Introduction

Hypertension and hypotension are important risk factors for vascular diseases [1]. Blood pressure changes, compared to mean blood pressure, were a potential risk factor for adverse outcomes [1, 2]. Relevant studies have demonstrated that blood pressure variability accelerated the progression of adverse health outcomes, such as cognitive decline [3,4,5], kidney disease [6], and the progression of prediabetes and diabetes [7]. In elderly individuals, blood pressure regulation mechanisms may be impaired [8], and vascular elasticity is greatly reduced, leading to blood pressure fluctuations. Studies have shown that a stronger association existed between higher systolic or diastolic blood pressure variability and the risk of death [9,10,11], but another study failed to find an association between blood pressure and mortality [12]. Overall, there is controversy regarding the association between systolic or diastolic blood pressure variability and the risk of all-cause mortality.

Frailty in older adults represents an ongoing and accumulative series of adverse health conditions. The greater the number of adverse health factors, the higher the likelihood of frailty, leading to increased risks of negative health consequences such as falls, disability, hospitalization, diminished quality of life, dementia, and mortality. The incidence of frailty is gradually increasing and is poised to become a new global burden, with significant implications for clinical practice and public health [13]. Several investigators have demonstrated that the estimated incidence of frailty in community-dwelling older adults was 10% [14], while in nursing homes, the incidence of frailty increased to 19%–75.6%. Frailty increases the complexity of late-life blood pressure changes [15]. The choice of hypertension treatment methods is influenced by frailty. Frail elderly individuals are at a higher risk of experiencing adverse drug reactions, and studies evaluating the effectiveness of hypertension treatment often exclude frail elderly individuals [16]. Inconsistencies between blood pressure changes and frailty have been reported. Cross-sectional studies had shown contradictory results between blood pressure and frailty, with one study indicating that changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) predicted higher frailty [17], while two other studies found that frailty was significantly associated with decreased blood pressure [18]. In a cohort study, it was found that baseline hypertension did not predict the incidence of frailty [19], but Boullion et al. found that hypertension was associated with an increased incidence of frailty/frailty composite outcome (P = 0.009) [20]. Long-term blood pressure variability is a non-random phenomenon, with reproducibility documented in individuals at higher cardiovascular and stroke risk [21,22,23]. Short-term blood pressure variability is more susceptible to the influence of behavioral, emotional, and postural effects on cardiovascular physiology and psychology [24, 25]. In elderly individuals, the regulatory mechanisms of blood pressure decline, leading to an increased risk of frailty with blood pressure changes, which in turn increases the risk of mortality. The coexistence of frailty in elderly individuals adds complexity to understanding blood pressure control. The impact of frailty on long-term blood pressure variability and mortality risk warrants further investigation [26].

The relationship between blood pressure changes and frailty has been sparsely examined in older people. Few studies have evaluated the relationship between systolic and diastolic blood pressure changes and mortality in elderly individuals, independent of frailty. Therefore, the purpose of this study was (1) to evaluate the association between systolic and diastolic blood pressure changes and frailty in the elderly population, and (2) to explore the effects of these blood pressure changes on the risk of mortality after adjusting for the degree of frailty. Our research hypothesis is that maintaining blood pressure at optimal levels is associated with a lower risk of frailty and mortality, while lower blood pressure levels are associated with a higher risk of frailty and mortality.

Methods

Study design and participants

Participants were recruited from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which included participants from 22 provinces across China. The CLHLS is a nationally representative longitudinal cohort study that focuses on older Chinese people. The details of the CLHLS design have been described in detail elsewhere [27]. The data quality of CLHLS has been evaluated [28, 29]. The baseline survey of the current research was conducted in 2008, and follow-up surveys were conducted in 2011 and 2014. In the frailty databases, we aimed to explore the association between changes in blood pressure and the occurrence of frailty during the three-year follow-up period from 2008 to 2011. We excluded participants younger than 65 years old (n = 391), elderly participants with baseline frailty (n = 3559), those with missing frailty data (n = 3124) and unavailable blood pressure values (n = 307). The final frailty database included 6929 participants in the study. In the mortality database, we aimed to observe the association between three-year blood pressure changes and the occurrence of mortality from 2011 to 2014. We excluded participants younger than 65 years old (n = 391), elderly participants who died before the follow-up in 2011 or loss of follow-up third visit(n = 8844), and participants without available blood pressure (n = 384). The final mortality frailty database included 7335 participants in the study. An overview of the study population is shown in Fig. S1. The CLHLS study received approval from the Biomedical Ethics Committee of Peking University (IRB00001052–13074), and all participants have provided written informed consent.

Assessments

Assessment of blood pressure

Blood pressure was evaluated by trained research assistants. After resting for at least five minutes, the blood pressure was measured using a mercury sphygmomanometer placed on the right arm of the seated subject at heart level. If the subject was unable to maintain a seated position, the measurement was taken in a supine position. Two blood pressure measurements were averaged and utilized for subsequent analysis.

Frailty index

The number of variables comprising the frailty index is variable, however, it is recommended to include at least 30 deficit items [30, 31]. Following a validated and published method, we used the CLHLS dataset to construct a frailty index comprising 40 health deficits (Supplementary Table 1) [31, 32]. Each deficit was dichotomized or trichotomized and then mapped onto the interval of 0 to 1 (e.g., daily task of bathing, where “without assistance” was assigned a value of 0, “partial assistance” a value of 0.5, and “need assistance” a value of 1) to reflect its seriousness. We added up the number of existing deficits and then divided by the total number of deficits under consideration. Exclusion criteria shall apply when a participant possesses fewer than 30 items. Following the computation of FI scores, we used the following cutoff values from a prior study to classify participants into non-frailty (FI ≤ 0.25) and frailty (FI > 0.25) groups [33].

Mortality

Survival status and date of death of the participants were collected in the 2014 wave survey. Information about death was obtained from family members or local residents’ committees. Participants who could not be located or contacted were deemed lost to follow-up. The survival time was calculated as the interval between the date of the baseline survey and the date of death. All participants were followed up for 3 to 6 years. Those who died prior to the 2011 survey were defined as censored due to the lack of 11 years of blood pressure information.

Covariates

The covariates included sociodemographic characteristics, socioeconomic status, and health-related behaviors. Sociodemographic characteristics included sex (male vs. female), age was calculated based on the interview date and verified date of birth and categorized into age groups (ages 65–79 years vs. ages 80+ years), marital status (currently married vs. separated/divorced/never married/widowed), region (urban vs. rural), years of education, living arrangements (with family/nursing home vs. alone), education (attend school years), BMI was classified into three groups: underweight (BMI < 18.5 kg/m2), normal weight and overweight (BMI < 30 kg/m2), obese (BMI > = 30 kg/m2). Socioeconomic status included education, and pension. Economic income was categorized as “high” and “medium or low” by the question “Compared with other locals, how do you think about your economic position?”, pension (yes vs. no). Health behavior was measured by current drinking (yes vs. no), current smoking (yes vs. no), and current exercise (yes vs. no).

Statistical analysis

Participants were stratified by survival status. Participants’ characteristics were described using mean ± standard deviation (SD) for continuous variables and frequency (%) for categorical or ordinal variables. Participants were then exploratorily classified into three groups based on blood pressure values (SBP < 130, 130–150, and >150 mmHg; DBP < 70, 70–90, and >90 mmHg) based on previous evidence [34,35,36,37]. Cross-tabulations were calculated at baseline and follow-up, with stable categories used as a reference. Regarding objective 1, multivariate logistic regression models were used to analyze the association between different change patterns of blood pressure during 3-year intervals and frailty at 3-year follow-up, presenting odds ratios and corresponding 95% confidence intervals (CIs). Regarding objective 2, Cox regression models were utilized to evaluate the risk of mortality associated with different change patterns of blood pressure during 3-year intervals, presenting hazard ratios (HRs) and associated 95% CIs. Adjustment was made for all factors listed above and frailty index (continuous score) when evaluating the risk of mortality associated with different change patterns of blood pressure during 3-year intervals. In the multivariate logistic and Cox regression analyses, we explored the differential effects of blood pressure change patterns on frailty and mortality across subgroups of age, sex, living arrangements, and BMI. Interaction terms were used to examine the impact of age, sex, living arrangements, and BMI on the association between different change patterns of blood pressure and frailty, as well as between different change patterns of blood pressure and mortality. Based on the results of the interaction analysis, we proceeded to perform any further evaluation of the association between blood pressure changes and the 3-year risk of frailty stratified by age, as well as the 6-year all-cause mortality. We performed a secondary analysis to evaluate reverse causation by excluding those subjects who died during the first two years of observation after the 3-year blood pressure measurement. A significance level of P < 0.05 was applied, and two-sided tests were employed for all reported probability analyses. We employed the coefficient of determination (R-squared) to evaluate the Goodness of Fit of the model. We used IBM SPSS 24.0 and R 3.6.2 for the statistical analyses.

Results

Table 1 presents the baseline characteristics of participants stratified by mortality status. Among the 7335 included participants, the mean age was 82.6 ± 10.7 years, the 6-year mortality proportion was 32.8% (N = 2409), and the mortality rate was 58.4 per 1,000 person-years. Among all frail patients, 25.3% were male, 65.5% had a medium economic status, 58.6% lived in rural areas, 8.6% lived alone, and 16.5% were married (Supplementary Table 3). The distribution of mortality status varied according to sex, economic status, retirement income, marital status, smoking status, alcohol consumption, exercise status, education, age, and BMI levels. Supplementary Table 4 presents the baseline characteristics of participants stratified by frailty status. In total, 6929 older adults were included in the frailty analysis and a 3-year frailty rate of 18.9% (N = 1312). Frail participants (FI ≥ 0.25) were more likely to be older (89.2 ± 9.0 years) and female (834, 63.6%).

Table 1 Descriptive baseline characteristics of participants about mortality
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Regarding objective 1 (the association between different change patterns of blood pressure during 3-year intervals and frailty), after adjusting for multiple covariates in the multivariate logistic model, we found a significant correlation between blood pressure changes and the risk of frailty (Table 2). Among participants who were at the optimal blood pressure level at baseline (SBP: 130–150 mmHg; DBP: 70–90 mmHg), decreasing blood pressure during the follow-up period was related to a higher risk of frailty. Compared to participants at the optimal baseline SBP level, the odds ratio (OR) and 95% confidence interval (CI) for those with a decreasing follow-up SBP (< 130 mmHg) were OR = 1.28, 95%CI: 1.02–1.61. For those at the optimal baseline DBP level (70–90 mmHg), the adjusted OR for those with a decreasing follow-up DBP (< 70 mmHg) was 1.42 (1.15–1.76). Among participants who were not at the optimal baseline blood pressure level, maintaining optimal level blood pressure during the 3-year follow-up period was associated with a lower risk of frailty. Compared to participants with lower baseline SBP, increasing SBP to optimal SBP level was associated with a lower risk of frailty (OR = 0.68, 95%CI: 0.54–0.86). Among participants who were related to higher baseline DBP (>  90 mmHg), decreasing DBP to meet lower DBP levels was significantly associated with higher frailty (OR = 1.93, 95%CI: 1.13–3.27).

Table 2 Risk of frailty by changes in blood pressure across two consecutive visits (3-year intervals)
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Regarding objective 2 (the association between different change patterns of blood pressure during 3-year intervals and mortality after adjusting for frailty index), in the Cox model adjusted for confounding factors, we observed that maintaining blood pressure at optimal levels during follow-up was associated with lower 6-year mortality risk, compared to participants with relatively lower baseline and follow-up blood pressures. These results persisted even after adjusting for the frailty index. For example, among participants with a lower baseline SBP, controlling blood pressure at the optimal level during the follow-up was associated with a lower mortality risk compared to those with a lower follow-up SBP, with a hazard ratio (HR) of 0.78, 95%CI: 0.67–0.90, and this association remained significant after adjusting for frailty index (HR = 0.83, 95%CI: 0.72–0.97). However, controlling blood pressure at the lower level during the follow-up period was associated with a higher 6-year mortality risk compared to those who had a stable optimal follow-up blood pressure level, with an HR of 1.20, 95%CI: 1.02–1.40 for SBP and 1.32, 95%CI: 1.16–189 1.52 for DBP, but this association remained significant only for DBP after adjusting for frailty index (HR = 1.23, 95%CI: 1.07–1.42), not for SBP (HR = 1.11, 95%CI: 0.95–1.30) (Table 3).

Table 3 Risk of mortality by changes in blood pressure across two consecutive visits (3-year intervals)
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In additional analyses, we found age to be a significant interaction factor, both in assessing the association between different blood pressure change patterns within 3 years and frailty and the association between different blood pressure change patterns within 3 years and mortality risk (adjusted for frailty index) (Supplementary Table 5). Gender, BMI, and lifestyle arrangements did not show any interaction effects in the association between different blood pressure change patterns within 3 years and frailty or mortality risk. After further stratifying participants by age, there were more significant results in the subgroup of individuals aged 80 years and above (P-value for interaction <0.001). In the stratified analysis of blood pressure changes and frailty based on age groups (Fig. 1 and Supplementary Table 6), we found a more significant association between blood pressure changes and frailty in individuals aged 80 years and older compared to those aged 65–70 years. Similar to the results for frailty (Fig. 2 and Supplementary Table 7), in participants aged 80 years and above analyzed through age-stratified analysis, the association between blood pressure changes and 6-year mortality was more pronounced. However, these associations were not observed in participants aged 65–79 years.

Fig. 1
figure 1

The association between blood pressure and 3-year frailty was examined, stratified by age groups: 65–79 years old and 80 years and above. The results were adjusted for baseline sex, economic income, educational background, living arrangements, residence, BMI, smoking status, drink status, and exercise

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Fig. 2
figure 2

The association between blood pressure and 6-year mortality was examined, stratified by age groups: 65–79 years old and 80 years and above. The results were adjusted for baseline sex, economic income, education, living arrangements, pension, residence, smoking status, drink status, exercise and frailty index (continuous score)

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Secondary analysis

We conducted a secondary analysis, excluding 1,696 participants who died during the first two years of observation after the 3-year blood pressure measurement. In the secondary analysis (Supplementary Table 8), there were 4,926 surviving participants (87.4%), with only 713 deceased participants (12.6%). Compared to the previous analysis, in which participants who died within the first two years were not excluded, the mortality rate was lower in this secondary analysis sample. Within this secondary analysis sample, we did not find a relationship between blood pressure changes and 6-year mortality, even after adjusting for the frailty index.

Discussion

This prospective cohort study aimed to investigate the relationship between late-life follow-up blood pressure changes and frailty, as well as the relationship between blood pressure and mortality after considering the degree of accumulated health deficits among participants. We observed that a decline in both systolic and diastolic blood pressure during the follow-up period was linked to an elevated frailty risk. A stable optimal blood pressure level (SBP, 130–150 mmHg; DBP, 70–90 mmHg) during follow-up was associated with a lower risk of frailty, while follow-up blood pressure below the optimal level was associated with a higher risk of frailty. We found that a decrease in SBP and DBP below the optimal blood pressure level during follow-up was associated with a higher mortality rate, regardless of whether frailty was controlled for. Conversely, increasing blood pressure to the optimal level during follow-up was associated with a lower mortality rate. Notably, in our study, only participants who were at the optimal SBP level (130–150 mmHg) at baseline showed an association between a decrease in SBP during follow-up (<130 mmHg) and a higher mortality rate, which disappeared after adjusting for frailty. We conducted a stratified analysis by age and found that compared to younger elderly individuals, the changes in blood pressure in those aged 80 and above are more significantly associated with the occurrence of frailty and risk of mortality.

Our findings are consistent with previous research. A study of elderly Brazilians living in the community found a statistically significant correlation between overall frailty status and DBP (P = 0.004), with blood pressure values in frail individuals lower than those in non-frail individuals [38]. A cohort study of 144,403 individuals aged 80 years or older found that low SBP (< 120 mmHg) was associated with a higher risk of mortality, regardless of whether individuals were classified as “frail” or “healthy,” suggesting that the association between lower blood pressure and mortality may not be related to increased disease burden or poor health status [39]. In a study using the CLHLS database to investigate the relationship between blood pressure categories and mortality in the elderly, it was demonstrated that the association between a decrease in SBP (< 107 mmHg) and increased mortality persisted in subjects with good health or functional status [40]. An epidemiological study evaluating the relationship between SBP and life expectancy in elderly hypertensive patients revealed that lower SBP levels increased overall mortality. Rådholm et al. indicated that low SBP was associated with increased all-cause mortality in nursing home residents using antihypertensive medications [41]. The results from a population study by Masoli et al. stratified elderly individuals by baseline frailty index and established that individuals aged 75 years or older with SBP < 130/80 mmHg had a higher mortality rate than those with SBP 130–139 mmHg and DBP 80–90 mmHg, regardless of frailty category [42]. Odden et al. found a modifying effect of frailty on the association between SBP and mortality, with higher SBP (≥ 140 mmHg) associated with greater mortality risk in individuals with faster walking speed (non-frail), while higher SBP was associated with lower mortality risk in participants unable to complete the walking test (frail) [43]. In our study, we found that a decrease in SBP and DBP blood pressure levels was associated with increased mortality risk, regardless of frailty status, and these differences may be explained by differences in subject selection and frailty assessment methods.

