261 results on '"Johan Ärnlöv"'
Search Results
2. Estimating the prevalence of chronic kidney disease while accounting for nonrandom testing with inverse probability weighting
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Faizan Mazhar, Arvid Sjölander, Edouard L. Fu, Johan Ärnlöv, Andrew S. Levey, Josef Coresh, and Juan Jesus Carrero
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Nephrology - Published
- 2022
3. Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes
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Elena Tremoli, Pär Hedberg, Tobias Feldreich, Bruna Gigante, Marju Orho-Melander, Jerzy Leppert, Lars Lind, Anders Hamsten, Johan Sundström, Carl Johan Östgren, Anders Mälarstig, Fabrizio Veglia, Christopher J. O'Donnell, Nora Franceschini, Fredrik H. Nystrom, Gunnar Engström, Johan Ärnlöv, Olle Melander, Yan Borné, Jan Nilsson, and Damiano Baldassarre
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Carotid Artery Diseases ,Male ,Proteomics ,medicine.medical_specialty ,Proteome ,medicine.drug_class ,Carotid Intima-Media Thickness ,Risk Assessment ,Risk Factors ,Matrix Metalloproteinase 12 ,medicine.artery ,Internal medicine ,Mendelian randomization ,medicine ,Natriuretic peptide ,Humans ,Cardiac and Cardiovascular Systems ,cardiovascular diseases ,Common carotid artery ,Myocardial infarction ,Receptor ,Aged ,Sweden ,Kardiologi ,business.industry ,Incidence ,Genetic Variation ,Mendelian Randomization Analysis ,Blood Proteins ,Middle Aged ,Prognosis ,medicine.disease ,Blood proteins ,Plaque, Atherosclerotic ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Lipoprotein - 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 =5.5×10 −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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- 2021
4. Obstructive sleep apnea is associated with specific gut microbiota species and functions in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS)
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Gabriel Baldanzi, Sergi Sayols-Baixeras, Jenny Theorell-Haglöw, Koen F Dekkers, Ulf Hammar, Diem Nguyen, Yi-Ting Lin, Shafqat Ahmad, Jacob Bak Holm, Henrik Bjørn Nielsen, Louise Brunkwall, Christian Benedict, Jonathan Cedernaes, Sanna Koskiniemi, Mia Phillipson, Lars Lind, Johan Sundström, Göran Bergström, Gunnar Engström, J Gustav Smith, Marju Orho-Melander, Johan Ärnlöv, Beatrice Kennedy, Eva Lindberg, and Tove Fall
- Abstract
Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. In animal models, OSA has been shown to alter the gut microbiota; however, little is known about such effects in humans. Here, we used respiratory polygraphy data from 3,570 individuals aged 50–64 from the Swedish CardioPulmonary bioImage Study (SCAPIS) and deep shotgun metagenomics to identify OSA-associated gut microbiota features. We found that OSA-related hypoxia parameters were associated with 128 bacterial species, including positive associations with Blautia obeum and Collinsela aerofacines. The latter was also associated with increased systolic blood pressure. Further, the cumulative time in hypoxia was associated with nine gut microbiota metabolic pathways, including propionate production from lactate, a biomarker of hypoxia. In conclusion, in this first large-scale study on gut microbiota alterations in OSA, we found that OSA-related hypoxia is associated with specific microbiota features. Our findings can direct future research on microbiota-mediated health effects of OSA.
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- 2022
5. Streptococcusspecies abundance in the gut is linked to subclinical coronary atherosclerosis in 8973 participants from the SCAPIS cohort
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Sergi Sayols-Baixeras, Koen F. Dekkers, Gabriel Baldanzi, Daniel Jönsson, Ulf Hammar, Yi-Ting Lin, Shafqat Ahmad, Diem Nguyen, Georgios Varotsis, Sara Pita, Nynne Nielsen, Aron C. Eklund, Jacob B. Holm, H. Bjørn Nielsen, Ulrika Ericson, Louise Brunkwall, Filip Ottosson, Anna Larsson, Dan Ericson, Björn Klinge, Peter M. Nilsson, Andrei Malinovschi, Lars Lind, Göran Bergström, Johan Sundström, Johan Ärnlöv, Gunnar Engström, J. Gustav Smith, Marju Orho-Melander, and Tove Fall
- Abstract
BACKGROUNDGut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography-based measures of coronary atherosclerosis, and to explore relevant clinical correlates.METHODSWe conducted a cross-sectional study of 8973 participants aged 50 to 65 without overt atherosclerotic disease from the population-based Swedish Cardiopulmonary BioImage Study (SCAPIS). Coronary atherosclerosis was measured using coronary artery calcium score (CACS) and coronary computed tomography angiography (CCTA). Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool samples, and their association with coronary atherosclerosis was evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTSThe mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3% of participants, and 5.4% had at least one stenosis with more than 50% occlusion. Sixty-four species were associated with CACS independent of cardiovascular risk factors, with the strongest associations observed forStreptococcus anginosusandS. oralissubsp. oralis(P-5). Associations were largely similar across CCTA-based measurements. Out of the 64 species, 19 species, including streptococci and other species commonly found in the oral cavity, were associated with high-sensitivity C-reactive protein plasma concentrations and 16 with neutrophil counts. Oral species in the gut were negatively associated with plasma indole propionate and positively associated with plasma secondary bile acids and imidazole propionate. Five species correlated with the same species in saliva and were associated with worse dental health in the Malmö Offspring Dental Study. Microbial functional potential of dissimilatory nitrate reduction, anaerobic fatty acid beta-oxidation and amino acid degradation was associated with CACS.CONCLUSIONSThis study provides evidence of an association of a gut microbiota composition characterized by increased abundance ofStreptococcusspp. and other species commonly found in the oral cavity with coronary atherosclerosis and systemic inflammation. Further longitudinal and experimental studies are warranted to explore the potential implication of a bacterial component in atherogenesis.CLINICAL PERSPECTIVEWHAT IS NEW?Shotgun metagenomics identified associations between gut species and subclinical atherosclerosis assessed with computed tomography-derived coronary artery calcium score (CACS) in 8973 participants, with an overrepresentation of theStreptococcusandOscillobactergenera.The relative abundance of CACS-associated oral species detected in fecal samples was negatively associated with indole propionate, while positively associated with secondary bile acids and imidazole propionate.GutStreptococcusspp. were positively associated with circulating biomarkers of systemic inflammation and infection response, and with the same species located in the mouth, which were in turn associated with oral pathologies.WHAT ARE THE CLINICAL IMPLICATIONS?We describe the link between gut microbiota composition, especially species commonly found in the mouth, with subclinical coronary atherosclerosis and biomarkers of inflammation in the largest cardiovascular and metagenomics study to date.The effects of gut and oralStreptococcusspp. on risk for coronary artery disease merit further longitudinal and experimental studies.
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- 2022
6. Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease
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Philippe Wagner, Emma Skau, Johan Ärnlöv, Jerzy Leppert, Pär Hedberg, and Egil Henriksen
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Male ,Proteomics ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Population ,030204 cardiovascular system & hematology ,Risk Assessment ,Peripheral Arterial Disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Outpatients ,medicine ,Humans ,education ,Aged ,education.field_of_study ,Framingham Risk Score ,Receiver operating characteristic ,business.industry ,Proportional hazards model ,Blood proteins ,Confidence interval ,030104 developmental biology ,Cohort ,Female ,GDF15 ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Follow-Up Studies - Abstract
Background and aims Patients with peripheral arterial disease (PAD) are at high risk for fatal events. We aimed to investigate the ability among several serum proteins to predict all-cause mortality in outpatients with PAD. Methods Consecutive outpatients with carotid and/or lower extremity PAD were included in the discovery cohort (n = 436), and subjects with PAD from a population-based sample in the validation cohort (n = 129). Blood samples were analyzed for 81 proteins by a proximity extension assay. The proteins best predicting incident all-cause mortality were identified using L1-regularized Cox regression. The added value of the identified proteins to clinical risk markers was evaluated by Cox regression models and presented by the area under the receiver operator characteristics curves (AUC). Results In the discovery cohort (mean age 70 years; 59% men), 195 died (4.8 events per 100 person-years) during a 10.3 years median follow-up. The clinical risk markers generated an AUC of 0.70 (95% confidence interval [95%CI] 0.65–0.76). The two serum protein biomarkers with best prediction of all-cause mortality were growth differentiation factor 15 and tumor necrosis factor-related apoptosis-inducing ligand receptor 2. Adding these proteins to the clinical risk markers significantly improved prediction (p Conclusions In a large-sample targeted proteomics assay, we identified two proteins that improved risk prediction beyond the COPART risk score. The use of high-throughput proteomics assays may identify potential biomarkers for improved risk prediction in patients with PAD.
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- 2020
7. Patterns of multimorbidity and pharmacotherapy: a total population cross-sectional study
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Johan Ärnlöv, Gunnar Ljunggren, Caroline Wachtler, Tomas Forslund, and Axel C. Carlsson
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Prescription drug ,multimorbidity ,Epidemiology ,Population ,frailty ,phamacology/drug reactions ,030204 cardiovascular system & hematology ,Chronic disease ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Ambulatory care ,Risk of mortality ,Humans ,Medicine ,030212 general & internal medicine ,Medical prescription ,AcademicSubjects/MED00780 ,education ,Polypharmacy ,education.field_of_study ,business.industry ,Mortality rate ,Public Health, Global Health, Social Medicine and Epidemiology ,primary health care ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,Cross-Sectional Studies ,Family Practice ,business ,population health ,Demography ,Cohort study - Abstract
Background Treatment of multimorbid patients can be improved. Development of patient-centred care of high-quality requires context-bound understanding of the multimorbid population’s patterns of demographics, co-morbidities and medication use. Objective The aim of this study was to identify patterns of multimorbidity in the total population of Region Stockholm, Sweden, by exploring demographics, claimed prescription drugs, risk of mortality and non-random association of conditions. Methods In this cross-sectional descriptive population-based cohort study, we extracted data from the Swedish VAL database (N = 2 323 667) including all consultations in primary and specialized outpatient care, all inpatient care and all prescriptions claimed during 2017. We report number of chronic conditions and claimed prescription drugs, physical and mental co-morbidity, and 1-year mortality. We stratified the analyses by sex. We examined non-random associations between diseases using cluster analysis. Results In total, 21.6% had multimorbidity (two or more chronic conditions) and 24.1% had polypharmacy (more than five claimed prescription drugs). Number of claimed drugs, co-occurrence of mental and physical conditions, and 1-year mortality increased as multimorbidity increased. We identified seven multimorbidity clusters with clinically distinct characteristics. The smallest cluster (7% of individuals) had prominent cardiovascular disease, the highest 1-year mortality rate, high levels of multimorbidity and polypharmacy, and was much older. The largest cluster (27% of individuals) was younger and heterogenous, with primarily mental health problems. Conclusions Individuals with chronic conditions often show clinical complexity with both concordant and discordant conditions and polypharmacy. This study indicates that clinical guidelines addressing clustering of conditions may be one strategy for managing complexity.
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- 2020
8. Impact of the Definition of Metabolically Healthy Obesity on the Association with Incident Cardiovascular Disease
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Ulf Risérus, Johan Ärnlöv, and Lars Lind
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Male ,medicine.medical_specialty ,Time Factors ,Endocrinology, Diabetes and Metabolism ,Disease ,Risk Assessment ,Terminology as Topic ,Internal medicine ,Epidemiology ,Metabolically healthy obesity ,Internal Medicine ,medicine ,Humans ,Longitudinal Studies ,Sweden ,Obesity, Metabolically Benign ,business.industry ,Incidence ,Cardiometabolic Risk Factors ,Middle Aged ,Prognosis ,medicine.disease ,Obesity ,Increased risk ,Cardiovascular Diseases ,Metabolic syndrome ,business - Abstract
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 i...
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- 2020
9. Plant-based diets, insulin sensitivity and inflammation in elderly men with chronic kidney disease
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Ailema González-Ortiz, Tommy Cederholm, Ángeles Espinosa-Cuevas, Carla Maria Avesani, Ulf Risérus, Bengt Lindholm, Hong Xu, Juan Jesus Carrero, and Johan Ärnlöv
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Male ,Nephrology ,Protein-energy wasting ,medicine.medical_specialty ,Potasssium ,Renal function ,Disease ,Vegetable ,Lower risk ,Gastroenterology ,Internal medicine ,Diabetes mellitus ,Urologi och njurmedicin ,Restriction ,medicine ,Animals ,Humans ,Urology and Nephrology ,Renal Insufficiency, Chronic ,Aged ,Inflammation ,business.industry ,Diet, Vegetarian ,Malnutrition ,Klinisk medicin ,Glucose clamp technique ,medicine.disease ,Cross-Sectional Studies ,Fruit ,Original Article ,Insulin Resistance ,Clinical Medicine ,business ,Glomerular Filtration Rate ,Kidney disease - Abstract
Background In persons with CKD, adherence to plant-based diets is associated with lower risk of CKD progression and death, but underlying mechanisms are poorly characterized. We here explore associations between adherence to plant-based diets and measures of insulin sensitivity and inflammation in men with CKD stages 3–5. Methods Cross-sectional study including 418 men free from diabetes, aged 70–71 years and with cystatin-C estimated glomerular filtration rate (eGFR) 2 and not receiving kidney-specific dietetic advice. Information from 7-day food records was used to evaluate the adherence to a plant-based diet index (PBDi), which scores positively the intake of plant-foods and negatively animal-foods. Insulin sensitivity and glucose disposal rate were assessed with the gold-standard hyperinsulinemic euglycemic glucose clamp technique. Inflammation was evaluated by serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6. Associations were explored through linear regression and restricted cubic splines. Results The majority of men had CKD stage 3a. Hypertension and cardiovascular disease were the most common comorbidities. The median PBDi was 38 (range 14–55). Across higher quintiles of PBDi (i.e. higher adherence), participants were less often smokers, consumed less alcohol, had lower BMI and higher eGFR (P for trend Conclusion In elderly men with non-dialysis CKD stages 3–5, adherence to a plant-based diet was associated with higher insulin sensitivity and lower inflammation, supporting a possible role of plant-based diets in the prevention of metabolic complications of CKD. Graphic abstract
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- 2020
10. 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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Gunnar Engström, Johan Ärnlöv, Fabrizio Veglia, Marju Orho-Melander, Lars Lind, Anders Mälarstig, Bruna Gigante, Johan Sundström, Elena Tremoli, Jan Nilsson, Anders Hamsten, Yan Borné, Erik Ingelsson, Olle Melander, and Damiano Baldassarre
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Male ,0301 basic medicine ,medicine.medical_specialty ,Carotid Artery, Common ,medicine.drug_class ,030204 cardiovascular system & hematology ,Carotid Intima-Media Thickness ,03 medical and health sciences ,0302 clinical medicine ,Osteoprotegerin ,Internal medicine ,medicine.artery ,medicine ,Natriuretic peptide ,Humans ,Longitudinal Studies ,cardiovascular diseases ,Common carotid artery ,Myocardial infarction ,Stroke ,Aged ,Sweden ,business.industry ,Incidence ,Blood Proteins ,Middle Aged ,musculoskeletal system ,medicine.disease ,Blood proteins ,030104 developmental biology ,Intima-media thickness ,Cardiovascular Diseases ,Meta-analysis ,cardiovascular system ,Cardiology ,Intercellular Signaling Peptides and Proteins ,Female ,Cardiology and Cardiovascular Medicine ,business ,tissues - Abstract
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.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.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).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.
