Blood Pressure Management

Elevated blood pressure is the single most important risk factor for stroke. One in five adult Canadians has blood pressure in the range of 130–139/85–89 mm Hg, and up to 60 percent of them will develop hypertension within four years. Among persons aged 55 and older with normal blood pressure, 90 percent will develop hypertension if they live to an average age. All adults require ongoing assessment of blood pressure throughout their lives.²⁰ Each 1 mm Hg increase in blood pressure increases the risk of poor late-life cognitive function by approximately one percent.¹⁰³ Epidemiologic studies have shown a graded increase in the risk of stroke as blood pressure increases.

Numerous population-based studies have found that elevated blood pressure is a significant risk factor for first and recurrent stroke; hypertension is estimated to account for about 60 percent of the population-attributable risk for cerebrovascular disease. A number of trials have shown a 28 percent risk reduction in recurrent stroke in patients treated with blood pressure lowering medication. The optimal target for blood pressure in people who have had a stroke has not been formally defined through randomized controlled trials. The current treatment recommendation is to attain a blood pressure of consistently lower than 140/90 mm Hg for people who have had a cerebrovascular event. Epidemiologic data have shown that those with a response to treatment with lower pressures have better outcomes yet these treatment trials have not yet clearly defined how far blood pressure should be lowered.

• Coordinated hypertension awareness programs at the provincial and community levels that involve community groups, pharmacists, primary care providers and other relevant partners.
• Stroke prevention, including routine blood pressure monitoring, offered by primary care providers in the community as part of comprehensive patient management.
• Increased availability and access to education programs for healthcare providers across the continuum of care on hypertension diagnosis and management for adults and children
• Increased programs for patients and families on home monitoring of blood pressure and blood pressure self-management programs

1. Proportion of persons at risk for stroke who had their blood pressure measured at their last healthcare encounter.
2. Proportion of the population who have diagnosed elevated blood pressure (hypertension).
3. Proportion of the population who are aware of hypertension and the risks of high blood pressure.
4. Proportion of the population who report having hypertension.
5. Percentage of the population with known hypertension who are on blood pressure lowering therapy.
6. Proportion of the population with hypertension who are being treated and have achieved control of their blood pressure within defined targets (as per Canadian Hypertension Education Program guidelines).
7. Proportion of stroke and transient ischemic attack patients who have received a prescription for blood pressure lowering agents on discharge from acute care.
8. Proportion of stroke and transient ischemic attack patients who have received a prescription for blood pressure lowering agents after assessment in a secondary prevention clinic.

Measurement Notes

• Performance measures 1 through 4: data may be available through the Canadian Hypertension Education Program database, the Canadian Community Health Survey, and other provincial and local health surveys and patient self-reports.
• Performance measures 5 and 6: data may be available through audit of primary care physician charts. Prescription information may also be available through provincial drug plan databases, although these may have limitations with respect to the age of those covered by the plans, and there is variation across provinces and territories.
• Performance measures 7 and 8: prescriptions for blood pressure lowering agents may be given during the inpatient stay or during a secondary prevention assessment and follow- up. When tracking these performance rates, it is important to record the setting where this therapy is initiated. Data sources may include physician order sheets, physicians’ or nurses’ notes, discharge summaries or copies of prescriptions given to patients.
• Prescriptions given to a patient do not imply compliance.
• Algorithms to identify incidence and prevalence of hypertension from administrative databases have been validated in Canada and should be used for consistency in measurement when possible.¹⁰⁴

• Canadian Hypertension Education Program:  http://www.hypertension.ca/chep-recommendations
• Home monitoring and other Canadian Hypertension Education Program resources:  http://hypertension.ca/bpc/resource-center/educational-tools-for-health-care-professionals/Hypertensioncanada.ca
• Aboriginal Hypertension Management Resources:  http://www.heartandstroke.com/site/c.ikIQLcMWJtE/b.3479041/k.FFD0/First_Nations_Inuit__M233tis_Resources.htm

Hypertension is a major problem in nearly all countries around the world, including Canada, and it is the most important modifiable risk factor for stroke. The INTERSTROKE study is an ongoing standardized case-controlled study of the contribution of specific risk factors to the burden of stroke across 22 countries.¹⁰⁵ The first report from this study, based on 3,000 stroke cases and 3,000 controls, identified five risk factors which account for more than 80 percent of the risk for stroke, including hypertension, current smoking, abdominal obesity, diet, and physical activity. Among these risk factors, hypertension was the most significant risk factor for stroke and contributed to 34.6 percent of the population-attributed risk (PAR), and this rose to 52 percent when measured blood pressures of greater than 160/90 mm Hg were added to the model. When these results were compared to a similar study conducted for heart disease, hypertension was found to have a more significant impact on stroke than on heart disease. The study further noted that “blood pressure is the most amenable to change in low-income settings because screening programs need modest equipment and little specialized expertise. Additionally, blood pressure is readily reduced by inexpensive generic drugs and non-pharmacological approaches (e.g., salt reduction)” (page 9).

