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1. Quality of Life and Kidney Function in Older Adults: Prospective Data of the SCOPE Study

Author

Melzer, Rada Artzi-Medvedik, Robert Kob, Mirko Di Rosa, Fabrizia Lattanzio, Andrea Corsonello, Ilan Yehoshua, Regina E. Roller-Wirnsberger, Gerhard H. Wirnsberger, Francesco U. S. Mattace-Raso, Lisanne Tap, Pedro G. Gil, Francesc Formiga, Rafael Moreno-González, Tomasz Kostka, Agnieszka Guligowska, Johan Ärnlöv, Axel C. Carlsson, Ellen Freiberger, and Itshak

Subjects
quality of life, chronic kidney disease, older adults, prospective studies, cohort studies, disease progression
Abstract

A longitudinal alteration in health-related quality of life (HRQoL) over a two-year period and its association with early-stage chronic kidney disease (CKD) progression was investigated among 1748 older adults (>75 years). HRQoL was measured by the Euro-Quality of Life Visual Analog Scale (EQ-VAS) at baseline and at one and two years after recruitment. A full comprehensive geriatric assessment was performed, including sociodemographic and clinical characteristics, the Geriatric Depression Scale-Short Form (GDS-SF), Short Physical Performance Battery (SPPB), and estimated glomerular filtration rate (eGFR). The association between EQ-VAS decline and covariates was investigated by multivariable analyses. A total of 41% of the participants showed EQ-VAS decline, and 16.3% showed kidney function decline over the two-year follow-up period. Participants with EQ-VAS decline showed an increase in GDS-SF scores and a greater decline in SPPB scores. The logistic regression analyses showed no contribution of a decrease in kidney function on EQ-VAS decline in the early stages of CKD. However, older adults with a greater GDS-SF score were more likely to present EQ-VAS decline over time, whereas an increase in the SPPB scores was associated with less EQ-VAS decline. This finding should be considered in clinical practice and when HRQoL is used to evaluate health interventions among older adults.

Published
2023
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2. OSA Was Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study

Author

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

Subjects
Pulmonary and Respiratory Medicine, Cardiology and Cardiovascular Medicine, Critical Care and Intensive Care Medicine
Published
2023

3. Association of omega 3 polyunsaturated fatty acids with incident chronic kidney disease : pooled analysis of 19 cohorts

Author

Kwok Leung Ong, Matti Marklund, Liping Huang, Kerry-Anne Rye, Nicholas Hui, Xiong-Fei Pan, Casey M Rebholz, Hyunju Kim, Lyn M Steffen, Anniek C van Westing, Johanna M Geleijnse, Ellen K Hoogeveen, Yun-Yu Chen, Kuo-Liong Chien, Amanda M Fretts, Rozenn N Lemaitre, Fumiaki Imamura, Nita G Forouhi, Nicholas J Wareham, Anna Birukov, Susanne Jäger, Olga Kuxhaus, Matthias B Schulze, Vanessa Derenji de Mello, Jaakko Tuomilehto, Matti Uusitupa, Jaana Lindström, Nathan Tintle, William S Harris, Keisuke Yamasaki, Yoichiro Hirakawa, Toshiharu Ninomiya, Toshiko Tanaka, Luigi Ferrucci, Stefania Bandinelli, Jyrki K Virtanen, Ari Voutilainen, Tharusha Jayasena, Anbupalam Thalamuthu, Anne Poljak, Sonia Bustamante, Perminder S Sachdev, Mackenzie K Senn, Stephen S Rich, Michael Y Tsai, Alexis C Wood, Markku Laakso, Maria Lankinen, Xiaowei Yang, Liang Sun, Huaixing Li, Xu Lin, Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Lars Lind, Mélanie Le Goff, Cécilia Samieri, Catherine Helmer, Frank Qian, Renata Micha, Adrienne Tin, Anna Köttgen, Ian H de Boer, David S Siscovick, Dariush Mozaffarian, Jason HY Wu, Clinicum, Department of Public Health, Ong, Kwok Leung [0000-0001-7229-7614], and Apollo - University of Cambridge Repository

Subjects
Omega-3-fatty-acids, Nutrition and Disease, Supplementation, Risk Factors, Decline, Voeding en Ziekte, Fatty Acids, Omega-3, Urologi och njurmedicin, Life Science, Humans, Urology and Nephrology, Prospective Studies, Renal Insufficiency, Chronic, VLAG, alpha-Linolenic Acid, General Medicine, Middle Aged, Metaanalysis, 3142 Public health care science, environmental and occupational health, N-3, Risk-factors, Pooling project, Glomerular-filtration-rate, Adipose-tissue, 3121 General medicine, internal medicine and other clinical medicine, Fatty Acids, Unsaturated, Biomarkers
Abstract

Peer reviewed: True, Funder: University of New South Wales; FundRef: http://dx.doi.org/10.13039/501100001773, OBJECTIVE: To assess the prospective associations of circulating levels of omega 3 polyunsaturated fatty acid (n-3 PUFA) biomarkers (including plant derived α linolenic acid and seafood derived eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) with incident chronic kidney disease (CKD). DESIGN: Pooled analysis. DATA SOURCES: A consortium of 19 studies from 12 countries identified up to May 2020. STUDY SELECTION: Prospective studies with measured n-3 PUFA biomarker data and incident CKD based on estimated glomerular filtration rate. DATA EXTRACTION AND SYNTHESIS: Each participating cohort conducted de novo analysis with prespecified and consistent exposures, outcomes, covariates, and models. The results were pooled across cohorts using inverse variance weighted meta-analysis. MAIN OUTCOME MEASURES: Primary outcome of incident CKD was defined as new onset estimated glomerular filtration rate

Published
2023

4. The association between sodium intake and coronary and carotid atherosclerosis in the general Swedish population

Author

Jonas Wuopio, Yi-Ting Ling, Marju Orho-Melander, Gunnar Engström, and Johan Ärnlöv

Subjects
Kardiologi, Hypertension, Salt, Sodium, Cardiac and Cardiovascular Systems, Atherosclerosis, Cardiovascular disease
Abstract

AimsA high intake of salt raises blood pressure and the risk of cardiovascular disease. Previous studies have reported on the association between salt intake and carotid stenosis, but the association with coronary atherosclerosis has not been reported. Therefore, this project aimed at studying the association between salt intake and both carotid and coronary atherosclerosis in a contemporary community-based cohort.Methods and resultsEstimated 24-h sodium excretion (est24hNa) was calculated by the Kawasaki formula for participants of two sites (Uppsala and Malmö) of the Swedish Cardiopulmonary bioImage Study, who underwent a coronary computed tomography (n = 9623) and measurement of coronary artery calcium score (CACS, n = 10 289). Carotid ultrasound was used to detect carotid plaques (n = 10 700). Ordered logistic regression was used to calculate odds ratios (OR) per 1000 mg increase in est24hNa. We also investigated potential J-formed associations using quintiles of est24hNa. Increased est24hNa was associated with increased occurrence of carotid plaques [OR: 1.09, P < 0.001, confidence interval (CI): 1.06–1.12], higher CACS (OR: 1.16, P < 0.001, CI: 1.12–1.19), and coronary artery stenosis (OR: 1.17, P < 0.001, CI: 1.13–1.20) in minimal adjusted models. Associations were abolished when adjusting for blood pressure. When adjusting for established cardiovascular risk factors (not including blood pressure), associations remained for carotid plaques but not for coronary atherosclerosis. There was no evidence of J-formed associations.ConclusionHigher est24hNa was associated with both coronary and carotid atherosclerosis in minimal adjusted models. The association seemed mainly mediated by blood pressure but to some degree also influenced by other established cardiovascular risk factors.

Published
2023

5. Large-Scale Metabolomics and the Incidence of Cardiovascular Disease

Author

Lars Lind, Tove Fall, Johan Ärnlöv, Sölve Elmståhl, and Johan Sundström

Subjects
amino acids, Kardiologi, cardiovascular disease, mass spectroscopy, epidemiology, Cardiac and Cardiovascular Systems, Cardiology and Cardiovascular Medicine, metabolomics
Abstract

Background The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. Methods and Results In 2278 individuals free from CVD in the EpiHealth study (aged 45–75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow‐up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age‐ and sex‐adjusted analyses and P P =0.0054). Thirty‐five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1‐carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. Conclusions Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.

Published
2023

6. Author Correction : An online atlas of human plasma metabolite signatures of gut microbiome composition

Author

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

Subjects
Mikrobiologi, Multidisciplinary, General Physics and Astronomy, General Chemistry, Microbiology, General Biochemistry, Genetics and Molecular Biology
Published
2023

7. Nondipping blood pressure pattern predicts cardiovascular events and mortality in patients with atherosclerotic peripheral vascular disease

Author

Nina Dahle, Johan Ärnlöv, Jerzy Leppert, and Pär Hedberg

Subjects
ambulatory blood pressure monitoring, Kardiologi, peripheral vascular disease, cardiovascular risk prediction, Cardiac and Cardiovascular Systems, Cardiology and Cardiovascular Medicine, peripheral artery disease (PAD)
Abstract

Background: Patients with peripheral vascular disease (PVD) are often underdiagnosed and undertreated. Nocturnal nondipping blood pressure (BP) pattern, as diagnosed by ambulatory BP monitoring (ABPM), is associated with increased cardiovascular risk, but has not been studied in patients with PVD. We aimed to investigate if a nondipping BP pattern predicts cardiovascular events or all-cause death in outpatients with PVD. Methods: Consecutive outpatients with carotid or lower-extremity PVD were examined with 24-hour ABPM ( n = 396). Nondipping was defined as a < 10% fall in systolic BP level during night-time. We used Cox regression models adjusting for potential confounders. We also evaluated the incremental prognostic value of dipping status in the COPART risk score. Our primary composite outcome was cardiovascular events or all-cause death. Results: In the cohort (mean age 70; 40% women), 137 events occurred during a 5.1-year median follow-up; incident rate of 7.35 events per 100 person-years. Nondipping was significantly associated with outcome (hazard ratio 1.55, 95% CI 1.07–2.26, p = 0.021) in a fully adjusted model. When adding nondipping to the risk markers in the COPART risk score, the model fit significantly improved (χ2 7.91, p < 0.005) and the C-statistic increased from 0.65 to 0.67. Conclusion: In a cohort of outpatients with PVD, nondipping was an independent risk factor for future cardiovascular events or mortality and seemed to be a strong predictor in patients with carotid artery disease but not in lower-extremity PVD. Additional studies are needed to evaluate the clinical utility of ABPM for improved prevention in these high-risk patients. (ClinicalTrials.gov Identifier: NCT01452165)

Published
2023

8. Albuminuria Testing in Hypertension and Diabetes

Author

Jung-Im Shin, Alex R. Chang, Morgan E. Grams, Josef Coresh, Shoshana H. Ballew, Aditya Surapaneni, Kunihiro Matsushita, Henk J.G. Bilo, Juan J. Carrero, Gabriel Chodick, Kenn B. Daratha, Simerjot K. Jassal, Girish N. Nadkarni, Robert G. Nelson, Christoph Nowak, Nikita Stempniewicz, Keiichi Sumida, Jamie P. Traynor, Mark Woodward, Yingying Sang, Ron T. Gansevoort, John Chalmers, Katherine Tuttle, Radica Alicic, Sterling McPherson, Cami Jones, Gurmukteshwar Singh, Jamie Green, H. Lester Kirchner, Varda Shalev, Erwin P. Bottinger, Ruth J.F. Loos, Stephen B. Ellis, John Cuddeback, Elizabeth Ciemins, Emily Carbonara, Stephan Dunning, William C. Knowler, Helen C. Looker, Lyane M. Kieneker, Stephan J.L. Bakker, Hans L. Hillege, Pim van der Harst, Jacklyn Bergstrom, Joachim Ix, Csaba P. Kovesdy, Praveen Potukuchi, Marco Trevisan, Carl Gustaf Elinder, Björn Wettermark, Johan Ärnlöv, Patrick B. Mark, Peter C. Thomson, Colin C. Geddes, Gijs W.D. Landman, Kornelis J.J. van Hateren, Nanne Kleefstra, Orlando Gutierrez, Tsuneo Konta, Andrew S. Levey, Kevan Polkinghorne, Elke Schäffner, Jingsha Chen, Aditya Surapeneni, Groningen Kidney Center (GKC), and Cardiovascular Centre (CVC)

Subjects
Adult, medicine.medical_specialty, Article, Diabetes mellitus, Internal medicine, Internal Medicine, Diabetes Mellitus, Medicine, Albuminuria, Humans, Renal Insufficiency, Chronic, Aged, business.industry, Incidence (epidemiology), Odds ratio, Middle Aged, medicine.disease, Blood pressure, Meta-analysis, Creatinine, Cohort, Hypertension, medicine.symptom, business, Kidney disease, Glomerular Filtration Rate
Abstract

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%–74.5%) in diabetes and 4.1% (1.3%–20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42–1.60]; in hypertension, 1.36 [1.28–1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR

Published
2021

9. Inflammaging and Blood Pressure Profiles in Late Life

Author

Lisanne Tap, Andrea Corsonello, Mirko Di Rosa, Paolo Fabbietti, Francesc Formiga, Rafael Moreno-González, Johan Ärnlöv, Axel C. Carlsson, Harmke A. Polinder-Bos, Regina E. Roller-Wirnsberger, Gerhard H. Wirnsberger, Tomasz Kostka, Agnieszka Guligowska, Rada Artzi-Medvedik, Ilan Yehoshua, Christian Weingart, Cornel C. Sieber, Pedro Gil, Sara Lainez Martinez, Fabrizia Lattanzio, Francesco U. S. Mattace-Raso, and Internal Medicine

Subjects
hypertension, inflammation, neutrophil-to-lymphocyte ratio, blood pressure, vascular aging, older adults, Klinisk medicin, General Medicine, Pressió sanguínia, Inflamació, Persones grans, Hipertensió, Older people, Clinical Medicine
Abstract

The neutrophil-to-lymphocyte ratio (NLR) is a marker for systemic inflammation. Since inflammation plays a relevant role in vascular aging, the aim of this study was to investigate whether NLR is associated with blood pressure profiles in older adults. This study was performed within the framework of the SCOPE study including 2461 outpatients aged 75 years and over. Mean blood pressure values, namely systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were investigated across tertiles of NLR. Change in blood pressure levels in 2 years of follow-up were compared across categories of baseline NLR. Data of 2397 individuals were used, of which 1854 individuals had hypertension. Mean values of blood pressure did not differ across categories of baseline NLR in individuals without hypertension. Individuals with hypertension with a high-range NLR had lower SBP and PP when compared to those in low-range NLR (mean difference SBP −2.94 mmHg, p = 0.032 and PP −2.55 mmHg, p = 0.030). Mean change in blood pressure in 2 years did only slightly differ in non-clinically relevant ranges, when compared across tertiles of baseline NLR. NLR as a marker of inflammaging was not associated with unfavorable blood pressure profiles in older individuals with or without hypertension.

