Major population studies assessing association between inflammatory markers, aging, disability, chronic diseases, mortality and interventions
| Study, author and year of publication | Measured inflammatory markers | Measures of association | Conclusions |
|---|---|---|---|
|
Health, Aging and Body Composition (HABC) Study cohort study of 3,075 well-functioning, 70–79 years old black and white men and women | |||
| Beasley (Beasley, Koster et al. 2009) | IL-6, TNF-alpha, CRP | β ≈ 0.1/cm2 of visceral fat area in men and black women; β ≈ 0.2/cm2 in white women | Visceral fat significantly and positively associated with IL-6 and CRP. |
| Yaffe (Yaffe, Lindquist et al. 2003) | IL-6, TNF-alpha, CRP | Adjusted OR for cognitive decline for highest vs. lowest tertiles of: IL-6 = 1.23, CRP = 1.24, TNF-alpha = 1.23 | High levels of IL-6, CRP associated with cognitive decline in the elderly. |
| Kalogeropoulos (Kalogeropoulos, Georgiopoulou et al. 2010) | IL-6, TNF-alpha, CRP | Adjusted HR of HF per doubling of: IL- 6=1.24; TNF-alpha= 1.41; CRP=1.01 | IL-6, TNF-alpha, CRP associated with HF risk among older adults and may improve HF risk stratification. |
| Cesari (Cesari, Penninx et al. 2003) | IL-6, TNF-alpha, CRP | RR for IL-6 (per SD increase) with CHD=1.27, stroke=1.45, CHF=1.72; RR for TNF-alpha (per SD increase) with CHD=1.22, CHF=1.59; RR for CRP (per SD increase) with CHF=1.48, | IL-6, TNF-alpha, CRP are independent predictors of cardiovascular events in older adults. |
| Cesari (Cesari, Penninx et al. 2003) | IL-6, TNF-alpha, CRP, sIL-6r, sIL-2r, sTNFR1, sTNFR2 | OR for highest vs. lowest tertile of IL-6 for subclinical CVD=1.58, clinical CVD=2.35; TNF-alpha for subclinical CVD=1.48, clinical CVD=2.05 | IL-6, TNF-alpha significantly associated with clinical and subclinical CVD. CRP had weaker association. |
| Rodondi (Rodondi, Marques-Vidal et al. 2010) | IL-6, TNF-alpha, CRP | HR CHD for highest vs. lowest quartile of IL-6=1.82 | IL-6 associated with future CHD events and improves risk prediction in older adults. |
| Il'yasova (Il'yasova, Colbert et al. 2005) | IL-6, TNF-alpha, CRP | HR for cancer death for: IL-6=1.63, TNF-alpha= 1.82, CRP=1.64 | Elevated levels of inflammatory markers more strongly associated with risk of cancer death than cancer incidence. |
| Hsu (Hsu, Kritchevsky et al. 2009) | IL-6, TNF-alpha, CRP, sIL-6r, sIL-2r, sTNFR1, sTNFR2 | Regression coefficient for knee strength and: TNF-alpha=−2.71, CRP=−0.88; physical performance battery score and: TNF-alpha=−0.05, CRP=−0.02 | TNF-alpha and CRP positively associated with walk time and inversely associated with grip strength. |
| Schaap (Schaap, Pluijm et al. 2009) | IL-6, TNF-alpha, CRP, sIL-6r, sIL-2r, sTNFR1, sTNFR2 | Regression coefficient (per SD change in marker) for 5 –year change in grip strength and TNF-alpha=−0.62; and 5 –year change in knee extensor strength and TNF-alpha=−1.02 | TNF-alpha had strongest and most consistent association with decline in muscle mass and strength. |
| Cauley (Cauley, Danielson et al. 2007) | IL-6, TNF-alpha, CRP, sIL-6r, sIL-2r, sTNFR1, sTNFR2 | RR for fracture with highest quartile vs. lower three quartiles of: CRP=1.34, IL- 6=1.28, TNF-alpha= 1.28 | Elevated inflammatory markers are prognostic for fractures. |
|
Cardiovascular Health Study (CHS) cohort study of 5,888, ≥65 years old black and white men and women | |||
| Tracy (Tracy, Lemaitre et al. 1997) | CRP | OR for incident MI for subjects with subclinical disease (highest vs. lower three quartiles of CRP)=2.67 | CRP associated with incident cardiovascular events in the elderly especially who had subclinical disease at baseline. |
| Cushman (Cushman, Arnold et al. 2005) | CRP | 10-year cumulative CHD incidence with elevated CRP: Men=33%, Women=17%; Adjusted RR of CHD (CRP>3mg/L vs. <1mg/L)=1.45 | Elevated CRP associated with increased 10-year risk of CHD in older adults. |
| Aviles (Aviles, Martin et al. 2003) | CRP | Adjusted HR for AF for highest vs. lowest quartile of CRP=1.31, HR for 1SD increase=1.24 | CRP associated with presence of AF, may also predict future development of AF. |
