Association between systemic inflammation markers and abdominal aortic calcification: a cross-sectional study

Abstract

Background: Systemic inflammatory markers are associated with cardiovascular disease. This study aimed to assess the relationship between systemic inflammatory markers and abdominal aortic calcification (AAC).

Methods: Data were collected from the 2013 to 2014 cycle of the National Health and Nutrition Examination Survey (NHANES). AAC was quantified using the Kauppila scoring system, which is based on dual-energy X-ray absorptiometry. Severe abdominal aortic calcification (sAAC) was defined as a total AAC score ≥6. Multivariate regression models were used to determine the relationships between systemic inflammation indicators, AAC scores, and sAAC.

Results: Data from 3047 participants were analyzed. After adjusting for multiple covariates, AAC scores increased slightly for every one-unit increase in standardized systemic immune-inflammation index (SII; β = 0.13; 95% confidence interval [CI]: 0.01-0.25, P=0.030). Neutrophil-to-lymphocyte ratio (NLR) was positively correlated with higher AAC scores (β = 0.15; 95% CI: 0.06-0.24, P=0.001) and sAAC (odds ratio [OR]: 1.10; 95% CI: 1.01-1.19, P=0.025). There was no significant correlation between platelet-to-lymphocyte ratio (PLR) and AAC scores (β = −0.0006; 95% CI: −0.0018 to 0.0030). Conversely, lymphocyte-to-monocyte ratio (LMR) was positively associated with lower AAC scores (β = −0.14; 95% CI: −0.22 to −0.05, P=0.001), with a 12% decrease in the odds of sAAC for every one-unit increase in LMR (OR: 0.88; 95% CI: 0.79-0.97, P=0.013).

Conclusion: Correlations between different systemic inflammation markers and AAC varied among the adult population of the United States. NLR was associated with higher AAC scores and an increased incidence of sAAC, whereas LMR had the opposite effect. NLR and LMR have emerged as potential biomarkers for AAC risk, highlighting their importance in understanding the inflammatory processes associated with AAC.

Keywords

Abdominal aortic calcification / Cross-sectional study / Systemic inflammation markers

Conflict of interest statement

Feng Xu is an editorial board member of Emergency and Critical Care Medicine. The article was subject to the journal’s standard procedures, with peer review handled independently of the Editorial Board member and their research groups. The authors declare no conflicts of interest.

Author contributions

Liu Y and Liu X designed this study and analyzed the data. Liu X collected the data. Liu Y completed the organization and writing of this article. Pan C, Yue H, Zhang X, and Xu F revised the manuscript. All authors approved the final manuscript.

Funding

This work was supported by the Taishan Young Scholar Programof Shandong Province (grant number tsqn202306349) and ECCM Program of Clinical Research Center of Shandong University (grant number 2021SDUCRCA001).

Ethical approval of studies and informed consent

The study followed the principles of the Declaration of Helsinki as revised in 2013. The NHANES study was reviewed and approved by the NCHS Research Ethics Review Board, and all participants provided written informed consent. This research used deidentified data from NHANES, in accordance with the data release and use agreement.

Acknowledgments

The authors thank all NHANES participants and staff for their valuable efforts and contributions.

References

[1] Faleeva M, Ahmad S, Theofilatos K, et al. Sox9 accelerates vascular aging by regulating extracellular matrix composition and stiffness. Circ Res. 2024; 134(3):307-324. doi:10.1161/circresaha.123.323365

[2] Tsai CH, Lin LY, Lin YH, Tsai IJ, Huang JW. Abdominal aorta calcification predicts cardiovascular but not non-cardiovascular outcome in patients receiving peritoneal dialysis: a prospective cohort study. Medicine (Baltimore). 2020; 99(37):e21730. doi:10.1097/md.0000000000021730

[3] Jurgens PT, Carr JJ, Terry JG, Rana JS, Duprez DA. Association of abdominal aorta calcium and coronary artery calcium with incident cardiovascular and coronary heart disease events in Black and White middle-aged people: the coronary artery risk development in young adults study. J Am Heart Assoc. 2021; 10(24):e023037. doi:10.1161/jaha.121.023037

[4] Szulc P. Abdominal aortic calcification: a reappraisal of epidemiological and pathophysiological data. Bone. 2016; 84:25-37. doi:10.1016/j.bone.2015.12.004

