Dementia and hypertension are highly prevalent, epidemiologically related chronic conditions disproportionately affecting older persons; approximately 97% of persons with dementia  and 66% with hypertension are over the age of 65 . With increasing life expectancy, the prevalence of both dementia and hypertension is projected to increase further. Both conditions increase morbidity and mortality, and are among the largest contributors to healthcare expenditure – the total estimated expenditure on dementia in the United States in 2020 was $ 305 billion , and the annual expenditure on hypertension is estimated to be around $ 131 billion . In addition, hypertension is an independent modifiable risk factor for dementia [5,6]. More recently, we analyzed data from randomized controlled trials (RCTs) to show that lowering blood pressure (BP) may slow decline in cognition . Unfortunately, BP control has declined in the recent years, from 54% in 2013 to 44% in 2017 . Here we will discuss some current logistical issues with hypertension management in older patients and future directions.
With up to half the cases of Alzheimer’s disease worldwide attributed to modifiable risk factors including hypertension, it would stand to reason that BP lowering would help with prevention and management of dementia. Indeed, it is estimated that BP lowering in midlife hypertension with 10% reduction in hypertension prevalence will reduce dementia by approximately 40,000 cases . However, despite these data, BP lowering in older patients is fraught with complexities and challenges. First, the definition of hypertension and the target BP for older patients has changed over the years. The Joint National Commission (JNC)-7 guidelines for the treatment of hypertension published in 2003 recommended 140/90 mmHg as the threshold to initiate anti-hypertensive therapy, with a target of achieving a BP of <140/90 mmHg . This was increased to 150/90 mmHg in 2014 under the JNC-8 guidelines in 2014  and was mirrored by the American Academy of Family Physicians guidelines of 2017 . After the landmark systolic blood pressure intervention (SPRINT) trial , the American College of Cardiology/American Heart Association (ACC/AHA) guidelines in 2017 lowered this threshold to 130/80 mmHg . The 2018 European Society of Cardiology/European Society of Hypertension guidelines for hypertension management, published a year after the ACC/AHA guidelines however continued to recommend a threshold of 140/90 mm Hg for initiating treatment . The latest Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for hypertension recommend a target BP of <120/80 mmHg in adults with Chronic Kidney Disease (CKD) using unattended BP measurements , and over 35% of adults with CKD in the United States are over the age of 65 . The trend over the years has been to lower BP goals. However, with a multitude of guidelines, each with a different BP goal, the message to lower BP is sometimes lost. Second, despite current evidence from RCTs and meta-analysis demonstrating safety and benefits of BP lowering in older patients , clinicians continue to have concerns about lowering BP in this population. Some of the concern is due to the fact that current evidence and hypertension guidelines are based on results of explanatory trials. These results may not be completely generalizable as explanatory trials have strict inclusion and exclusion criteria that tend to exclude sicker and frail patients such as those in nursing homes, and those with multiple comorbidities, orthostatic hypotension, severe kidney disease, history of stroke with residual deficits or balance issues . While these patients are excluded from the trials, in the real world, clinicians still have to manage hypertension in these patients, and in the absence of pragmatic trials, clinicians often do not have enough evidence to guide management. In addition, while RCTs demonstrate overall safety, the aggregate data does not guarantee safety of an individual patient, which is still the responsibility of the physician.
There are also other barriers to achieving BP goals at the patient, provider, and health system level, some of which are listed in Table 1. In addition, there are clinical concerns about safety of tolerability of BP lowering and side effects of anti-hypertensive medications in select hypertensive older adults. One of such clinical concerns is that lowering BP can cause cerebral hypoperfusion and decline in cognition. We performed a systematic review and metaanalysis, to analyze the effect of BP lowering on cognitive decline in older adults . This review was prompted by the clinical hesitancy to lower BP to current guidelines described above. We analyzed data from nine qualifying RCTs, including the Systolic Hypertension in the Elderly Program (SHEP) , the hypertension trial by the Medical Research Council , the Systolic Hypertension in Europe trial (Syst-Eur) , the Study on Cognition and Prognosis in the Elderly (SCOPE) , hypertension trial by Pantoni et al. , the Hypertension in the Very Elderly Trial-cognitive function assessment (HYVETCog) , The Telmisartan Randomized AssessmeNt Study in aCE iNtolerant subjects with cardiovascular Disease (TRANSCEND) , The Memory in Diabetes sub-study of the Action to Control Cardiovascular Risk in Diabetes study (ACCORD-MIND) , and SPRINTMIND . The PICO (population, intervention, control, and outcomes) criteria included RCTs on BP lowering with pharmacological agents in patients >60 years, with a pre-specified outcome of cognition, a standardized measure of cognition, presence of comparison group with either placebo, no intervention or a higher BP goal, and at least 1 year of follow up. We found a small improvement in cognition with BP lowering. Though the effect size for improvement in cognition is small, this study alleviates concerns for worsening of cognition with BP lowering. Furthermore, even a small positive effect is clinically significant due to the high prevalence of hypertension and dementia resulting in a large epidemiological impact. Indeed, the NNT to prevent mild cognitive impairment or probably dementia with this effect size was 63. We concluded that BP lowering did not cause worsening of cognitive decline in the older population. Consistent with our results,  other recent meta-analyses also indicate that lowering BP does not worsen cognitive decline. [28,29].
