Contributions to Hypertension Public Policy and Clinical Practice: A Review of Recent Reports

The clinical practice of hypertension continues to change. This reflects new research on the basic mechanisms of this condition, a broader understanding of therapeutic strategies, and a growing realization that hypertension is of critical importance worldwide as a cause of cardiovascular events and premature mortality. The definitions of hypertension are part of this change. During the past 40 or 50 years, the systolic blood pressure (SBP) thresholds for diagnosing hypertension and setting treatment targets have ranged from 160 mm Hg all the way down to a potential value of 120 mm Hg, assuming that the recent Systolic Blood Pressure Intervention Trial (SPRINT)1 will influence future hypertension practice. There is uncertainty regarding the best way to measure blood pressure (BP) in clinical practice: Should we remain with the conventional sphygmomanometer and stethoscope, or should we now depend on the newer automated oscillometric devices? Has ambulatory BP monitoring (ABPM) become the new gold standard for diagnosis? Or should we start to rely more on home BPs? There is a belief among some experts that BP, although important in itself, is also a surrogate measure of underlying arterial disease, so might it not be more appropriate to diagnose hypertension, and judge the success of its treatment, by depending on measures of vascular disease such as pulse wave velocity? And, from a public health point of view, might it not be possible to make a huge population-wide impact on the problem of hypertension by introducing major lifestyle changes into our communities, particularly reductions in sodium intake? We anticipate that SPRINT1 and other recent clinical trials and analyses will form the basis for new hypertension practice guidelines being prepared in the United States, Europe, and other major centers throughout the world. Certainly, there will be a call for the international organizations engaged in hypertension to provide guidance and advice on how best to manage hypertension, including countries and communities with severely limited resources. It is interesting, even as this important work gets underway, to look at recent publications by distinguished hypertension experts, many published within the pages of this Journal, which can give some sense of where the practice of hypertension will be heading during the next several years. The importance of hypertension has recently been highlighted by the World Health Organization (WHO).2 Of striking interest, for the first time a noncommunicable disease—hypertension—has been recognized as a primary cause of major illness and premature mortality across the globe. Among major efforts being made to address this problem is the Global Standardized Hypertension Treatment Project,3, 4 which aims in an immediate fashion to recommend simple and achievable ways to control BP across a wide range of economic and social conditions. The World Hypertension League (WHL) is one of the leading organizations involved in addressing global needs for broad and achievable strategies for hypertension management. The membership of the WHL comprises almost 100 national hypertension societies, associations, and partners. In addition, the WHL represents over 50,000 healthcare providers directly and over 100,000 indirectly through its communication network. This provides a powerful base for WHL's authoritative voice dealing with major aspects of hypertension policy, diagnosis, and management. This Journal is the official journal of the WHL and so its reach is now global in scope and plays a major part in the world's hypertension literature. The Journal of Clinical Hypertension has provided the forum for several authoritative policy statements and position papers by the WHL dealing with critical aspects of public policy and clinical practice in hypertension.5, 6 Clearly, it is difficult to make progress in this work unless there are reliable data to guide plans for addressing hypertension globally, and so the report by the WHL setting out standards for the uniform reporting of hypertension in adults using population survey data stands as a powerful recommendation to individual countries regarding such core indicators as BP distribution, prevalence of hypertension, awareness of this condition, antihypertensive drug treatment, and control of hypertension.7 Hopefully, this standardized approach to collecting data will provide critical information that will allow public health authorities as well as practitioners to optimize the care of hypertensive patients. One of the most important trends in hypertension, in common with other conditions, is the growing proportion of patients aged 80 years and older. There has been a rapid increase in the number of older people with hypertension,8 and, compared with younger age groups, these individuals have a substantially greater risk of major cardiovascular outcomes.9 In a major analysis of these trends in the United States, public health experts at the University of Alabama at Birmingham have reported that the critical areas of awareness, treatment, and control of hypertension, as well as the use of appropriate multidrug treatment regimens, have all improved progressively during the period from 1988 to 2010.10 It will be very interesting to see further reports in this group of patients aged 80 years and older to determine whether even in the few years since 2010 there has been even more progress. Major clinical trials such as SPRINT1 and the Hypertension in the Very Elderly Trial (HYVET)11 have emphasized the powerful cardiovascular protective