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70. Is self-reported 'moderate' drinking in the cardiovascular benefit range associated with alcoholic behavior? A population based study.

Author

Ammar KA, Samee S, Colligan R, Morse R, Faheem O, Shapiro M, Kors J, and Rodeheffer RJ

Abstract

This article aims at identifying a threshold number of drinks per day beyond which there is a high risk of developing alcoholic behavior that would enable physicians to more confidently support the use of alcohol for cardiovascular risk prevention. In a randomly selected, population-based sample of 2,042 adults 45 years or older, we graded alcohol drinking behavior using the Self-Administered Alcoholism Screening Test, quantified alcohol amount by questionnaire, and assessed the prevalence of cardiovascular disease (coronary, peripheral, or cerebrovascular disease) by medical record review. Although optimal alcohol use (

Published
2009
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72. Mapping the domain of medical informatics.

Author

Schuemie MJ, Talmon JL, Moorman PW, Kors JA, Schuemie, M J, Talmon, J L, Moorman, P W, and Kors, J A

Abstract

Objectives: The domain of medical informatics (MI) is not well defined. It covers a wide range of research topics. Our objective is to characterize the field of MI by means of the scientific literature in this domain.Methods: We used titles and abstracts from MEDLINE records of papers published between July 1993 and July 2008, and extracted uni-, bi- and trigrams as features. Starting with the ISI category of medical informatics, we applied a semi-automated procedure to identify the set of journals and proceedings pertaining to MI. A clustering algorithm was subsequently applied to the articles from this set of publications.Results: MI literature can be divided into three subdomains: 1) the organization, application, and evaluation of health information systems, 2) medical knowledge representation, and 3) signal and data analysis. Over the last fifteen years, the field has remained relatively stable, although most journals have shifted their focus somewhat.Conclusions: We identified the scientific literature pertaining to the field of MI, and the main areas of research. We were able to show trends in the field, and the positioning of different journals within this field. [ABSTRACT FROM AUTHOR]

Published
2009

80. Computerized ST depression analysis improves prediction of all-cause and cardiovascular mortality: the strong heart study.

Author

Okin, Peter M., Devereux, Richard B., Kors, Jan A., Herpen, Gerard, Crow, Richard S., Fabsitz, Richard R., Howard, Barbara V., Okin, P M, Devereux, R B, Kors, J A, van Herpen, G, Crow, R S, Fabsitz, R R, and Howard, B V

Abstract

Background: Nonspecific ST depression assessed by standard visual Minnesota coding (MC) has been demonstrated to predict risk. Although computer analysis has been applied to digital ECGs for MC, the prognostic value of computerized MC and computerized ST depression analyses have not been examined in relation to standard visual MC.Methods: The predictive value of nonspecific ST depression as determined by visual and computerized MC codes 4.2 or 4.3 was compared with computer-measured ST depression >or= 50 microV in 2,127 American Indian participants in the first Strong Heart Study examination. Computerized MC and ST depression were determined using separate computerized-ECG analysis programs and visual MC was performed by an experienced ECG core laboratory.Results: The prevalence of MC 4.2 or 4.3 by computer was higher than by visual analysis (6.4 vs 4.4%, P < 0.001). After mean follow-up of 3.7 +/- 0.9 years, there were 73 cardiovascular deaths and 227 deaths from all causes. In univariate Cox analyses, visual MC (relative risk [RR] 4.8, 95% confidence interval [CI] 2.6-9.1), computerized MC (RR 6.0, 95% CI 3.5-10.3), and computer-measured ST depression (RR 7.6, 95% CI 4.5-12.9) were all significant predictors of cardiovascular death. In separate multivariate Cox regression analyses that included age, sex, diabetes, HDL and LDL cholesterol, body mass index, systolic and diastolic blood pressure, microalbuminuria, smoking, and the presence of coronary heart disease, computerized MC (RR 3.0, 95% CI 1.6-5.6) and computer-measured ST depression (RR 3.1, 95% CI 1.7-5.7), but not visual MC, remained significant predictors of cardiovascular mortality. When both computerized MC and computer-measured ST depression were entered into the multivariate Cox regression, each variable provided independent risk stratification (RR 2.1, 95% CI 1.0-4.4, and RR 2.1, 95% CI 1.0-4.4, respectively). Similarly, computerized MC and computer-measured ST depression, but not visual MC, were independent predictors of all-cause mortality after controlling for standard risk factors.Conclusions: Computer analysis of the ECG, using computerized MC and computer-measured ST depression, provides independent and additive risk stratification for cardiovascular and all-cause mortality, and improves risk stratification compared with visual MC. These findings support the use of routine computer analysis of ST depression on the rest ECG for assessment of risk and suggest that computerized MC can replace visual MC for this purpose. [ABSTRACT FROM AUTHOR]

Published
2001
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86. Triage and Evaluation of Potential Safety Signals Identified from Electronic Healthcare Record Databases

Author

Coloma, P. M., Schuemie, M. J., Trifiro, G., Furlong, L., Mulligen, E., Bauer-Mehren, A., Avillach, P., Kors, J., Sanz, F., Mestres, J., Oliveira, J. L., Boyer, S., Helgee, E. A., Molokhia, M., Matthews, J., Prieto-Merino, D., Rosa Gini, Herings, R. M. C., Mazzaglia, G., Picelli, G., Scotti, L., Pedetsen, L., Lei, J., Sturkenboom, M. C. J. M., Coloma, P, Schuemie, M, Trifiro, G, Furlong, L, Van Mulligen, E, Bauer-Mehren, A, Avillach, P, Kors, J, Sanz, F, Mestres, J, Oliveira, J, Boyer, S, Helgee, E, Molokhia, M, Matthews, J, Prieto-Merino, D, Gini, R, Herings, R, Mazzaglia, G, Picelli, G, Scotti, L, Pedetsen, L, Van der Lei, J, and Sturkenboom, M

Subjects
Spontaneuous reporting, Validation studies, Electronic Healthcare Database, Adverse Drug Reaction, Signal detection
Abstract

Background: There is huge potential for mining electronic healthcare records (EHR) databases to augment current systems in pharmacovigilance.[1-3] Like any signal detection system, there is a need to establish ‘rules’ how to trigger an alert, when to consider a signal likely enough to be true to warrant follow-up or even to require immediate health policy intervention.[4,5] Objectives: To describe the process of prioritisation of drug-adverse event associations derived from signal detection using EHR databases in the EU-ADR Project. Methods: Association measures between drug use and acute myocardial infarction (AMI) were generated by first applying various statistical methods on healthcare data from seven databases of the EUADR network.[6] Association estimates were ranked based on the best performing method (Longitudinal Gamma Poisson Shrinker). Matched case-control and self-controlled case series methods were additionallyconducted to deal with temporality and confounding effect, while the LEOPARD method was applied to specifically detect protopathic bias. Consistency of the association among drugs of the same class and the number of excess cases attributable to the drug exposure were further assessed to prioritize the list of potential signals. Finally, signal filtering and signal substantiation were done using different bioinformatics workflows to determine the novelty and plausibility of the identified signals. Results: Demographic, clinical and prescription/dispensing data in three European Countries were obtained from 21 171 291 individuals with 154 474 063 person-years of follow-up within the period 1995–2011. Overall, 163 potential signals forAMI were identified based on statistical association. Of these, 72 signals were flagged by LEOPARDas likely due to protopathic bias. Further signal refinement to reduce possible confounding decreased the number of signals to 39. Nine signals remained after applying the criteria for novelty and plausibility. Conclusion: We propose a prioritisation strategy for drug safety signal detection using EHR by taking into account, in addition to statistical association, also public health relevance, novelty, and plausibility. This strategy needs to be further tested using other EHR data sources and other adverse events.

