14th July 2025, A/Prof Chee L Khoo
It’s amazing how we have learnt to accept declining muscle function and increasing frailty as part of our patients getting older. At GPVoice, we have explored muscle health and sarcopenia many times over the couple of years. We know that declining muscle health is associated not only with falls risk but also with increase mortality rates in COPD, heart disease, osteoporosis and post surgical outcomes. These are patients who are already frail. The data comes from clinical and observational trials and meta-analysis but what about people who were fit and robust and now not. Are they worse off?
A recent trial explored patients who were robust and now become pre-frail or frail and looked at its association with cardiometabolic morbidity and mortality. Wenjie Wang et al. focused on the association between changes in frailty status and risks of cardiometabolic diseases (CMD) and cardiometabolic multiple morbidity (CMM) (1). They obtained data from the China Health and Retirement Longitudinal Study. Through multiple rounds of random sampling, eligible people were selected from 150 counties in 28 provinces. 5 waves of surveys were conducted – 2011, 2013, 2015, 2018, and 2020.
Frailty index (FI) is one of the widely used measures of frailty and biological age, which is calculated by multiple age-related health deficits (2). Multiple age-related health deficits were accumulated to calculate the FI. Twenty-seven items were selected including disease (except for heart disease, stroke, and diabetes), symptoms, disability, physical function, depression, and cognition. Based on the present health deficits of participants, FI was calculated as the sum of the deficits present divided by 27 total deficits assessed.
Frailty status was classified into 3 categories: robust (FI ≤0.1), pre-frail (FI 0.1-0.25), and frail (FI ≥0.25). Total FI and change in FI (ΔFI) were divided into 3 tertiles. An evaluation of changes in frailty status was conducted by comparing the frailty status at baseline (in 2011) to the frailty status 2 years after the baseline (in 2013). The total FI was defined by adding the FI at baseline to the FI at the second stage, whereas the change in FI (ΔFI) was assessed by subtracting the FI at the second stage from the FI at the baseline. Mendelian randomization was used to clarify the relationship between FI and CMD from a genetic perspective.
Results
Compared with the robust and pre-frail patients, frail participants had the highest risks of incident CMD (HR 1.78, 95% CI: 1.59-1.99) and CMM (HR: 2.48, 95% CI: 1.98-3.10) in both unadjusted and adjusted models (all P < 0.001). Frail participants also had elevated risks of cardiovascular disease (CVD) (HR: 1.82, 95% CI: 1.58-2.10), stroke (HR: 2.28, 95% CI: 1.85-2.81), and diabetes (HR: 1.58, 95% CI: 1.32-1.88), respectively. Moreover, results were similar to those of the pre-frail group compared to the robust group.
Changes in frailty and CMD and CMM
In the baseline robust group, 1,056 (26.9%) participants progressed to pre-frail or frail status, and 456 (16.5%) pre-frail participants became frail status. Compared with the stable robust population, robust participants who progressed to pre-frail/frail status had significantly elevated risks of CMD (HR: 1.67, 95% CI: 1.45-1.92) and CMM (HR: 1.80, 95% CI: 1.30-2.50), respectively. In contrast, according to the stable frail group, frail participants who recovered well and were assessed as robust/pre-frail status had decreased risks of CMD (HR: 0.64, 95% CI: 0.52-0.79) and CMM (HR: 0.45, 95% CI: 0.28-0.67). Even within the robust group (F1), the lower tertile had increased CMD compared with the upper tertile.
Over the 2-year follow up period, using the robust group as a reference group, participants who were robust but deteriorated and participants who were pre-frail but became frail all had higher CMD and CMM risks. The prefrail participants who became robust had the lowest elevated risks (when compared with the robust) of CMD and CMM.
Conclusion
We already know that frailty is associated with increased CMD and CMM. This study shows that changes in frailty is also associated with increased in CMD and CMM. It also shows that prevention deterioration of frailty may mitigate against this increase in CMD and CMM. We are seeing increasingly more patients who are living longer with diseases which may increase their risks of frailty. We also have many medications that can contribute to this frailty. In primary care, we are in a position to recognise many of these patients and put in place strategies which can prevent decline in physical and muscle function.
References:
- Wang W, Wang K, Chen G, Niu J, Liu Y, Wang Z, Ge H. Changes in Frailty and Cardiometabolic Disease: Evidence From a Longitudinal Cohort Study and Genetic Analysis. JACC Adv. 2025 Jun;4(6 Pt 2):101782.
- Kojima G., Iliffe S., Walters K. “Frailty index as a predictor of mortality: a systematic review and meta-analysis”. Age Ageing . 2018;47:2: 193-200.