Joint association of LDL cholesterol and inflammation with mortality and the modifying effect of physical activity: findings from two population-based cohort studies.
5 affiliations
- 1Department of Epidemiology and Biostatistics, School of Public Health, Guilin Medical University, Guilin, P. R. China.
- 2Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, P. R. China.
- 3Department of Cardiology, The Key Laboratory of Myocardial Ischemia, The Second Affiliated Hospital of Harbin Medical University, Chinese Ministry of Education, Harbin, P. R. China.
- 4Department of Epidemiology and Biostatistics, School of Public Health, Guilin Medical University, Guilin, P. R. China. [email protected].
- 5Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, P. R. China. [email protected].
Abstract
Background: Low-density lipoprotein cholesterol (LDL-C) and inflammation are two main factors contributing to risk of cardiovascular disease (CVD) mortality. However, their joint associations remain controversial, and it is unknown whether physical activity (PA) can modify these associations.
Methods: A total of 18,416 US adults with a total of 150047.8 person-years follow-up from the National Health and Nutrition Examination Survey (NHANES) including general population, patients with atherosclerotic cardiovascular disease (ASCVD), and individuals at extreme risk, and 2575 Chinese adults with a total of 10736.8 person-years follow-up from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) including general population and patients with non-communicable diseases (NCDs) were analyzed. Restricted cubic spline, Cox regression models, and mediation analyses were employed to estimate associations between PA, LDL-C, systemic immune-inflammation index (SII) in the NHANES/platelet-to-lymphocyte ratio (PLR) in the CLHLS, and the risk of mortality from all-cause and CVD.
Results: The combined effects were significant, which included LDL-C with SII on mortality from all-cause and CVD among the general population and ASCVD patients in the NHANES, and LDL-C with PLR on all-cause mortality among NCDs patients in the CLHLS. Compared with participants with LDL-C in tertile 2 (T2) and SII/PLR in T2, the hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause/CVD mortality in participants with LDL-C in T1/T3 and SII/PLR in T1/T3 were 1.47 (1.23–1.76)/1.36 (1.01–1.84), 1.40 (1.06–1.86)/1.67 (1.01–2.75) in the NHANES, and 1.22 (0.96–1.55) for all-cause mortality in the CLHLS, respectively. PA significantly reduced the above-mentioned risks: compared with participants who did not engage in PA, the HRs (95%CIs) for those who engaged in PA were 0.56 (0.48–0.67)/0.54 (0.41–0.71), 0.62 (0.45–0.86)/0.78 (0.50–1.20) in the NHANES, and 0.67 (0.51–0.87) for all-cause mortality in the CLHLS, respectively. LDL-C and inflammation mediated 4.99%–20.01% of the association between PA and mortality from all-cause/CVD.
Conclusions: Either low LDL-C level or high inflammation level was associated with increased risk of mortality from all-cause and CVD. Engagement in PA can reduce the above mortality risks related to abnormal levels of LDL-C and inflammation, providing practical implications for public health interventions.
Graphical Abstract: US, United States; NHANES, National Health and Nutrition Examination Survey; ASCVD, atherosclerotic cardiovascular disease; Extreme risk, progressive ASCVD; CN, China; CLHLS, Chinese Longitudinal Healthy Longevity Survey; NCDs, non-communicable diseases; LDL-C, low-density lipoprotein cholesterol; CVD, cardiovascular disease; PA, physical activity; SII, systemic immune-inflammation index; T1: tertile1; T2: tertile2; T3: tertile3; group1: LDL-C in T2 & SII in T2; group2: LDL-C in T2 & SII in T1/T3; group3: LDL-C in T1/T3 & SII in T2; group4: LDL-C in T1/T3 & SII in T1/T3; S, Rothman's synergy index; HR, hazard ratio; CI, confidence interval.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12944-026-03026-w.