Published
2022

10. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Author

Liam Gaziano, Luanluan Sun, Matthew Arnold, Steven Bell, Kelly Cho, Stephen K. Kaptoge, Rebecca J. Song, Stephen Burgess, Daniel C. Posner, Katja Mosconi, Cassianne Robinson-Cohen, Amy M. Mason, Thomas R. Bolton, Ran Tao, Elias Allara, Petra Schubert, Lingyan Chen, James R. Staley, Natalie Staplin, Servet Altay, Pilar Amiano, Volker Arndt, Johan Ärnlöv, Elizabeth L.M. Barr, Cecilia Björkelund, Jolanda M.A. Boer, Hermann Brenner, Edoardo Casiglia, Paolo Chiodini, Jackie A. Cooper, Josef Coresh, Mary Cushman, Rachel Dankner, Karina W. Davidson, Renate T. de Jongh, Chiara Donfrancesco, Gunnar Engström, Heinz Freisling, Agustín Gómez de la Cámara, Vilmundur Gudnason, Graeme J. Hankey, Per-Olof Hansson, Alicia K. Heath, Ewout J. Hoorn, Hironori Imano, Simerjot K. Jassal, Rudolf Kaaks, Verena Katzke, Jussi Kauhanen, Stefan Kiechl, Wolfgang Koenig, Richard A. Kronmal, Cecilie Kyrø, Deborah A. Lawlor, Börje Ljungberg, Conor MacDonald, Giovanna Masala, Christa Meisinger, Olle Melander, Conchi Moreno Iribas, Toshiharu Ninomiya, Dorothea Nitsch, Børge G. Nordestgaard, Charlotte Onland-Moret, Luigi Palmieri, Dafina Petrova, Jose Ramón Quirós Garcia, Annika Rosengren, Carlotta Sacerdote, Masaru Sakurai, Carmen Santiuste, Matthias B. Schulze, Sabina Sieri, Johan Sundström, Valérie Tikhonoff, Anne Tjønneland, Tammy Tong, Rosario Tumino, Ioanna Tzoulaki, Yvonne T. van der Schouw, W.M. Monique Verschuren, Henry Völzke, Robert B. Wallace, S. Goya Wannamethee, Elisabete Weiderpass, Peter Willeit, Mark Woodward, Kazumasa Yamagishi, Raul Zamora-Ros, Elvis A. Akwo, Saiju Pyarajan, David R. Gagnon, Philip S. Tsao, Sumitra Muralidhar, Todd L. Edwards, Scott M. Damrauer, Jacob Joseph, Lisa Pennells, Peter W.F. Wilson, Seamus Harrison, Thomas A. Gaziano, Michael Inouye, Colin Baigent, Juan P. Casas, Claudia Langenberg, Nick Wareham, Elio Riboli, J.Michael Gaziano, John Danesh, Adriana M. Hung, Adam S. Butterworth, Angela M. Wood, Emanuele Di Angelantonio, Anna Koettgen, Jonathan Shaw, Robert Atkins, Paul Zimmet, Peter Whincup, Johann Willeit, Christoph Leitner, Anne Tybjaerg-Hansen, Peter Schnohr, Shoaib Afzal, David Lora Pablos, Cristina Martin Arriscado, Carmen Romero Ferreiro, Hannah Stocker, Ben Schöttker, Bernd Holleczek, Angela Chetrit, Lennart Welin, Kurt Svärdsudd, Lauren Lissner, Dominique Hange, Kirsten Mehlig, Dorothea Nagel, Paul E. Norman, Osvaldo Almeida, Leon Flicker, Jun Hata, Takanori Honda, Yoshihiko Furuta, Hiroyasu Iso, Akihiko Kitamura, Isao Muraki, Jukka T. Salonen, Tomi-Pekka Tuomainen, E. M. van Zutphen, N. M. van Schoor, Cinzia Lo Noce, Richard Kronmal, Georg Lappas, Peter M. Nilsson, Bo Hedblad, Jonathan Shaffer, Joseph Schwartz, Daichi Shimbo, Shinichi Sato, Mina Hayama-Terada, Simerjot Jassal, Thor Aspelund, Bolli Thorsson, Gunnar Sigurdsson, Layal Chaker, Kamran M. Ikram, Maryam Kavousi, Hugh Tunstall-Pedoe, Günay Can, Hüsniye Yüksel, Uğur Özkan, Hideaki Nakagawa, Yuko Morikawa, Masao Ishizaki, Edith Feskens, Johanna M Geleijnse, Daan Kromhout, Internal Medicine, Neurology, Epidemiology, Bell, Steven [0000-0001-6774-3149], Posner, Daniel C [0000-0002-3056-6924], Mason, Amy M [0000-0002-8019-0777], Allara, Elias [0000-0002-1634-8330], Staplin, Natalie [0000-0003-4482-4418], Arndt, Volker [0000-0001-9320-8684], Ärnlöv, Johan [0000-0002-6933-4637], Barr, Elizabeth LM [0000-0003-4284-1716], Boer, Jolanda MA [0000-0002-9714-4304], Brenner, Hermann [0000-0002-6129-1572], Casiglia, Edoardo [0000-0002-0003-3289], Chiodini, Paolo [0000-0003-0139-2264], Coresh, Josef [0000-0002-4598-0669], Cushman, Mary [0000-0002-7871-6143], Davidson, Karina W [0000-0002-9162-477X], de Jongh, Renate T [0000-0001-8414-3938], Engström, Gunnar [0000-0002-8618-9152], de la Cámara, Agustín Gómez [0000-0001-6827-6319], Gudnason, Vilmundur [0000-0001-5696-0084], Hankey, Graeme J [0000-0002-6044-7328], Hansson, Per-Olof [0000-0001-6323-0506], Heath, Alicia K [0000-0001-6517-1300], Hoorn, Ewout J [0000-0002-8738-3571], Imano, Hironori [0000-0002-6661-4254], Katzke, Verena [0000-0002-6509-6555], Kiechl, Stefan [0000-0002-9836-2514], Koenig, Wolfgang [0000-0002-2064-9603], Kronmal, Richard A [0000-0002-9897-7076], Kyrø, Cecilie [0000-0002-9083-8960], Ljungberg, Börje [0000-0002-4121-3753], MacDonald, Conor [0000-0002-4989-803X], Masala, Giovanna [0000-0002-5758-9069], Ninomiya, Toshiharu [0000-0003-1345-9032], Nordestgaard, Børge G [0000-0002-1954-7220], Onland-Moret, Charlotte [0000-0002-2360-913X], Palmieri, Luigi [0000-0002-4298-2642], Rosengren, Annika [0000-0002-5409-6605], Schulze, Matthias B [0000-0002-0830-5277], Sieri, Sabina [0000-0001-5201-172X], Sundström, Johan [0000-0003-2247-8454], Tikhonoff, Valérie [0000-0001-7846-0101], Tong, Tammy [0000-0002-0284-8959], Tzoulaki, Ioanna [0000-0002-4275-9328], van der Schouw, Yvonne T [0000-0002-4605-435X], Wannamethee, S Goya [0000-0001-9484-9977], Weiderpass, Elisabete [0000-0003-2237-0128], Willeit, Peter [0000-0002-1866-7159], Woodward, Mark [0000-0001-9800-5296], Yamagishi, Kazumasa [0000-0003-3301-5519], Zamora-Ros, Raul [0000-0002-6236-6804], Gagnon, David R [0000-0002-6367-3179], Tsao, Philip S [0000-0001-7274-9318], Edwards, Todd L [0000-0003-4318-6119], Damrauer, Scott M [0000-0001-8009-1632], Joseph, Jacob [0000-0002-7279-4896], Pennells, Lisa [0000-0002-8594-3061], Gaziano, Thomas A [0000-0002-5985-345X], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nick [0000-0003-1422-2993], Hung, Adriana M [0000-0002-3203-1608], Butterworth, Adam S [0000-0002-6915-9015], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Gaziano, Liam, Sun, Luanluan, Arnold, Matthew, Bell, Steven, Cho, Kelly, Kaptoge, Stephen K, Song, Rebecca J, Burgess, Stephen, Posner, Daniel C, Mosconi, Katja, Robinson-Cohen, Cassianne, Mason, Amy M, Bolton, Thomas R, Tao, Ran, Allara, Elia, Schubert, Petra, Chen, Lingyan, Staley, James R, Staplin, Natalie, Altay, Servet, Amiano, Pilar, Arndt, Volker, Ärnlöv, Johan, Barr, Elizabeth L M, Björkelund, Cecilia, Boer, Jolanda M A, Brenner, Hermann, Casiglia, Edoardo, Chiodini, Paolo, Cooper, Jackie A, Coresh, Josef, Cushman, Mary, Dankner, Rachel, Davidson, Karina W, de Jongh, Renate T, Donfrancesco, Chiara, Engström, Gunnar, Freisling, Heinz, de la Cámara, Agustín Gómez, Gudnason, Vilmundur, Hankey, Graeme J, Hansson, Per-Olof, Heath, Alicia K, Hoorn, Ewout J, Imano, Hironori, Jassal, Simerjot K, Kaaks, Rudolf, Katzke, Verena, Kauhanen, Jussi, Kiechl, Stefan, Koenig, Wolfgang, Kronmal, Richard A, Kyrø, Cecilie, Lawlor, Deborah A, Ljungberg, Börje, Macdonald, Conor, Masala, Giovanna, Meisinger, Christa, Melander, Olle, Moreno Iribas, Conchi, Ninomiya, Toshiharu, Nitsch, Dorothea, Nordestgaard, Børge G, Onland-Moret, Charlotte, Palmieri, Luigi, Petrova, Dafina, Garcia, Jose Ramón Quiró, Rosengren, Annika, Sacerdote, Carlotta, Sakurai, Masaru, Santiuste, Carmen, Schulze, Matthias B, Sieri, Sabina, Sundström, Johan, Tikhonoff, Valérie, Tjønneland, Anne, Tong, Tammy, Tumino, Rosario, Tzoulaki, Ioanna, van der Schouw, Yvonne T, Monique Verschuren, W M, Völzke, Henry, Wallace, Robert B, Wannamethee, S Goya, Weiderpass, Elisabete, Willeit, Peter, Woodward, Mark, Yamagishi, Kazumasa, Zamora-Ros, Raul, Akwo, Elvis A, Pyarajan, Saiju, Gagnon, David R, Tsao, Philip S, Muralidhar, Sumitra, Edwards, Todd L, Damrauer, Scott M, Joseph, Jacob, Pennells, Lisa, Wilson, Peter W F, Harrison, Seamu, Gaziano, Thomas A, Inouye, Michael, Baigent, Colin, Casas, Juan P, Langenberg, Claudia, Wareham, Nick, Riboli, Elio, Gaziano, J Michael, Danesh, John, Hung, Adriana M, Butterworth, Adam S, Wood, Angela M, Di Angelantonio, Emanuele, Internal medicine, AMS - Ageing & Vitality, AMS - Musculoskeletal Health, Amsterdam Gastroenterology Endocrinology Metabolism, Epidemiology and Data Science, APH - Aging & Later Life, and APH - Personalized Medicine

