What does this research mean for the field?

Triglyceride levels exhibited a U-shaped association with major adverse cardiac and cerebrovascular events in Japanese patients with acute coronary syndrome. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

What question did this study set out to answer?

To clarify the relationship between triglyceride and HDL cholesterol levels with major adverse cardiovascular events and heart failure hospitalization.

February 8, 2026

Triglyceride levels show a U-shaped association with cardiovascular events: insights from the CLIDAS database on the lipid paradox among Japanese patients with acute coronary syndrome

Key Result

Triglyceride levels have a U-shaped association with MACCE and HF hospitalization in ACS patients, with both high TG/low HDL-C and low TG/low HDL-C groups showing highest events.

Key Points

To clarify the relationship between triglyceride and HDL cholesterol levels with major adverse cardiovascular events and heart failure hospitalization.
Analyzed 3,608 acute coronary syndrome patients from the CLIDAS database.
Divided participants into four groups based on triglyceride and HDL cholesterol levels.
Compared event rates of MACCE and HF hospitalization across groups.
Conducted Cox proportional hazards analysis to evaluate associations between triglycerides, HDL cholesterol, and event rates.
Low HDL-C was linked to higher MACCE and heart failure hospitalization rates than high HDL-C.
Both high TG/low HDL-C and low TG/low HDL-C groups had the highest event rates.
A U-shaped relationship was found between triglyceride levels and event rates in Cox analysis.
The low TG/low HDL-C group experienced more heart failure events but fewer myocardial infarctions than the high TG/low HDL-C group.

Structured PICO

Does the combination of triglyceride and HDL-C levels predict the risk of MACCE and HF hospitalization in Japanese ACS patients undergoing PCI?

Population

3,608 Japanese patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) between April 2014 and March 2020 across seven tertiary hospitals.

Intervention

Stratification into four groups based on mean serum triglyceride (TG) levels (cutoff 175 mg/dL) and HDL-C levels (cutoff 40 mg/dL): high TG/low HDL-C, low TG/low HDL-C, high TG/high HDL-C, and low TG/high HDL-C.

Comparator

Comparison among the four TG/HDL-C groups.

Outcome

Major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) hospitalization.composite

Triglyceride levels exhibit a U-shaped association with MACCE and HF hospitalization in Japanese ACS patients, highlighting a 'lipid paradox' where low TG/low HDL-C patients have high event rates potentially driven by underlying frailty or heart failure.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Background The association between triglycerides (TG), HDL cholesterol (HDL-C), and the prognosis of cardiovascular disease remains unclear. Purpose The aim of this study was to elucidate the relationship between the combination of TG and HDL-C levels and the risk of major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) hospitalization. Additionally, we investigated the potential of TG and HDL-C as risk stratification factors using the Clinical Deep Data Accumulation System (CLIDAS) database. Methods CLIDAS is a database that accumulates electronic medical records in seven tertiary hospitals in Japan including patient characteristics, medications, laboratory test, physiological test, cardiac catheterization, and PCI treatment. We analyzed 3,608 acute coronary syndrome (ACS) patients who underwent PCI between April 2014 and March 2020. Patients were divided into four groups based on mean serum TG levels (175 mg/dL) and HDL-C levels (40 mg/dL) as cutoff values: high TG/low HDL-C, low TG/low HDL-C, high TG/high HDL-C, and low TG/high HDL-C. These groups were then compared for major adverse cardiac and cerebrovascular events (MACCE) and HF hospitalization. The median follow-up duration was 2.5 years. Results Low HDL-C was associated with a higher event rate of MACCE and HF hospitalization than high HDL-C. Notably, both patients with high TG/low HDL-C and those with low TG/low HDL-C exhibited the highest event rates in MACCE and HF hospitalization (log-rank P = 0.0091, Figure 1). Cox proportional hazards analysis revealed a U-shaped relationship between hazard ratio of the event rates and mean TG levels, whereas HDL-C levels showed an inverse correlation with event risk (Figure 2). Subgroup analysis showed that the patients with high TG/low HDL-C showed the highest event rates in myocardial infarction, while those with low TG/low HDL-C showed the highest event rates of cardiovascular death. The low TG/low HDL-C group experienced more HF-related events but fewer myocardial infarctions than the high TG/low HDL-C group among causes of cardiovascular death. Baseline characteristics showed that the low TG/low HDL-C group included a higher proportion of older patients, those with lower body mass index (BMI), and/or those with elevated brain natriuretic peptide (BNP) levels. Conclusion In the CLIDAS database, TG levels showed a U-shaped association with MACCE and HF hospitalization in Japanese patients with ACS. The presence of frailty and/or heart failure in the low TG/low HDL-C group may contribute to the so-called "lipid paradox" in real-world clinical settings.Figure 1 Figure 2

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