87. Feasibility and findings of electrocardiogram recording in older adults with intellectual disabilities: results of the Healthy Ageing and Intellectual Disabilities study.

Author

Leeuw, M. J., Böhmer, M. N., Leening, M. J. G., Kors, J. A., Bindels, P. J. E., Oppewal, A., and Maes‐Festen, D. A. M.

Subjects
*MYOCARDIAL infarction, *OLDER people, *ATRIAL fibrillation, *INTELLECTUAL disabilities, *CARDIOVASCULAR diseases
Abstract

Background Method Results Conclusions Older adults with intellectual disabilities (ID) have a high risk of cardiovascular diseases (CVD). At the same time, challenging diagnostic work‐up increases the likelihood of underdiagnosis of CVD in this population. To limit this underdiagnosis, it would be beneficial to use objective measures such as the electrocardiogram (ECG). However, little is known about the feasibility of ECG recording and the prevalence of ECG abnormalities in this population. Therefore, the aims of this study were to investigate the feasibility of resting ECG recording, to study the prevalence of ECG abnormalities, and to compare the frequency of ECG abnormalities with medical records in older adults with ID.A cross‐sectional study was performed within a cohort of older adults (≥60 years) with ID as part of the Healthy Ageing and Intellectual Disabilities (HA‐ID) study. A resting 12‐lead ECG was attempted, and the ECG recording was considered feasible if the recording could be made and if the ECG could be interpreted by a cardiologist and the Modular ECG Analysis System (MEANS). ECGs were assessed for the presence of ECG abnormalities and medical record review was performed. If the cardiologist or MEANS concluded that there was evidence of myocardial infarction, atrial fibrillation or QTc prolongation on the ECG in the absence of this ECG diagnosis in the participant's medical record, this was classified as a previously undiagnosed ECG diagnosis.ECG recording was feasible in 134 of the 200 participants (67.0%). Of these 134 participants (70.6 ± 5.8 years; 52.2% female), 103 (76.9%) had one or more ECG abnormality, with the most prevalent being prolonged P‐wave duration (27.6%), QTc prolongation (18.7%), minor T‐wave abnormalities (17.9%), first degree atrioventricular block (12.7%) and myocardial infarction (6.7%). Eight out of 9 (88.9%) myocardial infarctions and all cases of (significant) QTc prolongation (100%) were previously undiagnosed.This study showed that ECG recording is feasible in the majority of older adults with ID and revealed a substantial underdiagnosis of ECG abnormalities. These results stress the importance of ECG recording and warrant further research into the yield of opportunistic ECG screening in older adults with ID. [ABSTRACT FROM AUTHOR]

Published
2024
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88. A concept annotation system for clinical records

Author

Kang, N., Barendse, R., Zubair Afzal, Singh, B., Schuemie, M. J., Mulligen, E. M., and Kors, J. A.

Subjects
FOS: Computer and information sciences, J.3, Information Retrieval (cs.IR), Computer Science - Information Retrieval
Abstract

Unstructured information comprises a valuable source of data in clinical records. For text mining in clinical records, concept extraction is the first step in finding assertions and relationships. This study presents a system developed for the annotation of medical concepts, including medical problems, tests, and treatments, mentioned in clinical records. The system combines six publicly available named entity recognition system into one framework, and uses a simple voting scheme that allows to tune precision and recall of the system to specific needs. The system provides both a web service interface and a UIMA interface which can be easily used by other systems. The system was tested in the fourth i2b2 challenge and achieved an F-score of 82.1% for the concept exact match task, a score which is among the top-ranking systems. To our knowledge, this is the first publicly available clinical record concept annotation system., Comment: in Adrian Paschke, Albert Burger, Andrea Splendiani, M. Scott Marshall, Paolo Romano: Proceedings of the 3rd International Workshop on Semantic Web Applications and Tools for the Life Sciences, Berlin,Germany, December 8-10, 2010

89. A concept-based approach to text categorization

Author

Schijvenaars, B. J. A., Schuemie, M. J., Erik van Mulligen, Weeber, M., Jelier, R., Mons, B., Kors, J. A., Kraaij, W., and TNO Informatie- en Communicatietechnologie

Subjects
Infostructures, Informatics, Information Society
Abstract

The Biosemantics group (Erasmus University Medical Center, Rotterdam) participated in the text categorization task of the Genomics Track. We followed a thesaurus-based approach, using the Collexis indexing system, in combination with a simple classification algorithm to assign a document to one of the four categories. Our thesaurus consisted of a combination of MeSH, Gene Ontology, and a thesaurus with gene and protein symbols and names extracted from the Mouse Genome Database, Swiss-Prot and Entrez Gene. To increase the coverage of the gene thesaurus, several rewrite rules were applied to take possible spelling variations into account. Each document in the training set was indexed and the found concepts were ranked on term frequency, resulting in one concept vector per document. No particular care was taken to resolve ambiguous terms. For each of the four categories, two average concept vectors were computed, one by averaging the concept vectors of the documents in that category and the other by averaging all remaining concept vectors. The latter vector was then subtracted from the first, yielding a final category concept vector. The subtraction served to emphasize distinguishing concepts: high-ranked concepts in the final concept vector should, on average, occur relatively frequently in documents belonging to the category, while occurring infrequently or not at all in documents not belonging to the category. For all documents in the training set, a matching score between the concept vector of a document and each of the category concept vectors was computed. A score threshold to discriminate between category and non-category documents was then determined per category by optimizing the performance measure (normalized utility). Different matching algorithms and different cutoffs for the number of concepts in the category vectors were evaluated. A standard cosine similarity score and a category vector with the 40 highest-ranking concepts proved to perform best on the training set. These settings and the score thresholds were subsequently used to categorize all documents in the test set. Two runs were submitted: one based on the full text without any special treatment of particular sections, and one based on the Medline abstract, including the title and the MeSH headings. In addition two runs were submitted by TNO for the ad-hoc search task. The ad-hoc system was based on the TREC 2004 system, with a small experiment trying to leverage information about the authority level of specific journals.

91. De spoedlijn: een garantie voor bereikbaarheid?

Author

Groot, R., Schot, S., Kors, J., Bosveld, H., and Haan, J

Abstract

Copyright of Huisarts En Wetenschap is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Published
2001
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93. Accurate automatic detection of electrode interchange in the electrocardiogram.

Author

Kors, Jan A., van Herpen, Gerard, Kors, J A, and van Herpen, G

Subjects
*ELECTROCARDIOGRAPHY, *ELECTRODES
Abstract

In recording an electrocardiogram (ECG), an interchange of electrodes may easily go unnoticed. Automatic detection would be desirable, but current algorithms, when dealing with more than left arm-right arm reversal, have moderate sensitivity. We propose a novel approach that uses the redundancy of information in the standard 12-lead ECG. We assume that each of the 8 independent electrocardiographic leads can be reconstructed from the 7 others in reasonable approximation. The correlation between any electrocardiographic lead and its reconstruction should be higher if the electrodes are correctly placed than when some interchange were present. The difference in correlation should have discriminative power. This was verified on a set of 3,305 ECGs for 14 common electrode interchange errors. The material was split in a learning and test set, and general reconstruction coefficients were computed from the learning set. For each interchange, electrode-error ECGs were derived by rearranging leads of the unaltered ECGs. Correlations between the actual leads and their reconstructions were computed for all ECGs. From the differences in lead correlation, decision rules were derived for each kind of interchange. All 14 rules had specificities of > or =99.5% in the test set. Sensitivities were > or =93% for 11 rules, and left arm-left leg electrode reversal scored low. [ABSTRACT FROM AUTHOR]

Published
2001
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94. Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

