# High-density lipoprotein-related inflammatory markers and their association with all-cause and cardiovascular mortality in an ageing population: findings from a prospective cohort study based on NHANES data

## TL;DR

This study finds that higher neutrophil-to-HDL ratios are linked to increased mortality in older adults, while higher lymphocyte-to-HDL ratios are linked to lower mortality.

## Contribution

The study identifies novel associations between HDL-related inflammatory markers and mortality in an ageing population using NHANES data.

## Key findings

- Higher neutrophil/HDL ratio (NHR) was linearly associated with increased all-cause and cardiovascular mortality.
- Higher lymphocyte/HDL ratio (LHR) showed a non-linear inverse association with mortality in the highest tertile.
- Monocyte/HDL ratio (MHR) and platelet/HDL ratio (PHR) showed no significant mortality associations.

## Abstract

High-density lipoprotein cholesterol (HDL-C)-related inflammatory markers are increasingly being recognised as indicators of inflammation and metabolism associated with cardiovascular events. Here, we examined their associations with all-cause and cardiovascular disease (CVD) mortality in the ageing population.

We retrieved data on patients aged ≥60 years from the National Health and Nutrition Examination Survey (2001–2018). We ascertained exposures (neutrophil/HDL ratio (NHR), lymphocyte/HDL ratio (LHR), monocyte/HDL ratio (MHR), platelet/HDL ratio (PHR)) and covariates at baseline and cross-linked them to mortality outcomes via the National Death Index. We tested for associations using survey-weighted Cox proportional hazards models, with restricted cubic splines assessing nonlinearity and C-statistics evaluating discrimination.

We included 5700 patients in our sample. A total of 1817 deaths occurred over a mean follow-up of 7.51 years, including 618 CVD deaths. After multivariable adjustment, higher NHR showed a consistent linear association with increased all-cause and CVD mortality. Each standard deviation increase in NHR corresponded to 11% higher all-cause mortality (hazard ratio (HR) = 1.11) and 12% higher CVD mortality (HR = 1.12). Compared to the lowest tertile, the highest NHR tertile was associated with 29% higher all-cause mortality (HR = 1.29) and 70% higher CVD mortality (HR = 1.70). Higher LHR showed a non-linear relationship with 21% lower all-cause mortality (HR = 0.79) and 31% lower CVD mortality (HR = 0.69) in the highest tertile. MHR and PHR showed no significant associations with mortality.

Higher NHR was consistently associated with increased all-cause and CVD mortality among older adults, while higher LHR showed an inverse association. NHR may serve as a useful inflammatory-lipid marker for mortality risk assessment in ageing populations.