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Lind, L., Figarska, S., Sundström, J., Fall, T., Ärnlöv, J. & Ingelsson, E. (2020). Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging. Obesity, 28(1), 178-186
Öppna denna publikation i ny flik eller fönster >>Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging
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2020 (Engelska)Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 28, nr 1, s. 178-186Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

OBJECTIVE: This study investigated how changes in 84 proteins over a 10-year period of aging were related to changes in measures of body fat and distribution over the same period.

METHODS: Cardiovascular candidate proteins were measured using the proximal extension assay technique, along with BMI and waist-hip ratio (WHR), at ages 70, 75, and 80 in 1,016 participants of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Associations of changes in plasma protein levels, BMI, and WHR over time were analyzed using linear mixed models.

RESULTS: Changes in 19 and 16 proteins were significantly associated with changes in BMI and WHR, respectively (P < 0.00059), over the investigated 10-year period. Leptin and fatty acid-binding protein 4 were among the proteins most strongly associated with changes in both BMI and WHR. Four of the proteins significantly tracked with change in BMI (P < 0.00059) but not WHR (P > 0.05): endothelial cell-specific molecule 1, pentraxin-related protein PTX3, ST2 protein (also known as interleukin-1 receptor-like 1), and spondin-1. Five proteins tracked with change in WHR (P < 0.00059) but not BMI (P > 0.05): caspase-8, cathepsin L1, oxidized low-density lipoprotein receptor 1, interleukin-6 receptor subunit alpha, and C-C motif chemokine 20.

CONCLUSIONS: This is the first large longitudinal study of how changes in plasma protein signatures are associated with changes in measures of body fat and distribution over 10 years of aging.

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urn:nbn:se:du-31200 (URN)10.1002/oby.22660 (DOI)000500583200001 ()31804015 (PubMedID)2-s2.0-85077106134 (Scopus ID)
Tillgänglig från: 2019-12-09 Skapad: 2019-12-09 Senast uppdaterad: 2020-01-07Bibliografiskt granskad
Corsonello, A., Roller-Wirnsberger, R., Wirnsberger, G., Ärnlöv, J., Carlsson, A. C., Tap, L., . . . Lattanzio, F. (2020). Clinical Implications of Estimating Glomerular Filtration Rate with Three Different Equations Among Older People. Preliminary Results of the Project "Screening for Chronic Kidney Disease among Older People across Europe (SCOPE)".. Journal of clinical medicine, 9(2), Article ID E294.
Öppna denna publikation i ny flik eller fönster >>Clinical Implications of Estimating Glomerular Filtration Rate with Three Different Equations Among Older People. Preliminary Results of the Project "Screening for Chronic Kidney Disease among Older People across Europe (SCOPE)".
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2020 (Engelska)Ingår i: Journal of clinical medicine, ISSN 2077-0383, Vol. 9, nr 2, artikel-id E294Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

We aimed at investigating to what extent CKD may be staged interchangeably by three different eGFR equations in older people, and evaluating the source of discrepancies among equations in a population of 2257 patients older than 75 years enrolled in a multicenter observational study. eGFR was calculated by CKD-EPI, BIS and FAS equations. Statistical analysis was carried out by Bland-Altman analysis. κ statistic was used to quantify the agreement between equations in classifying CKD stages. The impact of selected variables on the difference among equations was graphically explored. The average difference between BIS and FAS was -0.24 (95% limits of agreement (95%LA = -4.64-4.14) mL/min/1.73 m2. The difference between CKD-EPI and BIS and between CKD-EPI and FAS was 8.97 (95%LA = -2.90-20.84) and 8.72 (95%LA = -2.11-19.56) mL/min/1.73 m2, respectively. As regards CKD stage classification, κ value was 0.47 for both CKD-EPI vs. FAS and CKD-EPI vs. BIS, while BIS and FAS had similar classificatory properties (κ = 0.90). Muscle mass was found related to the difference between CKD-EPI and BIS (R2 = 0.11) or FAS (R2 = 0.14), but not to the difference between BIS and FAS. In conclusion, CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people. Muscle mass may represent a relevant source of discrepancy among eGFR equations.

