Abstract
AimsSingle measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers.MethodsWe used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002–2006) and first follow-up (2007–2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders.ResultsBased on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6–2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5–6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1–16.8 per each doubling of follow up sTNF-R1 value).ConclusionSolely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.
Highlights
Human ageing is characterized by a chronic, sterile, low-grade inflammation, and this phenomenon has been termed "inflammaging" [1]
We used data of the population based cohort study CARLA and included 1408 subjects with Soluble tumor necrosis factor receptor 1 (sTNF-R1) measured at baseline (2002–2006) and first follow-up (2007–2010)
While sTNF-R1 levels are associated with mortality, cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role
Summary
Human ageing is characterized by a chronic, sterile (in the absence of an infection), low-grade inflammation, and this phenomenon has been termed "inflammaging" [1]. Soluble tumor necrosis factor receptor 1 (sTNF-R1) is the circulating form of their membrane bound counterparts [6]. Several studies demonstrated increased all-cause and cardiovascular mortality in patients with various diseases and higher levels of sTNF-R1 [7,8,9,10,11,12]. In the general population, elevated levels of sTNF-R1 were associated with all-cause and cardiovascular mortality after adjustment for lifestyle factors, inflammation due to chronic diseases, and established cardiovascular risk factors [13,14,15]
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