Aging and the burden of multimorbidity: associations with inflammatory and anabolic hormonal biomarkers

Abstract

Background: Multimorbidity increases with aging, but risk factors beyond age are unknown.

Objective: To investigate the association of inflammatory and anabolic hormonal biomarkers with presence and prospective development of multimorbidity.

Methods: Nine-year longitudinal study of 1018 participants aged 60 years or older (InCHIANTI Study). Multimorbidity was evaluated at baseline and follow-up visits as number of diagnosed diseases from a predefined list of 15 candidate chronic conditions, defined according to standard clinical criteria. Linear mixed models were used to test cross-sectional and longitudinal associations between candidate biomarkers and multimorbidity.

Results: At baseline, multimorbidity was significantly higher in older participants (p < .001) and higher IL-6, IL-1ra, TNF-α receptor II (TNFAR2), and lower dehydroepiandrosterone sulfate were associated with higher number of diseases, independent of age, sex, body mass index, and education. The rate of longitudinal increase in number of chronic diseases was significantly steeper in participants who were older at baseline (p < .001). In addition, higher baseline IL-6 and steeper increase of IL-6 levels were significantly and independently associated with a steeper increase in multimorbidity over time (p < .001 and p = .003, respectively). Sensitivity analyses, performed using 15 different models obtained by removing each of 15 conditions included in the original list of candidate diseases, confirmed that results were not driven by any specific condition.

Conclusions: Accumulation of chronic diseases accelerates at older ages and in persons with higher baseline levels and steeper increase over time of IL-6. High IL-6 and increase in IL-6 may serve as early warning sign to better target interventions aimed at reducing the burden of multimorbidity.

Keywords: Aging; Chronic diseases.; Inflammation; Interleukin-6; Multimorbidity.

Figure 1.

Crude mean number of chronic diseases according to different age groups in the baseline population (InCHIANTI Study, 1998–2000).

Figure 2.

Crude mean number of chronic diseases at baseline and at 9-year follow-up visit for participants with available data at 9-years follow-up (n = 683) and derived average trajectories of multimorbidity in different baseline age groups (InCHIANTI Study, 1998–2000, 2007–2009). The rough impression given by crude data that the increase in multimorbidity was steeper at older baseline ages was confirmed by liner mixed models (Model I, Table 2 and Supplementary Figure).

Figure 3.

Linear mixed model estimated trajectories of longitudinal increase in number of chronic diseases over the follow-up in different baseline age groups, according to baseline values of IL-6 (high vs low) and rate of increase in IL-6 levels (upper tertile vs medium-lower). Participants with high baseline levels and faster increase overtime in IL-6 (dashed red line) presented a significant steeper increase in number of chronic diseases over the follow-up compared with those with high baseline levels but slower increase in IL-6 overtime (solid red line, p = .019) and those with low baseline levels of IL-6 (reference group (REF), dark line, p < .001) (InCHIANTI Study: 1998–2000; 2001–2003; 2004–2006; 2007–2009).