Cardiometabolic Risks: Cellular and Molecular Mechanisms

Cardiometabolic diseases, including ischemic heart disease, hypertensive heart disease, and associated vascular conditions, have experienced a sharp global increase in prevalence and mortality over recent decades. According to the World Heart Federation, the global death toll from cardiovascular diseases grew from 12 million in 1990 to 20.5 million in 2021. The development of cardiometabolic diseases such as hypertension, type 2 diabetes, obesity, and vascular disorders is driven by a complex interplay of risk factors. These include oxidative stress, chronic inflammation, imbalances in blood glucose and lipid levels, formation of lipid peroxides, increased intima-media thickness (IMT), subclinical atherosclerosis, coronary artery calcification, arterial narrowing, the formation of vulnerable plaques, and activation of platelet and coagulation pathways. These risk factors contribute to metabolic disorders by promoting insulin resistance, endothelial dysfunction, and the progression of atherosclerosis. Despite this understanding, routine annual checkups often fail to prioritize early risk detection or the development of preventive and management strategies. Instead, these checkups typically focus on diagnosing existing metabolic conditions and managing them to prevent acute vascular events. However, the South Asian Society on Atherosclerosis and Thrombosis has been actively promoting global education and the development of preventive strategies. Recent research advances underscore the importance of addressing oxidative stress, inflammation, and lipid oxidation to slow disease progression. Innovative therapeutic approaches, including statins, small-interfering RNA (siRNA), non-coding RNA (ncRNA) therapies, and gene-editing tools like CRISPR/Cas9, have shown considerable promise in lowering cholesterol and lipoprotein(a) levels, lowering risks associated with type-2 diabetes, stabilizing arterial plaques, and reducing overall cardiovascular risk. Additionally, breakthroughs in mRNA vaccines and computational genomics emphasize the potential of precision medicine in tackling chronic diseases. This overview highlights key findings on the roles of oxidative stress, inflammation, atherosclerosis, platelet-vessel wall interactions, and acute vascular occlusion in the development and progress of cardiometabolic diseases. Major clinical trials indicate that addressing a few modifiable risk factors can significantly reduce premature deaths from cardiovascular diseases. Nevertheless, managing cardiometabolic diseases on a population scale remains a formidable challenge. Enhanced preventive measures, better diagnostic tools, and widespread education are critical. Collaborative efforts involving governments, healthcare systems, professional organizations, and communities are essential to alleviating the societal burden of these conditions and improving health outcomes globally. This, in turn, can improve health outcomes, particularly in low-and middle-income countries where healthcare infrastructure and resources are often limited.