Paying Homage to the Power of Proteomics: Insights Into Obesity and Heart Failure From the HOMAGE Trial

Abstract

Obesity is a known major risk factor for heart failure (HF), more than doubling the risk of incident HF compared to those with normal body mass indexes (BMIs), and there is increasing risk with each additional point of BMI. 1 Kenchaiah S Evans JC Levy D Wilson PWF Benjamin EJ Larson MG et al. Obesity and the risk of heart failure. N Engl J Med. 2002; 347: 305-313 Crossref PubMed Scopus (2082) Google Scholar The relationship between obesity and HF is still not well understood, though some studies have suggested that the relationship between obesity and HF may be driven by inflammation. 2 Bahrami H Bluemke DA Kronmal R Bertoni AG Lloyd-Jones DM Shahar E et al. Novel metabolic risk factors for incident heart failure and their relationship with obesity. J Am Coll Cardiol. 2008; 51: 1775-1783 Crossref PubMed Scopus (262) Google Scholar ,3 Sanders-van Wijk S, Tromp J, Beussink-Nelson L, Hage C, Svedlund S, Saraste A, et al. Proteomic evaluation of the comorbidity-inflammation paradigm in heart failure with preserved ejection fraction results from the PROMIS-HFpEF Study. https://doi.org/10.1161/CIRCULATIONAHA.120.045810Circulation. 2020;142:2029–44. Google Scholar Given the global prevalence of obesity, there is a clear imperative to understand the complex epidemiological, biological and clinical interrelationships between obesity and HF so we can develop strategies that reduce the risk of incident HF. 4 World Health Organization. Obesity and Overweight: Fact Sheet. Available at: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight. Accessed January 15, 2022. Google Scholar Emerging molecular technologies in proteomics are providing an unprecedented opportunity to assess the relative concentration of large numbers of proteins in a single, small sample, enabling diseases to be phenotyped at the molecular level. These strategies offer the opportunity to gain insight into the biological underpinnings of disease and disease risk factors to allow for better understanding of the impact of various therapies on these mechanisms and to identify the mechanisms through which those therapies operate.