Author

Dennis O. Mook-Kanamori, Yalda Jamshidi, Peter K. Joshi, Seung Hoan Choi, Henry J. Lin, Rebecca D. Jackson, Alison D. Murray, May E. Montasser, Veikko Salomaa, Charles Kooperberg, Moritz F. Sinner, Gianfranco Sinagra, Luisa Foco, James G. Wilson, Johan Sundström, Kathleen A. Ryan, Eric A. Whitsel, Bruno H. Stricker, Sandosh Padmanabhan, Christopher Newton-Cheh, Ozren Polasek, Unnur Thorsteinsdottir, Niek Verweij, Pier D. Lambiase, Nathan R. Tucker, Stefan Kääb, Jun Ding, Stefan Weiss, Daniel F. Gudbjartsson, David Conen, Lars Lind, Ivana Kolcic, Lu-Chen Weng, J. Wouter Jukema, Kirill V. Tarasov, Xiuqing Guo, Stella Trompet, Patricia B. Munroe, Albert V. Smith, Elsayed Z. Soliman, Andrew Tinker, Antti Jula, J. Gustav Smith, Alexander P. Reiner, Sébastien Thériault, Kathryn L. Lunetta, Vilmundur Gudnason, Mika Kähönen, Massimo Mangino, Raymond Noordam, Joshua C. Bis, Alan R. Shuldiner, Tim D. Spector, Borbala Mifsud, Stefan van Duijvenboden, Jeffrey R. O'Connell, Emelia J. Benjamin, M. Benjamin Shoemaker, Stephan B. Felix, Peter W. Macfarlane, Lorenz Risch, Uwe Völker, Stephanie M. Gogarten, Maria Fernanda Lima-Costa, Julia Ramirez, Morten S. Olesen, Konstantin Strauch, Annette Peters, Aaron Isaacs, Steven A. Lubitz, Eric Boerwinkle, Carolina Roselli, James H. Cartwright, Nathalia M. Araujo, Ruth J. F. Loos, Diane Fatkin, Harry Campbell, Blair H. Smith, Thomas Meitinger, André G. Uitterlinden, Paul L. Huang, Tamara B. Harris, Kathleen F. Kerr, David J. Porteous, Martina Müller-Nurasyid, Francesco Cucca, Michiel Rienstra, Davíð O. Arnar, Amanda A. Seyerle, Caroline Hayward, M. Abdullah Said, Catriona L. K. Barnes, Kent D. Taylor, Nona Sotoodehnia, Nina Mononen, Dan M. Roden, Jonathan Marten, Terho Lehtimäki, Dan E. Arking, Anna F. Dominiczak, Jan A. Kors, Olli T. Raitakari, Igor Rudan, Yordi J. van de Vegte, Christopher P. Nelson, Erik Ingelsson, Ulrike Peters, Girish N. Nadkarni, Eduardo Tarazona-Santos, Edward G. Lakatta, Nina Hutri-Kähönen, Bruce M. Psaty, Patrick T. Ellinor, Christian Fuchsberger, Katharina Schramm, Amelia W. Hall, M. Yldau van der Ende, Alvaro Alonso, James F. Wilson, Sheila Ulivi, Rosa B. Thorolfsdottir, Stefanie Aeschbacher, Mary L. Biggs, Marten E. van den Berg, Nilesh J. Samani, Thibaud Boutin, Vilmantas Giedraitis, Honghuang Lin, Kjell Nikus, Helen R. Warren, Arie C. Maan, James J. Cranley, Adolfo Correa, Martin Gögele, Ian Ford, Katri Sääksjärvi, Georg Ehret, Michele Orini, Susan R. Heckbert, Cecilia M. Lindgren, Jie Yao, Maria Pina Concas, Pim van der Harst, Ioanna Ntalla, Jeffrey Haessler, Jerome I. Rotter, Pashupati P. Mishra, Michael J. Cutler, Erwin P. Bottinger, Cornelia M. van Duijn, Jennifer A. Brody, Paolo Gasparini, Lenore J. Launer, Andrew P. Morris, Renée de Mutsert, Aki S. Havulinna, James P. Cook, Hilma Holm, Patrick Sulem, Alessandro De Grandi, Cristian Pattaro, Gardar Sveinbjornsson, Antonio Luiz Pinho Ribeiro, Mark J. Caulfield, Gudmar Thorleifsson, Marcus Dörr, Muhammad B. Riaz, Peter P. Pramstaller, Yong Qian, Anubha Mahajan, Cathy C. Laurie, Kenneth Rice, Mark Chaffin, Kari Stefansson, Andrew A. Hicks, Solmaz Assa, Hao Mei, Leo-Pekka Lyytikäinen, Fabiola Del Greco M, Renan P. Souza, Michael Preuss, Adrienne M. Stilp, Barry London, Melanie Waldenberger, Christy L. Avery, Daniel Levy, Michael R. Barnes, Medical Informatics, Epidemiology, Internal Medicine, Weng, Lu-Chen [0000-0003-1475-4930], Hall, Amelia Weber [0000-0002-7915-0313], Tucker, Nathan R [0000-0002-5071-4218], Chaffin, Mark D [0000-0002-1234-5562], Roselli, Carolina [0000-0001-5267-6756], Barnes, Michael R [0000-0001-9097-7381], Mifsud, Borbala [0000-0003-3429-3094], Hayward, Caroline [0000-0002-9405-9550], Concas, Maria Pina [0000-0003-3598-2537], Boutin, Thibaud [0000-0003-4754-1675], Kolcic, Ivana [0000-0001-7918-6052], Rudan, Igor [0000-0001-6993-6884], Souza, Renan P [0000-0002-9479-4432], Giedraitis, Vilmantas [0000-0003-3423-2021], Ingelsson, Erik [0000-0003-2256-6972], Mahajan, Anubha [0000-0001-5585-3420], Morris, Andrew P [0000-0002-6805-6014], Hicks, Andrew A [0000-0001-6320-0411], Sundström, Johan [0000-0003-2247-8454], Nelson, Christopher P [0000-0001-8025-2897], Riaz, Muhammad B [0000-0002-5512-1745], Sinagra, Gianfranco [0000-0003-2700-8478], Mishra, Pashupati P [0000-0001-5177-3431], Caulfield, Mark J [0000-0001-9295-3594], Dominiczak, Anna [0000-0003-4913-3608], Risch, Lorenz [0000-0003-2692-6699], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Isaacs, Aaron [0000-0001-5037-4834], van Duijn, Cornelia M [0000-0002-2374-9204], Gudnason, Vilmundur [0000-0001-5696-0084], Smith, Albert V [0000-0003-1942-5845], Loos, Ruth JF [0000-0002-8532-5087], Preuss, Michael H [0000-0001-5266-8465], Correa, Adolfo [0000-0002-9501-600X], Müller-Nurasyid, Martina [0000-0003-3793-5910], Waldenberger, Melanie [0000-0003-0583-5093], Mangino, Massimo [0000-0002-2167-7470], Rienstra, Michiel [0000-0002-2581-070X], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Fatkin, Diane [0000-0002-9010-9856], Brody, Jennifer A [0000-0001-8509-148X], Rice, Kenneth [0000-0002-3071-7278], Pattaro, Cristian [0000-0002-4119-0109], Wouter Jukema, J [0000-0002-3246-8359], Weiss, Stefan [0000-0002-3553-4315], Havulinna, Aki S [0000-0002-4787-8959], Sääksjärvi, Katri [0000-0002-5061-4911], Salomaa, Veikko [0000-0001-7563-5324], Rotter, Jerome I [0000-0001-7191-1723], Taylor, Kent D [0000-0002-2756-4370], Lakatta, Edward G [0000-0002-4772-0035], Lin, Honghuang [0000-0003-3043-3942], Lunetta, Kathryn L [0000-0002-9268-810X], Murray, Alison D [0000-0003-4915-4847], Porteous, David J [0000-0003-1249-6106], Smith, Blair H [0000-0002-5362-9430], Uitterlinden, André [0000-0002-7276-3387], Peters, Ulrike [0000-0001-5666-9318], Alonso, Alvaro [0000-0002-2225-8323], Ehret, Georg B [0000-0002-5730-0675], Soliman, Elsayed Z [0000-0001-5632-8150], Gogarten, Stephanie M [0000-0002-7231-9745], Kerr, Kathleen F [0000-0002-6438-9583], Abdullah Said, M [0000-0003-2920-7745], Orini, Michele [0000-0001-5773-0344], Ramirez, Julia [0000-0003-4130-5866], Van Duijvenboden, Stefan [0000-0001-8897-558X], Gudbjartsson, Daniel F [0000-0002-5222-9857], Sulem, Patrick [0000-0001-7123-6123], Thorolfsdottir, Rosa B [0000-0001-7475-0398], Benjamin, Emelia J [0000-0003-4076-2336], Stefansson, Kari [0000-0003-1676-864X], Ellinor, Patrick T [0000-0002-2067-0533], Jamshidi, Yalda [0000-0003-0151-6482], Lubitz, Steven A [0000-0002-9599-4866], Munroe, Patricia B [0000-0002-4176-2947], Apollo - University of Cambridge Repository, Medicum, Institute for Molecular Medicine Finland, Complex Disease Genetics, Helsinki Institute of Life Science HiLIFE, University of Helsinki, Cardiovascular Centre (CVC), Ntalla, I., Weng, L. -C., Cartwright, J. H., Hall, A. W., Sveinbjornsson, G., Tucker, N. R., Choi, S. H., Chaffin, M. D., Roselli, C., Barnes, M. R., Mifsud, B., Warren, H. R., Hayward, C., Marten, J., Cranley, J. J., Concas, M. P., Gasparini, P., Boutin, T., Kolcic, I., Polasek, O., Rudan, I., Araujo, N. M., Lima-Costa, M. F., Ribeiro, A. L. P., Souza, R. P., Tarazona-Santos, E., Giedraitis, V., Ingelsson, E., Mahajan, A., Morris, A. P., Del Greco M, F., Foco, L., Gogele, M., Hicks, A. A., Cook, J. P., Lind, L., Lindgren, C. M., Sundstrom, J., Nelson, C. P., Riaz, M. B., Samani, N. J., Sinagra, G., Ulivi, S., Kahonen, M., Mishra, P. P., Mononen, N., Nikus, K., Caulfield, M. J., Dominiczak, A., Padmanabhan, S., Montasser, M. E., O'Connell, J. R., Ryan, K., Shuldiner, A. R., Aeschbacher, S., Conen, D., Risch, L., Theriault, S., Hutri-Kahonen, N., Lehtimaki, T., Lyytikainen, L. -P., Raitakari, O. T., Barnes, C. L. K., Campbell, H., Joshi, P. K., Wilson, J. F., Isaacs, A., Kors, J. A., van Duijn, C. M., Huang, P. L., Gudnason, V., Harris, T. B., Launer, L. J., Smith, A. V., Bottinger, E. P., Loos, R. J. F., Nadkarni, G. N., Preuss, M. H., Correa, A., Mei, H., Wilson, J., Meitinger, T., Muller-Nurasyid, M., Peters, A., Waldenberger, M., Mangino, M., Spector, T. D., Rienstra, M., van de Vegte, Y. J., van der Harst, P., Verweij, N., Kaab, S., Schramm, K., Sinner, M. F., Strauch, K., Cutler, M. J., Fatkin, D., London, B., Olesen, M., Roden, D. M., Benjamin Shoemaker, M., Gustav Smith, J., Biggs, M. L., Bis, J. C., Brody, J. A., Psaty, B. M., Rice, K., Sotoodehnia, N., De Grandi, A., Fuchsberger, C., Pattaro, C., Pramstaller, P. P., Ford, I., Wouter Jukema, J., Macfarlane, P. W., Trompet, S., Dorr, M., Felix, S. B., Volker, U., Weiss, S., Havulinna, A. S., Jula, A., Saaksjarvi, K., Salomaa, V., Guo, X., Heckbert, S. R., Lin, H. J., Rotter, J. I., Taylor, K. D., Yao, J., de Mutsert, R., Maan, A. C., Mook-Kanamori, D. O., Noordam, R., Cucca, F., Ding, J., Lakatta, E. G., Qian, Y., Tarasov, K. V., Levy, D., Lin, H., Newton-Cheh, C. H., Lunetta, K. L., Murray, A. D., Porteous, D. J., Smith, B. H., Stricker, B. H., Uitterlinden, A., van den Berg, M. E., Haessler, J., Jackson, R. D., Kooperberg, C., Peters, U., Reiner, A. P., Whitsel, E. A., Alonso, A., Arking, D. E., Boerwinkle, E., Ehret, G. B., Soliman, E. Z., Avery, C. L., Gogarten, S. M., Kerr, K. F., Laurie, C. C., Seyerle, A. A., Stilp, A., Assa, S., Abdullah Said, M., Yldau van der Ende, M., Lambiase, P. D., Orini, M., Ramirez, J., Van Duijvenboden, S., Arnar, D. O., Gudbjartsson, D. F., Holm, H., Sulem, P., Thorleifsson, G., Thorolfsdottir, R. B., Thorsteinsdottir, U., Benjamin, E. J., Tinker, A., Stefansson, K., Ellinor, P. T., Jamshidi, Y., Lubitz, S. A., Munroe, P. B., Fysiologie, RS: FHML MaCSBio, RS: Carim - B01 Blood proteins & engineering, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Háskóli Íslands, and University of Iceland

