Investigation of Growth Differentiation Factor-15, and Lipid-Based Indices in Assessing Cardiovascular Risk in Overt and Subclinical Hypothyroidism

Background: Hypothyroidism, both overt and subclinical, has emerged as a notable contributor to increased cardiovascular disease (CVD) risk. This association is mediated by multifactorial mechanisms, including significant dyslipidemia, heightened oxidative stress, and vascular endothelial dysfunction. Materials and Methods: A case-control study was conducted at the Specialized Center for Diabetic Endocrinology, Baghdad/Russafa, between October 2024 and January 2025. The study included 130 participants: 35 patients with overt hypothyroidism, 35 with subclinical hypothyroidism, and 60 age-, sex-, and BMI-matched euthyroid controls. Blood samples were collected and processed for analysis of serum GDF-15, and lipid profiles. CRI-I, CRII-I, AIP, and AC were calculated. Statistical analyses included ANOVA with post hoc comparisons, Pearson’s correlation, and ROC curve analysis to evaluate biomarker performance. Results: GDF-15 levels were significantly elevated in these groups (p < 0.0001), indicating increased systemic stress. CRI-I and AC values were also significantly higher in hypothyroid patients, confirming an aggravated atherogenic lipid profile. ROC analysis revealed excellent diagnostic performance of GDF-15 (AUC = 0.862) in distinguishing overt hypothyroidism from euthyroidism. Significant correlations were found between the biomarker and lipid-based indices, suggesting a pathophysiological link between systemic stress responses, lipid metabolism, and cardiovascular risk in thyroid dysfunction. Conclusion: GDF-15 is promising biomarkers for cardiovascular risk assessment in hypothyroid patients. Its diagnostic performance, particularly in overt disease, surpasses traditional lipid indices, offering a more comprehensive understanding of cardiovascular compromise. Integration of this marker with established lipid-based indices could enhance early detection, facilitate personalized risk stratification, and inform timely therapeutic interventions in thyroid-associated cardiovascular risk.