Clinical problem solving based on the 1999 Canadian recommendations for the management of hypertension

Ross D. Feldman, MD; Norman R.C. Campbell, MD; Pierre Larochelle, MD

CMAJ 1999;161(12 Suppl):SF21.

• Introduction
• Case 1
• Case 2
• Case 3
• Summary
• References
• Table 1: Considerations in the use of antihypertensive drug classes
• Table 2: Considerations in the individualization of antihypertensive therapy

The cause of the gap between the rates of blood pressure control under optimal conditions (i.e., those achieved in clinical trials) and the current rates of blood pressure control achieved in the community is multifactorial; public health factors may have an impact on the low rates of awareness that patients have of their diagnosis of hypertension,¹ and behavioural factors may affect both the low levels of patient adherence to antihypertensive treatments and the relative insensitivity of health care providers in responding to inadequate degrees of blood pressure control.² In response to the perception that one factor contributing to this gap was the incomplete penetration among health care professionals of recommendations for the optimal diagnosis and treatment of hypertension, a revision of those recommendations was initiated. In addition, it was appreciated that the results of recent clinical trials that were not available when the recommendations were last revised have altered our approaches to the management of hypertension The generation of the 1999 recommendations, based on a critical review of the evidence, is intended to be the initial step in a multistep process to improve blood pressure control rates. This process includes the development of the recommendations that are outlined in the appended supplement, as well as the development of clinical practice guidelines that consider the following: (1) the therapies that can be proved to be most effective for an individual and (2) the cost-benefit relationship of these therapies. This process also includes the development of strategies to implement the clinical practice guidelines.

The 1999 Canadian Recommendations for the Management of Hypertension do not contain any revolutionary changes compared with the 1993 version.³ However, several evolutionary trends should be noted. Among the diagnostic recommendations, the utility of non-office-based measures of blood pressure (home blood pressure monitoring and automatic ambulatory blood pressure monitoring) was more strongly supported both in the assessment of prognosis as well as in the monitoring of therapy (see Le diagnostic, Sections IV and V, page SF6). In contrast, the role of echocardiography has remained restricted (see Le diagnostic, Section VI, page SF7). Among the pharmacological recommendations, the target blood pressures have been substantially lowered for those patients with diabetes and with renal disease (to less than 130/80 mm Hg and to less than 125/75 in patients with proteinuria of greater than 1 g/day). Notably, in the treatment of uncomplicated hypertension, ACE inhibitors have been added to thiazide diuretics and ß-adrenergic antagonists as first-line recommendations (see Le traitement pharmacologique, Section II, page SF8). In the treatment of older patients with systolic hypertension, both thiazide diuretics and longer-acting dihydropyridine calcium-channel blockers have been recommended as first-line therapies (see Le traitement pharmacologique, Section III, page SF9). However, the major theme underlying the pharmacological recommendations is that, for any individual patient, the specific choice of an antihypertensive is much more dependent on the existence of concomitant risk factors or concurrent diseases, or both, than the extent of blood pressure elevation.

What initial conclusions can practitioners reach regarding the impact of these recommendations on the management of their hypertensive patients? In the illustrative cases described below, we have tried to link these recommendations to practice.

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Marie is a 29-year-old pharmaceutical company representative whom you have seen once a month to check her blood pressure. Over the past 12 months, it has varied from 140/92 to 155/97 mm Hg. Eight years ago, she had gestational hypertension with her first pregnancy that resolved post partum. Over the past 4 months, her weight has increased by 3 kg. She does attempt to exercise at least 3 times weekly and tries to restrict the salt in her diet. She has less than one standard drink of alcohol daily. There is a family history of hypertension. On your examination, her blood pressure is 145/96 mm Hg. The findings of the rest of the physical examination, including funduscopic examination, are perfectly normal. Is she hypertensive? Should she be treated?

The diagnosis of hypertension is still primarily made in the office. A blood pressure elevation of greater than 140/90 on at least 5 occasions over a 6-month period is a recommended criterion of diagnosis of elevated blood pressure (see Le diagnostic, Section II, page SF4). However, it is important to note 2 significant caveats to determining diagnosis and prognosis (and, hence, management decisions) based solely on office determinations of blood pressure. First, recommended techniques for blood pressure measurement by sphygmomanometer are rarely followed in general practice.^4,5 This can lead to a significant discrepancy in blood pressure measurement (as compared with gold-standard approaches). These inaccuracies can significantly affect the ability of practitioners to determine a diagnosis of hypertension. Second, it has been appreciated that non-office-based measures of blood pressure monitoring (home blood pressure monitoring and automatic ambulatory blood pressure monitoring) play an important role in the determination of the prognosis of a patient who is classified as hypertensive based on office determinations (see Le diagnostic, Sections IV and V, page SF6). This is especially notable with regard to a diagnosis of office-induced hypertension (a disease that carries a much more benign prognosis than sustained hypertension). For the diagnosis of office-induced hypertension (versus sustained hypertension), either home blood pressure monitoring or automatic ambulatory blood pressure monitoring is required.

