Risks Factors Of Frailty And Its Association With Risk Of Diabetes And Cardiovascular Disease In Middle-Aged And Older Adults

BackgroundAs the ageing of the population becomes more apparent,frailty is emerging as one of the most important priorities in public health.Frailty has been identified in both middle-aged and older adults;analysis of the association between risk factors and frailty and estimation of the population-attributable risk in middle-aged and older people will provide evidence for health professionals in frailty prevention and intervention.With the changing age structure of the population,the association of frailty with diabetes and cardiovascular disease has gained traction.In particular,frailty has become a highpriority issue in cardiovascular disease.However,evidence on the association of frailty with the risk of diabetes and cardiovascular disease is more limited,especially in the Chinese population.Thus,the association of frailty with the risk of diabetes and cardiovascular disease was analysed,with a view to the development of prevention and intervention strategies for frailty in these diseases.MethodsThis study was based on the data of the China Health and Retirement Longitudinal Study(CHARLS)from 2011 to 2018.Frailty index was used to assess frailty status.Risk factors for frailty in middle-aged and older adults:Twelve modifiable risk factors associated with frailty were selected based on the results of previous studies,information collected in the CHARLS project,and public health implications,including two socioeconomic status(education level and residence),three social relationships(marital status,social activities,and life satisfaction),two lifestyle factors(smoking and sleep),and five metabolic risk factors(abdominal obesity,body mass index,hypertension,diabetes,and dyslipidemia).A score of 0-1 was assigned to each risk factor to give an overall score for each domain.The study outcome was the occurrence of frailty in middle-aged and older adults aged 45 years and older,defined as a frailty index≥0.25.Using the CHARLS data 2011 to 2018,Cox proportional hazards models were used to analyse the association of individual and combined risk factors with the risk of frailty among all middle-aged and older adults and in three age groups(45-54 years,55-64 years,and≥65 years),and to estimate the population attributable risk percentage(PAR%).Association of frailty with risk of diabetes or cardiovascular disease in middleaged and older adults:Association of baseline(2011)frailty with risk of diabetes or cardiovascular disease:Using CHARLS data from 2011 to 2015(for diabetes)or 2011 to 2018(for cardiovascular disease),baseline frailty status was defined in 3 categories:non-frail(frailty index ≤0.10),pre-frail(frailty index>0.10 to<0.25)and frail(frailty index≥0.25).Cox proportional hazards models were used to analyse the association between baseline frailty and risk of diabetes or cardiovascular disease.Restricted cubic splines(RCS)were used for analysis of the non-linear association of baseline frailty index as a continuous variable with risk of diabetes or cardiovascular disease.Association of the developmental trajectories of frailty with the risk of diabetes or cardiovascular disease:Using CHARLS data from 2011 to 2018,the group-based trajectory modelling was combined with survey data from 2011,2013 and 2015 to determine the developmental trajectories of frailty.Cox proportional hazards models were used to analyse the association between the developmental trajectories of frailty and risk of diabetes or cardiovascular disease in 2018.Results1 Risk factors for frailty in middle-aged and older adults:A total of 6852 participants were included in the analysis after exclusion of the presence of frailty at baseline,lack of information on risk factors and incident frailty.During a median follow-up period of 6.92(IQR 3.92-7.01)years,1133 frailty events occurred.In all populations,all risk factors were associated with a significantly increased risk of frailty,except for smoking and dyslipidemia.Among them,lower levels of education had the most significant association with the risk of frailty(HR=1.61,95%CI=1.40-1.83).Among the combined risk factors,socioeconomic status had the strongest association with the risk of frailty(HR=1.53,95%CI=1.41-1.67).Results by age group showed that low education was most strongly associated with frailty in adults aged<65 years(HR=1.79,95%CI=1.37-2.34 in the age group 45-54 years;HR=1.77,95%CI=1.442.19 in the age group 55-64 years),while unhealthy sleep had the strongest association with frailty in adults aged≥65 years(HR=1.43;95%CI=1.15 to 1.77).Among the combined risk factors,lower socioeconomic status had the strongest association with frailty risk in all age groups(HR 1.57[95%CI=1.32-1.87]in age group 45-54 years;HR in age group 55-64 years was 1.74[95%CI=1.52-2.00];HR in age group≥65 years was 1.30[95%CI=1.14-1.50]).At the population level,low educational level and rural residence were the main contributors to frailty risk among all middle-aged and older adults,with PAR%of 23.5%and 22.2%,respectively.Combined socioeconomic status is also the factor that contributes most to frailty risk,with a PAR%of 40.8%.Results by age group showed that the contribution of low education and rural residence to frailty decreased with age,both being major risk factors for frailty in adults under 65 years old(the PAR%associated with low education was 21.5%and the PAR%associated with living in a rural area was 18.1%in the age group 45-54 years;the PAR%associated with low education was 30.3%and the PAR%associated with living in a rural area was 31.6%in the age group 55-64 years).However,combined socioeconomic status was still the most important risk factor for frailty in all age groups(PAR%was 38.2%,51.8%and 28.0%in the 45-54,55-64,and≥65 age groups,respectively).The effect of social relationships on frailty in middle-aged and older adults was mainly due to low social activity,and the metabolic risk factors were mainly