Sun Fan, Yu Xia-Jing, Huang Xiao-Hong, Lin Jin, Zhang Jing, Xu Yan-Mei, Yang Wei-Ming, Wang Xiao-Zhong
Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
Lipids Health Dis. 2025 Apr 23;24(1):149. doi: 10.1186/s12944-025-02566-x.
The population of cancer survivors is growing markedly, facing an elevated risk of overall mortality as well as death from cardiovascular diseases (CVDs). Uncovering biomarkers that associated with CVDs among cancer survivors appears to be vital.
We collected data from NHANES (1999-2018), focusing on cancer survivors with comprehensive Glycated Hemoglobin (GH), High Density Lipoprotein Cholesterol (HDL-C), CVDs history and survival follow-up information. We first executed test for Proportional Hazards assumptions among the variables, paving the way for constructing the COX proportional hazards model. By stratifying participants by age, we explored the association between GH/HDL-C levels and the CVDs-caused mortality risk across various age segments. Restricted cubic spline (RCS) curves were employed to detect any potential non-linear associations. When non-linear associations were identified, we proceeded with segmented analyses based on reference values to better understand the association between GH/HDL-C and the risk of CVDs-related mortality among cancer survivors. To further affirm the robustness of our findings, subgroup and sensitivity analyses were conducted.
A total of 3,244 eligible participants were included in this study. The GH/HDL-C levels in cancer survivors died from CVDs were markedly higher than those who survived the follow-up period. According to the results from the Proportional Hazards assumptions test, the endpoint for CVDs mortality was established at 168 months, and the subjects were classified into three age groups: <60 years, between 60 and 74 years, and ≥ 75 years. For the young cohort (< 60 years), there was no significant association between GH/HDL-C levels and CVDs mortality. However, in the 60 ~ 74 age group, a linear association was noted, with higher GH/HDL-C levels indicating a greater CVDs-related mortality risk. For cancer survivors aged 75 and older, the association appeared nonlinear, resembling a U-shaped curve, where high GH/HDL-C levels were associated with higher mortality risk above the certain reference point (4.25mmol/L^-1), while lower levels were associated with reduced risk or no significant impact.
The study highlighted that in cancer survivors, the GH/HDL-C is significantly associated with the risk of CVDs mortality. Those between 60 and 74 years old showed a straightforward increase in CVD death risk with higher GH/HDL-C levels. In individuals aged 75 and older, the association was more complex, exhibiting a non-linear U-shaped trend.
癌症幸存者的数量正在显著增长，他们面临着全因死亡率以及心血管疾病（CVD）死亡风险升高的问题。在癌症幸存者中发现与心血管疾病相关的生物标志物似乎至关重要。
我们从美国国家健康与营养检查调查（NHANES，1999 - 2018年）收集数据，重点关注具有全面糖化血红蛋白（GH）、高密度脂蛋白胆固醇（HDL-C）、心血管疾病病史和生存随访信息的癌症幸存者。我们首先对变量进行比例风险假设检验，为构建COX比例风险模型铺平道路。通过按年龄对参与者进行分层，我们探讨了GH/HDL-C水平与不同年龄组中心血管疾病导致的死亡风险之间的关联。使用受限立方样条（RCS）曲线来检测任何潜在的非线性关联。当发现非线性关联时，我们基于参考值进行分段分析，以更好地理解GH/HDL-C与癌症幸存者中心血管疾病相关死亡风险之间的关联。为了进一步确认我们研究结果的稳健性，我们进行了亚组分析和敏感性分析。
本研究共纳入3244名符合条件的参与者。死于心血管疾病的癌症幸存者的GH/HDL-C水平明显高于随访期存活者。根据比例风险假设检验的结果，确定心血管疾病死亡率的终点为168个月，并将受试者分为三个年龄组：<60岁、60至74岁和≥75岁。对于年轻队列（<60岁），GH/HDL-C水平与心血管疾病死亡率之间无显著关联。然而，在60至74岁年龄组中，观察到线性关联，即GH/HDL-C水平越高，心血管疾病相关死亡风险越大。对于75岁及以上的癌症幸存者，这种关联呈现非线性，类似于U形曲线，即高于特定参考点（4.25mmol/L^-1）时，高GH/HDL-C水平与较高的死亡风险相关，而较低水平与风险降低或无显著影响相关。
该研究强调，在癌症幸存者中，GH/HDL-C与心血管疾病死亡风险显著相关。60至74岁的人群中，随着GH/HDL-C水平升高，心血管疾病死亡风险直接增加。在75岁及以上的个体中，这种关联更为复杂呈现非线性U形趋势。