Nyckelord
Berlin Initiative Study (BIS), Full Age Spectrum (FAS), chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), muscle mass, older patients, sarcopenia, sex
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urn:nbn:se:du-31735 (URN)10.3390/jcm9020294 (DOI)000518823000007 ()31973029 (PubMedID)
Tillgänglig från: 2020-01-29 Skapad: 2020-01-29 Senast uppdaterad: 2020-03-26
Shah, S., Henry, A., Roselli, C., Lin, H., Sveinbjörnsson, G., Fatemifar, G., . . . Center, R. G. (2020). Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nature Communications, 11(1), Article ID 163.
Öppna denna publikation i ny flik eller fönster >>Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
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2020 (Engelska)Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 11, nr 1, artikel-id 163Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

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urn:nbn:se:du-31615 (URN)10.1038/s41467-019-13690-5 (DOI)000511898900014 ()31919418 (PubMedID)2-s2.0-85077697294 (Scopus ID)
Tillgänglig från: 2020-01-15 Skapad: 2020-01-15 Senast uppdaterad: 2020-03-12
Nilsson, E., Kastrup, J., Sajadieh, A., Boje Jensen, G., Kjøller, E., Kolmos, H. J., . . . Carlsson, A. C. (2020). Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up: A CLARICOR Trial Sub-Study. Journal of clinical medicine, 9(1), Article ID 265.
Öppna denna publikation i ny flik eller fönster >>Pregnancy Associated Plasma Protein-A as a Cardiovascular Risk Marker in Patients with Stable Coronary Heart Disease During 10 Years Follow-Up: A CLARICOR Trial Sub-Study
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2020 (Engelska)Ingår i: Journal of clinical medicine, ISSN 2077-0383, Vol. 9, nr 1, artikel-id 265Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Elevated pregnancy-associated plasma protein A (PAPP-A) is associated with mortality in acute coronary syndromes. Few studies have assessed PAPP-A in stable coronary artery disease (CAD) and results are conflicting. We assessed the 10-year prognostic relevance of PAPP-A levels in stable CAD. The CLARICOR trial was a randomized controlled clinical trial including outpatients with stable CAD, randomized to clarithromycin versus placebo. The placebo group constituted our discovery cohort (n = 1.996) and the clarithromycin group the replication cohort (n = 1.975). The composite primary outcome was first occurrence of cardiovascular event or death. In the discovery cohort, incidence rates (IR) for the composite outcome were higher in those with elevated PAPP-A (IR 12.72, 95% Confidence Interval (CI) 11.0–14.7 events/100 years) compared to lower PAPP-A (IR 8.78, 8.25–9.34), with comparable results in the replication cohort. Elevated PAPP-A was associated with increased risk of the composite outcome in both cohorts (discovery Hazard Ratio (HR) 1.45, 95% CI 1.24–1.70; replication HR 1.29, 95% CI 1.10–1.52). In models adjusted for established risk factors, these trends were attenuated. Elevated PAPP-A was associated with higher all-cause mortality in both cohorts. We conclude that elevated PAPP-A levels are associated with increased long-term mortality in stable CAD, but do not improve long-term prediction of death or cardiovascular events when added to established predictors.

Nyckelord
biomarkers, cohort studies, coronary artery disease, pregnancy-associated plasma protein-A
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urn:nbn:se:du-31734 (URN)10.3390/jcm9010265 (DOI)000515388400265 ()31963719 (PubMedID)
Tillgänglig från: 2020-01-28 Skapad: 2020-01-28 Senast uppdaterad: 2020-03-12Bibliografiskt granskad
Schroder, J., Jakobsen, J. C., Winkel, P., Hilden, J., Jensen, G. B., Sajadieh, A., . . . Kastrup, J. (2020). Prognosis and Reclassification by YKL-40 in Stable Coronary Artery Disease. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 9(5)
Öppna denna publikation i ny flik eller fönster >>Prognosis and Reclassification by YKL-40 in Stable Coronary Artery Disease
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2020 (Engelska)Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, nr 5Artikel i tidskrift (Refereegranskat) Published
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Kardiologi
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urn:nbn:se:du-32335 (URN)10.1161/JAHA.119.014634 (DOI)2-s2.0-85080839662 (Scopus ID)
Tillgänglig från: 2020-03-19 Skapad: 2020-03-19 Senast uppdaterad: 2020-03-19Bibliografiskt granskad
Lind, L., Gigante, B., Borne, Y., Mälarstig, A., Sundström, J., Ärnlöv, J., . . . Engström, G. (2020). The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: A meta-analysis and a longitudinal evaluation.. Atherosclerosis, 295, 25-30, Article ID S0021-9150(20)30027-7.
Öppna denna publikation i ny flik eller fönster >>The plasma protein profile and cardiovascular risk differ between intima-media thickness of the common carotid artery and the bulb: A meta-analysis and a longitudinal evaluation.
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2020 (Engelska)Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 295, s. 25-30, artikel-id S0021-9150(20)30027-7Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND AND AIMS: Genetic loci associated with CHD show different relationships with intima-media thickness in the common carotid artery (IMT-CCA) and in the bulb (IMT-bulb). We evaluated if IMT-CCA and IMT-bulb differ also with respect to circulating protein profiles and risk of incident atherosclerotic disease.

