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

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. 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.