benefits of antihypertensive therapy in this age group. All of us who have worked in the field of hypertension know how inconsistent BP readings can be, even when they are taken carefully within the same patient. This problem is magnified when we consider how best to bring hypertension diagnosis and care into communities with limited resources where BP measurements are often made by nonprofessional health workers. This concern has led to a policy statement by the WHL on noninvasive BP devices.12 The WHL expert panel that issued this statement emphasized the importance of achieving consistency in measurements and the fact that the traditional auscultatory method for measuring BP is difficult to teach and perform.13 Thus, this panel has recommended a concerted effort to validate semiautomated and fully automated oscillometric devices that are reliable and—of critical importance in many areas of the world—affordable.12 There is by now a strong awareness of the so-called white-coat effect, in essence the increase in BP produced simply by the fact that a professional person such as a doctor or nurse is measuring a patient's BP. Dr Martin Myers and his colleagues have been highly influential in developing methods for measuring BP in the clinic or office that minimize this effect and so provide BPs that are representative for each patient. In an expert commentary,14 Dr Myers has discussed practical ways to minimize the white-coat effect or “human factor.” He points out that the most effective method for achieving a meaningful BP reading is to use automated devices in a setting where patients are “nonobserved”—in other words, without a doctor, nurse, or other professional person in the room.4 In fact, SPRINT based its method for measuring BP on this principle of nonobserved automated readings, a strong acknowledgement of the recognition of this approach. Of course, it will become necessary for us to find ways of translating BPs measured in this fashion into values that correspond to those normally obtained by “conventional” office or clinic readings. It is a matter of concern that there will be confusion in interpreting BP values from clinical trials such as SPRINT until there is broad agreement on exactly how BPs should be measured. Nighttime BP may be particularly predictive of future cardiovascular events. Clearly, to obtain meaningful BPs during the hours of sleep it is necessary to use techniques such as ABPM. It has been demonstrated, using ABPM, that cardiovascular outcomes such as silent cerebral infarcts15 or left ventricular hypertrophy16 are best predicted by nocturnal BP values. A more recent study by Chinese investigators has emphasized that nighttime BP is strongly associated with the risk for hemorrhagic strokes, and that patients whose BPs fail to show the normal fall or dipping pattern at night are particularly susceptible to these major events.17 These data, of course, raise the issue of how best to identify such patients and how to most effectively protect them; inevitably, there has been much interest in dosing antihypertensive drugs late in the evening in order to provide maximum BP reduction and cardiovascular protection during the nighttime hours. Heart rate is usually measured with BP but hasn't received as much attention as a predictor of outcomes. Even so, there is a good basis for believing that high heart rates, perhaps indicative of excess sympathetic activity, might be independently associated with events.18, 19 In trying to better understand this relationship, it is interesting to note that a recent publication showed that nighttime heart rate was related to important inflammatory markers such as leukocyte counts and C-reactive protein levels.20 These mechanisms that might possibly underlie the increased risk of adverse outcomes deserve further exploration. There are several clinical findings that are produced by hypertension and can serve to predict major outcomes. For instance, findings such as left ventricular hypertrophy, increased intima-media thickness of the carotid vessels, microalbuminuria, and reduced glomerular filtration rate (GFR) are highly suggestive of future cardiovascular outcomes. Recently, there has been a focus on the variability of BP from visit to visit during the treatment of hypertension, termed visit-to-visit variability (VVV); likewise, one of the best markers of arterial stiffness is pulse wave velocity, most commonly measured between the carotid and femoral arteries (cfPWV) or between the brachial and ankle vessels (baPWV). It has now been well described that an increase in VVV across several clinic visits is associated with increased fatal and nonfatal coronary and stroke outcomes.21, 22 Dr Paul Muntner and colleagues23 have reported the effects of differences in VVV across five to seven visits during the Antihypertensive and Lipid-Lowering Therapy to Prevent Heart Attack Trial (ALLHAT). In particular, these investigators looked at the effects of the primary drugs being examined in ALLHAT, namely chlorthalidone, amlodipine, and lisinopril. Compared with chlorthalidone, amlodipine had a lower VVV (as measured by the standard deviation of the mean BPs across the visits), whereas lisinopril had a higher VVV. Potentially, these findings could explain some of the differences in outcomes between these agents during the ALLHAT trial, and so might be a useful tool for further determining the effectiveness of therapeutic interventions. A similar approach looking at the variability of BP across visits has been applied by Dr John Kostis and colleagues to the Systolic Hypertension in the Elderly Program (SHEP) trial.24 Performing a 17-year