Interleukin-1 Receptor Antagonist, Interleukin-6, and C-Reactive Protein as Predictors of Mortality in Nonagenarians: The Vitality 90+ Study

Jylhä, Marja; Paavilainen, Paula; Lehtimäki, Terho; Goebeler, Sirkka; Karhunen, Pekka J.; Hervonen, Antti; Hurme, Mikko

doi:10.1093/gerona/62.9.1016

Cited by 93 publications

(70 citation statements)

References 28 publications

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“…Composite indicators of inflammation were adopted to increase specificity for ongoing inflammation, because of the influential role of IL-6 in CRP regulation and the generally low levels of circulating cytokines, in previous population studies investigating the association between inflammation and mobility limitation Reuben et al 2002) or mortality (Reuben et al 2002;Harris et al 1999;Giovannini et al 2011;Jylhä et al 2007). In contrast, our results do not support this theory regarding the association with global functioning in a representative sample of community-dwelling elderly persons.…”

Section: Clinical Marker For Identifying Functional Impairmentmentioning

confidence: 99%

“…In contrast, our results do not support this theory regarding the association with global functioning in a representative sample of community-dwelling elderly persons. A combination of sample size, wide age range, poorly selected donors, and variability in assays has continued to fuel the argument of composite indicators Giovannini et al 2011;Jylhä et al 2007;Reuben et al 2002).…”

Section: Clinical Marker For Identifying Functional Impairmentmentioning

confidence: 99%

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Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Adriaensen

Matheï

Pottelbergh

et al. 2013

AGE

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The large burden and coexistence of physical disability, cognitive impairment, and depression in the oldest old makes summary markers of global functioning of great value, allowing for risk stratification. Inflammation may be a common underlying cause or represents a final common pathway. The present study investigated the association between elevated serum inflammatory markers and global functioning and its underlying aspects. A representative sample of 415 communitydwelling elderly subjects participating in the BELFRAIL study, with a mean age of 85 years, was included in the present analysis. Data on physical performance, dependence, and mental aspects of functioning and serum levels of 15 inflammatory proteins, including cytokines, chemokines, and acute-phase proteins, were assessed. Interleukin (IL)-6 was negatively associated with global functioning (odds ratio (OR) 4.35). The odds ratios for C-reactive protein (CRP) (OR 2.37) and the combined score of IL-6 and CRP (OR 2.59) were lower or not significant. IL-6 was significantly associated with physical dependence and cognitive function, and only a highly elevated serum level was associated with physical performance. Physical dependence was associated with a highly elevated CRP serum level. The proportion of functionally impaired older persons with elevated IL-6 was 81.93 %, giving a low positive predictive value (0.38), but a high negative predictive value (0.87). So, IL-6 is strongly associated with global functioning and all of the individual aspects of functioning, except suspected depression, in communitydwelling persons 80 years and older.

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Section: Clinical Marker For Identifying Functional Impairmentmentioning

confidence: 99%

Section: Clinical Marker For Identifying Functional Impairmentmentioning

confidence: 99%

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Adriaensen

Matheï

Pottelbergh

et al. 2013

AGE

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“…Increased levels of the acute phase protein C-reactive protein (CRP), and the proinflammatory cytokines interleukin (IL)-6 and IL-18 were found to be associated with the risk of coronary heart disease (CHD; Blankenberg et al, 2003;Koenig et al, 2006;Kaptoge et al, 2010;Rodondi et al, 2010), death from CHD (Heidema et al, 2009) and all-cause mortality (Stork et al, 2006;Tuomisto et al, 2006;Jylha et al, 2007). In addition, single food components have been found to be related to inflammatory markers; higher intakes of dietary fibre (Ma et al, 2008;Herder et al, 2009;Wannamethee et al, 2009), whole-grain products (Qi et al, 2006;Lutsey et al, 2007), fruit and vegetables (Wannamethee et al, 2006;Holt et al, 2009), nuts (Salas-Salvado et al, 2008;Casas-Agustench et al, 2010), and a moderate alcohol intake (Wang et al, 2008;Oliveira et al, 2010) were associated with lower concentrations of several immune mediators in the circulation.…”

