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- Helmersson-Karlqvist, Johanna, et al.
(författare)
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Cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction
- 2011
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Ingår i: XIII Svenska Kardiovaskulära vårmötet. - Örebro.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with severe chronic kidney disease (CKD) are characterized by increased inflammatory activity and higher oxidative stress, conditions that have been suggested to mediate the substantially increased risk for cardiovascular disease (CVD) in these patients. However, also individuals with mild signs of kidney damage and dysfunction have been shown to have an increased risk for CVD. Yet, data on the association between mild signs of kidney damage and dysfunction and markers of inflammation and oxidative stress in the community is scarce. Research Design and Methods: Accordingly, we investigated the cross-sectional associations between cystatin C based glomerular filtration rate (GFR), urinary albumin creatinine ratio (ACR), and markers of cytokine mediated inflammation (interleukin 6 [IL-6], high sensitivity C reactive protein [hsCRP], serum amyloid A [SAA]), cyclooxygenas-mediated inflammation (urinary prostaglandin F2-alpha [PGF2alpha]) and oxidative stress (urinary F2-isprostanes) in a sub-sample of a community based cohort (Uppsala Longitudinal Study of Adult Men, ULSAM, n=648, mean age 77 year) with normal eGFR (>60 ml/min/1.73m2 ) and normal ACR (<30 µmol/L) Results: In multivariable linear regression models adjusting for age, BMI, smoking, systolic and diastolic blood pressure, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides and treatment with statin, ACE-inhibit-, ASA-, anti inflammation- , cortisone medication, eGFR was inversely associated with lower hsCRP (p<0.008), lower IL-6 (p<0.01), and ACR was positive associated with higher hsCRP (p=0.01), higher IL-6 (p=<0.004) and higher SAA (p=0.001). No significant association was seen between PGF2alpha, F2-isoprostanes and eGFR and ACR. Conclusion: Our community based data suggest that cytokine mediated inflammation is involved in the early stages of kidney damage and dysfunction, while cyclooxygenas-mediated inflammation and oxidative stress is not. Further studies are needed in order to evaluate to what extent cytokine mediated inflammation mediates the increased CVD risk seen in individuals with mild signs of kidney damage and dysfunction.
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- Jobs, Elisabeth, et al.
(författare)
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Cathepsin S is independently associated with cytokine mediated inflammation in elderly men
- 2009
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Ingår i: European Society of Cardiology Congress. - Uppsala.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Cathepsin S is independently associated with cytokine mediated inflammation in elderly men Conclusion: Higher serum levels of Cathepsin S were independently associated with higher CRP and IL-6 in a community– based sample of elderly men. Our data provides support for the notion that Cathepsin S is involved in inflammatory processes, possibly leading to atherosclerosis and cardiovascular disease. Background: Cathepsin S is a lysosomal protease that has been suggested to play a key role in the development of atherosclerosis and cardiovascular disease by degradation of vascular extracellular matrix. Previous studies have suggested that cathepsin S provides a molecular link between obesity and atherosclerosis, possibly via increased inflammatory activity. Yet, the association between circulating cathepsin S and inflammation markers has not previously been reported in the community. Aim: To investigate the association between plasma levels of cathepsin- S, C-reactive protein (CRP) and Interleukin 6 (IL-6), in the community. Methods: Serum levels of cathepsin S, CRP, IL-6 were measured in frozen samples from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men (n=999, mean age 71 years). Results: Cross-sectional association between Cathepsin S, CRP and IL-6 at age 70 showed that one standard deviation (SD) higher serum Cathepsin S was significantly associated with 0.14 SD higher serum CRP and 0.07-0.08 SD higher serum IL-6 when adjusting for age, life style factors (body mass index, physic activity and smoking), cardiovascular risk factors (hypertension, dyslipidemia, previous cardiovascular disease and diabetes and smoking), and the combination of all covariates
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- Nerpin, Elisabet, et al.