follow-up of mortality from the trial (using the United States National Death Index), these investigators showed that VVV was associated with mortality and appears to be particularly predictive of adverse events in actively treated patients (with chlorthalidone); it was less predictive in the placebo group. The investigators suggested that the variability between visits could simply be accounted for by a lack of consistency by patients in taking their medication, although a finding of increased VVV could also reflect the effects of large-vessel stiffness.25 There have been differing estimates of the effects of VVV on renal function. In one trial, it was shown that in patients with nondiabetic chronic kidney disease there was a clear relationship between increases in VVV and declines in renal function.26 However, in a later study, the same authors in a study of patients with diabetic CKD followed over 12 consecutive visits found that there was not a clear relationship between VVV and a decline in renal It is progressively more that there are differences between diabetic and nondiabetic patients in their vascular to BP, and so the between in nondiabetic and diabetic patients should not be wave is now as a useful and of arterial arteries to increased and have been associated with renal However, one recent trial looked at and and showed that of these increased as these not the pulse pressure between systolic and which can also serve as an of was associated with renal in the that was Clearly, we are for useful or surrogate to guide of renal but it at this time that VVV are the most useful measurements of changes in the It is that increased as a predictor of arterial is by changes in the arterial including and increased down of the relationship between arterial stiffness and coronary disease, investigators patients for coronary The was measured with an oscillometric which a greater in the coronary disease patients when compared with This study also found that was predictive not of the of coronary disease but also some of its is whether therapy for hypertension can and provide potential for a reduction in arterial It is that during there is an increase in which perhaps is greater in people with hypertension or at risk for hypertension in In a new report that patients with hypertension, the greater increase in that they compared with could be by the There is growing the effects of on arterial and the that could be a powerful guide in determining the effectiveness of hypertension treatment further exploration. It is that as a measure of arterial stiffness in hypertension has now been recommended by a There has been a to the of and the that oscillometric devices could be a for the more methods is One such approach an oscillometric in each of the and showed that such measurements in each of the or into a of all has a relationship with obtained by arterial measurements in patients It is that an range of devices will become for clinical use in the next few years. of cardiovascular in hypertension, for many years but not often has been of left It has been that for that left ventricular is an of heart a recent study of hypertensive patients that was more common This study also that an increase in was associated with heart with which is a common form of heart associated with The same that this relationship was in patients who had of This report that for could be an important of heart in This could be a very simple and useful clinical tool for of in patients with with and policy has become a and difficult There is agreement that excess of are associated with higher BP and an increased risk of cardiovascular but it is not clear at which a meaningful health The issue has been further by the fact that at the of at well there may be a for an increase in adverse outcomes. This of may be a of and simply reflect the fact that people with and fatal illness may be reduced and of that to the of this are related to the fact that measuring in individual people is the standard approach for is a for but this is often In addition, even when this is the measurements of can from to the fact that has been there is a strong belief among public health on a population a reduction in be associated with a BP reduction across the population and so a reduction in cardiovascular outcomes. of the lack of in the WHL in with other major organizations such as the Heart Heart of the World and the and the World Organization published a strong statement on for greater and standards for future In particular, the statement attention to improved methods for in individuals and the and of clinical and including regarding the of and This statement was by a by Dr who that one of the major underlying in Dr that dealing with excess may be even more important the use of drugs for the treatment of hypertension since a in when applied to could the from to hypertension that with with this the in with the of Hypertension published a call to and the to the of This approach was first by the which made the point that this approach could be particularly in and The by the WHL and in many has become a major of these organizations in their plans to with the global issue of In to these efforts by the WHL and the the has also recommended a reduction in by In with this the in a follow-up policy statement dealing with targets and for in that several and several reduction targets into their national health for The WHL on to that the to success is not a reduction in the of sodium in but also clear and that can serve to guide individual as well as health workers. The WHL also made the point that this be most countries could their it to and It has been that sodium