The National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has defined normal blood pressure as less than 120/80 mm Hg.¹⁰⁶ A continuous and linear relationship between blood pressure and risk of stroke has been reported, which holds even in individuals with normal blood pressure. Lewington found that an increase of 20 mm HG in systolic and 10 mm HG in diastolic blood pressure can lead to a two-fold increase in stroke mortality in persons aged 40 – 69.¹⁰⁷Weber reported that the high sensitivity of the relationship between blood pressure and stroke risk is now more fully realized.¹⁰⁸ Single studies do not always have the power to identify the impact that blood pressure changes of only a few millimetres of mercury have on risk. However, a meta-analysis of 61 studies with a total of more than 1 million participants, an average 12-year follow-up and 120 000 recorded deaths showed that each 2 mm Hg reduction in systolic blood pressure was associated with a 7 percent reduction in mortality from ischemic heart disease and a 10 percent reduction in mortality from stroke.¹⁰⁷ A subsequent prospective study by Bestehorn et al found an overall 10-year stroke rate of 26 percent in patients with hypertension and for 16.7 percent f the cohort the risk was greater than 50 percent if they had additional co-morbidities.¹⁰⁹In a meta-analysis of risk stratification for the prevention of cardiovascular complications of hypertension, Girerd and Giral conclude that each reduction of 2 mm Hg in systolic blood pressure is associated with a 25 percent reduction in stroke events.¹¹⁰

Du and associates reported that some 20–30 percent of adult populations are affected, as are over 60 percent of people over 65 years and about 70 percent of stroke patients. Hypertension is quantitatively the largest single risk factor for premature death and disability, because of the large number of people afflicted and the consequences of uncontrolled hypertension.¹¹¹ Hypertension is closely associated with the risk of total mortality and the risk of all types of stroke, coronary artery disease, diabetes and renal disease. No other modifiable factor has been identified that contributes more to the development of stroke than hypertension. The authors further emphasized that hypertension should not be regarded so much as a disease but more as one of the treatable or reversible risk factors for premature death due to arterial disease.¹¹¹ At least three-quarters of strokes in hypertensive patients are preventable by treatment of elevated blood pressure. However, strokes are caused not by a single risk factor such as hypertension but by the interaction of multiple risk factors, some having a stronger independent relationship with risk of stroke than others. The probability of stroke in an individual depends on the presence and level of other risk factors.

A collaborative meta-analysis was conducted to assess the age-specific relevance of blood pressure to cause-specific mortality.¹⁰⁷ Combining 61 prospective observational studies of blood pressure and vascular mortality, each difference of 20 mm Hg in systolic blood pressure (or, approximately equivalently, 10 mm Hg

in usual diastolic blood pressure) was associated with more than a two-fold difference in the stroke death rate, without any evidence of a threshold down to at least 115/75 mm Hg for all vascular deaths. Age-specific associations were found to be similar for men and women and for cerebral hemorrhage and cerebral ischemia.

In a study involving 3845 patients, the benefit of antihypertensive treatment for patients with hypertension who were 80 years or older was investigated (HYVET study).¹¹³ Patients were randomly assigned to receive either antihypertensive therapy or matching placebo. In this investigation, lowering mean blood pressure by 15.0/6.1 mm Hg was associated with a 30 percent reduction in the rate of fatal or nonfatal stroke (95% CI –1% to 51%, p = 0.06), a 39 percent reduction in the rate of death from stroke (95% CI 1% to 62%, p = 0.05), a 21 percent reduction in the rate of death from all causes (95% CI 4% to 35%, p = 0.02) and a 23 percent reduction in the rate of death from cardiovascular causes (95% CI –1% to 40%, p = 0.06).¹¹³ Fewer serious adverse events were reported in the active treatment group (358 v. 448 in the placebo group, p = 0.001). The authors concluded that antihypertensive treatment in patients 80 years of age or older was beneficial.

A Cochrane meta-analysis by Musini and associates also examined the effects of age and blood pressure lowering on overall mortality, cardiovascular mortality and morbidity and withdrawal due to adverse effects in people 60 years and older with mild to moderate systolic or diastolic hypertension.¹¹² Fifteen trials (24,055 subjects ≥ 60 years) with moderate to severe hypertension were included which mostly evaluated first-line thiazide diuretic therapy for a mean duration of treatment of 4.5 years. Treatment reduced total mortality, RR 0.90 (0.84, 0.97); event rates per 1000 participants reduced from 116 to 104. Treatment also reduced total cardiovascular morbidity and mortality, RR 0.72 (0.68, 0.77); event rates per 1000 participants reduced from 149 to 106. In the three trials restricted to persons with isolated systolic hypertension the benefit was similar. In very elderly patients ≥ 80 years the reduction in total cardiovascular mortality and morbidity was similar RR 0.75 [0.65, 0.87] however, there was no reduction in total mortality, RR 1.01 [0.90, 1.13]. Withdrawals due to adverse effects were increased with treatment, RR 1.71 [1.45, 2.00]. The authors concluded that treating healthy persons (60 years or older) with moderate to severe systolic and/or diastolic hypertension reduces all cause mortality and cardiovascular morbidity and mortality. The decrease in all cause mortality was limited to persons 60 to 80 years of age.

