joint National Committee. The 1980 report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1980;140: 1280-1285. 3. Joint National Committee. Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1984;144:1045-1057. 4. Joint National Committee. Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC IV). Arch Intern Med. 1988;148: 1023-1038. 5. Joint National Committee. Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1993;153:154-183. 6. Joint National Committee. Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157: 2413-2446. 7. Moser M. Treating hypertension: calcium channel blockers, diuretics, blockers, ACE inhibitors: is there a difference? J Clin Hypertens (Greenwich). 2000;2(5):301-304. 8. Moser M. Clinical Management of Hypertension. 6th ed. Caddo, OK: Professional Communications; 2002. 9. ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs. chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2000;283:1967-1975. 10. Wing LMH, Reifel CM, Ryan P, et al. A comparison of outcomes with angiotensin converting enzyme inhibitors and diuretics for hypertension in the elderly. Australian National Blood Pressure Study 2. N Engl J Med.2003;348:583-592. 11. Hansson L, Zanchetti A, Carrutyers SG, et al. Effects of intensive blood pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. The Hot Study Group. Lancet. 1998;351:1755-1762. 12. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in patients with Nephropathy Due to Type 2 Diabetes (IDNT). N Engl J Med. 2001;345:851-860. 13. Agodoa L, Appel L, Bakris G, et al. Effect of ramipril vs. amlodipine on renal outcomes in hypertensive nephrosclerosis. African American Study of Kidney Disease (AASK): a randomized controlled trial. JAMA.2001;285:2719-2728. 14. Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint Reduction in Hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359: 995-1003. 15. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy (RENAAL). N Engl J Med. 2001;345:861-869. 16. Moser M, Hebert P, Hennekens CH. An overview of the meta-analyses of the hypertension treatment trials. Arch Intern Med. 1991;151:1277-1279. 17. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 report. JAMA. 2003;289:2560-2572. 18. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet. DASH-Sodium Collaborative Research Group. N Engl J Med.2001;344(1):3-10.