Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Systemic inflammation-based scores and mortality for all causes in HIV-infected patients: a MASTER cohort study

Published in: BMC Infectious Diseases | Issue 1/2017

Login to get access

Abstract

Background

Two biomarkers, the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), have been shown to be indicative of systemic inflammation and predictive of mortality in general population. We aimed to assess the association of NLR and PLR, with risk of death in HIV-infected subjects when also taking account of HIV-related factors.

Methods

We conducted a multicenter Italian cohort study from 2000 to 2012 including HIV-infected subjects naïve at antiretroviral treatment.
The associations of NLR and PLR with all-cause mortality were tested by univariate and multivariate analyses using both time independent and dependent Cox proportional hazard models. We also fitted models with a cubic-spline for PLR and NLR to evaluate the possible non-linear relationship between biomarkers values and risk of death.

Results

Eight-thousand and two hundred thirty patients (73.1% males) with a mean age of 38.4 years (SD 10.1) were enrolled. During a median follow-up of 3.9 years, 539 patients died. PLR < 100 and ≥ 200, as compared to PLR of 100–200, and NLR ≥ 2, as compared to < 2, were associated with risk of death at both univariate and multivariate analyses. Using multivariate models with restricted cubic-splines, we found a linear relationship of increasing risk of death with increasing values for NRL over 1.1, and an U-shape curve for PLR, with higher mortality risk for values higher or lower than 120.

