Abstract Background The association between triglycerides (TG), HDL cholesterol (HDL-C) and the prognosis of cardiovascular disease has not been established. Purpose The aim of this study was to elucidate the relationships between the combination of TG and HDL-C levels and the risk of a major adverse cardiac and cerebral events (MACCE) and to verify the usefulness of TG and HDL-C as a risk stratification factor using the Clinical Deep Data Accumulation System (CLIDAS) database. Methods CLIDAS is a database that accumlates electronic medical records in seven tertiary hospitals in Japan including patient characteristics, medications, laboratory test, physiological test, cardiac catheterization, and PCI treatment. We analyzed 9,690 patients who underwent PCI between April 2014 and March 2020. These patients were stratified into the acute coronary syndrome (ACS) group (N=4,135; 43%) and the chronic coronary syndrome (CCS) group (N=5,555; 57%). Furthermore, 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, and compared for major adverse cardiac and cerebrovascular events (MACCE). The median follow-up duration was 2.5 years. Results The patients with high TG/low HDL-C showed the highest event rates in myocardial infarction among the ACS group. The hazard ratio for high TG/low HDL-C versus low TG/high HDL-C was 1.76 (95% CI, 1.08 to 2.87, P < 0.05) after adjustment for age, sex, eGFR, and mean LDL-C levels, while we observed no risk stratification by the combination of TG and HDL-C levels in the CCS group (Figure 1). In contrast, the patients with low TG levels showed the paradoxically higher event rates of MACCE in both the ACS and CCS groups, as well as cardiovascular death in the CCS group, compared to those with high TG levels (Figure 2). The hazard ratio for low TG/low HDL-C versus high TG/low HDL-C was 3.21 (95% CI, 1.44 to 7.13, P <0.005), and the hazard ratio for low TG/high HDL-C versus high TG/high HDL-C was 2.23 (95% CI, 1.03 to 4.84, P < 0.05) in the CCS group after adjustment for age, sex, eGFR, and mean LDL-C levels. Conclusion In the CLIDAS database, while high TG and low HDL-C levels stratified the risk of ACS, low TG levels showed worsening prognosis for CV death, suggesting a "Lipid paradox" in the real world.Figure 1Figure 2