The management of hypertension for primary stroke prevention: a proposed approach
Conflict of interest: Mukul Sharma: Speakers Bureau for Boehringer Ingelheim (BI), Sanofi/BMS, Merck and Pfizer (modest relationship), and consultant/advisory board for Boehringer Ingelheim (BI), Sanofi/BMS (modest relationship). Antoine Hakim: None declared.
Antoine M. Hakim*, University of Ottawa, 2413–451 Smyth Road, Ottawa, ON, Canada K1H 8M5. E-mail: email@example.com
The prevalence of hypertension in society is high and increasing. Untreated hypertension results in stroke, dementia, and damage to major organs. This article reviews the risks that hypertension causes and the issues now generally accepted as playing a role in the low level of hypertension control. These include lack of public awareness of the significance of elevated blood pressure, lack of impetus to measure blood pressure, lack of sites to perform the measurements, occasional therapeutic inertia on the part of the medical community, and poor compliance with treatment on the part of affected individuals. Innovative measures that may result in improved management of this risk factor are discussed. These include ubiquitous blood pressure measurement sites, expanding therapeutic potential by involving allied health professionals, and offering rewards for treatment and for compliance. The article also emphasises that the ideal blood pressure target for the primary prevention of stroke remains unclear.
Since 1965, with the publication of an article by William Kannel and colleagues from the Framingham Study, we have been aware of the risk factors leading to cardiovascular disease (1). Today, no one doubts the fact that elevated blood pressure (BP) increases the risk for stroke, and that lowering elevated BP profoundly reduces its occurrence, and yet there is ample evidence that individuals and health care systems around the world are struggling to control hypertension (2). This article attempts to describe the extent of the problem, focuses on the need to control hypertension for primary stroke prevention, and suggests some innovative means that may improve the management of this major stroke risk factor.
How big is the problem of hypertension?
Worldwide, 26·1% of adults were estimated to have hypertension in 2000, two-thirds of whom were thought to reside in developing countries (3). An increase of 60% in those suffering from hypertension is expected by 2025, resulting in 1·56 billion hypertensive individuals within 15 years. The rate of increase is expected to be higher in developed countries as the prevalence is strongly linked to age. According to a recent World Health Organization (WHO) report, 51% of stroke deaths worldwide are attributable to high systolic blood pressure (SBP) (4). In a previous report, WHO had confirmed that the majority of diagnosed hypertensive individuals were inadequately controlled worldwide (5).
Reports from individual countries confirm these alarming figures and trends. In a German cohort of 47 395 consecutive unselected patients with diagnosed hypertension in primary care settings, the mean SBP was 147/86 mmHg, and only 29·1% of patients had an SBP of <140 mmHg (6). This is despite the observation that drug treatment was given in 73·5% of the total cohort of patients, pointing to the issue of potential noncompliance with prescribed treatments. The mean 10 year risk of stroke was 26% in the total cohort.
A recent report by Statistics Canada showed that among Canadian adults aged 20–79, 19% were hypertensive, with SBP and diastolic blood pressure (DBP) above 140 and 90 mmHg, respectively (7). An additional 20% of the population had SBP between 120 and 139 mmHg or DBP between 80 and 89 mmHg, referred to as ‘prehypertension’. Another recent report showed a 77% increase in the prevalence of hypertension in Canada between 1994 and 2005 (8). Ominously, the prevalence increased from 1·0% to 3·7% in the 12–34 age group and from 5·6% to 12·8% in those aged 35–49, suggesting that we face an increased burden of cerebrovascular disease as these cohorts age. Hypertension is a very common condition worldwide, and its prevalence is increasing.
Hypertension as a risk factor
Hypertension has been identified as a major risk factor for strokes. Increasingly, the neurological literature also emphasises its association with cognitive disorders including dementia (9). The damage caused by hypertension also extends beyond the brain to include a number of other vascular organs.
The INTERSTROKE Study, using a matched case–control design, evaluated the contribution of various risk factors to the burden of stroke worldwide. The authors concluded that hypertension provided 34·6% of the population-attributable risk (PAR) for stroke (10). If, in addition to patient-reported history of hypertension, a BP higher than 160/90 mmHg was measured, PAR for stroke due to hypertension increased to 52%. When the risk from hypertension was combined with current smoking, abdominal obesity, poor diet, and lack of physical activity, it accounted for more than 80% of the global risk for all strokes. These findings are consistent with a previous study by Ezzati and colleagues, which attributed 70–76% of strokes occurring in 14 subregions of the world to a limited number of risk factors, with hypertension as the biggest driver of stroke risk (11).
