| 1. |
- Corsonello, Andrea, et al.
(författare)
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The relevance of geriatric assessments on the association between chronic kidney disease stages and mortality among older people : A secondary analysis of a multicentre cohort study
- 2022
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 51:7
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Tidskriftsartikel (refereegranskat)abstract
- Background: age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. Methods: our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. Results: overall, mortality was found to increase starting from eGFR = 30-44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81-5.95) to ACR = 30-300 mg/g (HR = 1.96, 95%CI = 1.23-3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45-59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78-0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71-0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. Conclusions: physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild-moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function. © 2022 The Author(s). Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.
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| 2. |
- Enarsson, Malin, et al.
(författare)
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Association between Cardiorespiratory Fitness and Circulating Proteins in 50-Year-Old Swedish Men and Women : a Cross-Sectional Study
- 2021
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Ingår i: SPORTS MEDICINE-OPEN. - : Springer. - 2199-1170 .- 2198-9761. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: A strong cardiorespiratory fitness is suggested to have beneficial effects on cardiovascular risk; the exact mechanisms underlying the cardioprotective effects of fitness remain uncertain. Our aim was to investigate associations between cardiorespiratory fitness and multiple plasma proteins, in order to obtain insights about physiological pathways associated with the effects of exercise on cardiovascular health.Methods: In the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n=444 adults aged 50 years, 50% women), cardiorespiratory fitness was measured by a maximal exercise test on bicycle ergometer with gas exchange (VO(2)peak) normalized for body lean mass (dual-energy X-ray absorptiometry (DXA)). We measured 82 cardiovascular proteins associated with cardiovascular pathology and inflammation in plasma samples with a proximity extension assay.Results: In sex-adjusted linear regression, VO(2)peak was associated with 18 proteins after Bonferroni correction for multiple testing (p<0.0006). Following additional adjustment for fat mass (DXA), fasting glucose (mmol/L), low-density lipoprotein (LDL, mmol/L), smoking status, waist/hip ratio, blood pressure (mmHg), education level, and lpnr (lab sequence number), higher VO(2)peak was significantly associated with lower levels of 6 proteins: fatty-acid binding protein-4 (FABP4), interleukin-6 (IL-6), leptin, cystatin-B (CSTB), interleukin-1 receptor antagonist (IL-1RA), and growth differentiation factor 15 (GDF-15), and higher levels of 3 proteins: galanin, kallikrein-6 (KLK6), and heparin-binding EGF-like growth factor (HB-EGF), at nominal p-values (p<0.05).Conclusions: We identified multiple novel associations between cardiorespiratory fitness and plasma proteins involved in several atherosclerotic processes and key cellular mechanisms such as inflammation, energy homeostasis, and protease activity, which shed new light on how exercise asserts its beneficial effects on cardiovascular health. Our findings encourage additional studies in order to understand the underlying causal mechanisms for these associations.
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| 3. |
- Larsson, Anders, et al.
(författare)
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Strong Associations between Plasma Osteopontin and Several Inflammatory Chemokines, Cytokines, and Growth Factors
- 2021
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Ingår i: Biomedicines. - : MDPI. - 2227-9059. ; 9:8, s. 908-
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Tidskriftsartikel (refereegranskat)abstract
- Osteopontin is a member of the proinflammatory cytokine network, a complex system that involves many chemokines, cytokines, and growth factors. The aim of the present study was to study the associations between osteopontin and a large number of chemokines, cytokines, and growth factors. We analyzed plasma and urine osteopontin in 652 men from the Uppsala Longitudinal Study of Adult Men (ULSAM) study cohort and compared the levels with the levels of eighty-five chemokines, cytokines, and growth factors. We found significant associations between plasma osteopontin and 37 plasma biomarkers in a model adjusted for age, and 28 of those plasma biomarkers were significant in a model also adjusting for cardiovascular risk factors. There were no significant associations after Bonferroni adjustment between urine osteopontin and any of the studied plasma cytokine biomarkers. This study shows that circulating osteopontin participates in a protein-protein interaction network of chemokines, cytokines, and growth factors. The network contains responses, pathways, and receptor binding interactions relating to cytokines, regulation of the immune system, and also regulation of apoptosis and intracellular signal transduction.
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| 4. |
- Lind, Lars, et al.