| Cao (Cao, Arnoldet al. 2007) | CRP | Elevated CRP (>3mg/L) HR CVD events=1.45; CVD deaths=1.72; all-cause mortality=1.52 | CRP associated with increased risk for CVD and all-cause mortality in patients with detectable atherosclerosis. |
| Suzuki (Suzuki, Katz et al. 2008) | IL-6, CRP | Heart Failure HR for CHF for elevated CRP (≥3mg/L)=1.53; IL-6 (≥2.21pg/mL)=1.37 | IL-6 and CRP together with metabolic syndrome (MetS) associated with incident CHF in non-diabetic men and women. |
| Geffken (Geffken, Cushman et al. 2001) | CRP, fibrinogen | Mean values of CRP for lowest vs. highest quartile of physical activity (mg/L)=2.24 vs. 1.82 | Increased exercise is associated with reduced inflammation. |
| Jenny (Jenny, Yanez et al. 2007) | CRP, fibrinogen | HR for early death comparing highest vs. lowest quartile of CRP: men=4.1; women=2.3 | CRP and fibrinogen strongly associated with early death in older adults. |
| Newman (Newman, Sachs et al. 2009) | IL-6, CRP | HR for total 16-year mortality with highest vs. lowest quintile of IL-6=1.66 | IL-6 consistently associated with death across multiple causes. |
| Walston (Walston, Matteini et al. 2009) | IL-6 | HR for total all-cause mortality with highest vs. lowest quartile of IL-6=2.34 | Elevated IL-6 strongly predicted future mortality in European-American and African American adults. |
|
InCHIANTI Study cohort study of 1,453, 20–102 years old men and women | |||
| Schrager (Schrager, Metter et al. 2007) | IL-6, sIL-6r, IL-1ra, TNF-alpha, CRP | Mean value of IL-6 in participants with central obesity with: normal strength=1.6 pg/mL, low strength=2.3 pg/mL | Sarcopenic obesity is associated with elevated IL-6, sIL-6r and CRP. Central obesity may negatively affect muscle strength by increasing cytokine production. |
| McDermott (McDermott, Guralnik et al. 2005) | CRP, fibrinogen, IL-1β, IL-6, IL-10, IL-18, TNF-alpha | Adjusted associations between markers and presence vs. absence of PAD: CRP=3.12 vs. 2.57; IL-6=1.60 vs. 1.37 | PAD is associated with increased IL-6, fibrinogen, CRP. |
| Zuliani (Zuliani, Volpato et al. 2007) | CRP, fibrinogen, IL-1β, IL-6, IL-10, IL-18, TNF-alpha | Adjusted OR low HDL-C and IL-6 (highest vs. lowest tertile)=2.10 | Low HDL-c is associated with high IL-6. |
| Elosua (Elosua, Bartali et al. 2005) | IL-6, sIL-6r, IL-1ra, IL-10, IL-1β, IL-18, TNF-alpha, CRP, fibrinogen | Physical activity (men): log CRP (mg/L) sedentary vs.: light=−0.43; moderate high=−0.73, log IL-6 (pg/mL)=−0.33; women: log CRP (mg/L) sedentary vs.: moderate-high=−0.31; log IL-6 (pg/mL) light=−0.18, moderate high=−0.30 | Physical activity, performance and fitness are inversely associated with pro-inflammatory biomarkers (especially fibrinogen, CRP and IL-6) in older adults. |
| Cesari (Cesari, Penninx et al. 2004) | IL-6, sIL-6r, IL-1ra, IL-10, TNF-alpha, CRP | Correlation (r) of physical performance and: CRP=−0.162, IL-6=−0.251, IL1RA=−0.127 | Elevated IL-6, IL1ra, CRP significantly and independently associated with poorer physical performance and muscle strength in older adults. |
| Barbieri (Barbieri, Ferrucci et al. 2003) | IL-6, sIL-6r | Correlation between IL-6 and: handgrip =−0.17, total power =−0.14 | IL-6 was an independent predictor of handgrip and muscle power (especially in subjects in higher tertile of IL-6). |
| Maggio (Maggio, Basaria et al. 2006) | IL-6, sIL-6r, IL-1β, TNF-alpha | Correlation between sIL-6r and testosterone after adjustments = −0.20 | Significant inverse relationship between testosterone and sIL-6r. |
| Ferrucci (Ferrucci, Corsi et al. 2005) | IL-6, sIL-6r, IL-1ra, IL-10, IL-1β, IL-18,TNF-alpha, CRP, fibrinogen | IL-6 levels in age group 20–39 vs. 85+=0.6 vs. 3.5 (men), 0.6 vs. 2.1 (women); CRP levels in age group 20–39 vs. 85+=1.0 vs. 5.4 (men), 1.1 vs. 3.3 (women) | Older age associated with higher levels of IL-6, IL-1ra, IL-18, CRP and fibrinogen in both men and women. |
|
The Framingham Heart Study cohort study originally consisting of 5,209, 30–62 years old men and women | |||
