Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study

Abstract Background Type 2 diabetes is a stronger risk factor for cardiovascular disease (CVD) in women compared with men possibly due to higher susceptibility to develop myocardial microvascular dysfunction. We investigated sex-dependent effects of risk factors on myocardial blood flow (MBF) and my...

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Main Authors: Anne-Cathrine Skriver-Møller, Philip Hasbak, Ida K. B. Rasmussen, Martin B. Blond, Victor S. Wasehuus, Mats C. H. Lassen, Morten Lindhardt, Allan Kofoed-Enevoldsen, Urd L. Kielgast, Emilie H. Zobel, Jens P. Goetze, Lene Holmvang, Tor Biering-Sørensen, Peter Rossing, Andreas Kjaer, Rasmus S. Ripa, Tine W. Hansen
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Cardiovascular Diabetology
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Online Access:https://doi.org/10.1186/s12933-025-02717-5
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author Anne-Cathrine Skriver-Møller
Philip Hasbak
Ida K. B. Rasmussen
Martin B. Blond
Victor S. Wasehuus
Mats C. H. Lassen
Morten Lindhardt
Allan Kofoed-Enevoldsen
Urd L. Kielgast
Emilie H. Zobel
Jens P. Goetze
Lene Holmvang
Tor Biering-Sørensen
Peter Rossing
Andreas Kjaer
Rasmus S. Ripa
Tine W. Hansen
author_facet Anne-Cathrine Skriver-Møller
Philip Hasbak
Ida K. B. Rasmussen
Martin B. Blond
Victor S. Wasehuus
Mats C. H. Lassen
Morten Lindhardt
Allan Kofoed-Enevoldsen
Urd L. Kielgast
Emilie H. Zobel
Jens P. Goetze
Lene Holmvang
Tor Biering-Sørensen
Peter Rossing
Andreas Kjaer
Rasmus S. Ripa
Tine W. Hansen
author_sort Anne-Cathrine Skriver-Møller
collection DOAJ
description Abstract Background Type 2 diabetes is a stronger risk factor for cardiovascular disease (CVD) in women compared with men possibly due to higher susceptibility to develop myocardial microvascular dysfunction. We investigated sex-dependent effects of risk factors on myocardial blood flow (MBF) and myocardial flow reserve (MFR) in individuals with type 2 diabetes without overt CVD. Methods Cross-sectional analysis of a prospective study including 901 individuals recruited between 2020 and 2023. All participants underwent a cardiac 82-Rubidium positron emission tomography/computed tomography scan to quantify MBF at rest and during pharmacologically induced stress, allowing for calculation of MFR. Linear regression, with/without interaction terms for sex, was used to test whether sex modified the association between MFR/MBF and risk factors. Results Mean (SD) age was 65 (8.9) years, diabetes duration was 14 (8.4) years, and 266 (29.5%) were women. Women had higher MBF at rest and stress but had lower MFR (mean (SD) 2.44 (0.67) vs. 2.59 (0.77), p = 0.003) than men. A similar proportion of men and women (21.1% vs. 23.7%) had an MFR < 2. The decline in predicted MFR with age differed between sexes. At age 55, women had a mean MFR that was 0.29 lower than men (95% CI: − 0.44 to − 0.14), but by age 75, this difference had nearly disappeared (− 0.04, 95% CI: − 0.19 to 0.11). However, after adjustment for other risk factors, the interaction between sex and age was not statistically significant (p = 0.057). No other risk factors exhibited significant sex-dependent interactions. Conclusions In individuals with type 2 diabetes without overt CVD, women exhibited lower MFR than men, primarily due to higher MBF at rest, suggesting sex-related differences. While MFR declined in both sexes, the sex difference was more pronounced in younger individuals and diminished over time. These findings underscore the need for further research into sex-specific thresholds for MFR in cardiovascular risk stratification. Graphical abstract
