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image of Predictive Model for the Detection of Subclinical Atherosclerosis in HIV Patients on Antiretroviral Treatment

Abstract

Objective

Patients living with HIV (PLHIV) have a higher cardiovascular risk than others, which is why the early detection of atherosclerosis in this population is important. The present study reports predictive models of subclinical atherosclerosis for this population of patients, made up of variables that are easily collected in the clinic.

Methods

The study design is a cross-sectional observational study. PLHIV without established cardiovascular disease were recruited for this study. Predictive models of subclinical atherosclerosis (Doppler ultrasound) were developed by testing sociodemographic variables, pathological history, data related to HIV infection, laboratory parameters, and capillaroscopy as potential predictors. Logistic regression with internal validation (bootstrapping) and machine learning techniques were used to develop the models.

Results

Data from 96 HIV patients were analysed, 19 (19.8%) of whom had subclinical atherosclerosis. The predictors that went into both machine learning models and the regression model were hypertension, dyslipidaemia, protease inhibitors, triglycerides, fibrinogen, and alkaline phosphatase. Age and C-reactive protein were also part of the machine learning models. The logistic regression model had an area under the receiver operating characteristic curve (AUC) of 0.91 (95% CI: 0.84-0.99), which became 0.80 after internal validation by bootstrapping. The machine learning techniques produced models with AUCs ranging from 0.73 to 0.86.

Conclusion

We report predictive models for subclinical atherosclerosis in PLHIV, demonstrating relevant predictive performance based on easily accessible parameters, making them potentially useful as a screening tool. However, given the study’s limitations—primarily the sample size-external validation in larger cohorts is warranted.

© 2025 Bentham Science Publishers
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2025-06-05
2025-09-04

