© Springer International Publishing AG 2016
Md. Shahidul Islam (ed.)Hypertension: from basic research to clinical practiceAdvances in Experimental Medicine and Biology95610.1007/5584_2016_149Challenges in the Management of Hypertension in Older Populations
(1)
Centre for Health System and Safety Research, Australian Institute of Health Innovation, Macquarie University, North Ryde, Australia
(2)
College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
Abstract
The prevalence of hypertension increases with age making it a significant health concern for older persons. Aging involves a range of physiological changes such as increases in arterial stiffness, widening pulse pressure, changes in renin and aldosterone levels, decreases in renal salt excretion, declining in renal function, changes in the autonomic nervous system sensitivity and function and changes to endothelial function all of which may not only affect blood pressure but may also affect individual response to pharmacotherapy used to manage hypertension and prevent end organ damage and other complications associated with poor blood pressure control.
Unlike many chronic conditions where there is limited evidence for management in older populations, there is good evidence regarding the management of hypertension in the elderly. The findings from multiple large, robust trials have provided a solid evidence-base regarding the management of hypertension in older adults, showing that reduction of blood pressure in older hypertensive populations is associated with reduced mortality and morbidity. Diuretics, agents action on the renin angiotensin system, beta blockers and calcium channel blockers have all been well studied in older populations both in view of the benefits associated with blood pressure lowering and the risks associated with associated adverse events. While all antihypertensive agents will lower blood pressure, when managing hypertension in older persons the choice of agent is dependent not only on the ability to lower blood pressure but also on the potential for harm with older persons. Understanding such potential harms in older populations is essential with older persons experiencing increased sensitivity to many of the adverse effects such as dizziness associated with the use of antihypertensive agents.
Despite the wealth of evidence regarding the benefits of managing hypertension in the old and very old, a significant proportion of older individuals with hypertension have suboptimal BP control. While there is good evidence supporting blood pressure lowering in older antihypertensive agents, these have not yet been optimally translated fully into clinical guidelines and clinical practice. There appear to be considerable differences between guidelines in terms of the guidance given to clinicians. Differences in interpretation of the evidence, as well as differences in study design and populations all contribute to differences in the guideline recommendations with respect to older populations, despite the strength of the underlying scientific evidence. Differences around who is considered “old” and what BP targets and management are considered appropriate may lead to confusion among clinicians and further contribute to the evidence-practice lag.
Keywords
HypertensionPharmacotherapyGuidelinesAntihypertensiveAgedOlderDrug therapyHypertension is the leading modifiable cause of mortality worldwide. The prevalence of hypertension increases with age making it a significant health concern for older persons. Unlike many chronic conditions, there is good evidence regarding the management of hypertension in the elderly exists and pharmacotherapy is the mainstay of treatment for most patients. Given predicted international increases in the elderly population and the wealth of evidence regarding management of hypertension in the elderly, understanding how the risks associated with hypertension increase with age as well as how physicians currently manage older patients with increased blood pressure is important. Furthermore, insight into current barriers to the provision of optimal management is essential if we are to meet the health needs of the growing older population.
1 Who Is Old?
Internationally the proportion of the population that is considered older is increasing. In 1950, 8 % of the population was aged over 65 years, this increased to 10 % in 2000 and is predicted to exceed 20 % by 2050.(Department of Economic and Social Affairs United Nations 2002) It has been estimated that life expectancy for those aged 65 years has increased by 19 years for men and 17 years for women over the past century.(Rai and Mulley 2007) Projections indicate that by 2050 there will be over 2 billion older persons worldwide.(Halter 2009) However while there is international agreement that the population is aging there is less agreement regarding who should be considered “old”. (Gambert 1994) Aging encompasses a number of domains and different definitions focus on different aspects of the aging process. Chronological age is the simplest and most commonly used parameter to define age and refers simply to the number of years since birth. Yet aging is multidimensional and not just related to the duration of time in an individual’s life. Physiologically, aging refers to the general and gradual changes that human body experiences over time. Physiological aging is characterized by declining functional capacity, decreasing fertility and increased mortality all of which may vary from individual to individual. (Kirkwood and Austad 2000; Masoro and Austad 2006) Such variation among older populations and how it affects their response to pharmacotherapy is one of the challenges facing clinicians in the management of hypertension among older populations.