METHODS: In three Swedish cohorts (MDC, IMPROVE, PIVUS, total n > 7000), IMT-CCA and IMT-bulb were assessed by ultrasound at baseline, and 86 cardiovascular-related proteins were analyzed. In the PIVUS study only, IMT-CCA and IMT-bulb were investigated in relation to incident atherosclerotic disease over 10 years of follow-up.

RESULTS: In a meta-analysis of the analysis performed separately in the cohorts, three proteins, matrix metalloproteinase-12 (MMP-12), hepatocyte growth factor (HGF) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were associated with IMT-CCA when adjusted for traditional cardiovascular risk factors. Five proteins were associated with IMT-bulb (MMP-12, growth/differentiation factor 15 (GDF-15), osteoprotegerin, growth hormone and renin). Following adjustment for cardiovascular risk factors, IMT-bulb was significantly more closely related to incident stroke or myocardial infarction (total number of cases, 111) than IMT-CCA in the PIVUS study (HR 1.51 for 1 SD, 95%CI 1.21-1.87, p < 0.001 vs HR 1.17, 95%CI 0.93-1.47, p = 0.16). MMP-12 levels were related to this combined end-point (HR 1.30, 95%CI 1.08-1.56, p = 0.0061).

CONCLUSIONS: Elevated levels of MMP-12 were associated with both IMT-CCA and IMT-bulb, but other proteins were significantly related to IMT in only one of these locations. The finding that IMT-bulb was more closely related to incident atherosclerotic disease than IMT-CCA emphasizes a difference between these measurements of IMT.

Nyckelord
Atherosclerosis, Carotid artery, Meta-analysis, Proteomics, Ultrasound
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Klinisk medicin
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urn:nbn:se:du-31737 (URN)10.1016/j.atherosclerosis.2020.01.011 (DOI)000512990500004 ()31981948 (PubMedID)2-s2.0-85078552368 (Scopus ID)
Tillgänglig från: 2020-01-30 Skapad: 2020-01-30 Senast uppdaterad: 2020-03-18Bibliografiskt granskad
Wuttke, M., Li, Y., Sieber, K. B., Feitosa, M. F., Gorski, M., Tin, A., . . . Pattaro, C. (2019). A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nature Genetics, 51(6), 957-972
Öppna denna publikation i ny flik eller fönster >>A catalog of genetic loci associated with kidney function from analyses of a million individuals
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2019 (Engelska)Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 6, s. 957-972Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

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urn:nbn:se:du-30209 (URN)10.1038/s41588-019-0407-x (DOI)000469996900008 ()31152163 (PubMedID)2-s2.0-85066607502 (Scopus ID)
Tillgänglig från: 2019-06-13 Skapad: 2019-06-13 Senast uppdaterad: 2019-06-20Bibliografiskt granskad
Lind, L., Salihovic, S., Ganna, A., Sundström, J., Broeckling, C. D., Magnusson, P. K., . . . Ärnlöv, J. (2019). A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke. Journal of Stroke & Cerebrovascular Diseases, 29(2), Article ID 104476.
Öppna denna publikation i ny flik eller fönster >>A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke
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2019 (Engelska)Ingår i: Journal of Stroke & Cerebrovascular Diseases, ISSN 1052-3057, E-ISSN 1532-8511, Vol. 29, nr 2, artikel-id 104476Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND AND PURPOSE: To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach.