Subjects
kidney disease, General Practice, Emerging Risk Factors Collaboration/EPIC-CVD/Million Veteran Program, Coronary Disease, coronary disease, Kidney, Malalties coronàries, 1117 Public Health and Health Services, Coronary diseases, SDG 3 - Good Health and Well-being, cardiovascular disease, Risk Factors, Physiology (medical), Diabetes Mellitus, Humans, Cardiac and Cardiovascular Systems, Prospective Studies, 1102 Cardiorespiratory Medicine and Haematology, Kardiologi, Kidney diseases, Malalties cardiovasculars, Cardiovascular Diseases, Kidney Diseases, Stroke, 1103 Clinical Sciences, Mendelian Randomization Analysis, kidney diseases, stroke, Allmänmedicin, Cardiovascular diseases, Cardiovascular System & Hematology, Malalties del ronyó, Cardiology and Cardiovascular Medicine, cardiovascular diseases
Abstract

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Published
2022

12. The relevance of geriatric assessments on the association between chronic kidney disease stages and mortality among older people

Author

Andrea, Corsonello, Luca, Soraci, Johan, Ärnlöv, Axel C, Carlsson, Regina, Roller-Wirnsberger, Gerhard, Wirnsberger, Francesco, Mattace-Raso, Lisanne, Tap, Francesc, Formiga, Rafael, Moreno-González, Tomasz, Kostka, Agnieszka, Guligowska, Rada, Artzi-Medvedik, Itshak, Melzer, Christian, Weingart, Cornell, Sieber, Fabrizia, Lattanzio, Tobias, Feldreich, and Internal Medicine

Subjects
Aging, glomerulus filtration rate, estimated glomerular filtration rate, very elderly, mortality rate, Persones grans, Cohort Studies, cognitive defect, Activities of Daily Living, eGFR, Renal Insufficiency, Prospective Studies, Chronic, Kidney diseases, Hand Strength, clinical trial, General Medicine, chronic kidney failure, cohort analysis, mild renal impairment, female, moderate renal impairment, prospective study, Glomerular Filtration Rate, ADL disability, albumin to creatinine ratio, Geriatrik, short physical performance battery, complication, malnutrition, Article, male, Mortalitat, Albuminuria, Humans, human, Renal Insufficiency, Chronic, Mortality, Geriatric Assessment, Aged, ACR, physical performance, daily life activity, major clinical study, multicenter study, disability, Geriatrics, grip strength, Malalties del ronyó, prognosis, Geriatrics and Gerontology, Older people, Geriatria
Abstract

Background age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. Methods our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. Results overall, mortality was found to increase starting from eGFR = 30–44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81–5.95) to ACR = 30–300 mg/g (HR = 1.96, 95%CI = 1.23–3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45–59.9 ml/min/1.73 m2, as well as patients with ACR Conclusions physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild–moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function.

Published
2022

13. Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes

Author

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

Subjects
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.

Published
2021

14. Obstructive sleep apnea is associated with specific gut microbiota species and functions in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS)

Author

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.

Published
2022

15. Streptococcusspecies abundance in the gut is linked to subclinical coronary atherosclerosis in 8973 participants from the SCAPIS cohort

Author

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.

Published
2022

16. A longitudinal study over 40 years to study the metabolic syndrome as a risk factor for cardiovascular diseases

Author

Johan Ärnlöv, Lars Lind, Johan Sundström, Ulf Risérus, and Erik Lampa

Subjects
Adult, Male, medicine.medical_specialty, Longitudinal study, Epidemiology, Science, Myocardial Infarction, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Article, Healthy Aging, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Genetics research, Prevalence, medicine, Humans, Cardiac and Cardiovascular Systems, Longitudinal Studies, Myocardial infarction, Risk factor, Aged, Ischemic Stroke, Aged, 80 and over, Heart Failure, Metabolic Syndrome, Multidisciplinary, Kardiologi, business.industry, Incidence, Cardiometabolic Risk Factors, Middle Aged, medicine.disease, Stroke, Risk factors, Ageing, Relative risk, Heart failure, Medicine, Observational study, Metabolic syndrome, business, Follow-Up Studies
Abstract

The impact of most, but not all, cardiovascular risk factors decline by age. We investigated how the metabolic syndrome (MetS) was related to cardiovascular disease (CVD) during 40 years follow-up in the Uppsala Longitudinal Study of Adult Men (ULSAM, 2,123 men all aged 50 at baseline with reinvestigations at age 60, 70, 77 and 82). The strength of MetS as a risk factor of incident combined end-point of three outcomes (CVD) declined with ageing, as well as for myocardial infarction, ischemic stroke and heart failure when analysed separately. For CVD, the risk ratio declined from 2.77 (95% CI 1.90–4.05) at age 50 to 1.30 (95% CI 1.05–1.60) at age 82. In conclusion, the strength of MetS as a risk factor of incident CVD declined with age. Since MetS was significantly related to incident CVD also at old age, our findings suggest that the occurrence of MetS in the elderly should not be regarded as innocent. However, since our data were derived in an observational study, any impact of MetS in the elderly needs to be verified in a randomized clinical intervention trial.

Published
2021

17. Kidney function and other factors and their association with falls

Author

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, and on behalf of the SCOPE investigators

Subjects
lcsh:RC952-954.6, Kidney function, Urinary incontinence, Falls, Fear of falling, Older people, Injurious falls, lcsh:Geriatrics
Abstract

Background Reduced kidney function has become a major public health concern, especially among older people, as Chronic Kidney Disease (CKD) is associated with increased risk of end stage renal disease and mortality. Falls are a serious negative health outcome in older persons with one third of people aged 65 years experiencing a fall per year and increasing fall rates with increasing age. The impact of CKD on falls in older community-dwelling persons is not well investigated. Additionally, lower urinary tract symptoms (LUTS) may also increase the risk of falls. Therefore, our aim was to investigate the impact of CKD and LUTS on falls as well as on injurious falls. Methods The SCOPE study is an observational, multinational, multicenter, prospective cohort study involving community-dwelling older persons aged 75 years and more recruited from August 2016 to March 2018 in seven European countries. The main outcomes of the present study were any falls and any injurious falls during the 12 months before enrolment. The cross-sectional association of estimated glomerular filtration rate (eGFR) and LUTS with study outcomes was investigated by logistic regression analysis adjusted for baseline characteristics of enrolled subjects. Results Our series consisted of 2256 SCOPE participants (median age = 79.5 years, 55.7% female). Of them, 746 participants experienced a fall and 484 reported an injurious fall in the 12 months prior to baseline assessment. CKD was not significantly associated with falls (OR = 0.95, 95%CI = 0.79–1.14 for eGFR

Published
2020

18. Association between kidney function, nutritional status and anthropometric measures in older people

Author

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, and on behalf of SCOPE investigators

Subjects
Aging, lcsh:RC952-954.6, MNA, Chronic kidney disease, Malnutrition, Undernutrition, Overweight, lcsh:Geriatrics
Abstract

Background Different mechanisms connect the nutritional status with the occurrence and the course of chronic kidney disease (CKD). The end-stage renal disease is complicated by catabolic inflammatory reactions and cachexia which leads to malnutrition (undernutrition). On the other hand, obesity is an important risk factor for the development and acceleration of CKD. Methods In the SCOPE study, community-dwelling persons aged 75 years and over, from 6 European countries and Israel were examined at the baseline phase. We assessed the relationship between anthropometric measures (Body Mass Index (BMI), circumferences of arm (AC), waist (WC), hip (HC), and calf (CC), waist-to-hip ratio - WHR, waist-to-height ratio - WHtR, risk of malnutrition (Mini Nutritional Assessment - MNA), serum albumin) and estimated glomerular filtration rate (eGFR) calculated by Berlin Initiative Study (BIS) equation. Results We studied 2151 subjects (932 men and 1219 women) with a mean age of 79.5 ± 5.9 years. A total of 1333 (62%) participants had CKD (GRF 60 (OR = 2.95, 95%CI = 1.77–4.94 for MNA

Published
2020

19. Targeted multiplex proteomics for prediction of all-cause mortality during long-term follow-up in outpatients with peripheral arterial disease

Author

Philippe Wagner, Emma Skau, Johan Ärnlöv, Jerzy Leppert, Pär Hedberg, and Egil Henriksen

Subjects
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.

Published
2020

20. Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance

Author

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, and on behalf of SCOPE investigators

Subjects
Short physical performance battery, Older, lcsh:RC952-954.6, Chronic kidney disease, Multimorbidity, lcsh:Geriatrics, urologic and male genital diseases, female genital diseases and pregnancy complications
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

Published
2020

21. Impaired kidney function is associated with lower quality of life among community-dwelling older adults

Author

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, and on behalf of the SCOPE investigators

Subjects
Quality of life, lcsh:RC952-954.6, Old adults, Chronic kidney disease, lcsh:Geriatrics
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

Published
2020

22. Is kidney function associated with cognition and mood in late life?

Author

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, and on behalf of SCOPE investigators

Subjects
lcsh:RC952-954.6, Cognition, Cognitive impairment, Chronic kidney disease, Mood, Depressive symptoms, Estimated glomerular filtration rate, lcsh:Geriatrics
Abstract

Background Chronic kidney disease (CKD), cognitive impairment and depression share common risk factors. Previous studies did not investigate the possible association between kidney function and cognitive and mood disorders in older persons in a broad range of kidney function. The present study explored associations between kidney function, cognition and mood in outpatients of 75 years and over. Methods Baseline data of 2252 participants of the SCOPE study, an international multicenter cohort observational study,were used in which community-dwelling persons of 75 years and over were enrolled to screen for CKD Kidney function was estimated with the BIS1-eGFR equation, cognition was assessed with the Mini-Mental State Examination (MMSE) and mood with the Geriatric Depression Scale 15 items (GDS-15). Characteristics were compared across stages of CKD. Mean eGFR values were also compared across categories of MMSE ( 5/≤5). Results In total, 63% of the population had an eGFR

Published
2020

23. Diabetes, sarcopenia and chronic kidney disease; the Screening for CKD among Older People across Europe (SCOPE) study

Author

Francesc, Formiga, Rafael, Moreno-González, Andrea, Corsonello, Axel, Carlsson, Johan, Ärnlöv, Francesco, Mattace-Raso, Tomasz, Kostka, Christian, Weingart, Regina, Roller-Wirnsberger, Lisanne, Tap, Agnieszka, Guligowska, Cornel, Sieber, Gerhard, Wirnsberger, Rada, Artzi-Medvedik, Ilan, Yehoshua, Cinzia, Giuli, Fabrizia, Lattanzio, Xavier, Corbella, Paul E, Stevens, Internal Medicine, Medical Informatics, ACS - Pulmonary hypertension & thrombosis, APH - Aging & Later Life, APH - Quality of Care, and APH - Global Health

Subjects
Male, Renal failure, Sarcopenia, Hand Strength, Diabetes, Cross-Sectional Studies, Elderly, SDG 3 - Good Health and Well-being, Chronic kidney disease, Diabetes Mellitus, Humans, Female, Prospective Studies, Renal Insufficiency, Chronic, Geriatrics and Gerontology, human activities, Aged
Abstract

Background Sarcopenia may be more present in older adults with diabetes (DM). Accordingly, we evaluated the prevalence of sarcopenia and its associated risk factors among community-dwelling older adults with DM. Methods A cross-sectional analysis of older people living in the community was carried out. Participants (aged 75 years and more) came from an European multicenter prospective cohort (SCOPE study). Global geriatric assessment including short physical performance battery, handgrip strength test and bioelectrical impedance analysis was performed. Sarcopenia was defined by the updated criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). Estimated glomerular filtration rate (eGFR) was calculated using Berlin Initiative Study (BIS) to define the stages of chronic kidney disease (CKD). Previous known DM was defined as physician-diagnosed DM registered in the patient's medical record or the use of DM-related medications. Hemoglobin A1c levels and specific DM therapies administered were collected. Time elapsed from the first diagnosis of DM was not collected and, therefore, was not included in the analyses. Results A total of 1,420 subjects were evaluated with a median age of 79.0 (6.0) years, of which 804 (56.6%) were women and 615 (43.3%) men; 315 (22.2%) participants had prior DM diagnosis, with a median age of 80.0 (6.0), 146 (46.3%) were women. Using EWGSOP2 definition, 150 (10.6%) participants in the SCOPE study met diagnostic criteria for sarcopenia. Participants without diabetes had more often normal results in the 3 sarcopenia components than participants with diabetes [887 (80.31%) vs. 227 (72.1%), p = 0.002], highlighting higher percentages of severe sarcopenia in participants with diabetes [27 (8.6%) vs. 58 (5.2%), p = 0.028]. Confirmed or severe sarcopenia was detected in 41 (13%) participants with diabetes and 109 (9.8%) participants without diabetes (p = 0.108). According to BIS equation, sarcopenia was not significantly more prevalent in the more advanced stages of CKD (p = 0.845). In multivariate analyses, older age (odds ratios [OR], 1.17; 95% confidence interval [CI], 1.08–1.27), and lower body mass index (OR, 0.79; 95% CI, 0.71–0.89 were associated with the presence of sarcopenia. Conclusions One tenth of all older community-dwelling subjects have sarcopenia. Older age and being thinner, but not worse renal function, were associated with higher prevalence of sarcopenia in older older adults with diabetes.

