The origins of age-related proinflammatory state

Abstract

We hypothesized that the rising levels of inflammatory markers with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. Information on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the "proinflammatory state" in older persons is related to the high prevalence of cardiovascular risk factor and morbidity.

Figure 1.. Mean values of inflammatory markers according to sex and age group expressed as number of standard deviations from the population mean to make them independent of different units of measure.

(Top row) ♦ indicates IL-6; □, IL-6r; ▲, IL-1ra; and ○, IL-18. (Bottom row) ♦ indicates CRP; □, fibrinogen.

Figure 2.. Age regression coefficients and their 95% CIs estimated from linear models predicting level of inflammatory markers.

Model “a” estimates the crude affect of age; model “b” is adjusted for cardiovascular risk factors; model “c” is also adjusted for subclinical cardiovascular diseases; and model “d” is adjusted for CHD, CHF, stroke, PAD, COPD, diabetes, hypertension, osteoporosis, CFR, cancer, dementia, and depression. R values reported below the confidence interval are for the model used to estimate the age regression coefficients.

Figure 3.. Mean values (dashed lines) and 95% CIs (gray shaded areas) of inflammatory markers estimated for men and women of different age groups, under the assumption of low risk profile and no major morbidity.

The continuous lines are crude mean values calculated in 51 healthy men and 45 healthy women with low risk profile and no morbidity. None of these healthy participants was older than 85 years.