Subjects
0301 basic medicine, Male, Multifactorial Inheritance, General Physics and Astronomy, Gene Expression, Genome-wide association study, 030204 cardiovascular system & hematology, Arrhythmias, Genome-wide association studies, CALCINEURIN, Electrocardiography, 0302 clinical medicine, Cardiovascular Disease, Multi-ancestry GWAS, ELEMENTS, Medicine, Cardiac and Cardiovascular Systems, Blóðrásarsjúkdómar, lcsh:Science, RISK, DECREASE, education.field_of_study, Multidisciplinary, Kardiologi, medicine.diagnostic_test, 1184 Genetics, developmental biology, physiology, Atrial fibrillation, 3142 Public health care science, environmental and occupational health, 3. Good health, Endophenotype, Arrhythmias, Cardiac, Cardiovascular Diseases, Endophenotypes, Female, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Quantitative Trait Loci, cardiovascular system, Cardiology, medicine.symptom, Erfðarannsóknir, Cardiac, Medical Genetics, Human, Bradycardia, medicine.medical_specialty, Science, GENOME-WIDE ASSOCIATION, ATRIAL-FIBRILLATION, MUTATIONS, DURATION, CARDIOMYOPATHY, BRADYCARDIA, Population, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Internal medicine, Cardiac conduction, PR interval, education, Medicinsk genetik, business.industry, Cardiovascular genetics, General Chemistry, Arfgengi, medicine.disease, 030104 developmental biology, lcsh:Q, business
Abstract

Publisher's version (útgefin grein), The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease., We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.

Published
2020

95. Relation between albumin in the urine and electrocardiographic markers of myocardial ischemia in patients without diabetes mellitus.