|Patient level||Lack of knowledge [5,39]|
|Inaccurately measured BP, use of inaccurate or non-validated BP cuff|
|Adherence to medications [40,41] and home BP monitoring|
|Logistical issues: access to care, distance from clinic, lack of time for clinic visits and transportation|
|Provider level||Lack of clinical decision support or treatment algorithms, clinical inertia, lack of physician incentives to lower BP [42-46]|
|Inability to set accurate BP goals due to incorrect in-clinic BP , masked hypertension or white coat hypertension|
|Limited time and resources for patient counselling in an already busy clinic|
|Health system level||Poorly aligned incentives, lack of decision support tools or their implementation, and lack of feedback [48-51]|
|Lack of clinic space and resources for timely follow up for hypertension management [42-46,52]|
|Improper and inconsistent BP measuring techniques in clinics |
Table 1: Barriers to achieving goal blood pressure.
Some older studies have linked treatment of hypertension with cerebral hypoperfusion [30,31]. While there is a U-shaped association between systolic BP and cognition [32,33], prospective observational studies have demonstrated that BP lowering reduces risk of dementia . Other recent studies, including some RCTs are also in agreement that lowering BP does not decrease cerebral perfusion- this might be due to cerebral autoregulation [35,36]. In a recent RCT, intensive lowering of systolic BP (mean of less than 130 mmHg) did not reduce cerebral perfusion even in participants with severe small vessel cerebral disease .
BP lowering is beneficial. However, consideration has be given to potential side effects and tolerability of antihypertensive therapy which can lead to non-adherence - the most common cause of failure to achieve BP goals. Patients on anti-hypertensive medications should be asked about symptoms of low BP or side effects of medications such as lightheadedness, syncope, falls, increased fatigue, drowsiness, orthostatic hypotension, cough and sexual dysfunction, and kidney function and electrolytes need to be monitored closely. In addition, polypharmacy and drug interaction also need to be considered. Combination pills should be encouraged to decreased pill burden and increase medication adherence.
In summary, despite a plethora of clinical trials and strong evidence to support BP lowering, we have not been successful in achieving BP goals in our clinics. Hypertension remains vastly undertreated, with only 30% of patients over 65 years achieving a BP of <140/90 mmHg . Real world management of hypertension has added difficulties when compared to BP lowering in privileged clinical trial setting with financial and personnel assistance. It is important to understand that methods used in clinical trials may not be directly transferable to clinical care in real world clinical practice. Barriers to achieving BP goals need to be evaluated and addressed (Table 1). Perhaps we need to revisit our current strategies for hypertension management and implement effective practices such as home BP monitoring, use modern technology and team science for remote BP monitoring and management. We also need to find practical solutions to barriers such as inability to obtain accurate BP measurement in clinics. We need better strategies to improve patient education, engagement and empowerment. It is time to move to pragmatic trials of BP lowering in the real world.
2. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27;131(4):e29-322.
3. Zhao LH. Alzheimer’s disease facts and figures. Alzheimers Dement. 2020;16:391-460.
4. Kirkland EB, Heincelman M, Bishu KG, Schumann SO, Schreiner A, Axon RN, et al. Trends in Healthcare Expenditures Among US Adults With Hypertension: National Estimates, 2003-2014. J Am Heart Assoc. 2018;7(11):e008731.
5. Elias MF, Wolf PA, D’Agostino RB, Cobb J, White LR. Untreated blood pressure level is inversely related to cognitive functioning: the Framingham Study. American Journal of Epidemiology. 1993 Sep 15;138(6):353-64.
6. Sharp SI, Aarsland D, Day S, Sønnesyn H, Alzheimer’s Society Vascular Dementia Systematic Review Group, Ballard C. Hypertension is a potential risk factor for vascular dementia: systematic review. International Journal of Geriatric Psychiatry. 2011 Jul;26(7):661-9.