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- 2020
11. Association of Test Results for 33 Frequently Used Laboratory Tests with Body Mass Index (BMI)
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Anders Larsson, Johan Ärnlöv, Johanna Helmersson-Karlqvist, Lars Lind, and Peter Ridefelt
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Creatinine ,medicine.medical_specialty ,education.field_of_study ,biology ,Apolipoprotein B ,business.industry ,Transferrin saturation ,Cholesterol ,Population ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Cystatin C ,Internal medicine ,biology.protein ,Medicine ,Apolipoprotein A1 ,business ,education ,Body mass index - Abstract
Once considered a problem only for high-income countries, obesity rates are now rising worldwide. When evaluating test results from obese patients it is important to be aware of the effect of obesity on individual laboratory test results. The aim of the present study was to study the association between body mass index (BMI) and a group of frequently requested laboratory tests to evaluate which of these analytes that are affected by BMI. We analyzed the association between body mass index (BMI) and Alanine aminotransaminase (ALT), Albumin, Alkaline phosphatase, Pancreatic amylase, Apolipoprotein A1, Apolipoprotein B, Apolipoprotein B/Apolipoprotein A1 ratio, Aspartate aminotransferase (AST), AST/ALT ratio, Bilirubin, Calcium, Calprotectin, Cholesterol, HDL-cholesterol, Creatinine kinase (CK), Creatinine, C-reactive protein, Cystatin C, Gamma-glutamyl transferase (GGT), Iron, Iron saturation, Lactate dehydrogenase (LDH), Magnesium, Phosphate, Transferrin, Triglycerides, Urate, Urea, Zink, Hemoglobin, Platelet count and White blood cell count in an 80-year old population (n=531, 266 females and 265 males). There were significant Spearman rank associations between BMI and laboratory test results for several of the studied markers in both females and males. The strongest associations with BMI were noted for ALT, Apolipoprotein A1, HDL-cholesterol, Hemoglobin, CRP, Cystatin C, Triglycerides and Urate. In conclusion, several of the most frequently used laboratory markers are significantly associated with BMI. To be able to correctly interpret a test result it is important to be aware of the effects of BMI on the test results.
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- 2020
12. Endostatin predicts mortality in patients with acute dyspnea – A cohort study of patients seeking care in emergency departments
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Rafid Tofik, Olle Melander, Johan Ärnlöv, Thoralph Ruge, Axel C. Carlsson, G Leijonberg, Torgny Wessman, and Anders Larsson
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Male ,030213 general clinical medicine ,medicine.medical_specialty ,Clinical Biochemistry ,Population ,macromolecular substances ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Epidemiology ,medicine ,Humans ,Hospital Mortality ,education ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,General Medicine ,Emergency department ,Middle Aged ,Triage ,Endostatins ,Dyspnea ,Acute Disease ,Cohort ,cardiovascular system ,Female ,Endostatin ,Emergency Service, Hospital ,business ,Body mass index ,Biomarkers ,Cohort study - Abstract
Background: Increased levels of circulating endostatin predicts cardiovascular morbidity and impaired kidney function in the general population. The utility of endostatin as a risk marker for mortality in the emergency department (ED) has not been reported. Aim: Our main aim was to study the association between plasma endostatin and 90-day mortality in an unselected cohort of patients admitted to the ED for acute dyspnea. Design Circulating endostatin was analyzed in plasma from 1710 adults and related to 90-day mortality in Cox proportional hazard models adjusted for age, sex, body mass index, oxygen saturation, respiratory rate, body temperature, C-reactive protein, lactate, creatinine and medical priority according to the Medical Emergency Triage and Treatment System–Adult score (METTS-A). The predictive value of endostatin for mortality was evaluated with receiver operating characteristic (ROC) analysis and compared with the clinical triage scoring system and age. Results: Each one standard deviation increment of endostatin was associated with a HR of 2.12 (95% CI 1.31–3.44 p < 0.01) for 90-day mortality after full adjustment. Levels of endostatin were significantly increased in the group of patients with highest METTS-A (p < 0.001). When tested for the outcome 90-day mortality, the area under the ROC curve (AUC) was 0.616 for METTS-A, 0.701 for endostatin, 0.708 for METTS -A and age and 0.738 for METTS-A, age and levels of endostatin. Conclusions: In an unselected cohort of patients admitted to the ED with acute dyspnea, endostatin had a string association to 90-day mortality and improved prediction of 90-day mortality in the ED beyond the clinical triage scoring system and age with 3%. (Less)
- Published
- 2020
13. Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study
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Shafqat Ahmad, Johan Ärnlöv, and Susanna C. Larsson
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Nutrition and Dietetics ,estimated glomerular filtration rate ,Nutrition. Foods and food supply ,circulating nutrients ,Mendelian Randomization Analysis ,kidney related disease ,Urologi och njurmedicin ,Mendelian randomization ,Urology and Nephrology ,Humans ,TX341-641 ,Genetic Predisposition to Disease ,Renal Insufficiency, Chronic ,Copper ,Food Science ,Glomerular Filtration Rate - Abstract
Elevated circulating copper levels have been associated with chronic kidney disease (CKD), kidney damage, and decline in kidney function. Using a two sample Mendelian randomization approach where copper-associated genetic variants were used as instrumental variables, genetically predicted higher circulating copper levels were associated with higher CKD prevalence (odds ratio 1.17; 95% confidence interval 1.04, 1.32; p-value = 0.009). There was suggestive evidence that genetically predicted higher copper was associated with a lower estimated glomerular filtration rate and a more rapid kidney damage decline. In conclusion, we observed that elevated circulating copper levels may be a causal risk factor for CKD. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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- 2022
14. The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation
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Linnea Malmgren, Carl Öberg, Emil den Bakker, Felicia Leion, Joanna Siódmiak, Anna Åkesson, Veronica Lindström, Erik Herou, Alain Dardashti, Liana Xhakollari, Gabriel Grubb, Helena Strevens, Magnus Abrahamson, Johanna Helmersson‐Karlqvist, Martin Magnusson, Jonas Björk, Ulf Nyman, Johan Ärnlöv, Peter Ridefelt, Torbjörn Åkerfeldt, Magnus Hansson, Anna Sjöström, Johan Mårtensson, Yoshihisa Itoh, David Grubb, Olav Tenstad, Lars‐Olov Hansson, Isleifur Olafsson, Araceli Jarquin Campos, Martin Risch, Lorenz Risch, Anders Larsson, Gunnar Nordin, Hans Pottel, Anders Christensson, Henrik Bjursten, Arend Bökenkamp, and Anders Grubb
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proteomics ,kidney disease ,Urologi och njurmedicin ,Internal Medicine ,Urology and Nephrology ,610 Medizin und Gesundheit - Abstract
Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous GFR-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterised by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules < 1kDa dominating the glomerular filtrate e.g., water, urea, creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterised by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines. This article is protected by copyright. All rights reserved.
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- 2022
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15. Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging
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Erik Ingelsson, Lars Lind, Johan Sundström, Johan Ärnlöv, Sylwia M. Figarska, and Tove Fall
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medicine.medical_specialty ,Longitudinal study ,Nutrition and Dietetics ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,030209 endocrinology & metabolism ,PTX3 ,Biology ,Blood proteins ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Cohort ,medicine ,sense organs ,030212 general & internal medicine ,skin and connective tissue diseases ,Prospective cohort study ,Receptor ,Body mass index ,Lipoprotein - Abstract
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 0.05): 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 0.05): 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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- 2019
16. An online atlas of human plasma metabolite signatures of gut microbiome composition
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Koen F. Dekkers, Sergi Sayols-Baixeras, Gabriel Baldanzi, Christoph Nowak, Ulf Hammar, Diem Nguyen, Georgios Varotsis, Louise Brunkwall, Nynne Nielsen, Aron C. Eklund, Jacob Bak Holm, H. Bjørn Nielsen, Filip Ottosson, Yi-Ting Lin, Shafqat Ahmad, Lars Lind, Johan Sundström, Gunnar Engström, J. Gustav Smith, Johan Ärnlöv, Marju Orho-Melander, and Tove Fall
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Multidisciplinary ,General Physics and Astronomy ,Gastroenterology and Hepatology ,General Chemistry ,Middle Aged ,Microbiology ,digestive system ,General Biochemistry, Genetics and Molecular Biology ,Gastrointestinal Microbiome ,Mikrobiologi ,Cross-Sectional Studies ,Gastroenterologi ,Metabolome ,Humans ,Metabolomics ,Uremic Toxins ,Biomarkers - Abstract
Summary paragraphThe human gut microbiota produces a variety of small compounds, some of which enter the bloodstream and impact host health. Conversely, various exogenous nutritional and pharmaceutical compounds affect the gut microbiome composition before entering circulation. Characterization of the gut microbiota–host plasma metabolite interactions is an important step towards understanding the effects of the gut microbiota on human health. However, studies involving large and deeply phenotyped cohorts that would reveal such meaningful interactions are scarce. Here, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for detailed characterization of the fecal microbiota and plasma metabolome, respectively, of 8,584 participants invited at age 50 to 64 of the Swedish CArdioPulmonary bioImage Study (SCAPIS). After adjusting for multiple comparisons, we identified 1,008 associations between species alpha diversity and plasma metabolites, and 318,944 associations between specific gut metagenomic species and plasma metabolites. The gut microbiota explained up to 50% of the variance of individual plasma metabolites (mean of 4.7%). We present all results as the searchable association atlas “GUTSY” as a rich resource for mining associations, and exemplify the potential of the atlas by presenting novel associations between oral medication and the gut microbiome, and microbiota species strongly associated with levels of the uremic toxin p-cresol sulfate. The association atlas can be used as the basis for targeted studies of perturbation of specific bacteria and for identification of candidate plasma biomarkers of gut flora composition.
- Published
- 2021
17. Plasma calprotectin in the emergency department: a potential clinical biomarker for patients with infectious diseases
- Author
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Per Wändell, Toralph Ruge, Mari Rosenqvist, Torgny Wessman, Johan Ärnlöv, Anders Larsson, Olle Melander, and Martin Wollmer
- Subjects
Male ,medicine.medical_specialty ,Infectious Medicine ,Clinical Biochemistry ,communicable diseases ,Infektionsmedicin ,leukocyte L1 antigen complex (calprotectin) ,Communicable Diseases ,C-reactive protein ,fluids and secretions ,Risk Factors ,Internal medicine ,medicine ,Leukocytes ,Humans ,Cardiac and Cardiovascular Systems ,hospital ,Aged ,Aged, 80 and over ,Kardiologi ,biology ,business.industry ,General Medicine ,Emergency department ,Pneumonia ,dyspnea ,Middle Aged ,medicine.disease ,Triage ,predictive value of tests ,C-Reactive Protein ,Predictive value of tests ,Heart failure ,biology.protein ,Biomarker (medicine) ,Female ,Calprotectin ,business ,Emergency Service, Hospital ,Leukocyte L1 Antigen Complex ,Emergency service ,Biomarkers - Abstract
Increased levels of plasma calprotectin are reported in patients with infectious diseases. However, the clinical usefulness of calprotectin as a biomarker to identify patients with infectious diseases in the emergency department (ED) setting has not been investigated. To study the ability of calprotectin to discriminate patients with acute infectious diseases and dyspnea from patients with other causes of acute dyspnea in the ED setting. Patients aged ≥18 years seeking ED during daytime on weekdays between March 2013 and July 2018, with acute dyspnea, were included. Participants (n = 1287) were triaged according to Medical Emergency Triage and Treatment System-Adult score (METTS-A) or Rapid Emergency Triage and Treatment System (RETTS), and blood samples were collected. The association between calprotectin and other markers of infectious diseases, i.e. biomarkers (CRP, leucocytes) and body temperature, was studied. The predictive value of calprotectin for the outcome of acute infection was evaluated with receiver operating characteristic (ROC) analysis. Univariate cross-sectional regression showed significant associations between calprotectin and leucocytes, CRP and body temperature. Patients with severe infections including pneumonia (n = 119) had significantly higher concentrations of calprotectin compared to patients with heart failure (n = 162) or chronic obstructive pulmonary disease (n = 183). When tested for the outcome of acute infection (n = 109), the area under the ROC curve (AUROC) was for CRP 0.83 and for calprotectin 0.78. Plasma calprotectin identifies infectious diseases in ED patients with acute dyspnea, and the clinical usefulness of Calprotectin in the ED has to be further studied.