Author

Diercks, Gilles F.H., Hillege, Hans L., Kors, Jan A., Diercks, G F, Hillege, H L, van Boven, A J, Kors, J A, Janssen, W M, Grobbee, D E, Crijns, H J, and van Gilst, W H

Subjects
*CORONARY disease, *ALBUMINS, *URINE, *DIABETES, *ALBUMINURIA, *CHI-squared test, *COMPARATIVE studies, *ELECTROCARDIOGRAPHY, *LONGITUDINAL method, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *LOGISTIC regression analysis, *EVALUATION research, *PREDICTIVE tests
Abstract

Studies the relationship electrocardiographic markers of myocardial ischemia and albumin in the urine of patients without diabetes mellitus. Key issues of interest; Analysis of pertinent topics and relevant issues; Implications on cardiology.

Published
2001
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96. Prolonged QT interval: a tricky diagnosis?

Author

de Bruyne MC, Hoes AW, Kors JA, Dekker JM, Hofman A, van Bemmel JH, Grobbee DE, de Bruyne, M C, Hoes, A W, Kors, J A, Dekker, J M, Hofman, A, van Bemmel, J H, and Grobbee, D E

Abstract

Prolonged heart-rate adjusted QT intervals on the electrocardiogram (ECG) are associated with an increased risk for coronary heart disease and sudden death. However, the diagnosis of the prolonged QT interval is hampered by lack of standards. We studied variations in the prevalence of prolonged QT, based on different common definitions, in a large nonhospitalized population, and compared our results with other studies applying the same definitions. The study population consisted of 2,200 men and 3,366 women participants of the Rotterdam Study, > or =55 years old. The QT interval was computed by our Modular ECG Analysis System (MEANS). Three different formulas to adjust QT for heart rate were used: Bazett's formula (QTc), a linear regression equation (QTlr), and the QT index (QTI). Prolonged QT occurred frequently in both men and women, and its prevalence increased with age. Women had longer heart-rate adjusted QT intervals than men (mean QTc 433 ms vs 422 ms), and mean values for QTlr were lower than for QTc (mean QTlr 422 ms in women and 412 ms in men). Prevalence was highest for prolonged QTlr (31% in men and 26% in women) and lowest for prolonged QTI (6% in men and 9% in women). Comparison with other studies applying the same correction formulas showed large discrepancies in prevalence estimates of prolonged QTc and QTlr, and to a lesser degree of prolonged QTI, possibly due to differences in measurement techniques. Future research is needed to relate QT interval to prognosis, to obtain measurement technique specific reference values of heart-rate adjusted QT measurements, and to obtain age- and sex-specific threshold values for prolonged QT. Such data are needed to use the QT interval with confidence. [ABSTRACT FROM AUTHOR]

Published
1997
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97. Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

