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A five-year risk prediction model of cardiovascular disease in individuals with bipolar disorder: a nationwide register study from Sweden

A five-year risk prediction model of cardiovascular disease in individuals with bipolar disorder: a nationwide register study from Sweden
A five-year risk prediction model of cardiovascular disease in individuals with bipolar disorder: a nationwide register study from Sweden

Cardiovascular disease (CVD) risk prediction models for the general population may not provide accurate predictions in individuals with bipolar disorder (BD) who have elevated risks of cardiometabolic conditions and premature mortality. Therefore, we aimed to: 1) develop a five-year CVD risk prediction model in this population by using nationwide register data from Sweden, 2) investigate whether the performance improved when we considered additional risk factors, including psychiatric comorbidity, psychotropic medication, and socio-demographic variables, compared to using established CVD risk factors only, and 3) whether machine learning approach provided improvements compared to standard logistic regression models. We followed 33,933 persons with BD aged 30-82 years old, without previous CVD, from the date of BD diagnosis registered between 2007-2014, for up to five years. The logistic regression model containing only established risk factors yielded an area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval 0.74-0.78) in the test dataset, while the logistic regression model and the best performing machine learning model including additional predictors yielded similar results (AUC was 0.77 (0.75, 0.79) in both models). The performance of logistic regression models slightly improved with additional predictors when continuous risk scores were used. In conclusion, standard logistic regression and established CVD risk factors may be sufficient to predict CVD in individuals with BD when using population register-based data from Sweden. External validation across diverse healthcare settings and rigorous assessment of clinical impact will be crucial next steps before implementing these models in clinical practice.

1359-4184
Dobrosavljevic, Maja
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Landén, Mikael
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Brikell, Isabell
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Chang, Zheng
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Kuja-Halkola, Ralf
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Lichtenstein, Paul
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Andell, Pontus
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Andreassen, Ole A
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Bauer, Michael
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Corcoy, Rosa
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de Girolamo, Giovanni
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Reif, Andreas
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Larsson, Henrik
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Garcia-Argibay, Miguel
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Dobrosavljevic, Maja
bb6ac6f9-9431-45c4-a705-1b9ae5ac40a2
Landén, Mikael
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Brikell, Isabell
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Chang, Zheng
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Kuja-Halkola, Ralf
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Lichtenstein, Paul
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Andell, Pontus
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Andreassen, Ole A
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Bauer, Michael
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Corcoy, Rosa
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de Girolamo, Giovanni
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Reif, Andreas
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Larsson, Henrik
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Garcia-Argibay, Miguel
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Dobrosavljevic, Maja, Landén, Mikael, Brikell, Isabell, Chang, Zheng, Kuja-Halkola, Ralf, Lichtenstein, Paul, Andell, Pontus, Andreassen, Ole A, Bauer, Michael, Corcoy, Rosa, de Girolamo, Giovanni, Reif, Andreas, Larsson, Henrik and Garcia-Argibay, Miguel (2025) A five-year risk prediction model of cardiovascular disease in individuals with bipolar disorder: a nationwide register study from Sweden. Molecular Psychiatry. (doi:10.1038/s41380-025-03381-7).

Record type: Article

Abstract

Cardiovascular disease (CVD) risk prediction models for the general population may not provide accurate predictions in individuals with bipolar disorder (BD) who have elevated risks of cardiometabolic conditions and premature mortality. Therefore, we aimed to: 1) develop a five-year CVD risk prediction model in this population by using nationwide register data from Sweden, 2) investigate whether the performance improved when we considered additional risk factors, including psychiatric comorbidity, psychotropic medication, and socio-demographic variables, compared to using established CVD risk factors only, and 3) whether machine learning approach provided improvements compared to standard logistic regression models. We followed 33,933 persons with BD aged 30-82 years old, without previous CVD, from the date of BD diagnosis registered between 2007-2014, for up to five years. The logistic regression model containing only established risk factors yielded an area under the receiver operating characteristic curve (AUC) of 0.76 (95% confidence interval 0.74-0.78) in the test dataset, while the logistic regression model and the best performing machine learning model including additional predictors yielded similar results (AUC was 0.77 (0.75, 0.79) in both models). The performance of logistic regression models slightly improved with additional predictors when continuous risk scores were used. In conclusion, standard logistic regression and established CVD risk factors may be sufficient to predict CVD in individuals with BD when using population register-based data from Sweden. External validation across diverse healthcare settings and rigorous assessment of clinical impact will be crucial next steps before implementing these models in clinical practice.

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e-pub ahead of print date: 19 December 2025

Identifiers

Local EPrints ID: 508799
URI: http://eprints.soton.ac.uk/id/eprint/508799
ISSN: 1359-4184
PURE UUID: 75480704-2f93-4923-a896-02d8a7521309
ORCID for Miguel Garcia-Argibay: ORCID iD orcid.org/0000-0002-4811-2330

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Date deposited: 03 Feb 2026 17:57
Last modified: 04 Feb 2026 03:11

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Contributors

Author: Maja Dobrosavljevic
Author: Mikael Landén
Author: Isabell Brikell
Author: Zheng Chang
Author: Ralf Kuja-Halkola
Author: Paul Lichtenstein
Author: Pontus Andell
Author: Ole A Andreassen
Author: Michael Bauer
Author: Rosa Corcoy
Author: Giovanni de Girolamo
Author: Andreas Reif
Author: Henrik Larsson
Author: Miguel Garcia-Argibay ORCID iD

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