Factors related to frailty syndrome in the elderly with systemic arterial hypertension

Abstract

Objective: To determine the factors related to frailty syndrome in elderly people diagnosed with systemic arterial hypertension. Methods: This study with a quantitative and cross-sectional approach was conducted with elderly individuals aged ?60 years, of both sexes and diagnosed with arterial hypertension. Sociodemographic profile, blood pressure measurements, lifestyle habits, Edmonton Frailty Scale, and Mini-Mental State Examination were assessed. Descriptive statistics, Pearson's correlation analysis, t test to compare means, and linear logistic regression were used. The significance level was p <0.05. The study was approved by the Ethics and Research Committee. Results: The 272 participants evaluated were diagnosed with systemic arterial hypertension (162), were women (119; 73.45%), most of them were aged between 60-79 years (82.1%), lived without a partner (85; 52.5%), had a mean education level of 5.14 years and morbidities of 5.18, in addition to high blood pressure. The Mini-Mental State Examination showed a positive value for cognitive deficit in individuals from the study population (96; 59.3%) and a mean frailty of 5.43 points. In the linear regression, lower education (p=0.005) and the number of morbidities (p<0.001) were the factors associated with frailty and women had a higher frailty score. Conclusion: The associated factors of sex, age, education, and multimorbidity (which directly affect frailty) lead to an increase in frailty in elderly people over time. This condition can cause a worsening of their health and the development of new comorbidities.

Alternate abstract:

Objetivo: Determinar os fatores relacionados à síndrome da fragilidade na pessoa idosa com diagnóstico de hipertensão arterial sistêmica. Métodos: Estudo de abordagem quantitativa e transversal realizado com indivíduos idosos com 60 anos ou mais de idade, de ambos os sexos, com diagnóstico de hipertensão arterial. Foram avaliados: perfl sociodemográfco, medidas da pressão arterial, hábitos de vida, Escala de Fragilidade de Edmonton e Miniexame do Estado Mental. Foram utilizadas a estatística descritiva, a análise de correlação de Pearson e o teste t para comparação das médias, além da regressão logística linear. Teve signifcância p<0,05. O estudo foi aprovado pelo Comitê de Ética e Pesquisa. Resultados: Dos 272 participantes avaliados, 162 tinham diagnóstico de hipertensão arterial sistêmica, 119 (73,45%) eram mulheres, a maioria com idade entre 60 e 79 (82,1%) anos, 85 (52,5%) sem companheiro, com média de escolaridade de 5,14 anos e de 5,18 morbidades, além da hipertensão arterial. O Miniexame do Estado Mental evidenciou rastreio positivo para défcit cognitivo em 96 (59,3%) indivíduos da população em estudo e fragilidade com média de 5,43 pontos. Na regressão linear, os fatores associados à fragilidade foram a menor escolaridade (p=0,005) e o número de morbidades (<0,001), sendo que as mulheres apresentaram maior pontuação na fragilidade. Conclusão: Os fatores associados sexo, idade, escolaridade e multimorbidade, que incidem diretamente na fragilidade, acarretam ao longo do tempo aumento da fragilidade da pessoa idosa. Tal condição pode ocasionar piora em seu estado de saúde e no desenvolvimento de novas comorbidades.

Alternate abstract:

Objetivo: Determinar los factores relacionados con el síndrome de fragilidad en adultos mayores con diagnóstico de hipertensión arterial sistémica. Métodos: Estudio de enfoque cuantitativo y transversal, realizado con personas de 60 años o más, de ambos sexos, con diagnóstico de hipertensión arterial. Se evaluó el perfl sociodemográfco, las medidas de la presión arterial, los hábitos de vida, la Escala de Fragilidad de Edmonton y el test Mini-Mental. Se utilizó la estadística descriptiva, el análisis de correlación de Pearson y el test-T para comparar las medidas, además de la regresión logística lineal. Hubo signifcación p<0,05. El estudio fue aprobado por el Comité de Ética e Investigación. Resultados: De los 272 participantes evaluados, 162 tenían diagnóstico de hipertensión arterial sistémica, 119 (73,45 %) eran mujeres, la mayoría entre 60 y 79 años (82,1 %), 85 sin pareja (52,5 %), con promedio de escolaridad de 5,14 años y de 5,18 morbilidades, además de la hipertensión arterial. El test Mini-Mental evidenció un rastreo positivo de defciencia cognitiva en 96 (59,3 %) individuos de la población estudiada y fragilidad promedio de 5,43 puntos. En la regresión lineal, los factores asociados a la fragilidad fueron la baja escolaridad (p=0,005) y la cantidad de morbilidades (<0,001), y las mujeres presentaron mayor puntaje de fragilidad. Conclusión: Los factores asociados sexo, edad, escolaridad y multimorbilidad, que inciden directamente en la fragilidad, conllevan un aumento de la fragilidad de las personas mayores a lo largo del tiempo. Esta condición puede empeorar el estado de salud y el desarrollo de nuevas comorbilidades.