Published
2022

24. Genetically Predicted Circulating Copper and Risk of Chronic Kidney Disease: A Mendelian Randomization Study

Author

Shafqat Ahmad, Johan Ärnlöv, and Susanna C. Larsson

Subjects
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.

Published
2022

25. Obesity is associated with coronary artery stenosis independently of metabolic risk factors : The population-based SCAPIS study

Author

Lars Lind, Hanna Markstad, Håkan Ahlström, Oskar Angerås, John Brandberg, Mattias Brunström, Gunnar Engström, Jan E. Engvall, Maria J. Eriksson, Mats Eriksson, Anders Gottsäter, Emil Hagström, Benno Krachler, Erik Lampa, Maria Mannila, Peter M. Nilsson, Fredrik H. Nyström, Anders Persson, Björn Redfors, Anette Sandström, Raquel Themudo, Sebastian Völz, Johan Ärnlöv, Carl Johan Östgren, and Göran Bergström

Subjects
Male, Metabolic Syndrome, Kardiologi, Epidemiology, Coronary Stenosis, Klinisk medicin, Middle Aged, Overweight, Atherosclerosis, Metabolic syndrome, Plaque, Atherosclerotic, Coronary arteries, Cross-Sectional Studies, Risk Factors, Humans, Female, Carotid Stenosis, Cardiac and Cardiovascular Systems, Obesity, Clinical Medicine, Cardiology and Cardiovascular Medicine, Carotid artery
Abstract

Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound.Methods: In the SCAPIS study (50-65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria.Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34-1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87-1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect.Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS. Funding Agencies|SCAPIS is the Swedish Heart -Lung Foundation; Knut and Alice Wallenberg Foundation; Swedish Research Council; VINNOVA (Swedens Innovation agency) the University of Gothenburg and Sahlgrenska University Hospital; Karolinska Institutet and Stockholm county council; Linkoping University and University Hospital; Lund University and Skane University Hospital; Ume University and University Hospital; Uppsala University and University Hospital

Published
2022

26. The complexity of kidney disease and diagnosing it - Cystatin C, selective glomerular hypofiltration syndromes and proteome regulation

Author

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

Subjects
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.

Published
2022
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27. The association between short-term, chronic localized and chronic widespread pain and risk for cardiovascular disease in the UK Biobank

Author

Ann-Sofie Rönnegård, Christoph Nowak, Björn Äng, and Johan Ärnlöv

Subjects
Heart Failure, Kardiologi, Epidemiology, Myocardial Infarction, Klinisk medicin, Chronic pain, Cardiovascular disease, United Kingdom, Stroke, Cardiovascular Diseases, Risk Factors, Chronic Disease, Humans, Cardiac and Cardiovascular Systems, Chronic Pain, Clinical Medicine, Cardiology and Cardiovascular Medicine, Biological Specimen Banks
Abstract

Aims The interplay between pain of different chronicity and cardiovascular disease (CVD) is incompletely understood. We aimed to investigate the association between different levels of chronic or nonchronic pain and risk of CVD. Methods and results Participants in the UK Biobank who reported pain at baseline were divided into three groups according to pain duration and widespreadness. Participants reporting no pain were controls. Multivariable Cox regression was used to investigate the association between pain and incidence of myocardial infarction, heart failure, stroke, cardiovascular mortality, and composite CVD (defined as any of the before-mentioned cardiovascular events). Of 475 171 participants, 189 289 reported no pain, 87 830 reported short-term pain, 191 716 chronic localized pain, and 6336 chronic widespread pain (CWP). During a median of 7.0 years’ follow-up, participants with chronic localized pain and CWP had, after adjustment for age, sex, established cardiovascular risk factors, physical activity, anxiety, depression, cancer, chronic inflammatory/painful disease, pain/anti-inflammatory medication, socioeconomic status, a significantly increased risk for composite CVD [hazard ratio (HR) 1.14, confidence interval (CI) 1.08–1.21, P < 0.001; and HR 1.48, CI 1.28–1.73, P < 0.001, respectively] compared with controls, with similar results when using the different specific CVDs as outcomes. Population attributable risk proportion for chronic pain as a risk factor for composite CVD was comparable with that of diabetes (8.6 vs. 7.3%, respectively). Conclusion Chronic pain is associated with an increased risk for myocardial infarction, stroke, heart failure, and cardiovascular death independent of established cardiovascular risk factors, socioeconomic factors, comorbidities and medication. Our study, the largest to date, confirms and extends our understanding of chronic pain as an underestimated cardiovascular risk factor with important public health implications.

Published
2022

28. Association between albuminuria, incident cardiovascular events, and mortality in persons without hypertension, diabetes, and cardiovascular disease

Author

Christoph Nowak and Johan Ärnlöv

Subjects
medicine.medical_specialty, Kardiologi, Epidemiology, business.industry, Disease, medicine.disease, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Risk Factors, Internal medicine, Diabetes mellitus, Hypertension, Research Letter, Albuminuria, medicine, Humans, Diabetic Nephropathies, Cardiac and Cardiovascular Systems, medicine.symptom, Cardiology and Cardiovascular Medicine, business
Published
2022

29. Dissatisfaction with teeth in type 2 diabetes is associated with increased risk of cardiovascular disease

Author

Edvin Ström, Tobias Rudholm Feldreich, Johan Ärnlöv, Carl Johan Östgren, Fredrik H Nystrom, and Magnus O Wijkman

Subjects
Kardiologi, Epidemiology, Cardiac and Cardiovascular Systems, type 2 diabetes, self-reported dental health
Abstract

Background and aim Poor dental health status has been linked to increased risk of cardiovascular events in type 2 diabetes (T2D). Less is known about self-perceived dental health and cardiovascular risk. Our aim with this study was to investigate this association. Methods Recruitment of T2D patients took place between 2005 and 2008 in Swedish primary care. Teeth satisfaction was assessed by questionnaire at baseline. The major adverse cardiovascular events (MACE) in this study were hospitalization due to myocardial infarction, stroke or cardiovascular death. Cox regression models were used. Results Out of 761 participants 601 had complete data. Ninety-two MACEs occurred (median follow-up time: 11.6 years). Those satisfied with their teeth (n = 458) had 61 events (1.2 events per 100 person-years), while those dissatisfied with teeth (n = 143) had 31 events (2.2 events per 100 person-years). Dissatisfaction with teeth was associated with an increased risk of MACE independent of age, sex and levels of CRP (HR 1.85, 95% CI 1.20 – 2.86). Conclusions In patients with T2D, dissatisfaction with teeth was associated with increased risk of MACE and may be considered as a marker of risk. Funding agencies: This work was supported by grant support from FORSS, the Medical Research Council of Southeast Sweden.

Published
2022

30. The association between length of stay in the emergency department and short-term mortality

Author

Ulf Ekelund, Johan Ärnlöv, Toralph Ruge, Torgny Wessman, Per Wändell, Axel C. Carlsson, and Olle Melander

Subjects
Adult, medicine.medical_specialty, Anestesi och intensivvård, Epidemiology, Short term mortality, Logistic regression, Elderly, Internal Medicine, medicine, Humans, In patient, Retrospective Studies, Emergency department crowding, Anesthesiology and Intensive Care, business.industry, Mortality rate, Emergency room, Emergency department, Length of Stay, University hospital, Triage, Hospitalization, Emergency department length of stay, Emergency medicine, Emergency Medicine, business, Emergency Service, Hospital
Abstract

The detrimental effects of increased length of stay at the emergency department (ED-LOS) for patient outcome have been sparsely studied in the Swedish setting. Our aim was to further explore the association between ED-LOS and short-term mortality in patients admitted to the EDs of two large University hospitals in Sweden. 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 retrospectively included. Logistic regression analysis was used to determine association between ED-LOS and 7- and 30-day mortality rates. All patients were triaged according to the RETTS-A into different levels of medical urgency and subsequently separated into five quintiles of ED-LOS. Mortality rate was highest in highest triage priority level (7-day mortality 5.24%, and 30-day mortality 9.44%), and decreased by lower triage priority group. For patients with triage priority levels 2–4, prolonged ED-LOS was associated with increased mortality, especially for lowest priority level, OR for priority level 4 and highest quintile of ED-LOS 30-day mortality 1.49 (CI 95% 1.20–1.85). For patients with highest triage priority level the opposite was at hand, with decreasing mortality risk with increasing quintile of ED-LOS for 7-day mortality, and lower mortality for the two highest quintile of ED-LOS for 30-day mortality. In patients not admitted to in-hospital care higher ED-LOS was associated with higher mortality. Our data suggest that increased ED-LOS could be associated with slightly increased short-term mortality in patients with lower clinical urgency and dismissed from the ED.

Published
2022

31. Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study

Author

Susanna C. Larsson, Ulf Risérus, Johan Ärnlöv, Beatrice Kennedy, Andrea Ganna, Tove Fall, Christian Berne, Samira Salihovic, Patrik K. E. Magnusson, Ulf Hammar, Shafqat Ahmad, Lars Lind, and Johan Sundström

Subjects
Adult, Male, Endocrinology, Diabetes and Metabolism, Population, Physiology, Endocrinology and Diabetes, Creatine, Body Mass Index, Cohort Studies, chemistry.chemical_compound, Framingham Heart Study, Endocrinology, Risk Factors, Germany, Mendelian randomization, Metabolome, Internal Medicine, Body Fat Distribution, Humans, Metabolomics, Medicine, education, Adiposity, Aged, Aged, 80 and over, Sweden, education.field_of_study, Waist-Hip Ratio, business.industry, Mendelian Randomization Analysis, Middle Aged, medicine.disease, Obesity, United Kingdom, United States, Diabetes and Metabolism, chemistry, Obesity, Abdominal, Cohort, Endokrinologi och diabetes, Female, business, Body mass index
Abstract

Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

Published
2022

32. Patterns of multimorbidity and pharmacotherapy: a total population cross-sectional study

Author

Johan Ärnlöv, Gunnar Ljunggren, Caroline Wachtler, Tomas Forslund, and Axel C. Carlsson

Subjects
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.

Published
2020

33. Impact of the Definition of Metabolically Healthy Obesity on the Association with Incident Cardiovascular Disease

Author

Ulf Risérus, Johan Ärnlöv, and Lars Lind

Subjects
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...

Published
2020

34. Plant-based diets, insulin sensitivity and inflammation in elderly men with chronic kidney disease

Author

Ailema González-Ortiz, Tommy Cederholm, Ángeles Espinosa-Cuevas, Carla Maria Avesani, Ulf Risérus, Bengt Lindholm, Hong Xu, Juan Jesus Carrero, and Johan Ärnlöv

Subjects
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

Published
2020

35. 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

Author

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

Subjects
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.

Published
2020

36. Association of Test Results for 33 Frequently Used Laboratory Tests with Body Mass Index (BMI)

Author

Anders Larsson, Johan Ärnlöv, Johanna Helmersson-Karlqvist, Lars Lind, and Peter Ridefelt

Subjects
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.

Published
2020

37. Endostatin predicts mortality in patients with acute dyspnea – A cohort study of patients seeking care in emergency departments

Author

Rafid Tofik, Olle Melander, Johan Ärnlöv, Thoralph Ruge, Axel C. Carlsson, G Leijonberg, Torgny Wessman, and Anders Larsson

Subjects
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

38. Changes in Proteomic Profiles are Related to Changes in BMI and Fat Distribution During 10 Years of Aging

Author

Erik Ingelsson, Lars Lind, Johan Sundström, Johan Ärnlöv, Sylwia M. Figarska, and Tove Fall

Subjects
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.

Published
2019

39. Growth differentiation factor 15 (GDF-15) is a potential biomarker of both diabetic kidney disease and future cardiovascular events in cohorts of individuals with type 2 diabetes: a proteomics approach

Author

Christoph Nowak, Johan Ärnlöv, Ulf Risérus, Johan Sundström, Carl Johan Östgren, Fredrik H. Nystrom, Juan Jesus Carrero, Lars Lind, Tove Fall, Erik Ingelsson, and Axel C. Carlsson

Subjects
Oncology, Male, Proteomics, medicine.medical_specialty, Growth Differentiation Factor 15, Albumin-creatinine ratio, type 2 diabetes mellitus, Renal function, lcsh:Medicine, 030209 endocrinology & metabolism, Type 2 diabetes, Disease, Endocrinology and Diabetes, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, proteomics, Risk Factors, Diabetes mellitus, Internal medicine, Medicine, Humans, Diabetic Nephropathies, Risk factor, Aged, Sweden, glomerular filtration rate, 030219 obstetrics & reproductive medicine, business.industry, lcsh:R, Klinisk medicin, Type 2 Diabetes Mellitus, General Medicine, Articles, Middle Aged, medicine.disease, diabetic kidney disease, 3. Good health, risk factor, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Endokrinologi och diabetes, Biomarker (medicine), biomarker, Female, GDF15, Clinical Medicine, business, Biomarkers
Abstract

Background: Diabetic kidney disease (DKD) is a leading risk factor for end-stage renal disease and is one of the most important risk factors for cardiovascular disease in patients with diabetes. It is possible that novel markers portraying the pathophysiological underpinning processes may be useful. Aim: To investigate the associations between 80 circulating proteins, measured by a proximity extension assay, and prevalent DKD and major adverse cardiovascular events (MACE) in type 2 diabetes. Methods: We randomly divided individuals with type 2 diabetes from three cohorts into a two-thirds discovery and one-third replication set (total n = 813, of whom 231 had DKD defined by estimated glomerular filtration rate = 3 g/mol). Proteins associated with DKD were also assessed as predictors for incident major adverse cardiovascular events (MACE) in persons with DKD at baseline. Results: Four proteins were positively associated with DKD in models adjusted for age, sex, cardiovascular risk factors, glucose control, and diabetes medication: kidney injury molecule-1 (KIM-1, odds ratio [OR] per standard deviation increment, 1.65, 95% confidence interval [CI] 1.27-2.14); growth differentiation factor 15 (GDF-15, OR 1.40, 95% CI 1.16-1.69); myoglobin (OR 1.57, 95% CI 1.30-1.91), and matrix metalloproteinase 10 (MMP-10, OR 1.43, 95% CI 1.17-1.74). In patients with DKD, GDF-15 was significantly associated with increased risk of MACE after adjustments for baseline age, sex, microalbuminuria, and kidney function and (59 MACE events during 7 years follow-up, hazard ratio per standard deviation increase 1.43 [95% CI 1.03-1.98]) but not after further adjustments for cardiovascular risk factors. Conclusion: Our proteomics approach confirms and extends previous associations of higher circulating levels of GDF-15 with both micro- and macrovascular disease in patients with type 2 diabetes. Our data encourage additional studies evaluating the clinical utility of our findings.

