Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies

Purpose of Review: The goal of this review is to evaluate the evolving role of triglycerides (TGs) and TG-rich lipoproteins (TRLs) in cardiovascular disease (CVD) risk and prevention. We examine the mechanistic rationale, genetic and epidemiological evidence, and therapeutic potential of targeting TGs in residual risk reduction, particularly in high-risk populations. Recent Findings: Emerging data from Mendelian randomization studies and large clinical cohorts support a causal link between elevated remnant lipoproteins and atherosclerotic CVD, in which apolipoprotein B may be the principal driver. Although traditional triglyceride-lowering agents have produced mixed results on cardiovascular outcomes, emerging therapies—such as ApoC-III and ANGPTL3 inhibitors—show robust lipid-lowering effects, while selective PPAR modulators have thus far not demonstrated cardiovascular benefit. However, outcome data remain limited. Summary: Residual CVD risk persists despite aggressive LDL-C reduction, especially in patients with diabetes, metabolic syndrome, or chronic kidney disease. Selective TG-lowering strategies targeting TRLs—especially those that decrease apolipoprotein B—may provide clinical benefit in high-risk phenotypes. Ongoing trials will clarify whether these promising agents confer meaningful cardiovascular protection and warrant integration into future guidelines.