Who Do We Look to for Guidance?

Geriatric cardiologists as a group of providers are facing an epidemiologic shift. By the year 2060, people living into their 8th, 9th and 10th decade of life will dominate our patient population. Of those individuals born today in the U.S., it may well be that upwards of 50% of persons will reach their 100th year.¹ Given a high prevalence of hypertension (up to 80% of those >60 years old) and its rising incidence over time, treatment of hypertension in this growing elderly population will be challenging.² The economic burden of hypertension is well established, the result of adverse effects on cardiovascular outcomes including heart failure, myocardial infarction, and stroke.^3,4 The effective and safe management of hypertension in this elderly cohort will be critical, both to improve patient outcomes and to reduce health care costs.

Treating hypertension in the elderly was somewhat controversial until significant cardiovascular benefits were seen in studies including the UK Prospective Diabetes Study (UKPDS), the Systolic Hypertension in the Elderly Program (SHEP), the Systolic Hypertension in China (Syst-China) trial, the Systolic Hypertension in Europe trial (Syst-Eur), the Stroke Prevention Trial in Sickle Cell Anemia (STOP), and the Hypertension in the Very Elderly Trial (HYVET) (the latter study in patients >80 years of age). It has also become apparent that treatment may be subtly beneficial in reducing the incidence of dementia compared to placebo.⁵ Interestingly, all of these trials included patients with baseline mean systolic pressures of 160 mm Hg or more, making it more difficult to determine target blood pressures (BPs) and anticipate benefits when an elderly patient presents with systolic blood pressure (SBP) in the 140-159 mm Hg range.

Previous guidelines including those produced by the Seventh Joint National Committee (JNC 7) focused on expert consensus recommendations, but with the recent publication of Eight Joint National Committee (JNC 8) guidelines in 2014, the authors moved towards a "best available evidence" approach as the gold standard. While this is ultimately seen as beneficial, this change has led to a subtle fragmentation of the overall message from the major societies. This is because of small differences in targets and therapy recommendations from the JNC 8, the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines from 2013, and the American Society of Hypertension (ASH) guidelines published in 2014.

Despite these challenges, effective treatment of hypertension is possible using the existing guidelines and a basic knowledge of the principles of targeted geriatric care.

What Are the Risks?

Elderly patients, in comparison to younger cohorts, have a higher baseline cardiac risk profile and benefit more than their counterparts from even modest reductions in blood pressure.⁶ In patients over the age of 60, isolated systolic hypertension is more common, and SBP is a better predictor of cardiovascular risk when compared to diastolic blood pressure (DBP).⁷ Data from The Second National Health and Nutrition Examination Survey (NHANES II) and the SHEP trial revealed that in patients over the age of 65 years of age, there is a linear relationship between cardiovascular risk, particularly stroke, and increasing SBP (the absolute stroke risk in the placebo group of the SHEP trial was 8.2% over five years, compared to 5% in the treatment arm).^8,9 Paradoxically, when DBP dropped below 65 mm Hg, there was an enhanced risk of mortality, possibly the result of decreased tissue perfusion and increased cardiovascular risk (this is known in the hypertension literature as the "J-curve" phenomenon).¹⁰ However, this risk may not be the result of reaching a lower target DBP with therapy, but instead may be due to less compliant vessels and more comorbidities in these patients.

Making the Diagnosis

As reported by JNC 8, the upper limit of normal for SBP is considered to be 140 mm Hg at all ages. Checking BP in both arms to assess for subclavian stenosis from atherosclerotic vascular disease is imperative, and using the highest value as the real BP is the standard of care. Three different pressure measurements taken on more than two office visits is sufficient, and can reliably predict natural variations in BP.¹⁰ Alternatively, checking BP at home can be done with a clinic-calibrated arm cuff, though errors in measurement and reproducibility can confound the clinical picture.¹⁰ When BP is high at home but not in the office, the so-called "masked hypertensive," the diagnosis of hypertension can be more challenging to make. Masked and situational hypertension (previously known as "white coat hypertension") must always be considered, and in addition to home and office BP measurements, 24-hour ambulatory BP monitoring may be helpful in selected patients. However, ambulatory BP monitoring is not always readily available, and it is only reimbursed by Medicare when used in cases of suspected white coat hypertension.¹¹

