Urine albumin excretion and the risk of incident atrial fibrillation: predictive or aetiological relevance?

Urine albumin excretion and the risk of incident atrial fibrillation: predictive or aetiological... Letters to the Editor 561 Coincidental ganglionated plexus modification during risk who have specific or unmet medical needs. If adjustments for established cardiovascular risk fac- radiofrequency pulmonary vein isolation and post- so, further work is warranted to address where a tors. We agree that we cannot rule out unmeas- ablation arrhythmia recurrence. Europace 2017;19: stratified analysis by micro or macro albuminuria ured confounding or reverse causality. 1967–72. can modify the effects of therapeutic or prevent- Theoretically, a randomized controlled trial or ive interventions on AF or AF-related health out- Mendelian randomization may be approaches to come risks later in life, opening new avenues for provide more causal evidence. However, the Georgios Giannopoulos*, stratified or precision medicine approaches. Mendelian randomization as brought forward Vasiliki Panagopoulou, and based on GWAS variants are also not immune Spyridon Deftereos Conflict of interest: I declare no competing against unmeasured confounding or reverse causal- 2nd Department of Cardiology, National and interests. ity, simply because the instrumental variable as- Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, sumptions are not satisfied here (e.g. supported by Greece strong biological understanding). To our know- References *Corresponding author. Tel: þ302105832352. ledge, there is no therapy available that solely tar- 1. Marcos EG, Geelhoed B, Van Der Harst P, Bakker SJL, E-mail address: ggiann@med.uoa.gr; Gansevoort RT, Hillege HL et al. Relation of renal dys- gets microalbuminuria that can be investigated to function with incident atrial fibrillation and cardiovascu- georgios.giannopolous@yale.edu reduce incident AF. In addition, even when such lar morbidity and mortality: The PREVEND study. therapies become available a large sample size will Europace 2017;19:1930–6. be required to perform a randomized trial in the 2. Abbasi A, Sahlqvist AS, Lotta L, Brosnan JM, Vollenweider P, Giabbanelli P et al. A systematic re- primary prevention setting. view of biomarkers and risk of incident type 2 diabetes: The magnitude of associations can indicate doi:10.1093/europace/eux043 an overview of epidemiological, prediction and aetiolo- the predictive value of a biomarker, in our case Published online 12 April 2017 gical research literature. PloS one 2016;11:e0163721. albumin excretion. Indeed potential improvements 3. Burgess S, Timpson NJ, Ebrahim S, Davey Smith G. Urine albumin excretion and in prediction need to be formally quantified in terms Mendelian randomization: where are we now and where are we going? Int. J. Epidemiol. 2015;44:379–88. the risk of incident atrial of calibration, discrimination and net reclassification 4. Cook NR. Use and misuse of the receiver operating improvement, before increased albumin excretion fibrillation: predictive or characteristic curve in risk prediction. Circulation can be implemented into the risk prediction of inci- 2007;115:928–35. aetiological relevance? dent AF. As a result of such analysis risk prediction 5. Abbasi A, Peelen LM, Corpeleijn E, van der Schouw I read with great interest the article by Marcos YT, Stolk RP, Spijkerman AM et al. Prediction models schemes, which need external validation, can be for risk of developing type 2 diabetes: systematic litera- et al. investigating observational associations of build or modified to better identify those at lowest ture search and independent external validation study. urine albumin measures either by a simple urine and highest AF risk. This was however not the aim BMJ 2012;345:e5900. albumin test or a more complex 24-h urine col- of our analysis. We sought to investigate in our ana- lection test with incident atrial fibrillation (AF) in lysis different measures of renal function such as an apparently healthy general population cohort 1,2,3 serum creatinine or cystatin C, estimated glomeru- Ali Abbasi * enriched with individuals having an urine albumin 1 lar filtration rates, and albumin excretion, in relation Department of Primary Care & Public Health concentration >10 mg/L at baseline. In line with to development of AF, and whether the magnitude Sciences, King’s College London, 3rd Floor, previously published epidemiological studies, the of effect of renal measures and cardiovascular out- Addison House, Guy’s Campus, London, SE1 1UL, 2 2 authors report a positive association between London, UK; MRC Epidemiology Unit, Institute of come may be influenced by AF. elevated urine albumin and an increased risk of Metabolic Science, University of Cambridge Finally, Abbasi brought up an interesting point School of Clinical Medicine, Cambridge Biomedical incident AF. While the associations were inde- that there may be a subset of individuals with Campus, Box 285, CB2 0QQ, Cambridge, UK; and pendent of common and novel risk factors in pro- increased urine albumin that may be considered as Department of Epidemiology, University Medical spective observations, but a possibility of high risk for incident AF. Indeed targeting high risk Center Groningen, PO Box 30.001, 9700 RB, unmeasured confounding or reverse causality groups specifically may help to reduce their risk of Groningen, The Netherlands cannot be ruled out. As the authors and others AF. However, more research is needed to study * Corresponding author. Tel: þ44 (0)20 7848 noted a complementary strand of evidence from the characteristics of such high risk groups, and 6631; fax: +44 (0)20 7848 6620. a randomized clinical trial or its analog, called which specific therapies are needed. Unfortunately, E-mail address: ali.abbasi@kcl.ac.uk; Mendelian randomization, needs to investigate ournumberofincidentAFcases wasrathermodest a.abbasi@umcg.nl whether the association between urine albumin to perform stratified analyses according to different and AF is causal or not. In this context, genetic evi- severities of albumin excretion. We hope that our dence from available genome-wide association analysis further increases the interest in albumin ex- studies (GWAS) for urine albumin and AF or a cretion and its link with AF, and motivate others to doi:10.1093/europace/eux088 meta-analysis of genome-wide genotype data help to investigate this further. Such research is Published online 10 June 2017 from large cohorts can enhance the likelihood of warranted to determine whether personalized pre- 2,3 causal or non-causal associations. cision medicine approaches can improve treatment Urine albumin excretion and In the context of prediction, the investigators outcomes and minimize adverse events. the risk of incident atrial need to examine whether additional information Conflict of interest: none declared. fibrillation: predictive or on urine albumin can improve AF prediction be- aetiological relevance— yond its classical risk factors. Here, the magnitude of associations can indicate the predictive value of Authors’ reply a biomarker where potential improvements in Funding prediction are formally quantified in terms of cali- We appreciate the continuing interest of Abbasi in bration, discrimination, and net reclassification im- the PREVEND cohort. Our article showed that in a The PREVEND study is supported by the Dutch 2,4,5 provement. Finally in another context, the community-based cohort increased albumin excre- Kidney Foundation (Grant E0.13) and the investigators may consider individuals with ele- tion, and not estimated glomerular filtration rate, Netherlands Heart Foundation (Grant vated urine albumin as a subgroup of those at high was associated with incident AF, even after NHS2010B280). Dr Rienstra is supported by a Downloaded from https://academic.oup.com/europace/article-abstract/20/3/561/3605214 by Ed 'DeepDyve' Gillespie user on 16 March 2018 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Europace Oxford University Press

