Skip Navigation
Skip to contents

CPP : Cardiovascular Prevention and Pharmacotherapy

Sumissioin : submit your manuscript
SEARCH
Search

Articles

Page Path
HOME > Cardiovasc Prev Pharmacother > Volume 7(1); 2025 > Article
Review Article
Nonalcoholic fatty liver disease and heart failure with preserved ejection fraction: a focus on risk factors and management
Joonpyo Leeorcid, Mi-Seung Shinorcid
Cardiovascular Prevention and Pharmacotherapy 2025;7(1):1-8.
DOI: https://doi.org/10.36011/cpp.2025.7.e2
Published online: January 21, 2025

Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea

Correspondence to Mi-Seung Shin, MD Department of Internal Medicine, Gachon University, Gil Medical Center, Gachon University College of Medicine, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon 21565, Korea Email: msshin@gilhospital.com
• Received: January 1, 2025   • Revised: January 9, 2025   • Accepted: January 13, 2025

© 2025 Korean Society of Cardiovascular Disease Prevention; Korean Society of Cardiovascular Pharmacotherapy.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

next
  • Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) are two increasingly prevalent conditions that share common risk factors, including obesity, diabetes, and aging. NAFLD, marked by hepatic steatosis, is a leading cause of liver disease globally, with cardiovascular disease accounting for most deaths among those affected. HFpEF, characterized by diastolic dysfunction and systemic inflammation, accounts for a growing share of heart failure cases, especially among older adults. The bidirectional relationship between NAFLD and HFpEF involves shared mechanisms such as systemic inflammation, insulin resistance, and metabolic dysfunction. These overlapping processes create a vicious cycle that exacerbates each condition. This review emphasizes the shared pathophysiology, risk factors, and management strategies for these interconnected diseases. Promising interventions, including exercise, weight loss, and emerging pharmacological treatments like sodium-glucose cotransporter 2 inhibitors, are effective in addressing both NAFLD and HFpEF. By targeting these common pathways, there is a unique opportunity to develop integrated treatment approaches that could improve outcomes for affected patients.
Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) are two disease entities that have seen an increase in prevalence over the past decade. NAFLD refers to the accumulation of fat in the liver not caused by significant alcohol consumption, viral hepatitis, or medications known to induce fatty liver [1,2]. It is the most prevalent liver disease in westernized countries, commonly associated with obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome [3,4]. Recently, with the emergence of the concept of metabolic dysfunction-associated disease, there has been a shift in terminology from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction associated steatotic liver disease (MASLD) [5]. However, this new terminology remains broad, and its scope is controversial. The terms MAFLD and MASLD were not adopted in this review because they could encompass conditions like viral hepatitis and alcoholic liver disease, which diverge from the focus of this review. Furthermore, the majority of studies referenced here target NAFLD specifically; thus, the term NAFLD was retained due to a lack of sufficient evidence supporting the newer terms. Although NAFLD can cause cirrhosis and liver failure, cardiovascular disease is the leading cause of death among individuals with NAFLD [6]. A meta-analysis involving 34,000 people with NAFLD over a 7-year period found that these individuals have a 65% higher risk of experiencing fatal or nonfatal cardiovascular events compared to those without NAFLD [7,8].
The prevalence of heart failure varies significantly across different countries and studies; however, it is notably high among older adults, along with a substantial mortality rate [9]. Healthcare costs associated with heart failure are also increasing [10]. HFpEF is defined as heart failure with a left ventricular ejection fraction (LVEF) of 50% or greater and evidence of increased left ventricular filling pressure [11], and it accounts for at least half of all patients with heart failure [12]. Notably, the prevalence of HFpEF is rising among older adults, evidenced by a 45% increase in its incidence in the general population [13,14]. In comparison to heart failure with reduced ejection fraction (HFrEF), conditions such as pulmonary disease, diabetes, anemia, and obesity are more common in patients with HFpEF [15,16].
