Association of high-density lipoprotein-related inflammatory markers with suicidal ideation: Data from the NHANES 2015 - 2023 survey

Abstract

Suicidal ideation (SI) is a strong predictor of suicide risk. High-density lipoprotein (HDL)-related inflammatory indicators, which combine HDL cholesterol (HDL-C) with other inflammation-related markers, provide a comprehensive assessment of the body’s inflammatory, immune, and metabolic states. However, limited research has examined the association between HDL-related inflammatory indicators and SI. This study analyzed data from 14,554 participants, including 588 individuals with SI, using information from the 2015 - 2023 National Health and Nutrition Examination Survey. SI was evaluated using the ninth item of the Patient Health Questionnaire-9. A weighted approach was applied to logistic regression, restricted cubic spline, and subgroup analyses to explore the relationship between six HDL-related inflammatory indicators and SI. In addition, weighted quantile sum regression was employed to account for the interactions among inflammatory markers and their influence on the outcomes. Among the various single-marker models, only high-sensitivity C-reactive protein/HDL-C (CHR) consistently demonstrated a significant linear association with SI. In Model 3 of the logistic regression analysis, the odds ratio with a 95% confidence interval was 1.11 (1.02, 1.21). Mixture analyses further identified CHR as the primary factor contributing to the increased prevalence of SI. This study provides the first epidemiological evidence linking multiple novel inflammatory markers to SI, identifying CHR as the most critical factor. Further prospective studies are needed to confirm this causal relationship.

Keywords

Suicidal ideation / Patient Health Questionnaire-9 / High-density lipoprotein-related inflammatory indicators / National Health and Nutrition Examination Survey

Funding

This study was supported by the Natural Science Foundation of Jiangsu Province (Grant No. BK20242002).

Conflict of interest

Chen Qu is an Editorial Board Member of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

References

[1] Bachmann S. Epidemiology of suicide and the psychiatric perspective. Int J Environ Res Public Health. 2018; 15(7):1425. doi: 10.3390/ijerph15071425

[2] Naghavi M. Global, regional, and national burden of suicide mortality 1990 to 2016: Systematic analysis for the Global Burden of Disease Study 2016. BMJ. 2019; 364:l94. doi: 10.1136/bmj.l94

[3] Large MM, Nielssen O. Suicidal ideation and later suicide. Am J Psychiatry. 2012; 169(6):662; author reply 663. doi: 10.1176/appi.ajp.2012.11111674

[4] Hubers AAM, Moaddine S, Peersmann SHM, et al. Suicidal ideation and subsequent completed suicide in both psychiatric and non-psychiatric populations: A meta-analysis. Epidemiol Psychiatr Sci. 2018; 27(2):186-198. doi: 10.1017/s2045796016001049

[5] Courtet P, Jaussent I, Genty C, et al. Increased CRP levels may be a trait marker of suicidal attempt. Eur Neuropsychopharmacol. 2015; 25(10):1824-1831. doi: 10.1016/j.euroneuro.2015.05.003

[6] Steiner J, Gos T, Bogerts B, Bielau H, Drexhage HA, Bernstein HG. Possible impact of microglial cells and the monocyte-macrophage system on suicidal behavior. CNS Neurol Disord Drug Targets. 2013; 12(7):971-979. doi: 10.2174/18715273113129990099

[7] Zhang J, McKeown RE, Hussey JR, Thompson SJ, Woods JR, Ainsworth BE. Low HDL cholesterol is associated with suicide attempt among young healthy women: The Third National Health and Nutrition Examination Survey. J Affect Disord. 2005; 89(1-3):25-33. doi: 10.1016/j.jad.2005.05.021

[8] Zhao J, Zheng Q, Ying Y, et al. Association between high-density lipoprotein-related inflammation index and periodontitis: Insights from NHANES 2009-2014. Lipids Health Dis. 2024; 23(1):321. doi: 10.1186/s12944-024-02312-9

[9] Gao J, Lu J, Sha W, et al. Relationship between the neutrophil to high-density lipoprotein cholesterol ratio and severity of coronary artery disease in patients with stable coronary artery disease. Front Cardiovasc Med. 2022;9:1015398. doi: 10.3389/fcvm.2022.1015398