[5] Setiawati R, Di Chio F, Rahardjo P, Nasuto M, Dimpudus FJ, Guglielmi G. Quantitative assessment of abdominal aortic calcifications using lateral lumbar radiograph, dual-energy X-ray absorptiometry, and quantitative computed tomography of the spine. J Clin Densitom. 2016; 19(2):242-249. doi:10.1016/j.jocd.2015.01.007

[6] Bastos Gonçalves F, Voûte MT, Hoeks SE, et al. Calcification of the abdominal aorta as an independent predictor of cardiovascular events: a meta-analysis. Heart. 2012; 98(13):988-994. doi:10.1136/heartjnl-2011-301464

[7] Reaven PD, Sacks J; Investigators for the Veterans Affairs Cooperative Study of Glycemic Control and Complications in Diabetes Mellitus Type 2. Reduced coronary artery and abdominal aortic calcification in Hispanics with type 2 diabetes. Diabetes Care. 2004; 27(5):1115-1120. doi:10.2337/diacare.27.5.1115

[8] O'Connor SD, Graffy PM, Zea R, Pickhardt PJ. Does nonenhanced CT-based quantification of abdominal aortic calcification outperform the Framingham risk score in predicting cardiovascular events in asymptomatic adults. Radiology. 2019; 290(1):108-115. doi:10.1148/radiol.2018180562

[9] Ban TH, Choi BS, Yoon SA, et al. Clinical significance of neutrophil-to-lymphocyte ratio on the risk of abdominal aortic calcification and decreased bone mineral density in patients with end-stage kidney disease. PloS One. 2023; 18(10):e0286612. doi:10.1371/journal.pone.0286612

[10] Li Y, Sun Z, Zhang L, et al. Role of macrophages in the progression and regression of vascular calcification. Front Pharmacol. 2020; 11:661. doi:10.3389/fphar.2020.00661

[11] Raucci A, Macrì F, Castiglione S, Badi I, Vinci MC, Zuccolo E. MicroRNA-34a: the bad guy in age-related vascular diseases. Cell Mol Life Sci. 2021; 78(23):7355-7378. doi:10.1007/s00018-021-03979-4

[12] Wang Y, Miao Y, Gong K, Cheng X, Chen Y, Zhao MH. Plasma complement protein C3a level was associated with abdominal aortic calcification in patients on hemodialysis. J Cardiovasc Transl Res. 2019; 12(5):496-505. doi:10.1007/s12265-019-09885-2

[13] Nøst TH, Alcala K, Urbarova I, et al. Systemic inflammation markers and cancer incidence in the UK biobank. Eur J Epidemiol. 2021; 36(8):841-848. doi:10.1007/s10654-021-00752-6

[14] Wu XB, Huang LX, Huang ZR, et al. The lymphocyte-to-monocyte ratio predicts intracranial atherosclerotic stenosis plaque instability. Front Immunol. 2022; 13:915126. doi:10.3389/fimmu.2022.915126

[15] Luo J, Qin X, Zhang X, et al. Prognostic implications of systemic immune-inflammation index in myocardial infarction patients with and without diabetes: insights from the NOAFCAMI-SH registry. Cardiovasc Diabetol. 2024; 23(1):41. doi:10.1186/s12933-024-02129-x

[16] Grimnes G, Horvei LD, Tichelaar V, Brækkan SK, Hansen JB. Neutrophil to lymphocyte ratio and future risk of venous thromboembolism and mortality: the Tromsø study. Haematologica. 2016; 101(10):e401-e404. doi:10.3324/haematol.2016.145151

[17] Ferro D, Matias M, Neto J, et al. Neutrophil-to-lymphocyte ratio predicts cerebral edema and clinical worsening early after reperfusion therapy in stroke. Stroke. 2021; 52(3):859-867. doi:10.1161/strokeaha.120.032130

[18] Xie R, Liu X, Wu H, Liu M, Zhang Y. Associations between systemic immune-inflammation index and abdominal aortic calcification: results of a nationwide survey. Nutr Metab Cardiovasc Dis. 2023; 33(7):1437-1443. doi:10.1016/j.numecd.2023.04.015

[19] Ahluwalia N, Dwyer J, Terry A, Moshfegh A, Johnson C. Update on NHANES dietary data: focus on collection, release, analytical considerations, and uses to inform public policy. Adv Nutr. 2016; 7(1):121-134. doi:10.3945/an.115.009258