HFpEF and NAFLD share similar risk factors, and previous studies have demonstrated that NAFLD is associated with a higher risk of developing HFpEF than HFrEF [17]. The prevalence of both NAFLD and HFpEF continues to rise due to an aging population and increasing rates of obesity and diabetes. This review seeks to explore the correlation between NAFLD and HFpEF and to identify strategies to address both conditions effectively.
NAFLD is defined as hepatic steatosis without evidence of chronic viral hepatitis, use of medications that induce steatosis, or other chronic liver diseases such as autoimmune hepatitis, hemochromatosis, Wilson disease, or significant alcohol consumption [2]. It is one of the most common types of chronic liver disease. The global prevalence of NAFLD is 32.4% and has been increasing significantly over time [18]. The prevalence of NAFLD varies by race, and factors such as being male, older age, an unhealthy diet, lack of physical activity, and poor sleep quality also contribute to its development [19]. NAFLD is characterized by excessive hepatic fat accumulation associated with insulin resistance [20]. The underlying mechanisms of NAFLD are not yet fully understood. However, genetic factors and environmental predispositions are known to influence its development. A previous twin study identified a genetic component associated with hepatic steatosis [21]. Environmental factors such as obesity, type 2 diabetes, dyslipidemia, and metabolic syndrome are recognized risk factors for NAFLD [20]. In cases of obesity, adipocytes become insulin resistant, which leads to impaired suppression of lipolysis and an increased release of free fatty acids. This influx of adipocyte-derived free fatty acids, along with dietary fat from gastrointestinal-derived chylomicrons, plays a significant role in pro-steatotic mechanisms [22,23]. Within hepatocytes, pathways for de novo lipogenesis are upregulated in obesity, coupled with a decrease in fatty acid oxidation [24]. Previous studies have linked NAFLD to metabolic syndrome and various infectious pathologies [25]. Among these associations, insulin resistance is known to be a major mechanism driving NAFLD [26,27].
Heart failure is a clinical syndrome characterized by symptoms and/or signs resulting from a structural and/or functional cardiac abnormality. It is often accompanied by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion [28]. Heart failure is categorized into three types depending on the LVEF; HFrEF, LVEF ≤40%; heart failure with mildly reduced ejection fraction, LVEF 41% to 49%; and HFpEF, LVEF ≥50%. The mortality has been found to be similarly high in each group of patients hospitalized for heart failure [29]. The pathophysiology of HFpEF is particularly complex due to its multifactorial causes. The main mechanisms include diastolic dysfunction, endothelial dysfunction, chronotropic incompetence, and oxidative stress [30]. Diagnosing HFpEF requires the presence of heart failure symptoms or signs, an LVEF of 50% or greater, and objective evidence of structural and/or functional heart abnormalities indicative of elevated left ventricular filling pressures [31]. Traditional risk factors for heart failure include coronary heart disease, diabetes mellitus, hypertension, obesity, and smoking [10]. Notably, obesity is a significant risk factor for HFpEF [3235]. Additionally, older age is closely associated with HFpEF, and reduced physical activity further increases the risk [36,37]. With the aging population, the prevalence of HFpEF is rising. Concurrently, the number of obese elderly individuals is increasing, and their decreased physical activity not only contributes to the prevalence of obesity but also to additional obesity-related diseases such as NAFLD.