(författare)
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Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes : Meta-Analyses and Mendelian Randomization Analyses
- 2021
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins. - 1079-5642 .- 1524-4636. ; 41:5, s. 1777-1788
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify causal pathophysiological mechanisms for atherosclerosis and incident cardiovascular events using protein measurements.APPROACH AND RESULTS: Carotid artery atherosclerosis was assessed by ultrasound, and 86 cardiovascular-related proteins were measured using the Olink CVD-I panel in 7 Swedish prospective studies (11 754 individuals). The proteins were analyzed in relation to intima-media thickness in the common carotid artery (IMT-CCA), plaque occurrence, and incident cardiovascular events (composite end point of myocardial infarction or ischemic stroke) using a discovery/replication approach in different studies. After adjustments for traditional cardiovascular risk factors, 11 proteins remained significantly associated with IMT-CCA in the replication stage, whereas 9 proteins were replicated for plaque occurrence and 17 proteins for incident cardiovascular events. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and MMP (matrix metalloproteinase)-12 were associated with both IMT-CCA and incident events, but the overlap was considerably larger between plaque occurrence and incident events, including MMP-12, TIM-1 (T-cell immunoglobulin and mucin domain 1), GDF (growth/differentiation factor)-15, IL (interleukin)-6, U-PAR (urokinase plasminogen activator surface receptor), LOX-1 (lectin-like oxidized LDL [low-density lipoprotein] receptor 1), and TRAIL-R2 (TNF [tumor necrosis factor]-related apoptosis-inducing ligand receptor 2). Only MMP-12 was associated with IMT-CCA, plaque, and incident events with a positive and concordant direction of effect. However, a 2-sample Mendelian randomization analysis suggested that increased MMP-12 may be protective against ischemic stroke (P=5.5x10(-7)), which is in the opposite direction of the observational analyses.CONCLUSIONS: The present meta-analysis discovered several proteins related to carotid atherosclerosis that partly differed in their association with IMT-CCA, plaque, and incident atherosclerotic disease. Mendelian randomization analysis for the top finding, MMP-12, suggests that the increased levels of MMP-12 could be a consequence of atherosclerotic burden rather than the opposite chain of events.
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| 5. |
- O'Keefe, James H., et al.
(författare)
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Omega-3 Blood Levels and Stroke Risk : A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies
- 2024
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Ingår i: Stroke. - : American Heart Association. - 0039-2499 .- 1524-4628. ; 55:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:The effect of marine omega-3 PUFAs on risk of stroke remains unclear.METHODS:We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome.RESULTS:Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76–0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74–0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81–0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78–0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD.CONCLUSIONS:Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.
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| 6. |
- Qian, Frank, et al.
(författare)
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Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation
- 2023
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 82:4, s. 336-349
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial.OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosa-pentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF.METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and sub-groups. Associations were pooled using inverse-variance weighted meta-analysis.RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively.CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.
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| 7. |
- Rudholm Feldreich, Tobias, et al.
(författare)
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The association between plasma proteomics and incident cardiovascular disease identifies MMP-12 as a promising cardiovascular risk marker in patients with chronic kidney disease
- 2020
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Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 307, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Previous proteomics efforts in patients with chronic kidney disease (CKD) have predominantly evaluated urinary protein levels. Therefore, our aim was to investigate the association between plasma levels of 80 cardiovascular disease-related proteins and the risk of major adverse cardiovascular events (MACE) in patients with CKD. Methods: Individuals with CKD stages 3-5 (eGFR below 60 ml min-1 [1.73 m]-2) from three community-based cohorts (PIVUS, ULSAM, SAVA), one diabetes cohort (CARDIPP) and one cohort with peripheral artery disease patients (PADVA) with information on 80 plasma protein biomarkers, assessed with a proximity extension assay, and follow-up data on incident MACE, were used as discovery sample. To validate findings and to asses generalizability to patients with CKD in clinical practice, an outpatient CKD-cohort (Malnutrition, Inflammation and Vascular Calcification (MIVC)) was used as replication sample. Results: In the discovery sample (total n = 1316), 249 individuals experienced MACE during 7.0 +/- 2.9 years (range 0.005-12.9) of follow-up, and in the replication sample, 71 MACE events in 283 individuals over a mean +/- SD change of 2.9 +/- 1.2 years (range 0.1-4.0) were documented. Applying Bonferroni correction, 18 proteins were significantly associated with risk of MACE in the discovery cohort, adjusting for age and sex in order of significance, GDF-15, FGF-23, REN, FABP4, IL6, TNF-R1, AGRP, MMP-12, AM, KIM-1, TRAILR2, TNFR2, CTSL1, CSF1, PlGF, CA-125, CCL20 and PAR-1 (p < 0.000625 for all). Only matrix metalloproteinase 12 (MMP-12) was significantly associated with an increased risk of MACE in the replication sample (hazard ratio (HR) per SD increase, 1.36, 95% CI (1.07-1.75), p = 0.013). Conclusions: Our proteomics analyses identified plasma MMP-12 as a promising cardiovascular risk marker in patients with CKD.
