| 1. |
- Degerman Gunnarsson, Malin, et al.
(författare)
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Pittsburgh compound-B and Alzheimer's disease biomarkers in CSF, plasma and urine: An exploratory study.
- 2010
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Ingår i: Dementia and geriatric cognitive disorders. - Basel : S. Karger AG. - 1421-9824 .- 1420-8008. ; 29:3, s. 204-12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PIB) is an in vivo ligand for measuring beta-amyloid (Abeta) load. Associations between PET PIB and cerebrospinal fluid (CSF) Abeta1-42 and apolipoprotein E epsilon4 (APOE epsilon4) have been observed in several studies, but the relations between PIB uptake and other biomarkers of Alzheimer's disease (AD) are less investigated. METHOD: PET PIB, PET 18Fluoro-2-deoxy-D-glucose and different AD biomarkers were measured twice in CSF, plasma and urine 12 months apart in 10 patients with a clinical diagnosis of mild to moderate AD. RESULTS: PIB retention was constant over 1 year, inversely related to low CSF Abeta1-42 (p = 0.01) and correlated positively to the numbers of the APOE epsilon4 allele (0, 1 or 2) (p = 0.02). There was a relation between mean PIB retention and CSF ApoE protein (r = -0.59, p = 0.07), and plasma cystatin C (r = -0.56, p = 0.09). CONCLUSION: PIB retention is strongly related to CSF Abeta1-42, and to the numbers of the APOE epsilon4 allele.
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| 2. |
- Jobs, Elisabeth, et al.
(författare)
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Association between serum cathepsin S and mortality in older adults
- 2011
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Ingår i: Journal of the American Medical Association (JAMA). - Chicago : American Medical Association. - 0098-7484 .- 1538-3598. ; 306:10, s. 1113-1121
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Tidskriftsartikel (refereegranskat)abstract
- Context: Experimental data suggest that cathepsin S, a cysteine protease, is involved in the complex pathways leading to cardiovascular disease and cancer. However, prospective data concerning a potential association between circulating cathepsin S levels and mortality are lacking. Objective To investigate associations between circulating cathepsin S levels and mortality in 2 independent cohorts of elderly men and women.Design, Setting, and Participants: Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995; median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women; mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end of follow-up: 2010). Serum samples were used to measure cathepsin S.Main Outcome Measure Total mortality.Results: During follow-up, 413 participants died in the ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In multivariable Cox regression models adjusted for age, systolic blood pressure, diabetes, smoking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment, and history of cardiovascular disease, higher serum cathepsin S was associated with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for 1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM cohort, serum cathepsin S also was associated with cardiovascular mortality (131 deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01) and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05 [95% CI, 1.01-1.10]; P = .01).Conclusions Among elderly individuals in 2 independent cohorts, higher serum cathepsin S levels were associated with increased mortality risk. Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility.
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| 3. |
- Jobs, Elisabeth, et al.
(författare)
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Serum cathepsin S is associated with serum C-reactive protein and interleukin-6 independently of obesity in elderly men
- 2010
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 95:9, s. 4460-4464
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cathepsin S has been suggested provide a mechanistic link between obesity and atherosclerosis, possibly mediated via adipose tissue-derived inflammation. Previous data have shown an association between circulating cathepsin S and inflammatory markers in the obese, but to date, community-based reports are lacking. Accordingly, we aimed to investigate the association between serum levels of cathepsin S and markers of cytokine-mediated inflammation in a community-based sample, with prespecified subgroup analyses in nonobese participants. METHODS: Serum cathepsin S, C-reactive protein (CRP), and IL-6 were measured in a community-based cohort of elderly men (Uppsala Longitudinal Study of Adult Men; mean age 71 years, n = 991). CRP and IL-6 were also measured at a reexamination after 7 yr. RESULTS: After adjustment for age, body mass index, fasting plasma glucose, diabetes treatment, systolic blood pressure, diastolic blood pressure, hypertension treatment, serum cholesterol, serum high-density lipoprotein cholesterol, prior cardiovascular disease, smoking, and leisure time physical activity, higher cathepsin S was associated with higher CRP (regression coefficient for 1 sd increase, 0.13; 95% confidence interval 0.07-0.19; P < 0.001) and higher serum IL-6 (regression coefficient for 1 sd increase, 0.08; 95% confidence interval 0.01-0.14; P = 0.02). These associations remained similar in normal-weight participants (body mass index <25 kg/m(2), n = 375). In longitudinal analyses, higher cathepsin S at baseline was associated with higher serum CRP and IL-6 after 7 yr. CONCLUSIONS: These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community.
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| 4. |
- Nerpin, Elisabet, et al.
