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

Anne-Cathrine Skriver-Møller; Philip Hasbak; Ida K B Rasmussen; Martin B Blond; Victor S Wasehuus; Mats Christian Højbjerg 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

doi:10.1186/s12933-025-02717-5

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

Anne-Cathrine Skriver-Møller
, Philip Hasbak
, Ida K B Rasmussen
, Martin B Blond
, Victor S Wasehuus
, Mats Christian Højbjerg 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

Research output: Contribution to journal › Article › Research › peer-review

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.

Original language	English
Article number	172
Number of pages	14
Journal	Cardiovascular Diabetology
Volume	24
Issue number	1
DOIs	https://doi.org/10.1186/s12933-025-02717-5
Publication status	Published - 18 Apr 2025

Funding

Funders
University of Copenhagen
Sjællands Universitetshospital

Keywords

Humans
Female
Male
Diabetes Mellitus, Type 2/diagnosis
Middle Aged
Cross-Sectional Studies
Sex Factors
Aged
Prospective Studies
Risk Assessment
Health Status Disparities
Fractional Flow Reserve, Myocardial
Positron Emission Tomography Computed Tomography
Myocardial Perfusion Imaging
Risk Factors
Heart Disease Risk Factors
Coronary Circulation
Type 2 diabetes
Cardiovascular imaging
Microvascular complications
Sex-differences

Access to Document

10.1186/s12933-025-02717-5

Cite this

Skriver-Møller, A.-C., Hasbak, P., Rasmussen, I. K. B., Blond, M. B., Wasehuus, V. S., Lassen, M. C. H., Lindhardt, M., Kofoed-Enevoldsen, A., Kielgast, U. L., Zobel, E. H., Goetze, J. P., Holmvang, L., Biering-Sørensen, T., Rossing, P., Kjaer, A., Ripa, R. S., & Hansen, T. W. (2025). Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study. Cardiovascular Diabetology, 24(1), Article 172. https://doi.org/10.1186/s12933-025-02717-5

@article{c678fbfdf19144809ec1c3827a02e99c,

title = "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 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.",

keywords = "Humans, Female, Male, Diabetes Mellitus, Type 2/diagnosis, Middle Aged, Cross-Sectional Studies, Sex Factors, Aged, Prospective Studies, Risk Assessment, Health Status Disparities, Fractional Flow Reserve, Myocardial, Positron Emission Tomography Computed Tomography, Myocardial Perfusion Imaging, Risk Factors, Heart Disease Risk Factors, Coronary Circulation, Type 2 diabetes, Cardiovascular imaging, Microvascular complications, Sex-differences",

author = "Anne-Cathrine Skriver-M{\o}ller and Philip Hasbak and Rasmussen, \{Ida K B\} and Blond, \{Martin B\} and Wasehuus, \{Victor S\} and Lassen, \{Mats Christian H{\o}jbjerg\} and Morten Lindhardt and Allan Kofoed-Enevoldsen and Kielgast, \{Urd L\} and Zobel, \{Emilie H\} and Goetze, \{Jens P\} and Lene Holmvang and Tor Biering-S{\o}rensen and Peter Rossing and Andreas Kjaer and Ripa, \{Rasmus S\} and Hansen, \{Tine W.\}",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = apr,

day = "18",

doi = "10.1186/s12933-025-02717-5",

language = "English",

volume = "24",

journal = "Cardiovascular Diabetology",

issn = "1475-2840",

publisher = "BioMed Central Ltd.",

number = "1",

}

Skriver-Møller, A-C, Hasbak, P, Rasmussen, IKB, Blond, MB, Wasehuus, VS, Lassen, MCH, Lindhardt, M , Kofoed-Enevoldsen, A , Kielgast, UL, Zobel, EH, Goetze, JP, Holmvang, L, Biering-Sørensen, T, Rossing, P, Kjaer, A, Ripa, RS & Hansen, TW 2025, 'Sex differences in myocardial flow reserve among individuals with type 2 diabetes: insights from the DiaHeart study', Cardiovascular Diabetology, vol. 24, no. 1, 172. https://doi.org/10.1186/s12933-025-02717-5

TY - JOUR

T1 - Sex differences in myocardial flow reserve among individuals with type 2 diabetes

T2 - insights from the DiaHeart study

AU - Skriver-Møller, Anne-Cathrine

AU - Hasbak, Philip

AU - Rasmussen, Ida K B

AU - Blond, Martin B

AU - Wasehuus, Victor S

AU - Lassen, Mats Christian Højbjerg

AU - Lindhardt, Morten

AU - Kofoed-Enevoldsen, Allan

AU - Kielgast, Urd L

AU - Zobel, Emilie H

AU - Goetze, Jens P

AU - Holmvang, Lene

AU - Biering-Sørensen, Tor

AU - Rossing, Peter

AU - Kjaer, Andreas

AU - Ripa, Rasmus S

AU - Hansen, Tine W.

PY - 2025/4/18

Y1 - 2025/4/18

N2 - 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.

AB - 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.

KW - Humans

KW - Female

KW - Male

KW - Diabetes Mellitus, Type 2/diagnosis

KW - Middle Aged

KW - Cross-Sectional Studies

KW - Sex Factors

KW - Aged

KW - Prospective Studies

KW - Risk Assessment

KW - Health Status Disparities

KW - Fractional Flow Reserve, Myocardial

KW - Positron Emission Tomography Computed Tomography

KW - Myocardial Perfusion Imaging

KW - Risk Factors

KW - Heart Disease Risk Factors

KW - Coronary Circulation

KW - Type 2 diabetes

KW - Cardiovascular imaging

KW - Microvascular complications

KW - Sex-differences

U2 - 10.1186/s12933-025-02717-5

DO - 10.1186/s12933-025-02717-5

M3 - Article

C2 - 40251660

SN - 1475-2840

VL - 24

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

IS - 1

M1 - 172

ER -

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

Abstract

Funding

Keywords

Access to Document

Fingerprint

Cite this