You send Marie home with a blood pressure monitor. (You have a dozen that you rent out for short-term use to your patients.) She reports back that the blood pressures she determines at home are similar to those that you have measured in the office. On her next visit, you review the laboratory studies taken in conjunction with her last visit. There are no abnormalities on urinalysis or complete blood count. Her serum potassium was 4.5 mmol/L. Serum creatinine was less than 100 mmol/L. Her fasting glucose was 5.2 mmol/L. Total cholesterol was 4.85 mmol/L with high-density lipoprotein (HDL) cholesterol of 1.32 mmol/L, low-density lipoprotein (LDL) cholesterol of 3.1 mmol/L and triglycerides of 2.2 mmol/L. Her ECG did not reveal any evidence of left ventricular hypertrophy.

Is she at increased risk of atherosclerotic complications due to her hypertension? Failing effective lifestyle modifications to lower her blood pressure, should she be treated pharmacologically?

Marie's risk of hypertension-related complications primarily reflects her risk of atherosclerotic complications, which would be mainly coronary artery disease and stroke. If she fails to lower her blood pressure, having made a genuine attempt at lifestyle modification (i.e., weight loss and increased exercise), the decision for instituting pharmacological therapy should be made based on considerations of the potential benefits of therapy versus risk. What are the potential benefits? Based on tables of risk ratios derived from the Framingham population base,⁶ one can estimate that Marie's 10-year risk of coronary atherosclerotic complications, reflecting both her level of blood pressure as well as her other risk factors, is less than 1%. Furthermore, based on clinical trial experience, the potential benefit of antihypertensive therapy in reducing cardiovascular event rates (specifically, coronary artery disease complications) is only approximately 15%.⁷ Thus, one would need to treat almost 700 patients like Marie in order to save one coronary event over the next 10 years. This "number needed to treat" of 700 does not compare favourably with those associated with other prophylactic treatment strategies (e.g., over the same period one would only need to prescribe Coumadin to fewer than 10 patients with atrial fibrillation to avoid a stroke). In summary, on a population basis, treatment of patients whose blood pressure is greater than 140/90 mm Hg in order to achieve a target blood pressure of less than 140/90 mm Hg does more good than harm (see Le traitement pharmacologique, Section I, page SF7). However, the decision to initiate drug therapy needs to include consideration not only of the level of blood pressure but also of the presence (or absence) of other concomitant risk factors and diseases. Thus, the approach you may take with Marie contrasts significantly with that taken with the patient with identical blood pressure who has diabetic nephropathy. In that patient, drug therapy should be considered for blood pressures greater than 130/80 mm Hg, with the aim of lowering the blood pressure to less than 130/80 mm Hg (see Le traitement pharmacologique, Section VII, page SF10).

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Doug is a 47-year-old middle manager with long-standing hypertension. He smokes a pack and a half of cigarettes a day and has symptoms consistent with a mild degree of chronic bronchitis, although he denies wheezing. His weight has been increasing steadily over the last 10 years, and he has a current body mass index of 27.4 kg/m2. His blood pressure has been well controlled in the past with a ß-adrenergic antagonist that was discontinued for reasons that are unclear. Currently, his blood pressures are in the range of 140/92 to 150/98 mm Hg. You have just taken him on as a new patient (his previous family physician relocated to an underserviced area in Toronto). On laboratory evaluation, his total cholesterol was 6.25 mmol/L with an HDL cholesterol of 0.97 mmol/L. Fasting serum glucose was 5.9 mmol/L. Should Doug be treated pharmacologically? With what?

In contrast to Marie, Doug presents with a significantly higher risk of cardiovascular complications. His 10-year risk of coronary heart disease complications approaches 20%. Adequate blood pressure control would be expected to reduce his risk at least 3%. This translates into a number needed to treat of 33.

Approach to therapy (i.e., reducing his overall cardiovascular risk) needs to start with attempts at lifestyle modification.⁸ It would be expected that giving up smoking would result in a much more significant reduction in cardiovascular risk (about 7%, number needed to treat 14) and should be encouraged. Weight reduction would be important, both for blood pressure control and for treatment of his hypercholesterolemia. As noted above, lifestyle modification therapy should be considered both as initial therapy and as an adjunct to pharmacological management.⁶

The choice of antihypertensive therapy reflects the nature of his hypertension (diastolic elevations in a patient under 60 years of age), his concomitant cardiovascular risk factors (i.e., smoking and hypercholesterolemia), as well as his obesity. The recommendations for first-line therapy for patients with uncomplicated hypertension include ß-adrenergic antagonists diuretics and angiotensin-converting-enzyme (ACE) inhibitors. However, the choice of therapy for Doug reflects further considerations that underscore the importance of individualizing therapy based on other cardiovascular risk factors and concomitant diseases. His previous therapy with ß-adrenergic antagonists may not be preferred therapy based on several considerations:

1. The benefits of ß-adrenergic antagonist therapy in hypertensive smokers remain uncertain, thus, they are not recommended for hypertensives who smoke, in the absence of target-organ damage or concurrent cardiovascular disease (see Le traitement pharmacologique, Section VI, page SF10).
2. ß-Adrenergic antagonists may impair the ability of the patient to benefit from exercise and may impede the ability of obese hypertensive patients to lose weight.⁹ Although ß-adrenergic antagonists are not contraindicated in hypertensive patients with hyperlipidemia, those without intrinsic sympathomimetic activity may develop a worse lipid profile (see Le traitement pharmacologique, Section V, page SF10).

