Associations Of High-Sensitivity C-Reactive Protein With Activities Of Daily Living Disability,Cognitive Impairment,and All-cause Mortality Among The Oldest Old

ObjectiveTo investigate the associations of high-sensitivity C-reactive protein(hs-CRP)with activities of daily living(ADL)disability,cognitive impairment,and all-cause mortality among the oldest old.MethodsThis study was based on the Healthy Aging and Biomarkers Cohort Study(HABCS),the subcohort of the Chinese Longitudinal Healthy Longevity Survey(CLHLS).In this study,we completed the 8th round of follow-up and newly added survey of 1094 participants in 2018 in 7 cities in Guangdong Province,In addition,the 9th round of field survey in 2021 included 541 participants in the longevity township of Guangdong Province and Sichuan Province.As one of the persons in charge of the field,I participated in and conducted the surveys in the 8th and 9th rounds.The oldest old were taken as study participants.The hs-CRP was measured to reflect the level of inflammation among the participants.The ADL and cognitive function were evaluated using the Katz Activities of Daily Living Scale and the Mini-Mental State Examination,respectively.The death outcome was tracked and the survival time was determined through follow-up.Based on the cross-sectional study designs,the odds ratios(OR)and 95%confidence interval(CI)were calculated by the Logistic regression model to estimate the correlations between hs-CRP level and ADL disability and cognitive impairment.Based on the prospective cohort studies,Cox proportional hazards regression models were used to calculate the hazard ratios(HR)and 95%CI to estimate the association between hs-CRP levels and risk of ADL disability,cognitive impairment,and all-cause mortality.Receiver operating characteristic curves(ROC)and the area under the ROC curves(AUC)were used to evaluate the predictive ability of hs-CRP alone,combined ADL or(and)cognitive function as predictors of all-cause mortality among the oldest old,respectively.The optimal cut-off value of the hs-CRP level among the oldest old was further determined by Youden’s index of the best model.Cox proportional hazards regression model was used to estimate the effect of the hs-CRP cut-off value combined with ADL and cognitive function on all-cause mortality among the oldest old.Results(1)Hs-CRP and ADL disability in the oldest old:In the cross-sectional study,compared with the lowest hs-CRP quartile,the oldest old in the fourth quartile had a higher risk of ADL disability(OR:1.08,95%CI:1.04,1.11),and the risk of ADL disability increased with the elevated hs-CRP level(P<0.001);However,there was no statistically significant association in the cohort study(HR:1.01,95%CI:0.69,1.49).(2)Hs-CRP and cognitive impairment in the oldest old:In the cross-sectional study,after adjusting for part of the confounding factors,the risk of cognitive impairment was higher in the fourth quintile group than in the lowest quintile group of hs-CRP(OR:1.04,95%CI:1.01,1.08),and there was no significant difference after further adjustment for history of diseases(OR:1.01,95%CI:0.98,1.04);In the cohort study,compared with the lowest quintile of hs-CRP,the risk of cognitive impairment was not significant increased in the fourth quintile(HR:1.03,95%CI:0.73,1.47).(3)Hs-CRP and all-cause mortality in the oldest old:Compared with the lowest quartile of hs-CRP,the oldest old in the fourth quartile had the highest risk of all-cause mortality(HR:1.46,95%CI:1.23,1.73),and the risk was significantly increased with the elevated hs-CRP level(P-trend<0.001);There were interactions between hs-CRP level and education,marriage,smoking,alcohol consumption,and BMI for the risk of all-cause mortality in the oldest old(P-interactin<0.05).ROC analysis showed that compared with the "hs-CRP" group,"hs-CRP combined with ADL" group,"hs-CRP combined with cognitive function" group,and "hs-CRP combined with ADL and cognitive function" group had higher predictive value for all-cause mortality in the oldest old(AUC=0.779,P<0.001 for all comparisons between groups).When hs-CRP combined with ADL and cognitive function were used as predictors,the optimal cut-off value of hs-CRP level in the oldest old was 2.59 mg/L.Cox regression results of hs-CRP combined with ADL and cognitive function showed that compared with whose hs-CRP<2.59 mg/L and the functional status were normal,hs-CRP>2.59 mg/L with ADL disability(HR:2.47,95%CI:2.01,3.02),hs-CRP>2.59 mg/L with cognitive impairment(HR:2.01,95%CI:1.62,2.48),hs-CRP>2.59 mg/L with two impaired functional status(HR:4.14,95%CI:3.20,5.35)had a higher risk of all-cause mortality among the oldest old.Conclusions(1)The hs-CRP level was positively correlated with ADL disability risk,but it was not correlated with cognitive impairment;(2)The increase of hs-CRP level was associated with a higher risk of all-cause mortality,but not associated with the risk of ADL disability and cognitive impairment;(3)The hs-CRP combined with ADL and cognitive function had a high predictive value in predicting all-cause mortality in the oldest old population.The combination of the optimal cut-off value of hs-CRP with ADL and cognitive function status can provide a scientific basis for the identification of high-risk populations of all-cause mortality in the oldest old.