A nonsmoking patient who apparently visits the gym with some
regularity presents with a case of the flu and is incidentally noted
to have a blood pressure reading of 139/88 mm Hg. According to the
new JNC 7 hypertension guidelines, this individual should be put on
a therapeutic regimen consisting of:
1. A low-dose ACE inhibitor for 2 months, then retesting to consider
up-titration
2. A diuretic only, with addition of a beta-blocker after 6 months
if blood pressure doesn't fall to 120/80 mm Hg
3. A diuretic plus a low-dose calcium channel blocker
4. Lifestyle counseling, emphasizing
possible dietary modifications
The JNC Guidelines, Past and Present
The basic treatment goals in JNC 7 are actually unchanged from those
of JNC 6, ie, the reduction of cardiovascular and renal morbidity
and mortality. The report emphasizes that the key message for hypertensive
patients is that they will benefit from blood pressure lowering, whether
it occurs as a result of lifestyle changes or drug therapies, or,
as in most cases, from a combination of the 2 approaches. For patients
with uncomplicated hypertension, the goal blood pressure is < 140/90
mm Hg. In patients with comorbidities such as diabetes or chronic
kidney disease, a goal blood pressure of < 130/80 mm Hg is recommended.
The most significant change from JNC 6 is the new category, prehypertension,
classified as SBP 120-139 mm Hg or DBP 80-89 mm Hg. It is estimated
that about 22% (approximately 46 million) of the adult population
falls into the prehypertension category. It is important to remember
that for these individuals, JNC 7 recommends only lifestyle changes
to prevent progression to actual hypertensive disease. These preventive
measures include weight reduction, exercise, adoption of the Dietary
Approaches to Stop Hypertension (DASH) eating plan,[12] salt reduction,
and limiting alcohol intake. Quitting smoking is also recommended
for overall cardiovascular health.
Antihypertensive Therapy
The first-step therapy for all prehypertensive individuals is lifestyle
modification, and indeed, for all levels of hypertension, it is important
to incorporate changes in unhealthy lifestyle that aggravate the underlying
pathologic physiology. However, it has always been recognized that
once blood pressure rises above the widely recognized threshold of
140/90 mm Hg, it will be necessary to introduce a program of medical
treatment.
Monotherapy has been the traditional route to control of hypertension
for many years. However, despite the availability of various classes
of antihypertensive agents that lower blood pressure by different
primary actions, the treatment of hypertension remains a difficult
task. This is especially true since the current goal of treatment
is the normalization of both SBP and DBP. However, in the patients
who are the most likely to be hypertensive -- those older than 50
-- elevated SBP is more important as a CVD risk factor than DBP, and
yet in the majority of patients SBP has been considerably more difficult
to control than DBP.
Thus, perhaps because of the highly heterogeneous character of essential
hypertension, monotherapy often proves insufficient to normalize blood
pressure, and, as seen in virtually all recent clinical trials, culminating
with ALLHAT, the result is that the use of only 1 drug to reduce arterial
pressure is usually successful in only about one third of all patients.
Unfortunately, most of the large clinical trials have historically
concentrated on studying the treatment effects of a single agent vs
placebo or "usual therapy," and thus our knowledge of combination
therapy in the treatment of hypertension is based, to a great extent,
on extrapolation from monotherapy.
The basic premise of monotherapy means increasing the dose of the
chosen agent until the blood pressure levels begin to decrease. Unfortunately,
this may mean raising the dose to levels that can produce toxic side
effects. As a simple rule of thumb for avoiding side effects, the
treating physician should refrain from increasing the dose of monotherapy
drug above that level that controls blood pressure in about half of
the patients. However, the antihypertensive efficacy of a single drug
is often mitigated due to the potential stimulation of compensatory
mechanisms that act to restore the blood pressure to its preset levels.
The result of these considerations is that, given the multifactorial
nature of hypertension, the approach that makes the most therapeutic
sense will be treatment with more than 1 agent or, more importantly,
more than 1 class of agent. By combining medications that act by different
mechanisms, it is possible to gain considerably in terms of antihypertensive
efficacy because of synergistic impacts on the cardiovascular system.
Combination therapy allows the use of lower doses of each antihypertensive
agent, meaning that compensatory stimulation may be diminished, and,
conceivably, the second component of combination may counteract this
stimulation. Furthermore, lower doses of antihypertensive agents are
generally sufficient when used in combination, which accounts for
the excellent tolerability of combination products.
Thus, a low-dose combination of 2 different agents reduces the risk
of dose-related adverse reactions while still allowing sufficient
blood pressure reduction, and this approach continues to be endorsed
by the new JNC 7 guidelines.
References
1. Major Outcomes in High-Risk Hypertensive Patients Randomized to
Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker
vs Diuretic: The Antihypertensive and Lipid-Lowering Treatment to
Prevent Heart Attack Trial (ALLHAT). The ALLHAT Officers and Coordinators
for the ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-3007.
2. Joint National Committee on Prevention, Detection, and Treatment
of High Blood Pressure. The Sixth Report of the Joint National Committee
on prevention, detection, evaluation, and treatment of high blood
pressure. Arch Intern Med. 1997;157:2413-2446.
3. Dahlof B, Devereux RB, Kjeldsen S, et al. Cardiovascular morbidity
and mortality in the Losartan Intervention For Endpoint reduction
in hypertension study (LIFE): a randomized trial against atenolol.
Lancet. 2002;359:995-1003.
4. Wing LMH, Reid CM, Ryan P, et al, for the Second Australian National
Blood Pressure Study Group. A comparison of outcome with angiotensin-converting-enzyme
inhibitors and diuretics for hypertension in the elderly. N Engl J
Med. 2003;348:583-592.
5. US Department of Health and Human Services. JNC 7 Express. The
Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. Available on the
NHLBI Web site at http://www.nhlbi.nih.gov or from the NHLBI Health
Information Center, PO Box 30105, Bethesda, MD 20824-0105. Phone 301-592-8573
or 240-629-3255 (TTY); Fax: 301-592-8563.
6. Chobanian AV, Bakris GL, Black HR, et al. 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.
7. Vasan RS, Larson MG, Leip EP, Kannel WB, Levy D. Assessment of
frequency of progression to hypertension in non-hypertensive participants
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8. United States Department of Health and Human Services Centers for
Disease Control and Prevention. National Health and Nutrition Examination
Survey IV (NHANES IV). 1999-2000 Data Files http://www.cdc.gov/nchs/about/major/nhanes/NHANES99_00.htm
9. United States Department of Health and Human Services Centers for
Disease Control and Prevention. National Health and Nutrition Examination
Survey III (NHANES III)
http://www.cdc.gov/nchs/ about/major/nhanes/nh3data.htm. Accessed
June 20, 2003.
10. U.S. Department of Health and Human Services. Healthy People 2010:
Understanding and Improving Health. 2nd ed. Washington, DC: U.S. Government
Printing Office, November 2000.
11. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective
Studies Collaboration. Age-specific relevance of usual blood pressure
to vascular mortality: a meta-analysis of individual data for one
million adults in 61 prospective studies. Lancet. 2002;360:1903-1913.
12. U.S. Department of Health and Human Services. National Institutes
for Health. Dietary Approaches to Stop Hypertension (DASH). Originally
Printed 1998, Reprinted February 1999, Revised May 2003.
http://www.nhlbi.nih.gov/health/ public/heart/hbp/dash/new_dash.pdf.
Accessed June 20, 2003.