[10] Fu YW, Li XX, Xu HZ, Gong YQ, Yang Y. Effects of periodontal therapy on serum lipid profile and proinflammatory cytokines in patients with hyperlipidemia: A randomized controlled trial. Clin Oral Investig. 2016; 20(6):1263-1269. doi: 10.1007/s00784-015-1621-2

[11] Lu CF, Cang XM, Liu WS, et al.Association between the platelet/high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: Results from NHANES2017-2020. Lipids Health Dis. 2023; 22(1):130. doi: 10.1186/s12944-023-01861-9

[12] Atehortua L, Davidson WS, Chougnet CA. Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties. Arterioscler Thromb Vasc Biol. 2024; 44(6):1191-1201. doi: 10.1161/atvbaha.124.320851

[13] De Nardo D, Labzin LI, Kono H, et al. High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3. Nat Immunol. 2014; 15(2):152-160. doi: 10.1038/ni.2784

[14] Sorci-Thomas MG, Thomas MJ. High density lipoprotein biogenesis, cholesterol efflux, and immune cell function. Arterioscler Thromb Vasc Biol. 2012; 32(11):2561-2565. doi: 10.1161/atvbaha.112.300135

[15] Guo X, Shen R, Su Y, Ma L. High-density lipoprotein-related inflammatory indices predict repeat revascularization in coronary drug-eluting stenting. Biomark Med. 2023; 17(22):959-969. doi: 10.2217/bmm-2023-0399

[16] Huang Y, Ding K, Dai Z, et al. The relationship of low-density-lipoprotein to lymphocyte ratio with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2022; 17:2175-2185. doi: 10.2147/copd.S369161

[17] Cândido FG, da Silva A, Zanirate GA, Oliveira N, Hermsdorff HHM. Lymphocyte to high-density lipoprotein cholesterol ratio is positively associated with pre-diabetes, metabolic syndrome, and non-traditional cardiometabolic risk markers: A cross-sectional study at secondary health care. Inflammation. 2024. doi: 10.1007/s10753-024-02063-w

[18] Guo B, Liu X, Si Q, et al.Associations of CBC-derived inflammatory indicators with sarcopenia and mortality in adults: Evidence from Nhanes1999 - 2006. BMC Geriatr. 2024; 24(1):432. doi: 10.1186/s12877-024-05012-2

[19] Huang H, Wei L, Chen X, et al. Cord serum elementomics profiling of 56 elements depicts risk of preterm birth: Evidence from a prospective birth cohort in rural Bangladesh. Environ Int. 2021;156:106731. doi: 10.1016/j.envint.2021.106731

[20] Huang D, Zhong S, Yan H, Lai S, Lam M, Jia Y. Association between serum zinc levels and suicidal ideation in US adults: A population-based cross-sectional study. J Affect Disord. 2023; 329:359-368. doi: 10.1016/j.jad.2023.02.039

[21] Jia J, Sun Z, Tao X, et al. Association between oxidative balance score and heart failure in the older adults: Results from the NHANES 2005-2018. Heart Lung. 2024; 68:107-115. doi: 10.1016/j.hrtlng.2024.06.006

[22] Li Y, Wang J, Cai Y, Chen H. Association of serum Vitamin D with periodontal disease. Int Dent J. 2023; 73(5):777-783. doi: 10.1016/j.identj.2023.06.004

[23] Chen H, Du N, Wang L, Yang L.A higher risk for melanoma in patients with Parkinson’s disease: Based on the results from National Health and Nutrition Examination Survey2001 - 2004. J Clin Basic Psychosom. 2023; 1(1):0571. doi: 10.36922/jcbp.0571

[24] Yin J, Wang H, Li S, et al. Nonlinear relationship between sleep midpoint and depression symptoms: A cross-sectional study of US adults. BMC Psychiatry. 2023; 23(1):671. doi: 10.1186/s12888-023-05130-y

