Pan D, Chen PF, Ji SY, Chen TL, Zhang H. Non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol is a predictor for cardiovascular mortality in patients with diabetes mellitus. World J Cardiol 2025; 17(7): 101434 [DOI: 10.4330/wjc.v17.i7.101434]
Corresponding Author of This Article
He Zhang, PhD, Department of Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing 100091, China. zhhe1112@163.com
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Jul 26, 2025; 17(7): 101434 Published online Jul 26, 2025. doi: 10.4330/wjc.v17.i7.101434
Non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol is a predictor for cardiovascular mortality in patients with diabetes mellitus
Deng Pan, Peng-Fei Chen, Si-Yan Ji, Tie-Long Chen, He Zhang
Deng Pan, Department of Cardiology, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou 310007, Zhejiang Province, China
Peng-Fei Chen, He Zhang, Department of Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing 100091, China
Si-Yan Ji, Department of Stomatology, Qiqihar Medical College School, Qiqihar 161000, Heilongjiang Province, China
Tie-Long Chen, Department of Cardiology, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310007, Zhejiang Province, China
Co-corresponding authors: Tie-Long Chen and He Zhang.
Author contributions: Pan D and Ji SY wrote the original manuscript and revised the manuscript; Chen PF conducted the statistical analysis; Chen TL and Zhang H acquired fundings, revised the manuscript, and contributed equally as co-first authors; and all authors read and approved the manuscript.
Supported by Hospital Capability Enhancement Project of Xiyuan Hospital, China Academy of Chinese Medical Sciences, No. XYZX0404-15; and Zhejiang Provincial Medical Association Clinical Medical Research Special Funding Projects, No. 2023ZYC-A13.
Institutional review board statement: The NHANES study was reviewed and approved by the NCHS Research Ethics Review Board.
Informed consent statement: This is a cohort study based on National Health and Nutrition Examination Survey (NHANES) without any intervention. All participants have provided the consent forms according to NHANES official.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets generated and/or analyzed during the current study are available from https://www.cdc.gov/nchs/nhanes/.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: He Zhang, PhD, Department of Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, No. 1 Xiyuan Playground, Haidian District, Beijing 100091, China. zhhe1112@163.com
Received: September 16, 2024 Revised: December 5, 2024 Accepted: March 28, 2025 Published online: July 26, 2025 Processing time: 311 Days and 6.3 Hours
Abstract
BACKGROUND
The non-high-density lipoprotein cholesterol (non-HDL-C)/HDL-C ratio (NHHR) is linked to cardiovascular event risk, but its prognostic value in diabetes mellitus (DM) patients remains unclear.
AIM
To explore the association of NHHR and cardiovascular mortality in patients with DM and generate predictive model.
METHODS
This cohort study analyzed data from 8425 DM patients in National Health and Nutrition Examination Survey. NHHR was calculated as (total cholesterol - HDL-C)/HDL-C. Cardiovascular mortality was determined via the National Death Index. Feature selection was performed using the Boruta algorithm and least absolute shrinkage and selection operator regression, followed by Cox proportional hazards models to evaluate NHHR’s relationship with cardiovascular mortality. Stratified and sensitivity analyses assessed the findings’ robustness. A nomogram was developed to predict cardiovascular mortality, with model performance evaluated using receiver operating characteristic curves and calibration plots.
RESULTS
Over an average follow-up of 94.2 months, 671 cardiovascular deaths (8.0%) occurred. Six key features including age, education, ethnicity, poverty-income ratio, history of heart failure, and NHHR, were selected. A non-linear association was found, with the highest NHHR quartile showing a 39% higher risk of cardiovascular death compared to the lowest quartile (Q4, hazard ratio: 1.39, 95% confidence interval: 1.11-1.73). Stratified analyses confirmed the increased risk across all subgroups. Sensitivity analyses supported the stability of the results. The nomogram for predicting cardiovascular mortality demonstrated high accuracy.
CONCLUSION
Elevated NHHR is associated with increased cardiovascular mortality risk in DM patients. NHHR could be a valuable prognostic marker, aiding in identifying high-risk patients and guiding targeted lipid management strategies.
Core Tip: This study investigates the association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and cardiovascular mortality in patients with diabetes mellitus (DM). Analysis of 8425 DM patients from the National Health and Nutrition Examination Survey revealed a non-linear relationship between NHHR and cardiovascular mortality. Patients in the highest NHHR quartile (≥ 4.01) had a 39% higher risk of cardiovascular death compared to the lowest quartile. A predictive model for 5, 8, and 10-year cardiovascular mortality was developed, showing high accuracy. These findings suggest NHHR as a valuable prognostic marker for cardiovascular risk in DM patients.
