Frailty index and all-cause and cause-specific mortality in Chinese adults: a prospective cohort study.

BACKGROUND: The fraily index is a useful proxy measure of accelerated biological ageing and in estimating all-cause and cause-specific mortality in older individuals in European and US populations. However, the predictive value of the frailty index in other populations outside of Europe and the USA and in adults younger than 50 years is unknown. We aimed to examine the association between the frailty index and mortality in a population of Chinese adults. METHODS: In this prospective cohort study, we used data from the China Kadoorie Biobank. We included adults aged 30-79 years from ten areas (five urban areas and five rural areas) of China who had no missing values for the items that made up the frailty index. We did not exclude participants on the basis of baseline morbidity status. We calculated the follow-up person-years from the baseline date to either the date of death, loss to follow-up, or Dec 31, 2017, whichever came first, through linkage with the registries of China's Disease Surveillance Points system and local residential records. Active follow-up visits to local communities were done annually for participants who were not linked to any established registries. Causes of death from official death certificates were supplemented, if necessary, by reviewing medical records or doing standard verbal autopsy procedures. The frailty index was calculated using 28 baseline variables, all of which were health status deficits measured by use of questionnaires and physical examination. We defined three categories of frailty status: robust (frailty index ≤0·10), prefrail (frailty index >0·10 to <0·25), and frail (frailty index ≥0·25). The primary outcomes were all-cause mortality and cause-specific mortality in Chinese adults aged 30-79 years. We used a Cox proportional hazards model to estimate the associations between the frailty index and all-cause and cause-specific mortality, adjusting for chronological age, education, and lifestyle factors. FINDINGS: 512 723 participants, recruited between June 25, 2004, and July 15, 2008, were followed up for a median of 10·8 years (IQR 10·2-13·1; total follow-up 5 551 974 person-years). 291 954 (56·9%) people were categorised as robust, 205 075 (40·0%) people were categorised as prefrail, and 15 694 (3·1%) people were categorised as frail. Women aged between 45 years and 79 years had a higher mean frailty index and a higher prevalence of frailty than did men. During follow-up, 49 371 deaths were recorded. After adjustment for established and potential risk factors for death, each 0·1 increment in the frailty index was associated with a higher risk of all-cause mortality (hazard ratio [HR] 1·68, 95% CI 1·66-1·71). Such associations were stronger among younger adults than among older adults (pinteraction<0·0001), with HRs per 0·1 increment of the frailty index of 1·95 (95% CI 1·87-2·03) for those younger than 50 years, 1·80 (1·76-1·83) for those aged 50-64 years, and 1·56 (1·53-1·59) for those 65 years and older. After adjustments, there was no difference between the sexes in the association between the frailty index and all-cause mortality (pinteraction=0·75). For each 0·1 increment of the frailty index, the corresponding HRs for risk of death were 1·89 (95% CI 1·83-1·94) from ischaemic heart disease, 1·84 (1·79-1·89) from cerebrovascular disease, 1·19 (1·16-1·22) from cancer, 2·54 (2·45-2·63) from respiratory disease, 1·78 (1·59-2·00) from infection, and 1·78 (1·73-1·83) from all other causes. INTERPRETATION: The frailty index is associated with all-cause and cause-specific mortality independent of chronological age in younger and older Chinese adults. The identification of younger adults with accelerated ageing by use of surrogate measures could be useful for the prevention of premature death and the extension of healthy active life expectancy. FUNDING: The National Natural Science Foundation of China, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, the Kadoorie Charitable Foundation, and the Wellcome Trust.

Association of low-activity ALDH2 and alcohol consumption with risk of esophageal cancer in Chinese adults: A population-based cohort study.