Urine albumin excretion and the risk of incident atrial fibrillation: predictive or aetiological relevance?

Europace , Volume 20 (3) – Mar 1, 2018
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Abstract

Letters to the Editor 561 Coincidental ganglionated plexus modification during risk who have specific or unmet medical needs. If adjustments for established cardiovascular risk fac- radiofrequency pulmonary vein isolation and post- so, further work is warranted to address where a tors. We agree that we cannot rule out unmeas- ablation arrhythmia recurrence. Europace 2017;19: stratified analysis by micro or macro albuminuria ured confounding or reverse causality. 1967–72. can modify the effects of therapeutic or prevent- Theoretically, a randomized controlled trial or ive interventions on AF or AF-related health out- Mendelian randomization may be approaches to come risks later in life, opening new avenues for provide more causal evidence. However, the Georgios Giannopoulos*, stratified or precision medicine approaches. Mendelian randomization as brought forward Vasiliki Panagopoulou, and based on GWAS variants are also not immune Spyridon Deftereos Conflict of interest: I declare no competing against unmeasured confounding or reverse causal- 2nd Department of Cardiology, National and interests. ity, simply because the instrumental variable as- Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, sumptions are not satisfied here (e.g. supported by Greece strong biological understanding). To our know- References *Corresponding author. Tel: þ302105832352. ledge, there is no therapy available that solely tar- 1. Marcos EG, Geelhoed B, Van Der Harst P, Bakker SJL, E-mail address: ggiann@med.uoa.gr; Gansevoort RT, Hillege HL et al. Relation of renal dys- gets microalbuminuria that can be investigated to function with incident atrial fibrillation and cardiovascu- georgios.giannopolous@yale.edu reduce incident AF. In addition, even when such lar morbidity and mortality: The PREVEND study. therapies become available a large sample size will Europace 2017;19:1930–6. be required to perform a randomized trial in the 2. Abbasi A, Sahlqvist AS, Lotta L, Brosnan JM, Vollenweider P, Giabbanelli P et al. A systematic re- primary prevention setting. view of biomarkers and risk of incident type 2 diabetes: The magnitude of associations can indicate doi:10.1093/europace/eux043 an overview of epidemiological, prediction and aetiolo- the predictive value of a biomarker, in our case Published online 12 April 2017 gical research literature. PloS one 2016;11:e0163721. albumin excretion. Indeed potential improvements 3. Burgess S, Timpson NJ, Ebrahim S, Davey Smith G. Urine albumin excretion and in prediction need to be formally quantified in terms Mendelian randomization: where are we now and where are we going? Int. J. Epidemiol. 2015;44:379–88. the risk of incident atrial of calibration, discrimination and net reclassification 4. Cook NR. Use and misuse of the receiver operating improvement, before increased albumin excretion fibrillation: predictive or characteristic curve in risk prediction. Circulation can be implemented into the risk prediction of inci- 2007;115:928–35. aetiological relevance? dent AF. As a result of such analysis risk prediction 5. Abbasi A, Peelen LM, Corpeleijn E, van der Schouw I read with great interest the article by Marcos YT, Stolk RP, Spijkerman AM et al. Prediction models schemes, which need external validation, can be for risk of developing type 2 diabetes: systematic litera- et al. investigating observational associations of build or modified to better identify those at lowest ture search and independent external validation study. urine albumin measures either by a simple urine and highest AF risk. This was however not the aim BMJ 2012;345:e5900. albumin test or a more complex 24-h urine col- of our analysis. We sought to investigate in our ana- lection test with incident atrial fibrillation (AF) in lysis different measures of renal function such as an apparently healthy general population cohort 