and will BP. However, a recent study based on adults without hypertension in the National Health and survey found between BP and sodium or This finding not mean that efforts to sodium and might not BP, but it to a in the possibly that individuals susceptible to excess or have a of hypertension, or that those for have become hypertensive may be more to sodium and In the of in hypertension, it be of interest to focus on patients with since they to be susceptible to of coronary a study in patients with a high more more to become hypertensive and as to have a cardiovascular as people with a lower It should be that most patients in that study years and that older people may be particularly to the effects of This is particularly interesting since it is that hypertensive patients have a of perhaps they to greater In fact, it has been shown in patients years and when to a for with or that they more individuals to a for the high This that is not a and should consider the of in their older hypertensive patients. It is that in countries there is a to greater of in the In for instance, it is that as many as of people 12 or more of this be an of people in are so to cardiovascular This may be further to a study which showed that hypertensive patients in had greater sodium by this the that hypertensive patients may simply have a when compared with people with normal In the to the National published their recommendation for BP targets in the treatment of This recommendation was since it that for people years and clinical trial best a systolic treatment of mm This recommendation was strongly in with that of other including that of the of Clinical which that the of mm Hg should remain for all adults with Clearly, these differences between guidelines important and there strong among experts from countries who to a issue of this Journal and their national recommendation with those of A of these was published in the same Of course, the on whether mm Hg or mm Hg should become the for the SPRINT trial, published a to make it clear that even in older patients many aged older the should be mm Hg office Clearly, this is a from the and one that almost in the to will the way practitioners manage the most patients with hypertension are and In hypertension in these people is to a that into and and a diagnosis of hypertension a BP the However, in a statement on hypertension, the is to the of benefits and of for high BP in to heart This a position to in essence a potential of with high BPs simply there has been clinical outcomes to of Even so, some experts of this that we not have information hypertension in and of this might to in The expert on to call for to the of BP in In a we have some important data on For instance, it is that surrogate such as left ventricular hypertrophy, increased carotid intima-media and can be in with in the very high of not to the of clinical may make such research to and further of surrogate outcomes. experts, also in on the with the approach of this out that the of BP in is since it is now as a part of between and and that to obtain an BP data base could in many patients with hypertension being One of the major in hypertension is including in younger A study of aged to years, compared with found higher higher and a higher prevalence of the of the of the these findings should also to the of lifestyle changes in such even in the of clinical trial This difficult and will be a for some time to it is in and adults where there might be the to the of vascular is a based on the that the renal will in reduced sodium and reduced of by the and a reduction in sympathetic This is usually by a into the renal arteries and or across the of the arteries to the renal that to the of these reports of in patients with hypertension powerful BP However, has been less important published in this Journal showed a in BP in patients to this the patients had strong mm Hg reductions in but other patients had including some patients whose these patients The can we predict which patients are to good clinical trials with more and using more may the benefits of this We should know more within the next 12 One of the with renal is the that across the of the renal could cause to the One method for renal arteries is to use the of to renal to measure the of and in renal arteries and renal There was in patients in of these measurements 12 the a control group of patients not to renal had for increased These investigators that this could BP without meaningful to renal In look at renal in patients renal it was shown that this was effective in BP in patients with chronic kidney In a follow-up study, it was that success in BP with renal might be an important of renal whose BP was by had higher at time points to 19 when compared with patients whose BPs not It is not clear whether the in BP might have been the cause of the improved renal or whether these but effects of the It is interesting that the in hypertension during the past of years has from a focus on to the public health and clinical practice aspects of this The by the that a noncommunicable such as hypertension is a major cause of premature mortality and cardiovascular disease has provided a major The often the pages of this Journal, has taken the in setting worldwide standards for many aspects of hypertension from a call for improved BP techniques to a focus on research in as well as a call for public and to start the sodium of clinical are leading the way to new hypertension practice almost will call for more control of BP in all of and For those of us to the field of hypertension, the future important new in an of that is of critical importance throughout the world.