Frailty, sarcopenia, cachexia and malnutrition as comorbid conditions and their associations with mortality: a prospective study from UK Biobank

Abstract

Background: Frailty, sarcopenia, cachexia and malnutrition are clinical conditions that share similar diagnostic criteria. This study aimed to investigate the clustering and mortality risk among these clinical conditions in middle- and older-aged adults.

Methods: 111 983 participants from UK Biobank were included. Sarcopenia was defined according to the EWGSOP 2019 while frailty using a modified version of the Fried criteria. Cachexia was defined using the Evans et al. classification and malnutrition using the Global Leadership Initiative on Malnutrition. The exposure variable was categorized as: no conditions; frailty only (one condition); frailty with sarcopenia (two conditions); frailty with ≥2 other conditions (three or four conditions). Its association with all-cause mortality was investigated using Cox-proportional hazard analysis.

Results: Frailty had the highest prevalence (45%) and was present in 92.1% of people with malnutrition and everyone with sarcopenia or cachexia. Compared with people with no conditions, those with frailty only and frailty with sarcopenia had higher risk of all-cause mortality. Individuals with frailty plus ≥2 other conditions had even higher risk (HR: 4.96 [95% CI: 2.73 to 9.01]).

Conclusions: The four clinical conditions investigated overlapped considerably, being frailty the most common. The risk of all-cause mortality increased with the increasing number of conditions in addition to frailty.

Keywords: cachexia; frailty; malnutrition; mortality; sarcopenia.

Fig. 1

Association between numbers of clinical conditions and all-cause mortality. Data presented as adjusted HR and its 95% CI by cumulative clinical conditions. People with no conditions were used as the reference group (normal). Frailty only represents 43 991 people with frailty (pre-frail or frail) and five people with only malnutrition. Frailty with sarcopenia represents 6390 people with frailty (pre-frail or frail) and sarcopenia (pre-sarcopenia, sarcopenia or severe sarcopenia). Frailty with ≥2 conditions represents the combination of frailty, sarcopenia and cachexia or malnutrition. All analyses were conducted using a 2-years landmark analysis and adjusted for age, sex, deprivation, smoking status, ethnicity, discretionary sedentary time, WC, dietary intake (alcohol, red meat and processed meat intake) and multimorbidity at baseline.

Fig. 2

Crude cumulative hazard plot of All-cause mortality by numbers of clinical conditions by follow-up. Frailty only represents 43 991 people with frailty (pre-frail or frail) and five people with only malnutrition. Frailty with sarcopenia represents 6390 people with frailty (pre-frail or frail) and sarcopenia (pre-sarcopenia, sarcopenia or severe sarcopenia). Frailty with ≥2 conditions represents the combination of frailty, sarcopenia and cachexia or malnutrition.