Author

Yuki Bradford, Toshiko Tanaka, Jeffrey R. O'Connell, Florence Kyndt, Unnur Thorsteinsdottir, Ivana Kolcic, Xiaoyan Yin, Vincent Probst, Manolis Kellis, Christopher Newton-Cheh, Stefan Kääb, Argelia Medeiros-Domingo, Markus M. Nöthen, Paolo Gasparini, Jean-Jacques Schott, Ruth J. F. Loos, Thomas W. Mühleisen, Annukka Marjamaa, Morris Brown, Igor Rudan, Runjun D. Kumar, Peter J. Schwartz, Lars Lind, Martina Müller-Nurasyid, Xinchen Wang, Joshua C. Denny, Roberto Insolia, Soumya Raychaudhuri, Stephen W. Scherer, Bruno H. Stricker, Alexander Kluttig, Adamo Pio D'Adamo, Laurie A. Boyer, Moritz F. Sinner, Norbert Frey, Nour Eddine El Mokhtari, Thomas Meitinger, Jesper V. Olsen, Gerjan Navis, Steven R. Cummings, Richard W Morris, Nynke Hofman, Marcel den Hoed, Rudolf A. de Boer, Gonçalo R. Abecasis, Mark J. Daly, Dan M. Roden, Christian Gieger, Lyudmyla Kedenko, Marcus Dörr, Thomas P. Cappola, Afshin Parsa, Kari Stefansson, Markus Perola, Mark Eijgelsheim, Fredrik Nyberg, Robert M. Hamilton, Yalda Jamshidi, W. H. Linda Kao, Terho Lehtimäki, Annette Peters, David Schlessinger, Peter P. Pramstaller, James F. Wilson, Vilmundur Gudnason, Florian Kronenberg, Aroon D. Hingorani, Connie R. Bezzina, Abdennasser Bardai, Marylyn D. Ritchie, Andrew S. Plump, Johan Sundström, Daryl Waggott, Chrysoula Dalageorgou, Paul I.W. de Bakker, Uwe Völker, Aaron Isaacs, Oscar H. Franco, Yongmei Liu, Andrew N. Nicolaides, Lia Crotti, Cornelia M. van Duijn, Ben A. Oostra, Arne Pfeufer, Karl Werdan, Michael Morley, Jan A. Kors, Julien Barc, Lewin Eisele, Siegfried Perz, Stéphanie Chatel, Pieter A. van der Vleuten, Sara L. Pulit, Anna F. Dominiczak, Harry Campbell, Alice Ghidoni, Irene Mateo Leach, Nona Sotoodehnia, Nina Mononen, Henriette E. Meyer zu Schwabedissen, Alvaro Alonso, Fabiola Del Greco M, Dan E. Arking, Vera Adamkova, Mike A. Nalls, Valur Emilsson, Edward G. Lakatta, Kirill Tarasov, Alan F. Wright, Lenore J. Launer, Erik Ingelsson, Karin Halina Greiser, Ozren Polasek, Massimo Carella, Daniel F. Gudbjartsson, Bouwe P. Krijthe, Hanna Prucha, Per Hoffmann, Maura Griffin, Stefan Kiechl, Angel Carracedo, Ilja M. Nolte, Christine E. Moravec, Johann Willeit, Joshua C. Bis, Patricia B. Munroe, Marcello Ricardo Paulista Markus, Hailiang Huang, Mika Kähönen, Albert Hofman, Peter H. Whincup, Dirk J. van Veldhuisen, Michael Knoflach, Alicia Lundby, Serena Sanna, Hagen Kälsch, Bernhard Paulweber, Kamil Slowikowski, Luigi Ferrucci, Melanie Waldenberger, Marco Bobbo, Annukka M. Lahtinen, Ann-Christine Syvänen, J. Gustav Smith, Åsa Torinsson Naluai, Jaroslav A. Hubacek, Jeffrey Brandimarto, Wendy S. Post, Lude Franke, Mark J. Caulfield, Folkert W. Asselbergs, André G. Uitterlinden, Stefan Gustafsson, Pim van der Harst, David J. Tester, David S. Siscovick, David O. Arnar, Sarah H Wild, Elizabeth J. Rossin, Albert V. Smith, Bruce M. Psaty, Georg Ehret, Alan R. Shuldiner, Stephen Newhouse, Kimmo Kontula, Maria Brion, Andre Franke, Peter W. Macfarlane, Mika Kivimäki, Tamara B. Harris, Lasse Oikarinen, Tamara T. Koopmann, Kenneth B. Margulies, Aravinda Chakravarti, Gianfranco Sinagra, Maarten P. van den Berg, Veikko Salomaa, Karl-Heinz Jöckel, Daniel S. Evans, Caroline Hayward, Kimmo Porthan, Michael J. Ackerman, Jacqueline C.M. Witteman, Arthur A.M. Wilde, Martin G. Larson, Kasper Lage, Manuela Uda, Susan R. Heckbert, Joel S. Bader, Graham Watt, María Dolores Torres, Stephan B. Felix, Jerome I. Rotter, Pau Navarro, Meena Kumari, Johan Ärnlöv, Andrew D. Paterson, Antti Jula, Olli T. Raitakari, Raimund Erbel, Christopher J. O'Donnell, Britt M. Beckmann, Peter A. Noseworthy, Tim D. Spector, Wai K. Lee, Leopoldo Zelante, Nilesh J. Samani, John R. Giudicessi, Harold Snieder, Dag S. Thelle, David Ellinghaus, Eimo Martens, James B. Strait, Jorma S. A. Viikari, Andrew D. Johnson, Antonella Mulas, Hilma Holm, Johannes Haerting, Annamaria Iorio, Rebecca L. Zuvich, Sheila Ulivi, Andrew A. Hicks, Elijah R. Behr, Leo-Pekka Lyytikäinen, Bernhard Strohmer, Marco Orru, Claudia Lamina, Sandosh Padmanabhan, Christian Fuchsberger, Andrie G. Panayiotou, Ehret, Georg Benedikt, Internal Medicine, Public Health, Epidemiology, Rehabilitation Medicine, Medical Informatics, Clinical Genetics, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Ethical, Legal, Social Issues in Genetics (ELSI), Stem Cell Aging Leukemia and Lymphoma (SALL), Arking, D, Pulit, S, Crotti, L, van der Harst, P, Munroe, P, Koopmann, T, Sotoodehnia, N, Rossin, E, Morley, M, Wang, X, Johnson, A, Lundby, A, Gudbjartsson, D, Noseworthy, P, Eijgelsheim, M, Bradford, Y, Tarasov, K, Dörr, M, Müller-Nurasyid, M, Lahtinen, A, Nolte, I, Smith, A, Bis, J, Isaacs, A, Newhouse, S, Evans, D, Post, W, Waggott, D, Lyytikäinen, L, Hicks, A, Eisele, L, Ellinghaus, D, Hayward, C, Navarro, P, Ulivi, S, Tanaka, T, Tester, D, Chatel, S, Gustafsson, S, Kumari, M, Morris, R, Naluai, A, Padmanabhan, S, Kluttig, A, Strohmer, B, Panayiotou, A, Torres, M, Knoflach, M, Hubacek, J, Slowikowski, K, Raychaudhuri, S, Kumar, R, Harris, T, Launer, L, Shuldiner, A, Alonso, A, Bader, J, Ehret, G, Huang, H, Kao, W, Strait, J, Macfarlane, P, Brown, M, Caulfield, M, Samani, N, Kronenberg, F, Willeit, J, Smith, J, Greiser, K, Meyer Zu Schwabedissen, H, Werdan, K, Carella, M, Zelante, L, Heckbert, S, Psaty, B, Rotter, J, Kolcic, I, Polašek, O, Wright, A, Griffin, M, Daly, M, Arnar, D, Hólm, H, Thorsteinsdottir, U, Denny, J, Roden, D, Zuvich, R, Emilsson, V, Plump, A, Larson, M, O'Donnell, C, Yin, X, Bobbo, M, D'Adamo, A, Iorio, A, Sinagra, G, Carracedo, A, Cummings, S, Nalls, M, Jula, A, Kontula, K, Marjamaa, A, Oikarinen, L, Perola, M, Porthan, K, Erbel, R, Hoffmann, P, Jöckel, K, Kälsch, H, Nöthen, M, den Hoed, M, Loos, R, Thelle, D, Gieger, C, Meitinger, T, Perz, S, Peters, A, Prucha, H, Sinner, M, Waldenberger, M, de Boer, R, Franke, L, van der Vleuten, P, Beckmann, B, Martens, E, Bardai, A, Hofman, N, Wilde, A, Behr, E, Dalageorgou, C, Giudicessi, J, Medeiros-Domingo, A, Kyndt, F, Probst, V, Ghidoni, A, Insolia, R, Hamilton, R, Scherer, S, Brandimarto, J, Margulies, K, Moravec, C, Greco, M, Fuchsberger, C, O'Connell, J, Lee, W, Watt, G, Campbell, H, Wild, S, El Mokhtari, N, Frey, N, Asselbergs, F, Mateo Leach, I, Navis, G, van den Berg, M, van Veldhuisen, D, Kellis, M, Krijthe, B, Franco, O, Hofman, A, Kors, J, Uitterlinden, A, Witteman, J, Kedenko, L, Lamina, C, Oostra, B, Abecasis, G, Lakatta, E, Mulas, A, Orrú, M, Schlessinger, D, Uda, M, Markus, M, Völker, U, Snieder, H, Spector, T, Arnlöv, J, Lind, L, Sundström, J, Syvänen, A, Kivimaki, M, Kähönen, M, Mononen, N, Raitakari, O, Viikari, J, Adamkova, V, Kiechl, S, Brion, M, Nicolaides, A, Paulweber, B, Haerting, J, Dominiczak, A, Nyberg, F, Whincup, P, Hingorani, A, Schott, J, Bezzina, C, Ingelsson, E, Ferrucci, L, Gasparini, P, Wilson, J, Rudan, I, Franke, A, Mühleisen, T, Pramstaller, P, Lehtimäki, T, Paterson, A, Parsa, A, Liu, Y, van Duijn, C, Siscovick, D, Gudnason, V, Jamshidi, Y, Salomaa, V, Felix, S, Sanna, S, Ritchie, M, Stricker, B, Stefansson, K, Boyer, L, Cappola, T, Olsen, J, Lage, K, Schwartz, P, Kääb, S, Chakravarti, A, Ackerman, M, Pfeufer, A, de Bakker, P, Newton-Cheh, C, Arking, Dan E., Pulit, Sara L., Crotti, Lia, Van Der Harst, Pim, Munroe, Patricia B., Koopmann, Tamara T., Sotoodehnia, Nona, Rossin, Elizabeth J., Morley, Michael, Wang, Xinchen, Johnson, Andrew D., Lundby, Alicia, Gudbjartsson, Daníel F., Noseworthy, Peter A., Eijgelsheim, Mark, Bradford, Yuki, Tarasov, Kirill V., Dörr, Marcu, Müller Nurasyid, Martina, Lahtinen, Annukka M., Nolte, Ilja M., Smith, Albert Vernon, Bis, Joshua C., Isaacs, Aaron, Newhouse, Stephen J., Evans, Daniel S., Post, Wendy S., Waggott, Daryl, Lyytikäinen, Leo Pekka, Hicks, Andrew A., Eisele, Lewin, Ellinghaus, David, Hayward, Caroline, Navarro, Pau, Ulivi, Sheila, Tanaka, Toshiko, Tester, David J., Chatel, Stéphanie, Gustafsson, Stefan, Kumari, Meena, Morris, Richard W., Naluai, Asa T., Padmanabhan, Sandosh, Kluttig, Alexander, Strohmer, Bernhard, Panayiotou, Andrie G., Torres, Maria, Knoflach, Michael, Hubacek, Jaroslav A., Slowikowski, Kamil, Raychaudhuri, Soumya, Kumar, Runjun D., Harris, Tamara B., Launer, Lenore J., Shuldiner, Alan R., Alonso, Alvaro, Bader, Joel S., Ehret, Georg, Huang, Hailiang, Kao, W. H. Linda, Strait, James B., Macfarlane, Peter W., Brown, Morri, Caulfield, Mark J., Samani, Nilesh J., Kronenberg, Florian, Willeit, Johann, Smith, J. Gustav, Greiser, Karin H., Zu Schwabedissen, Henriette Meyer, Werdan, Karl, Carella, Massimo, Zelante, Leopoldo, Heckbert, Susan R., Psaty, Bruce M., Rotter, Jerome I., Kolcic, Ivana, Polašek, Ozren, Wright, Alan F., Griffin, Maura, Daly, Mark J., Arnar, David O., Hólm, Hilma, Thorsteinsdottir, Unnur, Denny, Joshua C., Roden, Dan M., Zuvich, Rebecca L., Emilsson, Valur, Plump, Andrew S., Larson, Martin G., O'Donnell, Christopher J., Yin, Xiaoyan, Bobbo, Marco, D'Adamo, ADAMO PIO, Iorio, Annamaria, Sinagra, Gianfranco, Carracedo, Angel, Cummings, Steven R., Nalls, Michael A., Jula, Antti, Kontula, Kimmo K., Marjamaa, Annukka, Oikarinen, Lasse, Perola, Marku, Porthan, Kimmo, Erbel, Raimund, Hoffmann, Per, Jöckel, Karl Heinz, Kälsch, Hagen, Nöthen, Markus M., Den Hoed, Marcel, Loos, Ruth J. F., Thelle, Dag S., Gieger, Christian, Meitinger, Thoma, Perz, Siegfried, Peters, Annette, Prucha, Hanna, Sinner, Moritz F., Waldenberger, Melanie, De Boer, Rudolf A., Franke, Lude, Van Der Vleuten, Pieter A., Beckmann, Britt Maria, Martens, Eimo, Bardai, Abdennasser, Hofman, Nynke, Wilde, Arthur A. M., Behr, Elijah R., Dalageorgou, Chrysoula, Giudicessi, John R., Medeiros Domingo, Argelia, Barc, Julien, Kyndt, Florence, Probst, Vincent, Ghidoni, Alice, Insolia, Roberto, Hamilton, Robert M., Scherer, Stephen W., Brandimarto, Jeffrey, Margulies, Kenneth, Moravec, Christine E., Del Greco M, Fabiola, Fuchsberger, Christian, O'Connell, Jeffrey R., Lee, Wai K., Watt, Graham C. M., Campbell, Harry, Wild, Sarah H., El Mokhtari, Nour E., Frey, Norbert, Asselbergs, Folkert W., Leach, Irene Mateo, Navis, Gerjan, Van Den Berg, Maarten P., Van Veldhuisen, Dirk J., Kellis, Manoli, Krijthe, Bouwe P., Franco, Oscar H., Hofman, Albert, Kors, Jan A., Uitterlinden, André G., Witteman, Jacqueline C. M., Kedenko, Lyudmyla, Lamina, Claudia, Oostra, Ben A., Abecasis, Gonçalo R., Lakatta, Edward G., Mulas, Antonella, Orrú, Marco, Schlessinger, David, Uda, Manuela, Markus, Marcello R. P., Völker, Uwe, Snieder, Harold, Spector, Timothy D., Ärnlöv, Johan, Lind, Lar, Sundström, Johan, Syvänen, Ann Christine, Kivimaki, Mika, Kähönen, Mika, Mononen, Nina, Raitakari, Olli T., Viikari, Jorma S., Adamkova, Vera, Kiechl, Stefan, Brion, Maria, Nicolaides, Andrew N., Paulweber, Bernhard, Haerting, Johanne, Dominiczak, Anna F., Nyberg, Fredrik, Whincup, Peter H., Hingorani, Aroon D., Schott, Jean Jacque, Bezzina, Connie R., Ingelsson, Erik, Ferrucci, Luigi, Gasparini, Paolo, Wilson, James F., Rudan, Igor, Franke, Andre, Mühleisen, Thomas W., Pramstaller, Peter P., Lehtimäki, Terho J., Paterson, Andrew D., Parsa, Afshin, Liu, Yongmei, Van Duijn, Cornelia M., Siscovick, David S., Gudnason, Vilmundur, Jamshidi, Yalda, Salomaa, Veikko, Felix, Stephan B., Sanna, Serena, Ritchie, Marylyn D., Stricker, Bruno H., Stefansson, Kari, Boyer, Laurie A., Cappola, Thomas P., Olsen, Jesper V., Lage, Kasper, Schwartz, Peter J., Kääb, Stefan, Chakravarti, Aravinda, Ackerman, Michael J., Pfeufer, Arne, De Bakker, Paul I. W., Newton Cheh, Christopher, Cardiology, ACS - Amsterdam Cardiovascular Sciences, and Human Genetics