Headnote

Keywords

Aged; Frailty; Hypertension; Arterial pressure; Chronic disease; Cognitive dysfunction; Life style

Abstract

Objective: To determine the factors related to frailty syndrome in elderly people diagnosed with systemic arterial hypertension. Methods: This study with a quantitative and cross-sectional approach was conducted with elderly individuals aged ?60 years, of both sexes and diagnosed with arterial hypertension. Sociodemographic profile, blood pressure measurements, lifestyle habits, Edmonton Frailty Scale, and Mini-Mental State Examination were assessed. Descriptive statistics, Pearson's correlation analysis, t test to compare means, and linear logistic regression were used. The significance level was p <0.05. The study was approved by the Ethics and Research Committee. Results: The 272 participants evaluated were diagnosed with systemic arterial hypertension (162), were women (119; 73.45%), most of them were aged between 60-79 years (82.1%), lived without a partner (85; 52.5%), had a mean education level of 5.14 years and morbidities of 5.18, in addition to high blood pressure. The Mini-Mental State Examination showed a positive value for cognitive deficit in individuals from the study population (96; 59.3%) and a mean frailty of 5.43 points. In the linear regression, lower education (p=0.005) and the number of morbidities (p<0.001) were the factors associated with frailty and women had a higher frailty score. Conclusion: The associated factors of sex, age, education, and multimorbidity (which directly affect frailty) lead to an increase in frailty in elderly people over time. This condition can cause a worsening of their health and the development of new comorbidities.

Resumo

Objetivo: Determinar os fatores relacionados à síndrome da fragilidade na pessoa idosa com diagnóstico de hipertensão arterial sistêmica. Métodos: Estudo de abordagem quantitativa e transversal realizado com indivíduos idosos com 60 anos ou mais de idade, de ambos os sexos, com diagnóstico de hipertensão arterial. Foram avaliados: perfl sociodemográfco, medidas da pressão arterial, hábitos de vida, Escala de Fragilidade de Edmonton e Miniexame do Estado Mental. Foram utilizadas a estatística descritiva, a análise de correlação de Pearson e o teste t para comparação das médias, além da regressão logística linear. Teve signifcância p<0,05. O estudo foi aprovado pelo Comitê de Ética e Pesquisa. Resultados: Dos 272 participantes avaliados, 162 tinham diagnóstico de hipertensão arterial sistêmica, 119 (73,45%) eram mulheres, a maioria com idade entre 60 e 79 (82,1%) anos, 85 (52,5%) sem companheiro, com média de escolaridade de 5,14 anos e de 5,18 morbidades, além da hipertensão arterial. O Miniexame do Estado Mental evidenciou rastreio positivo para défcit cognitivo em 96 (59,3%) indivíduos da população em estudo e fragilidade com média de 5,43 pontos. Na regressão linear, os fatores associados à fragilidade foram a menor escolaridade (p=0,005) e o número de morbidades (<0,001), sendo que as mulheres apresentaram maior pontuação na fragilidade. Conclusão: Os fatores associados sexo, idade, escolaridade e multimorbidade, que incidem diretamente na fragilidade, acarretam ao longo do tempo aumento da fragilidade da pessoa idosa. Tal condição pode ocasionar piora em seu estado de saúde e no desenvolvimento de novas comorbidades.