2 Hypertension and Aging
Population aging presents a number of healthcare challenges. There are implications in terms of resources and funding, as well as in the type of care that is delivered. Non-communicable chronic diseases such as cardiovascular disease currently account for almost two-thirds of deaths worldwide. (Mathers and Loncar 2006; Daar et al. 2007) Cardiovascular disease contributes significantly to the disease burden, disability and death in both developed and developing countries (Beaglehole et al. 2008; Murray and Lopez 1997; Yang et al. 2008) with an increasing burden among the elderly..(Daar et al. 2007; Murray and Lopez 1997) Despite predicted increases in population aging, The World Health Organization (WHO) has predicted that ischemic heart disease and stroke will remain among the leading causes of death worldwide. (Mathers and Loncar 2006) Hypertension is a major risk factor for cardiovascular disease (Menotti et al. 2004; Lim et al. 2013), affecting up to one billion individuals internationally (Chobanian et al. 2003) (Kumar 2013). It is one of the leading cause of death worldwide (The World Health Organisation 2016). The prevalence of hypertension increases with age (Fagard 2002), with approximately 30 % of the population aged under 60 years being considered hypertensive. Once we start looking at older populations, the prevalence of hypertension doubles to over 60 % for those aged over 60 years, with even higher prevalence with further aging as demonstrated by data from both the UK Framingham study (Kannel and Gordan 1978; Vasan et al. 2002; Beckett et al. 2012) and the US National Health and Nutrition Survey (NHANES) (Lloyd-Jones et al. 2005). The NHANES data demonstrates that increases in hypertension prevalence begin in adulthood, with the prevalence doubling between the ages of 20 and 40 years, and doubling again between 40 and 60 years (Kannel and Gordan 1978), while the Framingham study showed that this pattern continues with ongoing aging, with the prevalence of hypertension increasing from 27.3 % in those aged ≥ 60 years to 74.0 % in those aged over 80 years (Vasan et al. 2002).
Gender differences in the prevalence of hypertension have been noted in both younger and older populations. A number of studies have shown found that while the prevalence of hypertension is higher in younger males, this reverse after the age of 60, when the prevalence in females is greater than that in males (Halter 2009; Franklin et al. 1997; Mann 1992; Hajjar and Kotchen 2003; Primatesta and Poulter 2004; Trenkwalder et al. 1994; Gambassi et al. 1998).
Differences in the hypertension phenotype with respect to increases in systolic (SBP) compared with diastolic blood pressure (DBP) have also been reported in older hypertensive populations. Both systolic (SBP) and diastolic blood pressure (DBP) increase with age, (Franklin et al. 1997) however it has been proposed that DBP may plateau or even decrease from the age of 60 years, leaving the SBP to increase (Franklin et al. 2001). Such differences may account for the increase in isolated systolic hypertension that is noted among older populations. Increases in hypertension among older persons may be due to pathophysiological changes associated with aging such as increased peripheral vascular resistance due to arterial stiffening (Franklin et al. 1997; Mitchell et al. 2004). This increase in arterial stiffness with ageing is proposed to alter the normal hemodynamic patterns causing an increase in pulse wave velocity which is an index of arterial stiffness and a widening pulse pressure may account for age related decreases in DBP and increases in SBP (Mann 1992; Mitchell et al. 2004; Pinto 2007; Mackey et al. 2002). Other age related factors such as the changes in renin and aldosterone levels, decreases in renal salt excretion, declining in renal function, changes in the autonomic nervous system sensitivity and function and changes to endothelial function may further contribute to the increases in hypertension seen with aging (Halter 2009; Weinberger 1996; Fliser and Ritz 1998; Wallace et al. 2007). Age related life style changes such as decreased physical activity, changes in body fat composition, high sodium intake and obesity may further contribute to the development of hypertension among older persons. Moreover a synergistic effect on the risk of hypertension has been observed when multiple factors exist together (Halter 2009; Carretero and Oparil 2000; MacMahon et al. 1984; Barreto et al. 2001).
