Aisling O’Halloran1, Eamon Laird1, Martin Healy2, Rachel Moran3, John Nolan3,
Stephen Beatty3, Anne Molloy1, Rose Anne Kenny1
1Trinity College, Dublin, Ireland
2St. James’s Hospital, Dublin, Ireland
3Waterford Institute of Technology, Waterford, Ireland
Background: Several circulating blood biomarkers have been linked to phenotype frailty
in cross-sectional studies and in longitudinal studies in women or the oldest old. In this
study we examined the relationships between three frailty instruments and plasma biomarkers
in older adults in Ireland.
Methods: Cross-sectional analyses were performed using data from community-living
adults aged ≥50 years (n = 4548) from Wave 1 of Irish Longitudinal Study on Ageing
(TILDA). Circulating blood biomarkers of micronutrient status (vitamin B12, vitamin D,
lutein and zeaxanthin), inflammatory stress (CRP), metabolic function (HbA1c, total,
HDL and LDL cholesterol) and renal function (creatinine and cystatin c) were transformed
and standardized. For each biomarker, one unit increase represented an increase
of 1 SD from the mean, this allowed comparability of associations across biomarkers.
Frailty was assessed using Phenotype Frailty (PF), Frailty Index (FI) and FRAIL Scale
(FS) instruments. Multinomial logistic regression determined associations between frailty
and each biomarker adjusted for age, sex, education, smoking status, BMI, and the number
of medications and supplements taken regularly.
Results: Adjusting for covariates, a unit increase in lutein was negatively associated with all
three frailty measures: PF (RR = 0.59), FI (RR = 0.86) and FS (RR = 0.53). Higher levels of
zeaxanthin were negatively associated with two of the frailty measures: PF (RR = 0.62) and
FS (RR = 0.65). A unit increase in cystatin c was positively associated with frailty: PF (RR =
1.52), FI (RR = 1.16) and FS (RR = 1.34). Finally higher vitamin D was negatively associated
with one frailty measure: PF (RR = 0.83), as was HDL cholesterol: FI (RR = 0.87).
Conclusions: Considerable variability exists in relation to associations between blood
biomarkers and frailty, depending on the frailty instrument used. The identification of
consistent cross-sectional associations with more than one frailty instrument strengthens
the evidence that a biomarker may be correlated with frailty over time. However, causation
cannot be inferred using cross-sectional data.