Molecular Interplay between hypertension and dyslipidemia in cardiovascular pathogenesis: toward precision-based therapeutic strategies

Cardiovascular disease (CVD) remains the foremost cause of global mortality. Hypertension and dyslipidemia, frequently coexisting, exert synergistic effects that substantially elevate CVD risk via interconnected molecular pathways. This review systematically examines the synergistic mechanisms underlying their combined contribution to CVD progression, with a focus on key pathways such as the RAAS/PPAR axis, AMPK/SIRT1 signaling, and NLRP3 inflammasome activation. We highlight how their interplay disrupts endothelial function, aggravates oxidative stress, and promotes chronic inflammation, thereby causing vascular damage and atherosclerosis. Furthermore, we examine emerging targeted therapies, including the combination of RAAS inhibitors with statins, PCSK9 inhibitors, as well as newer agents such as SGLT2 inhibitors and GLP-1 receptor agonists. These approaches represent promising multi-target strategies for improving clinical outcomes. Ultimately, this review underscores the need for a precision medicine framework that addresses the synergistic pathophysiology of hypertension and dyslipidemia, paving the way for personalized, pathway-integrated interventions aimed at restoring metabolic-vascular homeostasis rather than merely treating disease.