More local studies have reached the same conclusions. Danaei et al. (12) estimated the effect of four preventable risk factors on life expectancy in the United States and found that control of SBP would provide 31% of the life expectancy gain if it were reduced, along with BMI, fasting plasma glucose, and smoking. Similarly, in an Argentinean study, Rubinstein et al. (13) calculated that hypertension was responsible for 37% of the potential years of healthy life lost due to stroke and coronary heart disease. It is important to point out that covert strokes, which, depending on the age group, are estimated to have an incidence that is eight to 10 times higher than clinically evident stroke (14), also have a strong association with hypertension (15). Thus, very significant reductions in stroke incidence can be achieved within relatively short time horizons by lowering BP even by modest amounts.
Reduced cognitive function
In a large observational study of a healthy population, an increase of 10 mmHg in DBP was associated with 7% higher odds of cognitive impairment (16). Launer et al. (17) had earlier estimated that a 1 mmHg increase in SBP in midlife was associated with a 1% increase in the risk of cognitive decline later in life. Hypertension is also a risk factor for Alzheimer's disease, and the presence of a single lacune at autopsy increased the probability of dementia by a factor of 18 in the Nun Study (18). This occurred even if the lacune had not been symptomatic. Imaging and other studies have demonstrated that lesions in the white matter are common, related to hypertension, increase the risk of mild cognitive impairment, and more than double the risk of dementia (19–22). Also, when surveys reviewed the causes of dementia, taking into account the presence of vascular risk factors, they showed a decrease in pure Alzheimer's disease as a cause, in favour of a vascular aetiology (23). Finally, data from the PROGRESS and other trials have demonstrated that antihypertensive treatment is associated with a lowering in the grade of white matter lesions and their cognitive consequences (24, 25). Thus, hypertension is associated with a significantly increased risk for cognitive impairment including dementia, and the risk declines with a reduction in BP.
The brain is most at risk from hypertension
It is important to note that hypertension creates a higher risk for stroke than it does for damage to any other organ. Hypertension and prehypertension are known risk factors for coronary artery disease, renal failure, and blindness (26, 27). ALLHAT (Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial) confirmed the elevated incidence of coronary disease with hypertension and showed that antihypertensive drug therapy reduced the risk for myocardial infarction and death (28). A recent revaluation of this trial confirmed its findings (29). Comparison of the results of INTERSTROKE with the previously reported INTERHEART study revealed that hypertension provided 34·6% and 17·9% of the PAR for stroke and myocardial infarction, respectively (30). In population-based studies, individuals with stroke were more likely to be hypertensive than those with myocardial infarcts (31). At standard doses, drugs that lower BP reduce the incidence of stroke more than myocardial infarcts (32), and do so regardless of BP levels before treatment. In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, 4733 participants with type 2 diabetes were assigned target SBPs of <120 or <140 mmHg and followed for 4·7 years for vascular outcomes. Stroke was the only outcome with a significantly lower incidence in the intensive therapy group (33). The inescapable conclusion is that controlling hypertension would reduce the incidence of strokes and attenuate the reduction in cognitive function. Management of hypertension will also confer benefits to structures and organs beyond the nervous system, highlighting the need to deploy all possible measures to improve the control of this major risk factor.
Is there an ideal BP target for primary stroke prevention?
Considering the overwhelming evidence that hypertension is a major cause of damage, particularly to the brain, it is distressing to note that there is no clear guidance in the literature – for example, arising from a randomised clinical trial – as to the target BP for the effective prevention of first strokes. In a recent Cochrane review of BP targets for hypertension, the authors state that no trials comparing different SBP targets were found (34). In a meta-analysis of risk stratification for the prevention of cardiovascular complications of hypertension, Girerd and Giral conclude that each reduction of 2 mmHg in SBP is associated with a 25% reduction in stroke events (35). This reduction in stroke risk occurs quite rapidly in response to treatment. The Systolic Hypertension in the Elderly Program (SHEP) showed that treatment of hypertension reduces the incidence of all stroke types, including lacunar, within one-year of treatment (36). More recently, Beckett and colleagues showed that in patients 80 years of age or older, active treatment that lowered mean SBP and DBP by 15·0/6·1 mmHg resulted in a 39% reduction in the rate of fatal strokes at two-years of treatment (37), and Jones and colleagues estimated that a 35–44% reduction in the incidence of new strokes can be achieved by lowering BP (38).