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BibTeX
@article{wu2026joint,
title = {{Joint association of LDL cholesterol and inflammation with mortality and the modifying effect of physical activity: findings from two population-based cohort studies.}},
author = {Chunxin Wu and Linsen Chen and Lei Luo and Meng Sun and Shengqiang Huang and Wei Shao and Xiaoyan Wu},
journal = {Lipids in health and disease},
year = {2026},
month = aug,
doi = {10.1186/s12944-026-03026-w},
url = {https://europepmc.org/article/MED/42958341},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Joint association of LDL cholesterol and inflammation with mortality and the modifying effect of physical activity: findings from two population-based cohort studies.
AU - Chunxin Wu
AU - Linsen Chen
AU - Lei Luo
AU - Meng Sun
AU - Shengqiang Huang
AU - Wei Shao
AU - Xiaoyan Wu
PY - 2026
DA - 2026/08/01
JO - Lipids in health and disease
DO - 10.1186/s12944-026-03026-w
UR - https://europepmc.org/article/MED/42958341
AB - Background: Low-density lipoprotein cholesterol (LDL-C) and inflammation are two main factors contributing to risk of cardiovascular disease (CVD) mortality. However, their joint associations remain controversial, and it is unknown whether physical activity (PA) can modify these associations. Methods: A total of 18,416 US adults with a total of 150047.8 person-years follow-up from the National Health and Nutrition Examination Survey (NHANES) including general population, patients with atherosclerotic cardiovascular disease (ASCVD), and individuals at extreme risk, and 2575 Chinese adults with a total of 10736.8 person-years follow-up from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) including general population and patients with non-communicable diseases (NCDs) were analyzed. Restricted cubic spline, Cox regression models, and mediation analyses were employed to estimate associations between PA, LDL-C, systemic immune-inflammation index (SII) in the NHANES/platelet-to-lymphocyte ratio (PLR) in the CLHLS, and the risk of mortality from all-cause and CVD. Results: The combined effects were significant, which included LDL-C with SII on mortality from all-cause and CVD among the general population and ASCVD patients in the NHANES, and LDL-C with PLR on all-cause mortality among NCDs patients in the CLHLS. Compared with participants with LDL-C in tertile 2 (T2) and SII/PLR in T2, the hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause/CVD mortality in participants with LDL-C in T1/T3 and SII/PLR in T1/T3 were 1.47 (1.23–1.76)/1.36 (1.01–1.84), 1.40 (1.06–1.86)/1.67 (1.01–2.75) in the NHANES, and 1.22 (0.96–1.55) for all-cause mortality in the CLHLS, respectively. PA significantly reduced the above-mentioned risks: compared with participants who did not engage in PA, the HRs (95%CIs) for those who engaged in PA were 0.56 (0.48–0.67)/0.54 (0.41–0.71), 0.62 (0.45–0.86)/0.78 (0.50–1.20) in the NHANES, and 0.67 (0.51–0.87) for all-cause mortality in the CLHLS, respectively. LDL-C and inflammation mediated 4.99%–20.01% of the association between PA and mortality from all-cause/CVD. Conclusions: Either low LDL-C level or high inflammation level was associated with increased risk of mortality from all-cause and CVD. Engagement in PA can reduce the above mortality risks related to abnormal levels of LDL-C and inflammation, providing practical implications for public health interventions. Graphical Abstract: US, United States; NHANES, National Health and Nutrition Examination Survey; ASCVD, atherosclerotic cardiovascular disease; Extreme risk, progressive ASCVD; CN, China; CLHLS, Chinese Longitudinal Healthy Longevity Survey; NCDs, non-communicable diseases; LDL-C, low-density lipoprotein cholesterol; CVD, cardiovascular disease; PA, physical activity; SII, systemic immune-inflammation index; T1: tertile1; T2: tertile2; T3: tertile3; group1: LDL-C in T2 & SII in T2; group2: LDL-C in T2 & SII in T1/T3; group3: LDL-C in T1/T3 & SII in T2; group4: LDL-C in T1/T3 & SII in T1/T3; S, Rothman's synergy index; HR, hazard ratio; CI, confidence interval. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12944-026-03026-w.
SN - 1476-511X
ER -