Aggressive hypertension management in patients of advancing and advanced age.

Abstract: Many older patients are not being aggressively managed for hypertension. Healthcare providers are often hesitant to start or even aggressively titrate antihypertensive medication, especially in the aged. Multiple studies have demonstrated that morbidity and mortality can be significantly reduced by appropriate intervention in all age groups. There are some clinical situations, however, where the provider must approach cautiously, such as in patients with a wide pulse pressure or those with a propensity toward adverse reactions. The data are clear that in the United States, undertreatment, rather than overtreatment, appears to be the issue. This article reviews studies that support the aggressive treatment of hypertension. The nuances of aging, which often influence the healthcare provider's treatment decisions, are also discussed. Suggestions for reasonable approaches to these difficult cases will be considered.

Key Words: hypertension, aging, antihypertensive therapy, isolated systolic hypertension, J-curve

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Hypertension in the elderly population is rarely managed aggressively. This may be due to poor patient understanding regarding the significance of hypertension, or to the fact that healthcare providers are often hesitant to start or aggressively titrate antihypertensive medication in their older patients.

Although several studies have documented the increased mortality and morbidity risks in older hypertensive patients, (1-4) only about 70% of people with hypertension are aware of their condition, and of those, only 59% are actually being treated, while 34% are under control. (5) This is a very disturbing finding, considering the high prevalence of congestive heart failure and kidney failure, especially in the southeastern United States. (6)

Recent studies confirm the validity of aggressive hypertension management in older people, with reports of significant long-term benefits. (7) Treatment reduces the risk of stroke by 35-40%, myocardial infarction by 20-25%, and congestive heart failure by 50% or more. (8) Overall, in the very old, there appeared to be no benefit from hypertensive treatment in regards to death from cardiovascular events or all causes, probably because of the relatively short life expectancy, but much can be gained by reducing morbidity. Consequently, even advanced elderly patients should be provided treatment in an effort to improve quality of life, and blood pressure management should always include lifestyle modification, ven in the aging population. Wong and Wong have demonstrated that there is good evidence to support effective blood pressure reduction through a variety of conservative measures eration of dietary sodium, and decreased alcohol intake, in combination with pharmacological therapy. (9)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (10) was a study designed to incorporate a representative cross section of patients that physicians treat; those with at least one other concomitant risk factor. This study could have provided an excellent guideline for alternative drug selections for hypertensive treatment, but unfortunately was prematurely discontinued. The researchers' recommendation that alpha blockers not be utilized as monotherapy limited many physicians who once customized hypertensive treatment for patients with benign prostatic hypertrophy by utilizing alpha blockade (doxazosin).

Several studies have documented the deleterious effect of isolated systolic hypertension and the benefits of treating it in older people. The Systolic Hypertension in the Elderly Program (SHEP) trial, (11) which had over 4,000 participants, randomized patients ages 60 and over to receive either chlorthalidone (with the potential addition of atenolol), or placebo. The systolic pressures ranged from 160-219 mm Hg, with an average blood pressure of 170 mm Hg. After 5 years of followup, the placebo group was found to have an average blood pressure of 155/72 mm Hg compared to the treatment group, which had an average of 143/68 mm Hg. The 5-year absolute benefit was noted to have prevented 30 strokes and 55 myocardial infarctions per 1000 treated. The Systolic Hypertension in Europe (Syst-Eur) (12) and Systolic Hypertension in China (Syst-China) trials, (13) which were conducted in Europe and China as the SHEP trial was coming to its conclusion, revealed similar findings. These trials utilized the long-acting calcium channel blocker nitrendipine and included the potential addition of an angiotensin-converting enzyme inhibitor or hydrochlorothiazide. Interestingly, these two trials were being conducted in 1995, when calcium channel blockers were reported to possibly increase mortality. (14,15) These two trials revealed that there was no increased risk of morbidity or mortality with use of a long-acting dihydropyridine calcium channel blocker in hypertensive patients. Additionally, it was estimated that over a 5-year period, diabetic patients had further reductions of cardiovascular morbidity and mortality. The findings of these three studies appear to negate the hypothesis that coronary artery disease is precipitated by vigorously lowering diastolic blood pressure.

Elderly patients with isolated systolic hypertension should attempt to maintain a systolic blood pressure of about 140 mm Hg. However, caution should be exercised if the diastolic pressure falls below 65 mm Hg. Debate continues regarding the significance of the J-curve in diastolic pressure, which appears to indicate an increased risk of adverse events when the pressure is lowered beyond a certain level. There is evidence to both support and reject the possibility of a J-curve type of effect. (16-19) Until more concrete evidence becomes available, consideration should be given to less aggressive treatment in those patients with rigid arteries that may exhibit a wide pulse pressure, as they may be adversely affected by aggressive treatment. This is especially significant if medication is given at night because of the normal reduction of blood pressure in early sleep. In fact, one may need to settle for less than ideal reductions in systolic pressure in order to keep the diastolic at an acceptable level.