Conclusions

Our data suggest that NLR and PLR can reflect the severity of the underlying systemic disturbance of the inflammatory process and coagulation leading to augmented mortality in HIV positive subjects.
Appendix
Available only for authorised users
Literature
1.
Collaboration FS, Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294(14):1799–809.
2.
Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG, et al. C-reactive protein concentration andrisk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132–40.CrossRef
3.
Cohen HJ, Harris T, Pieper CF. Coagulation and activation of inflammatory pathways in the development of functional decline and mortality in the elderly. Am J Med. 2003;114:180–7.CrossRefPubMed
4.
Di Castelnuovo A, de Curtis A, Costanzo S, Persichillo M, Olivieri M, Zito F, et al. Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-S ANI study. Haematologica. 2013;98:1476–80.CrossRefPubMedPubMedCentral
5.
Proctor MJ, Mcmillan DC, Horgan PG, Fletcher CD, Talwar D, Morrison DS. Systemic inflammation predicts all-cause mortality: a glasgow inflammation outcome study. Plos One. 2015;10(3):e0116206.CrossRefPubMedPubMedCentral
6.
Wada NI, Jacobson LP, Margolick JB, Breen EC, Macatangay B, Penugonda S, et al. The effect of HAART-induced HIV suppression on circulating markers of inflammation and immune activation. AIDS. 2015;29(4):463–71.CrossRefPubMedPubMedCentral
7.
Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. Plos Med. 2008;5(10):e203.CrossRefPubMedPubMedCentral
8.
Tien PC, Choi AI, Zolopa AR, Benson C, Tracy R, Scherzer R, et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. J Acquir Immune Defic Syndr. 2010;55(3):316–22.CrossRefPubMedPubMedCentral
9.
Tenorio AR, Zheng Y, Bosch RJ, Krishnan S, Rodriguez B, Hunt PW, et al. Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. J Infect Dis. 2014;210(8):1248–59.CrossRefPubMedPubMedCentral
10.
Boulware DR, Hullsiek KH, Puronen CE, Rupert A, Baker JV, French MA, et al. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis. 2011;203(11):1637–46.CrossRefPubMedPubMedCentral
11.
French MA, Cozzi-Lepri A, Arduino RC, Johnson M, Achhra AC, Landay A, et al. Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested ina large clinical trial. AIDS. 2015;29(7):847–51.CrossRefPubMedPubMedCentral
12.
Wang X, Zhang G, Jiang X, Zhu H, Lu Z, Xu L. Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: a meta-analysis of observational studies. Atherosclerosis. 2014;234(1):206–13.CrossRefPubMed
13.
Templeton AJ, Mcnamara MG, Seruga B, Vera-Badillo FE, Aneja P, Ocaña A, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju124.CrossRefPubMed
14.
Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, Mcmillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88(1):218–30.CrossRefPubMed
15.
Templeton AJ, Ace O, Mcnamara MG, Al-Mubarak M, Vera-Badillo FE, Hermanns T, et al. Prognostic role of platelet to lymphocyte ratio in solid tumors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2014;23(7):1204–12.CrossRefPubMed
16.
Azab B, Camacho-Rivera M, Taioli E. Average values and racial differences of neutrophil lymphocyte ratio among a nationally representative sample of United States subjects. Plos One. 2014;9(11):e112361.CrossRefPubMedPubMedCentral
17.
Guo X, Zhang S, Zhang Q, Liu L, Wu H, Du H, et al. Neutrophil:lymphocyte ratio is positively related to type 2 diabetes in a large-scale adult population: a Tianjin Chronic Low-Grade Systemic Inflammation and Health cohort study. Eur J Endocrinol. 2015;173(2):217–25.CrossRefPubMed
18.
Raffetti E, Donato F, Pezzoli C, Digiambenedetto S, Bandera A, Di Pietro M, et al. Systemic inflammation-based biomarkers and survival in HIV-positive subject with solid cancer in an Italian multicenter study. J Acquir Immune Defic Syndr. 2015;69(5):585–92.CrossRefPubMed
19.
Raffetti E, Donato F, Castelnuovo F, Ladisa N, Paraninfo G, di Filippo E, et al. The prognostic role of systemic inflammatory markers on HIV-infected patients with non-Hodgkin Lymphoma, a multicenter Cohort Study. J Transl Med. 2015;13:89.CrossRefPubMedPubMedCentral
20.
Torti C, Raffetti e, Donato F, Castelli F, Maggiolo F, Angarano G, et al. Cohort Profile: Standardized Management of Antiretroviral Therapy Cohort (MASTER Cohort). Int J Epidemiol. 2015.
21.
Mocroft A, Lundgren JD, Sabin ML, Monforte A, Brockmeyer N, Casabona J, et al. Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE). Plos Med. 2013;10(9):e1001510.CrossRefPubMedPubMedCentral
22.
Harrell F. General aspects of fitting regression models. In: Regression modeling strategies - with applications to linear models, logistic regression and survival analysis. New York: Springer; 2001. p. 23–4.
23.
Akaike H. A New look at the statistical model identification. IEEE Trans Autom Control. 1974;AC-19(6):716–23.CrossRef
24.
Rönsholt FF, Ullum H, Katzenstein TL, Gerstoft J, Ostrowski SR. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy. Plos One. 2013;8(6):e65182.CrossRefPubMedPubMedCentral
25.