Subjects
Male, Candidate gene, Myocardium/metabolism, LOCI, Medizin, Heart electrophysiology, Genome-wide association study, Arrhythmias, Bioinformatics, Medical and Health Sciences, Heart Ventricle, Sudden cardiac death, Electrocardiography, PR INTERVAL, Arrhythmias, Cardiac/genetics, Death, Sudden, Cardiac/etiology, Genetics, ddc:616, Cardiac electrophysiology, Adult, Aged, Arrhythmias, Cardiac, Calcium Signaling, Death, Sudden, Cardiac, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Heart Ventricles, Humans, Long QT Syndrome, Middle Aged, Myocardium, Polymorphism, Single Nucleotide, COMMON VARIANTS, Heart Ventricles/metabolism, Single Nucleotide, Long QT Syndrome/genetics, CHRONIC HEART-FAILURE, Death, Heart ventricle arrhythmia, genetic association study, gene, SNP, heart, Genome-Wide Association Study/methods, Long QT syndrome, QRS DURATION, Cardiac, Cardiac/etiology, Human, QT interval, congenital, hereditary, and neonatal diseases and abnormalities, Electrocardiography/methods, TRPM7, BIO/18 - GENETICA, Cardiac/genetics, Biology, Article, sudden cardiac death, QRS complex, CARDIAC REPOLARIZATION, medicine, Repolarization, cardiovascular diseases, GENOME-WIDE ASSOCIATION, Polymorphism, MED/01 - STATISTICA MEDICA, calcium, ta1184, Calcium signaling, Calcium Signaling/genetics, MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE, ta3121, Cardiovascular risk, medicine.disease, SARCOPLASMIC-RETICULUM, Sudden, MODEL, Genetic association, myocardial repolarization, Genetic variability, Gene expression, Clinical Medicine, genetic, Controlled study
Abstract

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Published
2014

98. Drug-Induced Acute Myocardial Infarction: Identifying ‘Prime Suspects’ from Electronic Healthcare Records-Based Surveillance System

Author

Giampiero Mazzaglia, Miriam C. J. M. Sturkenboom, Johan van der Lei, Lorenza Scotti, Scott Boyer, Justin Matthews, José Luís Oliveira, Anna Bauer-Mehren, Jan A. Kors, Rosa Gini, Gino Picelli, Laura I. Furlong, Gianluca Trifirò, Preciosa M. Coloma, Martijn J. Schuemie, Jordi Mestres, Paul Avillach, David Prieto-Merino, Mariam Molokhia, Lars Pedersen, Erik M. van Mulligen, Ron M. C. Herings, Ferran Sanz, Ernst Ahlberg Helgee, Coloma, P, Schuemie, M, Trifirò, G, Furlong, L, van Mulligen, E, Bauer Mehren, A, Avillach, P, Kors, J, Sanz, F, Mestres, J, Oliveira, J, Boyer, S, Helgee, E, Molokhia, M, Matthews, J, Prieto Merino, D, Gini, R, Herings, R, Mazzaglia, G, Picelli, G, Scotti, L, Pedersen, L, van der Lei, J, Sturkenboom, M, Medical Informatics, Neurology, Epidemiology and Data Science, and Clinical pharmacology and pharmacy