The possibility of overtreatment warrants the need to step back and re-evaluate the treatment of patients who complain of lightheadedness, dizziness, or "just not feeling well." Ambulatory blood pressure readings can be quite helpful in the evaluation of patients with elevated blood pressure readings in the office, but who are suspected of having normal pressures otherwise. Ambulatory readings can also be helpful in determining the efficacy of hypertensive medication and correlate more closely to target organ damage than office readings. (20) Furthermore, instead of relying solely on clinic readings, if a patient prefers not to utilize an ambulatory monitor, prognostic accuracy can be improved by home readings. (21) In addition, if home readings are to be utilized for medication adjustments, it is important to validate the patient's readings by observing their technique on their own equipment. It is also recommended that the healthcare provider calibrate the patient's blood pressure monitor to ensure the most accurate reading possible.

When intensive management is pursued, one must be cognizant of the possibility of indigenous postural or post-prandial hypotension that can be seen in the aged population. Antihypertensive medication in elderly patients should be initiated on low doses with a slow gradual titration, and medication should be tailored to the patient's concomitant disorders or diseases (Table). For example, patients with recurrent calcium nephrolithiasis may benefit from a thiazide diuretic or indapamide to treat both the hypertension and prevent future calculi if they are a hyperexcretor of calcium. Although certain beta blockers can now be used in patients with a history of congestive heart failure, they should only be initiated at very small doses and in well compensated patients. Cardioselective beta blockers at low doses in patients with reactive lung disease who are recovering from myocardial infarction should be considered. (22) Other issues include use of a short-acting diuretic, such as furosemide, which should be avoided as an antihypertensive treatment unless it will be used two or three times a day. Torsemide may be a better choice because of its longer half-life. Gingival hyperplasia is a complication of calcium channel blockers and may become a problem in many patients, especially in those wearing partial dentures.

The healthcare provider should be aware of possible patient-initiated interventions that may be inhibiting good blood pressure control. For example, some over-the-counter medications, such as nonsteroidal anti-inflammatory drugs (NSAID), can cause salt retention or drug interactions. Specifically, thiazide diuretics, beta blockers, angiotensin-converting enzyme inhibitors, and alpha blockers are less effective in some patients who use NSAIDs. (23,24) Other preparations that may have a significant effect on the blood pressure include "natural" preparations such as saw palmetto for prostate trouble or ma huang for respiratory ailments or as an appetite suppressant. Alcohol can also have an effect on hypertension management. Since alcohol has a pressor effect, drinking more than one ounce a day may reduce the effectiveness of antihypertensive therapy. Inquiries should be made into the patient's utilization of sympathomimetics, such as those found in cold medicines, as they may blunt the hypotensive effect of several medications.

The efficacy of treatment should be followed closely. It is not appropriate to initiate medication without prompt and regular follow up. Two weeks should be allowed before followup if a long-acting antihypertensive is initiated, and probably no later than one or two months. If blood pressure is in stage 2 (systolic [greater than or equal to] 160 mm Hg or diastolic [greater than or equal to] 100 mm Hg) or if there are comorbid problems, then they should return for reassessment at intervals of approximately 1 to 3 weeks. (5) Close follow up allows the healthcare provider to titrate medication slowly, or make prompt adjustments, as the need arisen. It also provides an opportunity for further counseling and may help curtail noncompliance or adherence issues.

Probably the most challenging task for the healthcare provider, short of the patient's financial constraints, is that of convincing asymptomatic older patients that there is a need for pharmacologic intervention. Foremost, counseling the patient on diet and exercise is still very important in this age group. The elderly are often salt sensitive and should be encouraged to reduce salt intake or utilize a salt substitute. Many patients, especially those raised in the South, were brought up in homes with food laden in salt, and the provider should keep in mind that salt reduction may not be an easy accomplishment. Patients should be encouraged to use spices and herbs in lieu of salt. Providing patients with reassurance that they will be monitored closely and not abandoned is an approach that is likely to assist in easing fears.

In summary, healthcare providers should be aggressive in their approach in treating the aging population, as studies have shown that most patients are undertreated as opposed to overtreated. Medication can be tailored for concomitant medical problems and medication should not be withheld when the benefits of doing so may outweigh any potential preconceived side effect. Helping patients understand why intervention is necessary and being sensitive to the patient's upbringing and culture will help with adherence and compliance issues. Being thoroughly informed of potential side effects and treatment options provides optimal care for the patient. Most importantly, healthcare providers should be well aware of specific problems and adverse effects associated with certain antihypertensives in order to provide the best available treatment for their patients.

References

1. Kaplon NM. Clinical Hypertension. Baltimore, Williams & Wilkins, 1986:2.

2. Castelli WP. Epidemiology of coronary heart disease: the Framingham study. Am J Med 1984;76:4.

3. Neaton JD, Wentworth D, Sherwin R, et al. Comparison of 10 year coronary and cerebrovascular disease mortality rates by hypertensive status for black and non-black men screened in the Multiple Risk Factor Intervention Trial (MRFIT). Circulation 1989;80 (suppl 2):II300.

