Both Low and High NHHR Levels Associated with Increased Mortality in Hypertension: Study Finds

"NHHR levels below 2.32 and above 2.65 were associated with increased all-cause and cardiovascular mortality. Machine learning validated its predictive significance, highlighting the importance of NHHR in hypertension risk assessment," the researchers reported in Scientific Reports.

Hypertension is a key risk factor for cardiovascular disease, and disruptions in lipid balance further exacerbate adverse outcomes. Traditionally, cholesterol levels have been used to assess cardiovascular risk. However, emerging evidence suggests that the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio may serve as a more comprehensive indicator of lipid metabolism and overall cardiovascular health. NHHR reflects the delicate balance between pro-atherogenic and anti-atherogenic lipoproteins, offering a nuanced understanding of lipid-related risks in individuals with hypertension.

Against the above background, Xiaozhou Su, Department of Cardiology, Minzu Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China, and colleagues aimed to investigate the association between NHHR and mortality in individuals with hypertension.

For this purpose, the researchers analyzed data from 17,075 hypertensive adults in the National Health and Nutrition Examination Survey (NHANES). They employed multivariate Cox regression and restricted cubic splines to examine the association between NHHR and mortality. A segmented Cox model was used to assess threshold effects, while sensitivity analyses ensured the robustness of the findings. Additionally, machine learning algorithms were utilized to develop a predictive model, further strengthening the study's conclusions.

The following were the key findings of the study:

• During a median follow-up of 84 months, 3,625 deaths were recorded.
• A U-shaped relationship was identified between NHHR and both all-cause and cardiovascular mortality.
• Threshold values of NHHR were established at 2.32 and 2.65.
• NHHR below 2.32 showed a negative association with mortality, while values above 2.65 were positively associated.
• NHHR was a key variable in the prediction model.
• The random survival forest (RSF) algorithm demonstrated superior performance in predicting outcomes.

In their analysis of 17,075 hypertensive individuals from the NHANES database, the researchers identified a U-shaped association between NHHR and all-cause mortality. They found that NHHR levels below 2.32 were linked to a lower mortality risk, whereas levels exceeding 2.32—particularly above the cardiovascular mortality threshold of 2.65—were associated with an increased risk.

Based on these findings, the researchers suggest that NHHR could serve as a valuable prognostic marker in hypertension management, with both low and high levels indicating higher mortality risk. They emphasize the need for further research to explore the underlying mechanisms, such as lipid metabolism and endothelial dysfunction, and to assess the prognostic significance of NHHR changes in long-term studies.

Reference:

Su, X., Rao, H., Zhao, C., Wu, J., Zhang, X., & Li, D. (2025). Association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and mortality among hypertension patients. Scientific Reports, 15(1), 1-15. https://doi.org/10.1038/s41598-025-88539-7