(författare)
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A Cystatin C-based glomerular filtration rate equation is a stronger predictor of cardiovascular mortality compared to creatinine-based equations
- 2010
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Ingår i: Svenska Kardiovasculära vårmötet. - Göteborg.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Several prior studies report that decreased estimated glomerular filtration rate (eGFR) predicts cardiovascular disease in the general population, but this is less studied in a primary preventive setting. Currently, various methods are available to assess eGFR. In the present study, we aimed to evaluate different eGFR-equations (creatinine-based or cystatin C-based), for the prediction of cardiovascular death. Material and methods: In men without cardiovascular disease, participating in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM, n=649, mean age 71 years, median follow-up 12.9 years; 86 cardiovascular deaths during follow-up), eGFR was calculated from circulating creatinine by using the Modification of Diet in Renal Disease formula (eGFRMDRD) and the Chronic Kidney Disease Epidemiology Collaboration formula (eGFRCKD-EPI) and from circulating cystatin C using the following formula: 77.24x-1.2623 (eGFRcyst). Results: In Cox-proportional hazard models, 1-SD increase in eGFRcyst was associated with lower risk of cardiovascular mortality after adjustment for established cardiovascular risk factors and urinary albumin excretion rate (hazard ratio 0.74, 95% CI 0.59-0.92 (p=0.007). However, the creatinine-based GFR equations were not significantly associated with cardiovascular death (for eGFRMDRD: hazard ratio 0.84, 95% CI 0.67-1.06, (p=0.14), for eGFRCKD-EP : hazard ratio 0.86, 95% CI 0.69-1.07 (p=0.17)) in multivariable models. Moreover, when eGFRcyst was incorporated to a model with established risk factors, the integrated discrimination improvement was significantly increased 0.015, (p=0.02). Also eGFRcyst, provided improved discrimination beyond established risk factors and urinary albumine excretion rate (0.012, p=0.03). No improvement in integrated discrimination were seen with eGFRMDRD (p=0.25) or eGFRCKD-EPI (p=0.36). Conclusion: In our community-based cohort of elderly men free from cardiovascular disease at baseline, eGFRcyst significantly predicted cardiovascular death while the creatinine-based eGFR-equations did not. The fact that eGFRcyst improved model discrimination beyond established cardiovascular risk factors suggest that it may be a relevant risk marker for cardiovascular death in the elderly.
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- Nerpin, Elisabet, et al.
(författare)
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Insulin sensitivity measured with euglycemic clamp is independently associated with glomerular filtration rate in a community-based cohort
- 2008
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 31:8, s. 1550-1555
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Konferensbidrag (refereegranskat)abstract
- Objective: To investigate the association between insulin sensitivity and glomerular filtration rate (GFR) in the community, with pre-specified subgroup analyses in normoglycemic individuals with normal GFR. Research Design and Methods: We investigated the cross-sectional association between insulin sensitivity (M/I, assessed using euglycemic clamp) and cystatin C-based GFR in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men, ULSAM; n=1070). We also investigated whether insulin sensitivity predicted the incidence of renal dysfunction at a follow-up examination after 7 years. Results: Insulin sensitivity was directly related to GFR (multivariable-adjusted regression coefficient for 1-unit higher M/I 1.19, 95% CI 0.69-1.68, p<0.001) after adjusting for age, glucometabolic variables (fasting plasma glucose, fasting plasma insulin, 2-hour glucose after an oral glucose tolerance test), cardiovascular risk factors (hypertension, dyslipidemia, smoking), and lifestyle factors (BMI, physical activity, consumption of tea, coffee and alcohol). The positive multivariable-adjusted association between insulin sensitivity and GFR remained statistically significant also in participants with normal fasting plasma glucose, normal glucose tolerance and normal GFR (n=443, p<0.02). In longitudinal analyses, higher insulin sensitivity at baseline was associated with lower risk of impaired renal function (GFR<50ml/min/1.73 m2) during follow-up independently of glucometabolic variables (multivariable-adjusted odds ratio for 1-unit higher of M/I 0.58, 95 % CI 0.40-0.84, p<0.004). Conclusion: Our data suggest that impaired insulin sensitivity may be involved in the development of renal dysfunction at an early stage, prior to the onset of diabetes or pre-diabetic glucose elevations. Further studies are needed in order to establish causality.
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