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spelling doaj-art-41b7855aba0046d399d8979a1bf4248e2025-08-20T02:24:26ZengBMCCardiovascular Diabetology1475-28402025-04-0124111410.1186/s12933-025-02717-5Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart studyAnne-Cathrine Skriver-Møller0Philip Hasbak1Ida K. B. Rasmussen2Martin B. Blond3Victor S. Wasehuus4Mats C. H. Lassen5Morten Lindhardt6Allan Kofoed-Enevoldsen7Urd L. Kielgast8Emilie H. Zobel9Jens P. Goetze10Lene Holmvang11Tor Biering-Sørensen12Peter Rossing13Andreas Kjaer14Rasmus S. Ripa15Tine W. Hansen16Steno Diabetes Center CopenhagenDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - RigshospitaletSteno Diabetes Center CopenhagenSteno Diabetes Center CopenhagenSteno Diabetes Center CopenhagenDepartment of Cardiology, Herlev and Gentofte HospitalDepartment of Internal Medicine, Holbæk HospitalDepartment of Medicine, Zealand University HospitalDepartment of Medicine, Zealand University HospitalSteno Diabetes Center CopenhagenDepartment of Clinical Biochemistry, University of Copenhagen, RigshospitaletDepartment of Cardiology, RigshospitaletSteno Diabetes Center CopenhagenSteno Diabetes Center CopenhagenDepartment of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital - RigshospitaletDepartment of Clinical Medicine, University of CopenhagenSteno Diabetes Center CopenhagenAbstract Background Type 2 diabetes is a stronger risk factor for cardiovascular disease (CVD) in women compared with men possibly due to higher susceptibility to develop myocardial microvascular dysfunction. We investigated sex-dependent effects of risk factors on myocardial blood flow (MBF) and myocardial flow reserve (MFR) in individuals with type 2 diabetes without overt CVD. Methods Cross-sectional analysis of a prospective study including 901 individuals recruited between 2020 and 2023. All participants underwent a cardiac 82-Rubidium positron emission tomography/computed tomography scan to quantify MBF at rest and during pharmacologically induced stress, allowing for calculation of MFR. Linear regression, with/without interaction terms for sex, was used to test whether sex modified the association between MFR/MBF and risk factors. Results Mean (SD) age was 65 (8.9) years, diabetes duration was 14 (8.4) years, and 266 (29.5%) were women. Women had higher MBF at rest and stress but had lower MFR (mean (SD) 2.44 (0.67) vs. 2.59 (0.77), p = 0.003) than men. A similar proportion of men and women (21.1% vs. 23.7%) had an MFR < 2. The decline in predicted MFR with age differed between sexes. At age 55, women had a mean MFR that was 0.29 lower than men (95% CI: − 0.44 to − 0.14), but by age 75, this difference had nearly disappeared (− 0.04, 95% CI: − 0.19 to 0.11). However, after adjustment for other risk factors, the interaction between sex and age was not statistically significant (p = 0.057). No other risk factors exhibited significant sex-dependent interactions. Conclusions In individuals with type 2 diabetes without overt CVD, women exhibited lower MFR than men, primarily due to higher MBF at rest, suggesting sex-related differences. While MFR declined in both sexes, the sex difference was more pronounced in younger individuals and diminished over time. These findings underscore the need for further research into sex-specific thresholds for MFR in cardiovascular risk stratification. Graphical abstracthttps://doi.org/10.1186/s12933-025-02717-5Sex-differencesType 2 diabetesMicrovascular complicationsCardiovascular imaging
spellingShingle Anne-Cathrine Skriver-Møller
Philip Hasbak
Ida K. B. Rasmussen
Martin B. Blond
Victor S. Wasehuus
Mats C. H. Lassen
Morten Lindhardt
Allan Kofoed-Enevoldsen
Urd L. Kielgast
Emilie H. Zobel
Jens P. Goetze
Lene Holmvang
Tor Biering-Sørensen
Peter Rossing
Andreas Kjaer
Rasmus S. Ripa
Tine W. Hansen
Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study
Cardiovascular Diabetology
Sex-differences
Type 2 diabetes
Microvascular complications
Cardiovascular imaging
title Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study
title_full Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study
title_fullStr Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study
title_full_unstemmed Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study
title_short Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study
title_sort sex differences in myocardial flow reserve among individuals with type 2 diabetes insights from the diaheart study
topic Sex-differences
Type 2 diabetes
Microvascular complications
Cardiovascular imaging
url https://doi.org/10.1186/s12933-025-02717-5
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