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References

  1. Wandeler G. Johnson L.F. Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe. Curr. Opin. HIV AIDS 2016 11 5 492 500 10.1097/COH.0000000000000298 27254748
    [Google Scholar]
  2. Manfredi R. HIV infection and advanced age. Ageing Res. Rev. 2004 3 1 31 54 10.1016/j.arr.2003.07.001 15164725
    [Google Scholar]
  3. Teeraananchai S. Kerr S.J. Amin J. Ruxrungtham K. Law M.G. Life expectancy of HIV ‐positive people after starting combination antiretroviral therapy: A meta‐analysis. HIV Med. 2017 18 4 256 266 10.1111/HIV.12421 27578404
    [Google Scholar]
  4. Durand M. Sheehy O. Baril J.G. Lelorier J. Tremblay C.L. Association between HIV infection, antiretroviral therapy, and risk of acute myocardial infarction: A cohort and nested case-control study using Québec’s public health insurance database. J. Acquir. Immune Defic. Syndr. 2011 57 3 245 253 10.1097/QAI.0b013e31821d33a5 21499115
    [Google Scholar]
  5. Shah A.S.V. Stelzle D. Lee K.K. Global burden of atherosclerotic cardiovascular disease in people living with HIV. Circulation 2018 138 11 1100 1112 10.1161/CIRCULATIONAHA.117.033369 29967196
    [Google Scholar]
  6. Yang Y. Yao X. Liu Y. Global and regional estimate of HIV-associated stroke burden: A meta-analysis and population attributable modeling study. Stroke 2023 54 9 2390 2400 10.1161/STROKEAHA.123.043410 37477007
    [Google Scholar]
  7. Zhu S. Wang W. He J. Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis. J. Glob. Health 2024 14 04078 10.7189/jogh.14.04078 38666515
    [Google Scholar]
  8. Alonso A. Barnes A.E. Guest J.L. Shah A. Shao I.Y. Marconi V. HIV infection and incidence of cardiovascular diseases: An analysis of a large healthcare database. J. Am. Heart Assoc. 2019 8 14 e012241 10.1161/JAHA.119.012241 31266386
    [Google Scholar]
  9. Nou E. Lo J. Hadigan C. Grinspoon S.K. Pathophysiology and management of cardiovascular disease in patients with HIV. Lancet Diabetes Endocrinol. 2016 4 7 598 610 10.1016/S2213‑8587(15)00388‑5 26873066
    [Google Scholar]
  10. Sackoff J.E. Hanna D.B. Pfeiffer M.R. Torian L.V. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City. Ann. Intern. Med. 2006 145 6 397 406 10.7326/0003‑4819‑145‑6‑200609190‑00003 16983127
    [Google Scholar]
  11. Schwarcz S.K. Vu A. Hsu L.C. Hessol N.A. Changes in causes of death among persons with AIDS: San Francisco, California, 1996-2011. AIDS Patient Care STDS 2014 28 10 517 523 10.1089/apc.2014.0079 25275657
    [Google Scholar]
  12. Triant V.A. Lee H. Hadigan C. Grinspoon S.K. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J. Clin. Endocrinol. Metab. 2007 92 7 2506 2512 10.1210/jc.2006‑2190 17456578
    [Google Scholar]
  13. Freiberg M.S. Chang C.C.H. Kuller L.H. HIV infection and the risk of acute myocardial infarction. JAMA Intern. Med. 2013 173 8 614 622 10.1001/jamainternmed.2013.3728 23459863
    [Google Scholar]
  14. Hasse B. Ledergerber B. Furrer H. Morbidity and aging in HIV-infected persons: The Swiss HIV cohort study. Clin. Infect. Dis. 2011 53 11 1130 1139 10.1093/cid/cir626 21998280
    [Google Scholar]
  15. Feinstein M.J. Hsue P.Y. Benjamin L.A. Characteristics, prevention, and management of cardiovascular disease in people living with HIV: A scientific statement from the american heart association. Circulation 2019 140 2 e98 e124 10.1161/CIR.0000000000000695 31154814
    [Google Scholar]
  16. Raddusa P.M.S. Marino A. Celesia B.M. Atherosclerosis and cardiovascular complications in people living with HIV: A focused review. Infect. Dis. Rep. 2024 16 5 846 863 10.3390/idr16050066 39311207
    [Google Scholar]
  17. Obare L.M. Temu T. Mallal S.A. Wanjalla C.N. Inflammation in HIV and its impact on atherosclerotic cardiovascular disease. Circ. Res. 2024 134 11 1515 1545 10.1161/CIRCRESAHA.124.323891 38781301
    [Google Scholar]
  18. Friis-Møller N. Thiébaut R. Reiss P. Predicting the risk of cardiovascular disease in HIV-infected patients: The Data collection on Adverse Effects of Anti-HIV Drugs Study. Eur. J. Cardiovasc. Prev. Rehabil. 2010 17 5 491 501 10.1097/HJR.0b013e328336a150 20543702
    [Google Scholar]
  19. Post W.S. Budoff M. Kingsley L. Associations between HIV infection and subclinical coronary atherosclerosis. Ann. Intern. Med. 2014 160 7 458 467 10.7326/M13‑1754 24687069
    [Google Scholar]
  20. Serrano-Villar S. Estrada V. Gómez-Garre D. Diagnosis of subclinical atherosclerosis in HIV-infected patients: Higher accuracy of the D:A:D risk equation over Framingham and SCORE algorithms. Eur. J. Prev. Cardiol. 2014 21 6 739 748 10.1177/2047487312452964 22718798
    [Google Scholar]
  21. Cardinal R.M.H. Durand M. Chartrand-Lefebvre C. Soulez G. Tremblay C. Cloutier G. Associative prediction of carotid artery plaques based on ultrasound strain imaging and cardiovascular risk factors in people living with HIV and age-matched control subjects of the CHACS cohort. J. Acquir. Immune Defic. Syndr. 2022 91 1 91 100 10.1097/QAI.0000000000003016 35510848