The pathogenesis of NAFLD involves a complex interplay of factors including excessive triglyceride accumulation in the liver, insulin resistance, increased oxidative stress, chronic low-grade inflammation, and lipotoxicity. Two pathways implicated in the development and progression of NAFLD are lipotoxicity, which induces mitochondrial abnormalities and increases liver sensitivity to inflammatory markers, and enhanced lipid peroxidation by reactive oxygen species [38]. Research has established that factors such as advanced age, atrial fibrillation, diabetes mellitus, hypertension, and obesity elevate the risk of HFpEF [39]. HFpEF is not merely a single disease but rather a multisystem syndrome characterized by significant extracardiac involvement [40,41]. Conditions like obesity, metabolic syndrome, and diabetes mellitus, which are linked to HFpEF, are also associated with NAFLD. Furthermore, extracardiac comorbidities such as metabolic syndrome and hypertension are known to contribute to left ventricular remodeling and dysfunction via systemic inflammation in HFpEF [40]. Chronic systemic inflammation impacts not only the myocardium but also other organs including lungs, skeletal muscles, liver, and kidneys. Patients with HFpEF exhibit decreased exercise tolerance due to a rapid increase in left ventricular filling pressure caused by stiff myocardium, inappropriate pulmonary vasoconstriction, inadequate peripheral skeletal muscle vasodilation, and perfusion. Additionally, systemic inflammation compromises renal microcirculation and the kidneys' ability to excrete sodium, leading to systemic edema in patients with HFpEF [40].
NAFLD and HFpEF share similar risk factors. Patients with NAFLD are at a higher risk of developing heart failure, particularly HFpEF, compared to those without NAFLD [16]. NAFLD is linked to changes in myocardial structure and function. A study involving comprehensive echocardiography found that NAFLD was associated with increased left ventricular mass, impaired left ventricular relaxation, elevated left ventricular filling pressure, and deteriorated longitudinal strain, although obesity may explain the link between NAFLD and subclinical diastolic dysfunction [42]. Patients with HFpEF have twice the prevalence of NAFLD compared to the general population [43]. Extracardiac comorbidities of HFpEF can affect the liver, making it susceptible to inflammation, and the risk factors of HFpEF, along with reduced physical activity due to HFpEF, can accelerate fat accumulation in the liver. Furthermore, NAFLD produces inflammatory markers that make the heart more susceptible to inflammation, promote fat accumulation within the myocardium, or increase myocardial stiffness, potentially causing or exacerbating HFpEF. Thus, NAFLD and HFpEF may interact in a vicious cycle, exacerbating each other's condition. Insulin resistance, a common factor in both conditions, exacerbates systemic inflammation and mutually influences each disease.
Exercise
In a meta-analysis, the effect of interventions on hepatic fat mobilization was observed to be 30.2% in the exercise group and 49.8% in the group combining diet control with exercise among NAFLD patients [44]. No significant differences were found between aerobic and resistance exercises. Exercise positively influenced intrahepatic triglycerides even without weight loss. Additionally, integrating an exercise program with dietary control not only reduced liver triglycerides but also improved blood glucose levels and insulin sensitivity. Thus, exercise alone has been effective in improving NAFLD [44]. For HFpEF, multiple randomized controlled trials have established that exercise is both safe and beneficial in enhancing quality of life [45]. Exercise training not only boosts cardiopulmonary function but also increases patients' exercise tolerance. Therefore, it is recommended, despite the lack of evidence showing an improvement in the prognosis of HFpEF [46].
Weight loss
Guidelines recommend weight loss in the management of NAFLD [20]. Obesity, type 2 diabetes mellitus, and NAFLD are interconnected conditions, with an increase in obesity prevalence leading to higher rates of diabetes mellitus and NAFLD. Therefore, achieving proper weight loss is crucial, as adequate weight reduction can improve the prognosis of NAFLD [47]. In obese patients with HFpEF, meaningful weight loss has been shown to enhance quality of life and exercise capacity [48]. Several studies indicate that bariatric surgery for weight loss is beneficial for both NAFLD and HFpEF [4951]. A meta-analysis assessing whether NAFLD improves post-bariatric surgery revealed significant reductions in steatosis and steatohepatitis in a large patient cohort [49]. While bariatric surgery may offer benefits to patients with severe obesity and either NAFLD or HFpEF, the results are mixed and difficult to generalize due to the limited scale of the studies.
