Frailty and risk of cardiovascular disease and mortality.

Prospective cohort studies suggest that frailty is associated with an increased risk of incident

cardiovascular disease (CVD) morbidity and mortality, but their mechanistic and developmental

relations are not fully understood. We investigated whether frailty predicted an

increased risk of incident nonfatal and fatal CVD among community-dwelling older adults.

Methods

A population cohort of 5015 participants aged 55 years and above free of CVD at baseline

was followed for up to 10 years. Pre-frailty and frailty were defined as the presence of 1–2

and 3–5 modified Fried criteria (unintentional weight loss, weakness, slow gait speed,

exhaustion, and low physical activity), incident CVD events as newly diagnosed registered

cases of myocardial infarction (MI), stroke, and CVD-related mortality (ICD 9: 390 to 459 or

ICD-10: I00 to I99). Covariate measures included traditional cardio-metabolic and vascular

risk factors, medication therapies, Geriatric Depression Scale (GDS), Mini-Mental State

Exam (MMSE), and blood biomarkers (haemoglobin, albumin, white blood cell counts and

creatinine).

Results

Pre-frailty and frailty were significantly associated with elevated HR = 1.26 (95%CI: 1.02–

1.56) and HR = 1.54 (95%CI:1.00–2.35) of overall CVD, adjusted for cardio-metabolic and

vascular risk factors and medication therapies, but not after adjustment for GDS depression

and MMSE cognitive impairment. The HR of association between frailty status and both

CVD mortality and overall mortality, however, remained significantly elevated after full

adjustment for depression, cognitive and blood biomarkers.

Conclusion

Frailty was associated with increased risk of CVD morbidity and especially mortality, mediated in parts by traditional cardio-metabolic and vascular risk factors, and co-morbid depression and associated cognitive impairment and chronic inflammation. Given that prefrailty and frailty are reversible by multi-domain lifestyle and health interventions, there is potential benefits in reducing cardiovascular diseases burden and mortality from interventions targeting pre-frailty and early frailty population.