Existing evidence remains inconclusive as to how the association between inactive ALDH2 and esophageal cancer (EC) depends on alcohol consumption. The study is based on the China Kadoorie Biobank cohort, with 10 years follow-up of 0.5 million adults aged 30-79 years. ALDH2 activity was assessed by both self-reported flushing response and Glu504Lys (rs671 G > A) polymorphism. Among both male and female participants who consumed alcohol less than weekly (n = 69,519; 211 EC cases), low active or inactive ALDH2 was not associated with increased EC risk [HRs (95% CIs): GA vs. GG 0.75 (0.54, 1.04); AA vs. GG 1.01 (0.46, 2.20)]. Among male weekly alcohol consumers, both flushing response [n = 59,380; 501 EC cases; HRs (95% CIs): "soon after drinking" vs. "no" flushing response 1.45 (1.05, 2.01)] and rs671 [n = 10,692; 94 EC cases; GA vs. GG 3.31 (1.94, 5.67)] were associated with EC risk. The increased EC risk associated with "soon" response or rs671 GA was apparent in men consuming alcohol ≥30g/d. Among male daily consumers, the HRs (95% CIs) for EC associated with 15g/d of alcohol were 1.28 (1.15, 1.44) for "soon" response [vs. other responses: 1.12 (1.09, 1.15); pinteraction = 0.047; n = 36,401, 425 EC cases] and 1.41 (1.08, 1.82) for rs671 GA [vs. GG: 1.16 (1.06, 1.27); pinteraction = 0.493; n = 6,607, 80 EC cases]. Self-reported flushing response had low sensitivity (56.8%) and high specificity (88.4%) in identifying rs671 A allele among male weekly alcohol consumers. In conclusion, low-activity ALDH2 was associated with increased EC risk among male heavy alcohol consumers. More accurate measurement of alcohol-related EC risk allows better achievement of precision prevention.

Functionalized gold nanorods as an immunosensor probe for neuron specific enolase sensing via resonance light scattering.

A novel resonance light scattering assay for neuron specific enolase (NSE) with high selectivity and sensitivity has been developed by using functionalized gold nanorods as an immunosensor probe.

A highly sensitive label-free resonance light scattering assay of carcinoembryonic antigen based on immune complexes.

As a kind of glycoprotein, carcinoembryonic antigen (CEA) is the important tumor marker for clinical diagnosis of the presence or recurrence of cancer. In this work, a novel label-free resonance light scattering (RLS) spectral CEA assay was developed based on the combination of highly selective immunoreaction and ultrasensitive RLS technique. In Tris-HCl buffer solution (pH 7.5), the specific immunoreaction between CEA antigen and mouse anti-CEA formed immune complexes which had a maximum RLS spectral peak at 389.0 nm, with the existence of physiological saline and polyethylene glycol 20,000 (PEG 20,000). Under the optimal conditions, the magnitude of enhanced RLS intensity (ΔI(RLS)) was proportional to the concentration of CEA in the range from 0.1 to 60 ng mL(-1), with a detection limit (LOD, 3σ) of 0.03 ng mL(-1). The characteristics of RLS, the CEA immunocomplex, the immune response, the ratio of CEA antigen and mouse anti-CEA, and the optimum conditions of the immunoreaction have been investigated. The CEA concentrations of 20 serum specimens detected by the developed assay showed consistent results in comparison with those obtained by commercially available enzyme-linked immunosorbent assay (ELISA) kit. And this method has many satisfying merits including label-free, sensitivity and high selectivity.

An aptamer based resonance light scattering assay of prostate specific antigen.

Prostate specific antigen (PSA) is a valuable tumor marker for prostate cancer screening. In this work, a novel and sensitive resonance light scattering (RLS) spectral assay of PSA was proposed based on PSA aptamer modified gold nanoparticles (AuNPs). The sulfhydryl modified single-strand aptamer could interact with AuNPs, which made the AuNPs stable in high concentration of salt. In pH 7.0 BR buffer solution, the highly selective combination of PSA and AuNPs-labeling aptamer resulted in the aggregation of AuNPs which showed high RLS intensity. Under the optimal conditions, the magnitude of enhanced RLS intensity (ΔI(RLS)) was proportional to the concentration of PSA in the range from 0.13 to 110 ng/mL, with a detection limit (LOD, 3σ) of 0.032 ng/mL. This developed RLS assay as well as a commercially available enzyme-linked immunosorbent assay (ELISA) kit was successfully applied to the detection of PSA in 15 serum samples, and an excellent correlation of the levels of PSA measured was obtained. This is the first report of the aptamer based RLS assay for PSA and it is also a significant application of instrumental analysis technique.