In patients with resistant hypertension (uncontrolled BP despite compliance with three drugs of different classes including a diuretic), the differential diagnosis should include renal artery stenosis and hyperaldosteronism. These entities, however, are less prevalent in the elderly. Pseudo-hypertension is more common and should be considered early. Pseudo-hypertension is the result of age-related calcific arteriosclerosis that causes incompressible peripheral arteries. Essentially, the BP cuff is unable to measure the true intraluminal BP. A standing BP can be helpful in distinguishing pseudo-hypertension from true hypertension. For example, if a "resistant" patient is on several drugs and reporting symptoms of orthostasis, an elevated resting and standing BP would suggest pseudo-hypertension. Being aware of this entity in the elderly is important since unnecessary therapy escalation can lead to falls or functional impairment, causing significant disability in this population.

Screening for frailty can also help identify patients at higher risk for these types of adverse clinical outcomes. The degree of frailty can also help guide treatment targets as a higher target may be more appropriate in order to avoid iatrogenic falls, fatigue, or significant disability. The American Geriatrics Society recommends a criterion-based screening assessment using slow gait speed, poor grip strength, and unexplained weight loss or exhaustion as markers of frailty.^12,13,14 While this assessment for frailty adds additional time to the clinic evaluation, it could be performed by a nurse or mid-level provider.

Applying Geriatric Principles Is Essential to Everyday Practice

Remembering to treat patients conservatively is increasingly important with age. Elderly patients with similar BPs compared to their younger counterparts have a lower baseline cardiac output, higher peripheral resistance, wider pulse pressure, lower intravascular volume, and lower renal blood flow.^1,15,16 It can be inferred that because of these basic physiologic changes, treating the two groups similarly could be detrimental to the elderly patients. Also, understanding extraneous factors including psychosocial barriers, direct patient cost, comorbidities, and compliance history is important to achieve the maximal benefit of any prescribed regimen.

Before initiating medical therapy, it is important to encourage therapeutic lifestyle changes. Over time, taste sensitivity is reduced and the elderly often paradoxically increase salt intake, so a recommendation to reduce salt intake should not be forgotten. The combination of non-pharmacologic therapies, such as regular aerobic exercise, modest weight reduction in the obese, dietary sodium restriction, and treatment of sleep apnea, can make a large difference in the medical therapy required by elderly patients, and spare them from potential adverse effects of compounded pharmacotherapy.¹⁷

What Should Be Our Goals When It Comes to Medical Management?

Specific target recommendations differ depending on your choice of guideline, though generally reducing the SBP below 150 mm Hg in relatively fit elderly patients is reasonable and supported by JNC 8 and the 2013 ESC/ESH guidelines.^18,9 Both guideline groups agree that in the setting of diabetes or chronic kidney disease (CKD) the target should be less than 140 mm Hg.^18,19 In the absence of CKD or diabetes, the JNC 8 guideline did not recommend an SBP goal <140 mm Hg in elderly patients, even those with known atherosclerotic vascular disease. However, based on recent results published from a post-hoc analysis of the INVEST trial, it may be reasonable to push the SBP level below 140 mm Hg in fit elderly patients with ischemic heart disease.²⁰ The ESC/ESH guidelines do support an optional systolic blood pressure goal <140 mm Hg for any fit elderly patient <80 years of age.¹⁹ For frail patients (some combination of reduced gait speed, reduced grip strength, weight loss or exhaustion as defined by the American Geriatrics Society), treatment targets may need to be individualized. For example, reducing BP by an average of 20 mm Hg is a reasonable alternative if it is felt that reducing systolic pressure to even <150 mm Hg will require multiple agents at high doses.¹²

What Drugs Should We Consider?