METHODS: We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites.

RESULTS: In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR .69 per SD change, 95% CI .57-0.83, P value = .00014; FDR <5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P < .0069 and .0026, respectively).

CONCLUSIONS: An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies.

Nyckelord
Epidemiology, metabolomics, risk factor, stroke
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Klinisk medicin
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urn:nbn:se:du-31198 (URN)10.1016/j.jstrokecerebrovasdis.2019.104476 (DOI)000505793800001 ()31806450 (PubMedID)2-s2.0-85076201064 (Scopus ID)
Tillgänglig från: 2019-12-09 Skapad: 2019-12-09 Senast uppdaterad: 2020-03-19Bibliografiskt granskad
Mok, Y., Ballew, S. H., Sang, Y., Grams, M. E., Coresh, J., Evans, M., . . . Matsushita, K. (2019). Albuminuria as a predictor of cardiovascular outcomes in patients with acute myocardial infarction. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(8), Article ID e010546.
Öppna denna publikation i ny flik eller fönster >>Albuminuria as a predictor of cardiovascular outcomes in patients with acute myocardial infarction
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2019 (Engelska)Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, nr 8, artikel-id e010546Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background. In patients with myocardial infarction ( MI ), reduced kidney function is recognized as an important predictor of poor prognosis, but the impact of albuminuria, a representative measure of kidney damage, has not been extensively evaluated.

Methods and Results. In the SCREAM (Stockholm Creatinine Measurements) project (2006-2012), we identified 2469 patients with incident MI with dipstick proteinuria measured within a year before MI (427 patients also had urine albumin to creatinine ratio [ ACR ] measured concurrently) and obtained estimates for ACR with multiple imputation in participants with data solely on dipstick proteinuria. We quantified the association of ACR with the post- MI composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI , ischemic stroke, or heart failure using Cox models and then evaluated the improvement in C statistic. During a median follow-up of 1.0 year after MI , 1607 participants (65.1%) developed the post- MI composite outcome. Higher ACR levels were independently associated with all outcomes except for ischemic stroke. Per 8-fold higher ACR (eg, 40 versus 5 mg/g), the hazard ratio of composite outcome was 1.21 (95% CI , 1.08-1.35). The addition of the ACR improved the C statistic of the post- MI composite by 0.040 (95% CI, 0.030-0.051). Largely similar results were obtained regardless of diabetic status and when ACR or dipstick was separately analyzed without imputation.

Conclusions. In patients with MI , albuminuria was a potent predictor of subsequent outcomes, suggesting the importance of paying attention to the information on albuminuria, in addition to kidney function, in this high-risk population.

Nyckelord
albuminuria, chronic kidney disease, myocardial infarction, prognosis
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Klinisk medicin
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urn:nbn:se:du-29863 (URN)10.1161/JAHA.118.010546 (DOI)000484574500003 ()30947615 (PubMedID)2-s2.0-85064323096 (Scopus ID)
Tillgänglig från: 2019-04-08 Skapad: 2019-04-08 Senast uppdaterad: 2019-09-20Bibliografiskt granskad
Fellström, B., Helmersson-Karlqvist, J., Lind, L., Soveri, I., Wu, P.-H., Thulin, M., . . . Larsson, A. (2019). Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females. Journal of Interferon and Cytokine Research
Öppna denna publikation i ny flik eller fönster >>Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females
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2019 (Engelska)Ingår i: Journal of Interferon and Cytokine Research, ISSN 1079-9907, E-ISSN 1557-7465Artikel i tidskrift (Refereegranskat) Epub ahead of print
Abstract [en]

There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1α, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.

Nyckelord
HDL cholesterol, apolipoprotein A1, cytokines, multiplex assays, urine
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Klinisk medicin
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urn:nbn:se:du-30960 (URN)10.1089/jir.2019.0074 (DOI)000510520300001 ()31599692 (PubMedID)2-s2.0-85078867559 (Scopus ID)
Tillgänglig från: 2019-10-16 Skapad: 2019-10-16 Senast uppdaterad: 2020-03-18Bibliografiskt granskad
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ORCID-id: ORCID iD iconorcid.org/0000-0002-6933-4637

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