- Published
- 2021
18. Metabolic Profiling of Obesity With and Without the Metabolic Syndrome: A Multisample Evaluation
- Author
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Lars Lind, Samira Salihovic, Johan Sundström, Sölve Elmståhl, Ulf Hammar, Koen Dekkers, Johan Ärnlöv, J Gustav Smith, Gunnar Engström, and Tove Fall
- Subjects
Metabolic Syndrome ,Sphingolipids ,Endocrinology ,Cross-Sectional Studies ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Humans ,Obesity ,Insulin Resistance ,Waist Circumference ,Biochemistry ,Body Mass Index - Abstract
Context There is a dispute whether obesity without major metabolic derangements may represent a benign condition or not. Objective We aimed to compare the plasma metabolome in obese subjects without metabolic syndrome (MetS) with normal-weight subjects without MetS and with obese subjects with MetS. Methods This was a cross-sectional study at 2 academic centers in Sweden. Individuals from 3 population-based samples (EpiHealth, n = 2342, SCAPIS-Uppsala, n = 4985, and SCAPIS-Malmö, n = 3978) were divided into groups according to their body mass index (BMI) and presence/absence of MetS (National Cholesterol Education Program [NCEP]/consensus criteria). In total, 791 annotated endogenous metabolites were measured by ultra-performance liquid chromatography–tandem mass spectrometry. Results We observed major differences in metabolite profiles (427 metabolites) between obese (BMI ≥ 30 kg/m2) and normal-weight (BMI Conclusion Our data suggest a graded derangement of the circulating metabolite profile from lean to obese to MetS, in particular for metabolites involved in amino acid synthesis/metabolism and sphingolipid metabolism. Insulin resistance is a plausible mediator of this gradual metabolic deterioration.
- Published
- 2021
19. Strong Associations Between Early Tubular Damage and Urinary Cytokine, Chemokine, and Growth Factor Levels in Elderly Males and Females
- Author
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Lars Lind, Johan Ärnlöv, Johanna Helmersson-Karlqvist, Måns Thulin, Anders Larsson, Kim Kultima, Bengt Fellström, and Inga Soveri
- Subjects
Male ,medicine.medical_specialty ,Chemokine ,Urinary system ,medicine.medical_treatment ,Immunology ,Renal function ,Inflammation ,Lipocalin ,Virology ,Internal medicine ,Medicine ,Humans ,Prospective Studies ,Acute tubular necrosis ,Aged ,Sweden ,biology ,business.industry ,Cell Biology ,medicine.disease ,Endocrinology ,Cytokine ,Kidney Tubules ,Cystatin C ,biology.protein ,Cytokines ,Intercellular Signaling Peptides and Proteins ,Female ,medicine.symptom ,Chemokines ,business - Abstract
Acute tubular necrosis is associated with high mortality rates and it is important to develop new biomarkers for tubular damage. The aim of this study was to investigate the effect of early tubular damage on a large number of urinary cytokines, chemokines, and growth factors. We selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The tubular damage markers cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were analyzed in the urine samples and urinary cytokine levels were analyzed with 2 multiplex assays (proximity extension assay). After adjustment for sex, body mass index, estimated glomerular filtration rate, smoking, and multiplicity testing using the false discovery rate approach, there remained 26 cytokines that correlated significantly with urine cystatin C, 27 cytokines that correlated with NGAL, and 66 cytokines that correlated with KIM-1. Tubular damage shows a strong association with urinary cytokines, chemokines, and growth factors. Our findings indicate that multiplex proteomics could be a promising new approach to explore the complex effects of tubular damage.
- Published
- 2021
20. The metabolomic profile associated with clustering of cardiovascular risk factors—A multi-sample evaluation
- Author
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Lars Lind, Johan Sundström, Sölve Elmståhl, Koen F. Dekkers, J. Gustav Smith, Gunnar Engström, Tove Fall, and Johan Ärnlöv
- Subjects
Metabolic Syndrome ,Kardiologi ,Multidisciplinary ,Sulfates ,Cholesterol, HDL ,Fatty Acids ,Carbohydrates ,Public Health, Global Health, Social Medicine and Epidemiology ,Glycerophospholipids ,Vitamins ,Ceramides ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,Glucose ,Cardiovascular Diseases ,Heart Disease Risk Factors ,Risk Factors ,Cluster Analysis ,Humans ,Cardiac and Cardiovascular Systems ,Amino Acids ,Insulin Resistance ,Triglycerides - Abstract
Background A clustering of cardiovascular risk factors is denoted the metabolic syndrome (MetS), but the mechanistic underpinnings of this clustering is not clear. Using large-scale metabolomics, we aimed to find a metabolic profile common for all five components of MetS. Methods and findings 791 annotated non-xenobiotic metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in five different population-based samples (Discovery samples: EpiHealth, n = 2342 and SCAPIS-Uppsala, n = 4985. Replication sample: SCAPIS-Malmö, n = 3978, Characterization samples: PIVUS, n = 604 and POEM, n = 501). MetS was defined by the NCEP/consensus criteria. Fifteen metabolites were related to all five components of MetS (blood pressure, waist circumference, glucose, HDL-cholesterol and triglycerides) at a false discovery rate of Conclusion A complex metabolic profile was related to all cardiovascular risk factors included in MetS independently of BMI. This profile was also related to insulin sensitivity, which provide further support for the importance of insulin sensitivity as an important underlying mechanism in the clustering of cardiovascular risk factors.
- Published
- 2022
21. 1051-P: Inside CKD: Modeling the Future Global Burden of Chronic Kidney Disease in Patients with Type 2 Diabetes
- Author
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Jean-Michel Halimi, Francesco Saverio Mennini, Luca Denicola, Marcelo Costa Batista, Eiichiro Kanda, Johan Ärnlöv, Alyshah Abdul Sultan, Claudia Cabrera, Laura Webber, Jay B. Wish, Michael Xu, Joshua Card-Gowers, Juan Jose Garcia Sanchez, Lise Retat, Albert Power, Navdeep Tangri, Juan Navarro-Gonzalez, Steve Chadban, Stephen Nolan, Guisen Li, and Glenn M. Chertow
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,Internal Medicine ,Medicine ,In patient ,Type 2 diabetes ,business ,medicine.disease ,Kidney disease - Published
- 2021
22. 1028-P: Inside CKD: Modeling the Clinical and Economic Impact of Routine Screening for Albuminuria in People with Type 2 Diabetes
- Author
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Jay B. Wish, Alyshah Abdul Sultan, Steve Chadban, Johan Ärnlöv, Michael Xu, Navdeep Tangri, Stephen Nolan, Eiichiro Kanda, Lise Retat, Joshua Card-Gowers, Laura Webber, Claudia Cabrera, Luca Denicola, Juan Jose Garcia Sanchez, Albert Power, Glenn M. Chertow, Guisen Li, Juan Navarro-Gonzalez, Jean-Michel Halimi, Francesco Saverio Mennini, and Marcelo Costa Batista
- Subjects
medicine.medical_specialty ,Routine screening ,business.industry ,Endocrinology, Diabetes and Metabolism ,Psychological intervention ,Type 2 diabetes ,medicine.disease ,Shareholder ,Family medicine ,Health care ,Internal Medicine ,Albuminuria ,Medicine ,In patient ,Economic impact analysis ,medicine.symptom ,business - Abstract
Background: Early chronic kidney disease (CKD) diagnosis in patients with type 2 diabetes (T2D) followed by guideline-recommended interventions are key to slowing CKD progression, but adherence to screening recommendations is suboptimal. Inside CKD models the global clinical and economic burden of CKD using country-specific, patient-level microsimulation models. We model the effects of targeted implementation of urine albumin:creatinine ratio (UACR) measurement and intervention in patients with T2D. Methods: We used the Inside CKD microsimulation to model the impact of measuring UACR during routine primary care visits with subsequent intervention in patients with T2D aged ≥45 years, versus current practice. Virtual populations were constructed using published country-specific data on demographics, CKD, T2D, comorbidities and complications. Results: Preliminary data for three countries show that in 2020-2025, measurement of UACR in patients with T2D would prevent CKD progression to stages 3b-5 in 80 000 patients in the UK, 350 000 in the US and 70 000 in Canada (Figure). Associated cost savings would be £90M, $5B and C$1.7B. More countries will be analysed. Conclusion: Preliminary data show that routine UACR measurement with subsequent intervention could potentially reduce the global burden of CKD and healthcare costs in patients with T2D, and improve outcomes. Disclosure S. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Arnlov: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen. S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk. Funding AstraZeneca
- Published
- 2021
23. 817-P: Inside CKD: Modeling the Direct Economic Burden of Concomitant Chronic Kidney Disease and Type 2 Diabetes
- Author
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Juan Navarro-Gonzalez, Johan Ärnlöv, Juan Jose Garcia Sanchez, Albert Power, Alyshah Abdul Sultan, Jean-Michel Halimi, Navdeep Tangri, Francesco Saverio Mennini, Lise Retat, Guisen Li, Steve Chadban, Laura Webber, Luca Denicola, Jay B. Wish, Stephen Nolan, Michael Xu, Joshua Card-Gowers, Claudia Cabrera, Eiichiro Kanda, Marcelo Costa Batista, and Glenn M. Chertow
- Subjects
medicine.medical_specialty ,Demographics ,business.industry ,Endocrinology, Diabetes and Metabolism ,Psychological intervention ,Type 2 diabetes ,medicine.disease ,Indirect costs ,Shareholder ,Family medicine ,Health care ,Internal Medicine ,medicine ,business ,Kidney disease ,Healthcare system - Abstract
Background: Inside CKD aims to model the future global clinical and economic burden of chronic kidney disease (CKD). Type 2 diabetes (T2D) is a leading cause of CKD, and concomitant CKD and T2D place a significant burden on healthcare systems worldwide. Methods: We used the Inside CKD country-specific, patient-level microsimulation to model global healthcare costs for patients with concomitant CKD and T2D from 2020 to 2025. We constructed virtual populations using country-specific data including demographics, prevalence of CKD (by stage), T2D and complications, and direct costs, from multiple published sources (e.g., NHANES for US; HSE for UK). Results: Preliminary results from three countries show that annual healthcare costs for patients with both CKD and T2D are expected to increase from 2020 to 2025 (US, $51.1B-95.3B; Canada, C$6.5B-11.5B; UK, £2.3B-2.7B) (Figure). Costs attributable to CKD stage 4 are expected to increase the most (US, 4-9% of overall costs; Canada, 9-13%; UK, 7-11%). Conclusion: Healthcare costs for patients with both CKD and T2D are projected to increase in the UK, US and Canada from 2020 to 2025. Later CKD stages are associated with more pronounced cost increases, likely due to both increased prevalence and greater treatment complexity. Early diagnosis and interventions to slow CKD progression are needed to reduce the economic burden of concomitant stage 3-5 CKD and T2D. Disclosure J. Sanchez: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Halimi: None. E. Kanda: Speaker’s Bureau; Self; AstraZeneca K. K. G. Li: None. F. Mennini: None. J. Navarro-gonzalez: None. S. T. Nolan: Employee; Self; AstraZeneca, Employee; Spouse/Partner; Biomarin, Stock/Shareholder; Self; AstraZeneca, Stock/Shareholder; Spouse/Partner; Biomarin. A. Power: Advisory Panel; Self; AstraZeneca, Bayer U. S., Napp Pharmaceuticals, Vifor Pharma Management Ltd., Consultant; Self; AstraZeneca, Speaker’s Bureau; Self; Alexion Pharmaceuticals, Inc., AstraZeneca, Napp Pharmaceuticals, Vifor Pharma Management Ltd. L. Retat: Employee; Self; HealthLumen. N. Tangri: Consultant; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., ClinPredict Inc, Eli Lilly and Company, Mesentech, Otsuka America Pharmaceutical, Inc., PulseData, Roche Pharma, Tricida, Inc., Research Support; Self; Janssen Pharmaceuticals, Inc. L. Webber: Employee; Self; HealthLumen. A. Sultan: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Wish: Advisory Panel; Self; Akebia Therapeutics, Inc., AstraZeneca, Rockwell Medical, Vifor Pharma Management Ltd., Speaker’s Bureau; Self; Akebia Therapeutics, Inc., AstraZeneca. M. Xu: Employee; Self; HealthLumen. J. Arnlov: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; Novartis AG. M. C. Batista: None. C. Cabrera: Employee; Self; AstraZeneca, Stock/Shareholder; Self; AstraZeneca. J. Card-gowers: Employee; Self; HealthLumen . S. Chadban: Advisory Panel; Self; Astellas Pharma Inc., AstraZeneca, Novartis Pharmaceuticals Corporation. G. M. Chertow: Advisory Panel; Self; Ardelyx, Baxter, Cricket Health, DURECT Corporation, Gilead Sciences, Inc., Reata Pharmaceuticals, Inc., Other Relationship; Self; Akebia Therapeutics, Inc., AstraZeneca, Vertex Pharmaceuticals Incorporated. L. Denicola: Consultant; Self; AstraZeneca, Mundipharma International, Novo Nordisk. Funding AstraZeneca
- Published
- 2021
24. MO494INSIDE CKD: MODELLING THE ECONOMIC BURDEN OF CHRONIC KIDNEY DISEASE IN EUROPE USING PATIENT-LEVEL MICROSIMULATION
- Author
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Laura Webber, Johan Ärnlöv, Michael Xu, Joshua Card-Gowers, Juan F. Navarro-González, Jean-Michel Halimi, Francesco Saverio Mennini, Stephen Nolan, Claudia Cabrera, Luca De Nicola, Alyshah Abdul Sultan, Juan Jose Garcia Sanchez, Albert Power, and Lise Retat
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,medicine ,Microsimulation ,urologic and male genital diseases ,Intensive care medicine ,medicine.disease ,business ,female genital diseases and pregnancy complications ,Kidney disease - Abstract
Background and Aims Chronic kidney disease (CKD) is a debilitating and costly condition, affecting approximately 10% of people globally. Progression of CKD is associated with an increased incidence of adverse renal and cardiovascular outcomes, and premature mortality, as well as increased requirement for renal replacement therapies (RRTs), which are associated with significant healthcare costs and resource use. The trajectories of CKD prevalence, progression, outcomes and the related costs are therefore critical considerations for public health and policy planning. Using country-specific, patient-level microsimulation, Inside CKD aims to model the global clinical and economic burden of CKD from 2020 to 2025. Method We used the Inside CKD microsimulation to model the economic burden of CKD in Europe. A virtual general population was developed for each country using national survey data and relevant data from published literature. Data inputs included country demographics, the prevalence of CKD and RRT, comorbidities and complication rates, as well as associated healthcare costs. CKD stages were defined according to Kidney Disease Improving Global Outcomes (KDIGO) 2012 recommendations and patients were categorized according to estimated glomerular filtration rate and albuminuria status. RRT modelling was calibrated against historical trends from country-specific renal registries. Model validation and calibration were conducted following established methods for health economic modelling. Here, we report the initial results from the UK analysis, with further analyses currently underway for additional European countries. Results The UK analysis revealed that annual healthcare costs associated with CKD will increase linearly from £12.51B to £13.99B between 2020 and 2025. The largest absolute increase in cost was observed in CKD stage 3b (£0.75B); however, CKD stage 5 had the largest relative increase in cost with an approximately three-fold increase (£0.14B to £0.41B). By 2025, costs associated with CKD will increase across all age categories (18–34, 35–64 and 65+ years); the 35–64 age group had the largest absolute increase in costs with an increase of £1.14B (£2.02B to £3.16B). The largest relative increase in cost was observed in the 18–34 age category, with a three-fold increase in costs (£0.09B to £0.27B). Conclusion Initial results from Inside CKD demonstrate that CKD poses a significant economic burden over the next 5 years. CKD stages 3b and 5 were associated with the most pronounced cost increases, likely due to increased prevalence for stage 3b and greater treatment cost for stage 5. Notably, the largest increase in CKD costs was observed in the 35–64-year-old ‘working’ population. Further policy interventions aimed at early diagnosis and proactive management should be considered to slow disease progression, improve patient outcomes and reduce the economic burden associated with CKD.
