Harm vs. benefit of antihypertensive treatment in very old and frail people – do not miss the forest for the trees

In recent years, population ageing has led to a substantial increase in the number of older hypertensive persons requiring medical attention and management of hypertension in older adults has become a major public health concern [1]. Accumulating evidence encourages more intensive blood pressure (BP) lowering in hypertensive patients, showing a reduced risk of cardiovascular events and mortality in patients receiving strict BP control, also at old age [2,3]. Yet, cardiovascular benefits of intensive treatment may come at the expense of a significant increase in the risk of hypotension-related adverse events, particularly in older, multimorbid and frail patients. Indeed, aggressive BP lowering may predispose to syncope and falls, potentially resulting in severe injuries, decline of functional autonomy and disability [4–6]. Symptoms associated with low BP, for example, fatigue, sensory deficits and orthostatic intolerance, may significantly impair individuals’ well being and quality of life, leading to anxiety and restriction in working and social activities [7]. Finally, strict BP control may negatively affect renal function and cognitive performance [8]. While cardiovascular consequences associated with high BP are well known, there is limited awareness of potential complications associated with very low BP resulting from intensive antihypertensive therapy. Indeed, hypotension-related complications are scarcely investigated in clinical trials and are likely underestimated due to highly selective inclusion criteria precluding patients with frailty and multimorbidity from being eligible [9–11]. The review by Shantsila et al.[12], which is published in the current issue, extensively discusses the limitations of existing evidence as regards antihypertensive treatment in patients above 80 years of age. The authors illustrate the discrepancy between interventional study samples and the ‘real-world’ geriatric population, which derives from underrepresentation of frailer individuals in highly selected research settings or application of restrictive enrolment procedures. Such discrepancy accounts for several ‘gaps in evidence’ concerning hypertension management in older and more vulnerable population subgroups, which include antihypertensive treatment strategies, BP targets and deprescribing criteria. Shantsila et al. highlight cardiovascular, musculoskeletal, and endocrine age-related phenomena, which may disturb the maintenance of cardiovascular homeostasis in older adults, thus predisposing them to hypotension and related complications. Autonomic aging, for example, impaired baroreflex sensitivity and reduced chronotropic heart rate response, may hamper postural and postprandial BP responses, while arterial stiffness may reduce tissue perfusion. Numerous clinical conditions associated with increased risk of hypotension and falls frequently combine in a context of multimorbidity, for example, gait and balance disorders, muscle loss, autonomic dysfunction, and sensory deficits. Finally, age-related changes in glomerular and tubular function may alter drug excretion, electrolyte balance and blood volume, potentially increasing the risk of drug accumulation, dehydration, and electrolyte disorders. Over the last decades, cardiovascular prevention has clearly emerged as a healthcare priority and the role of cardiovascular risk factors have been emphasized, in order to identify patients at highest risk who deserve more aggressive prevention strategies. On the other hand, limited attention has been given to risk factors for hypotension and prevention of hypotension-related adverse events is frequently overlooked in current clinical practice. Hypotensive risk factors consist of clinical conditions which increase the risk of hypotension-related complications and/or might limit antihypertensive treatment benefits. At present, several hypotensive risk factors have been identified (Fig. 1).FIGURE 1: Cardiovascular and hypotensive risk factors. How to assess harm vs. benefit of antihypertensive treatment. Traditional cardiovascular risk factors include hypertension, diabetes, dyslipidaemia, hyperuricemia, smoking, and renal disease. Hypotensive susceptibility includes clinical manifestations such as past history of hypotensive syncope, recurrent hypotensive symptoms, and orthostatic intolerance, and hypotension detected on office/out-of-office blood pressure measurements, for example, orthostatic hypotension during active stand test, postprandial hypotension or other hypotensive episodes on 24-h ambulatory BP monitoring. Risk factors for falls include gait and balance disorders, vision deficits, low muscle mass. Harm vs. benefit assessment should include all appropriate elements listed on the left side. Final decision should be reached in agreement with the patient and his/her family. CV, cardiovascular; ECHO, echocardiography; cMRI, cardiac magnetic resonance imaging; 24-h ABPM, 24-h ambulatory blood pressure monitoring; home BP, home blood pressure monitoring.Hypotensive susceptibility is defined as a tendency to hypotension, predisposing to syncope with a predominant hypotensive mechanism [13]. It typically manifests with hypotensive episodes that can be detected on office, ambulatory and home BP measurements, for example, orthostatic hypotension during standing BP assessment, postprandial hypotension and other hypotensive episodes on 24-h ambulatory BP monitoring [14,15]. Hypotensive susceptibility and consequent hypotensive episodes are responsible for recurrent syncope, falls and/or hypotensive symptoms such as dizziness and orthostatic intolerance, which negatively affect quality of life and might be responsible for severe injuries, hospital admission and disability [16,17]. Cardiovascular autonomic dysfunction should be also considered in this clinical context. Cardiovascular dysautonomia is characterized by the loss of BP and heart rate regulation ability, leading to extreme hemodynamic variability and recurrent hypotensive episodes which typically manifest on standing (i.e. orthostatic hypotension and orthostatic intolerance) and during the postprandial period [18]. Hypotensive susceptibility is frequently exacerbated by antihypertensive medications, particularly if intensive BP control is pursued [19]. Previous history of accidental falls indicates an increased risk of hypotension-related complications. Accidental falls typically result from predisposing conditions such as gait and balance disorders, vision deficits, and low muscle mass, which imply increased vulnerability to hemodynamic changes. Indeed, even mild BP fluctuations might induce dizziness, balance instability and loss of postural tone, which substantially increase the risk of falls in presence of predisposing conditions [16,20]. Finally, cognitive impairment has been demonstrated to influence antihypertensive treatment benefits. Indeed, lower BP values were found to be associated with more rapid decline of cognitive performance in mild cognitive impairment, thus discouraging intensive BP control in these patients [16,21]. Abnormal BP regulation, impaired physical performance and cognitive decline frequently coexist in frail older individuals, thus making frailty a hallmark of hypotensive risk [22,23]. The above-described conditions encourage a more prudent approach to BP lowering and help identify older hypertensive patients who may benefit from deprescribing. While cardiovascular risk factors usually prompt antihypertensive treatment intensification, hypotensive risk factors may prompt treatment reduction, due to probability of treatment-related complications exceeding treatment benefits. A paradigm shift in treatment attitudes is advocated by Shantsila et al., who call for equal emphasis on both prescribing and deprescribing in the context of treatment optimization. Drawing attention to hypotensive risk factors is the first step towards this paradigm shift. As cardiovascular and hypotensive risk factors commonly overlap and oppose at old age, even more so in frailer patients, assessment of hypotensive and cardiovascular risk factors should be carried out in parallel, aiming to minimize the risk of hypotension-related complications while not excluding older patients from appropriate cardiovascular prevention. With a view to balance cardiovascular and hypotensive risk in older patients, there is an urgent need for geriatric perspective in hypertension research. Future studies should be more representative of older and frailer individuals with comorbidities who are more vulnerable to hypotension, with the final aim to increase clinicians’ and patients’ awareness on hypotensive risk and related negative outcomes. As once said by the famous French writer, Albert Camus, ‘Good intentions may do as much harm as malevolence, if they lack understanding’. We should better understand and beware of the potential harm of intensive blood pressure lowering in a vulnerable population of octogenarians. ACKNOWLEDGEMENTS None. Conflicts of interest There are no conflicts of interest.