[25] Du X, Xu X, Yu H, et al. Thyrotoxic effects of mixed exposure to perfluorinated compounds: Integrating population-based, toxicogenomic, animal, and cellular evidence to elucidate molecular mechanisms and identify potential effector targets. Environ Sci Technol. 2024; 58:18177-18189. doi: 10.1021/acs.est.4c06287

[26] Carrico C, Gennings C, Wheeler DC, Factor-Litvak P. Characterization of weighted quantile sum regression for highly correlated data in a risk analysis setting. J Agric Biol Environ Stat. 2015; 20(1):100-120. doi: 10.1007/s13253-014-0180-3

[27] Bergmans RS, Kelly KM, Mezuk B.Inflammation as a unique marker of suicide ideation distinct from depression syndrome among U.S. adults. J Affect Disord. 2019; 245:1052-1060. doi: 10.1016/j.jad.2018.11.046

[28] Vasupanrajit A, Jirakran K, Tunvirachaisakul C, Solmi M, Maes M. Inflammation and nitro-oxidative stress in current suicidal attempts and current suicidal ideation: A systematic review and meta-analysis. Mol Psychiatry. 2022; 27(3):1350-1361. doi: 10.1038/s41380-021-01407-4

[29] Courtet P, Giner L, Seneque M, Guillaume S, Olie E, Ducasse D. Neuroinflammation in suicide: Toward a comprehensive model. World J Biol Psychiatry. 2016; 17(8):564-586. doi: 10.3109/15622975.2015.1054879

[30] Kim KI, Oh SW, Ahn S, et al. CRP level and HDL cholesterol concentration jointly predict mortality in a Korean population. Am J Med. 2012; 125(8):787-795.e784. doi: 10.1016/j.amjmed.2012.02.013

[31] Tang H, Xiang Z, Li L, et al. Potential role of anti-inflammatory HDL subclasses in metabolic unhealth/ obesity. Artif Cells Nanomed Biotechnol. 2021; 49(1):565-575. doi: 10.1080/21691401.2021.1961798

[32] Tehrani DM, Gardin JM, Yanez D, et al. Impact of inflammatory biomarkers on relation of high density lipoprotein-cholesterol with incident coronary heart disease: Cardiovascular Health Study. Atherosclerosis. 2013; 231(2):246-251. doi: 10.1016/j.atherosclerosis.2013.08.036

[33] Gao Y, Wang M, Wang R, et al. The predictive value of the hs-CRP/HDL-C ratio, an inflammation-lipid composite marker, for cardiovascular disease in middle-aged and elderly people: Evidence from a large national cohort study. Lipids Health Dis. 2024; 23(1):66. doi: 10.1186/s12944-024-02055-7

[34] De Berardis D, Serroni N, Marini S, et al, Alexithymia, suicidal ideation, and serum lipid levels among drug-naïve outpatients with obsessive-compulsive disorder. Braz J Psychiatry. 2014; 36(2):125-130. doi: 10.1590/1516-4446-2013-1189

[35] O’Donovan A, Rush G, Hoatam G, et al. Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety. 2013; 30(4):307-314. doi: 10.1002/da.22087

[36] Lozupone M, Donghia R, Sardone R, et al. Apolipoprotein E genotype, inflammatory biomarkers, and non-psychiatric multimorbidity contribute to the suicidal ideation phenotype in older age. The Salus in Apulia Study. J Affect Disord. 2022; 319:202-212. doi: 10.1016/j.jad.2022.09.046

[37] Park RJ, Kim YH. Association between high sensitivity CRP and suicidal ideation in the Korean general population. Eur Neuropsychopharmacol. 2017; 27(9):885-891. doi: 10.1016/j.euroneuro.2017.06.010

[38] Zhang H, Reilly MP. Anti-inflammatory effects of high-density lipoprotein through activating transcription factor 3: Benefit beyond cholesterol transport-dependent processes. Arterioscler Thromb Vasc Biol. 2014; 34(6):e11-e12. doi: 10.1161/atvbaha.114.303553

[39] Aronson D, Avizohar O, Levy Y, Bartha P, Jacob G, Markiewicz W. Factor analysis of risk variables associated with low-grade inflammation. Atherosclerosis. 2008; 200(1):206-212. doi: 10.1016/j.atherosclerosis.2007.12.008