7. Gupta A, Perdomo S, Billinger S, Beddhu S, Burns J, Gronseth G. Treatment of hypertension reduces cognitive decline in older adults: a systematic review and metaanalysis. BMJ Open. 2020 Nov 1;10(11):e038971.
8. Muntner P, Hardy ST, Fine LJ, Jaeger BC, Wozniak G, Levitan EB, et al. Trends in blood pressure control among US adults with hypertension, 1999-2000 to 2017-2018. JAMA. 2020 Sep 22;324(12):1190-200.
9. Barnes DE, Yaffe K. The projected effect of risk factor reduction on Alzheimer’s disease prevalence. The Lancet Neurology. 2011 Sep 1;10(9):819-28.
10. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo Jr JL, 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 May 21;289(19):2560-71.
11. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidencebased 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 Feb 5;311(5):507-20.
12. Croke LM. Pharmacologic treatment of hypertension: ACP and AAFP release recommendations for adults 60 years and older. American Family Physician. 2017 May 1;95(9):588-9.
13. SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. New England Journal of Medicine. 2015 Nov 26;373(22):2103- 16.
14. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Journal of the American College of Cardiology. 2018 May 15;71(19):e127-248.
15. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). European Heart Journal. 2018 Sep 1;39(33):3021-104.
16. Cheung AK, Chang TI, Cushman WC, Furth SL, Hou FF, Ix JH, et al. Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney International. 2021 Mar 1;99(3):559-69.
17. United States Renal Data System. 2020 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2020.
18. Rich MW, Chyun DA, Skolnick AH, Alexander KP, Forman DE, Kitzman DW, et al. Knowledge gaps in cardiovascular care of the older adult population: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society. Circulation. 2016 May 24;133(21):2103-22.
19. Applegate WB, Pressel S, Wittes J, Luhr J, Shekelle RB, Camel GH, et al. Impact of the treatment of isolated systolic hypertension on behavioral variables: results from the Systolic Hypertension in the Elderly Program. Archives of Internal Medicine. 1994 Oct 10;154(19):2154-60.
20. Prince MJ, Bird AS, Blizard RA, Mann AH. Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council’s trial of hypertension in older adults. BMJ. 1996;312(7034):801-805.
21. Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, et al. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. The Lancet. 1998 Oct 24;352(9137):1347-51.
22. Lithell H, Hansson L, Skoog I, Elmfeldt D, Hofman A, Olofsson B, et al, SCOPE Study Group. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial. Journal of Hypertension. 2003 May 1;21(5):875-86.
23. Pantoni L, del Ser T, Soglian AG, Amigoni S, Spadari G, Binelli D, et al. Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebocontrolled trial. Stroke. 2005 Mar 1;36(3):619-24.
24. Peters R, Beckett N, Forette F, Tuomilehto J, Clarke R, Ritchie C, et al. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a doubleblind, placebo controlled trial. The Lancet Neurology. 2008 Aug 1;7(8):683-9.
25. Anderson C, Teo K, Gao P, Arima H, Dans A, Unger T, et al. Renin-angiotensin system blockade and cognitive function in patients at high risk of cardiovascular disease: analysis of data from the ONTARGET and TRANSCEND studies. The Lancet Neurology. 2011 Jan 1;10(1):43-53.
26. Williamson JD, Launer LJ, Bryan RN, Coker LH, Lazar RM, Gerstein HC, et al. Cognitive function and brain structure in persons with type 2 diabetes mellitus after intensive lowering of blood pressure and lipid levels: a randomized clinical trial. JAMA Internal Medicine. 2014 Mar 1;174(3):324-33.
27. Williamson JD, Pajewski NM, Auchus AP, Bryan RN, Chelune G, Cheung AK, et al. Effect of intensive vs standard blood pressure control on probable dementia: a randomized clinical trial. JAMA. 2019 Feb 12;321(6):553- 61.
28. Peters R, Warwick J, Anstey KJ, Anderson CS. Blood pressure and dementia: what the SPRINT-MIND trial adds and what we still need to know. Neurology. 2019 May 21;92(21):1017-8.
29. Hughes D, Judge C, Murphy R, Loughlin E, Costello M, Whiteley W, et al. Association of blood pressure lowering with incident dementia or cognitive impairment: a systematic review and meta-analysis. JAMA. 2020 May 19;323(19):1934-44.
30. Graham DI. Ischaemic brain damage of cerebral perfusion failure type after treatment of severe hypertension. British Medical Journal. 1975 Dec 27;4(5999):739.
31. Strandgaard S. Cerebral blood flow in the elderly: impact of hypertension and antihypertensive treatment. Cardiovascular Drugs and Therapy. 1991 Jan 1;4(6):1217- 21.