Published
2019

40. An online atlas of human plasma metabolite signatures of gut microbiome composition

Author

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

Subjects
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

41. A screening method to spot biomarkers that may warn of serious events in a chronic disease:Illustrated by cardiological CLARICOR trial data

Author

Erik Kjøller, Per Winkel, Jørgen Hilden, Mette Bjerre, Johan Ärnlöv, Jens Kastrup, Jane Lindschou, Christian Gluud, Anders Larsson, Ahmad Sajadieh, Hans Jørn Kolmos, Gorm B. Jensen, and Janus Christian Jakobsen

Subjects
medicine.medical_specialty, medicine.drug_class, Clinical Biochemistry, Renal function, ADJUDICATION, Coronary Artery Disease, reverse alignment, Coronary artery disease, Troponin T, Risk Factors, Internal medicine, Natriuretic Peptide, Brain, Natriuretic peptide, Screening method, Medicine, Humans, ARTERY-DISEASE, CORONARY-HEART-DISEASE, control charts, Survival analysis, REGISTER, business.industry, MORTALITY, Biochemistry (medical), biomarkers, General Medicine, personalized medicine, CLARITHROMYCIN, medicine.disease, Prognosis, Peptide Fragments, AGREEMENT, cardiology, Cohort, Chronic Disease, Biomarker (medicine), Personalized medicine, business, Biomarkers, Glomerular Filtration Rate
Abstract

Objectives To develop a crude screening method for detecting biomarkers which frequently exhibit a rise (or fall) in level prior to a serious event (e.g. a stroke) in patients with a chronic disease, signalling that the biomarker may have an alarm-raising or prognostic potential. The subsequent assessment of the marker’s clinical utility requires costly, difficult longitudinal studies. Therefore, initial screening of candidate-biomarkers is desirable. Methods The method exploits a cohort of patients with biomarkers measured at entry and with recording of first serious event during follow-up. Copying those individual records onto a common timeline where a specific event occurs on the same day (Day 0) for all patients, the baseline biomarker level, when plotted against the patient’s entry time on the revised timeline, will have a positive (negative) regression slope if biomarker levels generally rise (decline) the closer one gets to the event. As an example, we study 1,958 placebo-treated patients with stable coronary artery disease followed for nine years in the CLARICOR trial (NCT00121550), examining 11 newer biomarkers. Results Rising average serum levels of cardiac troponin T and of N-terminal pro-B-type natriuretic peptide were seen prior to a fatal cardiovascular outcome. C-reactive protein rose prior to non-cardiovascular death. Glomerular filtration rate, seven lipoproteins, and nine newer cardiological biomarkers did not show convincing changes. Conclusions For early detection of biomarkers with an alarm-raising potential in chronic diseases, we proposed the described easy procedure. Using only baseline biomarker values and clinical course of participants with coronary heart disease, we identified the same cardiovascular biomarkers as those previously found containing prognostic information using longitudinal or survival analysis.

Published
2021

42. Global, regional, and national burden of stroke and its risk factors, 1990–2019 : a systematic analysis for the Global Burden of Disease Study 2019

