Aging is an inevitable biological process marked by progressive functional decline and elevated risk of cardiovascular diseases (CVDs). This review systematically examines the clinical mechanisms linking aging to cardiovascular pathology, focusing on molecular, cellular, and physiological changes that contribute to cardiovascular aging, which in turn increases the incidence of heart failure, atherosclerosis, atrial fibrillation, and other diseases. Key mechanisms include metabolic dysregulation, mitochondrial dysfunction, chronic inflammation, cellular senescence, immune disorders, and epigenetic changes. Understanding these mechanisms is crucial for developing targeted interventions to delay cardiovascular aging and alleviate CVD burden in older people. Current therapeutic strategies, including lifestyle modifications, pharmacotherapy, gerotherapeutic interventions, and device-based management, are reviewed, along with future directions in precision medicine, development of novel therapeutic targets, multi-omics, and AI-powered strategies against cardiovascular aging.
OBJECTIVE
To explore whether the favorable association between weight loss and glycemic improvement in patients with obesity and type 2 diabetes mellitus (T2DM) is partially mediated by weight loss-induced changes in the hypothalamic-pituitary-thyroid (HPT) axis, including alterations in thyroid-stimulating hormone (ΔTSH), free triiodothyronine (ΔFT3), and free thyroxine (ΔFT4).
METHODS
A total of 364 patients with obesity and T2DM who underwent bariatric surgery, glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy, or standardized lifestyle intervention were enrolled in this retrospective real-world cohort study. Anthropometric, glycemic, and thyroid function indicators were measured at baseline and after a median follow-up of approximately 12 months.
RESULTS
Weight loss interventions led to significant reductions in body weight, glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and homeostatic model assessment for insulin resistance (HOMA-IR), as well as a significant increase in homeostatic model assessment for β-cell function (HOMA-β) (all P < 0.001). Serum TSH and FT3 levels decreased markedly after intervention (both P < 0.001), whereas FT4 levels remained stable (P = 0.542). Changes in TSH and FT3 were significantly correlated with changes in HbA1c (ΔTSH: r = 0.319, P < 0.001; ΔFT3: r = 0.135, P = 0.010). The HPT axis exerted a significant total indirect mediating effect of 10.7% on the association between weight loss and HbA1c improvement (P = 0.032), with ΔTSH contributing 5.5% and ΔFT3 contributing 5.2% of the total effect. Subgroup analysis showed that the indirect mediating effect was more prominent in patients with higher baseline TSH levels.
CONCLUSION
Changes in thyroid axis markers, specifically reductions in TSH and FT3, significantly and indirectly mediate the improvement in glycemic control following weight loss interventions in T2DM patients. Although this mediating effect is modest in overall magnitude, it is augmented in individuals with elevated baseline TSH levels. These findings suggest a novel auxiliary mechanism underlying the metabolic benefits of weight loss mediated by HPT axis remodeling.
Peng Li, Jingjing Zhang, Meiqi Li· American journal of translat...· 0 citations
Obesity, given its strong association with cardiovascular diseases (CVDs), is a major global public health issue attracting increasing attention. This comprehensive review systematically synthesizes clinical and basic research progress in elucidating the complex relationship between obesity and CVDs. We explore the epidemiology, pathophysiology, clinical manifestations, and management strategies for obesity-related CVDs. Drawing on recent studies, we highlight the effects of obesity on atherosclerotic disease, cardiomyopathy, heart failure, arrhythmias, hypertension, and venous thromboembolism. Understanding these mechanisms is essential for developing effective prevention and treatment strategies to decrease the cardiovascular burden associated with obesity. Furthermore, this review summarizes current therapeutic approaches for obesity-related CVDs, such as lifestyle interventions, pharmacotherapy, and metabolic surgery, and discusses future research directions, including precision medicine, exploration of novel therapeutic targets, and single-cell spatiotemporal omics.
Naiqi Liu, Yi Pan, Fuk L Liu et al.· Cardiovascular Innovations a...· 0 citations
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