Section: Introductionmentioning

confidence: 99%

Dietary patterns, subclinical inflammation, incident coronary heart disease and mortality in middle-aged men from the MONICA/KORA Augsburg cohort study

et al. 2011

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Background/Objectives: We aimed to identify dietary patterns associated with inflammatory markers and to examine their impact on the incidence of coronary heart disease (CHD) and all-cause mortality, as subclinical inflammation is a risk factor for these outcomes. Subjects/Methods: The study population comprised 981 middle-aged men participating in the first or third 'MONItoring of Trends and Determinants in CArdiovascular Diseases' (MONICA) Augsburg surveys who completed 7-day dietary records. Subjects were followed up until 2002 for CHD and until 2007 for mortality. Dietary patterns were derived using reduced rank regression (RRR) with C-reactive protein, interleukin (IL)-6 and IL-18 as responses. Alternatively, partial least squares and principal components regression were used. Results: A high score of the RRR-derived pattern was characterised by high intakes of meat, soft drinks and beer and low intakes of vegetables, fresh fruit, chocolates, cake, pastries, wholemeal bread, cereals, muesli, curd, condensed milk, cream, butter, nuts, sweet bread spread and tea. This score was associated with a higher risk for CHD (hazard ratio ¼ 1.33, 95% confidence interval: 1.06-1.67, P ¼ 0.013) and mortality (hazard ratio ¼ 1.34, 1.17-1.53, Po0.001) after multivariable adjustment. However, for CHD and CHD mortality the significant association disappeared after further adjustment for smoking status; for all-cause mortality it was attenuated but remained significant (hazard ratio ¼ 1.16, 1.00-1.33, P ¼ 0.046). Patterns derived from the other methods resembled the RRR pattern showing similar results regarding disease outcomes. Conclusions: Participants exhibiting higher dietary pattern scores had higher levels of inflammatory markers and higher risk for CHD and all-cause mortality, however, smoking was an important confounder, especially for CHD outcomes.

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“…An acute inflammatory response is beneficial for survival, but a chronic inflammatory state accompanies (and contributes to) age-associated diseases such as neurodegenerative disorders, autoimmunity and cancer Van Bodegom et al 2007). A reliable marker of inflammation is interleukin-6 (IL-6), the circulating level of which is increased in chronic diseases and aging (Mastorakos and Ilias 2006;Jylhä et al 2007). A single nucleotide polymorphism (SNP), named rs1800795 (consisting of a G → C transversion in position −174 from the transcription start site) located in the promoter region of the IL-6 gene (NM_000600) reduces IL-6 production at the transcriptional level (Fishman et al 1998).…”

Section: Introductionmentioning

confidence: 99%

“…The role of rs1800795 in longevity has been explored in the Italian population with conflicting results (Bonafè et al 2001;Capurso et al 2004;Christiansen et al 2004;Hurme et al 2005). Increased IL-6 is generally considered a negative modulator of longevity, as it correlates with disability and mortality (Gruenewald et al 2006;Jylhä et al 2007). …”

Section: Introductionmentioning

confidence: 99%

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

Albani

Batelli

Polito

et al. 2009

AGE

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The transcription rate of interleukin-6 (IL-6) can be reduced by the C-allele of a polymorphism (rs1800795) located in the 5′-flanking region of the IL-6 gene (NM_000600), and IL-6 plasma levels increase with age. We assembled an elderly Italian population ["The Treviso Longeva (Trelong) study", age range 70-106 years, n = 668 subjects] and assessed rs1800795 genotype and plasma IL-6 concentrations. The rs1800795 genotype was also assessed in an independent Italian study ("Milan" study, age range 70-96, n= 245 subjects). To verify an age-or sex-specific effect of rs1800795 genotype we compared people younger (70-85) and older (85+) than 85 years of age. We found a significant reduction in the frequency of rs1800795 C/C genotype in 85+ men from the Trelong study, while in the Milan study this data did not reach significance. However, considering the two studies together, the frequency of the rs1800795 C/C genotype was significantly lower in 85+ than in 70-85 males (4.0% and 10.7%, respectively), while it remained unchanged in females. As for IL-6 plasma levels, after a multivariate analysis to control for confounders, a correlation between age and plasma IL-6 concentrations was revealed (P <0.0001). An increase in circulating IL-6 levels in the entire 85+ group compared to the 70-85 group (P<0.05, Tukey′s test) was also noticed. We suggest a sex-specific pattern for genetic variability linked to inflammatory response and longevity, consistent with the age-related increase in IL-6.

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Interleukin-1 Receptor Antagonist, Interleukin-6, and C-Reactive Protein as Predictors of Mortality in Nonagenarians: The Vitality 90+ Study

Abstract: IL-1ra is a powerful prognostic marker in very old people. Our results implicate its role in the complex interaction between inflammatory markers in aging and disease.

Cited by 93 publications

References 28 publications

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Significance of serum immune markers in identification of global functional impairment in the oldest old: cross-sectional results from the BELFRAIL study

Dietary patterns, subclinical inflammation, incident coronary heart disease and mortality in middle-aged men from the MONICA/KORA Augsburg cohort study

Interleukin-6 plasma level increases with age in an Italian elderly population (“The Treviso Longeva”–Trelong–study) with a sex-specific contribution of rs1800795 polymorphism

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