Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study
Abstract Background Systemic microvascular dysfunction is proposed as a key pathophysiological process in heart failure with preserved ejection fraction (HFpEF). This study compared microvasculature across vascular beds in HFpEF patients and controls. Methods This prospective, case-control study inc...
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2025-07-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02850-1 |
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| author | Jerremy Weerts Blanche L. M. Schroen Arantxa Barandiarán Aizpurua Tos T. J. M. Berendschot Lloyd Brandts Carroll A. B. Webers Sami O. Simons Steven J. R. Meex Ronald Henry Carla J. H. van der Kallen Hans-Peter Brunner-La Rocca Christian Knackstedt Stephane R. B. Heymans Rudolf A. de Boer Vanessa P. M. van Empel Alfons J. H. M. Houben |
| author_facet | Jerremy Weerts Blanche L. M. Schroen Arantxa Barandiarán Aizpurua Tos T. J. M. Berendschot Lloyd Brandts Carroll A. B. Webers Sami O. Simons Steven J. R. Meex Ronald Henry Carla J. H. van der Kallen Hans-Peter Brunner-La Rocca Christian Knackstedt Stephane R. B. Heymans Rudolf A. de Boer Vanessa P. M. van Empel Alfons J. H. M. Houben |
| author_sort | Jerremy Weerts |
| collection | DOAJ |
| description | Abstract Background Systemic microvascular dysfunction is proposed as a key pathophysiological process in heart failure with preserved ejection fraction (HFpEF). This study compared microvasculature across vascular beds in HFpEF patients and controls. Methods This prospective, case-control study included subjects ≥ 60years. HFpEF patients were diagnosed in an expert centre. Controls without HF were selected from the Maastricht Study, a population cohort enriched with diabetes mellitus. Microvascular assessments included central retinal venular/arteriolar calibres (CRVE/CRAE), flicker-light-induced retinal dilation, skin microvascular flowmotion and heat-induced hyperemia, and urinary albumin-to-creatinine ratio (UACR). Group differences were evaluated with confounder-adjustments (age, sex, blood pressure, body mass index, diabetes, haemoglobin, smoking). Interactions with sex and diabetes mellitus were tested, and stratified analyses were performed when significant interactions were present. Results Microvascular assessments were performed in 138 HFpEF patients and 2140 controls. Microvascular differences were present between groups in all vascular beds. However, confounder-adjusted analyses attenuated differences. Confounder-adjusted analyses indicated that HFpEF patients versus controls still had retinal differences: narrower CRVE (− 8.1 μm, p = 0.008) and narrower CRAE trend (− 3.5 μm, p = 0.073), but similar flicker-light-induced retinal venular/arteriolar dilation (− 0.23%, p = 0.392; − 0.18%, p = 0.593, respectively). Confounder-adjusted analyses showed similar skin flowmotion measures (i.e. endothelial power − 0.09log(PU2), p = 0.181), and heat-induced hyperemia (0.02log(%), p = 0.605) between groups. UACR remained higher in HFpEF after confounder adjustments (0.56log(g/mol), p = < 0.001). Interaction analyses revealed that female patients had narrower CRVE versus controls (pint=0.023; females − 13.8 μm, p < 0.001; males 1.2 μm, p = 0.812). Patients had lower skin endothelial flowmotion power only when diabetes was co-occurring (pint=0.048; − 0.36 log(PU2 ), p = 0.014). UACR was higher in male and female patients versus controls, but was more pronounced in males (pint=0.002). Conclusions HFpEF patients showed microvascular differences versus controls across all vascular beds studied. However, confounder-adjusted differences remained significant in eyes and kidneys. The findings across multiple organs support that MVD is likely a more systemic process than only local MVD in HFpEF, and possible sex-specific underlying pathophysiology. Registration URL: https://onderzoekmetmensen.nl ; Unique identifier: NL7655. Graphical abstract Figure created in BioRender (i88u523). |
| format | Article |
| id | doaj-art-63c87542403e42f1ac984fa134d133be |
| institution | Kabale University |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-63c87542403e42f1ac984fa134d133be2025-08-20T03:42:29ZengBMCCardiovascular Diabetology1475-28402025-07-0124111410.1186/s12933-025-02850-1Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control studyJerremy Weerts0Blanche L. M. Schroen1Arantxa Barandiarán Aizpurua2Tos T. J. M. Berendschot3Lloyd Brandts4Carroll A. B. Webers5Sami O. Simons6Steven J. R. Meex7Ronald Henry8Carla J. H. van der Kallen9Hans-Peter Brunner-La Rocca10Christian Knackstedt11Stephane R. B. Heymans12Rudolf A. de Boer13Vanessa P. M. van Empel14Alfons J. H. M. Houben15Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)University Eye Clinic Maastricht, Maastricht University Medical Centre (MUMC+)Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre (MUMC+)University Eye Clinic Maastricht, Maastricht University Medical Centre (MUMC+)Department of Respiratory Medicine, NUTRIM Research Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre (MUMC+)Department of Clinical Chemistry, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre (MUMC+)Department of Internal Medicine, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Internal Medicine, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus MCDepartment of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Department of Internal Medicine, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre (MUMC+)Abstract Background Systemic microvascular dysfunction is proposed as a key pathophysiological process in heart failure with preserved ejection fraction (HFpEF). This study compared microvasculature across vascular beds in HFpEF patients and controls. Methods This prospective, case-control study included subjects ≥ 60years. HFpEF patients were diagnosed in an expert centre. Controls without HF were selected from the Maastricht Study, a population cohort enriched with diabetes mellitus. Microvascular assessments included central retinal venular/arteriolar calibres (CRVE/CRAE), flicker-light-induced retinal dilation, skin microvascular flowmotion and heat-induced hyperemia, and urinary albumin-to-creatinine ratio (UACR). Group differences were evaluated with confounder-adjustments (age, sex, blood pressure, body mass index, diabetes, haemoglobin, smoking). Interactions with sex and diabetes mellitus were tested, and stratified analyses were performed when significant interactions were present. Results Microvascular assessments were performed in 138 HFpEF patients and 2140 controls. Microvascular differences were present between groups in all vascular beds. However, confounder-adjusted analyses attenuated differences. Confounder-adjusted analyses indicated that HFpEF patients versus controls still had retinal differences: narrower CRVE (− 8.1 μm, p = 0.008) and narrower CRAE trend (− 3.5 μm, p = 0.073), but similar flicker-light-induced retinal venular/arteriolar dilation (− 0.23%, p = 0.392; − 0.18%, p = 0.593, respectively). Confounder-adjusted analyses showed similar skin flowmotion measures (i.e. endothelial power − 0.09log(PU2), p = 0.181), and heat-induced hyperemia (0.02log(%), p = 0.605) between groups. UACR remained higher in HFpEF after confounder adjustments (0.56log(g/mol), p = < 0.001). Interaction analyses revealed that female patients had narrower CRVE versus controls (pint=0.023; females − 13.8 μm, p < 0.001; males 1.2 μm, p = 0.812). Patients had lower skin endothelial flowmotion power only when diabetes was co-occurring (pint=0.048; − 0.36 log(PU2 ), p = 0.014). UACR was higher in male and female patients versus controls, but was more pronounced in males (pint=0.002). Conclusions HFpEF patients showed microvascular differences versus controls across all vascular beds studied. However, confounder-adjusted differences remained significant in eyes and kidneys. The findings across multiple organs support that MVD is likely a more systemic process than only local MVD in HFpEF, and possible sex-specific underlying pathophysiology. Registration URL: https://onderzoekmetmensen.nl ; Unique identifier: NL7655. Graphical abstract Figure created in BioRender (i88u523).https://doi.org/10.1186/s12933-025-02850-1Heart failure with preserved ejection fractionDiastolic heart failureMicrocirculationPathophysiologySex differencesHFpEF |
| spellingShingle | Jerremy Weerts Blanche L. M. Schroen Arantxa Barandiarán Aizpurua Tos T. J. M. Berendschot Lloyd Brandts Carroll A. B. Webers Sami O. Simons Steven J. R. Meex Ronald Henry Carla J. H. van der Kallen Hans-Peter Brunner-La Rocca Christian Knackstedt Stephane R. B. Heymans Rudolf A. de Boer Vanessa P. M. van Empel Alfons J. H. M. Houben Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study Cardiovascular Diabetology Heart failure with preserved ejection fraction Diastolic heart failure Microcirculation Pathophysiology Sex differences HFpEF |
| title | Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study |
| title_full | Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study |
| title_fullStr | Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study |
| title_full_unstemmed | Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study |
| title_short | Microvascular dysfunction across organs in heart failure with preserved ejection fraction: the PROSE-HFpEF case-control study |
| title_sort | microvascular dysfunction across organs in heart failure with preserved ejection fraction the prose hfpef case control study |
| topic | Heart failure with preserved ejection fraction Diastolic heart failure Microcirculation Pathophysiology Sex differences HFpEF |
| url | https://doi.org/10.1186/s12933-025-02850-1 |
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