32. Glynn RJ, Beckett LA, Hebert LE, Morris MC, Scherr PA, Evans DA. Current and remote blood pressure and cognitive decline. JAMA. 1999 Feb 3;281(5):438-45.
33. Bohannon AD, Fillenbaum GG, Pieper CF, Hanlon JT, Blazer DG. Relationship of race/ethnicity and blood pressure to change in cognitive function. Journal of the American Geriatrics Society. 2002 Mar;50(3):424-9.
34. Ou YN, Tan CC, Shen XN, Xu W, Hou XH, Dong Q, et al. Blood pressure and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 209 prospective studies. Hypertension. 2020 Jul;76(1):217-25.
35. Lipsitz LA, Gagnon M, Vyas M, Iloputaife I, Kiely DK, Sorond F, et al. Antihypertensive therapy increases cerebral blood flow and carotid distensibility in hypertensive elderly subjects. Hypertension. 2005 Feb 1;45(2):216-21.
36. Tryambake D, He J, Firbank MJ, O’Brien JT, Blamire AM, Ford GA. Intensive blood pressure lowering increases cerebral blood flow in older subjects with hypertension. Hypertension. 2013 Jun;61(6):1309-15.
37. Croall ID, Tozer DJ, Moynihan B, Khan U, O’Brien JT, Morris RG, et al. Effect of standard vs intensive blood pressure control on cerebral blood flow in small vessel disease: the preserve randomized clinical trial. JAMA Neurology. 2018 Jun 1;75(6):720-7.
38. Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005 Jul 27;294(4):466- 72.
39. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988- 2008. JAMA. 2010 May 26;303(20):2043-50.
40. Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation. 2009 Oct 20;120(16):1598-605.
41. Naik AD, Kallen MA, Walder A, Street Jr RL. Improving hypertension control in diabetes mellitus: the effects of collaborative and proactive health communication. Circulation. 2008 Mar 18;117(11):1361-8.
42. Nelson SA, Dresser GK, Vandervoort MK, Wong CJ, Feagan BG, Mahon JL, et al. Barriers to blood pressure control: a STITCH substudy. The Journal of Clinical Hypertension. 2011 Feb;13(2):73-80.
43. Daugherty SL, Powers JD, Magid DJ, Masoudi FA, Margolis KL, O’Connor PJ, et al. The association between medication adherence and treatment intensification with blood pressure control in resistant hypertension. Hypertension. 2012 Aug;60(2):303-9.
44. Egan BM, Zhao Y, Axon RN, Brzezinski WA, Ferdinand KC. Uncontrolled and apparent treatment resistant hypertension in the United States, 1988 to 2008. Circulation. 2011;124(9):1046-1058.
45. Cabana MD, Rand CS, Powe NR, Wu AW, Wilson MH, Abboud PA, et al. Why don’t physicians follow clinical practice guidelines?: A framework for improvement. JAMA. 1999 Oct 20;282(15):1458-65.
46. Varsi C, Ekstedt M, Gammon D, Ruland CM. Using the Consolidated Framework for Implementation Research to Identify Barriers and Facilitators for the Implementation of an Internet-Based Patient-Provider Communication Service in Five Settings: A Qualitative Study. J Med Internet Res. 2015;17(11):e262.
47. Minor DS, Butler Jr KR, Artman KL, Adair C, Wang W, McNair V, et al. Evaluation of blood pressure measurement and agreement in an academic health sciences center. The Journal of Clinical Hypertension. 2012 Apr;14(4):222-7.
48. Reschovsky JD, Hadley J, Landon BE. Effects of compensation methods and physician group structure on physicians’ perceived incentives to alter services to patients. Health Serv Res. 2006;41(4):1200-1220.
49. Racine DP. Reliable effectiveness: a theory on sustaining and replicating worthwhile innovations. Adm Policy Ment Health. 2006;33(3):356-387.
50. Damschroder LJ, Aron DC, Keith RE, Kirsh SR, Alexander JA, Lowery JC. Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science. Implement Sci. 2009;4:50.
51. Muntner P, Einhorn PT, Cushman WC, Whelton PK, Bello NA, Drawz PE, et al. Blood pressure assessment in adults in clinical practice and clinic-based research: JACC Scientific Expert Panel. Journal of the American College of Cardiology. 2019 Jan 29;73(3):317-35.
52. Chalmers J, MacMahon S, Bousser MG, Cutler J, Donnan G, Hansson L, et al. PROGRESS-perindopril protection against recurrent stroke study: Status in July 1996. Journal of Hypertension, Supplement. 1996;14(6).