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- Shepherd, L., et al.
(författare)
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Infection-related and -unrelated malignancies, HIV and the aging population
- 2016
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Ingår i: HIV Medicine. - : Wiley. - 1464-2662 .- 1468-1293. ; 17:8, s. 590-600
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.
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- Andersson, J., et al.
(författare)
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Echogenecity of the carotid intima-media complex is related to cardiovascular risk factors, dyslipidemia, oxidative stress and inflammation The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2009
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 204:2, s. 612-618
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased carotid artery intima-media thickness (IMT), measured by ultrasound, is related to an increased risk of cardiovascular disease. Since presence of echolucent plaques increases the risk further, we investigated if echogenecity of the carotid intima-media complex is related to markers of cardiovascular risk. Our aim was therefore to investigate if intima-media echogenecity is related to cardiovascular risk factors, or to markers of inflammation and oxidation in an exploratory investigation. Methods: The PIVUS cohort study is an observational study of 1016 (509 women and 507 men) randomly chosen individuals aged 70 living in Uppsala, Sweden. Carotid artery ultrasound measurements were performed. IMT and the grey scale median (GSM) value were calculated in the intima-media complex (IM-GSM) in the far wall of the common carotid artery. Traditional risk factors were evaluated together with indices of oxidative stress and inflammation. Results: In the multiple regression analysis, HDL-cholesterol, body mass index, conjugated diens, glutathione, e-selectin and TNF alfa were significantly related to IM-GSM. IMT was independently related to blood pressure, smoking and body mass index. Conclusion: The echolucency of the carotid intima-media was related to several cardiovascular risk factors not related to IMT, such as dyslipidemia, oxidative stress and inflammation. Since the echogenecity of the carotid intima-media complex was related to different risk factors compared to carotid IMT, it is worthwhile to further explore the usefulness of this new marker of the vascular wall. (C) 2009 Published by Elsevier Ireland Ltd.
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- Andersson, J., et al.
(författare)
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The Carotid Artery Plaque Size and Echogenicity are Related to Different Cardiovascular Risk Factors in the Elderly
- 2009
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Ingår i: Lipids. - : Wiley. - 0024-4201 .- 1558-9307. ; 44:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- Carotid plaques can be characterised by ultrasound by size and echogenicity. Both size and echogenicity are predictors of cardiovascular events. The aim of this study was to examine whether traditional risk factors and markers of inflammation and oxidation were associated with plaque size and echogenicity. Computerised analysis of carotid plaque size and echogenicity (grey scale median, GSM) were performed by ultrasound in a population-based health survey in 1,016 subjects aged 70 years (PIVUS study). Information on cardiovascular risk factors was collected, together with markers of inflammation and oxidation. Increased Framingham risk score, systolic blood pressure, higher BMI and decreased HDL, lower glutathione levels were related to echolucent plaques. Previous or present smoking was common with significantly more pack-years related to the echorich plaques. Plaque size was associated with increased Framingham risk score, systolic blood pressure, blood glucose levels, smoking, ApoB/A1 ratio, OxLDL, TNF alpha, HOMA insulin resistance, leucocyte count, decreased BCD-LDL and low levels of l-selectin. Low HDL, increased BMI and decreased glutathione levels were associated with the echolucency of carotid plaques, implying metabolic factors to play a role for plaque composition. Markers of inflammation were related to plaque size alone, implying inflammation to be predominantly associated with the amount of atherosclerosis. These results suggest that plaque size and echogenicity are influenced by different risk factors.
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- Annuk, Margus, et al.
(författare)
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Oxidative stress markers in pre-uremic patients
- 2001
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Ingår i: Clinical Nephrology. - 0301-0430. ; 56:4, s. 308-314
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- AIM: The present study was designed to investigate a complex of oxidative stress (OS) markers in patients with chronic renal failure (CRF) and to study the relationship between different OS markers and degree of renal failure. The following indices of OS were measured in plasma: oxidized glutathione (GSSG), reduced glutathione (GSH), total glutathione (TGSH), glutathione redox ratio (GSSG/GSH) and resistance of lipoprotein fraction to oxidation (lag phase of LPF). Baseline diene conjugation level of lipoprotein fraction (BDC-LPF), total antioxidative activity (TAA), diene conjugates (DC), lipid hydroperoxides (LOOH) and thiobarbituric acid-reactive substances (TBARS) were measured in serum. All markers in plasma and serum were measured both in patients with CRF and in healthy controls. SUBJECTS AND METHODS: Blood samples were obtained from 38 patients with CRF and from 61 healthy controls. Routine biochemical analyses were performed by using commercially available kits. RESULTS: Levels of DC, BDC-LPF, LOOH, GSSG and GSSG/GSH ratio were significantly increased and lag phase of LPF was significantly shortened in patients with CRF compared with healthy controls. Serum creatinine and urea levels correlated significantly with GSSG level and GSSG/GSH in patients with CRF. A significant inverse correlation was found between glutathione redox ratio and lag phase of LPF and between GSSG level and BDC-LPF. CONCLUSIONS: The findings suggest that renal patients are in a state of oxidative stress compared with healthy controls. The most informative indices to evaluate the degree of OS in CRF were: GSSG level, GSSG/GSH status, lag phase of LPF and BDC-LPF.
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- Bogdanovic, N, et al.
(författare)
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The Swedish APP670/671 Alzheimer's disease mutation: the first evidence for strikingly increased oxidative injury in the temporal inferior cortex
- 2001
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1420-8008 .- 1421-9824. ; 12:6, s. 364-370
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the level of oxidative stress (OS) in familial Alzheimer’s disease (FAD), we analysed four cerebrocortical areas from patients with Swedish FAD bearing the APP670/671 mutation. The temporal inferior cortex (TIC) from Swedish FAD patients revealed a striking 2- to 3-fold increase in diene conjugates, lipid peroxides and protein carbonyls, compared to sporadic Alzheimer’s disease (AD). Compared with TIC from sporadic AD patients, the mutation carriers showed a markedly decreased activity of catalase (CAT) in the same area, and the same trend was found for another antioxidant enzyme, superoxide dismutase. These results are consistent with the deep oxidative injury of TIC in Swedish FAD. In the frontal inferior cortex (FIC), sensory postcentral cortex (SPCC) and occipital primary cortex (OPC) from Swedish FAD, the parameters of oxidative injury tended to be higher than in sporadic AD. Only the increase in the levels of lipid hydroperoxides in SPCC and of protein carbonyls in OPC was significant. Compared to sporadic AD, Swedish FAD showed a significant increase in GSSG levels and the GSSG/2GSH ratio in the FIC, SPCC and OPC. A significantly decreased activity of CAT was detectable for the SPCC and OPC in Swedish FAD. Increased OS might play a crucial role in the rapid progression of Swedish FAD from the associative temporal cortex to the primary cerebrocortical areas.
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| 10. |
- Ganna, Andrea, et al.
(författare)
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Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease
- 2014
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:12, s. e1004801-
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
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