Axel C Carlsson1, C Christofer Juhlin2, Tobias E Larsson3, Anders Larsson4, Erik Ingelsson5, Johan Sundström4, Lars Lind4, Johan Arnlöv6. 1. Centre for Family Medicine, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. Electronic address: axelcefam@hotmail.com. 2. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. 3. Department of Clinical Science, Intervention and Technology, Renal Unit, Karolinska Institutet, Stockholm, Sweden; Department of Nephrology, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 5. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden. 6. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
Abstract
BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers. METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years). RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatings TNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation. CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumornecrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers. METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years). RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatings TNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation. CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.
Authors: Richard R Reich; Cecile A Lengacher; Thomas W Klein; Cathy Newton; Steve Shivers; Sophia Ramesar; Carissa B Alinat; Carly Paterson; Alice Le; Jong Y Park; Versie Johnson-Mallard; Maya Elias; Manolete Moscoso; Matthew Goodman; Kevin E Kip Journal: Biol Res Nurs Date: 2017-05-01 Impact factor: 2.522
Authors: Axel C Carlsson; Lina Nordquist; Tobias E Larsson; Juan-Jesús Carrero; Anders Larsson; Lars Lind; Johan Ärnlöv Journal: Cardiorenal Med Date: 2015-07-31 Impact factor: 2.041
Authors: Axel C Carlsson; Carl Johan Östgren; Fredrik H Nystrom; Toste Länne; Pär Jennersjö; Anders Larsson; Johan Ärnlöv Journal: Cardiovasc Diabetol Date: 2016-02-29 Impact factor: 9.951
Authors: Axel C Carlsson; Toralph Ruge; Erik Kjøller; Jørgen Hilden; Hans Jørn Kolmos; Ahmad Sajadieh; Jens Kastrup; Gorm Boje Jensen; Anders Larsson; Christoph Nowak; Janus Christian Jakobsen; Per Winkel; Christian Gluud; Johan Ärnlöv Journal: J Am Heart Assoc Date: 2018-04-23 Impact factor: 5.501