| Pou (Pou, Massaro et al. 2007) | IL-6, CRP, fibrinogen, TNF-alpha | Pearson correlation coefficients: CRP & SAT women=0.45, men=0.30; CRP & VAT women=0.47, men=0.33; IL-6 & SAT=0.23, IL-6 & VAT=0.23 | Subcutaneous adipose tissue and visceral adipose tissue similarly associated with elevated inflammatory biomarkers. |
| Haider (Haider, Roubenoff et al. 2004) | IL-6, IL-1, CRP, TNF-alpha | Correlation IL-6 and CRP (r)=0.10 | IL-6 correlated with CRP levels. IL-6, IL-1, TNF-alpha not associated with CVD in very elderly population. |
| Vasan (Vasan, Sullivan et al. 2003) | IL-6, CRP, TNF-alpha | HR for CHF risk with highest vs. lowest tertile of IL-6=2.85; TNF-alpha=2.70 | Elevated IL-6, TNF-alpha and CRP associated with increased risk of CHF in people without prior MI. |
| Murabito (Murabito, Keyes et al. 2009) | IL-6, TNF-alpha, TNFR2, fibrinogen, CRP, CD40 ligand, LpPLA2 | OR for change in ABI level per SD change in: IL-6=1.21; TNFR2=1.19 | IL-6 and TNFR2 significantly associated with PAD independent of established risk factors and each other. |
| Other studies | |||
| Weaver (Weaver, Huang et al. 2002) (MacArthur Studies of Successful Aging) | IL-6 | Highest tertile of IL-6 with cognitive decline OR at baseline = 1.46; at 2.5 years = 2.03; at 7 years = 1.90 | Elevated baseline IL-6 associated with poor cognitive function and risk for further cognitive decline. |
| Reuben (Reuben, Judd-Hamilton et al. 2003) (MacArthur Studies of Successful Aging) | IL-6, CRP | Adjusted OR for high levels of recreational activity in highest tertile of: IL-6=0.65, CRP=0.70 | High levels of recreational activity significantly associated with lower levels of IL-6 and CRP in high functioning older people. |
| Taaffe (Taaffe, Harris et al. 2000) (MacArthur Studies of Successful Aging) | IL-6, CRP | Log IL-6 and 6-m walk quartiles: 1.27 ± 0.05, 1.18 ± 0.05, 1.09 ± 0.05, and 1.02 ± 0.05; log CRP and 6-m walk 0.83 ± 0.07, 0.62 ± 0.06, 0.60 ± 0.06, and 0.44 ± 0.07 | High levels of IL-6 and CRP related to poor performance for walking speed and grip strength in high functioning older people. |
| Cartier (Cartier, Cote et al. 2009) (Quebec Family Study) | IL-6, CRP | Correlation of visceral adipose tissue with: CRP=0.39, IL-6=0.32, TNF-alpha=0.14 | IL-6 and CRP are significantly and positively associated with visceral adipose tissue. |
| Cesari (Cesari, Onder et al. 2009) (ilSIRENTE study) | CRP | Spearman’s correlation between CRP and: total cholesterol=−0.169, LDL-C=−0.151, HDL-C=−0.199 | CRP significantly and inversely related to total, LDL and HDL cholesterol. CRP also a strong predictor of mortality. |
| Harris (Harris, Ferrucci et al. 1999) (Iowa 65+Rural Health Study) | IL-6, CRP | RR of death with highest vs. lowest quartile of IL-6=1.9; CRP=1.6; both=2.6 | Elevated levels of IL-6 and CRP associated with mortality in healthy older people. |
| Nicklas (Nicklas, Hsu et al. 2008) (LIFE-P study) | IL-6, CRP | 12 months physical activity resulted in 32% reduction in CRP and 16% reduction in IL-6 levels in comparison to baseline levels | Greater physical activity resulted in lower levels of IL-6 and CRP. |
| Ravaglia (Ravaglia, Forti et al. 2007) (The Conselice Study of Brain Aging) | IL-6, CRP | Combination of high CRP and high IL6 associated with risk of vascular dementia: HR=2.56 | IL-6 and CRP associated with increased risk of vascular dementia. |
| Pradhan (Pradhan, Manson et al. 2001) (The Women’s Health Study) | IL-6, CRP | Multivariate RR of T2DM with (highest vs. lowest quartile of) IL-6=2 .3 CRP=4.2 | Elevated levels of IL-6 and CRP predict development of type 2 diabetes. |
| Schaap (Schaap, Pluijm et al. 2006) (LASA) | IL-6, CRP | OR for loss of muscle strength with IL-6 (highest vs. lowest tertile)=3.65; CRP (highest vs. lowest quartile)=1.90 | Higher levels of IL-6 and CRP increase the risk of muscle strength loss. |
| Ferrucci (Ferrucci, Penninx et al. 2002) (Women’s Health and Aging Study) | IL-6 | Adjusted RR for women in highest vs. lowest tertile of IL-6 with: incident mobility disability=1.50, ADL disability=1.41, severe limitation in walking=1.61 | Higher IL-6 associated with higher risk of developing physical disability and steeper decline in walking ability in older women. |