Screening and treatment intervention for insulin resistance/hyperinsulinemia hoping to prevent heart failure or slow its worsening.

Heart failure (HF) is the common endpoint of most heart diseases, affecting between 1 and 3% of the adult population worldwide, but increases to approximately 10% in adults over 70 years of age, exceeding 20% in those over 80-85 years of age [1, 2].
Serafino Fazio Jun 30, 2026

HF is the leading cause of hospital admissions in Italy and in most of developed and developing countries, accounting for approximately 2% of total hospital admissions, with high rehospitalization rates and very high healthcare costs [2]. In recent years, cases of HFpEF have been increasing steadily, particularly in women, and have now exceeded 50% of HF cases. It is well known that HFrEF and HFpEF have completely different causes and pathophysiological mechanisms. Therefore, also therapies are different. In fact, while HFrEF has treatments well defined by guidelines, HFpEF has few useful drugs identified only in recent years (finerenone, SGLT-2 Is, GLP-1 Ras) [3]. Important recognized causes of HF, particularly HFpEF, are cardiometabolic diseases. Among these, very prevalent in the general population worldwide is insulin resistance with associated hyperinsulinemia [4, 5]. It is the principal cause of type 2 diabetes, preceding its development by many years – even 15 or more [6, 7]. In the meantime, hyperinsulinemia produces significant damage to the cardiovascular system, to the extent that individuals with type 2 diabetes are treated, according to guidelines, as they had already experienced a cardiovascular event [8]. It has been shown that hyperinsulinemia of insulin resistance is also associated with concentric remodeling of left ventricle and diastolic dysfunction, main features of HFpEF  [9] . Therefore, in the hope of reducing hospitalizations, deaths, and healthcare costs resulting from HF, we believe that would be extremely important to implement a more thorough cardiovascular disease prevention plan, particularly by intervening early in the recognition and treatment of insulin resistance in the general population, and finding treatments that more effectively could block or slow the worsening progression of HF. 

References

  1. HFSA-Heart Failure Society of America. 2025-Scientific Statement. HFStats 2025: Heart Failure Epidemilogy and outcome Statistics. https://hfsa.org/hf-stats-2025-heart-failure-epidemiology-and-outcomes-statistics. Accessed on June 23, 2026.
  2. Malfatto, G.; Soranna, D.; Mazzucco, R.; Villani, A.; Giglio, A.; Zambon, A.; Parati, G. Prevalence and incidence of heart failure hospitalizations from 2005 to 2023 and determinants of optimal treatment implementation in clinical practice: A population-based study in Northern Italy. Int J Cardiol Cardiovasc Risk Prev. 2026 Mar 27;29:200627. doi: 10.1016/j.ijcrp.2026.200627. PMID: 41971703; PMCID: PMC13068524.
  3. Borlaug, B.A.; Sharma, K.; Shah, S.J.; Ho, J.E. Heart Failure With Preserved Ejection Fraction: JACC Scientific Statement. J Am Coll Cardiol. 2023 May 9;81(18):1810-1834. doi: 10.1016/j.jacc.2023.01.049. Epub 2023 Apr 19. PMID: 37137592.
  4. Hill, M.A.; Yang, Y.; Zhang, L.; Sun, Z.; Jia, G.; Parrish, A.R.; Sowers, J.R. Insulin resistance, cardiovascular stiffening and cardiovascular disease. Metabolism. 2021 Jun;119:154766. doi: 10.1016/j.metabol.2021.154766. Epub 2021 Mar 22. PMID: 33766485.
  5. Ormazabal, V.; Nair, S.; Elfeky, O.; Aguayo, C.; Salomon, C.; Zuñiga, F.A. Association between insulin resistance and the development of cardiovascular disease. Cardiovasc Diabetol. 2018 Aug 31;17(1):122. doi: 10.1186/s12933-018-0762-4. PMID: 30170598; PMCID: PMC6119242.
  6. Accili, D.; Deng, Z.; Liu, Q. Insulin resistance in type 2 diabetes mellitus. Nat Rev Endocrinol. 2025 Jul;21(7):413-426. doi: 10.1038/s41574-025-01114-y. Epub 2025 Apr 17. PMID: 40247011.
  7. Freeman, A.M.; Acevedo, L.A.; Pennings, N. Insulin Resistance. 2023 Aug 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan–. PMID: 29939616.
  8. Cosentino, F.; Grant, P.J.; Aboyans, V.; Bailey, C.J.; Ceriello, A.; Delgado, V.; et al. ESC Scientific Document Group. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020 Jan 7;41(2):255-323. doi: 10.1093/eurheartj/ehz486. Erratum in: Eur Heart J. 2020 Dec 1;41(45):4317. doi: 10.1093/eurheartj/ehz828. PMID: 31497854.
  9. Sundström, J.; Lind, L.; Nyström, N.; Zethelius, B.; Andrén, B.; Hales, C.N.; Lithell, H.O. Left ventricular concentric remodeling rather than left ventricular hypertrophy is related to the insulin resistance syndrome in elderly men. Circulation. 2000 Jun 6;101(22):2595-600. doi: 10.1161/01.cir.101.22.2595. PMID: 10840010.