When it is time to initiate medical therapy, consideration should be given to the following variables: 1) the frailty of the patient, 2) their ability to follow instructions, 3) the complexity of their current medication regimen, and 4) supporting care (i.e., spouses and family). Carefully review the patient's medication list and stop or reduce nonsteroidal anti-inflammatory drugs (NSAIDs) and decongestants due to their propensity for causing hypertension. Reviewing the patient's electrolytes and renal function prior to initiation of therapy is prudent, particularly if considering angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or aldosterone antagonists.

Antihypertensive doses should start low, and BP should be lowered gradually. A strategy of initiating two drugs when the baseline BP is >20 mm Hg above goal should probably be avoided in elderly patients because of an increased risk for hypotension.

Results from the Medical Research Council (MRC) trial would suggest that unless there is another primary indication, initiating a beta-blocker as first-line therapy might actually worsen cardiovascular outcomes in those over 60 years old²¹ Furthermore, beta-blockers are not recommended as initial therapy in the JNC 8 guidelines.¹⁸ ACE inhibition is reasonable, especially if there is concurrent coronary artery disease, diabetes, proteinuria CKD, or heart failure. While the JNC 8 guidelines have no preference among ACEIs, calcium channel blockers, or diuretics as the initial medication, the ESH/ESC guideline recommends a calcium antagonist or diuretic in elderly patients with isolated systolic hypertension.^18,19 Robust randomized evidence, specifically the The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) data, would suggest that low-dose daily chlorthalidone is the most effective agent in this population.²² However, consideration of the patients free water intake and comorbid alcohol intake is important due to a real risk of hyponatremia with this medication. Hypokalemia is also relatively common with thiazide diuretics, and there are small, adverse effects on lipids and glucose levels. In a primarily elderly Scandinavian population, the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) study showed significant overall mortality benefit in subjects aged >60 years when using a combination regimen of calcium channel blocker and ACEI, when compared to a beta-blocker and thiazide regimen.²³ For these reasons, the authors of this article suggest a long-acting dihydropyridine calcium channel blocker as the initial agent for the elderly. Combination therapy may well be necessary in follow-up, and the authors recommend adding an ACEI or low-dose thiazide diuretic to the calcium channel blocker.

Conclusions

• Our elderly population is growing rapidly, and along with a high prevalence of hypertension, morbidity and mortality from hypertension is expected to increase.
• Treatment is clearly demonstrated to be beneficial in this population.
• Make the diagnosis with serial measurements, at least once checking BP in both arms; look for cases of pseudo-hypertension, masked hypertension, and situational hypertension, and, if available, consider ambulatory BP measurements to help identify situational hypertension.
• Exclude secondary causes in cases of resistant hypertension.
• Consider potential adverse effects of your treatment, especially in frail patients (as determined by slow gait speed, poor grip strength, signs of functional impairment, weight loss, or exhaustion).
• If non-pharmacologic interventions have not been successful at lowering blood pressure to target, we recommend a long-acting dihydropyridine calcium channel blocker, unless there is comorbid diabetes, ischemic heart disease, or CKD, in which case an ACEI is preferred.
• Monitor BP frequently after therapy is initiated, and include home measurements in your decision making. In follow-up, ask questions about low tissue perfusion, orthostasis, and falls.
• Target an initial SBP below 150 mm Hg, and a DBP below 90 mm Hg. For patients with diabetes or CKD, the goal SBP is <140 mm Hg. If there is concurrent ischemic heart disease without diabetes or CKD, and the patient is fit, also consider reducing the systolic pressure below 140 mm Hg. In a frail patient, treatment and BP goals should be individualized.
• Be wary of the "lower is better" approach given the J-curve effect and a possible increase in adverse events at very low DBPs.