Resumen

Objetivo: Determinar los factores relacionados con el síndrome de fragilidad en adultos mayores con diagnóstico de hipertensión arterial sistémica. Métodos: Estudio de enfoque cuantitativo y transversal, realizado con personas de 60 años o más, de ambos sexos, con diagnóstico de hipertensión arterial. Se evaluó el perfl sociodemográfco, las medidas de la presión arterial, los hábitos de vida, la Escala de Fragilidad de Edmonton y el test Mini-Mental. Se utilizó la estadística descriptiva, el análisis de correlación de Pearson y el test-T para comparar las medidas, además de la regresión logística lineal. Hubo signifcación p<0,05. El estudio fue aprobado por el Comité de Ética e Investigación. Resultados: De los 272 participantes evaluados, 162 tenían diagnóstico de hipertensión arterial sistémica, 119 (73,45 %) eran mujeres, la mayoría entre 60 y 79 años (82,1 %), 85 sin pareja (52,5 %), con promedio de escolaridad de 5,14 años y de 5,18 morbilidades, además de la hipertensión arterial. El test Mini-Mental evidenció un rastreo positivo de defciencia cognitiva en 96 (59,3 %) individuos de la población estudiada y fragilidad promedio de 5,43 puntos. En la regresión lineal, los factores asociados a la fragilidad fueron la baja escolaridad (p=0,005) y la cantidad de morbilidades (<0,001), y las mujeres presentaron mayor puntaje de fragilidad. Conclusión: Los factores asociados sexo, edad, escolaridad y multimorbilidad, que inciden directamente en la fragilidad, conllevan un aumento de la fragilidad de las personas mayores a lo largo del tiempo. Esta condición puede empeorar el estado de salud y el desarrollo de nuevas comorbilidades.

Introduction

The elderly population progressively grows over the years and aging is often seen as a negative scenario. A stereotype was created in which old age is linked only to illness and dependence, ignoring that aging is a heterogeneous process, permeated by biological, psychological, and social dimensions. Aging is marked as a complex situation, resulting from the interaction of various processes and events in the course of people's lives. This can cause a gradual decline in physical and mental abilities over time. Old age can be marked by the emergence of geriatric syndromes and impaired quality of life.0 2)

Population aging has caused major changes in the scenario of Chronic Non-Communicable Diseases (CNCD). They are currently responsible for the increase in diagnosed diseases and the mortality rate, increasing their prevalence and incidence. The growing number of diagnoses is a negative reflection of the lifestyle adopted by people throughout their lives, such as lack of physical exercise, consumption of processed foods, and lack of a balanced diet.6,4'

The presence of CNCD modifies healthcare costs as long periods of treatment are necessary. Consequently, greater financial resources are also needed to continue healthcare, and systemic arterial hypertension (SAH) is highlighted among them.(1,4,5)

Worldwide, the prevalence of arterial hypertension was 29.7% in 2006 and this percentage exceeded 33.5% in 2016.(6) In Brazil, its incidence reached 32.3% from 2013 on.(5) As a result of the disease, individuals can present serious complications, such as stroke, acute myocardial infarction, chronic kidney disease, and cardiac arrhythmia.'6'

Systemic arterial hypertension is characterized by the Brazilian Society of Cardiology (BSC) as a constant high level of systolic (>140 mm Hg) and diastolic (>90 mm Hg) pressures. This blood pressure is exerted on the arteries and can cause damage to their structure. Generally, individuals do not present symptoms, but vertigo, dyspnea, palpitations, frequent headaches, and vision changes are warning signs when they occur.(5)

Some factors associated with SAH (such as a sedentary lifestyle, tobacco use, overweight, abdominal obesity, diabetes mellitus, abandonment of pharmacological treatment, and sociodemographic profile) contribute to making aging more complex. These elements contribute to increasing the fragility of elderly people.'7'

Frailty syndrome is the result of physiological and functional dysregulation in some systems, being related to age or due to some morbidity that people present.0' Furthermore, it can be physical, psychological, or both can be associated, leaving people in a state of extreme vulnerability, exhausting them when facing external stressors. This is a condition that can improve or worsen over time. Elderly people may experience falls, increased morbidity functional disability, decreased strength, resistance, and physiological function, increasing the risk of individual dependence.'2'

Evidence of relationships between frailty and arterial hypertension is scarce and related to studies with distinct criteria to characterize frailty, compromising the evidence of association. It was estimated that 46.2% of the population has some comorbidity and a concomitant frailty syndrome. This topic has been little explored and studies are therefore needed to better understand the relationships between both diseases.'8'

As arterial hypertension is the most prevalent CNCD in elderly people0' and can increase the risks of this population group developing frailty syndrome, the objective of the present study was to determine the factors related to frailty syndrome in elderly people diagnosed with systemic arterial hypertension. Methods

This was a cross-sectional and analytical study with a quantitative approach. It was developed in a District Basic Health Unit in the city of Ribeirao Preto (SP), Brazil.

