Treatment targets for hypertension in older persons

Contributed by: Dr. David B. Hogan MD, FACP, FRCPC - View bio

Case

Mrs. BB is an 82-year-old female living at home. She has mild cognitive impairment (MCI) and limited mobility. Her office blood pressure is 162/71. Should she be treated for hypertension? If yes, what would her blood pressure (BP) target be?

SPRINT

After three and a quarter years of therapy, the Systolic Blood Pressure Intervention Trial (SPRINT) showed that treating study participants to a target systolic BP (SBP) of less than 120 mm Hg (i.e., intensive therapy) compared to less than 140 (i.e., standard therapy) resulted in:

• lower SBPs (at the end of year one mean SBP in the intensive therapy group was 121.4 vs mean SBP of 136.2 among those on standard therapy);
• ~25% lower rates of the composite cardiovascular outcome (i.e., nonfatal myocardial infarction, acute coronary syndrome, nonfatal stroke, nonfatal heart failure, death from cardiovascular cause) and all-cause mortality;
• and higher but still infrequent rates of certain serious adverse events (i.e., hypotension, syncope, electrolyte abnormalities, acute kidney injury or renal failure).¹

Injurious falls were rare (2.2% over the course of the study) and did not become more common with intensive therapy.²

The trial enrolled 2,636 community-dwelling individuals who were 75 and older.³ Similar benefits with intensive therapy (that typically required three drugs; on average one more than used with standard therapy) were found in this 75 and older sub-group. The absolute benefits for the composite cardiovascular outcome and all-cause mortality were 1.26%/year and 0.85%/year respectively. While a number of serious adverse effects were more common with intensive therapy, they were not statistically significant. Study measures included gait speed and a 37-item frailty index. The benefits of intensive therapy were seen across all gait speed and frailty (fit, less fit, frail) stratums. A sub-study (SPRINT Memory and Cognition IN Decreased Hypertension (SPRINT MIND) study) examined the effects of therapy on the development of dementia and/or MCI. Preliminary results presented at the 2018 Alzheimer’s Association International Conference showed an insignificant 17% reduction in new dementia cases, a significant 19% decline in MCI ones and a significant decrease in the average growth of cerebral white matter lesions.⁴ The results have not yet been peer-reviewed.

To be included in SPRINT participants had to be a minimum of 50-years-old with an SBP of 130 to 180 and an increased risk of cardiovascular events (e.g., age 75 and older). Exclusion criteria particularly relevant to an older population included one-minute standing BP <110; diabetes mellitus; stroke; cardiovascular event or procedure <3 months; end stage renal disease; symptomatic heart failure within last 6 months or ejection fraction <35%; life expectancy <3 years; the presence of dementia; and residence in a nursing home. It is estimated that about two-thirds of those 75 and older in North America with hypertension would meet SPRINT entry criteria.⁵

Blood Pressure Treatment Targets

SPRINT has led to a reconsideration of BP targets in older patients. Its results indicate that we should be more aggressive in treating hypertension. This is discordant with epidemiological studies that have shown an inverse relationship between SBP and mortality in older adults.^5,6 The latter finding might be explained by reverse causality (i.e., the direction of cause-and-effect is not in the direction assumed) as a terminal decline in blood pressure appears to occur over the last few years of life.⁷

Concerns with more intensive therapy include the possibility of a J-curve phenomenon (risks from too low a BP [e.g., diastolic BP ≤60] as a consequence of antihypertensive drug [AHD] treatment),⁸ polypharmacy and adverse drug effects including cognitive decline and falls. In the Leiden 85-plus cohort study lower BP among those on AHDs was associated with a faster decline in cognitive function⁶ while another study indicated low SBP correlated with greater cognitive decline in older patients with pre-existing cognitive impairment treated with AHDs.⁹ As for falls, AHD initiation and intensification in a database study was associated in the short-term with a higher risk for injurious falls.¹⁰

Recent guidelines provide a range of treatment targets. The 2017 ACC/AHA guidelines recommend an SBP goal of <130 for non-institutionalized ambulatory community-dwelling adults 65 and older with an average SBP of 130+. For those with a high burden of comorbidity and/or limited life expectancy the use of clinical judgment, patient preferences and a team-based approach assessing relative risks/benefits was suggested for deciding on the intensity of BP lowering and medication choice.¹¹ The ACP/AAFP guidelines for patients ≥60 published in 2017 proposed initiating treatment if SBP is persistently ≥150. The treatment target would be <150 unless there is a history of cerebrovascular disease or the patient is at high cardiovascular risk. In those cases the BP target would be <140.¹²

Hypertension Canada guidelines are the most aggressive. Starting in 2017 older age and frailty were removed as treatment considerations, though caution was recommended in treating older institutionalized patients and those with orthosis. For high-risk patients (those who are 75 and older) BP treatment is recommended if SBP is ≥130. It was suggested that a target of ≤120 be considered. ^13,14