Medical treatment
To date, there are no specific medications approved for the treatment of NAFLD. Studies have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors are more effective in reducing weight, liver fat content, and improving transaminase levels in patients with NAFLD [5255]. Additionally, the use of SGLT2 inhibitors in patients with HFpEF has been associated with reduced hospitalizations for heart failure and lower cardiovascular mortality [56]. The beneficial effects of SGLT2 inhibitors on NAFLD and HFpEF are linked to weight loss and seem to be directly mediated through the regulation of multiple processes, including endoplasmic reticulum stress, oxidative stress, low-grade inflammation, autophagy, and apoptosis, as demonstrated by in vitro, animal, and clinical studies [57]. SGLT2 inhibitors may be a promising treatment option due to their anti-inflammatory and weight control effects in patients with HFpEF and NAFLD.
Clinical studies have demonstrated that metformin can modestly decrease body mass index, liver fat content, and liver enzyme levels in NAFLD patients with diabetes [58]. Additionally, metformin has been shown to improve liver fibrosis, liver enzyme levels, and insulin resistance in this patient group [59]. Furthermore, a meta-analysis indicated that metformin treatment reduced mortality in patients with HFpEF [60].
Previous studies have shown that certain statins, such as atorvastatin and rosuvastatin, can help ameliorate NAFLD [61]. The use of statins in patients with NAFLD has been linked to improved liver enzyme levels, histological improvements, and protection against progression to hepatocellular carcinoma. Research has also confirmed the benefits of statin use in HFpEF patients without coronary artery disease [62]. Statin use has been associated with a reduced rate of noncardiac death and fewer readmissions for heart failure in the HFpEF group [62]. The suggested mechanisms behind the beneficial effects of statins in patients with HFpEF include the pleiotropic effects of statin therapy, such as regression of left ventricular hypertrophy and fibrosis, anti-inflammatory and antioxidant effects, and improvements in impaired renal function.
Recent studies have shown that the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide reduced the risk of worsening heart failure in patients with obesity-related HFpEF [63,64]. The beneficial effects of tirzepatide on HFpEF are linked to reductions in left ventricular mass, paracardiac adipose tissue, circulatory volume-pressure overload, and systemic inflammation [63,65]. In addition to promoting weight loss, GLP-1 receptor agonists have proven effective in improving clinical, biochemical, and histological markers of hepatic steatosis, inflammation, and fibrosis in patients with NAFLD [66]. Tirzepatide significantly reduced liver enzyme levels and liver fat content, suggesting its potential role in managing patients with NAFLD [67]. In a recent trial, tirzepatide effectively resolved steatohepatitis without exacerbating fibrosis in patients with metabolic dysfunction-associated steatohepatitis [68]. Furthermore, a recent study demonstrated that survodutide, a dual agonist of the glucagon receptor and GLP-1 receptor, effectively improved steatohepatitis [69]. This finding raises the possibility that it may be helpful in treating HFpEF in the future.
NAFLD and HFpEF are closely linked through overlapping risk factors and pathophysiological mechanisms, such as systemic inflammation, insulin resistance, and metabolic dysfunction. This interconnection fosters a bidirectional relationship in which each condition exacerbates the other, perpetuating a cycle of deteriorating clinical outcomes. Effective management of these conditions necessitates a comprehensive strategy that includes lifestyle modifications like exercise and weight loss, complemented by emerging pharmacological treatments. Promising therapies, including SGLT2 inhibitors and tirzepatide, provide dual benefits for both disorders. Nonetheless, additional research is essential to determine the most effective integrated management approaches. By targeting the shared pathways between NAFLD and HFpEF, the progression of both diseases can be mitigated, while overall patient prognosis is improved, highlighting the importance of a holistic and targeted therapeutic approach.