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Roy is a 67-year-old retired bureaucrat who facilitates consensus conferences in his leisure time. Several months ago, in conjunction with his yearly rectal examination, you noted that his blood pressure was 176/85 mm Hg. Repeated blood pressure measurements over the next 6 months demonstrated a consistent level of systolic hypertension. There were no other abnormalities in the rest of his physical examination. On laboratory studies, his total cholesterol was marginally elevated at 5.7 mmol/L, as was his fasting serum glucose at 8.3 mmol/L. You were able to convince him to reduce his alcohol intake, lose 4 kg and exercise more. Notwithstanding, his systolic blood pressures remained consistently greater than 160 mm Hg. Serum glucose, although decreased, was still elevated at 7.3 mmol/L. There were no other abnormalities on serum electrolytes, creatinine or urinalysis. Should you treat his hypertension pharmacologically? With what?

In patients over the age of 60 years, systolic elevations of blood pressure greater than 160 mm Hg should be treated, even in the absence of other risk factors (see Le traitement pharmacologique, Section III, page SF9). Major considerations affecting your choice of therapy would include consideration of the recommendations for first line-therapy in the treatment of systolic hypertension, as well as the recommendations for the treatment of the hypertensive patient with diabetes. For older patients with systolic hypertension, preferred therapy is either a low-dose thiazide diuretic or a long-acting dihydropyridine calcium channel antagonist. Both of these classes of drugs have been shown to reduce both blood pressure and cardiovascular complications in older patients with systolic hypertension. Furthermore, in the absence of diabetic nephropathy, low-dose thiazides or long-acting dihydropyridine calcium channel antagonists remain the drug of choice for patients with systolic hypertension and Type II diabetes mellitus. However, your target for blood pressure control should be lower for those patients with diabetes than for those without (based on the findings of the HOT¹⁰ and UKPDS 38¹¹ studies). As noted above, in the revised recommendations a target of less than 130/80 mm Hg is recommended for patients with hypertension and diabetes.

How would the development of proteinuria affect your choice for Roy?

For patients with diabetes, hypertension and overt nephropathy (defined as albuminuria greater than 300 mg/day), preferred therapy is an ACE inhibitor (see Le traitement pharmacologique, Section VII, page SF10).

To achieve target blood pressures, the increasing use of combination therapies should be considered. The 1999 recommendations note that a long-acting calcium-channel blocker may be combined with an ACE inhibitor or a low-dose thiazide diuretic may be added to an ACE inhibitor without adversely affecting microalbuminuria. Furthermore, for patients with adverse reactions to an ACE inhibitor, an angiotensin II receptor antagonist may be substituted.

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The 1999 Canadian Recommendations for the Management of Hypertension are notable for the trends that they represent with regard to the evolution of the management of hypertension. Diagnostically, the Recommendations endorse the greater use of non-office-based measures of blood pressure control and greater emphasis on the assessment of other atherosclerotic risk factors, both when considering prognosis in hypertension and in the choice of therapy.

On the treatment side of the equation, lower targets for blood pressure control have been advocated in subgroups of hypertensive patients, particularly in those with diabetes and renal disease. In conjunction with the recently published recommendations on lifestyle management, there is a greater emphasis on lifestyle modification, both as initial and adjunctive therapy in hypertension. Implicit in the recommendations for therapy is the principle that for the vast majority of hypertensive patients treated pharmacologically, practitioners should not follow a stepped-care approach. Instead, therapy should be individualized, primarily based on consideration of concurrent diseases, both cardiovascular and noncardiovascular (Tables 1 and 2). Through the consensus process, there was a general appreciation of how far we have come in the development of evidence-based recommendations for hypertension management. However, there was also an increasing appreciation of how far we have to go in effectively translating these recommendations into better blood pressure control.

The authors gratefully acknowledge the expert assistance of Kellie Ross and Teresa Atkinson in the preparation of this manuscript.

Competing interests: Dr. Feldman has conducted industry-supported research; he is a member of advisory boards for, and has received speaker's fees from, various pharmaceutical companies. Dr. Campbell has received consultancy fees and speaker's fees from various pharmaceutical companies. Dr. Larochelle has conducted industry-supported research and has received consultancy fees from various pharmaceutical companies.

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