Our estimated prevalence of frailty was 3.1% among the Chinese population aged 40 years or older, which is very similar to the reported by Hanlon and colleagues that around 3% of people aged 37 to 73 were considered frail in the United Kingdom[25]. To our knowledge, our research is the first survey reporting the middle-aged of frailty in China, showing prevalence of 2.4% aged 40-49 and 3.6% aged 50-59, which was lower than the middle-age of frailty in community-dwelling Europeans was 4.1% and was much lower than reported the prevalence of frailty was 7.6% and 13.4% among adult white Americans aged 35-44 and 45-54, respectively[27,28]. It can be seen that frailty not only has a higher incidence in the elderly, but also occurs in the middle-aged population. Research has shown that the frailty of the body may lead to disability in the future, but in the early stages of intervention, this outcome can be changed [29]. So many studies published about the prevalence of pre-frailty, such as United States (45.0%), UK(38.0%), Japan (48.1%), Israel (57.4%), similarly, the proportion of pre-frail Chinese in our research was also very high (53.7%) [3,25,30,31].
These distinctions might be mainly due to differences in socioeconomic background, ethnicity, and lifestyle of people living in different countries and regions [31]. In addition, using different frailty measurement tools for the same population, such as Fried frailty phenotype, Frail index, and FRAIL scales, would have an impact on the outcome of the prevalence of pre-frailty and frailty [32].
We found in the multivariate analysis, people who reported hypertension had 1.8 times the risk of developing frailty compared to those who did not, and the risk of pre-frailty is 1.1 times. Even after adjusting for potential confounding factors, the higher the blood pressure level, the greater the chance of suffering from frailty. Also in previous studies, there was a strong association between hypertension and frailty, and it was confirmed that patients with frailty and pre-frailty had significant subclinical vascular and cardiac changes [33,34]. However, the conclusions of blood pressure and frailty research are divergent, and some authors have shown that measured mean blood pressure was lower in frail compared to non-frail individuals [35]. They thought low blood pressure may reduce blood perfusion and oxygenation of vital organs, resulting in damage, loss of function, and a frail state [36]. This difference in blood pressure was explained that high blood pressure is harmful to people's health, whether the population was frail or not, it was possible to use antihypertensive treatment. Studies have shown that hypertension can cause frailty, and as a variable, frailty may affect changes in blood pressure. These findings raise questions about statistical differences regarding the blood pressure values in different frail states of the population require additional evidence.
We observed there was a strong association between frail status and elevated serum cystatin C. Multivariate analysis showed that participants with higher cystatin C had 4.5-fold increased risk of frailty and 2.4-fold increased risk of pre-frailty. Hart et al found that higher serum cystatin C was associated with increased risks of progression of frailty status and death [37]. Cystatin C is a low molecular weight protein with a stable productivity and can be freely filtered by the glomeruli [38], which is more appropriate for the group who are susceptible to be frail because it seems to be less affected by muscle mass or dietary protein intake[39]. Our findings, like those of other studies, suggest that cystatin C is more sensitive to the detection of frailty than other blood biomarkers such as creatinine [40]. These results may partially explain the increased sensitivity of cystatin C in identifying older people with less muscle. Because cystatin C was not affected by muscle mass or dietary protein intake, it was more reflective of changes in physical performance than other kidney function markers such as creatinine [39]. Inflammation may play a role as a potential mechanism linking cystatin C to frailty [41]. Due to the limitations of current frailty knowledge, the mechanism linking higher cystatin C to frailty was unclear and future research is needed to further explore this phenomenon [37].
In this study, we also identified other relative factors associated with frailty and pre-frailty in the Chinese community population. Gender, education level, BMI, glycated hemoglobin (HbA1C), PEF and pain are major relative factors for frailty. The prevalence of frailty and pre-frailty in women was higher than in men, which is consistent with previously published studies [5,42].We also found that higher education has a strong protective effect on the prevalence of frailty. The education level of individuals is one of the important indicators to measure their socioeconomic status [43]. Lower economic income is associated with an increased risk of frailty [5,28]. The prevalence of frailty increased with low BMI. Our findings corroborate the views that a lower BMI may indicate insufficient reserve capacity and weight loss, which was a key factor in the formation of frailty [44]. Underweight may be due to chronic illness or malnutrition and sarcopenia, which were also associated with increased risk of frailty [45].
Our study indicated that the decrease in PEF and the increase in HbA1C may be good indicators for detecting frailty. The result is similar to previous studies on respiratory function and frailty, in which PEF values were lower in frail elderly people than in non-frail people [46]. This mechanism may be related to decreased function of the respiratory muscles or chronic inflammation of the lungs that led to a decline in the body's energy reserves and physical strength [47]. Similarly, our results showed that for every 1 percent increased in serum HbA1C, the risk of frailty had higher odds. Several studies had shown that diabetes and HbA1C were risk factors for frailty and patients with poor blood sugar control had a higher risk of developing frailty [17,48]. Thus, frailty is an increasingly common condition and will become an increasingly important health issue for people over middle age. Next, how to prevent the frailty of the population should become one of the major medical concerns.
Our study has several limitations. First, the chronic diseases and symptoms were self-reported, therefore, it would cause reporting bias and recall bias. Second, because the biological and clinical characteristics of middle-aged people were different from those of the elderly, the concept of frailty, especially the definition of Fried frailty phenotype, when applied to non-elderly, the applicable conditions and principles of definition here need to be further studied in the future. Third, due to the survey of CHARLS was only included community-dwellers, not including those in hospitals and nursing homes, and some people who may have serious illnesses that cannot be interviewed and measured were excluded. In addition, the proportion of the elderly population in the surveyed population was low (age ≥ 60 years had 48.1% and age ≥ 80 years had 4.1%), while the elderly population was a high-risk group with frailty. Therefore, the actual incidence of frailty may be underestimated. Fourth, We found that in the above studies on the frailty and pre-frailty, due to the large or minor modifications to the Fried frailty phenotype or other frailty assessment instruments in order to accommodate the data, would have a significant impact on the estimation of frailty and pre-frailty population, and we should be cautious about the publication of this conclusion. The last, since this research was a retrospective cross-sectional study, there was insufficient clinical evidence to assess the role of chronic diseases in different stages of the frailty process, and we could not understand the causal and temporal relationship between frailty and chronic diseases. The next step is to conduct prospective cohort studies and randomized controlled trials to serve clinical guidelines.