The population consisted of people aged >60 years who were treated at the aforementioned health unit (geriatrics specialty). The sample size calculation considered a coefficient of determination R (10.02) in a multiple linear regression model with predictors. The level of significance or errors of types I (a=0.1) and II ((3=1.0) resulted in an a priori statistical power of 90%. Using the Power Analysis and Sample Size (PASS; v. 13) application and introducing the described values, the minimum sample size (n=206) was obtained. Considering a sample loss of 20% (refusal to participate), 258 was the final number of attempts initially predicted.

The inclusion criteria adopted were as follows: age >60 years old and men and women with a clinical diagnosis of systemic arterial hypertension without cognitive impairment. All of them signed the Free and Informed Consent Form. Thus, the final sample consisted of 162 elderly people diagnosed with systemic arterial hypertension.

The independent sociodemographic and clinical variables were as follows: sex, age, marital status, education, living alone, family income, multi-morbidities, cognitive status, use and time of use of antihypertensive medications, time since diagnosis of arterial hypertension, and blood pressure control, considering the three measurements taken at the time of data collection. The independent variables were collected using an instrument from the Geriatrics and Gerontology Research Center (Ribeirao Preto Nursing School, University of Sao Paulo). To measure blood pressure, the steps of the VII Brazilian Guideline on Arterial Hypertension were followed.'9'

To assess cognition, the Mini-Mental State Examination (MMSE) was used.'10' It was validated for the Portuguese language (1994)'11' and its score varies in the range of 0-30 points. However, the cutoff points suggested by the authors were changed. New scores were established as indicative of positive screening for illiterates (<20) and those with 1-4 (24), 5-8 (26.5), 9-11 (28), and >11 years of schooling (29).'12'

Frailty syndrome was the dependent variable of the study. For its measurement, the Edmonton Frailty Scale'13' validated for the Portuguese language was used.'14' The scale has a score of 0-17 points and the highest score represents the highest level of frailty. According to the cut-off point, the frailty of the elderly can be categorized as non-frail (0-4), apparently frail (5-6) and mild (7-8), moderate (9-10), and severe (>11) frailty.'14'

The data collection team was composed of the researcher and undergraduate and postgraduate students who participated in constant training and supervision to ensure the validity of the participant's responses in the study. A pilot evaluation was performed to consider questions and suggestions throughout the evaluations. Elderly people were randomly invited to participate before medical consultations at the health facility and assessments were performed after consultations by the data collection team. Participants were taken to a quiet room where they sat for 5 min before having their blood pressure checked using an OMRON oscillometric device (model HEM-7122). The assessments were performed from November 2019 to March 2020.

The data were tabulated with double entry using the Microsoft Excel program and a consistency analysis was then performed to compare the entries. The data were then exported to the Statistical Package for the Social Sciences (SPSS; v. 22.0) program. Descriptive analyses were performed with measures of central tendency, dispersion, and proportions; data were then analyzed with Pearson's correlation analysis, Student's f-test, and multiple linear regression. Alpha values with 0.05 significance were considered.

The project was approved by the Ethics and Research Committee (Ribeirao Preto School of Nursing, University of Sao Paulo) under the guidelines of the National Health Council (Resolution: 466/2012; Opinion: 3,582,859; Certificate of Presentation of Ethical Appreciation: 14098819.0.0000.5393). Results

Regarding the sociodemographic characteristics of participants diagnosed with systemic arterial hypertension, most of them presented the following characteristics: age range of 60-79 years (82.1%), female (73.5%), without a partner (52.5%), did not live alone (77.2%), and income of two minimum wages (44.4%). (Table 1). The mean age was 72.9 years (SD=7.54), with a minimum-maximum range of 60-103 years. Regarding education, the average was 5.14 years (SD=4.06) ranging from 0-19 years of study.

