High Triglycerides Drive Residual Cardiovascular Risk Despite Optimal Lipid-Lowering Therapy: Study Shows

"Elevated triglyceride levels strongly predicted higher residual risk in patients with established CVD. Each 1-unit increase in log-TG was linked to greater risk of myocardial infarction (HR 1.34), recurrent cardiovascular events (HR 1.17), cardiovascular mortality (HR 1.23), and a 12% rise in all-cause mortality—independent of LDL-C, non-HDL-C target achievement, HDL-C levels, or lipid-lowering therapy intensity," the researchers reported.

While low-density lipoprotein cholesterol (LDL-C) management is a central pillar of CVD treatment, many patients continue to experience residual cardiovascular risk even after reaching guideline-recommended LDL-C levels. The research team investigated whether elevated triglycerides contribute to this persistent risk and whether this risk is influenced by LDL-C and non-HDL-C target achievement, high-density lipoprotein cholesterol (HDL-C) levels, or the intensity of lipid-lowering therapy (LLT).

The prospective cohort study included 9,436 individuals with established CVD. Researchers used Cox regression models to evaluate the relationship between triglyceride levels and the incidence of cardiovascular events and mortality over a median follow-up period of 9 years (interquartile range: 4.5 to 14.1 years).

The study led to the following findings:

• Each one-unit rise in log-transformed triglyceride levels was associated with a 17% higher risk of recurrent cardiovascular events.
• A 34% higher risk of myocardial infarction was linked to elevated triglyceride levels.
• Triglyceride elevation corresponded to a 23% increase in cardiovascular mortality.
• All-cause mortality increased by 12% with higher triglyceride levels.
• These risks remained consistent regardless of LDL-C or non-HDL-C target achievement, HDL-C levels, or lipid-lowering therapy intensity.
• During the study, there were 2,075 recurrent cardiovascular events, 736 myocardial infarctions, 586 strokes, 1,231 cardiovascular deaths, and 2,729 all-cause deaths.
• No significant association was found between elevated triglycerides and stroke risk alone.

According to the authors, these findings emphasize the importance of monitoring and managing triglyceride levels in patients with CVD, alongside traditional lipid targets like LDL-C. The research highlights the potential benefit of incorporating targeted interventions—such as lifestyle changes and dietary adjustments—into secondary prevention plans to address the residual cardiovascular risk associated with elevated TGs.

The study concludes that triglyceride management should be prioritized as part of comprehensive cardiovascular care to help mitigate ongoing risk in patients already receiving intensive lipid-lowering therapy.

Reference:

Schuitema, P. C., Visseren, F. L., Nordestgaard, B. G., Teraa, M., Van der Meer, M. G., Ruigrok, Y. M., Onland-Moret, N. C., & Koopal, C. (2025). Elevated triglycerides are related to higher residual cardiovascular disease and mortality risk independent of lipid targets and intensity of lipid-lowering therapy in patients with established cardiovascular disease. Atherosclerosis, 120411. https://doi.org/10.1016/j.atherosclerosis.2025.120411