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

Pauline C E Schuitema; Frank L J Visseren; Børge G Nordestgaard; Martin Teraa; Manon G van der Meer; Ynte M Ruigrok; N Charlotte Onland-Moret; Charlotte Koopal; UCC-SMART Study Group

doi:10.1016/j.atherosclerosis.2025.120411

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. 2025 Jun 14:120411. doi: 10.1016/j.atherosclerosis.2025.120411. Online ahead of print.

Authors

Pauline C E Schuitema¹, Frank L J Visseren², Børge G Nordestgaard³, Martin Teraa⁴, Manon G van der Meer⁵, Ynte M Ruigrok⁶, N Charlotte Onland-Moret⁷, Charlotte Koopal¹; UCC-SMART Study Group

Affiliations

¹ Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
² Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: F.L.J.Visseren@umcutrecht.nl.
³ Department of Clinical Biochemistry and the Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
⁴ Department of Vascular Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁵ Department of Cardiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁶ Department of Neurology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁷ Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.

PMID: 40579281
DOI: 10.1016/j.atherosclerosis.2025.120411

Abstract

Background and aims: Despite optimal management of low-density lipoprotein cholesterol (LDL-C), substantial residual cardiovascular risk persists in patients with cardiovascular disease (CVD), which may be attributed to other atherogenic lipoproteins. We tested the hypotheses that elevated triglycerides (TGs) are related to higher residual CVD and mortality risk in patients with established CVD, and that such relationships depend on guideline-recommended lipid target achievement, high-density lipoprotein cholesterol (HDL-C) levels, and intensity of lipid-lowering therapy (LLT).

Methods: In a prospective cohort study of 9436 patients with manifest CVD, the relationships between log-transformed TG levels and recurrent cardiovascular events and all-cause mortality were analyzed overall using Cox regression models. Subsequently, analyses were stratified by achievement of low-density lipoprotein cholesterol (LDL-C) and non-HDL-C treatment goals, HDL-C levels, and LLT intensity.

Results: During a median follow-up of 9.0 years (IQR 4.5-14.1), 2075 recurrent cardiovascular events, 736 myocardial infarctions, 586 strokes, 1231 cardiovascular deaths, and 2729 all-cause deaths occurred. Per 1-unit higher log-TG level, the hazard ratio was 1.17 (95 % CI: 1.07-1.28) for recurrent cardiovascular events, 1.34 (1.16-1.56) for myocardial infarction, 1.10 (0.92-1.30) for stroke, 1.23 (1.09-1.38) for cardiovascular mortality, and 1.12 (1.03-1.21) for all-cause mortality. These hazard ratios did not depend on achievement of LDL-C and non-HDL-C treatment goals, HDL-C levels, or LLT intensity (all p for interaction ≥0.05).

Conclusions: Elevated TGs are related to higher residual CVD and mortality risk in patients with established CVD. These relationships were unrelated to guideline-recommended lipid target achievement, HDL-C levels, and LLT intensity.

Keywords: Cardiovascular disease; Lipid targets; Lipid-lowering therapy; Residual cardiovascular risk; Secondary prevention; Triglycerides.