Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives
Insulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-trea...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/8/2188 |
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| author | Maria Perticone Raffaele Maio Simona Gigliotti Ermal Shehaj Alfredo Francesco Toscani Antonella Capomolla Ginevra Fabiani Angela Sciacqua Francesco Perticone |
| author_facet | Maria Perticone Raffaele Maio Simona Gigliotti Ermal Shehaj Alfredo Francesco Toscani Antonella Capomolla Ginevra Fabiani Angela Sciacqua Francesco Perticone |
| author_sort | Maria Perticone |
| collection | DOAJ |
| description | Insulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-treated hypertensives. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. During the follow-up [median: 117 months (range: 31–211)], we documented 223 new cases of HF (3.3 events/100 patient-years). We stratified the study population into progressors and non-progressors; progressors showed an older age and a higher prevalence of females, as well as higher mean values of baseline glucose, insulin, homeostasis model assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP), whereas the estimated glomerular filtration rate (e-GFR) and endothelium-dependent vasodilation were lower. In the multiple Cox regression analysis, serum hs-CRP (HR = 1.362, (95% CI = 1.208–1.536), HOMA (HR = 1.293, 95% CI = 1.142–1.465), maximal acetylcholine (Ach)-stimulated forearm blood flow (FBF) (100% increment, HR = 0.807, 95% CI = 0.697–0.934), and e-GFR (10 mL/min/1.73 m<sup>2</sup> increment, HR = 0.552, 95% CI = 0.483–0.603) maintained an independent association with incident HF. HOMA and endothelial dysfunction interact between them in a competitive manner (HR = 6.548, 95% CI = 4.034–10.629), also showing a mutual effect modification. Our findings demonstrate that both endothelial dysfunction and HOMA are independent and strong predictors of incident HF in hypertensives, these two risk factors interact between them with a competitive mechanism. |
| first_indexed | 2024-03-11T00:06:52Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T00:06:52Z |
| publishDate | 2023-08-01 |
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| series | Biomedicines |
| spelling | doaj.art-c4782b97be424c0c81abc19cea19e8882023-11-19T00:20:39ZengMDPI AGBiomedicines2227-90592023-08-01118218810.3390/biomedicines11082188Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in HypertensivesMaria Perticone0Raffaele Maio1Simona Gigliotti2Ermal Shehaj3Alfredo Francesco Toscani4Antonella Capomolla5Ginevra Fabiani6Angela Sciacqua7Francesco Perticone8Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyGeriatrics Unit, Azienda Ospedaliero-Universitaria Renato Dulbecco, 88100 Catanzaro, ItalyDepartment of Health Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyCardiology and CICU Unit, Giovanni Paolo II Hospital, 88046 Lamezia Terme, ItalyDepartment of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDon Mottola Medical Center, 89862 Drapia, ItalyDepartment of Experimental and Clinical Medicine, University of Florence, 50121 Florence, ItalyDepartment of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyDepartment of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, 88100 Catanzaro, ItalyInsulin resistance and endothelial dysfunction are associated with heart failure (HF). Our objective was to investigate whether endothelial dysfunction and insulin resistance are independent predictors of incident HF and if a possible interaction exists between them. We enrolled 705 white never-treated hypertensives. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine. During the follow-up [median: 117 months (range: 31–211)], we documented 223 new cases of HF (3.3 events/100 patient-years). We stratified the study population into progressors and non-progressors; progressors showed an older age and a higher prevalence of females, as well as higher mean values of baseline glucose, insulin, homeostasis model assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP), whereas the estimated glomerular filtration rate (e-GFR) and endothelium-dependent vasodilation were lower. In the multiple Cox regression analysis, serum hs-CRP (HR = 1.362, (95% CI = 1.208–1.536), HOMA (HR = 1.293, 95% CI = 1.142–1.465), maximal acetylcholine (Ach)-stimulated forearm blood flow (FBF) (100% increment, HR = 0.807, 95% CI = 0.697–0.934), and e-GFR (10 mL/min/1.73 m<sup>2</sup> increment, HR = 0.552, 95% CI = 0.483–0.603) maintained an independent association with incident HF. HOMA and endothelial dysfunction interact between them in a competitive manner (HR = 6.548, 95% CI = 4.034–10.629), also showing a mutual effect modification. Our findings demonstrate that both endothelial dysfunction and HOMA are independent and strong predictors of incident HF in hypertensives, these two risk factors interact between them with a competitive mechanism.https://www.mdpi.com/2227-9059/11/8/2188heart failureinsulin resistanceendothelial dysfunctionhypertensioncardiovascular risk factors |
| spellingShingle | Maria Perticone Raffaele Maio Simona Gigliotti Ermal Shehaj Alfredo Francesco Toscani Antonella Capomolla Ginevra Fabiani Angela Sciacqua Francesco Perticone Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives Biomedicines heart failure insulin resistance endothelial dysfunction hypertension cardiovascular risk factors |
| title | Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives |
| title_full | Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives |
| title_fullStr | Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives |
| title_full_unstemmed | Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives |
| title_short | Mutual Effect Modification between Insulin Resistance and Endothelial Dysfunction in Predicting Incident Heart Failure in Hypertensives |
| title_sort | mutual effect modification between insulin resistance and endothelial dysfunction in predicting incident heart failure in hypertensives |
| topic | heart failure insulin resistance endothelial dysfunction hypertension cardiovascular risk factors |
| url | https://www.mdpi.com/2227-9059/11/8/2188 |
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