3 Pseudohypertension
Pseudohypertension is occasionally observed in older persons. In pseudohypertension, measurement of blood pressure using a sphygmomanometer results in a falsely elevated reading.(Kleman et al. 2013) This phenomenon is more common in older persons due to increased arterial stiffness, which results in falsely high reading upon blood pressure measurement due to the inability of the arteries to compress. Pseudohypertension is estimated to affect up to 7 % of patients with resistant hypertension (Kleman et al. 2013) and should be considered when older patients presenting with consistently elevated blood pressure over time but who show no signed of end organ damage or in those who treatment with antihypertensive agents result in ongoing symptoms of hypotension. In patients for whom pseudohypertension is suspected an intra-arterial blood pressure measurement is required.
3.1 Pharmacological Management of Hypertension in Older Populations
Unlike many conditions where limited evidence exists for management of those aged over 65 years due to the exclusion of older populations from clinical trials,(White 2010; Devlin 2010) the findings of multiple large, robust trials have provided a solid evidence-base regarding the management of hypertension in older adults. Adverse outcomes associated with poor blood pressure (BP) control in older persons have been well documented. A Cochrane review of 12 clinical trials showed that the management of hypertension in people aged 60 years and over was associated with a reduction in mortality (Relative Risk (RR)) = 0.9, 95 % confidence interval ((CI) 0.84–0.97).(Musini et al. 2009) The same review reported pharmacological management of hypertension in older adults was associated with significant reductions in both cardiovascular (RR = 0.77, 95 % CI 0.68–0.86) and cerebrovascular mortality (RR = 0.66, 95 % CI 0.53–0.82). (Musini et al. 2009) While life-style interventions are generally considered first-line for the management of all persons with hypertension, the majority of hypertensive patients, including older persons, will require pharmacotherapy to adequately control their blood pressure (Wallace et al. 2007). There have been a number of large well-conducted clinical trials exploring pharmacological management of hypertension in older populations and there is good evidence for the use of a variety of different antihypertensive agents in the management of hypertension in older persons (Pimenta and Oparil 2012).
3.1.1 Thiazide and Thiazide – Like Diuretics
Thiazides diuretics are one of the oldest drug classes used in the treatment of hypertension. (Huebschmann et al. 2006) Evidence of their effectiveness in lowering BP and preventing the cardiovascular and cerebrovascular adverse outcomes associated with hypertension in older people has been provided by several clinical trials, including the Hypertension in the very elderly trial (HyVET) (Beckett et al. 2012), the Swedish Trial in Old Patients with Hypertension (STOP) (Dahlöf et al. 1991; Hansson et al. 1999) and the Antihypertensive and Lipid-Lowering Treatment to prevent Heart Attack Trial; (ALLHAT) (Officers et al. 2002) studies While not all of these studies specifically recruited older participants, the mean participant age for all 3 was over 65 years, making their findings particularly pertinent to older populations.
Use of thiazide and thiazide like diuretics for the management of hypertension in older persons has declined over the past decade (Primatesta and Poulter 2004; Trenkwalder et al. 1994; Triantafyllou et al. 2010; Prencipe et al. 2000; Psaty et al. 2002). There are a number of factors that may have contributed to this decline including increased use of other non-thiazide diuretics, particularly by older persons with complicated hypertension (Van Kraaij et al. 1998) the advent of newer antihypertensives such as Calcium channel blockers (CCBs) and agents acting on the Renin Angiotensin System (RAS) and caution by prescribers due to increased risk of potential adverse drug reactions associated with the use of thiazide diuretics in frail, older persons (Onder et al. 2001; Moser 1998). Despite this general decline, the use of thiazide diuretics for the management of hypertension in the older individual remains high (Bromfield et al. 2014; Rodriguez-Roca et al. 2013; Tu et al. 2006), especially in fixed-dose combination products where they are among the most commonly used antihypertensive agents (Primatesta and Poulter 2004; Trenkwalder et al. 1994; Triantafyllou et al. 2010; Prencipe et al. 2000; Rodriguez-Roca et al. 2013; Svetkey et al. 1996).