- Published
- 2021
25. End-Stage Kidney Diseases in Immigrant Groups: A Nationwide Cohort Study in Sweden
- Author
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Johan Ärnlöv, Per Wändell, Xinjun Li, Axel C. Carlsson, Danijela Gasevic, Kristina Sundquist, and Jan Sundquist
- Subjects
Male ,Population ,030232 urology & nephrology ,Emigrants and Immigrants ,030204 cardiovascular system & hematology ,Article ,End stage renal disease ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Humans ,Medicine ,Registries ,education ,Socioeconomic status ,Proportional Hazards Models ,Sweden ,education.field_of_study ,Proportional hazards model ,business.industry ,Incidence ,Incidence (epidemiology) ,Hazard ratio ,Health Status Disparities ,Socioeconomic Factors ,Nephrology ,Kidney Failure, Chronic ,Marital status ,Female ,business ,Demography ,Cohort study - Abstract
Background: Our aim was to study the association between the country of birth and incident end-stage kidney disease (ESKD) in several immigrant groups in Sweden, using individuals born in Sweden or with Swedish-born parents as referents. Methods: A cohort study of first- and second-generation immigrants residing in Sweden between January 1, 1998 and December 31, 2012 was performed. Outcomes were defined as having at least one registered diagnosis of ESKD in the National Patient Register. The incidence of ESKD in different immigrant groups was used in the Cox regression models to estimate hazard ratios (HRs) and 95% CIs. All models were stratified by sex and adjusted for age, geographical residence, educational level, marital status, and neighbourhood socioeconomic status. Results: Compared to their referents, higher incidence rates and HRs of ESKD (HR; 95% CI) were observed in general among foreign-born men (1.10; 1.04–1.16) and women (1.12; 1.04–1.21) but not among second-generation immigrants (persons born in Sweden with foreign-born parents). A particularly high incidence was noted among men and women from East-European countries, as well as from non-European regions. A lower incidence of ESKD was noted among men from Finland. Conclusions: We observed substantial differences in incidence of ESKD between immigrant groups and the Swedish-born population, which may be clinically relevant when monitoring preventive measures in patient subgroups with a higher risk of deteriorating kidney disease, and suggest higher attention to hypertension and diabetes control in immigrants. Mechanisms attributable to the migration process or ethnic differences may lead to an increased risk of ESKD.
- Published
- 2019
26. Cathepsin B and S as markers for cardiovascular risk and all-cause mortality in patients with stable coronary heart disease during 10 years: a CLARICOR trial sub-study
- Author
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Jørgen Hilden, Jonas Wuopio, Johan Ärnlöv, Janus Christian Jakobsen, Hans Jørn Kolmos, Erik Kjøller, Anders Larsson, Ahmad Sajadieh, Jens Kastrup, Carl Bring, Axel C. Carlsson, Christian Gluud, Gorm B. Jensen, and Per Winkel
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Proteases ,Denmark ,Ischemic heart disease ,Cardiovascular biomarkers ,Myocardial Infarction ,Coronary Disease ,030204 cardiovascular system & hematology ,Gastroenterology ,Cathepsin B ,Cathepsin ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Clarithromycin ,Internal medicine ,medicine ,Humans ,In patient ,Angina, Unstable ,Registries ,Mortality ,Aged ,Proportional Hazards Models ,Peripheral Vascular Diseases ,business.industry ,Middle Aged ,Atherosclerosis ,Cardiovascular risk ,Cathepsins ,Cardiovascular biomarker ,Coronary heart disease ,Cerebrovascular Disorders ,Treatment Outcome ,030104 developmental biology ,Cardiovascular Diseases ,Female ,Lysosomes ,Cardiology and Cardiovascular Medicine ,business ,All cause mortality ,Follow-Up Studies ,Glomerular Filtration Rate - Abstract
Background and aims: The lysosomal cysteine proteases cathepsin B and S have been implicated in the atherosclerotic process. The present paper investigates the association between serum levels of cathepsin B and S and cardiovascular events and mortality in patients with stable coronary heart disease. Methods: The CLARICOR trial is a randomised, placebo-controlled trial investigating the effect of clarithromycin versus placebo in patients with stable coronary heart disease. The outcome was time to either a cardiovascular event or all-cause mortality. The placebo group was used as discovery sample and the clarithromycin group as replication sample: n = 1998, n = 1979; mean age (years) 65, 65; 31%, 30% women; follow-up for 10 years; number of composite outcomes n = 1204, n = 1220; respectively. We used a pre-defined multivariable Cox regression model adjusting for inflammation, established cardiovascular risk factors, kidney function, and use of cardiovascular drugs. Results: Cathepsin B was associated with an increased risk of the composite outcome in both samples after multivariable adjustment (discovery: multivariable ratio (HR) per standard deviation increase 1.12, 95% confidence interval (CI) 1.05–1.19, p < 0.001, replication; HR 1.14, 95% CI 1.07–1.21, p < 0.001). There was no significant association between cathepsin S and the composite outcome in either the discovery or replication sample after multivariable adjustment (p>0.45). Secondary analyses suggest that cathepsin B was predominantly associated with mortality rather than specific cardiovascular events. Conclusions: Cathepsin B, but not serum cathepsin S, was associated with an increased risk of cardiovascular events in patients with stable coronary heart disease. The clinical implications of our findings remain to be established.
- Published
- 2018
27. Life-Time Covariation of Major Cardiovascular Diseases
- Author
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Albert Henry, Johan Ärnlöv, Erik Lampa, Martin Ingelsson, Lars Lind, R. Thomas Lumbers, and Johan Sundström
- Subjects
Male ,0301 basic medicine ,2019-20 coronavirus outbreak ,medicine.medical_specialty ,Longitudinal study ,Health Status ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Myocardial Infarction ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,medicine ,Humans ,Longitudinal Studies ,Myocardial infarction ,Stroke ,Heart Failure ,business.industry ,Incidence ,Life time ,Atrial fibrillation ,Original Articles ,General Medicine ,Mendelian Randomization Analysis ,Middle Aged ,medicine.disease ,030104 developmental biology ,Cardiovascular Diseases ,Genetic Loci ,Heart failure ,Cardiology ,business ,Genome-Wide Association Study - Abstract
Background: It is known that certain cardiovascular diseases (CVD) are associated, like atrial fibrillation and stroke. However, for other CVDs, the links and temporal trends are less studied. In this longitudinal study, we have investigated temporal epidemiological and genetic associations between different CVDs. Methods: The ULSAM (Uppsala Longitudinal Study of Adult Men; 2322 men aged 50 years) has been followed for 40 years regarding 4 major CVDs (incident myocardial infarction, ischemic stroke, heart failure, and atrial fibrillation). For the genetic analyses, publicly available data were used. Results: Using multistate modeling, significant relationships were seen between pairs of all of the 4 investigated CVDs. However, the risk of obtaining one additional CVD differed substantially both between different CVDs and between their temporal order. The relationship between heart failure and atrial fibrillation showed a high risk ratio (risk ratios, 24–26) regardless of the temporal order. A consistent association was seen also for myocardial infarction and atrial fibrillation but with a lower relative risk (risk ratios, 4–5). In contrast, the risk of receiving a diagnosis of heart failure following a myocardial infarction was almost twice as high as for the reverse temporal order (risk ratios, 16 versus 9). Genetic loci linked to traditional risk factors could partly explain the observed associations between the CVDs, but pathway analyses disclosed also other pathophysiological links. Conclusions: During 40 years, all of the 4 investigated CVDs were pairwise associated with each other regardless of the temporal order of occurrence, but the risk magnitude differed between different CVDs and their temporal order. Genetic analyses disclosed new pathophysiological links between CVDs.
- Published
- 2021
28. Poorly controlled ambulatory blood pressure in outpatients with peripheral arterial disease
- Author
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Johan Ärnlöv, Jerzy Leppert, Nina Dahle, Pär Hedberg, and Emma Skau
- Subjects
cardiovascular risk factors ,preventive efforts ,medicine.medical_specialty ,Ambulatory blood pressure ,hypertension ,Blood Pressure ,carotid artery disease ,Endocrinology and Diabetes ,smoking ,chemistry.chemical_compound ,Peripheral Arterial Disease ,Risk Factors ,Carotid artery disease ,Internal medicine ,Diabetes mellitus ,Hyperlipidemia ,Outpatients ,Medicine ,hyperlipidemia ,Humans ,Cardiac and Cardiovascular Systems ,Kardiologi ,business.industry ,General Medicine ,Blood Pressure Monitoring, Ambulatory ,medicine.disease ,Blood pressure ,chemistry ,Ambulatory ,Endokrinologi och diabetes ,Hypertension ,Cardiology ,Original Article ,Glycated hemoglobin ,business ,Blood sampling - Abstract
Background: Patients with peripheral arterial disease (PAD) are generally less intensively managed than patients with coronary heart disease (CHD), despite that their risk of complications is believed to be equivalent. Identification of PAD patients at risk of poorly controlled blood pressure (BP) could lead to improved treatment, thus lowering the risk of cardiovascular (CV) complications. We aimed to describe the prevalence of poorly controlled cardiovascular (CV) risk factors, focusing on BP, in outpatients with PAD diagnosed in a vascular ultrasound laboratory. Methods: Consecutive outpatients with carotid and/or lower extremity PAD were included (n = 402) and examined with blood sampling, clinical BP, and 24-h ambulatory BP measurements. A poorly controlled clinical BP was defined as ≥140/90 mmHg, ambulatory BP ≥130/80 mmHg, low-density lipoprotein (LDL)-cholesterol level ≥2.5 mmol/L, and glycated hemoglobin (HbA1c) level >53 mmol/mol in those with diabetes. Results: Most of the patients had poorly controlled clinical (76.6%) and ambulatory BP (51.7%) profiles. Antihypertensive medications were prescribed in 84% of the patients. However, >40% of them used only 0–1 medication, and 53 mmol/mol was present in 55% of diabetic patients. Conclusion: Poorly controlled clinical and ambulatory systolic BP profiles were common. In addition, suboptimal control of other important CV risk factors was detected. The findings of this study highlight the need for better preventive efforts against CV risk factors in outpatients with PAD.