Author contributions

Conceptualization: all authors; Supervision: MSS; Writing–original draft: JL; Writing–review & editing: MSS. All authors read and approved the final manuscript.

Conflicts of interest

The authors have no conflicts of interest to declare.

Funding

The authors received no financial support for this study.

  • 1. Marjot T, Moolla A, Cobbold JF, Hodson L, Tomlinson JW. Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management. Endocr Rev 2020;41:bnz009.ArticlePubMedPDF
  • 2. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease: meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016;64:73–84. ArticlePubMed
  • 3. Younossi ZM, Stepanova M, Afendy M, Fang Y, Younossi Y, Mir H, et al. Changes in the prevalence of the most common causes of chronic liver diseases in the United States from 1988 to 2008. Clin Gastroenterol Hepatol 2011;9:524–30. ArticlePubMed
  • 4. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology 2023;77:1335–47. ArticlePubMedPMC
  • 5. Rinella ME, Lazarus JV, Ratziu V, Francque SM, Sanyal AJ, Kanwal F, et al. A multisociety Delphi consensus statement on new fatty liver disease nomenclature. Hepatology 2023;78:1966–86. ArticlePubMed
  • 6. Byrne CD, Targher G. NAFLD: a multisystem disease. J Hepatol 2015;62(1 Suppl):S47–64. ArticlePubMed
  • 7. Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018;24:908–22. ArticlePubMedPMCPDF
  • 8. Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol 2016;65:589–600. ArticlePubMed
  • 9. Emmons-Bell S, Johnson C, Roth G. Prevalence, incidence and survival of heart failure: a systematic review. Heart 2022;108:1351–60. ArticlePubMedPMC
  • 10. Tsao CW, Aday AW, Almarzooq ZI, Anderson CA, Arora P, Avery CL, et al. Heart disease and stroke statistics: 2023 update: a report from the American Heart Association. Circulation 2023;147:e93–621. ArticlePubMed
  • 11. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, et al. 2022 AHA/ACC/HFSA Guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol 2022;79:e263–421. ArticlePubMed
  • 12. Magana-Serrano JA, Almahmeed W, Gomez E, Al-Shamiri M, Adgar D, Sosner P, et al. Prevalence of heart failure with preserved ejection fraction in Latin American, Middle Eastern, and North African Regions in the I PREFER study (identification of patients with heart failure and preserved systolic function: an epidemiological regional study). Am J Cardiol 2011;108:1289–96. ArticlePubMed
  • 13. Borlaug BA, Paulus WJ. Heart failure with preserved ejection fraction: pathophysiology, diagnosis, and treatment. Eur Heart J 2011;32:670–9. ArticlePubMedPMC
  • 14. Tsao CW, Lyass A, Enserro D, Larson MG, Ho JE, Kizer JR, et al. Temporal trends in the incidence of and mortality associated with heart failure with preserved and reduced ejection fraction. JACC Heart Fail 2018;6:678–85. ArticlePubMedPMC
  • 15. Mentz RJ, Kelly JP, von Lueder TG, Voors AA, Lam CS, Cowie MR, et al. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol 2014;64:2281–93. ArticlePubMedPMC
  • 16. Fudim M, Zhong L, Patel KV, Khera R, Abdelmalek MF, Diehl AM, et al. Nonalcoholic fatty liver disease and risk of heart failure among Medicare beneficiaries. J Am Heart Assoc 2021;10:e021654. ArticlePubMedPMC
  • 17. Mantovani A, Petracca G, Csermely A, Beatrice G, Bonapace S, Rossi A, et al. Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals. Gut 2023;72:372–80. ArticlePubMed
  • 18. Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2022;7:851–61. ArticlePubMed
