Norm Campbell, MD, FRCPC, Departments of Medicine, Community Health Sciences, and Pharmacology and Therapeutics, University of Calgary, Calgary; Libin
Cardiovascular Institute, Calgary, AB.

Sailesh Mohan, MD, MPH, Departments of Medicine, Community Health Sciences, and Pharmacology and Therapeutics, University of Calgary, Calgary; Libin Cardiovascular Institute,
Calgary, AB.

Abstract:

As over 9 in 10 older adults will develop hypertension, it is important for clinicians to routinely assess blood pressure. It is as important to treat hypertension in older adults as it is in
younger people. In general, select a low-dose diuretic. Beta-blockers are not as effective at preventing stroke as other major antihypertensive drug classes. Specifi c indications for drug classes
are provided. Target the blood pressure levels to <140/90 mmHg in general, <130/80 mmHg in people with diabetes or chronic kidney disease, and focus on systolic blood pressure control. If blood
pressure control is not achieved using a moderate dose of your initial selection, add a second antihypertensive drug.

Key Words: hypertension, antihypertensive drugs, pharmacotherapy, cardiovascular disease, stroke.

Introduction

It is estimated that over 90% of normotensive people age 55-65 will eventually develop hypertension if they live an average lifespan.¹ Hypertension is not to be ignored as it is the
leading risk for death and disability in older people, and is both preventable and treatable.^2,3 Two-thirds of stroke and half of ischemic heart disease and heart failure are attributable
to elevated blood pressure, and the absolute risk from hypertension increases with age.⁴ Most older adults are or will become candidates for antihypertensive therapy.



Lifestyle changes can both prevent and treat hypertension. When used in combination with antihypertensive drugs, such changes can considerably reduce the number and doses of medication
required.⁵ Recent data indicate that few Canadians make lifestyle changes after a diagnosis of hypertension. In Canadians over age 60, there is only a 3.2% reduction in smoking after a
diagnosis of hypertension, and there is no change in body mass index, physical inactivity, or excess alcohol consumption.⁶ Lifestyle changes are thus markedly underutilized and this leads
to overreliance on pharmacotherapy.



As pharmacotherapy does offer important benefits, especially in light of the difficulty in promoting lifestyle changes that could result in lowered blood pressure, it is important to review the
principles of instituting antihypertensive therapy. This article aims to assist clinicians in selecting appropriate initial antihypertensive therapy.



Prior to prescribing antihypertensive drugs it is important to assess the person for white coat hypertension, secondary hypertension, and factors such as pain or stress that may temporarily increase
blood pressure. White coat hypertension and secondary hypertension are more common among older people. White coat hypertension can be easily detected and followed by home measurement of blood
pressure. Importantly the threshold for hypertension using home measurement of blood pressure is 135/85 mmHg or higher. Ambulatory blood pressure is recommended to be considered to confirm the
diagnosis of white coat hypertension.

Initiation of Therapy

There are a large number of specific antihypertensive drugs that both lower blood pressure and reduce death and disability for older people.⁷ The initial drug to be used is an important
choice. The blood pressure lowering to be expected by the use of one drug alone is about 9/5 mmHg; hence most people will require combinations of drugs to bring blood pressure down to recommended
levels for optimal cardiovascular protection (Table 1).⁸ Initial therapy using two antihypertensive drugs is a consideration if the pretreatment blood pressure is 160/100 mmHg or more (or
150/90 mmHg or more in people with diabetes).⁷

For older people, drug therapy generally should be initiated if the blood pressure averages above 140 mmHg systolic or 90 mmHg diastolic and in most people should be lowered to less than 140 mmHg
systolic and less than 90 mmHg diastolic.⁷ For people with diabetes or chronic kidney disease, treatment should be initiated if the blood pressure averages greater than 130 mmHg systolic
or 80 mmHg diastolic and should be lowered to less than these values.⁷ Systolic blood pressure is a more important cardiovascular risk than diastolic blood pressure in older adults, is
often less well controlled, and requires greater clinician attention.