3.1.2 Agents Acting on the Renin-Angiotensin System (RAS)
There are three main three antihypertensive classes that act on the RAS. These are the angiotensin blocking agents (ARBs), the Angiotensin converting enzyme inhibitors (ACEI) and the direct renin inhibitors (DRI). The use of both ARBs (Triantafyllou et al. 2010; Bromfield et al. 2014; Rodriguez-Roca et al. 2013) and ACEIs (Primatesta and Poulter 2004; Trenkwalder et al. 1994; Triantafyllou et al. 2010; Psaty et al. 2002; Bromfield et al. 2014; Rodriguez-Roca et al. 2013; Svetkey et al. 1996; Barker et al. 1998; Prince et al. 2012) in older populations has increased over recent years and now surpasses the use of many other antihypertensive classes. The increase in use of these agents for the management of hypertension in older populations has been supported by clinical trials such as the Second Australian National Blood Pressure (ANBP2) (Wing et al. 2003). ANBP2 demonstrated that ACEI were superior to thiazide diuretics in terms of cardiovascular outcomes in a population comprising 6083 older persons aged between 65 and 84 years. Despite benefits in cardiovascular outcomes no difference between ACEI and diuretics in terms of all cause mortality was observed. (Wing et al. 2003) In addition to increased use as monotherapy for the management of hypertension among older individuals, the use of ACEIs and ARBs in combination with other antihypertensive medications has also increased over recent years (Primatesta and Poulter 2004; Trenkwalder et al. 1994; Triantafyllou et al. 2010; Rodriguez-Roca et al. 2013; Svetkey et al. 1996). In contrast the uptake of aliskiren, a direct renin inhibitor has been slow. Aliskiren has been approved for use in older populations with hypertension since 2007 yet use of daily practice is limited in comparison to other antihypertensive agents (Bromfield et al. 2014; Rodriguez-Roca et al. 2013). The slow uptake of aliskiren for use among older persons may be in part due to concerns around limited efficacy and a poor safety profile (Parving et al. 2012; Gheorghiade et al. 2013).
3.1.3 Calcium Channel Blockers (CCBs)
Since the introduction of CCBs, the prescribing pattern of this antihypertensive medication class in older populations has increased both as monotherapy and combination therapy (Trenkwalder et al. 1994; Prencipe et al. 2000; Bromfield et al. 2014; Svetkey et al. 1996; Barker et al. 1998) and use remained steady until the mid 1990s (Psaty et al. 2002). Despite publication of the findings from the Systolic Hypertension in the Europe Trial (Syst-Eur) in 1997, which showed that treating 1000 patients for 5 years with a CCB prevented 29 strokes or 53 myocardial infarctions (MI), a decline in the use of CCB has generally been noticed in older and the very old patients since the mid-1990s.(Primatesta and Poulter 2004; Triantafyllou et al. 2010; Rodriguez-Roca et al. 2013) This decline may in part be due safety concerns with the use of CCBs older populations, including increased risk of cancer, MI and gastrointestinal haemorrhage with long-term use (Pahor et al. 1996a, b; Maclure et al. 1998).
3.1.4 Beta Blockers (BBs)
Beta blockers have been among the most commonly prescribed antihypertensive agents since their introduction into hypertension treatment (Psaty et al. 2002; Svetkey et al. 1996; Barker et al. 1998) However in recent years, use in older persons has declined following publication of a meta-analysis questioning the efficacy of the BB for hypertension and highlighting safety concerns, with an increased risk of stroke reported with use as monotherapy. (Larochelle et al. 2014) Consequently use of BBs for the management of hypertension in older populations has declined particularly as monotherapy for uncomplicated hypertension management. (Primatesta and Poulter 2004; Trenkwalder et al. 1994; Triantafyllou et al. 2010; Prencipe et al. 2000; Onder et al. 2001).
3.1.5 Alpha Blockers
While several studies have shown a slight increase in the use of alpha blockers in the management of hypertension in the old and very old (Psaty et al. 2002; Bromfield et al. 2014) in general, there has been a downward trend in the use of these agents (Trenkwalder et al. 1994; Rodriguez-Roca et al. 2013; Svetkey et al. 1996; Barker et al. 1998). This decline in use may be due to the poorer adverse effect profile of the alpha-blockers for older persons in comparison to newer agents such as the ACEI and ARBs, as well as to a lack of mortality evidence when compared with other antihypertensive agents.