  • 19. Huh Y, Cho YJ, Nam GE. Recent epidemiology and risk factors of nonalcoholic fatty liver disease. J Obes Metab Syndr 2022;31:17–27. ArticlePubMedPMC
  • 20. European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol 2016;64:1388–402. ArticlePubMed
  • 21. Loomba R, Schork N, Chen CH, Bettencourt R, Bhatt A, Ang B, et al. Heritability of hepatic fibrosis and steatosis based on a prospective twin study. Gastroenterology 2015;149:1784–93. ArticlePubMedPMC
  • 22. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343–51. ArticlePubMedPMC
  • 23. Meex RC, Watt MJ. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance. Nat Rev Endocrinol 2017;13:509–20. ArticlePubMedPDF
  • 24. Song Z, Xiaoli AM, Yang F. Regulation and metabolic significance of de novo lipogenesis in adipose tissues. Nutrients 2018;10:1383.ArticlePubMedPMC
  • 25. Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocr Disord 2022;22:63.ArticlePubMedPMCPDF
  • 26. Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183–92. ArticlePubMed
  • 27. Koo DJ, Lee WY. The crosstalk between insulin resistance and nonalcoholic fatty liver disease/metabolic dysfunction-associated fatty liver disease: a culprit or a consequence? Cardiovasc Prev Pharmacother 2022;4:132–41. ArticlePDF
  • 28. Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid CM, Adamopoulos S, Albert N, et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association. Eur J Heart Fail 2021;23:352–80. ArticlePubMed
  • 29. Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, et al. Heart failure with preserved, borderline, and reduced ejection fraction: 5-year outcomes. J Am Coll Cardiol 2017;70:2476–86. ArticlePubMed
  • 30. Nair N. Epidemiology and pathogenesis of heart failure with preserved ejection fraction. Rev Cardiovasc Med 2020;21:531–40. ArticlePubMed
  • 31. McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Bohm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599–726. ArticlePubMedPDF
  • 32. Redfield MM, Borlaug BA. Heart failure with preserved ejection fraction: a review. JAMA 2023;329:827–38. ArticlePubMed
  • 33. Campbell P, Rutten FH, Lee MM, Hawkins NM, Petrie MC. Heart failure with preserved ejection fraction: everything the clinician needs to know. Lancet 2024;403:1083–92. ArticlePubMed
  • 34. Haass M, Kitzman DW, Anand IS, Miller A, Zile MR, Massie BM, et al. Body mass index and adverse cardiovascular outcomes in heart failure patients with preserved ejection fraction: results from the Irbesartan in Heart Failure with Preserved Ejection Fraction (I-PRESERVE) trial. Circ Heart Fail 2011;4:324–31. ArticlePubMedPMC
  • 35. Jung MH, Shin MS. Obesity-related heart failure with preserved ejection fraction: diagnostic and therapeutic challenges. Korean J Intern Med 2023;38:157–66. ArticlePubMedPMCPDF
  • 36. Ho JE, Enserro D, Brouwers FP, Kizer JR, Shah SJ, Psaty BM, et al. Predicting heart failure with preserved and reduced ejection fraction: the International Collaboration on Heart Failure Subtypes. Circ Heart Fail 2016;9:e003116.ArticlePubMedPMC
  • 37. Pandey A, LaMonte M, Klein L, Ayers C, Psaty BM, Eaton CB, et al. Relationship between physical activity, body mass index, and risk of heart failure. J Am Coll Cardiol 2017;69:1129–42. ArticlePubMedPMC
  • 38. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012;482:179–85. ArticlePubMedPMCPDF
  • 39. Lee MP, Glynn RJ, Schneeweiss S, Lin KJ, Patorno E, Barberio J, et al. Risk factors for heart failure with preserved or reduced ejection fraction among Medicare beneficiaries: application of competing risks analysis and gradient boosted model. Clin Epidemiol 2020;12:607–16. ArticlePubMedPMC
