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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
Open this publication in new window or tab >>Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging
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2020 (English)In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 28, no 1, p. 178-186Article in journal (Refereed) 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.

National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-31200 (URN)10.1002/oby.22660 (DOI)000500583200001 ()31804015 (PubMedID)2-s2.0-85077106134 (Scopus ID)
Available from: 2019-12-09 Created: 2019-12-09 Last updated: 2020-01-07Bibliographically approved
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.
Open this publication in new window or tab >>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 (English)In: Journal of clinical medicine, ISSN 2077-0383, Vol. 9, no 2, article id E294Article in journal (Refereed) 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.

Keywords
Berlin Initiative Study (BIS), Full Age Spectrum (FAS), chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), muscle mass, older patients, sarcopenia, sex
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-31735 (URN)10.3390/jcm9020294 (DOI)000518823000007 ()31973029 (PubMedID)
Available from: 2020-01-29 Created: 2020-01-29 Last updated: 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.
Open this publication in new window or tab >>Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
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2020 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 11, no 1, article id 163Article in journal (Refereed) 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.

National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-31615 (URN)10.1038/s41467-019-13690-5 (DOI)000511898900014 ()31919418 (PubMedID)2-s2.0-85077697294 (Scopus ID)
Available from: 2020-01-15 Created: 2020-01-15 Last updated: 2020-03-12
Lind, L., Risérus, U. & Ärnlöv, J. (2020). Impact of the Definition of Metabolically Healthy Obesity on the Association with Incident Cardiovascular Disease. Metabolic Syndrome and Related Disorders
Open this publication in new window or tab >>Impact of the Definition of Metabolically Healthy Obesity on the Association with Incident Cardiovascular Disease
2020 (English)In: Metabolic Syndrome and Related Disorders, ISSN 1540-4196, E-ISSN 1557-8518Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background: Whether subjects with metabolically healthy obesity (MHO) have an increased risk of cardiovascular disease (CVD) is controversial. Some of this discrepancy could be due to differences in the definition of MHO. Therefore, we investigated how the definition of MHO affected the risk of CVD. Methods: In the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort (total n = 2122, mean age 50 years), obese (n = 134), overweight (n = 845), and normal weight (n = 1143) individuals were subdivided according to the number of Metabolic Syndrome (MetS) risk factors (excluding waist circumference). During a median follow-up of 28.0 years, 877 individuals experienced a CVD event (defined as fatal or nonfatal myocardial infarction, stroke, or heart failure). Results: All obese groups, except that without any MetS risk factors (n = 3), showed an increased risk compared to the control group of normal weight without any MetS risk factors (n = 235), ranging from a hazard ratio (HR) of 3.0 (95% confidence interval [CI] 1.7-5.3, P = 0.0002) in those with one MetS risk factor to HR 5.5 (95% CI 3.0-9.8, P < 0.00001) in those with four MetS risk factors. The overweight group without any MetS risk factor (n = 74) showed a similar risk of incident CVD as the normal weight group, whereas all other overweight groups showed an increased risk with increasing number of MetS risk factors. Conclusions: The results suggest that the definition of MHO played a major role on the risk of CVD. No increased risk was seen in overweight/obese individuals with no MetS risk factor, but they were very rare.

Keywords
cardiovascular disease, epidemiology, metabolic syndrome, metabolically healthy obesity, obesity
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-32894 (URN)10.1089/met.2020.0016 (DOI)32397901 (PubMedID)
Available from: 2020-05-18 Created: 2020-05-18 Last updated: 2020-05-18Bibliographically approved
Kinyoki, D., Ross, J., Lazzar-Atwood, A., Munro, S., Schaeffer, L., Abbasalizad-Farhangi, M., . . . Hai, S. (2020). Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017. Nature Medicine, 26, 750-759
Open this publication in new window or tab >>Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017
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2020 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 26, p. 750-759Article in journal (Refereed) In press
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-32859 (URN)10.1038/s41591-020-0807-6 (DOI)2-s2.0-85084142866 (Scopus ID)
Available from: 2020-05-11 Created: 2020-05-11 Last updated: 2020-05-11
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.
Open this publication in new window or tab >>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 (English)In: Journal of clinical medicine, ISSN 2077-0383, Vol. 9, no 1, article id 265Article in journal (Refereed) 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.