1,2,3 serum creatinine or cystatin C, estimated glomeru- Ali Abbasi * enriched with individuals having an urine albumin 1 lar filtration rates, and albumin excretion, in relation Department of Primary Care & Public Health concentration >10 mg/L at baseline. In line with to development of AF, and whether the magnitude Sciences, King’s College London, 3rd Floor, previously published epidemiological studies, the of effect of renal measures and cardiovascular out- Addison House, Guy’s Campus, London, SE1 1UL, 2 2 authors report a positive association between London, UK; MRC Epidemiology Unit, Institute of come may be influenced by AF. elevated urine albumin and an increased risk of Metabolic Science, University of Cambridge Finally, Abbasi brought up an interesting point School of Clinical Medicine, Cambridge Biomedical incident AF. While the associations were inde- that there may be a subset of individuals with Campus, Box 285, CB2 0QQ, Cambridge, UK; and pendent of common and novel risk factors in pro- increased urine albumin that may be considered as Department of Epidemiology, University Medical spective observations, but a possibility of high risk for incident AF. Indeed targeting high risk Center Groningen, PO Box 30.001, 9700 RB, unmeasured confounding or reverse causality groups specifically may help to reduce their risk of Groningen, The Netherlands cannot be ruled out. As the authors and others AF. However, more research is needed to study * Corresponding author. Tel: þ44 (0)20 7848 noted a complementary strand of evidence from the characteristics of such high risk groups, and 6631; fax: +44 (0)20 7848 6620. a randomized clinical trial or its analog, called which specific therapies are needed. Unfortunately, E-mail address: ali.abbasi@kcl.ac.uk; Mendelian randomization, needs to investigate ournumberofincidentAFcases wasrathermodest a.abbasi@umcg.nl whether the association between urine albumin to perform stratified analyses according to different and AF is causal or not. In this context, genetic evi- severities of albumin excretion. We hope that our dence from available genome-wide association analysis further increases the interest in albumin ex- studies (GWAS) for urine albumin and AF or a cretion and its link with AF, and motivate others to doi:10.1093/europace/eux088 meta-analysis of genome-wide genotype data help to investigate this further. Such research is Published online 10 June 2017 from large cohorts can enhance the likelihood of warranted to determine whether personalized pre- 2,3 causal or non-causal associations. cision medicine approaches can improve treatment Urine albumin excretion and In the context of prediction, the investigators outcomes and minimize adverse events. the risk of incident atrial need to examine whether additional information Conflict of interest: none declared. fibrillation: predictive or on urine albumin can improve AF prediction be- aetiological relevance— yond its classical risk factors. Here, the magnitude of associations can indicate the predictive value of Authors’ reply a biomarker where potential improvements in Funding prediction are formally quantified in terms of cali- We appreciate the continuing interest of Abbasi in bration, discrimination, and net reclassification im- the PREVEND cohort. Our article showed that in a The PREVEND study is supported by the Dutch 2,4,5 provement. Finally in another context, the community-based cohort increased albumin excre- Kidney Foundation (Grant E0.13) and the investigators may consider individuals with ele- tion, and not estimated glomerular filtration rate, Netherlands Heart Foundation (Grant vated urine albumin as a subgroup of those at high was associated with incident AF, even after NHS2010B280). Dr Rienstra is supported by a Downloaded from https://academic.oup.com/europace/article-abstract/20/3/561/3605214 by Ed 'DeepDyve' Gillespie user on 16 March 2018

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EuropaceOxford University Press

Published: Mar 1, 2018

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