Hypertension in frail older adults: current perspectives

Introduction

Hypertension is a prevalent chronic disease among the elderly, serving as a primary risk factor for cardiovascular disease, cerebrovascular disease, chronic kidney disease, and mortality in older people (Mills, Stefanescu & He, 2020; Lawes, Vander Hoorn & Rodgers, 2008). The prevalence of hypertension in people aged >60 years is estimated to exceed 60% (Williams et al., 2018), and it will continue to increase with the aging of the population (Mills, Stefanescu & He, 2020; Williams et al., 2018). The global number of deaths attributed to hypertension and its associated complications exceeds 10 million every year (Murray et al., 2020). Reasonable management of blood pressure (BP) in older people is crucial for improving patient prognosis and alleviating the burden of healthcare system. Noticeably, elderly individuals are a unique population, and the management of BP is different from that of the general population. In addition, there is substantial heterogeneity in the biological age of older people due to chronic diseases and functional impairment, and chronological age does not accurately reflect their biological age (Muller et al., 2014).

Frailty is closely related to biological age (Mitnitski et al., 2015). It is an age-related geriatric syndrome that differs from disability and illness. The characteristics of frailty are decreased reserves of multiple organs and systems and increased sensitivity to stressors (Dent et al., 2019; Clegg et al., 2013), leading to the risk of adverse outcomes increased in older people, including mortality, dependence, hospitalization, and falls (Dent et al., 2019; Clegg et al., 2013; Kojima et al., 2016; Hu et al., 2021). Based on different definitions and assessment instruments of frailty, the prevalence of frailty ranged from 4.0% to 59.1% among community-dwelling older people (Collard et al., 2012; Santos-Eggimann et al., 2009; He et al., 2019). Frailty becomes progressively more common with advancing age: 4% for individuals aged 65–69 years, 7% for those aged 70–74 years, 9% for those aged 75–79 years, 16% for those aged 80–84 years, and 26% for those aged >85 years (Clegg et al., 2013).

Frailty and hypertension often coexist in older people (Zhu et al., 2020; Vetrano et al., 2018). As frailty is closely related to biological age, it can objectively reflect the health status and medical and healthcare needs of older people. Frailty has an important influence on the risk-benefit ratio of hypertension treatment in older people. However, there is a paucity of available research on the management of BP for frail older people. The benefits of treatment, the optimal BP target, and the choice of antihypertensive drugs for older hypertensive patients with frailty remain subjects of ongoing debate. Based on current evidence and guidelines, this narrative review provides a brief overview of hypertension in frail older people, especially for the management of BP for this population, which may help in providing valuable ideas for future research in this field.

Survey/search methodology

The authors conducted an in-depth search on PubMed, Web of Science, Embase, and the Cochrane Library. The search was carried out by combining subject words and free words, and the following heading terms were used when performing the search: “frail”, “frailty”, “old people”, “old adults”, “frail elderly”, “hypertension”, “hypertensive”, “blood pressure”, and “management of hypertension”. The titles of the literatures underwent an initial screening, followed by a secondary screening of abstracts and keywords, and finally, the full texts were obtained for further evaluation. Additionally, relevant literature references were also searched to identify more eligible studies.

The association between frailty and hypertension

A systematic review revealed that the overall prevalence of frailty among hypertensive patients was 14.0%, and the overall prevalence of hypertension among frail patients was 72.0% (Vetrano et al., 2018). Frailty and hypertension share some common pathophysiological mechanisms, and hypertension and frailty are significantly correlated and influence each other in elderly people. However, the causal relationship between them remains unclear. On the one hand, frailty is associated with an increased risk of hypertension in older adults. For instance, a study conducted in Korea revealed that frail older adults had a significantly higher prevalence of hypertension than non-frail older adults (67.8% vs. 49.8%) (Kang et al., 2017). Another study from Brazil also showed that frail patients had a higher prevalence of hypertension than healthy patients (83.0% vs. 51.7%) (Aprahamian et al., 2018). Interestingly, Aliberti et al. (2021) found frailty could modify the association of hypertension with cognitive performance and impairment in older people, it showed that hypertension was associated with better memory and global cognitive scores among frail older adults. On the other hand, hypertension also increases the risk of frailty in older adults. For instance, a cohort study from China showed that hypertensive patients exhibited an approximately twofold greater prevalence of frailty than those non-hypertensive patients (13.8% vs. 7.4%) (Ma et al., 2020). In addition, there are some complex relationships between frailty and BP in older adults. The relationship between systolic BP (SBP) and frailty in hypertensive patients receiving antihypertensive therapy was found to exhibit a U-shaped pattern, as demonstrated by a study from Canada (Rockwood & Howlett, 2011). Blauth et al. (2022) performed a cross-sectional study in patients aged >80 years, and reported that frail patients had greater SBP during sleep than non-frail patients (128 ± 15 mm Hg vs. 122 ± 13 mm Hg). This study emphasizes the importance of sleep in investigations of frailty and hypertension, however, the sample size of this study was relatively small (38 frail and 36 non-frail patients) (Blauth et al., 2022), and more research can be conducted in the future. O’Connell et al. (2015) showed that frailty is related to a high risk of orthostatic hypotension.

Frailty has a significant impact on the prognosis of older hypertensive patients. Frailty markedly increases the risk of fall injuries (Bromfield et al., 2017), hospitalization (Pajewski et al., 2016), and mortality (Li et al., 2023; Ma et al., 2018) in elderly patients with hypertension, which seriously affects the quality of life of older people, reduces their independence, and decreases their life expectancy. Table 1 summarizes current research examining the impact of frailty on the prognosis of elderly patients with hypertension.