Author

Mosiur Rahman, Rehab Salah, Mario F P Peres, Licia Iacoviello, Benjamin A Stark, Mahalaqua Nazli Khatib, Amir Radfar, Kamarul Imran Musa, Yannick Béjot, Deanna Anderlini, Carlos Cantú-Brito, Feng Sha, V. E. Nwatah, Pradip Gyanwali, Boris Bikbov, Bartosz Miazgowski, Sindhura Lakshmi Koulmane Laxminarayana, Ali Bijani, Imteyaz A Khan, Yaser Mokhayeri, Bogdan Oancea, Tarang Parekh, Martin Dichgans, Linh Gia Vu, Naohiro Yonemoto, Ahmad Ghashghaee, Marcos Roberto Tovani-Palone, Gebiyaw Wudie Tsegaye, Mona Pathak, Maciej Banach, Marissa B Reitsma, Derrick A Bennett, Treska S Hassan, Allen Seylani, Gdiom Gebreheat Abady, Islam Y. Elgendy, Hassan Mehmood Lak, Ismael R. Campos-Nonato, Sorin Hostiuc, Sheikh Mohammed Shariful Islam, Alessandra C. Goulart, Silvia Schiavolin, Simona Sacco, Atif Amin Baig, Azeem Majeed, Sahar Eftekharzadeh, Badr Hasan Sobaih, Archith Boloor, Aimé Bonny, Graeme J. Hankey, Jiregna Darega Gela, Mohamed I Hegazy, Pedram Keshavarz, Segun Emmanuel Ibitoye, Maseer Khan, Hatem Abdelaziz Mohamed Wafa, Hualiang Lin, Enayet Karim Chowdhury, Simon I. Hay, Vanessa De la Cruz-Góngora, Xuefeng Liu, Arokiasamy Perianayagam, Maryam Zamanian, Sezer Kisa, Preetam Bhalchandra Mahajan, Junmei Miao Jonasson, Alberto Raggi, Shubha Jayaram, Tahira Ashraf, Ejaz Ahmad Khan, Matthias Endres, Masoumeh Sadeghi, Dominique Vervoort, Hanadi Al Hamad, Mowafa Househ, Elena V. Gnedovskaya, Johan Ärnlöv, Andrea Sylvia Winkler, Yousef Khader, Mikhail Sergeevich Zastrozhin, Yuming Guo, Yunquan Zhang, Sami Almustanyir, Lalit Dandona, Amir Masoud Rahmani, Chythra R Rao, Giancarlo Lucchetti, Irena Ilic, Suzanne Barker-Collo, Priya Rathi, Emerito Jose A. Faraon, Mohamad-Hani Temsah, Reza Ghanei Gheshlagh, Gyu Ri Kim, Carlos A Castañeda-Orjuela, Alaa Makki, Yun Jin Kim, Vida Abedi, Shanshan Li, Kewal Krishan, David Flood, Abdollah Mohammadian-Hafshejani, Michele Romoli, Gregory A. Roth, Jagdish Khubchandani, Isabela M. Benseñor, Rupak Desai, Mohammed Shannawaz, Aziz Sheikh, Claudiu Herteliu, Xiaoyue Xu, Santi Martini, Kenji Shibuya, Jasvinder A. Singh, Ravi Prakash Jha, Kairat Davletov, Mahya Beheshti, Rahmatollah Moradzadeh, Ismaeel Yunusa, Maria Inês Schmidt, Koustuv Dalal, Sohail Ahmad, Patrick D. M. C. Katoto, Oladimeji Adebayo, Nima Hafezi-Nejad, Ranil Jayawardena, Giampiero Mazzaglia, Mitra Abbasifard, Usman Iqbal, Hamid Yimam Hassen, Alireza Rafiei, Catherine O. Johnson, Mark Thomaz Ugliara Barone, Simona Giampaoli, Gaetano Isola, Ricardo Lutzky Saute, Mandira Lamichhane Dhimal, Vishnu Renjith, Farshad Farzadfar, Irina Filip, Daniel Diaz, André Karch, Samer Hamidi, Diego Augusto Santos Silva, David Colozza, Gbenga A. Kayode, Dinh-Toi Chu, Truong-Minh Pham, Arielle Wilder Bell, Aziz Rezapour, David Laith Rawaf, Anasthasia Zastrozhina, Yves Miel H Zuniga, Ivo Iavicoli, Adrian Pana, Salman Rawaf, Pankaj Bhardwaj, Omid Dadras, Anayat Ullah, Gina Agarwal, Shafiu Mohammed, Bing-Fang Hwang, Eyayou Girma Tadesse, Charles D.A. Wolfe, Sanjay Basu, Michael Brauer, Tanuj Kanchan, Ahmad Azam Malik, Brigid Unim, Min Seo Kim, Kia Vosoughi, Tomasz Miazgowski, Warren D. Lo, Vivek Podder, Dana Bryazka, Chuanhua Yu, Hassan Magdy Abd El Razek, Rufus Akinyemi, Zhi-Jiang Zhang, Ettore Beghi, Xiaochen Dai, Meghnath Dhimal, Mehrnoosh Samaei, Sathish Kumar Jayapal, Bay Vo, Amanual Getnet Mersha, Rajaa Al-Raddadi, Savita Lasrado, Jalal Arabloo, Pablo M. Lavados, Samaneh Akbarpour, Khezar Hayat, Ritesh G. Menezes, Vahid Alipour, Sowmya J. Rao, Mariam Molokhia, Trang Huyen Nguyen, Aletta E. Schutte, Zahra Kamiab, Lidia Morawska, Mohammad Ali Moni, Bo Norrving, Tommi Vasankari, Bruno Ramos Nascimento, Ai Koyanagi, Tissa Wijeratne, Rizwan Kalani, Chenwen Zhong, Bright Opoku Ahinkorah, Sepideh Ahmadi, Bruce Bartholow Duncan, Andrzej Rynkiewicz, Pradyumna Agasthi, Saeed Shahabi, Adnan Kisa, Fares Alahdab, Vafa Rahimi-Movaghar, Adnan Ansar, Matilde Leonardi, Ali Koolivand, Jefferson Antonio Buendia Rodriguez, Leonardo Roever, Daniel Asfaw Erku, Alok Atreya, Jean Jacques Noubiap, Dhaval Kolte, Shajedur Rahman Shawon, Michael Ekholuenetale, Navid Manafi, Narayanaswamy Venketasubramanian, Syed Amir Gilani, Mohamed M. Gad, Christopher J L Murray, Louis Jacob, Robert Ancuceanu, Simona Costanzo, Erkin M. Mirrakhimov, Seyed Hossein Yahyazadeh Jabbari, Nazanin Rajai, Muhammed Elhadi, Abdelrahman Ibrahim Abushouk, Alireza Zandifar, Walter Muruet, Jagadish Rao Padubidri, Promit Ananyo Chakraborty, Hans Orru, Mikk Jürisson, Rajeev Gupta, Kurnia Dwi Artanti, Till Bärnighausen, Mark Woodward, Masao Iwagami, Brijesh Sathian, Bingyu Li, Vijay Krishnamoorthy, Ahamarshan Jayaraman Nagarajan, Sherief Ghozy, Amanda G. Thrift, Michael A. Piradov, Florian Fischer, Mayowa O. Owolabi, Lorenzo G. Mantovani, Aman Yesuf Endries, Sara Sheikhbahaei, Stefan Lorkowski, Muhammed Shahriar Zaman, Ali Yadollahpour, Abdiwahab Hashi, Sreenivas Narasimha Swamy, Krittika Bhattacharyya, Hiroshi Yatsuya, Mika Kivimäki, Olayinka Stephen Ilesanmi, Irmina Maria Michalek, Ruxandra Irina Negoi, Alberico L. Catapano, Gholamreza Bazmandegan, Ahmed Al Montasir, Fakher Rahim, Amirhossein Sahebkar, Syed Mohamed Aljunid, Giang Thu Vu, G Anil Kumar, Juan Jesus Carrero, Hiroyasu Iso, Abdallah M. Samy, Stefan Stortecky, Reza Malekzadeh, Ashwin Kamath, Nevine El Nahas, Ayesha Humayun, Miguel A Barboza, Sheng-Chia Chung, Carlo La Vecchia, Oluwakemi Ololade Odukoya, Rita Krishnamurthi, Masood Ali Shaikh, Milena Ilic, Lalit Yadav, Nahlah Elkudssiah Ismail, Abdel Douiri, Yousef Mohammad, Jason H Y Wu, Sahar Saeedi Moghaddam, Ramesh Holla, Sadaf G. Sepanlou, Itamar S. Santos, Jost B. Jonas, Dian Kusuma, Atte Meretoja, Yasir Waheed, Ben Lacey, Zahra Aryan, Mulugeta Molla Birhanu, Moien Ab Khan, K. M. Saif-Ur-Rahman, Ramin Zand, Anna Aleksandrovna Skryabina, Sung In Jang, Rakhi Dandona, Emanuele D'Amico, Priyanga Ranasinghe, Jaykaran Charan, Bhaskaran Unnikrishnan, Davide Sattin, Akram Pourshams, Markus P. Schlaich, Arief Hargono, Samaneh Asgari, Ovidiu Baltatu, Ippazio Cosimo Antonazzo, Sandhya Neupane Kandel, Nizal Sarrafzadegan, Jakub Morze, Man Mohan Mehndiratta, Manjari Tripathi, Panniyammakal Jeemon, Rohollah Kalhor, Yogeshwar Kalkonde, Soraya Siabani, Sojib Bin Zaman, Seyed Sina Naghibi Irvani, Shilpa Gaidhane, Sahel Valadan Tahbaz, Yihienew Mequanint Bezabih, Samath D Dharmaratne, Ingan Ukur Tarigan, Vivek Gupta, Klara Dokova, Alireza Vakilian, Vardhmaan Jain, Akshaya Srikanth Bhagavathula, Sarah Wulf Hanson, Umar Farooque, Mohammad Ali Mansournia, Vera Marisa Costa, Alessandro Gialluisi, Valery L. Feigin, Himal Kandel, Suzanne Polinder, Nermin Ghith, Deepak Dhamnetiya, Michael H. Criqui, Asif Hanif, Ahmed Abualhasan, Veer Bala Gupta, Mahaveer Golechha, Bach Xuan Tran, Jason A. Anderson, Catherine Bisignano, Kazumasa Yamagishi, Zahid A Butt, Budi Aji, Baye Dagnew, Rasmus Havmoeller, Victor Volovici, Jitendra Singh, Paramjit Gill, Saverio Stranges, Eun Cheol Park, Andrew T Olagunju, Milena Santric-Milicevic, Woldesellassie M. Bezabhe, Sheikh M. Alif, Junjie Huang, Foad Abd-Allah, Yvonne Teuschl, Rajkumar Doshi, Nelson Alvis-Guzman, Marcel Ausloos, Mohsen Naghavi, Yusra Ahmed Salih, Mohsen Abbasi-Kangevari, Maarten J. Postma, Ghozali Ghozali, Yanzhong Wang, Ali H. Mokdad, Valentin Yurievich Skryabin, Nitin Joseph, Andre M. N. Renzaho, Muhammad Aziz Rahman, Mohammad Athar, Rustam Al-Shahi Salman, Albertino Damasceno, Fatemeh Pashazadeh Kan, Marcello Tonelli, Florentino Luciano Caetano dos Santos, Sonali G. Choudhari, Abdullah Hamid Feroze, Walter D. Johnson, Ro-Ting Lin, Francesca Giulia Magnani, Hermann Brenner, Shaimaa I. El-Jaafary, Tea Lallukka, Niveen M E Abu-Rmeileh, Jacek Jerzy Jozwiak, GBD 2019 Stroke Collaborators, Feigin, V. L., Stark, B. A., Johnson, C. O., Roth, G. A., Bisignano, C., Abady, G. G., Abbasifard, M., Abbasi-Kangevari, M., Abd-Allah, F., Abedi, V., Abualhasan, A., Abu-Rmeileh, N. M. E., Abushouk, A. I., Adebayo, O. M., Agarwal, G., Agasthi, P., Ahinkorah, B. O., Ahmad, S., Ahmadi, S., Salih, Y. A., Aji, B., Akbarpour, S., Akinyemi, R. O., Al Hamad, H., Alahdab, F., Alif, S. M., Alipour, V., Aljunid, S. M., Almustanyir, S., Al-Raddadi, R. M., Salman, R. A. -S., Alvis-Guzman, N., Ancuceanu, R., Anderlini, D., Anderson, J. A., Ansar, A., Antonazzo, I. C., Arabloo, J., Arnlov, J., Artanti, K. D., Aryan, Z., Asgari, S., Ashraf, T., Athar, M., Atreya, A., Ausloos, M., Baig, A. A., Baltatu, O. C., Banach, M., Barboza, M. A., Barker-Collo, S. L., Barnighausen, T. W., Barone, M. T. U., Basu, S., Bazmandegan, G., Beghi, E., Beheshti, M., Bejot, Y., Bell, A. W., Bennett, D. A., Bensenor, I. M., Bezabhe, W. M., Bezabih, Y. M., Bhagavathula, A. S., Bhardwaj, P., Bhattacharyya, K., Bijani, A., Bikbov, B., Birhanu, M. M., Boloor, A., Bonny, A., Brauer, M., Brenner, H., Bryazka, D., Butt, Z. A., Dos Santos, F. L. C., Campos-Nonato, I. R., Cantu-Brito, C., Carrero, J. J., Castaneda-Orjuela, C. A., Catapano, A. L., Chakraborty, P. A., Charan, J., Choudhari, S. G., Chowdhury, E. K., Chu, D. -T., Chung, S. -C., Colozza, D., Costa, V. M., Costanzo, S., Criqui, M. H., Dadras, O., Dagnew, B., Dai, X., Dalal, K., Damasceno, A. A. M., D'Amico, E., Dandona, L., Dandona, R., Gela, J. D., Davletov, K., De La Cruz-Gongora, V., Desai, R., Dhamnetiya, D., Dharmaratne, S. D., Dhimal, M. L., Dhimal, M., Diaz, D., Dichgans, M., Dokova, K., Doshi, R., Douiri, A., Duncan, B. B., Eftekharzadeh, S., Ekholuenetale, M., El Nahas, N., Elgendy, I. Y., Elhadi, M., El-Jaafary, S. I., Endres, M., Endries, A. Y., Erku, D. A., Faraon, E. J. A., Farooque, U., Farzadfar, F., Feroze, A. H., Filip, I., Fischer, F., Flood, D., Gad, M. M., Gaidhane, S., Gheshlagh, R. G., Ghashghaee, A., Ghith, N., Ghozali, G., Ghozy, S., Gialluisi, A., Giampaoli, S., Gilani, S. A., Gill, P. S., Gnedovskaya, E. V., Golechha, M., Goulart, A. C., Guo, Y., Gupta, R., Gupta, V. B., Gupta, V. K., Gyanwali, P., Hafezi-Nejad, N., Hamidi, S., Hanif, A., Hankey, G. J., Hargono, A., Hashi, A., Hassan, T. S., Hassen, H. Y., Havmoeller, R. J., Hay, S. I., Hayat, K., Hegazy, M. I., Herteliu, C., Holla, R., Hostiuc, S., Househ, M., Huang, J., Humayun, A., Hwang, B. -F., Iacoviello, L., Iavicoli, I., Ibitoye, S. E., Ilesanmi, O. S., Ilic, I. M., Ilic, M. D., Iqbal, U., Irvani, S. S. N., Islam, S. M. S., Ismail, N. E., Iso, H., Isola, G., Iwagami, M., Jacob, L., Jain, V., Jang, S. -I., Jayapal, S. K., Jayaram, S., Jayawardena, R., Jeemon, P., Jha, R. P., Johnson, W. D., Jonas, J. B., Joseph, N., Jozwiak, J. J., Jurisson, M., Kalani, R., Kalhor, R., Kalkonde, Y., Kamath, A., Kamiab, Z., Kanchan, T., Kandel, H., Karch, A., Katoto, P. D. M. C., Kayode, G. 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A., Al Montasir, A., Moradzadeh, R., Morawska, L., Morze, J., Muruet, W., Musa, K. I., Nagarajan, A. J., Naghavi, M., Swamy, S. N., Nascimento, B. R., Negoi, R. I., Kandel, S. N., Nguyen, T. H., Norrving, B., Noubiap, J. J., Nwatah, V. E., Oancea, B., Odukoya, O. O., Olagunju, A. T., Orru, H., Owolabi, M. O., Padubidri, J. R., Pana, A., Parekh, T., Park, E. -C., Kan, F. P., Pathak, M., Peres, M. F. P., Perianayagam, A., Pham, T. -M., Piradov, M. A., Podder, V., Polinder, S., Postma, M. J., Pourshams, A., Radfar, A., Rafiei, A., Raggi, A., Rahim, F., Rahimi-Movaghar, V., Rahman, M., Rahman, M. A., Rahmani, A. M., Rajai, N., Ranasinghe, P., Rao, C. R., Rao, S. J., Rathi, P., Rawaf, D. L., Rawaf, S., Reitsma, M. B., Renjith, V., Renzaho, A. M. N., Rezapour, A., Rodriguez, J. A. B., Roever, L., Romoli, M., Rynkiewicz, A., Sacco, S., Sadeghi, M., Moghaddam, S. S., Sahebkar, A., Saif-Ur-Rahman, K. M., Salah, R., Samaei, M., Samy, A. M., Santos, I. S., Santric-Milicevic, M. 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L., Public Health, Neurosurgery, Department of Public Health, University of Helsinki, Faculty of Medicine, Helsinki Inequality Initiative (INEQ), HUS Neurocenter, Neurologian yksikkö, Helsinki University Hospital Area, Feigin, V, Stark, B, Johnson, C, Roth, G, Bisignano, C, Abady, G, Abbasifard, M, Abbasi-Kangevari, M, Abd-Allah, F, Abedi, V, Abualhasan, A, Abu-Rmeileh, N, Abushouk, A, Adebayo, O, Agarwal, G, Agasthi, P, Ahinkorah, B, Ahmad, S, Ahmadi, S, Salih, Y, Aji, B, Akbarpour, S, Akinyemi, R, Al Hamad, H, Alahdab, F, Alif, S, Alipour, V, Aljunid, S, Almustanyir, S, Al-Raddadi, R, Salman, R, Alvis-Guzman, N, Ancuceanu, R, Anderlini, D, Anderson, J, Ansar, A, Antonazzo, I, Arabloo, J, Arnlov, J, Artanti, K, Aryan, Z, Asgari, S, Ashraf, T, Athar, M, Atreya, A, Ausloos, M, Baig, A, Baltatu, O, Banach, M, Barboza, M, Barker-Collo, S, Barnighausen, T, Barone, M, Basu, S, Bazmandegan, G, Beghi, E, Beheshti, M, Bejot, Y, Bell, A, Bennett, D, Bensenor, I, Bezabhe, W, Bezabih, Y, Bhagavathula, A, Bhardwaj, P, Bhattacharyya, K, Bijani, A, Bikbov, B, Birhanu, M, Boloor, A, Bonny, A, Brauer, M, Brenner, H, Bryazka, D, Butt, Z, Dos Santos, F, Campos-Nonato, I, Cantu-Brito, C, Carrero, J, Castaneda-Orjuela, C, Catapano, A, Chakraborty, P, Charan, J, Choudhari, S, Chowdhury, E, Chu, D, Chung, S, Colozza, D, Costa, V, Costanzo, S, Criqui, M, Dadras, O, Dagnew, B, Dai, X, Dalal, K, Damasceno, A, D'Amico, E, Dandona, L, Dandona, R, Gela, J, Davletov, K, De La Cruz-Gongora, V, Desai, R, Dhamnetiya, D, Dharmaratne, S, Dhimal, M, Diaz, D, Dichgans, M, Dokova, K, Doshi, R, Douiri, A, Duncan, B, Eftekharzadeh, S, Ekholuenetale, M, El Nahas, N, Elgendy, I, Elhadi, M, El-Jaafary, S, Endres, M, Endries, A, Erku, D, Faraon, E, Farooque, U, Farzadfar, F, Feroze, A, Filip, I, Fischer, F, Flood, D, Gad, M, Gaidhane, S, Gheshlagh, R, Ghashghaee, A, Ghith, N, Ghozali, G, Ghozy, S, Gialluisi, A, Giampaoli, S, Gilani, S, Gill, P, Gnedovskaya, E, Golechha, M, Goulart, A, Guo, Y, Gupta, R, Gupta, V, Gyanwali, P, Hafezi-Nejad, N, Hamidi, S, Hanif, A, Hankey, G, Hargono, A, Hashi, A, Hassan, T, Hassen, H, Havmoeller, R, Hay, S, Hayat, K, Hegazy, M, Herteliu, C, Holla, R, Hostiuc, S, Househ, M, Huang, J, Humayun, A, Hwang, B, Iacoviello, L, Iavicoli, I, Ibitoye, S, Ilesanmi, O, Ilic, I, Ilic, M, Iqbal, U, Irvani, S, Islam, S, Ismail, N, Iso, H, Isola, G, Iwagami, M, Jacob, L, Jain, V, Jang, S, Jayapal, S, Jayaram, S, Jayawardena, R, Jeemon, P, Jha, R, Johnson, W, Jonas, J, Joseph, N, Jozwiak, J, Jurisson, M, Kalani, R, Kalhor, R, Kalkonde, Y, Kamath, A, Kamiab, Z, Kanchan, T, Kandel, H, Karch, A, Katoto, P, Kayode, G, Keshavarz, P, Khader, Y, Khan, E, Khan, I, Khan, M, Khatib, M, Khubchandani, J, Kim, G, Kim, M, Kim, Y, Kisa, A, Kisa, S, Kivimaki, M, Kolte, D, Koolivand, A, Laxminarayana, S, Koyanagi, A, Krishan, K, Krishnamoorthy, V, Krishnamurthi, R, Kumar, G, Kusuma, D, Vecchia, C, Lacey, B, Lak, H, Lallukka, T, Lasrado, S, Lavados, P, Leonardi, M, Li, B, Li, S, Lin, H, Lin, R, Liu, X, Lo, W, Lorkowski, S, Lucchetti, G, Saute, R, Abd El Razek, H, Magnani, F, Mahajan, P, Majeed, A, Makki, A, Malekzadeh, R, Malik, A, Manafi, N, Mansournia, M, Mantovani, L, Martini, S, Mazzaglia, G, Mehndiratta, M, Menezes, R, Meretoja, A, Mersha, A, Jonasson, J, Miazgowski, B, Miazgowski, T, Michalek, I, Mirrakhimov, E, Mohammad, Y, Mohammadian-Hafshejani, A, Mohammed, S, Mokdad, A, Mokhayeri, Y, Molokhia, M, Moni, M, Al Montasir, A, Moradzadeh, R, Morawska, L, Morze, J, Muruet, W, Musa, K, Nagarajan, A, Naghavi, M, Swamy, S, Nascimento, B, Negoi, R, Kandel, S, Nguyen, T, Norrving, B, Noubiap, J, Nwatah, V, Oancea, B, Odukoya, O, Olagunju, A, Orru, H, Owolabi, M, Padubidri, J, Pana, A, Parekh, T, Park, E, Kan, F, Pathak, M, Peres, M, Perianayagam, A, Pham, T, Piradov, M, Podder, V, Polinder, S, Postma, M, Pourshams, A, Radfar, A, Rafiei, A, Raggi, A, Rahim, F, Rahimi-Movaghar, V, Rahman, M, Rahmani, A, Rajai, N, Ranasinghe, P, Rao, C, Rao, S, Rathi, P, Rawaf, D, Rawaf, S, Reitsma, M, Renjith, V, Renzaho, A, Rezapour, A, Rodriguez, J, Roever, L, Romoli, M, Rynkiewicz, A, Sacco, S, Sadeghi, M, Moghaddam, S, Sahebkar, A, Saif-Ur-Rahman, K, Salah, R, Samaei, M, Samy, A, Santos, I, Santric-Milicevic, M, Sarrafzadegan, N, Sathian, B, Sattin, D, Schiavolin, S, Schlaich, M, Schmidt, M, Schutte, A, Sepanlou, S, Seylani, A, Sha, F, Shahabi, S, Shaikh, M, Shannawaz, M, Shawon, M, Sheikh, A, Sheikhbahaei, S, Shibuya, K, Siabani, S, Silva, D, Singh, J, Skryabin, V, Skryabina, A, Sobaih, B, Stortecky, S, Stranges, S, Tadesse, E, Tarigan, I, Temsah, M, Teuschl, Y, Thrift, A, Tonelli, M, Tovani-Palone, M, Tran, B, Tripathi, M, Tsegaye, G, Ullah, A, Unim, B, Unnikrishnan, B, Vakilian, A, Tahbaz, S, Vasankari, T, Venketasubramanian, N, Vervoort, D, Vo, B, Volovici, V, Vosoughi, K, Vu, G, Vu, L, Wafa, H, Waheed, Y, Wang, Y, Wijeratne, T, Winkler, A, Wolfe, C, Woodward, M, Wu, J, Hanson, S, Xu, X, Yadav, L, Yadollahpour, A, Jabbari, S, Yamagishi, K, Yatsuya, H, Yonemoto, N, Yu, C, Yunusa, I, Zaman, M, Zaman, S, Zamanian, M, Zand, R, Zandifar, A, Zastrozhin, M, Zastrozhina, A, Zhang, Y, Zhang, Z, Zhong, C, Zuniga, Y, Murray, C, Value, Affordability and Sustainability (VALUE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Microbes in Health and Disease (MHD)

