Key result
Baseline NHHR ≥5 was associated with an increased risk of MACE in patients with peripheral artery disease (HR 1.44; 95% CI 1.30-1.59; P<0.001).
Why the study?
The association between the non-HDL-C to HDL-C ratio (NHHR) and major adverse cardiovascular events in patients with peripheral artery disease remains underexplored.
Does the baseline level and longitudinal trajectory of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) impact the risk of MACE in patients with peripheral artery disease?
Cohort (n=13,224)
Does the baseline level and longitudinal trajectory of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) impact the risk of MACE in patients with peripheral artery disease?
Both high and low baseline NHHR, as well as persistently high NHHR trajectories, are associated with increased MACE risk in PAD patients, while declining trajectories normalize this risk.
NHHR extremes may stratify MACE risk in PAD; hypothesis-generating and should not yet change practice.
Background The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and major adverse cardiovascular events (MACE) in patients with peripheral artery disease (PAD) remains underexplored. Purpose We aimed to examine whether NHHR levels and their trajectories impact the risk of MACE, including all-cause death, non-fatal stroke, and non-fatal myocardial infarction, and to what extent optimal lipid control benefits patients at risk of cardiovascular outcomes. Methods A territory-wide retrospective cohort of patients with PAD from 2003–2023 was identified. Spline models were used to evaluate the association between baseline NHHR and MACE. Latent class growth modeling (LCGM) identified NHHR trajectories during the follow-up period after PAD diagnosis. Cox proportional hazards models were used to quantify association between both baseline NHHR and NHHR trajectories with MACE. Results Among 13,224 patients, with a median follow-up of 3.4 years, a U-shaped association was observed between baseline NHHR and MACE (Figure 1A). The risk of MACE was significantly higher in patients with NHHR ≥5 (HR = 1.44 [95% CI: 1.30–1.59], P < 0.001) and NHHR <1 (HR = 1.37 [95% CI: 1.17–1.59], P = 0.002)(Figure 2). Furthermore, LCGM identified five distinct NHHR trajectory groups(Figure 1B). Compared to the optimal-stable NHHR group, patients with higher NHHR levels exhibited proportionally higher risk of MACE, in the moderate-high-stable group (HR = 1.19 [95% CI: 1.06–1.34], P = 0.003) and high-stable group (HR = 1.28 [95% CI: 1.08–1.51], P = 0.04). Notably, decline of NHHR from high to optimal showed normalization of MACE risk (HR = 1.02 [95% CI: 0.87–1.20], P = 0.782)(Figure 2). Conclusions Both high and low baseline NHHR were associated with increased risk of MACE in PAD patients. Persistently high NHHR trajectory further elevated MACE risk, whereas declining trajectory was associated with normalization of risk. Longitudinal NHHR monitoring may enhance risk stratification and inform treatment strategies to optimize cardiovascular outcomes.
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Zhang et al. (2025) conducted a cohort in Peripheral artery disease (PAD) (n=13,224). Non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) vs. Optimal NHHR levels was evaluated on Major adverse cardiovascular events (MACE), including all-cause death, non-fatal stroke, and non-fatal myocardial infarction (HR 1.44, 95% CI 1.30-1.59, p=<0.001). Baseline NHHR ≥5 was associated with an increased risk of MACE in patients with peripheral artery disease (HR 1.44; 95% CI 1.30-1.59; P<0.001).
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