Commentaries of these guidelines have focused on the challenges in translating them to “real world” clinical practice. Bavishi et al. stated that, “to lower [systolic] BP of all hypertensive patients uniformly to ≤120 is clearly absurd.”¹⁵ It was noted that SPRINT was stopped early; studies stopped early typically lead to exaggerated estimates of benefit.¹⁶

Concluding Comments: How BP is determined is an underappreciated issue. SPRINT used multiple automated office BP determinations (which is the preferred approach of Hypertension Canada)¹⁴ under ideal circumstances to guide treatment. SBP measured this way may be 5-10 mmHg lower than typical office BPs^5,17, which needs to be considered when implementing into practice recommendations based on SPRINT.^16,18 In addition to reconsidering how sitting BP is measured, routinely checking for a postural drop in BP should be done.¹⁹

At the present time the most defensible approach to managing hypertension in older patients is to tailor therapy to the patient. In those who are healthier, interested and willing to embark on aggressive therapy targeting SBP to ≤120 should be considered. Among those less healthy who have limited life expectancy, those who are institutionalized, experiencing adverse effects and/or not interested in aggressive therapy, a target of ≤150 would be reasonable.¹⁹

References

1. The SPRINT Research Group: A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015, 373: 2103-16.
2. Sink KM, Evans GW, Shorr RI, Bates JT, Berlowitz D, et al: Syncope, Hypotension, and Falls in the Treatment of Hypertension: Results from the Randomized Clinical Systolic Blood Pressure Intervention Trial. J Am Geriatr Soc 2018, 66: 679-86.
3. Williamson JD, Supiano MA, Applegate WB, Berlowitz DR, Campbell RC, et al: Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged ≥ 75 Years – A Randomized Clinical Trial. JAMA 2016, 315: 2673-82.
4. Kjeldsen SE, Narkiewicz K, Burnier M, Oparil S: Intensive blood pressure lowering prevents mild cognitive impairment and possible dementia and slows development of white matter lesions in brain: the SPRINT Memory and Cognition IN Decreased Hypertension (SPRINT MIND) study. Blood Press 2018, 27: 247-48.
5. Supiano MA, Williamson JD: Applying the Systolic Blood Pressure Intervention Trial Results to Older Adults. J Am Geriatr Soc 2017, 65: 16-21.
6. Streit S, Poortvliet RKE, Gussekloo J: Lower blood pressure during antihypertensive treatment is associated with higher all-cause mortality and accelerated cognitive decline in the oldest-old. Data from the Leiden 85-plus Study. Age Ageing 2018, 47: 545-50.
7. Ravindrarajah R, Hazra NC, Hamada S, Charlton J, Jackson SHD, et al: Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age – Cohort Study Using Electronic Health Records. Circulation 2017, 135: 2357-68.
8. Chrysant SG: Aggressive systolic blood pressure control in older subjects: benefits and risks. Postgrad Med 2018, 130: 159-65.
9. Mossello E, Pieraccioloi M, Nesti N, Bulgaresi M, Lorenzi C, et al: Effects of Low Blood Pressure in Cognitively Impaired Elderly Patients Treated With Antihypertensive Drugs. JAMA Intern Med 2015, 175: 578-85.
10. Shimbo D, Bowling B, Levitan EB, Deng L, Sim JJ, et al: Short-Term Risk of Serious Fall Injuries in Older Adults Initiating and Intensifying Treatment With Antihypertensive Medication. Circ Cardiovasc Qual Outcomes 2016, 9: 222-29.
11. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, et al: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2018, 71: 1269-1324.
12. Qaseem A, Wilt TJ, Rich R, Humphrey LL, Frost J, et al: Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017, 166: 430-37.
13. Leung AA, Daskalopoulou SS, Dasgupta K, McBrien K, Butalia S, et al: Guidelines – Hypertension Canada’s 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol 2017, 33: 557-76.
14. Nerenberg KA, Zarnke KB, Leung AA, Dasgupta K, Butalia S, et al: Guidelines – Hypertension Canada’s 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children. Can J Cardiol 2018, 34: 506-25.
15. Bavishi C, Goel S, Messerli FH: Isolated Systolic Hypertension: An Update After SPRINT. Am J Med 2016, 129: 1251-58.
16. Ioannidis JPA: Diagnosis and Treatment of Hypertension in the 2017 ACC/AHA Guidelines and in the Real World. JAMA 2018, 319: 115-16.
17. Chobanian AV: Hypertension in 2017 – What Is the Right Target? JAMA 2017, 317: 579-80.
18. Cohen JB, Townsend RR: The ACC/AHA 2017 Hypertension Guidelines: Both Too Much and Not Enough of a Good Thing? Ann Intern Med 2018, 168: 287-88.
19. Feldman RD, Padwal RS: Application of Hypertension Guidelines in the Elderly: Revisiting Where the Bridge to Nowhere Might Actually Be Going. Can J Cardiol 2017, 33: 591-93.