The relationship between blood pressure and cardiovascular risk is “continuous, consistent, and independent of other risk factors.”¹⁰⁶ The American Heart Association guidelines for the primary prevention of ischemic stroke report that the higher the blood pressure, the greater the stroke risk.⁹ The working group acknowledged the benefit of treatment of hypertension for the primary prevention of stroke and concluded that the reduction of blood pressure is generally more important than the agent used to aid in this goal.

Hypertensive patients with a history of cerebral vascular disease are at particularly high risk of stroke recurrence. Gueyffier and associates performed a meta-analysis using all available randomized controlled clinical trials assessing the effect of blood pressure lowering drugs on clinical outcomes (recurrence of stroke, coronary events, cause-specific and overall mortality) in patients with prior stroke or transient ischemic attack.¹¹⁴ Nine trials that included a total of 6752 patients were identified, and it was found that the recurrence of stroke, fatal and nonfatal, was significantly reduced in treatment groups compared with control groups consistently across the different sources of data (RR = 0.72, 95% CI 0.61–0.85). There was no evidence that this intervention induced serious adverse effects.

For several reasons, categorizing patients as “hypertensive” or “normotensive” based on an arbitrary blood pressure threshold may not be helpful with respect to secondary stroke prevention. First, the relationship between blood pressure and stroke is continuous and graded, with no evidence of a lower blood pressure threshold for stroke risk.^107,115 Second, several controlled trials have demonstrated that blood pressure reduction benefits patients who would not normally be designated as hypertensive (Heart Outcomes Prevention Evaluation [HOPE],¹¹⁶PROGRESS¹¹⁷). Blood pressure lowering therapy reduces the risk of vascular events across a wide spectrum of initial blood pressures.^116,117

Angiotensin receptor blockers have demonstrated efficacy for the prevention of stroke in both the primary and secondary prevention settings. Three recently completed trials of angiotensin receptor blockers were the Losartan Intervention For Endpoint Reduction Study (LIFE),¹¹⁸ the Acute Candesartan Cilexetil Therapy in

Stroke Survivors Study (ACCESS),¹¹⁹ and the Study on Cognition and Prognosis in the Elderly (SCOPE).¹²⁰ All 3 trials demonstrated consistent relative risk reductions for stroke in the range of 24 percent to 34 percent, despite the enrolment of different patient populations, the use of varying angiotensin receptor blockers and differing interventions in the control group (placebo-based or conventional therapy).

The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) compared the ACE inhibitor ramipril, the angiotensin-receptor blocker telmisartan and the combination of the 2 drugs in patients with vascular disease or high-risk diabetes.¹²¹ Patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke or hospitalization for heart failure. The researchers found that telmisartan was equivalent to ramipril in patients with vascular disease or high-risk diabetes and was associated with less angioedema. The combination of the 2 drugs was associated with more adverse events without an increase in benefit.

Launer and coworkers assessed the long-term relationship of midlife blood pressure levels to late-life cognitive function in the surviving cohort members of the prospective Honolulu Heart Program.¹⁰³ The subjects were 3735 Japanese American men living in Hawaii either in the community or in institutions, with an average age of 78 years at the fourth examination. Cognitive function, measured by the 100-point Cognitive Abilities Screening Instrument, was categorized as good (reference category, with score of 92 to 100), intermediate (score < 92 to 82) and poor (score < 82). Midlife systolic blood pressure and diastolic blood pressure values were measured in 1965, 1968 and 1971. A respondent was classified into one of the following categories if 2 of 3 measurements fell into the following groups: for systolic blood pressure, < 110, 110 to 139, 140 to 159 and ≥ 160 mm Hg; and for diastolic blood pressure, < 80, 80 to 89, 90 to 94 and 95 mm Hg. The risk for intermediate and poor cognitive function increased progressively with increasing level of midlife systolic blood pressure category (p for trend < 0.03 and < 0.001, respectively) when controlled for age and education. For every 10 mm Hg increase in systolic blood pressure there was an increase in risk for intermediate cognitive function of 7 percent (95% CI 3%–11%) and for poor cognitive function of 9 percent (95% CI 3%–16%). The level of cognitive function was not associated with midlife diastolic blood pressure. The authors concluded that early control of systolic blood pressure levels may reduce the risk for cognitive impairment in old age.