Integrative cardiovascular disease therapy: Linoleic acid restriction, enhanced external counterpulsation, and emerging nanotherapies.

Abstract

Cardiovascular disease remains the leading global cause of mortality, projected to increase by 73.4% from 2025 to 2050 despite declining age-standardized rates. Contemporary interventions, such as percutaneous coronary intervention and statins, reduce major adverse cardiovascular events (MACE) by 25%-30%, yet a 20% five-year MACE risk persists in high-risk cohorts. These approaches, historically focused on luminal stenosis, fail to address systemic atherogenesis drivers like endothelial dysfunction and inflammation. Specifically, dietary linoleic acid restriction (< 5 g/day) reduces oxidized low-density lipoprotein by approximately 15% by limiting peroxidation-prone bisallylic bonds, mitigating arterial inflammation, a key atherogenic trigger. Enhanced external counterpulsation, through pulsatile shear stress, enhances nitric oxide-mediated coronary perfusion, alleviating angina in approximately 70% of refractory cases unresponsive to revascularization. Nanoparticle-facilitated chelation targets atherosclerotic plaques with precision, reducing calcium content by up to 30% in preclinical models, offering a novel avenue for lesion reversal. These innovations collectively address residual risk by tackling root causes, oxidative stress, endothelial dysfunction, and plaque instability, potentially halving MACE rates with widespread adoption. Despite promising preliminary data, gaps remain in long-term safety and scalability. Robust clinical trials are needed to validate these approaches, which collectively aim to transform cardiovascular disease management by prioritizing prevention and vascular restoration, potentially reducing coronary events to a public health rarity.