Baseline and longitudinal patterns of Non-HDL-C to HDL-C ratio (NHHR) and major adverse cardiovascular events in peripheral artery disease

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is an innovative lipid parameter for atherosclerosis risk, yet its association with major adverse cardiovascular events (MACE) in peripheral artery disease (PAD) patients remains unclear. We retrospectively analyzed 13,224 PAD patients in Hong Kong, assessing baseline NHHR and longitudinal NHHR trajectories as predictors of MACE using spline models, latent class growth modeling, and Cox proportional hazards models. Over a median follow-up of 3.4 years, a U-shaped relationship emerged between baseline NHHR and MACE risk. Patients in the highest quintile of NHHR (Q5) had a significantly increased risk of MACE (HR = 1.16, 95% CI: 1.07-1.25, P < 0.001), as did those in the lowest quintile (Q1) (HR = 1.17, 95% CI: 1.08-1.27, P < 0.001), compared with the reference group. Among five NHHR trajectories, moderate-high-stable (HR = 1.17 [95% CI: 1.04-1.32], P < 0.001) and high-stable groups (HR = 1.35 [95% CI: 1.14-1.60], P < 0.001) showed higher risk, whereas the declining group had no increased risk (HR = 1.04 [95% CI: 0.88-1.23], P = 0.356). High and low baseline NHHR, as well as persistently elevated trajectories, were associated with higher MACE risk in PAD, whereas declining trajectories normalized this risk. NHHR may serve as a useful marker for cardiovascular risk stratification in PAD patients.