driven by abdominal obesity.There was also a decrease with age in the risk of frailty due to social relationships and several individual metabolic risk factors(except dyslipidemia).Unhealthy sleep was the main factors of lifestyle on frailty in middle-aged and older people.In contrast to other risk factors,the contribution of unhealthy sleep to frailty gradually increases with age.In adults aged 65 years and over,it was the main cause of frailty,with a PAR%of 21.2%.2 Association between frailty and risk of diabetes in middle-aged and older adults:Association between frailty at baseline(2011)and risk of diabetes:Of the 13689 participants without diabetes at baseline included in the analysis,7468(54.55%)were classified as non-frail,4954(36.19%)as pre-frail,and 1267(9.26%)as frail.During the median follow-up of 4.00 years(IQR 3.60-4.00),513 diabetes events occurred.Compared with non-frail at baseline,pre-frail and frail at baseline had an increased risk of diabetes,with HRs(95%CI)adjusted for all potential confounders of 1.55(1.27-1.89)and 2.09(1.56-2.79),respectively.Restricted cubic spline analyses suggested that a frailty index≥0.09 was associated with an increased risk of diabetes.Association between developmental trajectories of frailty and risk of diabetes:9461 participants who were free of diabetes during 2011-2015 survey were included in this analysis.Using group-based trajectory modelling and survey data from 2011,2013 and 2015,three distinct groups of frailty trajectories were identified:low-stable(n=6216,65.7%),medium-increasing(n=2673,28.3%),and high-increasing(n=572,6.0%).During the median follow-up of 3.00 years(IQR 2.92-3.00),505 diabetes events occurred.Compared with the low-stable group,both the medium-increasing and high-increasing groups had an increased risk of diabetes,the HRs(95%CI)after adjusting for all potential confounders were 1.50(1.22-1.84)and 1.70(1.21-2.38),respectively.No effect on the association of baseline or developmental trajectories of frailty with diabetes was observed for traditional diabetes risk factors,including smoking,alcohol consumption,sleep,obesity,hypertension,and dyslipidemia.The above results were robust through a series of sensitivity analyses.3 Association between frailty and risk of cardiovascular disease in middleaged and older adults:Association between frailty at baseline(2011)and risk of cardiovascular disease:Of the 12575 participants without cardiovascular disease at baseline included in the analysis,7255(57.69%)were classified as non-frail,4360(34.67%)as pre-frail,and 960(7.63%)as frail.During a median follow-up period of 6.92 years(IQR 3.05-7.09),2004 cardiovascular disease events occurred.Compared with the non-frail population at baseline,those who were pre-frail and frail at baseline had an increased risk of cardiovascular disease,the HRs(95%CI)after adjustment for all potential confounders were 1.45(1.31-1.60)and 2.05(1.76-2.38),respectively.Restricted cubic spline analyses suggested that a frailty index≥0.09 was associated with an increased risk of cardiovascular disease.Association between developmental trajectories of frailty and risk of cardiovascular disease:8331 participants who were free of cardiovascular disease during 2011-2015 were included in this analysis.Using groupbased trajectory modelling and survey data from 2011,2013,and 2015,three distinct groups of frailty trajectories were identified:low-stable(n=5480,65.8%),mediumincreasing(n=2393,28.7%),and high-increasing(n=458,5.5%).During a median follow-up of 3.00 years(IQR 2.92-3.00),1008 cardiovascular disease events were identified.Compared with the low-stable group,the medium-increasing and highincreasing groups had an increased risk of cardiovascular disease,the HRs(95%CI)after adjusting for all potential confounders were 1.85(1.61-2.13)and 2.42(1.94-3.02),respectively.No effect on the association of baseline or developmental trajectories of frailty with cardiovascular disease was observed for traditional cardiovascular risk factors,including smoking,alcohol consumption,sleep,obesity,hypertension,diabetes,and dyslipidemia.The above results were robust through a series of sensitivity analyses.Conclusion1 Socioeconomic status was the factor which contributed most to the risk of frailty in middle-aged and older adults,with low education and rural residence were the main risk factors.However,the effect of low education and rural residence on the risk of frailty decreased with age,both being the main risk factors for frailty in adults under 65 years of age.In contrast,the effect of unhealthy sleep on the risk of frailty increased with age and was the main risk factor for frailty in people aged 65 years and over.In short,the effect of risk factors on frailty varied by age.Prioritising risk factors that have a greater impact on frailty at different ages will maximise the reduction of the burden of frailty.2 Both frailty at baseline and the increasing trajectories of frailty over time were positively associated with the risk of diabetes.These results were independent of chronological age and common diabetes risk factors(including smoking,alcohol consumption,sleep,obesity,hypertension,and dyslipidemia),and a series of subgroup and sensitivity analyses also demonstrated the robustness of the findings.Developing frailty screening and interventions for middle-aged and older adults will help reduce the risk of diabetes.3 Both frailty at baseline and the increasing trajectories of frailty over time were positively associated with the risk of cardiovascular disease in middle-aged and older Chinese populations.These results were independent of chronological age and common cardiovascular disease risk factors(including smoking,alcohol consumption,sleep,obesity,hypertension,diabetes,and dyslipidemia),and a series of subgroup and sensitivity analyses further demonstrated the robustness of the findings.Developing frailty screening and interventions in middle-aged and older adults will help reduce the burden of cardiovascular disease.