In 2009, CHEP is emphasizing maintaining blood pressure below 130/80 mmHg in people with diabetes. Up to 80% of deaths in people with diabetes are due to cardiovascular disease and up to 75% of
specific cardiovascular complications in people with diabetes are attributable to high blood pressure.⁹ Controlling blood pressure in people with hypertension and diabetes results in very
large reductions in death and cardiovascular event rates, and reduces the progression of renal disease and retinopathy.^10,11 However, despite the strong clinical benefits of blood pressure
lowering, a recent Ontario survey found that two-thirds of individuals with diabetes and hypertension were not achieving blood pressure targets.¹² Both diabetes and hypertension commonly
coexist in older people, and hence clinicians need to be vigilant for the deadly duo and pay particular attention to blood pressure control.



There have been concerns that treatment may prevent stroke in the oldest old but increase other adverse events, including total mortality.¹³ However, in 2008, a large randomized controlled
trial demonstrated large reductions in cardiovascular events and total mortality by lowering blood pressure with a diuretic with or without a angiotensin-converting enzyme (ACE) inhibitor in people
over age 80.¹⁴ Most studies, including this latter trial, included predominantly healthy people. Caution should be exercised in lowering blood pressure in older adults who are frail or
have significant postural hypotension or have substantial comorbidity, in whom reduction in blood pressure would not be expected to improve quality or quantity of life.⁷

Uncomplicated Hypertension

Initial therapy should be selected from antihypertensive drugs that optimally reduce cardiovascular events. These include low-dose thiazide-type diuretics, ACE inhibitors, long-acting calcium channel
blockers and angiotensin receptor blockers.⁷ Beta-blockers are not as effective at preventing stroke as low-dose thiazide-type diuretics, long-acting calcium channel blockers, and
angiotensin receptor blockers in older adults and therefore should not be selected as initial therapy in those over age 60 unless there is a compelling indication (Table 2).^15-20
Currently, there are no clinical trials to assess whether direct renin inhibitors improve cardiovascular outcomes of hypertensive patients, hence prescription of the newly released class should only
be considered in patients where proven therapies are unable to control blood pressure.

Choosing between Possible First-Line Choices

Table 2 outlines the specific pharmacotherapeutic recommendations of CHEP (2009) in different clinical settings.⁷ There are often several different potential first-line therapies to choose
among. Some principals can be used to help guide the initial selection. In the absence of a specific indication for a drug class, in general, older people have a better hypotensive response to
monotherapy with a low-dose diuretic or long-acting calcium channel blocker.²¹ Thiazide-like diuretics are very inexpensive, are well tolerated, and have the same cardiovascular benefits
as other classes, and therefore, in the authors’ opinion, should be the default choice if there is no contraindication to diuretics or specific indication for a different drug class (Figure 1).
Persistence with diuretic therapy is slightly lower than other drug classes and erectile dysfunction related to diuretics occurs in about 2% of people. Active gout can be precipitated by diuretic
therapy and hence diuretics should be avoided as initial therapy in people who have gout unless they are already prescribed therapy to prevent gout (e.g., allopurinol). Diuretics can also cause a
slight increase in blood glucose and lipid levels. The outcomes of people with diabetes, impaired glucose tolerance, or normal glucose levels are improved to the same extent with diuretics as with an
ACE inhibitor or calcium channel blocker. Hence, these clinical situations are not a valid reason to avoid prescribing a diuretic.²² Initial starting drugs and doses include
hydrochlorothiazide 12.5-25 mg/day, indapamide 1.25-2.5 mg/day, and chlorthalidone 12.5-25 mg/day (1/4-1/2 tablet). If single-drug antihypertensive therapy is anticipated, using a combination
diuretic tablet (hydrochlorothizide 12.5-25 mg with spironolactone or amiloride) will reduce the risk of developing hypokalemia and dysglycemia.

