Liu Yu, Fan Zheng, Ren Hongmei, Zheng Cuixia
Department of Respiratory and Critical Care Medicine, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Med (Lausanne). 2025 Apr 3;12:1533744. doi: 10.3389/fmed.2025.1533744. eCollection 2025.
The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) plays a potential role in metabolic and cardiovascular diseases. However, its association with chronic obstructive pulmonary disease (COPD) is not well-defined. Here, we aim to investigate the potential association of NHHR with both the prevalence of COPD and all-cause mortality among individuals with COPD.
This population-based NHANES (2007-2016) study utilized weighted statistical analyses. Multivariable logistic regression assessed the NHHR-COPD prevalence association, with restricted cubic spline (RCS) testing for non-linearity. The association between NHHR and all-cause mortality in COPD was evaluated using Cox proportional hazards models and Kaplan-Meier, with RCS testing for non-linearity. Subgroup and sensitivity analyses confirmed the findings' reliability.
This study included 6349 participants, of whom 1271 were diagnosed with COPD. Participants in the highest NHHR tertile demonstrated 62% higher odds of COPD prevalence compared to those in the lowest tertile (OR = 1.62, 95% CI:1.11-2.39, = 0.017). Results from RCS analysis indicated a nonlinear relationship between NHHR and the prevalence of COPD ( for nonlinear = 0.007), with the curve demonstrating an inverted L-shape. Over an average follow-up period of 93 months, 320 participants with COPD died. In the weighted Kaplan-Meier survival analysis, participants with COPD in the lower NHHR tertile demonstrated greater cumulative probability of all-cause mortality compared to higher tertiles ( < 0.001). Weighted multivariable Cox regression models revealed an inverse association between NHHR levels and COPD all-cause mortality, with the highest NHHR tertile showing 11% lower likelihood of COPD all-cause mortality relative to the lowest tertile (HR = 0.89, 95% CI:0.80-0.99, = 0.027). In addition, RCS analysis demonstrated a significant negative linear association between NHHR levels and all-cause mortality in COPD patients ( for nonlinear = 0.081). Subgroup and sensitivity analyses further confirmed the associations of NHHR on both morbidity and all-cause mortality.
Higher NHHR levels were associated with increased COPD prevalence yet inversely correlated with all-cause mortality in COPD patients. These paradoxical associations underscore the need for COPD-specific lipid management strategies that balance disease progression and mortality risks.
非高密度脂蛋白胆固醇与高密度脂蛋白胆固醇比值（NHHR）在代谢性疾病和心血管疾病中发挥着潜在作用。然而，其与慢性阻塞性肺疾病（COPD）的关联尚不明确。在此，我们旨在研究NHHR与COPD患病率以及COPD患者全因死亡率之间的潜在关联。
这项基于人群的美国国家健康与营养检查调查（2007 - 2016年）研究采用加权统计分析。多变量逻辑回归评估NHHR与COPD患病率的关联，并使用受限立方样条（RCS）检验非线性关系。使用Cox比例风险模型和Kaplan - Meier法评估NHHR与COPD患者全因死亡率之间的关联，同样采用RCS检验非线性关系。亚组分析和敏感性分析证实了研究结果的可靠性。
本研究纳入6349名参与者，其中1271人被诊断患有COPD。与处于最低三分位数的参与者相比，处于最高NHHR三分位数的参与者患COPD的几率高62%（比值比[OR]=1.62，95%置信区间[CI]：1.11 - 2.39，P = 0.017）。RCS分析结果表明NHHR与COPD患病率之间存在非线性关系（非线性P = 0.007），曲线呈倒L形。在平均93个月的随访期内，320名COPD患者死亡。在加权Kaplan - Meier生存分析中，与较高三分位数的COPD患者相比，处于较低NHHR三分位数的患者全因死亡累积概率更高（P < 0.001）。加权多变量Cox回归模型显示NHHR水平与COPD全因死亡率呈负相关，与最低三分位数相比，最高NHHR三分位数的COPD患者全因死亡可能性低11%（风险比[HR]=0.89，95% CI：0.80 - 0.99，P = 0.027）。此外，RCS分析表明NHHR水平与COPD患者全因死亡率之间存在显著的负线性关联（非线性P = 0.081）。亚组分析和敏感性分析进一步证实了NHHR与发病率和全因死亡率之间的关联。
较高的NHHR水平与COPD患病率增加相关，但与COPD患者的全因死亡率呈负相关。这些矛盾的关联凸显了制定特定于COPD的脂质管理策略的必要性，以平衡疾病进展和死亡风险。
