Associations of non-traditional lipid-inflammatory parameters with all-cause mortality in middle-aged and older adults: Insights from two nationally representative cohorts

Q: What are the key findings of this study?

Non-traditional lipid-inflammatory parameters were positively associated with all-cause mortality, with top-quartile CRI-I-CRP increasing risk by 59% (HR 1.59, 95% CI 1.40-1.81, P<0.001).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Middle-aged and older adults assessed for all-cause mortality risk (n=19352). Intervention: Eight non-traditional lipid-inflammatory parameters (non-HDL-C-CRP, RC-CRP, AIP-CRP, AC-CRP, CRI-I-CRP, CRI-II-CRP, LCI-CRP, and RC/HDL-C-CRP) vs. Lowest quartile (Q1) or per 1-SD decrease in lipid-inflammatory parameter. Primary outcome: All-cause mortality (HR 1.59, 95% CI 1.40-1.81, p=<0.001).

Q: What does this research mean for the field?

Non-traditional lipid-inflammatory parameters are independently and positively associated with all-cause mortality in middle-aged and older adults, with highest-quartile CRI-I-CRP conferring a 59% increased mortality risk. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To systematically evaluate the associations between non-traditional lipid-inflammatory parameters and all-cause mortality in middle-aged and older adults across two nationally representative cohorts.

Xiaohang Yang; Luna Liu; Xiaoqian Du; Ling Gao; Yue Liu

doi:10.1016/j.metop.2026.100507

October 9, 2026Metabolism OpenOpen Access

Associations of non-traditional lipid-inflammatory parameters with all-cause mortality in middle-aged and older adults: Insights from two nationally representative cohorts

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Key result

Top-quartile CRI-I-CRP is linked to ~59% higher all-cause mortality.

HR 1.59
95% CI 1.40-1.81
P<0.001
n=19,352

Figures

Why the study?

Non-traditional lipid-inflammatory parameters integrate lipid metabolism and inflammation, but their association with all-cause mortality in middle-aged and older adults had not been systematically evaluated.

Are elevated non-traditional lipid-inflammatory parameters associated with an increased risk of all-cause mortality in middle-aged and older adults?

Key Points

To systematically evaluate the associations between non-traditional lipid-inflammatory parameters and all-cause mortality in middle-aged and older adults across two nationally representative cohorts.
Analyzed 9,943 participants from the US National Health and Nutrition Examination Survey (NHANES) followed for a mean of 80.3 months, and 9,409 participants from the China Health and Retirement Longitudinal Study (CHARLS) followed for a mean of 100.2 months.
Survey weights were incorporated into Kaplan–Meier survival curves, multivariable Cox proportional hazards models, restricted cubic splines, and time-dependent ROC analyses to evaluate mortality risk and discriminative performance.
A total of 2,377 deaths occurred in NHANES and 1,246 in CHARLS; all eight parameters analyzed as continuous variables showed positive associations with all-cause mortality in both cohorts (P < 0.001).
In quartile analyses comparing the highest to lowest quartiles, risk was significantly elevated for all parameters in NHANES (e.g., CRI-I-CRP HR=1.59, 95% CI: 1.40–1.81, P < 0.001), but non-significant for AIP-CRP (HR=1.16, 95% CI: 0.88–1.52, P=0.295) and LCI-CRP (HR=1.28, 95% CI: 0.99–1.64, P=0.056) in CHARLS.
AIP-CRP displayed a significant nonlinear dose–response relationship across both cohorts (P-nonlinear < 0.001), and adding these parameters significantly improved risk discrimination over baseline models based on DeLong tests.

Study Design

Type

Cohort (n=19,352)

Multicenter

Yes

Structured PICO

Are elevated non-traditional lipid-inflammatory parameters associated with an increased risk of all-cause mortality in middle-aged and older adults?

P

Population

19,352 middle-aged and older adults aged 45 years and older from two national cohorts (9,943 in NHANES, median age 66 years, 55% female; 9,409 in CHARLS, median age 58 years, 52.7% female) followed for a mean of 80.3 and 100.2 months, respectively.

E

Exposure

Exposure to eight baseline non-traditional lipid-inflammatory parameters (calculated as non-traditional lipid parameter × CRP [mg/L]/10): non-HDL-C-CRP, RC-CRP, AIP-CRP, AC-CRP, CRI-I-CRP, CRI-II-CRP, LCI-CRP, and RC/HDL-C-CRP, analyzed as Z-standardized continuous variables (per 1-SD) and in quartiles (Q4 vs Q1).

C

Comparator

Lowest quartile (Q1) of each respective non-traditional lipid-inflammatory parameter (or lower continuous values per 1-SD).