  • 40. Shah SJ, Kitzman DW, Borlaug BA, van Heerebeek L, Zile MR, Kass DA, et al. Phenotype-specific treatment of heart failure with preserved ejection fraction: a multiorgan roadmap. Circulation 2016;134:73–90. ArticlePubMedPMC
  • 41. Capone F, Vettor R, Schiattarella GG. Cardiometabolic HFpEF: NASH of the heart. Circulation 2023;147:451–3. ArticlePubMed
  • 42. VanWagner LB, Wilcox JE, Ning H, Lewis CE, Carr JJ, Rinella ME, et al. Longitudinal association of non-alcoholic fatty liver disease with changes in myocardial structure and function: the CARDIA Study. J Am Heart Assoc 2020;9:e014279. ArticlePubMedPMC
  • 43. Miller A, McNamara J, Hummel SL, Konerman MC, Tincopa MA. Prevalence and staging of non-alcoholic fatty liver disease among patients with heart failure with preserved ejection fraction. Sci Rep 2020;10:12440.ArticlePubMedPMCPDF
  • 44. Golabi P, Locklear CT, Austin P, Afdhal S, Byrns M, Gerber L, et al. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: systematic review. World J Gastroenterol 2016;22:6318–27. ArticlePubMedPMC
  • 45. Sachdev V, Sharma K, Keteyian SJ, Alcain CF, Desvigne-Nickens P, Fleg JL, et al. Supervised exercise training for chronic heart failure with preserved ejection fraction: a scientific statement from the American Heart Association and American College of Cardiology. Circulation 2023;147:e699–715. ArticlePubMed
  • 46. Crisci G, De Luca M, D’Assante R, Ranieri B, D’Agostino A, Valente V, et al. Effects of exercise on heart failure with preserved ejection fraction: an updated review of literature. J Cardiovasc Dev Dis 2022;9:241.ArticlePubMedPMC
  • 47. Finer N. Weight loss interventions and nonalcoholic fatty liver disease: optimizing liver outcomes. Diabetes Obes Metab 2022;24 Suppl 2:44–54. ArticlePubMedPDF
  • 48. El Hajj EC, El Hajj MC, Sykes B, Lamicq M, Zile MR, Malcolm R, et al. Pragmatic weight management program for patients with obesity and heart failure with preserved ejection fraction. J Am Heart Assoc 2021;10:e022930. ArticlePubMedPMC
  • 49. Mummadi RR, Kasturi KS, Chennareddygari S, Sood GK. Effect of bariatric surgery on nonalcoholic fatty liver disease: systematic review and meta-analysis. Clin Gastroenterol Hepatol 2008;6:1396–402. ArticlePubMed
  • 50. Mikhalkova D, Holman SR, Jiang H, Saghir M, Novak E, Coggan AR, et al. Bariatric surgery-induced cardiac and lipidomic changes in obesity-related heart failure with preserved ejection fraction. Obesity (Silver Spring) 2018;26:284–90. ArticlePubMedPMCPDF
  • 51. Laursen TL, Hagemann CA, Wei C, Kazankov K, Thomsen KL, Knop FK, et al. Bariatric surgery in patients with non-alcoholic fatty liver disease: from pathophysiology to clinical effects. World J Hepatol 2019;11:138–49. ArticlePubMedPMC
  • 52. Euh W, Lim S, Kim JW. Sodium-glucose cotransporter-2 inhibitors ameliorate liver enzyme abnormalities in Korean patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease. Front Endocrinol (Lausanne) 2021;12:613389.ArticlePubMedPMC
  • 53. Kuchay MS, Krishan S, Mishra SK, Farooqui KJ, Singh MK, Wasir JS, et al. Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care 2018;41:1801–8. ArticlePubMedPDF
  • 54. Mantovani A, Byrne CD, Scorletti E, Mantzoros CS, Targher G. Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: an updated systematic review of randomized controlled trials. Diabetes Metab 2020;46:427–41. ArticlePubMed
