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1. 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

2. Editor's Choice – Acute Kidney Injury (AKI) in Aortic Intervention: Findings From the Midlands Aortic Renal Injury (MARI) Cohort Study

Author

Athanasios Saratzis, Shivam Joshi, Ruth A. Benson, David Bosanquet, Nikesh Dattani, Andrew Batchelder, Owain Fisher, Eva Ioannidou, Matthew J. Bown, Christopher H. Imray, David Sidloff, George Dovell, Rachael Forsythe, Loretta Barnett, Henrietta Barnet, Julie Wollaston, Stephen Goodyear, Asif Mahmood, Nicholas Matharu, Seamus Harrison, Jonathan Boyle, Emma Parker, Abigail Carlin, Mandy Burrows, Tristan Lane, Joseph Shalhoub, Andrew Garnham, Safia Begum, Phil Stather, Jessica Thrush, Terry Martin, Jack Fairhead, Julien Al Shakarchi, Tom Wallace, Elaine Wall, Christopher Twine, Wissam Al-Jundi, Huw Davies, Tom Barker, and Edward Lopez

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Urology, Renal function, 030204 cardiovascular system & hematology, 030230 surgery, Kidney, urologic and male genital diseases, Risk Assessment, Endovascular aneurysm repair, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Risk Factors, medicine, Humans, Prospective Studies, Renal replacement therapy, Prospective cohort study, Dialysis, Aged, business.industry, Incidence, Endovascular Procedures, Age Factors, Acute kidney injury, Acute Kidney Injury, medicine.disease, Creatinine, Female, Surgery, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract

Objectives The incidence of acute kidney injury (AKI) after open (OAR) or endovascular (EVAR) aortic repair is unknown. This research assessed the proportion of patients who develop AKI after aortic intervention using validated criteria, and explored AKI risk factors. Methods This was a multicentre national prospective cohort study. Eleven centres recruited patients undergoing EVAR or OAR (September 2017–December 2018). Serum creatinine (SCr) and urine outputs were measured over a minimum of 48 h or throughout the index inpatient stay to define post-operative AKI using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Renal decline at 30 days was calculated using estimated glomerular filtration rate (eGFR) and the Major Adverse Kidney Events (MAKE) 30 day composite endpoint (consisting of: death, new dialysis, > 25% eGFR decline). Results 300 patients (mean age: 71 years, standard deviation [SD] 4 years; 9% females) were included, who underwent: infrarenal endovascular aneurysm repair (EVAR) 139 patients, fenestrated EVAR (fEVAR) 30, branched EVAR (bEVAR) seven, infrarenal open aneurysm repair (OAR) 98, juxtarenal OAR 26. Overall, 24% of patients developed stage 1 AKI (defined at 48 h as per KDIGO), 2.7% stage 2 AKI and 1% needed renal replacement therapy before discharge. AKI proportions per intervention were: infrarenal EVAR 18%; fEVAR 27%; bEVAR 71%; infrarenal OAR 41%; juxtarenal OAR 63%. Older age (odds ratio [OR] 1.44 for EVAR, 1.58 for OAR), lower baseline eGFR (OR 0.88 EVAR, 0.74 OAR), and ischaemic heart disease (OR 4.42 EVAR, 5.80 OAR) were the main predictors of AKI for infrarenal EVAR and OAR. Overall, 24% developed the MAKE30 endpoint. All patients who died (0.6%) or developed a major cardiac event (5.6%) at one year had developed AKI. Conclusion AKI and short term renal decline after aortic intervention are common. Age, renal function, and cardiovascular disease are the main risk factors. Research should now focus on AKI prevention in this high risk group.

Published
2020

3. Multicentre Post-EVAR Surveillance Evaluation Study (EVAR-SCREEN)

Author

Matthew J. Grima, Alan Karthikesalingam, Peter J. Holt, Daniele Kerr, Ian Chetter, Seamus Harrison, Rob Sayers, Iain Roy, Srinivasa R. Vallabhaneni, Pang Dominic, Paul Bachoo, John Griffin, David Lewis, John Hardman, Ahmed Rihan, Marcus Brooks, Ken Woodburn, Dean Godfrey, Ian Nordon, Alberto Vidal-Diez, Kate Stenson, Sandeep Bahia, Benjamin Patterson, Dare Oladokun, Jorg De Bruin, Ian Loftus, Matt M. Thompson, Chris Lowe, Mohammed Ashrafi, Jonathan Ghosh, and Raymond Ashleigh

Subjects
Male, Reoperation, medicine.medical_specialty, Time Factors, Computed Tomography Angiography, medicine.medical_treatment, 030204 cardiovascular system & hematology, 030230 surgery, Prosthesis Design, Endovascular aneurysm repair, Aortography, 03 medical and health sciences, Blood Vessel Prosthesis Implantation, 0302 clinical medicine, Postoperative Complications, Predictive Value of Tests, Risk Factors, Epidemiology, medicine, Humans, Lost to follow-up, Survival analysis, Aged, Retrospective Studies, Aged, 80 and over, Ultrasonography, Doppler, Duplex, business.industry, Hazard ratio, Endovascular Procedures, medicine.disease, Abdominal aortic aneurysm, Confidence interval, United Kingdom, Blood Vessel Prosthesis, Treatment Outcome, Population Surveillance, Emergency medicine, Patient Compliance, Surgery, Female, Surveillance imaging, Cardiology and Cardiovascular Medicine, business, Aortic Aneurysm, Abdominal
Abstract

OBJECTIVE: Surveillance imaging is considered mandatory after endovascular aneurysm repair (EVAR), but many patients are lost to follow up and the impact of this is poorly understood. This study aimed to examine compliance with post-operative surveillance in the UK and the impact of mal-/non-compliance on endograft re-interventions and survival. METHODS: EVAR-SCREEN centres reported EVAR for intact infrarenal abdominal aortic aneurysms (AAA) from 1 January 2007 to 31 December 2010, with follow up included up to 31 July 2014. Non-compliance was defined by the presence of a single 18 month period in which no surveillance imaging was performed. The outcomes were reported in compliant and non-compliant groups with survival analysis. RESULTS: EVAR was performed in 1414 patients in 10 UK centres. At the end of the study period there were 378 patients with five years of follow up available for analysis. Compliance with surveillance was 66% (61-68%). Compliance varied widely, from 9% to 88% between centres. Age (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.01-1.05; p = .02) and distance from hospital (HR 1.01, 95% CI 1.00-1.01; p

Published
2019

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