The qualitative clinical data of the participants showed that most of them had a probable cognitive decline (59.3%), controlled blood pressure (69.1%), and used antihypertensive medication (96.9%). Regarding the quantitative clinical variables, the mean times (years) were calculated for the diagnosis of SAH (14.73; SD=12.28) and antihypertensive medication (14.36; SD=12.10). To analyze the

In the stratification of multimorbidities, participants presented musculoskeletal diseases (98.76%), mental disorders (52.46%) and metabolic (49.38%), circulatory system (41.35%), ocular (33.3%), and urological (27.16%) diseases. In the bivariate analysis (Pearson correlation) between age, multimorbid-ities, education, and time since diagnosis of SAH (in years) with frailty, it was found that the same occurs with frailty, with a moderate and positive correlation as multimorbidities increase. Regarding education, the correlation was moderate and negative, i.e., frailty increased as education decreased. Higher age showed a borderline correlation with greater frailty. Females presented a greater mean fragility compared to males. The variables marital status, blood pressure, and cognitive status did not show a significant correlation. Linear regression analysis indicated that education and multimorbidities were predictors of frailty. Regarding education, frailty increased as years of study decreased, and the greater the multimorbidities, the higher the frailty scores (Table 3).

Discussion

The objective of this study was to determine the factors related to the frailty syndrome in elderly people diagnosed with systemic arterial hypertension who were treated in a health unit. We highlight education and multimorbidities, with effects also identified for sex and borderline age.

The results obtained in this research strengthen previous scientific evidence that points to an increase in the risk associated with frailty with advancing age.'8'15'16' Demographic analysis of the data revealed a mean age of 72.9 years with a predominance of younger elderly (60-79 years) and women. These results agree with those of a study conducted in Ghana(17) where some variables showed a notable relationship with an increased chance of developing

frailty: age >70 years, presence of complications related to arterial hypertension, and low and medium adherence to treatment. Another study also identified a positive correlation between frailty and age, in both the group with normal blood pressure control and individuals diagnosed with SAH.(18)

In the analysis of frailty, it was found that women presented a score of apparently more vulnerable compared to that of men; this agrees with the previous findings of another study that indicated a higher prevalence of vulnerability to frailty in hypertensive women.'18' Reinforcing this trend, the analysis revealed that the female gender is identified as a significant predictor of frailty as observed in previous studies,'815' including the Brazilian context.'16' These results confirm the association between sex and frailty, highlighting that understanding the disparities between men and women is relevant.

Multimorbidities direcdy impact the frailty score as they are associated with a high risk of progressive disease development. In addition, the greater the increase in frailty, the greater the risk of individuals developing new morbidities, which suggests a bidirectional association between these two conditions.'19' Among multimorbidities, musculoskeletal diseases that are linked to the aging of individuals and are associated with significant functional limitations prevail, impacting the loss of independence of elderly people.'19'20' An increase was observed in multimorbidity and frailty concomitant with another study that used these variables.'15' Frailty is closely related to aging and multi-morbidity,'21' presenting a correlation with unfavorable clinical outcomes.'18' These data highlight the need to support multidisciplinary teams in disease management, rehabilitation, nutrition, and psychosocial support in supporting 'frail or pre-frail' older people diagnosed with SAH.

When the education level of the elderly was analyzed, we observed that it decreased as frailty increased. This finding agrees with other studies in which elderly people with a lower level of education have higher rates of prevalence of frailty. (16,18,21) Additionally, high education is a predictor of adequate adherence to treatment and, thus, better control of arterial hypertension and a reduction in deaths and injuries.'3'

Regarding the cognitive assessment in this study, the majority of elderly people diagnosed with SAH presented potential cognitive decline as the screening was positive; however, no correlation with greater frailty was observed. A previous study suggested that arterial hypertension is associated with impaired cognitive function,(22) recognizing that arterial hypertension is an important risk factor for cardiovascular disease and reduction in cognitive function/23'24' Although the mechanisms related to blood pressure variability and cognitive functions are unclear, we know that cerebrovascular disorders resulting from blood pressure variability cause reduced cognitive functions/22'

