Neutrophil-to-high-density lipoprotein cholesterol ratio and prevalent cardiometabolic multimorbidity in older adults: an exploratory cross-sectional analysis.
Chen Y, Ju H, et al. • BMC endocrine disorders • 2026
NHR is closely and positively associated with CMM prevalence in the elderly population, with older adults in the highest NHR quartile having 2.33-fold higher odds of CMM compared to those in the lowest quartile.
Key Findings
Results
Older adults in the highest quartile of NHR had significantly higher odds of cardiometabolic multimorbidity compared to those in the lowest quartile.
Compared with older adults in the lowest quartile (Q1) of NHR, those in the highest quartile (Q4) had 2.33-fold higher odds of CMM (95% CI: 1.56–3.48)
P for trend < 0.001
Analysis was based on multivariable weighted logistic regression
Study included 5,987 older adults from NHANES data
CMM was defined as the coexistence of at least two cardiometabolic diseases (diabetes mellitus, coronary heart disease, and stroke) within the same individual
Results
The relationship between NHR and CMM risk was nonlinear.
Restricted cubic splines (RCS) analysis revealed a nonlinear relationship between NHR and CMM risk
P for non-linearity < 0.0001
RCS was used to model the dose-response relationship across the continuous range of NHR values
Results
The triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, statistically accounted for a portion of the NHR-CMM association in exploratory mediation analysis.
TyG accounted for 23.78% (95% CI: 16.08%–54.60%) of the NHR-CMM association
This was characterized as exploratory mediation analysis
Authors caution that 'given the cross-sectional nature of the present study, these findings should not be interpreted as evidence of temporal or causal mediation'
Results
Uric acid statistically accounted for a portion of the NHR-CMM association in exploratory mediation analysis.
Uric acid accounted for 13.69% (95% CI: 9.31%–56.83%) of the NHR-CMM association
The mediation patterns were described as 'consistent with the potential involvement of insulin resistance and uric acid-related metabolic-inflammatory pathways'
Authors note that 'direct inflammatory mediators were not measured,' limiting causal interpretation
Results
NHR demonstrated modest but statistically higher discriminatory ability for CMM compared to other comparison indices.
ROC (receiver operating characteristic) curve analysis was used to evaluate discriminatory ability
NHR's discriminatory ability was described as 'modest but statistically higher' than comparison indices
Specific AUC values were not reported in the abstract
Methods
The study population consisted of 5,987 older adults drawn from NHANES, analyzed using a cross-sectional design.
Data source was the National Health and Nutrition Examination Survey (NHANES)
Total sample size was 5,987 older adults
Analytical methods included weighted logistic regression, restricted cubic splines, subgroup analyses, exploratory mediation analyses, and ROC curve analysis
Cross-sectional design limits causal or temporal inference
Findings are described as 'association-based and hypothesis-generating'
What This Means
This research examined whether a blood marker called the neutrophil-to-HDL cholesterol ratio (NHR) — which combines a measure of immune cell activity (neutrophils) with levels of 'good' cholesterol (HDL) — is linked to having multiple heart and metabolic diseases at the same time in older adults. Using data from nearly 6,000 older Americans in the NHANES survey, the study found that people with the highest NHR levels were about 2.3 times more likely to have cardiometabolic multimorbidity (meaning two or more conditions such as diabetes, coronary heart disease, or stroke) compared to those with the lowest NHR levels. The relationship was not a simple straight line — risk increased in a more complex, nonlinear pattern as NHR rose.
The study also explored whether two other biological factors — insulin resistance (measured by the TyG index) and uric acid levels — might help explain the link between NHR and having multiple cardiometabolic diseases. Statistically, insulin resistance appeared to account for roughly 24% of the association, and uric acid for about 14%, suggesting these pathways may play a role. However, the authors are careful to note that because this was a cross-sectional study (a snapshot in time rather than a follow-up study), it cannot establish whether NHR causes these diseases or whether these pathways are truly the mechanism — only that the associations exist together.
This research suggests that NHR, a relatively simple and inexpensive marker calculated from routine blood tests, may be useful for identifying older adults at higher risk of having multiple serious cardiometabolic conditions simultaneously. The findings point toward possible involvement of inflammatory and metabolic processes, but further studies tracking people over time would be needed to confirm these relationships and determine whether NHR could be clinically useful for screening or risk prediction in older populations.
Chen Y, Ju H, Zhou Q, Kong X, Zhao X. (2026). Neutrophil-to-high-density lipoprotein cholesterol ratio and prevalent cardiometabolic multimorbidity in older adults: an exploratory cross-sectional analysis.. BMC endocrine disorders. https://doi.org/10.1186/s12902-026-02442-4