- Published
- 2021
29. The association between BMI and 90-day mortality in patients with and without diabetes seeking care at the emergency department
- Author
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Per Wändell, Anders Larsson, Torgny Wessman, Axel C. Carlsson, Johan Ärnlöv, Olle Melander, and Toralph Ruge
- Subjects
Adult ,triage level ,medicine.medical_specialty ,Adolescent ,emergency department ,Population ,Overweight ,Endocrinology and Diabetes ,Lower risk ,Body Mass Index ,BMI ,Thinness ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Cardiac and Cardiovascular Systems ,education ,education.field_of_study ,Kardiologi ,business.industry ,Hazard ratio ,Diabetes ,General Medicine ,medicine.disease ,Obesity ,Comorbidity ,mortality ,Endokrinologi och diabetes ,Medicine ,Original Article ,medicine.symptom ,business ,Emergency Service, Hospital ,Body mass index - Abstract
Background: The impact of body mass index (BMI) on mortality varies with age and disease states. The aim of this research study was to analyse the associations between BMI categories and short- and long-term mortality in patients with or without diabetes seeking care at the emergency department (ED) with acute dyspnoea. Population and methods: Patients aged ≥18 years at ED during daytime on weekdays from March 2013 to July 2018 were included. Participants were triaged according to the Medical Emergency Triage and Treatment System-Adult score (METTS-A), and blood samples were collected. Totally, 1,710 patients were enrolled, with missing values in 113, leaving 1,597 patients, 291 with diabetes and 1,306 without diabetes. The association between BMI and short-term (90-day) and long-term (mean follow-up time 2.1 years) mortality was estimated by Cox regression with normal BMI (18.5–24.9) as referent category, with adjustment for age, sex, METTS-A scoring, glomerular filtration rate, smoking habits and cardiovascular comorbidity in a fully adjusted model. The Bonferroni correction was also used. Results: Regarding long-term mortality, patients with diabetes and BMI category ≥30 kg/m2 had a fully adjusted Hazard Ratio (HR) of 0.40 (95% confidence interval [CI]: 0.23–0.69), significant after the Bonferroni correction. Amongst patients without diabetes, those with underweight had an increased risk but only of borderline significance, whilst risks in those with overweight or obesity did not differ from reference. Regarding short-term mortality, risks did not differ from reference amongst patients with or without diabetes. Conclusions: We found divergent long-term mortality risks in patients with and without diabetes, with lower risk in obese patients (BMI ≥ 30 kg/m2) with diabetes, but no increased risk for patients without diabetes and overweight (BMI: 25–29.9 kg/m2) and obesity.
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- 2021
30. 'Concerns regarding the 'meta-analysis' by A. S. Bhagavathula and J. Rahmani'
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Christoph Nowak, Johan Ärnlöv, and Jonas Wuopio
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medicine.medical_specialty ,Nutrition and Dietetics ,Risk Factors ,business.industry ,Internal medicine ,Meta-analysis ,Atrial Fibrillation ,medicine ,Humans ,Critical Care and Intensive Care Medicine ,business - Published
- 2021
31. Addition of cystatin C predicts cardiovascular death better than creatinine in intensive care
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Miklos Lipcsey, Bo Ravn, Johan Ärnlöv, Anders Larsson, Johanna Helmersson-Karlqvist, Max Bell, and Alain Dardashti
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Adult ,Male ,medicine.medical_specialty ,Anestesi och intensivvård ,Critical Care ,Critical Illness ,Renal function ,urologic and male genital diseases ,law.invention ,chemistry.chemical_compound ,law ,Intensive care ,Internal medicine ,biomarkers ,epidemiology ,Urologi och njurmedicin ,Medicine ,Urology and Nephrology ,Humans ,Cystatin C ,Renal Insufficiency, Chronic ,Child ,Creatinine ,Anesthesiology and Intensive Care ,biology ,business.industry ,Proportional hazards model ,medicine.disease ,Intensive care unit ,female genital diseases and pregnancy complications ,chemistry ,Cardiovascular Diseases ,biology.protein ,Female ,Cystatin ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Kidney disease ,Glomerular Filtration Rate - Abstract
ObjectiveDecreased kidney function increases cardiovascular risk and predicts poor survival. Estimated glomerular filtration rate (eGFR) by creatinine may theoretically be less accurate in the critically ill. This observational study compares long-term cardiovascular mortality risk by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation; Caucasian, Asian, paediatric and adult cohort (CAPA) cystatin C equation and the CKD-EPI combined creatinine/cystatin C equation.MethodsThe nationwide study includes 22 488 intensive care patients in Uppsala, Karolinska and Lund University Hospitals, Sweden, between 2004 and 2015. Creatinine and cystatin C were analysed with accredited methods at admission. Reclassification and model discrimination with C-statistics was used to compare creatinine and cystatin C for cardiovascular mortality prediction.ResultsDuring 5 years of follow-up, 2960 (13 %) of the patients died of cardiovascular causes. Reduced eGFR was significantly associated with cardiovascular death by all eGFR equations in Cox regression models. In each creatinine-based GFR category, 17%, 19% and 31% reclassified to a lower GFR category by cystatin C. These patients had significantly higher cardiovascular mortality risk, adjusted HR (95% CI), 1.55 (1.38 to 1.74), 1.76 (1.53 to 2.03) and 1.44 (1.11 to 1.86), respectively, compared with patients not reclassified. Harrell’s C-statistic for cardiovascular death for cystatin C, alone or combined with creatinine, was 0.73, significantly higher than for creatinine (0.71), pConclusionsA single cystatin C at admission to the intensive care unit added significant predictive value to creatinine for long-term cardiovascular death risk assessment. Cystatin C, alone or in combination with creatinine, should be used for estimating GFR for long-term risk prediction in critically ill.
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- 2020
32. Response to letter about 'Estimated salt intake and risk of atrial fibrillation in a prospective community-based cohort'
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Christoph Nowak, Jonas Wuopio, and Johan Ärnlöv
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Community based ,medicine.medical_specialty ,business.industry ,Cardiovascular risk factors ,Atrial fibrillation ,medicine.disease ,Cohort Studies ,Risk Factors ,Internal medicine ,Epidemiology ,Cohort ,Atrial Fibrillation ,Internal Medicine ,medicine ,Humans ,Prospective Studies ,Salt intake ,Sodium Chloride, Dietary ,business - Published
- 2020
33. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study
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Gregory A. Roth, George A. Mensah, Catherine O. Johnson, Giovanni Addolorato, Enrico Ammirati, Larry M. Baddour, Noël C. Barengo, Andrea Z. Beaton, Emelia J. Benjamin, Catherine P. Benziger, Aimé Bonny, Michael Brauer, Marianne Brodmann, Thomas J. Cahill, Jonathan Carapetis, Alberico L. Catapano, Sumeet S. Chugh, Leslie T. Cooper, Josef Coresh, Michael Criqui, Nicole DeCleene, Kim A. Eagle, Sophia Emmons-Bell, Valery L. Feigin, Joaquim Fernández-Solà, Gerry Fowkes, Emmanuela Gakidou, Scott M. Grundy, Feng J. He, George Howard, Frank Hu, Lesley Inker, Ganesan Karthikeyan, Nicholas Kassebaum, Walter Koroshetz, Carl Lavie, Donald Lloyd-Jones, Hong S. Lu, Antonio Mirijello, Awoke Misganaw Temesgen, Ali Mokdad, Andrew E. Moran, Paul Muntner, Jagat Narula, Bruce Neal, Mpiko Ntsekhe, Glaucia Moraes de Oliveira, Catherine Otto, Mayowa Owolabi, Michael Pratt, Sanjay Rajagopalan, Marissa Reitsma, Antonio Luiz P. Ribeiro, Nancy Rigotti, Anthony Rodgers, Craig Sable, Saate Shakil, Karen Sliwa-Hahnle, Benjamin Stark, Johan Sundström, Patrick Timpel, Imad M. Tleyjeh, Marco Valgimigli, Theo Vos, Paul K. Whelton, Magdi Yacoub, Liesl Zuhlke, Christopher Murray, Valentin Fuster, Noel C. Barengo, Andrea Beaton, Aime Bonny, Jonathan R. Carapetis, Sumeet Chugh, Michael H. Criqui, Nicole K. DeCleene, Joaquim Fernández-Sola, F. Gerry R. Fowkes, Nicholas J. Kassebaum, Walter J. Koroshetz, Awoke T. Misganaw, Ali H. Mokdad, Gláucia M.M. Oliveira, Catherine M. Otto, Mayowa O. Owolabi, Marissa B. Reitsma, Nancy A. Rigotti, Craig A. Sable, Saate S. Shakil, Karen Sliwa, Benjamin A. Stark, Imad I. Tleyjeh, Liesl J. Zuhlke, Mohsen Abbasi-Kangevari, Alireza Abdi, Aidin Abedi, Victor Aboyans, Woldu A. Abrha, Eman Abu-Gharbieh, Abdelrahman I. Abushouk, Dilaram Acharya, Tim Adair, Oladimeji M. Adebayo, Zanfina Ademi, Shailesh M. Advani, Khashayar Afshari, Ashkan Afshin, Gina Agarwal, Pradyumna Agasthi, Sohail Ahmad, Sepideh Ahmadi, Muktar B. Ahmed, Budi Aji, Yonas Akalu, Wuraola Akande-Sholabi, Addis Aklilu, Chisom J. Akunna, Fares Alahdab, Ayman Al-Eyadhy, Khalid F. Alhabib, Sheikh M. Alif, Vahid Alipour, Syed M. Aljunid, François Alla, Amir Almasi-Hashiani, Sami Almustanyir, Rajaa M. Al-Raddadi, Adeladza K. Amegah, Saeed Amini, Arya Aminorroaya, Hubert Amu, Dickson A. Amugsi, Robert Ancuceanu, Deanna Anderlini, Tudorel Andrei, Catalina Liliana Andrei, Alireza Ansari-Moghaddam, Zelalem A. Anteneh, Ippazio Cosimo Antonazzo, Benny Antony, Razique Anwer, Lambert T. Appiah, Jalal Arabloo, Johan Ärnlöv, Kurnia D. Artanti, Zerihun Ataro, Marcel Ausloos, Leticia Avila-Burgos, Asma T. Awan, Mamaru A. Awoke, Henok T. Ayele, Muluken A. Ayza, Samad Azari, Darshan B. B, Nafiseh Baheiraei, Atif A. Baig, Ahad Bakhtiari, Maciej Banach, Palash C. Banik, Emerson A. Baptista, Miguel A. Barboza, Lingkan Barua, Sanjay Basu, Neeraj Bedi, Yannick Béjot, Derrick A. Bennett, Isabela M. Bensenor, Adam E. Berman, Yihienew M. Bezabih, Akshaya S. Bhagavathula, Sonu Bhaskar, Krittika Bhattacharyya, Ali Bijani, Boris Bikbov, Mulugeta M. Birhanu, Archith Boloor, Luisa C. Brant, Hermann Brenner, Nikolay I. Briko, Zahid A. Butt, Florentino Luciano Caetano dos Santos, Leah E. Cahill, Lucero Cahuana-Hurtado, Luis A. Cámera, Ismael R. Campos-Nonato, Carlos Cantu-Brito, Josip Car, Juan J. Carrero, Felix Carvalho, Carlos A. Castañeda-Orjuela, Ferrán Catalá-López, Ester Cerin, Jaykaran Charan, Vijay Kumar Chattu, Simiao Chen, Ken L. Chin, Jee-Young J. Choi, Dinh-Toi Chu, Sheng-Chia Chung, Massimo Cirillo, Sean Coffey, Sara Conti, Vera M. Costa, David K. Cundiff, Omid Dadras, Baye Dagnew, Xiaochen Dai, Albertino A.M. Damasceno, Lalit Dandona, Rakhi Dandona, Kairat Davletov, Vanessa De la Cruz-Góngora, Fernando P. De la Hoz, Jan-Walter De Neve, Edgar Denova-Gutiérrez, Meseret Derbew Molla, Behailu T. Derseh, Rupak Desai, Günther Deuschl, Samath D. Dharmaratne, Meghnath Dhimal, Raja Ram Dhungana, Mostafa Dianatinasab, Daniel Diaz, Shirin Djalalinia, Klara Dokova, Abdel Douiri, Bruce B. Duncan, Andre R. Duraes, Arielle W. Eagan, Sanam Ebtehaj, Aziz Eftekhari, Sahar Eftekharzadeh, Michael Ekholuenetale, Nevine El Nahas, Islam Y. Elgendy, Muhammed Elhadi, Shaimaa I. El-Jaafary, Sadaf Esteghamati, Atkilt E. Etisso, Oghenowede Eyawo, Ibtihal Fadhil, Emerito Jose A. Faraon, Pawan S. Faris, Medhat Farwati, Farshad Farzadfar, Eduarda Fernandes, Carlota Fernandez Prendes, Pietro Ferrara, Irina Filip, Florian Fischer, David Flood, Takeshi Fukumoto, Mohamed M. Gad, Shilpa Gaidhane, Morsaleh Ganji, Jalaj Garg, Abadi K. Gebre, Birhan G. Gebregiorgis, Kidane Z. Gebregzabiher, Gebreamlak G. Gebremeskel, Lemma Getacher, Abera Getachew Obsa, Alireza Ghajar, Ahmad Ghashghaee, Nermin Ghith, Simona Giampaoli, Syed Amir Gilani, Paramjit S. Gill, Richard F. Gillum, Ekaterina V. Glushkova, Elena V. Gnedovskaya, Mahaveer Golechha, Kebebe B. Gonfa, Amir Hossein Goudarzian, Alessandra C. Goulart, Jenny S. Guadamuz, Avirup Guha, Yuming Guo, Rajeev Gupta, Vladimir Hachinski, Nima Hafezi-Nejad, Teklehaimanot G. Haile, Randah R. Hamadeh, Samer Hamidi, Graeme