The available evidence from trials where DBP was managed also suggests that the current target BP of 140/90 mmHg is too high for effective stroke prevention. Sokol and colleagues concluded from their review of the effect of BP management on the incidence of primary and secondary strokes that prolonged reductions in DBP of 5, 7·5, and 10 mmHg would be associated with lower stroke rates of at least 34%, 46%, and 56%, regardless of the starting BP level (39). Taken as a whole, this information shows a linear relationship between BP reduction and the benefit in terms of strokes avoided. That confirms the conclusions of published analyses that for both SBP and DBP, there was no threshold value below which the linear association between lower BP and lower risk of strokes changed (40, 41).
Published recommendations for the management of hypertension for primary stroke prevention remain as high as they are because of the lack of firm evidence to do otherwise. The 2008 recommendations of the Canadian Hypertension Education Program (CHEP) for the management of hypertension suggest that BP should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease, without further specification (42). Similarly, the WHO recommends that the primary goal of therapy for low- and medium-risk individuals should be below an SBP of 140 mmHg. In patients with diabetes, a target of <130 mmHg systolic and 80 mmHg diastolic should be the goal (5). These recommendations lend unwarranted credibility to the value of 140/90 mmHg as a therapeutic upper limit, which is unfortunate not only because it is a value that clearly results in a high incidence of stroke but also because it has affected our evaluation of how well we are managing hypertension in society. While Flack and colleagues state that these goal levels should be considered more like ceilings than floors (43), a recent report declaring that a population's BP is now ‘controlled’ because 60% of the individuals maintained their BP below 140/90 mmHg gives a false sense of accomplishment (44).
A major deficit in our ability to manage hypertension for primary stroke prevention is the absence of firm guidance, based on evidence, as to what the target BP should be for improved primary prevention of strokes and hypertension's other major consequences. This can only be answered by a new study that attempts to define a target, and the challenges of designing such a trial have been described recently (45). The SBP Intervention Trial (SPRINT) launched by NIH recently, where target SBP will be <120 mmHg, should go a long way towards filling this gap. In the meantime, despite our ignorance of the ideal BP target, we can set for ourselves the goal of improving management of hypertension at the population level, the only therapeutic guide being that within reason, lower is better for optimum brain protection.
Innovative methods for hypertension control
In his article ‘Sick individuals and sick populations’, Rose (46) coined the term ‘prevention paradox’ to refer to the observation that the majority of vascular disease occurs in individuals with average risk factor levels, and proposed population-based approaches aimed at shifting population means downward. Increasingly, however, the consensus appears to be that the most effective approach to control hypertension is to combine a population-based strategy, one that provides an opportunity to give lifestyle advice, with focused interventions in those found to be at a high risk (47, 48).
The reasons for the less than optimal control of hypertension have been studied. Of the 167 countries surveyed by the WHO, national hypertension guidelines were not available in 61%, health professionals were not trained to manage this condition in 45%, and antihypertensive treatment was not affordable in 25% (49). The World Stroke Organization has attempted to respond to this need by publishing best practice guidelines on its website. A study performed in Canada showed that a large part of the problem is the lack of awareness by individuals of their hypertension and its significance (50). In the United States, 31% of white, 27% of African American, and 41% of Mexican American people with hypertension were unaware of their condition (51). In a significant percentage of individuals, becoming aware of hypertension did not result in therapy. ‘Therapeutic inertia’ is offered as an explanation for the fact that 87% of clinic visits where BP values were above 140/90 mmHg did not elicit a treatment response (52). This is a clear indication that a larger percentage of therapists need to be firmly convinced to take this risk factor more seriously and offer to treat it. In some settings, serious gaps have been reported between the perception of therapists, as to how well they managed their patients' hypertension, and the reality (53). For a variety of economic reasons, and sometimes side effects, patient noncompliance with BP treatment can be high, with some studies reporting that half the treated hypertensive patients discontinued their medications within one-year (54). This has led to suggestions we make below for methods to increase public awareness of the problem of hypertension and its impact while simultaneously maximising opportunities for its treatment. Many of these ideas still need to be proven by an accepted trial methodology, but the literature already suggests that they may prove successful in reducing the burden of illness by moderating the impact of hypertension.