Frailty assessment in older hypertensive patients

Frailty is affected by genetics, lifestyle, chronic diseases, environment and other factors (Clegg et al., 2013). It is closely related to biological age, and can objectively reflect the health status of older people. Assessing frailty status in older people prior to initiating antihypertensive therapy is very important for developing antihypertensive strategies and optimizing BP management, which could reduce adverse health outcomes and alleviate the burden of healthcare systems. Frailty screening and evaluation should be conducted for people aged ≥70 years or those who have experienced unintentional weight loss (≥5%) within the past year (Morley et al., 2013). In recent years, many international hypertension management guidelines or expert consensus have recommended to assess frailty status before initiating antihypertensive treatment in older people. Although many tools for assessing frailty have been developed worldwide, a gold standard is still lacking at present.

Currently, the Fried phenotype and Frailty Index (FI) are two most widely used tools for frailty assessment. The Fried phenotype originated in the United States and includes five indicators: slowness, weight loss, weakness, exhaustion, and low activity (Fried et al., 2001). Older people with three or more of the aforementioned indicators were defined as frailty, those with one or two components were defined as pre-frailty, and those without any components were defined as non-frailty. Subsequently, this method has been validated and widely used in many countries (Ding, 2017; Joosten et al., 2014). However, social psychology and cognitive function were not included in the Fried phenotype (Bieniek, Wilczynski & Szewieczek, 2016), and slowness and weakness may not accurately reflect the actual status of patients with acute illness or some special conditions. The FI was developed by Mitnitski, Mogilner & Rockwood (2001). FI is an age-related cumulative health deficit model, it evaluates frailty across many dimensions: physical, psychological, cognitive function, social function, and others (Mitnitski, Mogilner & Rockwood, 2001; Rockwood & Mitnitski, 2007). Each item of FI was assigned a score of 0–1, and an individual’s FI was calculated as the total score of all items divided by the number of items included. The FI ranged from 0–1, and the greater the FI was, the more severity of the frailty status. Subsequently, researchers have appropriately modified the items of constructing FI according to different study populations, and variations exist in the definition of frailty according to FI cut-off values across different studies (Searle et al., 2008; Gu et al., 2009; Shrauner et al., 2022). Liu et al. (2022) used FI to assess frailty status and found FI was significantly associated with cardiovascular disease (CVD) in older adults, which emphasize the importance of frailty screening and effective interventions for improving primary prevention of CVD. The FI contains multiple health dimensions that can be used to evaluate the frailty status of patients relatively accurate. However, the inclusion of a substantial number of items may impede its practicality for evaluating frailty in busy clinical settings (Aprahamian et al., 2017).

In addition to the two commonly used frailty assessment tools, many others have been developed. Table 2 summarizes several widely used tools for assessing frailty (Morley, Malmstrom & Miller, 2012; Bilotta et al., 2012; Gobbens et al., 2010; Bielderman et al., 2013; Ma et al., 2019; Satake et al., 2016; Pilotto et al., 2008; Daniels et al., 2012; Rolfson et al., 2006). The ideal frailty screening and assessment tools should be selected according to the clinical context, and the characteristics of the subjects (Richter et al., 2022). Developing a sensitive and rapid tool to accurately identify frailty status among elderly people is very important in the future.

Hypertension management in frail older adults

Management of frailty in older hypertensive patients

Frailty changes dynamically over time and it is partially reversible (Kojima et al., 2019; Hoogendijk et al., 2019). Given that frailty has an important influence on the management of hypertension in elderly patients, it is necessary to identify and assess frailty at an early stage and take appropriate measures to prevent it. Genes, aging, gender, lifestyle, nutrition, chronic diseases, psychosocial support, sociodemographic, and polypharmacy are associated with the occurrence and development of frailty (Dent et al., 2019; He et al., 2019; Zazzara et al., 2019; Angulo et al., 2020; Lochlainn et al., 2021).

Effective management of frailty could reduce the burden on health systems and families (Dent et al., 2019). Frailty can be managed in the following ways in elderly hypertensive patients (Dent et al., 2019; Clegg et al., 2013; Angulo et al., 2020; Lochlainn et al., 2021; Dent et al., 2017): (1) physical activity is widely regarded as the optimal approach for preventing and managing frailty, older people with frailty should appropriately participate in aerobic exercise, resistance training, stretching exercise, and balance training; (2) focusing on the management of chronic diseases and polypharmacy. The effective management of multiple chronic diseases necessitates collaboration among geriatrics, cardiologists, endocrinologists, primary care providers, and doctors in other departments; in addition, polypharmacy should be addressed by reducing or deprescribing any inappropriate or unnecessary medications; (3) supplementation with protein/calories should be considered when frail older adults experience weight loss or are diagnosed with malnutrition; (4). vitamin D supplementation should be considered for older people with vitamin D deficiency; (5) psychosocial support should be provided for the elderly population. In addition, hyperglycemia drives the transition from pre-frailty to frailty in hypertensive patients (Mone et al., 2023), and it drives physical impairment in frail hypertensive (Pansini et al., 2022), therefore, strict blood glucose monitoring and management is very important in preventing frailty.

Conclusion

Frailty assessment is necessary for elderly patients with hypertension. For frail older hypertensive patients, a personalized antihypertensive therapeutic strategy should be developed according to the patient’s condition, and BP and drug-related adverse events should be closely monitored (Fig. 1). Although great progress has been made in the fields of frailty and hypertension in recent decades, there remains a dearth of international guidelines or consensuses regarding BP management in older people with frailty. In the future, more longitudinal studies based on frail older people are needed to provide strong evidence of antihypertensive therapeutic strategies for this population, and the potential causal relationship between frailty and hypertension requires further investigation.