J. Hankey, Arief Hargono, Risky K. Hartono, Maryam Hashemian, Abdiwahab Hashi, Shoaib Hassan, Hamid Y. Hassen, Rasmus J. Havmoeller, Simon I. Hay, Khezar Hayat, Golnaz Heidari, Claudiu Herteliu, Ramesh Holla, Mostafa Hosseini, Mehdi Hosseinzadeh, Mihaela Hostiuc, Sorin Hostiuc, Mowafa Househ, Junjie Huang, Ayesha Humayun, Ivo Iavicoli, Charles U. Ibeneme, Segun E. Ibitoye, Olayinka S. Ilesanmi, Irena M. Ilic, Milena D. Ilic, Usman Iqbal, Seyed Sina N. Irvani, Sheikh Mohammed Shariful Islam, Rakibul M. Islam, Hiroyasu Iso, Masao Iwagami, Vardhmaan Jain, Tahereh Javaheri, Sathish Kumar Jayapal, Shubha Jayaram, Ranil Jayawardena, Panniyammakal Jeemon, Ravi P. Jha, Jost B. Jonas, Jitendra Jonnagaddala, Farahnaz Joukar, Jacek J. Jozwiak, Mikk Jürisson, Ali Kabir, Tanvir Kahlon, Rizwan Kalani, Rohollah Kalhor, Ashwin Kamath, Ibrahim Kamel, Himal Kandel, Amit Kandel, André Karch, Ayele Semachew Kasa, Patrick D.M.C. Katoto, Gbenga A. Kayode, Yousef S. Khader, Mohammad Khammarnia, Muhammad S. Khan, Md Nuruzzaman Khan, Maseer Khan, Ejaz A. Khan, Khaled Khatab, Gulam M.A. Kibria, Yun Jin Kim, Gyu Ri Kim, Ruth W. Kimokoti, Sezer Kisa, Adnan Kisa, Mika Kivimäki, Dhaval Kolte, Ali Koolivand, Vladimir A. Korshunov, Sindhura Lakshmi Koulmane Laxminarayana, Ai Koyanagi, Kewal Krishan, Vijay Krishnamoorthy, Barthelemy Kuate Defo, Burcu Kucuk Bicer, Vaman Kulkarni, G. Anil Kumar, Nithin Kumar, Om P. Kurmi, Dian Kusuma, Gene F. Kwan, Carlo La Vecchia, Ben Lacey, Tea Lallukka, Qing Lan, Savita Lasrado, Zohra S. Lassi, Paolo Lauriola, Wayne R. Lawrence, Avula Laxmaiah, Kate E. LeGrand, Ming-Chieh Li, Bingyu Li, Shanshan Li, Stephen S. Lim, Lee-Ling Lim, Hualiang Lin, Ziqiang Lin, Ro-Ting Lin, Xuefeng Liu, Alan D. Lopez, Stefan Lorkowski, Paulo A. Lotufo, Alessandra Lugo, Nirmal K. M, Fabiana Madotto, Morteza Mahmoudi, Azeem Majeed, Reza Malekzadeh, Ahmad A. Malik, Abdullah A. Mamun, Navid Manafi, Mohammad Ali Mansournia, Lorenzo G. Mantovani, Santi Martini, Manu R. Mathur, Giampiero Mazzaglia, Suresh Mehata, Man Mohan Mehndiratta, Toni Meier, Ritesh G. Menezes, Atte Meretoja, Tomislav Mestrovic, Bartosz Miazgowski, Tomasz Miazgowski, Irmina Maria Michalek, Ted R. Miller, Erkin M. Mirrakhimov, Hamed Mirzaei, Babak Moazen, Masoud Moghadaszadeh, Yousef Mohammad, Dara K. Mohammad, Shafiu Mohammed, Mohammed A. Mohammed, Yaser Mokhayeri, Mariam Molokhia, Ahmed A. Montasir, Ghobad Moradi, Rahmatollah Moradzadeh, Paula Moraga, Lidia Morawska, Ilais Moreno Velásquez, Jakub Morze, Sumaira Mubarik, Walter Muruet, Kamarul Imran Musa, Ahamarshan J. Nagarajan, Mahdi Nalini, Vinay Nangia, Atta Abbas Naqvi, Sreenivas Narasimha Swamy, Bruno R. Nascimento, Vinod C. Nayak, Javad Nazari, Milad Nazarzadeh, Ruxandra I. Negoi, Sandhya Neupane Kandel, Huong L.T. Nguyen, Molly R. Nixon, Bo Norrving, Jean Jacques Noubiap, Brice E. Nouthe, Christoph Nowak, Oluwakemi O. Odukoya, Felix A. Ogbo, Andrew T. Olagunju, Hans Orru, Alberto Ortiz, Samuel M. Ostroff, Jagadish Rao Padubidri, Raffaele Palladino, Adrian Pana, Songhomitra Panda-Jonas, Utsav Parekh, Eun-Cheol Park, Mojtaba Parvizi, Fatemeh Pashazadeh Kan, Urvish K. Patel, Mona Pathak, Rajan Paudel, Veincent Christian F. Pepito, Arokiasamy Perianayagam, Norberto Perico, Hai Q. Pham, Thomas Pilgrim, Michael A. Piradov, Farhad Pishgar, Vivek Podder, Roman V. Polibin, Akram Pourshams, Dimas R.A. Pribadi, Navid Rabiee, Mohammad Rabiee, Amir Radfar, Alireza Rafiei, Fakher Rahim, Vafa Rahimi-Movaghar, Mohammad Hifz Ur Rahman, Muhammad Aziz Rahman, Amir Masoud Rahmani, Ivo Rakovac, Pradhum Ram, Sudha Ramalingam, Juwel Rana, Priyanga Ranasinghe, Sowmya J. Rao, Priya Rathi, Lal Rawal, Wasiq F. Rawasia, Reza Rawassizadeh, Giuseppe Remuzzi, Andre M.N. Renzaho, Aziz Rezapour, Seyed Mohammad Riahi, Ross L. Roberts-Thomson, Leonardo Roever, Peter Rohloff, Michele Romoli, Gholamreza Roshandel, Godfrey M. Rwegerera, Seyedmohammad Saadatagah, Maha M. Saber-Ayad, Siamak Sabour, Simona Sacco, Masoumeh Sadeghi, Sahar Saeedi Moghaddam, Saeed Safari, Amirhossein Sahebkar, Sana Salehi, Hamideh Salimzadeh, Mehrnoosh Samaei, Abdallah M. Samy, Itamar S. Santos, Milena M. Santric-Milicevic, Nizal Sarrafzadegan, Arash Sarveazad, Thirunavukkarasu Sathish, Monika Sawhney, Mete Saylan, Maria I. Schmidt, Aletta E. Schutte, Subramanian Senthilkumaran, Sadaf G. Sepanlou, Feng Sha, Saeed Shahabi, Izza Shahid, Masood A. Shaikh, Mahdi Shamali, Morteza Shamsizadeh, Md Shajedur Rahman Shawon, Aziz Sheikh, Mika Shigematsu, Min-Jeong Shin, Jae Il Shin, Rahman Shiri, Ivy Shiue, Kerem Shuval, Soraya Siabani, Tariq J. Siddiqi, Diego A.S. Silva, Jasvinder A. Singh, Ambrish Singh Mtech, Valentin Y. Skryabin, Anna A. Skryabina, Amin Soheili, Emma E. Spurlock, Leo Stockfelt, Stefan Stortecky, Saverio Stranges, Rizwan Suliankatchi Abdulkader, Hooman Tadbiri, Eyayou G. Tadesse, Degena B. Tadesse, Masih Tajdini, Md Tariqujjaman, Berhane F. Teklehaimanot, Mohamad-Hani Temsah, Ayenew K. Tesema, Bhaskar Thakur, Kavumpurathu R. Thankappan, Rekha Thapar, Amanda G. Thrift, Binod Timalsina, Marcello Tonelli, Mathilde Touvier, Marcos R. Tovani-Palone, Avnish Tripathi, Jaya P. Tripathy, Thomas C. Truelsen, Guesh M. Tsegay, Gebiyaw W. Tsegaye, Nikolaos Tsilimparis, Biruk S. Tusa, Stefanos Tyrovolas, Krishna Kishore Umapathi, Brigid Unim, Bhaskaran Unnikrishnan, Muhammad S. Usman, Muthiah Vaduganathan, Pascual R. Valdez, Tommi J. Vasankari, Diana Z. Velazquez, Narayanaswamy Venketasubramanian, Giang T. Vu, Isidora S. Vujcic, Yasir Waheed, Yanzhong Wang, Fang Wang, Jingkai Wei, Robert G. Weintraub, Abrha H. Weldemariam, Ronny Westerman, Andrea S. Winkler, Charles S. Wiysonge, Charles D.A. Wolfe, Befikadu Legesse Wubishet, Gelin Xu, Ali Yadollahpour, Kazumasa Yamagishi, Lijing L. Yan, Srikanth Yandrapalli, Yuichiro Yano, Hiroshi Yatsuya, Tomas Y. Yeheyis, Yigizie Yeshaw, Christopher S. Yilgwan, Naohiro Yonemoto, Chuanhua Yu, Hasan Yusefzadeh, Geevar Zachariah, Sojib Bin Zaman, Muhammed S. Zaman, Maryam Zamanian, Ramin Zand, Alireza Zandifar, Afshin Zarghi, Mikhail S. Zastrozhin, Anasthasia Zastrozhina, Zhi-Jiang Zhang, Yunquan Zhang, Wangjian Zhang, Chenwen Zhong, Zhiyong Zou, Yves Miel H. Zuniga, and Christopher J.L. Murray
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BMI, body mass index ,GBD, Global Burden of Diseases, Injuries, and Risk Factors Study ,IS, ischemic stroke ,030204 cardiovascular system & hematology ,MV, mitral valve ,SDI, sociodemographic index ,Global Health ,UI, uncertainty interval ,Global Burden of Disease ,GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group ,0302 clinical medicine ,Cost of Illness ,LDL, low-density lipoprotein ,Case fatality rate ,Global health ,030212 general & internal medicine ,IKF, impaired kidney function ,1102 Cardiorespiratory Medicine and Haematology ,Incidence (epidemiology) ,Health Policy ,IHD, ischemic heart disease ,1. No poverty ,AC, alcoholic cardiomyopathy ,3. Good health ,HICs, high-income countries ,Cardiovascular Diseases ,DALYs, disability-adjusted life years ,TMREL, theoretical minimum risk exposure level ,Public Health ,HHD, hypertensive heart disease ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,AF, atrial fibrillation ,Population health ,CVD, cardiovascular disease ,LMICs, low- and middle-income countries ,PM, particulate matter ,1117 Public Health and Health Services ,03 medical and health sciences ,JACC State-of-the-Art Review ,RHD, rheumatic heart disease ,Environmental health ,medicine ,Humans ,LPA, low physical activity ,YLLs, years of life lost ,Health policy ,Disease burden ,PAD, peripheral artery disease ,business.industry ,SBP, systolic blood pressure ,Public health ,CKD, chronic kidney disease ,The Present and Future ,AFL, atrial flutter ,Correction ,HAP, household air pollution ,ICD, International Classification of Diseases ,CAVD, calcific aortic valve disease ,YLDs, years lived with disability ,Years of potential life lost ,CHA, congenital heart anomalies ,Cardiovascular System & Hematology ,Heart Disease Risk Factors ,business ,population health - Abstract
Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases., Central Illustration, Highlights • The burden of CVD, in number of DALYs and deaths, continues to increase globally. • CVD burden attributable to modifiable risk factors continues to increase globally. • Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.
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- 2020
34. Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance
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Rafael Moreno-Gonzalez, Francesc Formiga, Paolo Fabbietti, Pedro Gil, Andrea Corsonello, Johan Ärnlöv, Christian Weingart, Regina Roller-Wirnsberger, Itshak Melzer, Gerhard Wirnsberger, Tomasz Kostka, Agnieszka Guligowska, Fabrizia Lattanzio, Francesco U.S. Mattace-Raso, Ellen Freiberger, Ilhan Yehoshua, Lisanne Tap, Sara Lainez Martinez, and Axel C. Carlsson
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medicine.medical_specialty ,Medicina ,Anemia ,Osteoporosis ,Population ,030232 urology & nephrology ,Multimorbilitat ,urologic and male genital diseases ,Angina ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Chronic renal failure ,medicine ,030212 general & internal medicine ,Insuficiencia renal crónica ,education ,Stroke ,education.field_of_study ,Hip fracture ,business.industry ,Multimorbidity ,Multimorbilidad ,medicine.disease ,female genital diseases and pregnancy complications ,3. Good health ,Heart failure ,Insuficiència renal crònica ,Medicine ,Geriatrics and Gerontology ,business ,Kidney disease - Abstract
Background Chronic kidney disease (CKD) is known to be associated with several co-occurring conditions. We aimed at exploring multimorbidity patterns associated with CKD, as well as the impact of physical performance and CKD severity on them in a population of older outpatients. Methods Our series consisted of 2252 patients enrolled in the Screening of CKD among Older People across Europe multicenter observational study. Hypertension, stroke, transient ischemic attack, cancer, hip fracture, osteoporosis, Parkinson’s disease, asthma, chronic obstructive pulmonary disease, congestive heart failure, angina, myocardial infarction, atrial fibrillation, anemia, CKD (defined as GFR 2), cognitive impairment, depression, hearing impairment and vision impairment were included in the analyses. Physical performance was assessed by the Short Physical Performance Battery (SPPB) and used as stratification variable. Pairs of co-occurring diseases were analyzed by logistic regression. Patterns of multimorbidity were investigated by hierarchical cluster analysis. Results CKD was among the most frequently observed conditions and it was rarely observed without any other co-occurring disease. CKD was significantly associated with hypertension, anemia, heart failure, atrial fibrillation, myocardial infarction and hip fracture. When stratifying by SPPB, CKD was also significantly associated with vision impairment in SPPB = 5–8 group, and hearing impairment in SPPB = 0–4 group. Cluster analysis individuated two main clusters, one including CKD, hypertension and sensory impairments, and the second including all other conditions. Stratifying by SPPB, CKD contribute to a cluster including diabetes, anemia, osteoporosis, hypertension and sensory impairments in the SPPB = 0–4 group. When defining CKD as eGFR2, the strength of the association of CKD with hypertension, sensory impairments, osteoporosis, anemia and CHF increased together with CKD severity in pairs analysis. Severe CKD (eGFR2) contributed to a wide cluster including cardiovascular, respiratory and neurologic diseases, as well as osteoporosis, hip fracture and cancer. Conclusions CKD and its severity may contribute significantly to specific multimorbidity patterns, at least based on the cluster analysis. Physical performance as assessed by SPPB may be associated with not negligible changes in both co-occurring pairs and multimorbidity clusters. Trial registration The SCOPE study is registered at clinicaltrials.gov (NCT02691546).