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| 8. |
- Ström, Edvin, 1992-, et al.
(författare)
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Dissatisfaction with teeth in type 2 diabetes is associated with increased risk of cardiovascular disease
- 2022
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Ingår i: Diabetes Epidemiology and Management. - : Elsevier. - 2666-9706. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background and aimPoor dental health status has been linked to increased risk of cardiovascular events in type 2 diabetes (T2D). Less is known about self-perceived dental health and cardiovascular risk. Our aim with this study was to investigate this association.MethodsRecruitment of T2D patients took place between 2005 and 2008 in Swedish primary care. Teeth satisfaction was assessed by questionnaire at baseline. The major adverse cardiovascular events (MACE) in this study were hospitalization due to myocardial infarction, stroke or cardiovascular death. Cox regression models were used.ResultsOut of 761 participants 601 had complete data. Ninety-two MACEs occurred (median follow-up time: 11.6 years). Those satisfied with their teeth (n = 458) had 61 events (1.2 events per 100 person-years), while those dissatisfied with teeth (n = 143) had 31 events (2.2 events per 100 person-years). Dissatisfaction with teeth was associated with an increased risk of MACE independent of age, sex and levels of CRP (HR 1.85, 95% CI 1.20 – 2.86).ConclusionsIn patients with T2D, dissatisfaction with teeth was associated with increased risk of MACE and may be considered as a marker of risk.
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| 9. |
- Vavruch, Camilla, et al.
(författare)
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Using proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in patients with type 2 diabetes
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to discover novel associations between leptin and circulating proteins which could link leptin to the development of cardiovascular disease in patients with type 2 diabetes (T2DM). In a discovery phase, we investigated associations between 88 plasma proteins, assessed with a proximity extension assay, and plasma leptin in a cohort of middle-aged patients with T2DM. Associations passing the significance threshold of a False discovery rate of 5% (corresponding to p < 0.0017) were replicated in patients with T2DM in an independent cohort. We also investigated if proteins mediated the longitudinal association between plasma leptin and the incidence of major cardiovascular events (MACE). One protein, adipocyte fatty acid binding protein (A-FABP), was significantly associated with leptin in both the discovery phase [95% CI (0.06, 0.17) p = 0.00002] and the replication cohort [95% CI (0.12, 0.39) p = 0.0003]. Multiplicative interaction analyses in the two cohorts suggest a stronger association between A-FABP and leptin in men than in women. In longitudinal analyses, the association between leptin and MACE was slightly attenuated after adding A-FABP to the multivariate model. Our analysis identified a consistent association between leptin and A-FABP in two independent cohorts of patients with T2DM, particularly in men.Trial registration: ClinicalTrials.gov identifier NCT01049737.
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| 10. |
- Wändell, Per, et al.
(författare)
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The C-reactive protein Albumin ratio was not consistently associated with cardiovascular and all-cause mortality in two community-based cohorts of 70-year-olds.
- 2023
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - 0036-5513 .- 1502-7686. ; , s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- C-reactive protein (CRP)/Albumin ratio (CAR) seems to mirror disease severity and prognosis in several acute disorders particularly in elderly patients, which we aimed to study. As method we use a prospective study design; the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 912, women 50%; mean age 70 years, baseline 2001 and 2004, median follow-up 15.0 years, end of follow-up 2019) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 924 mean age 71 years, baseline 1991-1995, median follow-up 15.6 years, end of follow-up 2016). Serum samples were used for analyses of CRP and Albumin. Cox regression analyses were performed for cardiovascular and all-cause mortality in models adjusting for several factors (age; physical activity; Interleukin-6; cardiovascular (CVD) risk factors: smoking, BMI level, systolic blood pressure, LDL-cholesterol, and diabetes), with 95% confidence interval (CI). When adjusting for age and CVD risk factors, CAR was significantly associated with cardiovascular mortality for meta-analyzed results from PIVUS and ULSAM, HR 1.09 (95% 1.01-1.18), but neither in PIVUS (HR 1.14, 95% CI 0.99-1.31) nor in ULSAM (1.07, 95% CI 0.98-1.17). Additionally, CAR was significantly associated with all-cause mortality in ULSAM 1.31 (95% CI 1.12-1.54) but not in PIVUS HRs 1.01 (95% 0.089-1.15). The predictive value of CAR was similar to CRP alone in PIVUS and ULSAM and slightly better than albumin for the prediction of CVD-mortality in ULSAM. In conclusion, CAR was not consistently associated with cardiovascular and all-cause mortality in the two cohorts. The prognostic value of CAR for long-term CVD-mortality was similar to CRP.
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