Keywords
biomarkers, cohort studies, coronary artery disease, pregnancy-associated plasma protein-A
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-31734 (URN)10.3390/jcm9010265 (DOI)000515388400265 ()31963719 (PubMedID)
Available from: 2020-01-28 Created: 2020-01-28 Last updated: 2020-03-12Bibliographically approved
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), Article ID e014634.
Open this publication in new window or tab >>Prognosis and Reclassification by YKL-40 in Stable Coronary Artery Disease
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2020 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 9, no 5, article id e014634Article in journal (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-32335 (URN)10.1161/JAHA.119.014634 (DOI)000527012600030 ()32114892 (PubMedID)2-s2.0-85080839662 (Scopus ID)
Available from: 2020-03-19 Created: 2020-03-19 Last updated: 2020-05-08Bibliographically approved
Bjerre, M., Hilden, J., Winkel, P., Jensen, G. B., Kjøller, E., Sajadieh, A., . . . Gluud, C. (2020). Serum osteoprotegerin as a long-term predictor for patients with stable coronary artery disease and its association with diabetes and statin treatment: A CLARICOR trial 10-year follow-up substudy. Atherosclerosis, 301, 8-14
Open this publication in new window or tab >>Serum osteoprotegerin as a long-term predictor for patients with stable coronary artery disease and its association with diabetes and statin treatment: A CLARICOR trial 10-year follow-up substudy
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2020 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 301, p. 8-14Article in journal (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-32636 (URN)10.1016/j.atherosclerosis.2020.03.030 (DOI)2-s2.0-85083007916 (Scopus ID)
Available from: 2020-05-06 Created: 2020-05-06 Last updated: 2020-05-06Bibliographically approved
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.
Open this publication in new window or tab >>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 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 295, p. 25-30, article id S0021-9150(20)30027-7Article in journal (Refereed) 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.

Keywords
Atherosclerosis, Carotid artery, Meta-analysis, Proteomics, Ultrasound
National Category
Clinical Medicine
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-31737 (URN)10.1016/j.atherosclerosis.2020.01.011 (DOI)000512990500004 ()31981948 (PubMedID)2-s2.0-85078552368 (Scopus ID)
Available from: 2020-01-30 Created: 2020-01-30 Last updated: 2020-03-18Bibliographically approved
Wändell, P., Carlsson, A. C., Larsson, A., Melander, O., Wessman, T., Ärnlöv, J. & Ruge, T. (2020). TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department. Acta Diabetologica
Open this publication in new window or tab >>TNFR1 is associated with short-term mortality in patients with diabetes and acute dyspnea seeking care at the emergency department
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2020 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233Article in journal (Refereed) Epub ahead of print
Abstract [en]

Background Circulating levels of TNF alpha receptor 1 (TNFR1) and 2 (TNFR2) are associated with increased long-term mortality and impaired kidney function. Aim To study association between circulating levels of TNFR1 and TNFR2 and short-term mortality in patients with diabetes and dyspnea. Population and methods Patients aged >= 18 years seeking at emergency department (ED) during daytime on weekdays between December 2013 and July 2018, with diabetes and acute dyspnea, identified at the triage process, were included. Participants (n = 291) were triaged according to Medical Emergency Triage and Treatment System-Adult score, and blood samples were collected. Association between TNFR1 and TNFR2, respectively, and 90-day mortality were estimated by Cox regression models adjusted for age, sex, BMI, creatinine and CRP. Results Univariate models showed significant associations between TNFR1 and TNFR2, respectively, and CRP, age and creatinine. TNFR1 and TNFR2 tended to be elevated in patients with the highest triage level, compared to patients with lower triage levels (ns). In longitudinal analyses, TNFR1 but not TNFR2 was associated with increased short-term mortality, HR adjusted for age, BMI and creatinine 1.43 (95% CI 1.07-1.91), but not in the model also adjusted for CRP, HR 1.29 (95% CI 0.94-1.77). In secondary analysis for quartile 4 versus quartiles 1-3 of TNFR1, corresponding HRs were 2.46 (95% CI 1.27-5.15) and 2.21 (95% CI 1.07-2.56). Conclusions We found a trend for the association between circulating TNFR1 levels and short-term mortality in patients with diabetes and acute dyspnea at the ED, possibly suggesting an inflammatory pathway for the association.

National Category
Health Sciences
Research subject
Health and Welfare
Identifiers
urn:nbn:se:du-32620 (URN)10.1007/s00592-020-01527-3 (DOI)000525337600002 ()32281000 (PubMedID)2-s2.0-85083110063 (Scopus ID)
Available from: 2020-05-06 Created: 2020-05-06 Last updated: 2020-05-06Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6933-4637

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