3.1.6 Nitrates
While nitrates have an important role in the management of coronary artery disease, the lack of studies in older populations using nitrates for the management of hypertension have resulted in these drugs no longer having a major role in the management of hypertension. There has been some discussion around the potential benefit of nitrates for the management of hypertension in older populations, however to date they are not currently recommended in the main hypertension guidelines (Weber et al. 2014; Mancia et al. 2013a).
3.1.7 Choice of Antihypertensive Agent in Older Populations
While all antihypertensive agents will lower blood pressure, when managing hypertension in older persons the choice of agent is dependent not only on the ability to lower blood pressure but also on the potential for harm with older persons showing an increased sensitivity to many adverse effects. In general low dose thiazides, calcium channel blockers or agents acting on the renin angiotensin system appear to present the lowest risks for older populations.
3.2 Barriers to the Optimal Management of Hypertension in Older Persons
Despite the wealth of evidence regarding the benefits of managing hypertension in the old and very old, a significant proportion of older individuals with hypertension have suboptimal BP control (Falaschetti et al. 2014). A number of barriers to optimal blood pressure control in older persons have been identified. These barriers can be considered as system, prescriber or patient related (Alhawassi et al. 2015).
System–related barriers affecting blood pressure control in older populations include the variability in treatment recommendations for this population. (Schäfer et al. 2012; Psaty et al. 1995). While a number of clinical trials have been conducted in older populations, the extent to which this evidence has been incorporated into treatment guidelines and translated into practice remains unknown.
While older persons are often excluded from clinical trials for many conditions (Gross et al. 2002; Heiat et al. 2002), multiple large, well-designed trials exploring hypertension in older persons have been conducted (Dahlöf et al. 1991; Bulpitt et al. 2011). A Cochrane review published in 2009 reported 15 studies (n = 24,055 subjects) exploring the management of hypertension in those aged over 60 years (Musini et al. 2009). These findings demonstrated the considerable benefits of actively managing hypertension in older populations, as well as providing evidence regarding appropriate blood pressure (BP) targets and pharmacotherapy for this population.
Physician related barriers include differences in physician attitudes towards the risks and benefits of managing hypertension in older persons as well as differences in interpretation of the evidence. (Trenkwalder et al. 1994; Rodriguez-Roca et al. 2013).
Establishing the evidence is the first step in ensuring optimal care, yet it is well documented that there is a considerable lag in the translation of scientific evidence into current clinical practice. Moreover, incorporating the latest evidence into daily practice is something many physicians often find problematic (Spranger et al. 2004). One strategy aimed at minimizing the evidence-practice gap is the development and implementation of evidence based guidelines. Guidelines have the potential to improve care and improve patient outcomes (Grimshaw and Russell 1993) and multiple international guidelines for the management of hypertension exist.
Management of hypertension in older persons is one area where there appear to be considerable differences between guidelines in terms of the guidance given to clinicians. Differences in interpretation of the evidence, as well as differences in study design and populations all contribute to differences in the guideline recommendations with respect to older populations, despite the strength of the underlying scientific evidence. Differences around who is considered “old” and what BP targets and management are considered appropriate may lead to confusion among clinicians and further contribute to the evidence-practice lag and a recent systematic review of international hypertension guidelines found considerable variation in recommendations regarding the management of hypertension (Alhawassi et al. 2014).
4 Who Is Considered “Older” in International Guidelines?
In the 13 international guidelines for the management of hypertension included in the systematic review, three different age ranges were used to define older populations. Approximately half of the guidelines defined older populations as those aged 80 years or older, while other guidelines defined older populations as those above 65 years and one guideline included individuals aged over 60 years as older. To further add to the discussion, In the American Society of Hypertension/International Society of Hypertension (ASH/ISH) guideline (Weber et al. 2014), recommendations were given for the “middle aged to elderly population” which was defined as 55–80 years. The European Society of Cardiology (ESC) (Mancia et al. 2013a) and National Institute of Clinical excellence (NICE) (Jaques et al. 2013) guidelines referred explicitly to differing needs among older persons and provide recommendations for older populations aged below 80 years and those aged above 80.
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