(författare)
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The combined contribution of albuminuria and glomerular filtration rate to the prediction of cardiovascular mortality in elderly men
- 2011
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:9, s. 2820-2827
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cardiovascular risk prediction is particularly important in the primary prevention of cardiovascular disease (CVD). Yet, data on whether the combined addition of albuminuria and estimated glomerular filtration rate (eGFR) improves cardiovascular risk prediction in individuals without CVD in the community is scarce.METHODS: We investigated associations between urinary albumin excretion rate (UAER), cystatin C-based eGFR and cardiovascular mortality in a community-based cohort of elderly men (ULSAM study; n = 1113, mean age 71 years, 208 cardiovascular deaths, median follow-up 12.9 years) with prespecified analyses in participants without CVD (n = 649, 86 cardiovascular deaths).RESULTS: Using multivariable Cox regression, higher UAER and lower eGFR were associated with increased risk for cardiovascular mortality independently of established cardiovascular risk factors in the whole sample and in men without CVD at baseline [subsample without CVD: UAER; hazard ratio (HR) per 1 SD 1.26, 95% confidence interval (CI) 1.05-1.51, P = 0.01; eGFR: HR per 1 SD 0.74, 95% CI 0.59-0.92, P = 0.007]. Analyses of model discrimination, calibration, reclassification and global fit suggested that UAER and eGFR also add relevant prognostic information beyond established cardiovascular risk factors in participants without prevalent CVD. Interestingly, established cutoffs used to diagnose microalbuminuria (UAER > 20 μg/min) and chronic kidney disease Stage 3 (eGFR < 60 mL/min/1.73m(2)), appeared less suitable for cardiovascular risk prediction [integrated discrimination improvement (IDI) 0.006, P = 0.11], while cutoffs UAER > 6 μg/min and eGFR < 45 mL/min/1.73m(2) significantly improved IDI (0.047, P < 0.001).CONCLUSIONS: UAER and eGFR improved cardiovascular risk prediction beyond established cardiovascular risk factors, suggesting that these kidney biomarkers may be useful in predicting cardiovascular death in elderly men.
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| 5. |
- Basu, Samar, et al.
(författare)
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Cytokine-mediated inflammation is independently associated with insulin sensitivity measured by the euglycemic insulin clamp in a community-based cohort of elderly men
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - : E-Century Publishing. - 1940-5901. ; 4:2, s. 164-168
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Tidskriftsartikel (refereegranskat)abstract
- Both clinical and experimental studies suggest a close relation between an inflammatory state and insulin resistance. We investigated the association between cytokine-mediated inflammation (high sensitivity C reactive protein [hsCRP] and interleukin [IL] 6) and insulin sensitivity (insulin-mediated glucose disposal rate, assessed by the euglycemic insulin clamp) in a community-based cohort, with subgroup analyses of normal weight individuals without diabetes mellitus and metabolic syndrome (NCEP). hsCRP and IL- 6 were inversely associated with insulin sensitivity (multivariable-adjusted regression coefficient for 1-SD increase of hsCRP -0.12 (-0.21-(-0.03), p=0.01) and of IL-6 - 0.11 (-0.21-(-0.02), p=0.01) in models adjusting for age and components of the metabolic syndrome (systolic and diastolic blood pressure, antihypertensive drugs, HDL-cholesterol, triglycerides, fasting plasma glucose, waist circumference). The multivariable-adjusted association between hsCRP, IL-6 and insulin sensitivity were of a similar magnitude in normal weight individuals without diabetes and without the metabolic syndrome. Our data show that cytokine -mediated subclinical inflammation is independently associated with decreased insulin sensitivity also in apparently metabolically healthy normal weight individuals, indicating that the interplay between inflammatory processes and insulin resistance is present already in the early stages of the development of glucometabolic disease. (IJCEM1012002).
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| 6. |
- 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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| 7. |
- Jobs, Elisabeth, et al.
(författare)
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Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men
- 2012
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Ingår i: Diabetes Care. - : American diabetes association. - 0149-5992 .- 1935-5548. ; 36:1, s. 163-165
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE. To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.RESEARCH DESIGN AND METHODS. Serum cathepsin S, insulin sensitivity (euglycaemic-hyperinsulinaemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.RESULTS. After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).CONCLUSIONS. Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.
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| 8. |
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| 9. |
- Nerpin, Elisabet, et al.
(författare)
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Inflammation, oxidative stress, glomerular filtration rate, and albuminuria in elderly men : a cross-sectional study
- 2012
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Ingår i: BMC research notes. - : BioMed Central. - 1756-0500. ; 5:1, s. 537-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men. FINDINGS: Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2alpha [PGF2alpha]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years). RESULTS: In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (beta-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (beta-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (beta- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (beta-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR. CONCLUSION: Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.
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| 10. |
- Helmersson-Karlqvist, Johanna, et al.
(författare)
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24-Hour ambulatory blood pressure associates inversely with prostaglandin F-2 alpha, interleukin-6 and F-2-isoprostane formation in a Swedish population of older men
- 2012
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 5:2, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- Vasoconstrictive prostaglandins (PGs), such as PGF(2 alpha), F-2-isoprostanes, and systemic inflammation may be involved in the physiological regulation of blood pressure (BP) and the pathophysiology leading to hypertension. However, studies evaluating these parameters and BP in human populations are sparse. We analysed the cross-sectional associations between 24-hour ambulatory BP and urinary 15-keto-dihydro-PGF(2 alpha) (indicator of PG-mediated vasoconstriction and inflammation), plasma interleukin-6 (IL-6), C-reactive protein (CRP), serum amyloid A (SAA) and urinary F-2-isoprostanes (indicator of vasoconstriction and oxidative stress) in 619 men in a Swedish older population (Uppsala Longitudinal Study of Adult Men, age 78 years). Both systolic and diastolic 24-hour BP correlated inversely with concentrations of 15-keto-dihydro-PGF(2 alpha) (P < 0.01) and F-2-isoprostanes (P< 0.01) independent on other cardiovascular risk factors. Additionally, diastolic 24-hour BP inversely correlated with plasma IL-6 (P< 0.05) and 24-hour pulse pressure showed a positive linear correlation with IL-6, CRP and SAA. In conclusion, high BP is associated with decreased formation of vasoconstrictive PGF(2 alpha) and F-2-isoprostanes in this population of older men. These findings, although unlike our original hypothesis, might have an important physiological function which needs to be further evaluated.
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