Strategies for managing arterial hypertension in the elderly should consider the degree of frailty, multimorbidities, and associated factors mentioned. This is because antihypertensive treatment in frail elderly individuals has potential risks, such as increased hypotension, syncope, electrolyte imbalance, and acute kidney injury.(25) In the analysis of multimorbidities, the average was 5.18 morbidities per elderly person (min.-max.: 1-17) in addition to arterial hypertension. A study evaluated multimorbidities and identified that the number of comorbidities increases frailty, increasing the demand for health services and complications such as disability and death.(26) Thus, adopting an individualized approach to establish care according to the needs of the elderly is essential/18'25'

We emphasize that managing arterial hypertension control is not an easy task for elderly people with low levels of education who live on a low salary to stay healthy. Multimorbidities associated with aging under detrimental conditions of understanding and maintaining life harm health, predisposing to the development of frailty and thus to a decline in functional capacity. Then, highlighting the importance of longitudinal studies with the elderly population aiming to identify the relationship between frailty and chronic diseases, such as arterial hypertension, is necessary. This disease has been studied more globally, making it difficult to precisely relate some related factors, in addition to not being possible to precisely estimate the impact of systemic arterial hypertension on the frailty syndrome. This is a path to be followed by researchers and public managers.

We highlight that the cross-sectional design of the study was a limitation of the research. It allowed observing the behavior of variables at a single moment (e.g., the blood pressure control variable) but did not allow observing its variation over time and its possible relationship with the increase or decrease in frailty. However, we confirm the importance of identifying factors related to frailty, highlighting the need for longitudinal monitoring to explore these relationships in more depth, thus contributing to the health of this population.

Conclusion

The associated factors that directly affect frailty increase the frailty of elderly people over time. Such a condition can worsen their health status and develop new comorbidities, and the increase in frailty can bring new diseases. More in-depth studies on the topic are necessary to guide the development of public policies that will provide specific care for the needs of this population group.

Acknowledgments

National Council for Scientific and Technological Development (CNPq)- number 314228/2021-7. "This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) - Finance Code 001"

Collaborations

Matiello FB, Kobayasi DY, Fernandes DS, Alcantara e Silva MP, Azevedo KB, Fhon JR, Lima NKC, and Rodrigues RAP contributed to the design of the study, analysis and interpretation of the data, writing of the manuscript, critical review of relevant intellectual content, and approval of the final version to be published.

References

References

1. Soares MS, Brito GA, Horta IC, Gomes IR, Carneiro JA, Costa FM. Worsening frailty in community-dweling older people with hypertension and associated factors. Rev Bras Geriatr Gerontol. 2022;25(3):e220188.

2. Duarte YA, Nunes DP, Andrade FB, Corona LP, Brito TR, Santos JL, et al.. Frailty in older adults in the city of Sao Paulo: Prevalence and associated factors. Rev Bras Epidemiol. 2018;21 :e180021.

3. Silva LM, SouzaAC, Fhon JR, Rodrigues RA. Treatment adherence and frailty syndrome in hypertensive older adults. Rev Esc Enferm USP 2020;54:e03590.

4. Figueiredo AE, Ceccon RF, Figueiredo JH. Chronic non-communicable diseases and their implications in the life of dependente eldery people, dene Saude Coletiva. 2021 ;26(1):77-88.

5. Barroso WK, Rodrigues CI, Bortolotto LA, Mota-Gomes MA, Brandao AA, Feitosa AD, et al. Diretrizes Brasileiras de Hipertensao Arterial -2020. Arq Bras Cardiol. 2021 ;116(3):516-658.

6. VosT,AbajobirAA, Abate KH.Abbafati C, Abbas KM, Abd-Allah F, etal. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211 -59.

7. Fried LP,Tangen CM,Walston J, Newman AB, Hirsh C, Gottdiener J, et al. Frailty in older adults. J Gerontol A Biol Sci Med Sci. 2001 ;56:M146-57.

8. Aprahamian I, Sassaki E, Dos Santos MF, Izbicki R, Pulgrossi RC, Biella MM, et al. Hypertension and frailty in older adults. J Clin Hypertens (Greenwich). 2018;20(1):186-92.