Subjects
Male, Aging, 030204 cardiovascular system & hematology, Stroke data, GUIDELINES, 3124 Neurology and psychiatry, Body Mass Index, Global Burden of Disease, 0302 clinical medicine, RA0421, Risk Factors, Epidemiology, Strokes, YOUNG-ADULTS, Prevalence, 80 and over, Aetiology, 610 Medicine & health, Stroke, POPULATION, 1103 Clinical Sciences, 1109 Neurosciences, Cause of death, Aged, 80 and over, education.field_of_study, Mortality rate, Incidence (epidemiology), Incidence, 1. No poverty, Articles, Hälsovetenskaper, Middle Aged, Stroke types, ddc, 3. Good health, ISCHEMIC-STROKE, Income, Female, Quality-Adjusted Life Years, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, GBD, Population, Clinical Sciences, Clinical Neurology, 03 medical and health sciences, Clinical Research, MIDDLE-INCOME COUNTRIES, Health Sciences, medicine, Humans, Risk factor, education, GBD 2019 Stroke Collaborators, Cerebral Hemorrhage, Aged, Ischemic Stroke, Global burden, Science & Technology, Neurology & Neurosurgery, HYPERTENSION, business.industry, MORTALITY, Prevention, 3112 Neurosciences, Neurosciences, 1103 Clinical Sciences, SERVICES, Subarachnoid Hemorrhage, medicine.disease, PREVENTION, Brain Disorders, Good Health and Well Being, Attributable risk, Human medicine, Neurology (clinical), Neurosciences & Neurology, business, 1109 Neurosciences, 030217 neurology & neurosurgery, Demography, 2.4 Surveillance and distribution, RC
Abstract

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding Bill & Melinda Gates Foundation.

Published
2021

43. Plasma calprotectin in the emergency department: a potential clinical biomarker for patients with infectious diseases

Author

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

44. Metabolic Profiling of Obesity With and Without the Metabolic Syndrome: A Multisample Evaluation

Author

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

45. The genomics of heart failure: design and rationale of the HERMES consortium

Author

Svati H. Shah, Olle Melander, Neneh Sallah, Quinn S. Wells, Jerome I. Rotter, Faye Zhao, Charlotte Andersson, Guðmundur Thorgeirsson, Ghazaleh Fatemifar, Alex S. F. Doney, Michael E. Dunn, David E. Lanfear, Ian Ford, Eric Boersma, Sonia Shah, Christopher Newton-Cheh, Douglas L. Mann, Niek Verweij, Carolina Roselli, Laura M. Yerges-Armstrong, Jian Yang, Christian Torp-Pedersen, Veikko Salomaa, Mary L. Biggs, Alaa Shalaby, Christoph Nowak, Stefan Gross, Patrick T. Ellinor, Mari Liis Tammesoo, Diane T. Smelser, Peter M. Visscher, Hans L. Hillege, Ruth C. Lovering, Honghuang Lin, Colin N. A. Palmer, Louis Philippe Lemieux Perreault, Jeffrey Brandimarto, Uwe Völker, Perttu Salo, Andrea Koekemoer, Rebecca Gutmann, Åsa K. Hedman, Nilesh J. Samani, Heming Xing, Faiez Zannad, Jaison Jacob, Harry Hemingway, Michael R. Brown, Franco Giulianini, Anubha Mahajan, Xing Chen, Alexander Niessner, Peter Almgren, Daniel I. Swerdlow, Gunnar Engström, Lars Lind, Tõnu Esko, Tomasz Czuba, Anna Helgadottir, Harvey D. White, David J. Stott, Johan Ärnlöv, Lars Køber, Chim C. Lang, Krishna G. Aragam, Kent D. Taylor, Anders Mälarstig, Frederick K. Kamanu, Kenneth B. Margulies, Michelle L. O'Donoghue, Andrew D. Morris, Sahar Ghasemi, J. Wouter Jukema, Jessica van Setten, Abbas Dehghan, Guillaume Paré, Luca A. Lotta, Giorgio E. M. Melloni, Albert Henry, Bruce M. Psaty, Paul M. Ridker, David J. Carey, Marie-Pierre Dubé, John S. Gottdiener, Xiaosong Wang, Per H. Svensson, Xu Chen, Patrik K. E. Magnusson, Claudia Langenberg, Alexander Teumer, Vilmantas Giedraitis, Simon de Denus, Michael W. Nagle, Marcus Dörr, Thomas P. Cappola, André G. Uitterlinden, Michael Morley, Eliana Portilla-Fernandez, J. Gustav Smith, Abirami Veluchamy, Peter Weeke, Ify R. Mordi, Unnur Thorsteinsdottir, Naveed Sattar, Folkert W. Asselbergs, Daniel I. Chasman, Daníel F. Guðbjartsson, Jonathan H. Chung, Marcus E. Kleber, Raul Weiss, Christopher P. Nelson, Spiros Denaxas, Bing Yu, Simon P. R. Romaine, Nicholas A Marston, Anjali T. Owens, Cecilia M. Lindgren, John J.V. McMurray, Joshua D. Backman, Michael V. Holmes, Stella Trompet, Hilma Holm, Kerri L. Wiggins, Jian'an Luan, Stephan B. Felix, Yifan Yang, Jemma B. Wilk, Maryam Kavousi, Markus Perola, Christian T. Ruff, Jean-Claude Tardif, G Sveinbjörnsson, Samuel C. Dudley, Nicholas J. Wareham, Teemu J. Niiranen, Andrew P. Morris, Danny Tuckwell, Maris Teder-Laving, R. Thomas Lumbers, James P. Cook, Géraldine Asselin, William A. Chutkow, Winfried März, Steven A. Lubitz, John G.F. Cleland, Bill Kraus, Ramachandran S. Vasan, Christopher M. Haggerty, Olympe Chazara, Chris Finan, Heather L. Bloom, Hans-Peter Brunner-La Rocca, Francoise Fougerousse, Kenneth Rice, Craig L. Hyde, Graciela E. Delgado, Mark Chaffin, Marc S. Sabatine, Alanna C. Morrison, Kay-Tee Khaw, Kari Stefansson, Felix Vaura, Barry London, Isabella Kardys, Aroon D. Hingorani, Hongsheng Gui, Steen Stender, René Fouodjio, Mohsen Ghanbari, Pim van der Harst, Nicholas L. Smith, Karoline Kuchenbaecker, Adriaan A. Voors, Benoit Tyl, University College of London [London] (UCL), University College London Hospitals (UCLH), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Lund University [Lund], Pfizer, Karolinska Institutet [Stockholm], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Groningen [Groningen], University of Oxford [Oxford], Dalarna University, Massachusetts General Hospital [Boston], Montreal Heart Institute - Institut de Cardiologie de Montréal, Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, University of Washington [Seattle], Emory University [Atlanta, GA], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Pennsylvania [Philadelphia], The University of Texas Health Science Center at Houston (UTHealth), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Department of Molecular and Functional Genomics, Geisinger, Danville, PA, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AstraZeneca, Novartis Institutes for BioMedical Research (NIBR), University of Glasgow, University of Liverpool, Université de Montréal (UdeM), Imperial College London, University of Heidelberg, Medical Faculty, University of Dundee, Universität Greifswald - University of Greifswald, University of Minnesota Medical School, University of Minnesota System, German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institut de Recherches Internationales Servier [Suresnes] (IRIS), Uppsala University, University of Maryland School of Medicine, University of Maryland System, University of Iceland [Reykjavik], deCODE genetics [Reykjavik], Henry Ford Hospital, Carver College of Medicine, University of Iowa, Geisinger Autism & Developmental Medicine Institute [Danville, PA, USA] (ADMI), ICIN - Netherlands Heart Institute, Leiden University Medical Center (LUMC), Netherlands Heart Institute, Partenaires INRAE, University of Cambridge [UK] (CAM), Rigshospitalet [Copenhagen], Copenhagen University Hospital, University of Leicester, Duke University [Durham], University of Iowa [Iowa City], Genentech, Inc., Genentech, Inc. [San Francisco], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Skane University Hospital [Malmo], University of Edinburgh, Medizinische Universität Wien = Medical University of Vienna, University of Turku, National Institute for Health and Welfare [Helsinki], McMaster University [Hamilton, Ontario], Kaiser Permanente Washington Health Research Institute [Seattle] (KPWHRI), Harbor UCLA Medical Center [Torrance, Ca.], University Medical Center [Utrecht], University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), University of Tartu, Aalborg University [Denmark] (AAU), Leiden University, University of Queensland [Brisbane], Ohio State University [Columbus] (OSU), Auckland City Hospital, GlaxoSmithKline, Glaxo Smith Kline, University of Texas Health Science Center, Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Duke University Medical Center, Regeneron Pharmaceuticals [Tarrytown], Vanderbilt University [Nashville], European Project, Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Cardiology, University of Oxford, University of Pennsylvania, Universiteit Leiden, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H02 Cardiomyopathy, Epidemiology, and Internal Medicine

Subjects
Male, Study Designs, Cardiomyopathy, Disease, 030204 cardiovascular system & hematology, 0302 clinical medicine, AFRICAN ANCESTRY, Epidemiology, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, Cardiac and Cardiovascular Systems, AGING RESEARCH, RISK, Aged, 80 and over, 0303 health sciences, Kardiologi, Genomics, Middle Aged, Prognosis, 3. Good health, Female, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Heart failure, CLASSIFICATION, Heart Failure/genetics, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, Genetic model, medicine, Genetics, Diseases of the circulatory (Cardiovascular) system, Humans, Allele frequency, Genotyping, METAANALYSIS, 030304 developmental biology, Aged, Association studies, Study Design, business.industry, Odds ratio, ADULTS, COHORTS, medicine.disease, RC666-701, REPLICATION, business, Biomarkers, Genome-Wide Association Study
Abstract

Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure.Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model.Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.