O

Outcome

All-cause mortality (death events caused by heart disease, cancer, and all other causes), determined via National Death Index linkage in NHANES (over a mean follow-up of 80.3 months) and standardized follow-up wave questionnaires in CHARLS (over a mean follow-up of 100.2 months).hard clinical

Main Result

Hazard Ratio: 1.59 (95% CI 1.4–1.81)

p-value: p=<0.001

Composite non-traditional lipid-inflammatory parameters derived from routine lipid panels and CRP tests independently predict all-cause mortality and improve risk discrimination over traditional risk factors in middle-aged and older adults.

Limitations

Observational study design cannot exclude residual confounding despite adjustment for multiple confounders.
Parameters were derived solely from single baseline measurements, precluding assessment of dynamic trajectories or therapeutic interventions during follow-up.
LDL-C in certain NHANES cycles was estimated using the Friedewald formula, which may have affected accuracy.
Objective differences existed between the two cohorts in death confirmation, follow-up mode, and baseline medication recording.
Potential influence of participation bias common in population-based studies.
Observational study design where residual confounding cannot be excluded despite multivariable adjustment
Parameters were derived solely from single baseline measurements, precluding evaluation of dynamic trajectories over time or impact of therapeutic interventions
LDL-C in certain NHANES cycles was estimated using the Friedewald formula, which may affect accuracy
Objective differences between NHANES and CHARLS in death confirmation, follow-up mode, and baseline medication recording
Potential participation bias common in population-based studies

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Implication

Non-traditional lipid-inflammatory parameters were associated with higher all-cause mortality; extends prior observational data but leaves clinical adoption open pending trials.

Abstract

Background Non-traditional lipid-inflammatory parameters are emerging biomarkers integrating lipid metabolism and inflammation. However, their association with all-cause mortality in middle-aged and older adults has not been systematically evaluated. Methods This study enrolled 9,943 participants from the National Health and Nutrition Examination Survey (NHANES) and 9,409 participants from the China Health and Retirement Longitudinal Study (CHARLS). Survey weights were applied to account for the complex sampling design. Kaplan–Meier analyses were performed to estimate cumulative survival probabilities. Cox proportional hazards models were used to examine the associations. Restricted cubic splines were fitted to explore potential dose–response relationships. Time-dependent ROC analyses were conducted to evaluate predictive performance at follow-up time points. DeLong tests were used to assess the statistical significance of differences in the areas under the curve. Calibration curves were constructed to assess the model calibration. Subgroup and sensitivity analyses were conducted to explore heterogeneity and assess the robustness of the results. Results Over a mean follow-up of 80.3 months in NHANES and 100.2 months in CHARLS, 2,377 and 1,246 deaths were recorded, respectively. Cumulative survival probabilities decreased across quartiles for all parameters except LCI-CRP (Log-rank P =0.960) in NHANES. After adjusting for confounders, all parameters were positively associated with all-cause mortality in continuous analyses. In quartile analyses, the highest quartile carried a higher risk than the lowest, except for AIP-CRP (HR=1.16, 95% CI:0.88–1.52, P =0.295) and LCI-CRP (HR=1.28, 95% CI:0.99–1.64, P =0.056) in CHARLS. AIP-CRP exhibited a nonlinear dose–response relationship in both cohorts. The predictive performance of parameters improved with longer follow-up time in NHANES, whereas it fluctuated in CHARLS. DeLong tests showed that models incorporating parameters had better discriminative ability than the base model. Calibration curves indicated good calibration of the parameter-incorporating models. Hypertension significantly modified the associations of certain parameters in CHARLS. The results remained robust across all sensitivity analyses. Conclusions Non-traditional lipid-inflammatory parameters demonstrate significant independent associations with an elevated risk of all-cause mortality among middle-aged and older adults. Based on routine lipid and inflammatory tests, these parameters are simple, low-cost tools for early risk stratification.

Discussion

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Cite This Study

Yang et al. (2026) conducted a cohort in Middle-aged and older adults assessed for all-cause mortality risk (n=19,352). Eight non-traditional lipid-inflammatory parameters (non-HDL-C-CRP, RC-CRP, AIP-CRP, AC-CRP, CRI-I-CRP, CRI-II-CRP, LCI-CRP, and RC/HDL-C-CRP) vs. Lowest quartile (Q1) or per 1-SD decrease in lipid-inflammatory parameter was evaluated on All-cause mortality (HR 1.59, 95% CI 1.40-1.81, p=<0.001). Non-traditional lipid-inflammatory parameters were positively associated with all-cause mortality, with top-quartile CRI-I-CRP increasing risk by 59% (HR 1.59, 95% CI 1.40-1.81, P<0.001).

synapsesocial.com/papers/6aee6b6871a75948062208ec https://doi.org/10.1016/j.metop.2026.100507

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Associations of non-traditional lipid-inflammatory parameters with all-cause mortality in middle-aged and older adults: Insights from two nationally representative cohorts

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Associations of non-traditional lipid-inflammatory parameters with all-cause mortality in middle-aged and older adults: Insights from two nationally representative cohorts

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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