Mussini C, Lorenzini P, Cozzi-Lepri A, Lapula G, Marchetti G, Nicastri E, et al. CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study. Lancet HIV. 2015;2(3):e98–106.CrossRefPubMed
26.
Karaman M, Balta S, Seyit Ahmet AY, Cakar M, Naharci I, Demirkol S, et al. The comparative effects of valsartan and amlodipine on vWf levels and N/L ratio in patients with newly diagnosed hypertension. Clin Exp Hypertens. 2013;35(7):516–22.CrossRefPubMed
27.
Buyukkaya E, Karakas MF, Karakas E, Akçay AB, Tanboga IH, Kurt M, et al. Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome. Clin Appl Thromb Hemost. 2014;20(2):159–63.CrossRefPubMed
28.
Öztürk ZA, Yesil Y, Kuyumcu ME, Bilici M, Öztürk N, Yeşil NK, et al. Inverse relationship between neutrophil lymphocyte ratio (NLR) and bone mineral density (BMD) in elderly people. Arch Gerontol Geriatr. 2013;57(1):81–5.CrossRefPubMed
29.
Balta S, Demirko SI, Unlu M, Arslan Z, Celik T. Neutrophil to lymphocyte ratio may be predict of mortality in all conditions. Br J Cancer. 2013;109(12):3125–6.CrossRefPubMedPubMedCentral
30.
Azab B, Shah N, Akerman M, Mcginn Jr JT. Value of platelet/lymphocyte ratio as a predictor of all-cause mortality after non-ST-elevation myocardial infarction. J Thromb Thrombolysis. 2012;34:326–34.CrossRefPubMed
31.
Miguez MJ, Rodrıguez A, Hadrigan S, Asthana D, Burbano X, Fletcher MA. Interleukin-6 and platelet protagonists in T lymphocyte and virological response. Platelets. 2005;16:281–6.CrossRefPubMed
32.
Zetterberg E, Neuhaus J, Baker JV, Somboonwit C, Llibre JM, Palfreeman A, et al. Platelet count kinetics following interruption of antiretroviral treatment. AIDS. 2013;27:59–68.CrossRefPubMedPubMedCentral
33.
Borges ÁH, Silverberg MJ, Wentworth D, Grulich AE, Fätkenheuer G, Mitsuyasu R, et al. Predicting risk of cancer during HIV infection: the role of inflammatory and coagulation bio-markers. AIDS. 2013;27:1433–41.CrossRefPubMedPubMedCentral
34.
Duprez DA, Neuhaus J, Kuller LH, Tracy R, Belloso W, De Wit S, et al. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. Plos One. 2012;7:e44454.CrossRefPubMedPubMedCentral
35.
Borges ÁH, Lundgren JD, Ridolfo A, Katlama C, Antunes F, Grzeszczuk A, et al. Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease. AIDS. 2014;28(17):2565–71.CrossRefPubMed
36.
37.
Hearps AC, Martin GE, Rajasuriar R, Crowe SM. Inflammatory co-morbidities in HIV+ individuals: learning lessons from healthy ageing. Curr HIV/AIDS Rep. 2014;11:20–34.CrossRefPubMed
38.
Stepanova M, Rodriguez E, Birerdinc A, Baranova A. Age-independent rise of inflammatory scores may contribute to accelerated aging in multi-morbidity. Oncotarget. 2015;6(3):1414–21.CrossRefPubMedPubMedCentral
39.
Bastard JP, Fellahi S, Couffignal C, Raffi F, Gras G, Hardel L, et al. Increased systemic immune activation and inflammatory profile of long-term HIV-infected ART-controlled patients is related to personal factors, but not to markers of HIV infection severity. J Antimicrob Chemother. 2015;70(6):1816–24.PubMed
40.
Hattab S, Guihot A, Guiguet M, Fourati S, Carcelain G, Caby F, et al. Comparative impact of antiretroviral drugs on markers of inflammation and immune activation during the first 2 years of effective therapy for HIV-1 infection: an observational study. BMC Infect Dis. 2014;14:122.CrossRefPubMedPubMedCentral
41.
Massanella M, Ouchi D, Marfil S, Llibre JM, Puertas MC, Buzón MJ, et al. Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals. Plos One. 2014;9(12):e114142.CrossRefPubMedPubMedCentral
Metadata
Title
Systemic inflammation-based scores and mortality for all causes in HIV-infected patients: a MASTER cohort study
Publication date
01-12-2017
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-017-2280-5

Other articles of this Issue 1/2017

BMC Infectious Diseases 1/2017 Go to the issue

Research article

“Does the Salmonella Genomic Island 1 (SGI1) confer invasiveness properties to human isolates?”

Case report

Zoonotic necrotizing myositis caused by Streptococcus equi subsp. zooepidemicus in a farmer

Research article

Evaluation of vaccination herd immunity effects for anogenital warts in a low coverage setting with human papillomavirus vaccine—an interrupted time series analysis from 2005 to 2010 using health insurance data

Research article

Routine monitoring and assessment of adults living with HIV: results of the British HIV Association (BHIVA) national audit 2015

Research article

Molecular epidemiology of bla OXA-23 -producing carbapenem-resistant Acinetobacter baumannii in a single institution over a 65-month period in north China

Research article

Outbreak of caliciviruses in the Singapore military, 2015

ACC 2024 Congress Coverage

Cardiology Video

Highlights from the ACC 2024 Congress

Watch now

Watch official videos from the ACC congress summarizing key highlights from the last year in heart failure, cardiomyopathies, valvular disease, pulmonary vascular disease, and pediatric cardiology.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits