The effect of frailty on the 24‐hour blood pressure pattern in the very elderly

Abstract Frailty plays a crucial role in the management of hypertension in the very elderly and has a strong association with cardiovascular diseases. Nevertheless, its influence on the 24‐hour blood pressure pattern, including elevated asleep systolic blood pressure (BP) and the lack of BP fall during sleep (non‐dipping) has not been explored in a population above 80 years. Patients older than 80 years were classified into frail or robust subtypes by the five item frailty phenotype criteria. All participants were submitted to office blood pressure measurements and ambulatory BP monitoring over a 24‐hour period. Nocturnal dipping was defined as nighttime BP fall ≥10%. Thirty‐eight frail and 36 non‐frail individuals (mean age 85.3 ± 3.7 years; 67% females) were analyzed. Awake systolic and diastolic BP were similar for frail and robust individuals. Frail patients had higher systolic BP during sleep (128 ± 15 mm Hg vs. 122 ±13 mm Hg p = .04) and reduced systolic BP fall [1 (‐4.5 – 5)% vs. 6.8 (2.1 – 12.8)% p < .01]. Frailty was independently associated with higher risk of non‐dipping (OR 12.4; CI 1.79 – 85.9) and reduced nighttime systolic BP fall (‐6.1%; CI ‐9.6 – ‐2.6%). In conclusions, frailty has a substantial influence on nighttime BP values and pattern in patients older than 80 years.

biological age, play a crucial role in interpreting and managing health problems in this population. [8][9][10] Studies show that well known CVD behave differently between the frail and robust population regardless of age. While the frail population tends to have higher cardiovascular risk, greater disease burden and increased disability and mortality; the non-frail of the same age behave in an opposite manner. 11,12 Many theories have raised plausible explanations for the association between frailty and CVD but few studies have used clinical measures along the circadian cycle such as 24-hour ambulatory blood pressure monitoring (ABPM) in order to obtain a better understanding of the problem. 10 Elevated asleep systolic blood pressure (BP) and the lack of BP fall (dipping) have been associated with poorer cardiovascular outcome and are, amongst ABPM findings, the best prognostic markers of future cardiovascular events. [13][14][15][16] Studies have indicated that older patients have higher nighttime systolic BP as well as a reduced dipping and we hypothesize that these findings might be influenced by frailty. 8,17 No studies have been designed so far to analyze the role of frailty on these important cardiovascular risk markers in individuals above 80 years old. Therefore, the objective of the present study was to examine the effect of frailty on the 24-hour blood pressure profile, in a population above 80 years, with specific focus on nighttime BP values and pattern.

Participants
All participants were enrolled from March 2019 to April 2021 at a geri-  Table 3.
The effect of each variable over systolic BP fall was individually estimated by coefficient in logistic regression as shown in Table 4. The pres- Separate sensitivity analyses were performed with linear regressions considering the effect of awake systolic BP in non-dipping status and systolic BP fall but no association was found.

DISCUSSION
This was a cross-sectional study, designed to determine the role of frailty on the 24-hour blood pressure pattern in a population above  Data are mean ± SD or median (interquartile range) for continuous variables or n (%) for categorical variables. p < .05 between frail and non-frail individuals.
Abbreviations: BPM, beats per minute.; DBP, diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; PP, pulse pressure; SBP, systolic blood pressure.  The ABPM findings in this study showed that frailty was associated with higher asleep systolic BP and a higher risk of non-dipping even after adjustment for confounding variables. Recent evidence suggests that elevated asleep systolic BP and the lack of BP fall are mainly influenced by diurnal physical activity and changes in sleep patterns. [26][27][28] Considering that frailty also exerts important effect on sleep and mobility, this conjunction might be a plausible explanation for these find-ings. The higher risk associated with BMI also suggests that sleep disorders, like undiagnosed obstructive sleep apnea, might be associated with these findings since it has strong association with overweight. 29 Despite no difference in the prevalence of diabetes or orthostatic hypotension between groups in our findings, conditions associated with blood pressure non-dipping pattern, other plausible explanations would be advanced endothelial dysfunction associated with impairment in the autonomic system and insulin resistance regularly found in the frail. 30 The overall presence of dipping was low when compared to a general population and might be explained, in addition to what was previously mentioned, by the effect of age, since older individuals tend to have less dipping. 31 The strong and independent effect of frailty on BP fall supports that even with these possible mechanisms involved, frailty plays an independent role over cardiovascular disease and must be considered as a crucial aspect when evaluating older adults, especially the very elderly.

TA B L E 3 Logistic regression models for the risk of nondipping
The American Heart Association raises the issue by pointing to the heterogeneity of this population and by suggesting emphasis in studies that include the role of frailty in cardiovascular diseases. 32 Since they have similar risk factors there is a bi-directional relation between them that supports this perspective, furthermore, frailty has been proved to predict mortality and hospitalization for cardiovascular diseases. 33,34 The estimated effect of frailty over nocturnal BP decrease in our findings, -6.1% (CI -9.6 --2.6 % p = .01), might represent a 20% higher risk of cardiovascular mortality in 9 years according to previous prospective study. 35 To our knowledge, this was the first study to analyze the role of Since comorbidities are implied in some definitions of frailty, it was not possible to equalize nor adjust this variable between groups.
Further studies objectively measuring daily mobility and sleep quality in this specific population are suggested for a better understanding of this patient. Based in the present study, a focus in frailty and sleep treatment could be cited as promising adjuvant therapies for cardiovascular disease in the very elderly, although intervention trials designed to include frailty are warranted to clarify treatment.

CONCLUSIONS
In conclusions, frailty has a substantial influence on nighttime BP values and pattern in patients older than 80 years.