Effect of Weight Loss on Cardiac Function and Biomarkers in Patients With Cardiovascular Risk Factors, Obesity, or Overweight

Obesity is one of the leading global health issues, with a high impact on morbidity, mortality, and quality of life. In Mexico, the prevalence of obesity has significantly increased in the past two decades, ranking fifth worldwide. Obesity is strongly associated with other cardiovascular risk factors, including hypertension, diabetes, and dyslipidemia.

In obese individuals, a chronic low-grade inflammatory state and endothelial dysfunction contribute to adverse cardiovascular remodeling. These mechanisms-driven by adipose tissue inflammation, reduced nitric oxide bioavailability, and insulin resistance-can lead to myocardial hypertrophy, ventricular dilation, and impaired cardiac function. Structural and functional changes include increased left ventricular mass, larger right and left ventricular end-diastolic volumes, and subclinical diastolic dysfunction, as demonstrated by echocardiography and cardiac magnetic resonance imaging (MRI). Obesity-related adipose tissue dysfunction also induces an imbalance between anti-inflammatory adiponectin and pro-inflammatory adipocytokines, promoting myocardial and vascular remodeling.

Furthermore, epicardial adipose tissue exhibits high immune cell activity, including elevated expression of IL-1, IL-6, and TNF-α, contributing to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Alterations in gut microbiota (dysbiosis) also play a role in obesity-related inflammation by producing bacterial metabolites and lipopolysaccharides associated with endothelial activation and atherosclerotic plaque instability. Pharmacological interventions such as GLP-1 receptor agonists and SGLT2 inhibitors have shown potential benefits in reducing inflammation and improving cardiac metabolism. Weight loss-whether achieved through lifestyle modification, pharmacotherapy, or bariatric surgery-has been associated with improvements in hemodynamic load, blood pressure, and metabolic parameters. However, evidence regarding the reversibility of cardiac structural and functional changes remains insufficient. This study will prospectively evaluate adult patients (≥18 years) with overweight (BMI ≥25 kg/m²) or obesity (BMI ≥30 kg/m²) and at least one cardiovascular risk factor. Participants will receive individualized nutritional counseling and weight loss interventions (pharmacological or non-pharmacological) according to standard clinical practice at the TecSalud Institute of Cardiology and Vascular Medicine.

The primary objective is to determine whether significant weight loss (>10% reduction in body weight) results in measurable changes in cardiac morphology and function assessed by cardiac MRI and echocardiography. Secondary objectives include evaluating changes in inflammatory and cardiac biomarkers. An exploratory analysis will assess differences according to the weight loss strategy (pharmacological vs. non-pharmacological), including possible associations with gut microbiota composition. Ultimately, this study seeks to provide new evidence on the reversibility of obesity-related cardiac changes and the potential role of inflammatory and metabolic biomarkers in cardiovascular risk reduction.