High Non-HDL-C/HDL-C Ratio in Adults With Obesity Increases Depression Risk

In adults with obesity, a higher ratio of non-high-density lipoprotein (HDL) to high-density lipoprotein cholesterol (HDL-C) [NHHR] was significantly associated with an increased risk of depression, according to new research published by investigators in Diabetology & Metabolic Syndrome.¹

What is the Non-HDL-C to HDL-C Ratio?

NHHR is rapidly becoming a reliable indicator of metabolic abnormalities. It can offer a more comprehensive lipid outlook as compared with traditional, single markers of irregularities. Investigators have spoken positively of its ability to be an integrative, stable, and easily accessible tool for evaluating cardiovascular risk.^1,2

Numerous investigations have employed NHHR as a tool to evaluate cardiovascular and metabolic risk. Wang et al found in a cohort study that NHHR is a more valuable predictor of new-onset non-alcoholic fatty liver disease than non-HDL-C alone. Meanwhile, authors of a retrospective study of adults in China found that NHHR was closely associated with a greater risk of hypertension and other heart diseases.^3,4

Whether NHHR can be effective in elucidating the relationship between obesity and conditions like depression has yet to be seen. Investigators have established a bidirectional relationship between obesity and depression that involves a constellation of factors, including inflammation, neuroendocrine dysregulation, and behavioral pathways. When NHHR is abnormal, individuals with obesity tend to exhibit greater vulnerability to depression.^1,5

In the current study, the investigators examined the relationship between NHHR and depressive symptoms in adults with obesity, with the expectation that a higher NHHR would make it more likely that depressive symptoms appear. Further, they hypothesized that body mass index (BMI) could potentially service as a mediator of those symptoms. These insights would be able to better inform concurrent treatment and prevention strategies for obesity and depression.¹

Is NHHR Associated With Depression?

The cross-sectional analysis utilized national data from 2013 to 2023, comprising a sample of 13,991 individuals. Depression was determined using the Patient Health Questionnaire-9 (PHQ-9), which is widely used and highly sensitive and specific for depressive disorders. The index includes 9 factors, including diminished interest, fatigue, and concentration difficulties. According to demographic data, the mean age of participants was 52.02 years, with an average NHHR of 2.97 and an overall prevalence of depression at 10.33%.¹

In the unadjusted model, each 1-unit increase in NHHR was associated with a 7% higher risk of depression (odds ratio [OR] = 1.07 [95% CI, 1.03—1.11). Specifically in model 1, which adjusted for demographic variables, each 1-unit increase corresponded to a 12% higher risk of depression (OR = 1.12 [95% CI, 1.07­—1.16]). In model 2, which was fully adjusted, each 1-unit increase was associated with a 5% higher risk of depression (OR = 1.05 [95% CI, 1.01—1.09]). Stronger associations were observed in the unadjusted model and model 1, according to the investigators.¹

A mediation analysis was initiated to elucidate the mediating role of BMI in the association between NHHR and depression. The total effect of NHHR on depression was significant, featuring both a direct and indirect effect via BMI. BMI was shown to partially mediate the association between NHHR and depression, accounting for 15.81% of the total effect.¹

Obesity is only growing more burdensome across the globe. As it increases in prevalence, determining new indicators for its relationship with metabolic conditions is crucial for patient health. Pharmacists can utilize the easy-to-calculate NHHR for patients struggling with dyslipidemia and weight management to get a more comprehensive landscape of their health and provide targeted treatment. Because depression can worsen obesity—and vice versa—calculating a patient’s NHHR early on in counseling efforts can help better inform management strategies for both.¹

“Future studies should further validate these associations in longitudinal cohorts and investigate the underlying mechanisms through which lipid metabolism abnormalities influence depression, in order to inform targeted intervention strategies for high-risk populations,” the study authors wrote in their conclusion.¹

REFERENCES

1. Qiu K, Liu Y, Zhang Y, Hu C, Gu J, Huang Y. BMI partially mediates the association between the non–HDL-C/HDL-C ratio and depression in obese adults. Diabetol Metabol Synd. 2025;17(399). doi.org/10.1186/s13098-025-01971-7

2. Deng S, Qiu Y, Wang Q, et al. The relationship between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and rheumatoid arthritis: a cross-sectional study. Front Nutr. 2025;12:1594218. doi:10.3389/fnut.2025.1594218

3. Wang K, Shan S, Zheng H, et al. Non-HDL-cholesterol to HDL-cholesterol ratio is a better predictor of new-onset non-alcoholic fatty liver disease than non-HDL-cholesterol: a cohort study. Lipids in Health and Disease. 2018;17:196. doi:10.1186/s12944-018-0848-8

4. Halpern L. High ratio of non-HDL cholesterol to HDL cholesterol associated with heightened hypertension, heart disease risk. Pharmacy Times. Published February 27, 2025. Accessed October 24, 2025. https://www.pharmacytimes.com/view/high-ratio-of-non-hdl-cholesterol-to-hdl-cholesterol-associated-with-heightened-hypertension-heart-disease-risk

5. Celik FGH, Simsek MH, Pusuroglu M, Korkmaz U. The relationship among hopelessness, suicide risk, body mass index and eating motivations in major depressive disorder comorbid with obesity: a case-control study. Ann Gen Psychiatry. 2025;24(1):43. doi:10.1186/s12991-025-00580-y