Increase opportunities for public sensitisation and BP measurement
The Airdrie Community Hypertension Awareness and Management Program (A-CHAMP) (38) was a community-based programme for seniors designed to increase awareness in the public as well as the health care providers about hypertension, and improve its management. Volunteer peer health educators were recruited from the community and trained to manage BP screening sessions in local pharmacies. Residents who were 65 years of age and older were invited by their family physicians to attend the A-CHAMP sessions. The volunteer educators identified participants' cardiovascular risk factors, assessed BP using a validated automated device, and implemented a management algorithm. As a result, during the three-month programme, 36·5% of the patients were identified as having elevated BP, and of these, 71% returned for a follow-up session four- to six-months later. At that time, the mean SBP was reduced by 16·9±17·2 mmHg and 56% of the participants achieved predefined BP targets. A follow-up study that extended the programme to 39 communities and used a similar methodology has just been published. It showed that in the participating communities, within one-year, there was a 9% relative reduction (P<0·002) in hospital admissions with a primary diagnosis of acute myocardial infarction, stroke, or congestive heart failure (55). Similar programmes have been successful in the United States (56) and in Australia as part of the ‘know your numbers’ programme (57). In the United Kingdom, in addition to a public education programme, pharmacists are allowed to prescribe medications for BP management (58). Individuals are willing to learn, can clearly benefit from educational and therapeutic opportunities when offered, and the cost of health care can be reduced by population-based programmes that can identify individuals at risk.
It would seem reasonable, then, that we should strive to substantially increase the public's knowledge about the consequences of uncontrolled hypertension and the opportunities available to citizens for measurement and treatment of hypertension. Trained volunteers can be stationed in pharmacies where clients could be encouraged to have their BP measured while they wait and depending on the results, educated or directed to therapeutic venues. Also, validated BP measurement devices and education on the meaning of a particular value can be made available on a volunteer basis in locations where citizens are likely to ‘wait their turn’– grocery stores, barber shops, hairdresser salons, car-repair garages – and therefore have some time on their hands. These stations would be supplied with educational material in simple language describing the consequences of hypertension and identifying locations where opportunities for hypertension management exist in that area.
Increase opportunities for the management of hypertension
The data strongly suggest that more opportunities must be created to treat hypertension once it is recognised. This can be accomplished by involving trained health providers who work in partnership with MDs in the provision of BP treatment. Nurses and pharmacists, to name but two groups, could be trained to treat this condition, monitor any side effects of the therapies provided, improve adherence to the treatment regimen, and refer the individuals to MDs when needed, akin to the role of midwives in obstetrics (59). Home-based monitoring of BP and adjustment of therapy can be effective, as can brief but regular reinforcement of messages by telephone as seen in other medical conditions (60).
Establish a pervasive reward system for improved BP management
A reward, no matter how small, applied at multiple levels, would improve the odds of hypertension recognition and successful management. Cash rewards have been used as a means of improving the odds of obtaining the desired outcomes even in unlikely settings such as increasing physicians' response to survey requests (61). Cash rewards are being used to increase the likelihood of successful obesity management (62, 63) and smoking cessation (64). Thus, physicians could offer rewards to their hypertensive patients if on return visits they show that they followed prescribed therapies with the desired BP outcomes. Finally, if the conditions for a successful programme are satisfied, physicians themselves may be rewarded in a pay-for-performance policy that is currently being discussed and put into practice in some jurisdictions (65, 66). While some may decry the potential for these programmes to put undue emphasis on monetary rewards – rather than ‘doing the right thing’– rewards do work, they do not have to be large to be effective and can be used safely towards this important goal of health management. The literature suggests that the cost of such programmes is an investment that will result in significant returns through reductions in health care costs.
In summary, hypertension is a major risk factor particularly for stroke and dementia, causes damage to multiple organs in addition to the brain, represents a major social and economic burden, and yet it is easily measured and treated. What is needed is the definition of a reasonable target for BP in the population for effective primary prevention of stroke, a plan to reach it, and the will to invest in making effective BP management a reality.