The essence of obesity is the accumulation of abnormal adipose tissue, often accompanied by ectopic fat deposition in the liver, arterial walls, epicardium, and other sites. Such ectopic deposition significantly increases the risk of CVD, including atherosclerosis-induced hypertension, dyslipidemia, and a prediabetic state. Visceral fat deposition also impairs the function of other organs, such as sleep apnea syndrome associated with severe obesity. These clinical manifestations are clearly defined as cardiovascular risk factors.
The well-known “three highs” — hyperglycemia, hypertension, and hyperlipidemia — as well as the extended “four highs” (adding high body weight) and “five highs” (adding hyperuricemia), represent common pathological changes comorbid with obesity. Therefore, obesity should be regarded as a systemic chronic disease requiring long-term comprehensive management, rather than merely focusing on changes in body weight.
The core mechanism by which obesity or metabolic abnormalities lead to CVD is insulin resistance. In China and globally, type 2 diabetes mellitus (T2DM) accounts for more than 95% of all diabetes cases, and insulin resistance is its key pathological basis. Insulin resistance can affect multiple cell types in the cardiovascular system, including endothelial cells, smooth muscle cells, adventitial cells, cardiomyocytes, and renal fibroblasts, inducing oxidative stress and releasing large amounts of superoxide.
Meanwhile, under the influence of insulin resistance and oxidative stress, monocytes and macrophages in the peripheral circulation can modify low-density lipoprotein cholesterol (LDL-C), oxidizing it into a potent pro-inflammatory mediator, thereby triggering chronic low-grade inflammation, namely metabolic inflammation.
Metabolic inflammation and oxidative stress act synergistically to damage tissue and organ function, resulting in vascular endothelial dysfunction — a critical precursor to atherosclerosis. This process also activates bone marrow-derived monocytes, which differentiate into macrophages and migrate into the subendothelial space. Through the expression of scavenger receptors, macrophages take up oxidized LDL-C and transform into foam cells, ultimately promoting the formation of atherosclerotic plaques.
Similar mechanisms damage tubular and glomerular cells in the kidney, leading to reduced glomerular filtration rate and loss of nephrons. In the liver, studies published in Journal of Hepatology have shown that oxidative stress inhibits fatty acid oxidation in hepatocytes, causing lipid accumulation, which can progressively develop into fatty liver disease, cirrhosis, and even hepatocellular carcinoma. As a key organ for cholesterol synthesis and inflammatory factor secretion, liver injury further exacerbates cardiovascular damage.
Together, these pathological processes promote the development of severe cardiovascular outcomes, including atherosclerosis, coronary heart disease, myocardial infarction, heart failure, and sudden cardiac death.