[20] Dalla Via J, Gebre AK, Smith C, et al. Machine-learning assessed abdominal aortic calcification is associated with long-term fall and fracture risk in community-dwelling older Australian women. J Bone Miner Res. 2023; 38(12):1867-1876. doi:10.1002/jbmr.4921

[21] Pan W, Jie W, Huang H. Vascular calcification: molecular mechanisms and therapeutic interventions. MedComm (2020). 2023; 4(1):e200. doi:10.1002/mco2.200

[22] Kong Y, Liang Q, Chen Y, et al. Hyaluronan negatively regulates vascular calcification involving BMP2 signaling. Lab Invest. 2018; 98(10):1320-1332. doi:10.1038/s41374-018-0076-x

[23] Durham AL, Speer MY, Scatena M, Giachelli CM, Shanahan CM. Role of smooth muscle cells in vascular calcification: implications in atherosclerosis and arterial stiffness. Cardiovasc Res. 2018; 114(4):590-600. doi:10.1093/cvr/cvy010

[24] Lee HY, Lim S, Park S. Role of inflammation in arterial calcification. Korean Circ J. 2021; 51(2):114-125. doi:10.4070/kcj.2020.0517

[25] Choi SR, Lee YK, Cho AJ, et al. Malnutrition inflammation, progression of vascular calcification and survival: inter-relationships in hemodialysis patients. PloS One. 2019; 14(5):e0216415. doi:10.1371/journal.pone.0216415

[26] Song M, Graubard BI, Rabkin CS, Engels EA. Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci Rep. 2021; 11(1):464. doi:10.1038/s41598-020-79431-7

[27] Fries RC, Kadotani S, Stack JP, Kruckman L, Wallace G. Prognostic value of neutrophil-to-lymphocyte ratio in cats with hypertrophic cardiomyopathy. Front Vet Sci. 2022; 9:813524. doi:10.3389/fvets.2022.813524

[28] Mirna M, Schmutzler L, Topf A, Hoppe UC, Lichtenauer M. Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio predict length of hospital stay in myocarditis. Sci Rep. 2021; 11(1):18101. doi:10.1038/s41598-021-97678-6

[29] Hong S, He H, Fang P, Liu S, Chen C. Association of neutrophil-to-lymphocyte ratio and risk of cardiovascular and all-cause mortality in hypertension patients. Heliyon. 2024; 10(6):e27517. doi:10.1016/j.heliyon.2024.e27517

[30] Hu G, Liu G, Ma JY, Hu RJ. Lymphocyte-to-monocyte ratio in esophageal squamous cell carcinoma prognosis. Clin Chim Acta. 2018; 486:44-48. doi:10.1016/j.cca.2018.07.029

[31] Castanheira FVS, Kubes P. Neutrophils and NETs in modulating acute and chronic inflammation. Blood. 2019; 133(20):2178-2185. doi:10.1182/blood-2018-11-844530

[32] Liew PX, Kubes P. The neutrophil's role during health and disease. Physiol Rev. 2019; 99(2):1223-1248. doi:10.1152/physrev.00012.2018

[33] Zulfic Z, Weickert CS, Weickert TW, Liu D, Myles N, Galletly C. Neutrophil-lymphocyte ratio — a simple, accessible measure of inflammation, morbidity and prognosis in psychiatric disorders. Australas Psychiatry. 2020; 28(4):454-458. doi:10.1177/1039856220908172

[34] Mulholland M, Jakobsson G, Lei Y, et al. IL-2Rβγ signalling in lymphocytes promotes systemic inflammation and reduces plasma cholesterol in atherosclerotic mice. Atherosclerosis. 2021; 326:1-10. doi:10.1016/j.atherosclerosis.2021.04.010

[35] Auffray C, Sieweke MH, Geissmann F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Annu Rev Immunol. 2009; 27:669-692. doi:10.1146/annurev.immunol.021908.132557

[36] Radzyukevich YV, Kosyakova NI, Prokhorenko IR. Participation of monocyte subpopulations in progression of experimental endotoxemia (EE) and systemic inflammation. J Immunol Res. 2021; 2021:1762584. doi:10.1155/2021/1762584

[37] Austermann J, Roth J, Barczyk-Kahlert K. The good and the bad: monocytes' and macrophages' diverse functions in inflammation. Cells. 2022; 11(12):1979. doi:10.3390/cells11121979