  • 55. Sinha B, Datta D, Ghosal S. Meta-analysis of the effects of sodium glucose cotransporter 2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes. JGH Open 2020;5:219–27. ArticlePubMedPMCPDF
  • 56. Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med 2021;385:1451–61. ArticlePubMed
  • 57. Androutsakos T, Nasiri-Ansari N, Bakasis AD, Kyrou I, Efstathopoulos E, Randeva HS, et al. SGLT-2 inhibitors in NAFLD: expanding their role beyond diabetes and cardioprotection. Int J Mol Sci 2022;23:3107.ArticlePubMedPMC
  • 58. Pinyopornpanish K, Leerapun A, Pinyopornpanish K, Chattipakorn N. Effects of metformin on hepatic steatosis in adults with nonalcoholic fatty liver disease and diabetes: insights from the cellular to patient levels. Gut Liver 2021;15:827–40. ArticlePubMedPMC
  • 59. Feng W, Gao C, Bi Y, Wu M, Li P, Shen S, et al. Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease. J Diabetes 2017;9:800–9. ArticlePubMedPDF
  • 60. Halabi A, Sen J, Huynh Q, Marwick TH. Metformin treatment in heart failure with preserved ejection fraction: a systematic review and meta-regression analysis. Cardiovasc Diabetol 2020;19:124.ArticlePubMedPMCPDF
  • 61. Doumas M, Imprialos K, Dimakopoulou A, Stavropoulos K, Binas A, Athyros VG. The role of statins in the management of nonalcoholic fatty liver disease. Curr Pharm Des 2018;24:4587–92. ArticlePubMedPDF
  • 62. Marume K, Takashio S, Nagai T, Tsujita K, Saito Y, Yoshikawa T, et al. Effect of statins on mortality in heart failure with preserved ejection fraction without coronary artery disease: report from the JASPER Study. Circ J 2019;83:357–67. ArticlePubMed
  • 63. Borlaug BA, Zile MR, Kramer CM, Baum SJ, Hurt K, Litwin SE, et al. Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med 2024 Nov 17 [Epub]. https://doi.org/10.1038/s41591-024-03374-zArticlePubMed
  • 64. Zile MR, Borlaug BA, Kramer CM, Baum SJ, Litwin SE, Menon V, et al. Effects of tirzepatide on the clinical trajectory of patients with heart failure, a preserved ejection fraction, and obesity. Circulation 2024 Nov 18 [Epub]. https://doi.org/10.1161/CIRCULATIONAHA.124.072679ArticlePubMed
  • 65. Kramer CM, Borlaug BA, Zile MR, Ruff D, DiMaria JM, Menon V, et al. Tirzepatide reduces LV mass and paracardiac adipose tissue in obesity-related heart failure: SUMMIT CMR Substudy. J Am Coll Cardiol 2024 Nov 5 [Epub]. https://doi.org/10.1016/j.jacc.2024.11.001ArticlePubMed
  • 66. Shin J, Kim R, Kim HS. Liraglutide, a glucagon-like peptide-1 analog, in individuals with obesity in clinical practice. Cardiovasc Prev Pharmacother 2023;5:49–53. ArticlePDF
  • 67. Lee HA, Kim HY. Therapeutic mechanisms and clinical effects of glucagon-like peptide 1 receptor agonists in nonalcoholic fatty liver disease. Int J Mol Sci 2023;24:9324.ArticlePubMedPMC
  • 68. Loomba R, Hartman ML, Lawitz EJ, Vuppalanchi R, Boursier J, Bugianesi E, et al. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med 2024;391:299–310. ArticlePubMed
  • 69. Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis. N Engl J Med 2024;391:311–9. ArticlePubMed

Figure & Data

References

    Citations

    Citations to this article as recorded by  

      Nonalcoholic fatty liver disease and heart failure with preserved ejection fraction: a focus on risk factors and management
      Nonalcoholic fatty liver disease and heart failure with preserved ejection fraction: a focus on risk factors and management

      CPP : Cardiovascular Prevention and Pharmacotherapy
      TOP