4. The sixth report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure (JNC VI). Arch Intern Med 1997;157:2413-2414.

5. The seventh report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure. The JNC Report. JAMA 2003;289;2560-2572.

6. Hall WD, Ferrario CM, Moore MA, et al. Hypertension-related morbidity and mortality in the southeastern United States. Am J Med Sci 1997;313:195-206.

7. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality. Lancet 2002;360:1903-1913.

8. Neal B, MacMahon N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration Lancet: 2000:356:1955-64.

9. Wong J, Wong S. Evidence-based care for the elderly with isolated systolic hypertension. Nurs Health Sci 2005 1:67-75.

10. Major cardiovascular events in hypertensive patients randomized to doxazosin vs. chlorthalidone: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). ALLHAT Collaborative Research Group. JAMA 2000;283:1967-1975.

11. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-3264.

12. Staessen JA, Fagard R, Thijs L. et al, for the Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Randomized double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. Lancet 1997;350:757-764.

13. Liu L, Wang JG, Gong L, et al. for the Systolic Hypertension in China (Syst-China) Collaborative Group. Comparison of active treatment and placebo for older patients with isolated systolic hypertension. J Hypertens 1998;16:1823-1829.

14. Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with coronary heart disease. Circulation 1995;92:1326-1331.

15. Psaty BM, Heckbert SR, Koepsell TD, et al. The risk of myocardial infraction associated with antihypertensive drug therapies. JAMA 1995;274:620-625.

16. Cruickshank J. The J-curve in hypertension. Curr Cardiol Rep 2003;5:441-452.

17. Hansson L. Treatment of hypertension and the J curve. J Clin Hypertens 1999;1:136-140.

18. Kaplan N. J-curve not burned off by HOT study. Hypertension Optimal Treatment. Lancet 1998;351:1748-1749.

19. Simon G, Chesler E. Understanding and managing isolated systolic hypertension in the elderly. Am J Geriatr Cardiol 1998;7:35-39.

20. Verdecchia P. Prognostic value of ambulatory blood pressure. Hypertension 2000;35:844-851.

21. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of "masked hypertension" detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA 2004;291:1342-1349.

22. Glaab T, Weiss T. Use of beta blockers in cardiovascular disease and bronchial asthma/COPD. Internist 2004;45:221-227.

23. Johnson A. NSAIDs and increased blood pressure. Drug Safety 1997;17:277-289.

24. Polonia J. Interaction of antihypertensive drugs with anti-inflammatory drugs. Cardiology 1997;88(suppl. 3); 47-51.

I love quotations because it is a joy to find thoughts one might have,
beautifully expressed with much authority by someone recognized wiser
than oneself.
--Marlene Dietrich

Stephanie C. Leeper, MD, FACP 

From the Department of Internal Medicine, East Tennessee State University, Quillen College of Medicine, Johnson City, TN.

Accepted April 13, 2005.

Stock holdings as of February 22, 2005: Johnson & Johnson COM (JNJ) 100 shares, King Pharmaceutical (KG) 400 shares, Medco Health Solutions Inc (MHS) 27 shares, Merck & Co (MRK) 238 shares.

Reprint requests to Stephanie C. Leeper, MD, FACP, TTUHSC, Regional Dean's Office, 1400 S. Coulter, Amarillo, TX 79106. Email: [e-mail]

RELATED ARTICLE: Key Points

* The treatment of hypertension reduces the risk of morbidity and mortality, even in those with advancing age.

* Nuances of healthy versus unhealthy aging often modulate the choice of therapy.

* Treatment should be tailored to the aging patient's concomitant diseases.

* Over the past several years, there has been new thought about old drugs that once were considered contraindicated in certain diseases or disorders.

* Healthcare providers should have a thorough understanding of potential adverse reactions that can occur when utilizing antihypertensive therapy.

Table. Examples as to how antihypertensive medication can be
tailored (a)

65 y/o male with elevated
urine microalbumin                  ACEI and/or ARB

67 y/o female recovering from MI    ACEI/beta blocker
75 y/o male with congestive heart   ACEI/ARB/thiazide/aldosterone
  failure                             antagonist/beta blocker
65 y/o male with BPH symptoms       Alpha blocker (but not as
                                      monotherapy)
69 y/o female with osteoporosis     Thiazide
66 y/o male with recurrent calcium  Thiazide/indapamide
  nephrolithiasis
70 y/o with essential tremor        Beta blocker
65 y/o female with migraines        Beta blocker or calcium channel
                                      blocker
68 y/o male with chronic renal      Torsemide
  failure
66 y/o male with left ventricular   ACEI/beta blocker/calcium channel
  hypertrophy                         blocker

(a) ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II
receptor antagonist; MI, myocardial infarction; BPH, benign prostetic
hypertrophy.