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- 2020
35. Estimated salt intake and risk of atrial fibrillation in a prospective community-based cohort
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Johan Ärnlöv, Marju Orho-Melander, Christoph Nowak, and Jonas Wuopio
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dietary salt ,0301 basic medicine ,Adult ,Male ,medicine.medical_specialty ,hypertension ,030204 cardiovascular system & hematology ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,Sex Factors ,Risk Factors ,Internal medicine ,Atrial Fibrillation ,Internal Medicine ,medicine ,Humans ,atrial fibrillation ,Cardiac and Cardiovascular Systems ,Prospective Studies ,Risk factor ,Salt intake ,Sodium Chloride, Dietary ,Aged ,Proportional Hazards Models ,Kardiologi ,Proportional hazards model ,business.industry ,Hazard ratio ,Klinisk medicin ,blood pressure ,Public Health, Global Health, Social Medicine and Epidemiology ,Atrial fibrillation ,Original Articles ,Middle Aged ,medicine.disease ,Kawasaki formulae ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,030104 developmental biology ,Blood pressure ,Cohort ,Hypertension ,Original Article ,Female ,Clinical Medicine ,sodium excretion ,business ,Follow-Up Studies - Abstract
Introduction: Hypertension predisposes to atrial fibrillation (AF) – a major risk factor for ischaemic stroke. Since a high dietary salt consumption is associated with hypertension, we investigated the association between urinary sodium excretion as a marker for dietary sodium intake and risk of new-onset AF in community-dwelling adults. Method: The UK Biobank includes 40- to 69-year-old British residents recruited 2006–2010. Participants were divided into sex-specific quintiles according to 24-hour sodium excretion estimated based on spot samples with the Kawasaki equation. We excluded participants with AF at baseline. Cox regression adjusted for cardiovascular risk factors was used to assess associations with risk of AF, using the third quintile as reference. Results: A total of 257 545 women and 215 535 men were included. During up to 10 years' follow-up, 2221 women and 3751 men were diagnosed with AF. There was a tendency for an increased risk of AF in the lowest and highest quintiles of estimated daily salt intake in both women and men. In the fully adjusted model, significant associations were seen amongst men in the lowest and highest quintiles of sodium excretion (hazard ratio, HRQv1, 1.20; 95% CI, 1.08–1.32, P < 0.001, and HRQv5 1.15, 95% CI, 1.03–1.27, P = 0.011). Conclusion: We found evidence for a U-shaped association between estimated daily salt intake and AF risk amongst men. A suggestive J-shaped association in women was not statistically confirmed, but analyses were likely underpowered. Our results suggest that above a certain physiological minimum level progressively higher salt intake is associated with increasing risk of AF. (Less)
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- 2020
36. Kidney Disease Biomarkers Improve Heart Failure Risk Prediction in the General Population
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Johan Ärnlöv and Christoph Nowak
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Adult ,Male ,medicine.medical_specialty ,Population ,Renal function ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Medicine ,Albuminuria ,Humans ,030212 general & internal medicine ,Cystatin C ,education ,Renal biomarkers ,Aged ,Heart Failure ,education.field_of_study ,Kidney ,business.industry ,Incidence ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Heart failure ,Creatinine ,Cardiology ,Female ,Kidney Diseases ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Kidney disease ,Glomerular Filtration Rate - Abstract
Background: The kidneys play an important role in heart failure (HF), but it is unclear if renal biomarkers improve HF risk prediction beyond established risk factors. We aimed to assess whether adding biomarkers of kidney disease to conventional risk factors improved 10-year risk prediction for incident HF in a contemporary community sample. Methods: We included 450 212 participants in the UK Biobank aged 39 to 70 years without HF who had been assessed in 2006 to 2010 with the urine albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C. There were 1701 incident cases of HF during up to 10.3 years of follow-up (mean 8.2±0.7 years). We used the Atherosclerosis Risk in Communities study heart failure risk score excluding natriuretic peptides as the base model to which we added eGFR and urine albumin-to-creatinine ratio. Harrell’s C-statistic of ARIC-HF was 0.845 (95% CI, 0.831–0.859). Results: Each combination of added kidney measures (creat-eGFR, cysC-eGFR, and urine albumin-to-creatinine ratio) led to significant improvement in risk discrimination, calibration, and reclassification. The optimal pair of added kidney measures was cysC-eGFR and urine albumin-to-creatinine ratio (ΔC=0.019 [95% CI, 0.015–0.022]). Addition of cysC-eGFR made the largest contribution to reclassification improvement (continuous net reclassification improvement 0.323 [95% CI, 0.278–0.360]). Conclusions: In a large community sample, the addition of kidney disease markers to conventional risk factors improved prediction of 10-year HF risk. Our results support including kidney disease markers in the identification of persons at highest risk of HF and demonstrate a possible role of impaired kidney function in HF development in asymptomatic persons.
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- 2020
37. Impaired kidney function is associated with lower quality of life among community-dwelling older adults : The screening for CKD among older people across Europe (SCOPE) study
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Fabrizia Lattanzio, Rafael Moreno-Gonzalez, Yehudit Melzer, Johan Ärnlöv, Gerhard Wirnsberger, Andrea Corsonello, Axel C. Carlsson, Robert Kob, Francesco U.S. Mattace-Raso, Regina Roller-Wirnsberger, Francesc Formiga, Tomasz Kostka, Agnieszka Guligowska, Paolo Fabbietti, Pedro Gil, Lisanne Tap, Itshak Melzer, Rada Artzi-Medvedik, Ellen Freiberger, Sara Lainez Martinez, and Internal Medicine
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Quality of life ,medicine.medical_specialty ,Old adults ,Geriatrik ,030232 urology & nephrology ,Kidney ,Persones grans ,03 medical and health sciences ,0302 clinical medicine ,Lower urinary tract symptoms ,Internal medicine ,Diabetes mellitus ,Chronic kidney disease ,Chronic renal failure ,medicine ,Humans ,Gerontologi, medicinsk/hälsovetenskaplig inriktning ,030212 general & internal medicine ,Gerontology, specialising in Medical and Health Sciences ,Renal Insufficiency, Chronic ,Aged ,Geriatrics ,Polypharmacy ,Aged, 80 and over ,COPD ,business.industry ,Klinisk medicin ,medicine.disease ,3. Good health ,Europe ,Qualitat de vida ,Insuficiència renal crònica ,Quality of Life ,Geriatric Depression Scale ,Female ,Independent Living ,Older people ,Clinical Medicine ,Geriatrics and Gerontology ,business ,Kidney disease ,Glomerular Filtration Rate - Abstract
Background Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). Methods Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR 2) and low EQoL-VAS was investigated by multivariable logistic regression models. Results CKD was found to be significantly associated with low EQoL-VAS in crude analysis (OR = 1.47, 95%CI = 1.16–1.85 for eGFR Conclusions CKD may significantly affect QoL in community-dwelling older adults. Physical performance, polypharmacy, diabetes, hypertension and COPD may affect such association, which suggests that the impact of CKD on QoL is likely multifactorial and partly mediated by co-occurrent conditions/risk factors.
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- 2020
38. Global Plasma Metabolomics to Identify Potential Biomarkers of Blood Pressure Progression
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Tove Fall, Samira Salihovic, Johan Sundström, Lars Lind, Johan Ärnlöv, Yi-Ting Lin, Erik Ingelsson, and Ulf Hammar
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Male ,0301 basic medicine ,hypertension ,body mass index ,Blood Pressure ,030204 cardiovascular system & hematology ,Ceramides ,Bioinformatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Metabolomics ,Humans ,Medicine ,Triglycerides ,Aged ,Aged, 80 and over ,glomerular filtration rate ,business.industry ,Klinisk medicin ,blood pressure ,Middle Aged ,medicine.disease ,030104 developmental biology ,Blood pressure ,oleic acid ,Potential biomarkers ,Pathophysiology of hypertension ,Hypertension ,Clinical Medicine ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Oleic Acid - Abstract
Objective: The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approach and Results: Circulating metabolite levels were assessed with liquid- and gas-chromatography coupled to mass spectrometry among persons without BP-lowering medication at baseline. We studied associations of baseline levels of metabolites with changes in BP levels and the clinical BP stage between baseline and a follow-up examination 5 years later. In the discovery cohort, we investigated 504 individuals that contributed with 757 observations of paired BP measurements. The mean baseline systolic and diastolic BPs were 144 (19.7)/76 (9.7) mm Hg, and change in systolic and diastolic BPs were 3.7 (15.8)/−0.5 (8.6) mm Hg over 5 years. The metabolites associated with diastolic BP change were ceramide, triacylglycerol, total glycerolipids, oleic acid, and cholesterylester. No associations with longitudinal changes in systolic BP or BP stage were observed. Metabolites with similar structures to the 5 top findings in the discovery cohort were investigated in the validation cohort. Diacylglycerol (36:2) and monoacylglycerol (18:0), 2 glycerolipids, were associated with diastolic BP change in the validation cohort. Conclusions: Circulating baseline levels of ceramide, triacylglycerol, total glycerolipids, and oleic acid were positively associated with longitudinal diastolic BP change, whereas cholesterylester levels were inversely associated with longitudinal diastolic BP change. Two glycerolipids were validated in an independent cohort. These metabolites may point towards pathophysiological pathways of hypertension.
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- 2020
39. The association between length of stay in the emergency department and short term mortality
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Torgny Wessman, Johan Ärnlöv, Axel Carlsson, Ulf Ekelund, Olle Melander, and Thoralph Ruge
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Background: Prolonged length of stay at the emergency department (ED-LOS) has been associated with increased mortality and hospital stay. The aim of this study was to investigate the association between ED-LOS and 7- and 30-days mortality in patients triaged according to Rapid Emergency Triage and Treatment System – Adult (RETTS-A), the most common used triage tool in Sweden. Methods: All adult patients (> 18 years) visiting the ED at the Karolinska University Hospital, Sweden, from 1/1/2010 to 1/1/2015 (n=639 385) were included. Logistic regression analysis was used to determine association between prolonged ED-LOS and 7 and 30-days mortality rates. All patients were triaged according to the RETTS-A and subsequently separated into five quintiles of ED-LOS. Results : In patients triaged with the highest medical urgency, longer ED-LOS was associated with a lower risk for 7-days mortality, for triage priority 1: OR 0.94 (CI 95% 0.92-0.96) compared to OR 1.03 (CI 95% 0.99-1.07) for triage priority 4, and for 30-days mortality: OR 0.97 (CI 95% 0.96-0.99) OR for triage priority 1 compared to 1.03 (CI 95% 1.01-1.05) for triage priority 4. In contrast, the opposite pattern appeared evident in the 3 other triage groups, where a longer ED-LOS was generally associated with an increased mortality risk. Pro-longed ED-LOS in patients admitted to in-hospital care was associated with lower 30- and 7-days mortality independently of triage priority whereas the opposite was observed for patients not admitted to in-hospital care. Conclusion: Prolonged ED-LOS was associated with increased short term mortality in patients with lower clinical urgency and in patients not admitted to in-hospital care.
