What is the prevalence of frailty in middle aged and older adults, and what is its association with multimorbidity and mortality in different age groups?

Problem

Frailty describes increased susceptibility to decompensation in response to physiological stress. Frailty is associated with older age and multimorbidity (≥2 long-term conditions (LTCs)). Most research on frailty focuses on people aged over 65 years. However the majority of people with multimorbidity are aged less than 65 years. Little is known about the prevalence or effects of frailty on mortality in younger populations. This paper examines the relationship between frailty, multimorbidity, specific LTCs, and mortality in a middle-older aged population.

Approach

Data source: UK Biobank community cohort; 493,737 participants aged 37-73 years (81% aged less than 65 years). Frailty was based on 5 criteria adapted from Fried et al’s frailty phenotype model (weight loss, exhaustion, grip strength, low physical activity, slow walking pace). Participants were deemed frail (n=16,538, 3.3%) if met ≥3 criteria, pre-frail (n=185,360, 37.5%) if fulfilled 1-2 criteria, and not frail (n=291,839) if no criteria met. Sociodemographic characteristics and LTCs (n=43) defined by self-report. Outcome: all-cause mortality median 7 years follow-up. Multinomial logistic regression compared sociodemographic characteristics and LTCs of frail/pre-frail participants to non-frail (odds ratios (OR) with 95% confidence intervals (CI)). Cox Proportional hazards models examined associations between frailty/pre-frailty and mortality (hazard ratios (HR) and CI). Results stratified by age (37-45, 45-55, 55-65, 65-73 years) and sex; adjusted for multimorbidity count, socioeconomic status, body mass index, smoking, and alcohol.

Findings

Frailty was significantly associated with multimorbidity (prevalence 17·5% (4435/25,338) in those with ≥4 LTCs) as well as socioeconomic deprivation (42% of frail participants in most deprived quintile, OR 3.71, CI 3·49-3·94), smoking (20·2% current smokers versus 8·9% of non-frail participants, OR 2·47, CI 2·36-2·60) and obesity (52% had a BMI >30 vs. 18% in the non-frail group, OR 4·10, CI 3·90-4·31). Top 5 LTCs associated with frailty: multiple sclerosis (OR 9.05; CI 7.50-10.90); chronic fatigue syndrome (OR 5.2; CI 4.4-6.08); connective tissue disease (OR 2.34; OR 2.17 – 2.54); chronic obstructive pulmonary disease (OR 1.96; 1.79-2.14); diabetes (OR 1.95; CI 1.85-2.07). Both pre-frailty and frailty were significantly associated with mortality for all age strata in males/females except females aged 37-45 (e.g. males 37-45 HR 2.7 CI 1.58-4.64) after adjustment for number of LTCs,, socioeconomic status, smoking, BMI, alcohol intake.

Consequences

Identification, management and prevention of frailty needs to consider middle-aged people (particularly with multimorbidity or associated LTCs) in whom frailty is significantly associated with mortality, after adjustment for multimorbidity, sociodemographics, and lifestyle. Clinical guidelines, medical education and research need greater focus on this issue.