The mechanism underlying the association between decreased blood pressure and mortality in the elderly remains unclear. Aging is accompanied by a decline in autonomic nervous system function and stress reflex sensitivity, leading to a loss of ability to adapt to changes in blood pressure [44]. In the elderly, hypotension may result in inadequate perfusion of central organs, most notably the heart and brain tissue during diastole. Another study of individuals with cardiovascular disease found that low diastolic blood pressure was associated with the progression of brain atrophy and functional deterioration [45]. A recently published study demonstrated that patients with a combination of low blood pressure and inadequate cerebral perfusion had smaller brain volumes than patients with either low blood pressure or inadequate cerebral perfusion alone [46, 47]. Another possible explanation is that our participants experienced a decrease in blood pressure due to increased vascular frailty during the aging process, or as a result of deteriorating health status with age [48]. The increased prevalence of chronic diseases may increase the risk of death in participants with lower blood pressure, such as those with cancer or other wasting diseases [49]. In our study, only individuals who were at the optimal SBP level (130–150 mmHg) at baseline had an association between a decrease in SBP (< 130 mmHg) during follow-up and higher mortality rates, which could be explained by frailty. This result may be explained by the fact that in this subgroup of elderly individuals, blood pressure regulation was better at baseline, the risk of cardiovascular disease was lower, and frailty increased the risk of death during follow-up due to non-cardiovascular diseases [50]. Studies have shown that lower systolic blood pressure is associated with a higher risk of non-cardiovascular death [45]. Severe non-cardiovascular diseases may be related to low blood pressure in frail patients [42]. In our study, we observed a more pronounced association between blood pressure fluctuations and the incidence of frailty and mortality in the very elderly population. This association may be attributed to impaired automatic blood pressure regulation in extremely elderly individuals, leading to more frequent inadequate perfusion of crucial organs such as the brain, kidneys, and heart [51].

Our secondary analysis revealed that the relationship between blood pressure changes and all-cause mortality risk disappeared after excluding patients who died within the first two years after the three-year follow-up period. This phenomenon might be attributed to the accelerated decline in functional status in the last 2 years of life among elder adults [52]. These findings could be explained by late-life weight loss, weakened nutritional status, and systemic chronic inflammation. A significant decrease in systolic blood pressure (SBP) might serve as a marker of imminent death [39, 53, 54].

In the existing randomized controlled trials focusing on intensified blood pressure control for hypertensive patients [55,56,57], elder individuals with multiple chronic diseases or limited life expectancy might not meet the inclusion criteria and were excluded. Additionally, elderly individuals residing in long-term care facilities were also excluded [58]. In our study, which is a large-scale cohort study, we included more diverse elderly participants, taking into account those with multiple chronic illnesses and those residing in care facilities. This approach made our study results more representative, providing additional evidence for blood pressure control guidelines. In clinical practice, it is advisable for older adults to maintain blood pressure at optimal levels to reduce the risk of frailty and mortality. Further analysis revealed that individuals aged 80 years and above are more sensitive to blood pressure changes. Compared to younger elderly individuals, those aged 80 years and above should pay closer attention to blood pressure management.

Strengths and limitations

Our study had a large sample size, a long follow-up period, and a very high follow-up rate (94.7%), with relatively complete information on mortality and population demographics. We comprehensively explored the correlation between various patterns of blood pressure changes in late life and frailty and mortality rates in Chinese elderly individuals. Subgroup analyses were also performed. We constructed a frailty index using a series of measures and divided frailty status into two levels to maximize statistical power. However, this study has some limitations. Firstly, the data for this study came from a prospective cohort, and although we adjusted for many potential confounding factors, other unknown factors may still exist, and the results cannot reveal causality. Secondly, information on lifestyle factors and prevalent diseases at baseline was collected, which may introduce recall bias, and we lack information on the use of relevant anti-hypertensive medications. Thirdly, due to limitations in the study design and measurement intervals, we only used 3-year blood pressure changes as the primary exposure. Further research incorporating more intricate exposure metrics is necessary.

Perspective of Asia

In Asian populations, the therapeutic response to drug treatment, as well as the risk and outcomes of complications, exhibit differences when contrasted with Western counterparts [59]. Moreover, the concept of frailty in public health and clinical practice has not yet received the attention it deserves [60]. In the future management of hypertension among Asian populations, treatment strategies should be formulated to suit the unique characteristics and individual differences of Asians.

Conclusion

This prospective cohort study of Chinese elderly individuals demonstrated that regardless of their frailty status, having blood pressure below the optimal level during follow-up was associated with higher mortality rates, while maintaining blood pressure at the optimal level was associated with lower mortality rates. However, among participants who were at the optimal SBP level (130–150 mmHg) at baseline, a decrease in SBP (< 130 mmHg) during follow-up was associated with higher mortality rates, which could be explained by frailty.