9. Sociedade Brasileira de Cardiologia (SBC). Diretriz brasileira de hipertensao arterial. Arq Bras Cardiol. 2021 ;116(3):516-658.

10. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for clinician. J Psychiatr Res. 1975;12(3)189-98.

11. Bertolucci PH, Brucki SM, Campacd S, Juliana Y. The Mini-Mental State Examination in na outpatient population: influence of literacy. Arq Neuropsiquiatr. 1994;52(1):1-7.

12. Brucki SM, Nitrini R, Caramelli P, Bertolucci PH, Okamoto IH. Suggestions for utilization of the mini-mental state examination in Brazil. Arq Neuropsiquiatr. 2003;61(3B):777-81.

13. Rolfson DB, Majumdar SR, Tsuyuki RT, Tahir A, Rockwood K. Validity and reliability of the Edmonton Frail Scale. Age Ageing. 2006;35(5):526-9.

14. Fabrido-Wehbe SC, Schiaveto FV, Vendrusculo TR, Haas VJ, Dantas RA, Rodrigues RAP. Cross-cultural adaptation and validity of the "Edmonton Frail Scale - EFS in a Brazilian elderly sample. Rev Latino-Am Enfermagem. 2009;17(6)1043-9.

15. Li L, Wang Y, Yang C, Huang C, Duan L, Zhou J, et al. Frailty in hypertensive population and its association with all-cause mortality: data from the National Health and Nutrition Examination Survey. Front Cardiovasc Med. 2023;10:945468.

16. Oliveira PR, RodriguesVE, OliveiraAK, Oliveira FG, Rocha GA, Machado AL. Factors associated with frailty in elderly patients followed up in primary health care. Esc Anna Nery. 2021 ;25(4):e20200355.

17. Sakyi SA, Tawiah P, Senu E, Ampofo RO, Enimil AK, Amoani B, et al. Frailty syndrome and associated factors among patients with hypertension: A cross-sectional study in Kumasi, Ghana. Health Sci Rep. 2023;6(10):e1664.

18. Ma L, Chhetri JK, Liu P, Ji T, Zhang L,Tang Z. Epidemiological characteristics and related factors of frailty in older Chinese adults with hypertension: a population-based study. J Hypertens. 2020;38(11):2192-7.

19. Vetrano DL, Palmer K, Marengoni A, Marzetti E, Lattanzio F, Roller-Wirnsberger R, et al.; Joint Action ADVANTAGE WP4 Group. Frailty and multimorbidity: a systematic review and meta-analysis. J Gerontol A Biol Sci Med Sci. 2019;74(5):659-66.

20. Oliveira BD, Dilelio AS, Saes MO. Prevalenda de disturbios osteomusculares e fatores associados na populagao idosa: revisao sistematica. Acta Fisiatr. 2020;27(4):248-55.

21. Hoogendijk EO, Afilalo J, Kristine EE, Kowal P, Onder G, Fried LP. Frailty: implications for clinical practice and public health. Lancet. 2020;394:1365-75.

22. Yildinm E, Ermis E, Allahverdiyev S, Ucar H, Yavuzer S, Yavuzer H, et al. Relationship between blood pressure variability and cognitive function in geriatric hypertensive patients with well-controlled blood pressure. Aging Clin Exp Res. 2020;32(1):93-8.

23. Lu S, Xu Q, Yu J, Yang Y, Wang Z, Zhang B, et al. Prevalence and possible factors of cognitive frailty in the elderly with hypertension and diabetes. Front Cardiovasc Med. 2022;91054208.

24. Murukesu RR, Singh DK, Subramaniam P, Tan XV, Izhar IA, Ponvel P, et al. Prevalence of frailty and its association with cognitive status and functional fitness among ambulating older adults residing in institutions withinwest coast of Peninsular Malaysia. Int J Environ Res Public Health. 2019;16(23):4716.

25. Guasti L, Ambrosetti M, Ferrari M, Marino F, Ferrini M, Sudano I, et al. Management of hypertension in the elderly and frail patient. Drugs Aging. 2022;39(10):763-72.

26. Sinclair AJ, Abdelhafiz AH. Multimorbidity, frailty and diabetes in older people-identifying interrelationships and outcomes. J Pers Med. 202212(11)1911.