The association between Glycated Hemoglobin to High Density Lipoprotein Cholesterol Ratio and risk of cardiovascular diseases caused death among adult cancer survivors: evidence from NHANES 1999-2018.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.