Published
2021

46. Strong Associations Between Early Tubular Damage and Urinary Cytokine, Chemokine, and Growth Factor Levels in Elderly Males and Females

Author

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

47. The metabolomic profile associated with clustering of cardiovascular risk factors—A multi-sample evaluation

Author

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

48. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study

Author

Roth, Gregory A, Mensah, George A, Johnson, Catherine O, Addolorato, Giovanni, Ammirati, Enrico, Baddour, Larry M, Barengo, Noël C, Beaton, Andrea Z, Benjamin, Emelia J, Benziger, Catherine P, Bonny, Aimé, Brauer, Michael, Brodmann, Marianne, Cahill, Thomas J, Carapetis, Jonathan, Catapano, Alberico L, Chugh, Sumeet S, Cooper, Leslie T, Coresh, Josef, Criqui, Michael, DeCleene, Nicole, Eagle, Kim A, Emmons-Bell, Sophia, Feigin, Valery L, Fernández-Solà, Joaquim, Fowkes, Gerry, Gakidou, Emmanuela, Grundy, Scott M, He, Feng J, Howard, George, Hu, Frank, Inker, Lesley, Karthikeyan, Ganesan, Kassebaum, Nicholas, Koroshetz, Walter, Lavie, Carl, Lloyd-Jones, Donald, Lu, Hong S, Mirijello, Antonio, Temesgen, Awoke Misganaw, Mokdad, Ali, Moran, Andrew E, Muntner, Paul, Narula, Jagat, Neal, Bruce, Ntsekhe, Mpiko, Moraes de Oliveira, Glaucia, Otto, Catherine, Owolabi, Mayowa, Pratt, Michael, Rajagopalan, Sanjay, Reitsma, Marissa, Ribeiro, Antonio Luiz P, Rigotti, Nancy, Rodgers, Anthony, Sable, Craig, Shakil, Saate, Sliwa-Hahnle, Karen, Stark, Benjamin, Sundström, Johan, Timpel, Patrick, Tleyjeh, Imad M, Valgimigli, Marco, Vos, Theo, Whelton, Paul K, Yacoub, Magdi, Zuhlke, Liesl, Murray, Christopher, Fuster, Valentin, GBD-NHLBI-JACC Global, Burden of, Cardiovascular Diseases, Writing Group, Gregory A, Roth George, A Mensah, Catherine O, Johnson, Giovanni, Addolorato, Enrico, Ammirati, Larry M, Baddour Noel, C Barengo, Andrea, Beaton, Emelia J, Benjamin Catherine, P Benziger, Aime, Bonny, Michael, Brauer, Marianne, Brodmann, Thomas J, Cahill Jonathan, R Carapetis, Alberico L, Catapano, Sumeet, Chugh, Leslie T, Cooper, Josef, Coresh, Michael H, Criqui Nicole, K DeCleene, Kim A, Eagle, Sophia, Emmons-Bell, Valery L, Feigin, Joaquim, Fernández-Sola, F Gerry, R Fowkes, Emmanuela, Gakidou, Scott M, Grundy Feng, J He, George, Howard, Frank, Hu, Lesley, Inker, Ganesan, Karthikeyan, Nicholas J, Kassebaum Walter, J Koroshetz, Carl, Lavie, Donald, Lloyd-Jones, Hong S, Antonio, Mirijello, Awoke T, Misganaw Ali, H Mokdad, Andrew E, Moran, Paul, Muntner, Jagat, Narula, Bruce, Neal, Mpiko, Ntsekhe, Gláucia M, M Oliveira, Catherine M, Otto Mayowa, O Owolabi, Michael, Pratt, Sanjay, Rajagopalan, Marissa B, Reitsma Antonio, Luiz P, Ribeiro Nancy, A Rigotti, Anthony, Rodgers, Craig A, Sable Saate, S Shakil, Karen, Sliwa, Benjamin A, Stark, Johan, Sundström, Patrick, Timpel, Imad I, Tleyjeh, Marco, Valgimigli, Theo, Vos, Paul K, Whelton, Magdi, Yacoub, 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, Cirillo, Massimo, 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, 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Subjects
cardiovascular disease, global health, health policy, 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.

Published
2020

49. Development of Risk Prediction Equations for Incident Chronic Kidney Disease

Author

Robert G, Nelson Morgan, E Grams, Shoshana H, Ballew, Yingying, Sang, Fereidoun, Azizi, Steven J, Chadban, Layal, Chaker, Stephan C, Dunning, Caroline, Fox, Yoshihisa, Hirakawa, Kunitoshi, Iseki, Joachim, Ix, Tazeen H, Jafar, Anna, Köttgen, David M, J Naimark, Takayoshi, Ohkubo, Gordon J, Prescott Casey, M Rebholz, Charumathi, Sabanayagam, Toshimi, Sairenchi, Ben, Schöttker, Yugo, Shibagaki, Marcello, Tonelli, Luxia, Zhang, Ron T, Gansevoort, Kunihiro, Matsushita, Mark, Woodward, Josef, Coresh, Varda, Shalev, CKD Prognosis Consortium, John, Chalmers, Hisatomi, Arima, Vlado, Perkovic, Morgan, Grams, Kevan, Polkinghorne, Robert, Atkins, Steven, Chadban, Ming-Hui, Zhao, Fang, Wang, Jinwei, Wang, Frank, Sacks, Gary, Curhan, Michael, Shlipak, Mark, Sarnak, Ronit, Katz, Jade, Hiramoto, Hiroyasu, Iso, Isao, Muraki, Kazumasa, Yamagishi, Mitsumasa, Umesawa, Hermann, Brenner, Kai-Uwe, Saum, Dietrich, Rothenbacher, Shih-Jen, Hwang, Alex, Chang, Jamie, Green, Gurmukteshwar, Singh, H Lester, Kirchner, Corri, Black, Angharad, Marks, Gordon, Prescott, Laura, Clark, Nick, Fluck, Cirillo, Massimo, Stein, Hallan, Marius, Øvrehus, Knut, Langlo, Solfrid, Romundstad, Fujiko, Irie, Adolfo, Correa, Casey, Rebholz, Bessie, Young, L Ebony, Boulware, Stanford, Mwasongwe, Tsuyoshi, Watanabe, Kunihiro, Yamagata, Koichi, Asahi, Gabriel, Chodick, Carmen, Peralta, Erwin, Bottinger, Girish, Nadkarni, Stephen, Ellis, Rajiv, Nadukuru, Timothy, Kenealy, C Raina, Elley, John, Collins, Paul, Drury, Kei, Asayama, Masahiro, Kikuya, Hirohito, Metoki, Masaaki, Nakayama, Chiho, Iseki, Robert, Nelson, Helen, Looker, William, Knowler, Ron, Gansevoort, Stephan, Bakker, Hiddo, Heerspink, Simerjot, Jassal, Jaclyn, Bergstrom, Elizabeth, Barrett-Connor, Csaba, Kovesdy, Keiichi, Sumida, Kamyar, Kalantar-Zadeh, Sanaz, Sedaghat, Arfan, Ikram, Ewout, Hoorn, Abbas, Dehghan, Juan, Carrero, Marie, Evans, Carl-Gustaf, Elinder, Tien, Wong, Ching-Yu, Cheng, Chi-Pang, Wen, Chwen-Keng, Tsao, Min-Kuang, Tsai, Chien-Hua, Chen, Farhad, Hosseinpanah, Farzad, Hadaegh, Mohammadhassan, Mirbolouk, Marit, Solbu, Bjørn, Eriksen, Trond, Jenssen, Anne, Eggen, Lars, Lannfelt, Anders, Larsson, Johan, Ärnlöv, Henk, Bilo, Gijs, Landman, Kornelis, Hateren, Nanne, Kleefstra, Stephan, Dunning, Nikita, Stempniewicz, John, Cuddeback, Elizabeth, Ciemins, Shoshana, Ballew, Andrew, Levey, Jingsha, Chen, Lucia, Kwak, Aditya, Surapeneni, Mark, Woodward., Robert, G, Nelson, Morgan, E, Gram, Shoshana, H, Ballew, Yingying, Sang, Fereidoun, Azizi, Steven, J, Chadban, Layal, Chaker, Stephan, C, Dunning, Caroline, Fox, Yoshihisa, Hirakawa, Kunitoshi, Iseki, Joachim, Ix, Tazeen, H, Jafar, Anna, Köttgen, David, M, J, Naimark, Takayoshi, Ohkubo, Gordon, J, Prescott, Casey, M, Rebholz, Charumathi, Sabanayagam, Toshimi, Sairenchi, Ben, Schöttker, Yugo, Shibagaki, Marcello, Tonelli, Luxia, Zhang, Ron, T, Gansevoort, Kunihiro, Matsushita, Mark, Woodward, Josef, Coresh, Varda, Shalev, CKD Prognosis, Consortium, John, Chalmer, Hisatomi, Arima, Vlado, Perkovic, Morgan, Gram, Kevan, Polkinghorne, Robert, Atkin, Steven, Chadban, Ming-Hui, Zhao, Fang, Wang, Jinwei, Wang, Frank, Sack, Gary, Curhan, Michael, Shlipak, Mark, Sarnak, Ronit, Katz, Jade, Hiramoto, Hiroyasu, Iso, Isao, Muraki, Kazumasa, Yamagishi, Mitsumasa, Umesawa, Hermann, Brenner, Kai-Uwe, Saum, Dietrich, Rothenbacher, Shih-Jen, Hwang, Alex, Chang, Jamie, Green, Gurmukteshwar, Singh, H, Lester, Kirchner, Corri, Black, Angharad, Mark, Gordon, Prescott, Laura, Clark, Nick, Fluck, Cirillo, Massimo, Stein, Hallan, Marius, Øvrehu, Knut, Langlo, Solfrid, Romundstad, Fujiko, Irie, Adolfo, Correa, Casey, Rebholz, Bessie, Young, L, Ebony, Boulware, Stanford, Mwasongwe, Tsuyoshi, Watanabe, Kunihiro, Yamagata, Koichi, Asahi, Gabriel, Chodick, Carmen, Peralta, Erwin, Bottinger, Girish, Nadkarni, Stephen, Elli, Rajiv, Nadukuru, Timothy, Kenealy, C, Raina, Elley, John, Collin, Paul, Drury, Kei, Asayama, Masahiro, Kikuya, Hirohito, Metoki, Masaaki, Nakayama, Chiho, Iseki, Robert, Nelson, Helen, Looker, William, Knowler, Ron, Gansevoort, Stephan, Bakker, Hiddo, Heerspink, Simerjot, Jassal, Jaclyn, Bergstrom, Elizabeth, Barrett-Connor, Csaba, Kovesdy, Keiichi, Sumida, Kamyar, Kalantar-Zadeh, Sanaz, Sedaghat, Arfan, Ikram, Ewout, Hoorn, Abbas, Dehghan, Juan, Carrero, Marie, Evan, Carl-Gustaf, Elinder, Tien, Wong, Ching-Yu, Cheng, Chi-Pang, Wen, Chwen-Keng, Tsao, Min-Kuang, Tsai, Chien-Hua, Chen, Farhad, Hosseinpanah, Farzad, Hadaegh, Mohammadhassan, Mirbolouk, Marit, Solbu, Bjørn, Eriksen, Trond, Jenssen, Anne, Eggen, Lars, Lannfelt, Anders, Larsson, Johan, Ärnlöv, Henk, Bilo, Gijs, Landman, Kornelis, Hateren, Nanne, Kleefstra, Stephan, Dunning, Nikita, Stempniewicz, John, Cuddeback, Elizabeth, Ciemin, Shoshana, Ballew, Andrew, Levey, Jingsha, Chen, Lucia, Kwak, Aditya, Surapeneni, Mark, Woodward., Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Epidemiology, and Internal Medicine

Subjects
Male, medicine.medical_specialty, Renal function, Disease, Risk Assessment, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, Internal medicine, Diabetes mellitus, medicine, CKD, Humans, 030212 general & internal medicine, 0101 mathematics, Renal Insufficiency, Chronic, Statistic, Aged, Original Investigation, business.industry, 010102 general mathematics, General Medicine, Middle Aged, Models, Theoretical, medicine.disease, MODEL, RENAL-DISEASE, Albuminuria, Female, medicine.symptom, business, Body mass index, Glomerular Filtration Rate, Kidney disease
Abstract

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Published
2019

50. 1051-P: Inside CKD: Modeling the Future Global Burden of Chronic Kidney Disease in Patients with Type 2 Diabetes

Author

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

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