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- 2020
40. Use of a proximity extension proteomics assay to discover novel biomarkers associated with circulating leptin levels in two populations with type 2 diabetics
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Tobias R. Feldreich, Christoph Nowak, Carl Johan Östgren, Stefan Söderberg, Johan Sundström, Johan Ärnlöv, Fredrik H. Nystrom, Camilla Vavruch, and Lars Lind
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Leptin ,Computational biology ,Biology ,Proteomics - Abstract
Background We used a multiplex proteomics assay with the aim to discover novel associations between leptin and 88 circulating proteins in order to provide additional insights into the role of leptin in the development of CVD in patients with type 2 diabetes (T2DM). Material and methods 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 (CARDIPP, n=661). Associations that passed the significance threshold of a False discovery rate of 5% (corresponding to p
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- 2020
41. Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance
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Andrea Corsonello, Paolo Fabbietti, Francesc Formiga, Rafael Moreno-Gonzalez, Lisanne Tap, Francesco Mattace-Raso, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Johan Ärnlöv, Axel C. Carlsson, Christian Weingart, Ellen Freiberger, Tomasz Kostka, Agnieszka Guligowska, Pedro Gil, Sara Lainez Martinez, Itshak Melzer, Ilan Yehoshua, Fabrizia Lattanzio
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- 2020
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42. Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals
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Tom Palmer, Lars Lind, George Davey Smith, Ting Qi, Michael W. Nagle, Paul W. Franks, Bram P. Prins, Julie Lee, Jingyuan Fu, Niclas Eriksson, Peter K. Joshi, Chris Haley, Ljubica Perisic Matic, Jeremy D. Gale, Mika Ala-Korpela, Michael V. Holmes, Urmo Võsa, Adam S. Butterworth, Eric B. Fauman, Anette Kalnapenkis, Reedik Mägi, Åsa Johansson, James F. Wilson, Mikael Landén, Gunnar Engström, Johan Ärnlöv, Anders Hamsten, Ozren Polasek, Andres Ingason, Andrew J. Schork, Agneta Siegbahn, Lasse Folkersen, Qin Wang, Andrew P. Morris, Johan Sundström, Daria V. Zhernakova, Olle Melander, Erik Ingelsson, Federico De Masi, Lude Franke, James E. Peters, Alexandra Zhernakova, Seung Hoan Choi, Rasmus Wernersson, Thibaud Boutin, Karl Michaëlsson, Stefan Gustafsson, Bianca E. Suur, Karen Page, Yang Wu, Caroline Hayward, Marketa Sjögren, Cecilia M. Lindgren, Stefan Enroth, Tõnu Esko, Amira Quazi, John Danesh, Anders Mälarstig, Daniel Hvidberg Hansen, Åsa K Hedman, Jan Nilsson, Ulf Gyllensten, Vilmantas Giedraitis, J. Gustav Smith, Martin Magnusson, Marju Orho-Melander, Steven A. Lubitz, Erin Macdonald-Dunlop, Thomas Werge, Praveen Surendran, Yan Chen, Céline Fernandez, Weidong Zhang, Lars Wallentin, Andrew D. Bretherick, Jian Yang, Peter M. Nilsson, Jesper R. Gådin, Annique Claringbould, Sölve Elmståhl, Sarah E Bergen, Harm-Jan Westra, Erik Pålsson, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), United Kingdom Research and Innovation, Folkersen, Lasse [0000-0003-0708-9530], Hansen, Daniel Hvidberg [0000-0003-3285-605X], Wu, Yang [0000-0002-0128-7280], Eriksson, Niclas [0000-0002-2152-4343], Bretherick, Andrew D [0000-0001-9258-3140], Enroth, Stefan [0000-0002-5056-9137], Lee, Julie [0000-0001-6090-6718], Ala-Korpela, Mika [0000-0001-5905-1206], Claringbould, Annique [0000-0002-9201-6557], Davey Smith, George [0000-0002-1407-8314], Fauman, Eric [0000-0002-9739-0249], Fernandez, Celine [0000-0003-1290-4982], Franke, Lude [0000-0002-5159-8802], Franks, Paul W [0000-0002-0520-7604], Giedraitis, Vilmantas [0000-0003-3423-2021], Haley, Chris [0000-0002-9811-0210], Johansson, Åsa [0000-0002-2915-4498], Lubitz, Steven [0000-0002-9599-4866], Palmer, Tom [0000-0003-4655-4511], Macdonald-Dunlop, Erin [0000-0001-6569-6086], Magnusson, Martin [0000-0003-1710-5936], Michaelsson, Karl [0000-0003-2815-1217], Nagle, Michael W [0000-0002-4677-7582], Nilsson, Peter M [0000-0002-5652-8459], Nilsson, Jan [0000-0002-9752-7479], Prins, Bram [0000-0001-5774-034X], Sundström, Johan [0000-0003-2247-8454], Werge, Thomas [0000-0003-1829-0766], Westra, Harm-Jan [0000-0001-7038-567X], Fu, Jingyuan [0000-0001-5578-1236], Esko, Tõnu [0000-0003-1982-6569], Hayward, Caroline [0000-0002-9405-9550], Landen, Mikael [0000-0002-4496-6451], Butterworth, Adam S [0000-0002-6915-9015], Holmes, Michael V [0000-0001-6617-0879], Ingelsson, Erik [0000-0003-2256-6972], Mälarstig, Anders [0000-0003-2608-1358], Apollo - University of Cambridge Repository, and 30387078 - Magnusson, P. Martin
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Proteomics ,Proteome ,Endocrinology, Diabetes and Metabolism ,Asthma ,ATP Binding Cassette Transporter 1 ,Cardiovascular System ,Chromosome Mapping ,Drug Delivery Systems ,Gene Knockdown Techniques ,Genome-Wide Association Study ,Genomics ,Humans ,Inflammatory Bowel Diseases ,Interleukin-1 Receptor-Like 1 Protein ,Intracellular Signaling Peptides and Proteins ,Linkage Disequilibrium ,Mendelian Randomization Analysis ,Protein-Serine-Threonine Kinases ,Quantitative Trait Loci ,Receptors, CCR2 ,Receptors, CCR5 ,Genome-wide association study ,030204 cardiovascular system & hematology ,Chemokine receptor ,0302 clinical medicine ,RECEPTOR ANTAGONIST ,GWAS ,Cardiac and Cardiovascular Systems ,0303 health sciences ,Molecular medicine ,3. Good health ,Medical genetics ,Medical Genetics ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Computational biology ,Biology ,Protein Serine-Threonine Kinases ,Article ,03 medical and health sciences ,Endocrinology & Metabolism ,Physiology (medical) ,Mendelian randomization ,Internal Medicine ,medicine ,030304 developmental biology ,Science & Technology ,Cell Biology ,GENE ,ANTIBODY - Abstract
Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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- 2020
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43. Impaired kidney function is associated with lower quality of life among community-dwelling older adults
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Rada Artzi-Medvedik, Robert Kob, Paolo Fabbietti, Fabrizia Lattanzio, Andrea Corsonello, Yehudit Melzer, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Francesco Mattace-Raso, Lisanne Tap, Pedro Gil, Sara Lainez Martinez, Francesc Formiga, Rafael Moreno-González, Tomasz Kostka, Agnieszka Guligowska, Johan Ärnlöv, Axel C. Carlsson, Ellen Freiberger, Itshak Melzer
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- 2020
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44. Kidney function and other factors and their association with falls
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Sabine Britting, Rada Artzi-Medvedik, Paolo Fabbietti, Lisanne Tap, Francesco Mattace-Raso, Andrea Corsonello, Fabrizia Lattanzio, Johan Ärnlöv, Axel C. Carlsson, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Tomasz Kostka, Agnieszka Guligowska, Francesc Formiga, Rafael Moreno-Gonzalez, Pedro Gil, Sara Lainez Martinez, Robert Kob, Itshak Melzer, Ellen Freiberger
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- 2020
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45. Association between kidney function, nutritional status and anthropometric measures in older people
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Agnieszka Guligowska, Andrea Corsonello, Małgorzata Pigłowska, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Johan Ärnlöv, Axel C. Carlsson, Lisanne Tap, Francesco Mattace-Raso, Francesc Formiga, Rafael Moreno-Gonzalez, Ellen Freiberger, Cornel Sieber, Pedro Gil Gregorio, Sara Laínez Martínez, Rada Artzi-Medvedik, Ilan Yehoshua, Paolo Fabbietti, Fabrizia Lattanzio, Tomasz Kostka
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- 2020
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46. Prevalence of sarcopenia in community-dwelling older adults using the updated EWGSOP2 definition according to kidney function and albuminuria
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Rafael Moreno-Gonzalez, Xavier Corbella, Francesco Mattace-Raso, Lisanne Tap, Cornel Sieber, Ellen Freiberger, Tomasz Kostka, Agnieszka Guligowska, Itshak Melzer, Yehudit Melzer, Axel C. Carlsson, Johan Ärnlöv, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Pedro Gil, Sara Lainez Martinez, Paolo Fabbietti, Andrea Corsonello, Fabrizia Lattanzio, Francesc Formiga
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- 2020
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47. Association between Atherosclerotic Aortic Calcification-Associated Genetic Variation in HDAC9 with Mortality, Cardiovascular Disease and Kidney Disease
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Christoph Nowak, Douglas F. Dluzen, and Johan Ärnlöv
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medicine.medical_specialty ,business.industry ,medicine.disease ,Pulse pressure ,Blood pressure ,Diabetes mellitus ,Heart failure ,Internal medicine ,medicine ,Albuminuria ,Cardiology ,Myocardial infarction ,medicine.symptom ,business ,Stroke ,Kidney disease - Abstract
Importance: Histone deacetylase 9 (HDAC9) has recently been demonstrated as a key regulator of vascular smooth muscle cell (VSMC) phenotype and is associated with abdominal aortic calcification, myocardial infarction and ischemic stroke. It is uncertain whether HDAC9 is also implicated in other VSMC-driven diseases. Objective: To investigate associations between abdominal aortic calcification-associated genetic variation in HDAC9 and VSMC-associated phenotypes. Design: Prospective population study.Setting: UK Biobank.Participants: 335,146 European, non-related person aged 40-69 years (mean 57±8 years, 54% women). Main outcomes: Blood pressure, heart rate, hypertension, myocardial infarction, stroke, arterial aneurysm, heart failure, glomerular filtration rate, albuminuria, end-stage renal disease, all-cause and cardiovascular mortality, HbA1c, diabetes, serum lipids, body mass index, and smoking. Results: We used the aortic calcification-raising A-allele of rs57301765 in HDAC9 as a genetic instrumental variable to query the long-term effects of HDAC9 variation. At the Bonferroni significance level, rs57301765 was associated with systolic blood pressure (effect per added risk allele in standard deviation units, 0.022; 95% CI, 0.016-0.029, P=1.71×10-11), pulse pressure (0.035; 95% CI, 0.028-0.041, P=5.76×10-27), hypertension (odds ratio, OR, 1.04; 95% CI, 1.02-1.05, P=1.26×10-6), myocardial infarction (OR, 1.08; 95% CI, 1.04-1.12, P=1.72×10-5, driven by non-ST segment elevation myocardial infarction, OR, 1.11; 95% CI, 1.04-1.17, P=0.001), and ischemic stroke (OR, 1.14; 95% CI, 1.07-1.22, P=6.29×10-5). There was a suggestive protective association with kidney disease outcomes that, however, did not reach experiment-wise significance. Look-ups in public genome-wide association study results concur with our findings for cardiovascular outcomes. Conclusions and Relevance: The genetic results in our study lend further support for HDAC9 as a key determinant of VSMC-associated cardiovascular pathology and its potential as a therapeutic target for arterial stenotic and calcific disease.
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- 2020
48. Is kidney function associated with cognition and mood in late life?
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Lisanne Tap, Andrea Corsonello, Francesc Formiga, Rafael Moreno-Gonzalez, Johan Ärnlöv, Axel C. Carlsson, Regina Roller-Wirnsberger, Gerhard Wirnsberger, Gijsbertus Ziere, Ellen Freiberger, Cornel Sieber, Tomasz Kostka, Agnieszka Guligowska, Pedro Gil, Sara Lainez Martinez, Rada Artzi-Medvedik, Ilan Yehoshua, Paolo Fabbietti, Fabrizia Lattanzio, Francesco Mattace-Raso
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- 2020
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49. Associations of Circulating Protein Levels With Lipid Fractions in the General Population
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Johan Ärnlöv, Johan Sundström, Sylwia M. Figarska, Anders Mälarstig, Sölve Elmståhl, Erik Ingelsson, Tove Fall, Lars Lind, and Stefan Gustafsson
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Male ,Proteomics ,0301 basic medicine ,medicine.medical_specialty ,Genotype ,Population ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Protein Interaction Maps ,education ,Triglycerides ,Aged ,Aged, 80 and over ,Sweden ,education.field_of_study ,Triglyceride ,business.industry ,Cholesterol ,Cholesterol, HDL ,Lipid metabolism ,Blood Proteins ,Cholesterol, LDL ,Mendelian Randomization Analysis ,Middle Aged ,Lipid Metabolism ,medicine.disease ,Blood proteins ,Phenotype ,030104 developmental biology ,Endocrinology ,chemistry ,Female ,lipids (amino acids, peptides, and proteins) ,Resistin ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Lipoprotein - Abstract
Objective— Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. Approach and Results— We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima–Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels. Conclusions— Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.
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- 2018
50. 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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Johan Ärnlöv, Francesc Formiga, Pedro Gil, Tomasz Kostka, Agnieszka Guligowska, Lisanne Tap, Gerhard Wirnsberger, Itshak Melzer, Sara Lainez Martinez, Andrea Corsonello, Regina Roller-Wirnsberger, Axel C. Carlsson, Rafael Moreno-Gonzalez, Francesco U.S. Mattace-Raso, Christian Weingart, Fabrizia Lattanzio, Cornel C. Sieber, Rada Artzi-Medvedik, and Internal Medicine
- Subjects
Gerontology ,030232 urology & nephrology ,lcsh:Medicine ,Renal function ,chronic kidney disease (CKD) ,Muscle mass ,urologic and male genital diseases ,Persones grans ,Article ,sarcopenia ,03 medical and health sciences ,0302 clinical medicine ,Older patients ,Medizinische Fakultät ,Urologi och njurmedicin ,medicine ,Urology and Nephrology ,sex ,ddc:610 ,030212 general & internal medicine ,Berlin Initiative Study (BIS) ,Full Age Spectrum (FAS) ,Kidney diseases ,Scope (project management) ,business.industry ,Muscles ,estimated glomerular filtration rate (eGFR) ,lcsh:R ,Músculs ,Klinisk medicin ,General Medicine ,medicine.disease ,older patients ,female genital diseases and pregnancy complications ,3. Good health ,muscle mass ,Sarcopenia ,Malalties del ronyó ,Clinical Medicine ,Older people ,business ,Kidney disease - Abstract
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&ndash, Altman analysis. &kappa, 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 &minus, 0.24 (95% limits of agreement (95%LA = &minus, 4.64&ndash, 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 = &minus, 2.90&ndash, 20.84) and 8.72 (95%LA = &minus, 2.11&ndash, 19.56) mL/min/1.73 m2, respectively. As regards CKD stage classification, &kappa, value was 0.47 for both CKD-EPI vs. FAS and CKD-EPI vs. BIS, while BIS and FAS had similar classificatory properties (&kappa, = 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.
- Published
- 2019
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