References

1. Chaudhry, KN, Chavez P, Gasowski J, et al. Hypertension in the elderly: some practical considerations. Cleve Clin J Med 2012;79:694-704.
2. Vasan RS, Beiser A, Sheshadri S, et. al. Residual lifetime risk for developing hypertension in middle aged women and men: The Framingham Heart Study. JAMA 2002;287:1003-10.
3. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21–181.
4. Vasan, Ramachandran S, Larson M, et. al. Impact of high-normal blood pressure on the risk of cardiovascular disease. N Engl J Med 2001;345:1291-7.
5. Forette F, Seux ML, Staessen JA, et. al. Prevention of dementia in randomized double blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet 1998;352:1347-51.
6. Wang JG, Staessen JA. Antihypertensive drug therapy in older patients. Curr Opin Nephrol Hypertens 2001;10:263-9.
7. Franklin SS, Larson MG, Khan SA, et al. Does the relation of blood pressure to coronary heart disease risk change with aging? The Framingham Heart study. Circulation 2001;103:1245-9.
8. Prevention of Stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results from the Systolic Hypertension in the Elderly Program (SHEP) SHEP cooperative research group. JAMA 1991;265:3255-64.
9. Brown, David W, Giles Wayne H, et al. Blood pressure parameters and risk of fatal stroke, NHANES II mortality study. Am J Hypertens 2007;20:338-41.
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11. Centers for Medicare & Medicaid Services. National Coverage Determination (NCD) for Ambulatory Blood Pressure Monitoring (20.19) (CMS website). 2003. Available at: http://www.cms.gov/transmittals/downloads/R168CIM.pdf. Accessed 11/11/2014.
12. Abellan Van Kan G, Rolland Y. et. al. The assessment of frailty in older adults. Clin Geriatr Med 2010;26:275-86.
13. Pacala JT, Sullivan GM, eds. Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine. 7th ed. New York, NY: American Geriatrics Society; 2010.
14. Odden MC, Prealta CA, et al. Rethinking the association of high blood pressure with mortality in elderly adults: the impact of frailty. Arch Intern Med 2012;172:1162-8.
15. Boss GR, Seegmiller JE. Age-related physiological changes and their clinical significance. West J Med 1981;135:434-40.
16. Messerli FH, Sundgaard-Riise K, Ventura HO, et. al. Essential hypertension in the elderly: haemodynamics, intravascular volume, plasma renin activity, and circulating catecholamine levels. Lancet 1983;2:983-6.
17. Whelton PK, Appel LJ, Espeland MA, et al. Sodium restriction and weight loss in the treatment of hypertension in older persons: a randomized control trial of nonpharmacologic interventions in the elderly (TONE) TONE Collaborative Research Group. JAMA 1998;279:839.
18. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311:507-20.
19. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. J Hypertens 2013,31:1281-357.
20. Bangalore, S, Gong Y, Cooper-DeHoff RM, et al. 2014 Eighth Joint National Committee panel recommendation for Blood pressure targets revisited: Results from the INVEST study. J Am Coll Cardiol 2014;64:784-93.
21. Medical Research Council trial of treatment of hypertension in Older Adults: principal results: MRC working party. BMJ 1992;304:405-12.
22. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: he Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981-97.
23. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian cardiac outcomes trial- Blood pressure lowering arm (ASCOT-BPLA): A multicentre randomized control trial. Lancet 2005;366:895-906.

Keywords: Geriatrics, Aged, Anemia, Sickle Cell, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Anti-Inflammatory Agents, Non-Steroidal, Antihypertensive Agents, Arteries, Biomedical Research, Blood Pressure, Blood Pressure Monitoring, Ambulatory, Hypertension, Hypotension, Calcium Channel Blockers, Cardiac Output, Cardiovascular Diseases, Chlorthalidone, Comorbidity, Constriction, Pathologic, Coronary Artery Disease, Dementia, Diabetes Mellitus, Dihydropyridines, Diuretics, Dizziness, Drinking, Electrolytes, Exercise, Gait, Glucose, Hand Strength, Heart Failure, Hyperaldosteronism, Hypokalemia, Hyponatremia, Iatrogenic Disease, Lipids, Masked Hypertension, Mineralocorticoid Receptor Antagonists, Medicare, Myocardial Infarction, Prospective Studies, Proteinuria, Renal Artery Obstruction, Renal Circulation, Renal Insufficiency, Risk Factors, Sleep Apnea Syndromes, Sodium, Sodium Chloride Symporter Inhibitors, Sodium, Dietary, Spouses, Thiazides, Vascular Resistance, Weight Loss, White Coat Hypertension

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