Subjects
Non-Clinical Medicine, Epidemiology, Myocardial Infarction, lcsh:Medicine, 030204 cardiovascular system & hematology, Pharmacology, Azithromycin, Cardiovascular, Betamethasone, Disease Informatics, 0302 clinical medicine, Engineering, Health care, Medicine, Data Mining, Electronic Health Records, Clinical Epidemiology, 030212 general & internal medicine, lcsh:Science, Fluconazole, Epidemiological Methods, education.field_of_study, Cisapride, Multidisciplinary, Medical record, Medicine (all), Megestrol Acetate, Clinical Pharmacology, Drug Information, Drug Marketing, 3. Good health, Medicaments -- Efectes secundaris, Acute Disease, Electronic Health Record, Biological plausibility, Human, Research Article, medicine.medical_specialty, Drugs and Devices, Drug Research and Development, Metoclopramide, Population, Health Informatics, Cardiovascular Pharmacology, 03 medical and health sciences, Pharmacotherapy, SDG 3 - Good Health and Well-being, Adverse Reactions, Pharmacovigilance, Adverse Drug Reaction Reporting Systems, Humans, Medical prescription, Intensive care medicine, education, MED/01 - STATISTICA MEDICA, Cardiovascular Disease Epidemiology, Biochemistry, Genetics and Molecular Biology (all), Health Care Policy, business.industry, Pharmacoepidemiology, lcsh:R, Health Risk Analysis, Triage, Domperidone, Drug Licensing and Regulation, Agricultural and Biological Sciences (all), Pharmacodynamics, Signal Processing, lcsh:Q, Adverse Drug Reaction Reporting System, business
Abstract

Background: Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in ‘real-world’ settings. Objective: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Methods: Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996–2010. Primary care physicians’ medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Results: Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs (‘prime suspects’): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Limitations: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. Conclusion: A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association, but also public health relevance, novelty, and biological plausibility. Although this strategy needs to be further evaluated using other healthcare data sources, the list of ‘prime suspects’ makes a good starting point for further clinical, laboratory, and epidemiologic investigation. This research has been funded by the European Commission’s Seventh Framework Programme (FP7/2007–2013) under grant no. 215847–The EU-ADR Project.

Published
2013

99. Psychotropic Drugs Associated With Corrected QT Interval Prolongation

Author

Miriam C. J. M. Sturkenboom, Christopher Newton-Cheh, Sabine M. J. M. Straus, Albert Jan L H J Aarnoudse, Albert Hofman, Vincenzo Bagnardi, Charlotte van Noord, Bruno H. Stricker, Jacqueline C.M. Witteman, Jan A. Kors, Epidemiology, Medical Informatics, van Noord, C, Straus, S, Sturkenboom, M, Hofman, A, Aarnoudse, A, Bagnardi, V, Kors, J, Newton Cheh, C, Witteman, J, and Stricker, B

Subjects
Male, medicine.medical_specialty, Long QT syndrome, Population, QTc interval, Antidepressive Agents, Tricyclic, Pharmacology, arrhythmia, QT interval, Cohort Studies, Electrocardiography, SDG 3 - Good Health and Well-being, Internal medicine, Humans, Medicine, Pharmacology (medical), Prospective Studies, cardiovascular diseases, education, Prospective cohort study, Maprotiline, MED/01 - STATISTICA MEDICA, Aged, Aged, 80 and over, Psychotropic Drugs, education.field_of_study, business.industry, Middle Aged, medicine.disease, Confidence interval, Long QT Syndrome, Psychiatry and Mental health, Cardiology, cardiovascular system, Female, Nortriptyline, business, psychotropic drug, medicine.drug, Cohort study
Abstract

AIMS: To study whether listed putative corrected QT (QTc)-prolonging psychotropic drugs indeed prolong the QTc interval under everyday circumstances and to evaluate whether this is a class effect or an individual drug effect, we conducted a prospective population-based cohort study. METHODS: This study was conducted as part of the Rotterdam Study and included 3377 men and 4845 women (>or=55 years) who had triennial electrocardiograms (ECGs). The primary end points of the study were the length of the QTc interval at each ECG, the difference in QTc interval between consecutive ECGs within one person, and the risk of an abnormally prolonged QTc interval. Drug use at the index date was obtained from automated dispensing records. The associations were examined by means of a repeated measurement analysis, adjusted for age, sex, diabetes mellitus, hypertension, myocardial infarction, heart failure, and use of class 1 QTc-prolonging drugs. RESULTS: Of the 8222 participants, 813 participants (9.9%) developed QTc prolongation during follow-up and 492 participants (74.4% women) used psychotropic drugs at the time of an ECG. Starting tricyclic antidepressants increased the QTc interval significantly with 6.9 milliseconds (95% confidence interval [CI], 3.1-10.7 milliseconds) between consecutive ECGs in comparison with consecutive ECGs of participants not using tricyclic antidepressants, in particular starting amitriptyline (8.5 milliseconds; 95% CI, 2.8-14.2 milliseconds), maprotiline (13.9 milliseconds; 95% CI, 3.6-24.3 milliseconds), and nortriptyline (35.3 milliseconds; 95% CI, 8.0-62.6 milliseconds). Starting lithium also increased the QTc interval significantly (18.6 milliseconds; 95% CI, 4.8-32.4 milliseconds). CONCLUSIONS: In this population-based prospective cohort study, we confirmed the importance of antidepressants and antipsychotics as potential contributors to QTc prolongation. Especially, starting tricyclic antidepressant drugs (as a class) is associated with a significant intraindividual increase in the QTc interval in comparison to the change in nonusers. The tricyclic antidepressants seem to prolong the QTc interval as a class effect.

Published
2009

100. Feasibility and findings of electrocardiogram recording in older adults with intellectual disabilities: results of the Healthy Ageing and Intellectual Disabilities study.

Author

de Leeuw MJ, Böhmer MN, Leening MJG, Kors JA, Bindels PJE, Oppewal A, and Maes-Festen DAM

Abstract

Background: Older adults with intellectual disabilities (ID) have a high risk of cardiovascular diseases (CVD). At the same time, challenging diagnostic work-up increases the likelihood of underdiagnosis of CVD in this population. To limit this underdiagnosis, it would be beneficial to use objective measures such as the electrocardiogram (ECG). However, little is known about the feasibility of ECG recording and the prevalence of ECG abnormalities in this population. Therefore, the aims of this study were to investigate the feasibility of resting ECG recording, to study the prevalence of ECG abnormalities, and to compare the frequency of ECG abnormalities with medical records in older adults with ID., Method: A cross-sectional study was performed within a cohort of older adults (≥60 years) with ID as part of the Healthy Ageing and Intellectual Disabilities (HA-ID) study. A resting 12-lead ECG was attempted, and the ECG recording was considered feasible if the recording could be made and if the ECG could be interpreted by a cardiologist and the Modular ECG Analysis System (MEANS). ECGs were assessed for the presence of ECG abnormalities and medical record review was performed. If the cardiologist or MEANS concluded that there was evidence of myocardial infarction, atrial fibrillation or QTc prolongation on the ECG in the absence of this ECG diagnosis in the participant's medical record, this was classified as a previously undiagnosed ECG diagnosis., Results: ECG recording was feasible in 134 of the 200 participants (67.0%). Of these 134 participants (70.6 ± 5.8 years; 52.2% female), 103 (76.9%) had one or more ECG abnormality, with the most prevalent being prolonged P-wave duration (27.6%), QTc prolongation (18.7%), minor T-wave abnormalities (17.9%), first degree atrioventricular block (12.7%) and myocardial infarction (6.7%). Eight out of 9 (88.9%) myocardial infarctions and all cases of (significant) QTc prolongation (100%) were previously undiagnosed., Conclusions: This study showed that ECG recording is feasible in the majority of older adults with ID and revealed a substantial underdiagnosis of ECG abnormalities. These results stress the importance of ECG recording and warrant further research into the yield of opportunistic ECG screening in older adults with ID., (© 2024 The Author(s). Journal of Intellectual Disability Research published by John Wiley & Sons and MENCAP.)

Published
2024
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