In older people for whom initial use of a low-dose thiazide-like diuretic is not indicated, a long-acting calcium channel blocker will lower blood pressure to a similar extent or slightly greater
extent as a diuretic.²³ Edema is a more common problem with dihydropyridine (e.g., amlodipine, nifedipine) than nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazam).
When using nondihydropyridine calcium channel blockers, be alert for potential drug interactions (nondihydropyridine calcium channel blockers are CYP 3A4 inhibitors), the contraindication in people
with systolic heart failure and the potential to cause heart block in people with atrio-ventricular (A-V) conduction defects or people who are using other drugs that reduce A-V conduction (e.g.,
beta-blocker). Typical initial choices of calcium channel blockers and their doses include amlodipine 2.5-5 mg/day, Adalat (nifedipine) XL 20-30 mg/day, diltiazam (in extended release form) 120-240
mg/day and verapamil (in extended release form) 240 mg/day. A recent randomized controlled trial has concluded that calcium channel blocker therapy paired with an ACE inhibitor is superior to a
diuretic paired to a ACE inhibitor.²⁴ However, methodological issues in the conduct of the trial may preclude the study affecting therapeutic recommendations.



Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be used as initial choices of antihypertensive drugs for older adults although, based on differing efficacy to lower
blood pressure, the National Institute of Clinical Evaluation suggests they be selected after considering a diuretic and calcium channel blocker first.^7,21 In general, the ACE inhibitors
and angiotensin receptor blockers are excellent to add to the initial choice if blood pressure targets are not achieved with single drug treatment.²¹ A large randomized controlled trial
using ACE inhibitors in isolated systolic hypertension has not been conducted, and hence CHEP does not recommend ACE inhibitors in that setting. Cough and angioedema are adverse effects of specific
concern with ACE inhibitors. Numerous ACE inhibitors and angiotensin receptor blockers with different starting doses are in common use.



Conclusion

Maximal blood pressure lowering effect from most antihypertensive drug classes requires about 4-6 weeks, and therefore titration of therapy in the absence of a medical urgency can occur at that
interval. About 80% of the blood pressure lowering of most drug classes is achieved at half of the maximum dose, while side effects are much more common in the higher half of the dose
range.⁸ Therefore, use a combination of two drugs if there is an inadequate response to the initial therapy at moderate dose. Notably, based on a new clinical trial in 2008, CHEP now
recommends the combination of an ACE inhibitor with a ARB only be considered in selected and closely monitored people with advanced heart failure or proteinuric nephropathy.



When prescribing the initial drug it is reasonable to advise the patient that good blood pressure control usually requires lifestyle changes plus two or more drugs. This helps avoid the potential
disappointment and concerns if the initial therapy does not control the blood pressure.

The unhealthy lifestyles that cause hypertension (especially nutrition) usually elevate other cardiovascular risks, and hence a comprehensive approach to identifying and managing cardiovascular risks
is required. In particular, carefully screening for dyslipidemia and diabetes is required as these diagnoses will have a major impact on cardiovascular outcomes and treatments. Age itself is the
greatest risk factor for cardiovascular disease,⁴ and therefore all older adults with hypertension should be considered for blood pressure-lowering pharmacotherapy. Nevertheless, care
needs to be taken that the person truly has hypertension by excluding white coat hypertension and acute hypertensive responses to physical or emotional stresses, performing an appropriate diagnostic
work-up, and assessing the person for increased risks of hypotensive complications.



Appropriate antihypertensive pharmacotherapy is an effective mechanism to reduce cardiovascular morbidity and mortality in older adults. Individualized, simplified, but rational regimes of relatively
inexpensive antihypertensive drugs can control the blood pressure of most people. More information on treatment of hypertension including patient handouts can be found at "http://www.hypertension.ca">www.hypertension.ca.

Dr. Mohan has no stated conflicts of interest. Dr. Campbell has given talks sponsored by Bayer, Sanofi Aventis, Biovail, Bristol Myers Squibb, Pfizer, Novartis and Merck-Frosst, and also has
been on advisory boards for Novartis, Pfizer, Servier, Boehringer Ingelheim and Schering-Plough.

KEY POINTS / CLINICAL PEARLS

Hatim Al Lawati, MD, FRCPC, Cardiology Resident, Division of Cardiology, Faculty of Medicine, University of Toronto, Toronto, ON.
Fatemeh Akbarian, MD, Dermatologist, Research Fellow, University of Toronto, Toronto, ON.
Mohammad Ali Shafiee, MD, FRCPC, General Internist, Nephrologist, Department of Medicine, Toronto General Hospital, University Health Network; Clinician Teacher, University of Toronto, Toronto, ON.

Atrial fibrillation (AF) is by the far the most common cardiac rhythm disturbance encountered in clinical practice. It is associated with significant morbidity and mortality and has potentially lifelong implications in terms of therapy and complications. This disease is more commonly seen now given the increased life expectancy and the remarkable advances made in health care. The already at-risk older adult population is particularly vulnerable to complications from AF, especially embolic cerebrovascular events. This article reviews the evidence-based management of AF with a particular focus on the older adult population.
Key words: atrial fibrillation, older adults, stroke, rate control, rhythm control, stroke prophylaxis, anticoagulation.

Janis J. Daly, PhD, MS, Director, Cognitive and Motor Learning Laboratory; Associate Director, FES Center of Excellence, Louis Stokes Cleveland Department of Veterans Affairs Medical Center; Research Career Scientist, DVA, Washington, DC; Associate Professor, Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

For those with persistent gait and upper limb deficits after stroke, it is difficult to obtain recovery of motor control and functional capability in response to standard care methods. Functional electrical stimulation (FES) is a promising intervention. Surface FES for wrist and hand muscles can result in improved impairment sufficient to produce important gains in functional capability. In addition, an FES gait training system with multiple channels and implanted electrodes has shown a statistically significant additive advantage for the recovery of coordinated gait components versus a comparable comprehensive gait training treatment without FES. Results were sufficiently robust to show important gains in quality of life.
Key words: stroke, functional electrical stimulation, neuromuscular electrical stimulation, functional neuromuscular stimulation, functional recovery, rehabilitation.

Pippa Tyrrell, FRCP, Salford Royal Foundation Trust and University of Manchester; UK NICE Guidelines Development Group, Acute Stroke and TIA, London, UK.
Sharon Swain,PhD, National Coordinating Centre for Chronic Conditions, Royal College of Physicians; UK NICE Guidelines Development Group, Acute Stroke and TIA, London, UK.
Anthony Rudd, FRCP, St Thomas’s Hospital London; UK NICE Guidelines Development Group, Acute Stroke and TIA, London, UK.

The investigation and management of stroke has changed beyond recognition in the last two decades. The management of frail older patients with stroke represents a particular clinical challenge. Recognition of symptoms in people with significant comorbidities may be difficult and while intensive investigation may be inappropriate for a very frail aging patient, older people can gain a great deal from expert treatment and secondary prevention following stroke.
Key words: stroke, frail older adults, ischemic stroke, intracerebral hemorrhage.

Aleksandra Klimkowicz-Mrowiec, PhD, Department of Neurology, University Hospital Cracow, Poland.

Stroke and dementia are major health problems affecting older people. Cerebrovascular disease is the second-leading cause of dementia after Alzheimer’s disease, the third- leading cause of death, and one of 10 leading causes of physical disability. In parallel with the increased prevalence of stroke in aging populations and the decline in mortality from stroke, the rate of diagnosed poststroke dementia has increased, causing a growing financial burden for health care systems. This article discusses the epidemiology, etiology, and determinants of poststroke dementia and outlines the search for a suitable treatment.
Key words: dementia, stroke, cognition, risk factors, cognitive impairment.

Ashok Devasenapathy, MD, Assistant Professor of Medicine and Neurology, Penn State University, Milton S. Hershey Medical Center, Hershey, PA, USA.
Rathna Muthukumaran, MD, Graduate Student, Faculty of Psychology, Penn State University, Harrisburg, PA, USA.
Vladimir Hachinski, MD, Distinguished Professor Emeritus, Professor of Neurology, Clinical Neurosciences, University of Western Ontario, London, ON.

The term “vascular dementia” should be considered obsolete, a reflection of the 20th century concept that dementia does not respond to preventive measures, is always a neuro-degenerative disease, is not reversible, and has no treatment. A new approach necessitates the redefinition of vascular dementia as vascular cognitive impairment (VCI), with “dementia” as the terminal manifestation of a treatable process. Vascular cognitive impairment encompasses the vascular component of all dementias and is hence the only treatable element of a disease that has a highly significant impact on the health of older adults at risk for both strokes and coronary artery disease (cardiovascular disease).
The principal aim of this article is to illustrate the relationship between cognitive loss among older adults with vascular risk factors, stroke, and cardiovascular disease. Such an approach should help in understanding the basis for VCI, its prevention, and treatment.
Key words: vascular cognitive impairment, preventable senility, brain at risk, dementia, stroke.

Guido Falcone, MD, Department of Neurology, Raul Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina.
Ji Y. Chong, MD, Assistant Professor of Neurology, Columbia University, New York, NY, U.S.A.

Stroke is a common disease in the older population. Many gender differences are seen in the epidemiology, outcomes, and treatment of geriatric stroke. Although these differences are not fully understood, recognition of gender differences may help with appropriate treatment and improve outcomes.
Key words: stroke, gender, outcomes, prevention, treatment.

Elizabeth A. Johnson, RN, PhD(c), Board Certified Geriatric Clinical Nurse Specialist, Doctoral Candidate, Indiana University School of Nursing; Department of Adult Health, Indiana University School of Nursing, Indianapolis, IN, USA.
Tamilyn Bakas, RN, DNS, FAHA, Associate Professor, Department of Adult Health, Indiana University School of Nursing, Indianapolis, IN, USA.
Linda S. Williams, MD, Chief of Neurology, Roudebush Veterans Administration Medical Center; Research Coordinator, VA Stroke QUERI; Associate Professor of Neurology, Indiana University School of Medicine; Research Scientist, Regenstrief Institute, Indianapolis, IN, USA.

Depression, the most frequent neuropsychological problem after stroke, is greatly influenced by the complex relationships between the neurobiological and psychological changes that occur after stroke. Post-stroke depression leads to negative rehabilitation outcomes including less participation in therapy, extended recovery time, significantly decreased quality of life, and increased utilization of health care resources. Because of the high prevalence of post-stroke depression, all stroke survivors should be screened early in the rehabilitation process. Use of a biopsychosocial framework acknowledges the multifactorial etiology of post-stroke depression and contributes to effective, evidence-based treatment. Attention to the needs of the family caregivers further promotes successful post-stroke rehabilitation.
Key words: stroke, depression, risk factors, recovery, treatment.

In academic medicine, July 1st is the beginning of a new educational year, bringing new trainees eager to learn. Every year, one of the first things I teach these trainees is the word “stroke.” For some reason, this common term that both health care providers and health care recipients understand is replaced in medical school by the term “cerebrovascular accident,” or even worse, CVA. Not only is this term incomprehensible to most speakers of the English language, it is very inaccurate as well. Some of the articles in this month’s edition of Geriatrics & Aging clearly demonstrate the predictable and preventable pathogenesis of stroke, thus making the term “accident” a complete misnomer. The past decade has seen tremendous improvements in stroke care from the emergency room to the rehab centre. Much more remains to be learned, and currently one of the great challenges in health care is ensuring that everyone who has had a stroke receives rapid and coordinated care.

Clearly it is better to prevent a stroke than to provide even the most optimal treatment. The use of acetylsalicylic acid in the setting of transient ischemic attack (or prior ischemic stroke), anticoagulants in atrial fibrillation, and control of hypertension are the mainstays of stroke prevention. Dr. Nikolai Steffenhagen and Dr. Michael Hill explore the topic further in our CME article “Prevention of Ischemic Stroke among Older Adults: Primary and Secondary.”

Depression can complicate stroke and impair functional recovery, and the article “Post-Stroke Depression: Focus on Diagnosis and Management during Stroke Rehabilitation” by Elizabeth Johnson, Tamilyn Bakas, and Dr. Linda Williams will be helpful for those of us who are involved in stroke rehabilitation. As well, as the population gets older, the proportion of women becomes larger. Thus, the article “Gender Differences in Stroke among Older Adults” by Drs. Ji Chong and Guido Falcone, is particularly important for those of us who care for older adults. Even two of our regular columns this month deal with our focus on stroke. Our dementia column this month is on “Brain at Risk: Vascular Dementia Revisited and Redefined” by Drs. Ashok Devasenapathy, Rathna Muthukumaran and Vladimir Hachinksi. Dr. Hachinski, a Canadian neurologist, is one of the world’s foremost experts in the field of stroke and vascular dementia, and it is truly an honour for us to count him among our contributors. Our Drugs & Aging column this month is on the topic of stroke prevention and is entitled “Ischemic Stroke Prevention: Are Two Antiplatelet Agents Better than One in Older Adults?” by Dr. Sheri L. Koshman and Dr. Glen Pearson.

We also have our usual collection of articles on other geriatric topics. Particularly in family practice, the complaint of swollen legs is extremely common. Dr. Karen Yeates and Dr. Daniel Tascona provide an approach to this topic in our CVD feature “Leg Edema among Older Adults.” Our nutrition column this month is on “Zinc Deficiency among Older Adults” and is written by Dr. Maitreyi Raman, Dr. Elaheh Aghdassi, and Dr. Johane P. Allard. Physicians who work in long-term care settings know that pain is frequent among residents, but the communication with patients and thus the diagnosis of pain can be quite problematic. This difficult but important area is addressed in the article “Optimizing Pain Management in Long-Term Care Residents” by Dr. Evelyn Hutt, Dr. Martha Buffum, Dr. Regina Fink, Dr. Katherine Jones, and Dr. Ginette Pepper.

Enjoy this issue,
Barry Goldlist

Lana S. Rothenburg, BSc(Hons), Neuropsychopharmacology Research Program, Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON.
Nathan Herrmann, MD FRCP(C), Neuropsychopharmacology Research Program; Department of Psychiatry, Sunnybrook Health Sciences Centre; Department of Psychiatry, University of Toronto, Toronto, ON.
Krista L. Lanctôt, PhD, Neuropsychopharmacology Research Program; Department of Psychiatry, Sunnybrook Health Sciences Centre; Departments of Psychiatry and Pharmacology, University of Toronto, Toronto, ON.

Depression is a common sequela of stroke, occurring in approximately 33% of all patients. Post-stroke depression (PSD) is associated with greater cognitive and functional impairments, excess mortality, and increased health care costs, although symptoms are often mild. Diagnosis of PSD can be made using standard clinical criteria, despite the potential overlap with the somatic and vegetative symptoms of stroke. Post-stroke depression responds to standard antidepressant pharmacotherapies, but use of tricyclic antidepressants may result in increased cardiac adverse events. Given the high prevalence and major negative impact of PSD, active screening of all stroke patients for depression and aggressive treatment is recommended.
Key words: stroke, depression, diagnosis, risk factors, treatment.