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Biomarkers Of Frailty:From Physical Function To Inflammation And Oxidative Stress

Posted on:2021-07-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:S JiangFull Text:PDF
GTID:1484306308982329Subject:Geriatric medicine
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Objective:To investigate the characteristics of frailty and influencing factors among elderly community-dwelling residents,explore the relationship between inflammatory and oxidative stress biomarkers and frailty and functional status among elderly community residents,and explore the value of combinations of multiple types of biomarkers in the diagnosis of frailty.Methods:For this cross-sectional study,we recruited 230 older adults living in a senior community in Beijing from June to August 2018.All participants were aged 75 years or older and were in stable physical condition.We excluded residents with acute disease because inflammatory markers may change during acute medical problems.We also excluded residents with severe dementia or communication difficulties.Informed consent was obtained from all participants in written form.Participants received comprehensive geriatric assessment,which included Charlson comorbidity index,activities of daily living,frailty status,cognitive impairment.mental health,physical function,nutrition,geriatric syndrome and quality of life.Serum high-sensitivity C-reactive protein(hsCRP),white blood cell count(WBC),urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine,and 8-oxo-Gsn were measured.According to Fried frailty phenotype,participants were divided into non-frail group,pre-frail group and frail group.Results of comprehensive assessment and inflammatory and oxidative stress biomarkers were compared.Pearson correlation analysis was used to analyze the relationship between biomarkers of inflammation and oxidative stress and physical functional indicators.The contributing factors of frailty were analyzed by Logistic regression.The ROC curve was used to analyze the predictive value of inflammatory and oxidative stress indicators in the diagnosis of frailty,and the predictive probability model of various combinations of biomarkers was established to analyze the ability in the diagnosis of frailty.Results:(1)Overall,230 participants were enrolled in the study,with a mean age of 83.9±4.4 years,and 57.7%were women.Of the 230 participants,50(22%)were non-frail,105(45%)were pre-frail,and 75(33%)were frail.At baseline,the frail group was significantly older than the non-frail and pre-frail groups.The comorbidity index score was significantly higher in the frail group.There were no significant differences in sex among the three groups.(2)The results of geriatric comprehensive assessment:?The differences among the three groups in ADL and IADL scores were statistically significant(Z=46.038,77.848,P<0.05).The prevalence of frailty with normal ADL score was 23.7%.The prevalence of frailty with IADL score on 6?8 was 17.4%.?High prevalence rates of low physical activity,slowness,and weakness were observed in the frail group.The time of 5-time chair stand test and timed-up-and-go test in frail group were significantly higher than the other two groups(F=29.639,36.15,P<0.001).SPPB score in the frail group was lower than the other two groups(Z=90.870,P<0.001).?Scores on the MNA-SF,and MMSE were significantly lower in the frail group than in the other two groups.Scores on the GDS was higher than the other groups.?The prevalence of geriatric syndromes in frail group such as urinary incontinence,hearing impairment,constipation,insomnia,falls in the last year were significantly higher than the other two groups(?2=9.561,10.796,12.602,7.764,11.564,P<0.05).?Self-assessment of quality of life:the EQ-5D health index of the frail group was lower than the other groups(F=34.027)P<0.001).The score of EQ-VAS in the frail group was lower than the other two groups(Z=20.302,P<0.05).(3)Serum hsCRP level in the frail group was 3.7(1.3-5.2)mg/L,significantly higher than the pre-frail group 1.5(1.0-2.7)mg/L and the non-frail group 1.4(0.7-2.1)mg/L(Z=15.214,P<0.001).Serum WBC level of the frail group(5.9±1.1)*109/L was higher than the pre-frail group(5.8±1.3)*109/L and the non-frail group(5.4±1.2)*109/L(Z=3.738,P<0.05).(4)Urinary 8-oxo-Gsn in the frail group was 3.8(3.2-4.8)?mol/mol,significantly higher than the pre-frail group 3.1(2.5-4.0)?mol/mol and the non-frail group 2.8(2.0-3.5)?mol/mol.There were no significant differences in urinary 8-oxo-dGsn among the three groups(Z=1.306,P>0.05)?(5)Pearson correlation analysis showed that serum hsCRP level and grip strength,walking speed and SPPB score were significantly negative correlation(r=0.142,0.278,0.279,P<0.05);Serum hsCRP level and 5-time chair stand,timed-up-and-go were positively correlation(r=0.158,0.176,P<0.05);There was no significant relationship between serum WBC level and physical function.Urinary 8-oxo-Gsn level was negatively correlated with grip strength,walking speed,and SPPB score(r=-0.302,-0.550,-0.350,P<0.001).Urinary 8-oxo-Gsn level was positively correlated with 5-time chair stand,timed-up-and-go(r=0.257,0.246,P<0.001).There was no significant relationship between urinary 8-oxo-dGsn level and physical function(P>0.05).(6)After adjusting for age,sex,and Charlson comorbidity index,urinary 8-oxo-Gsn level independently predicted 98%higher risk of frailty(OR=1.98,95%CI:1.480-2.651,P<0.001)and serum hsCRP was also significantly associated with frailty status(OR=1.19,95%CI:1.022?1.38,P=0.025).There was no significant association between serum WBC and urinary 8-oxo-dGsn and frailty.(7)Using the non-frail group as the standard,we further performed ROC analysis to test the predictive value of 8-oxo-Gsn level for frailty.An 8-oxo-Gsn level of 3.175 ?mol/mol had the optimal predictive value for frailty,with an area under the ROC curve(AUC)of 0.72(p<0.001,95%CI:0.649-0.788).At this level,the sensitivity was 0.81 and the specificity was 0.58.The AUC for hsCRP was 0.69(p<0.001,95%CI:0.610-0.775).The AUC for WBC was 0.55,with a non-significant p-value of 0.202.(8)The prediction probability model was established by using the combination of biomarkers.Combined walking speed and urine 8-oxo-Gsn AUC was 0.84(95%CI:0.794-0.894,P<0.001).Combined walking speed and hsCRP AUC was 0.83(95%CI:0.780?0.885,P<0.001).Combined walking speed and urine 8-oxo-Gsn and hsCRP AUC was 0.85(95%CI:0.805?0.902,P<0.001).Combined FRAIL scale and urine 8-oxo-Gsn AUC was 0.93(95%CI:0.897?0.960,P<0.001),which were higher than other combination of markers,and could improve the accuracy of frailty diagnosis.Conclusion:In the elderly community,the incidence of frailty is still high even in the older individual who live independently.Physical functional indicators such as grip strength,walking speed and SPPB are biomarkers reflecting physical frailty.Inflammatory biomarker such as serum hsCRP is correlated with frailty and the decline function.Increased urinary 8-oxo-Gsn,an indicator of oxidative stress,is associated with an increased risk of frailty in elderly residents living in the community.This urinary biomarker is a promising indicator of frailty in older adults.Its measurement may be implemented to screen widely for frailty among community-dwelling older adults.Investigating the relationship between oxidative stress and frailty by examining biomarkers provides more accurate prediction and improves the probability of early intervention for frailty.Different types of biomarker combinations can improve the diagnostic value of frailty,and provide a reversible multi-target intervention of frailty.
Keywords/Search Tags:8-oxo-Gsn, frailty, inflammation, oxidative stress, community residents
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