    [Google Scholar]
  22. Socio D.G.V.L. Martinelli C. Ricci E. Relations between cardiovascular risk estimates and subclinical atherosclerosis in naïve HIV patients: Results from the HERMES study. Int. J. STD AIDS 2010 21 4 267 272 10.1258/ijsa.2009.009165 20378899
    [Google Scholar]
  23. Soto F.J. Romero-Jiménez M.J. García A.J.C. Estruch B.E. Ramos S.J.L. López C.M.Á. Predictors of subclinical atherosclerosis in HIV. BMC Infect. Dis. 2023 23 1 17 10.1186/s12879‑022‑07976‑1 36627565
    [Google Scholar]
  24. Verdejo-Muñoz G. Gálvez-Barrón C. Tello G.B. Capillaroscopy, microangiopathy, and HIV. Descriptive study of capillaroscopy findings in HIV positive patients. An. Sist. Sanit. Navar. 2022 45 3 e1015 10.23938/ASSN.1015 36468584
    [Google Scholar]
  25. Verdejo-Muñoz G. Gálvez-Barrón C. Gamarra-Calvo S. Conde C.I. Catena A. Ramos B.J.R. Usefulness of artery femoral ultrasound complementary to carotid exploration for the detection of subclinical atheromatosis in patients with human immunodeficiency virus infection. Med. Clin. 2023 160 10 443 446 10.1016/j.medcli.2022.11.024 36759302
    [Google Scholar]
  26. Smith V. Herrick A.L. Ingegnoli F. Standardisation of nailfold capillaroscopy for the assessment of patients with Raynaud’s phenomenon and systemic sclerosis. Autoimmun. Rev. 2020 19 3 102458 10.1016/j.autrev.2020.102458 31927087
    [Google Scholar]
  27. Bergman R. Sharony L. Schapira D. Nahir M.A. Balbir-Gurman A. The handheld dermatoscope as a nail-fold capillaroscopic instrument. Arch. Dermatol. 2003 139 8 1027 1030 10.1001/archderm.139.8.1027 12925391
    [Google Scholar]
  28. Touboul P.J. Hennerici M.G. Meairs S. Mannheim intima-media thickness consensus. Cerebrovasc. Dis. 2004 18 4 346 349 10.1159/000081812 15523176
    [Google Scholar]
  29. Touboul P.J. Hennerici M.G. Meairs S. Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc. Dis. 2007 23 1 75 80 10.1159/000097034 17108679
    [Google Scholar]
  30. Touboul P.J. Hennerici M.G. Meairs S. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th european stroke conferences, mannheim, germany, 2004, brussels, belgium, 2006, and hamburg, germany, 2011. Cerebrovasc. Dis. 2012 34 4 290 296 10.1159/000343145 23128470
    [Google Scholar]
  31. Lorenz M.W. Markus H.S. Bots M.L. Rosvall M. Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation 2007 115 4 459 467 10.1161/CIRCULATIONAHA.106.628875 17242284
    [Google Scholar]
  32. O’Leary D.H. Polak J.F. Wolfson S.K. Use of sonography to evaluate carotid atherosclerosis in the elderly. The Cardiovascular Health Study. Stroke 1991 22 9 1155 1163 10.1161/01.STR.22.9.1155 1926258
    [Google Scholar]
  33. Peters S.A.E. Ruijter D.H.M. Bots M.L. Moons K.G.M. Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: A systematic review. Heart 2012 98 3 177 184 10.1136/heartjnl‑2011‑300747 22095617
    [Google Scholar]
  34. Hanna D.B. Moon J.Y. Haberlen S.A. Carotid artery atherosclerosis is associated with mortality in HIV-positive women and men. AIDS 2018 32 16 2393 2403 10.1097/QAD.0000000000001972 30102657
    [Google Scholar]
  35. Mangili A. Polak J.F. Quach L.A. Gerrior J. Wanke C.A. Markers of atherosclerosis and inflammation and mortality in patients with HIV infection. Atherosclerosis 2011 214 2 468 473 10.1016/j.atherosclerosis.2010.11.013 21130995
    [Google Scholar]
  36. Belcaro G. Nicolaides A.N. Ramaswami G. Carotid and femoral ultrasound morphology screening and cardiovascular events in low risk subjects: A 10-year follow-up study (the CAFES-CAVE study). Atherosclerosis 2001 156 2 379 387 10.1016/S0021‑9150(00)00665‑1 11395035
    [Google Scholar]
  37. Protogerou A.D. Fransen J. Zampeli E. The Additive value of femoral ultrasound for subclinical atherosclerosis assessment in a single center cohort of 962 adults, including high risk patients with rheumatoid arthritis, human immunodeficiency virus infection and type 2 diabetes mellitus. PLoS One 2015 10 7 e0132307 10.1371/journal.pone.0132307 26230728
    [Google Scholar]
  38. Postley J.E. Luo Y. Wong N.D. Gardin J.M. Identification by ultrasound evaluation of the carotid and femoral arteries of high-risk subjects missed by three validated cardiovascular disease risk algorithms. Am. J. Cardiol. 2015 116 10 1617 1623 10.1016/j.amjcard.2015.08.031 26434511
    [Google Scholar]
  39. Simon N. Friedman J. Hastie T. Tibshirani R. Regularization paths for cox’s proportional hazards model via coordinate descent. J. Stat. Softw. 2011 39 5 1 13 10.18637/jss.v039.i05 27065756
    [Google Scholar]
  40. Moons K.G.M. Altman D.G. Reitsma J.B. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): Explanation and elaboration. Ann. Intern. Med. 2015 162 1 W1 W73 10.7326/M14‑0698 25560730
    [Google Scholar]
  41. Burnham K.P. Efron B. The jackknife, the bootstrap and other resampling plans. Biometrics 1983 39 3 816 817 10.2307/2531123
    [Google Scholar]
  42. Rossum V.G. Drake F.L. Python 3 Reference Manual. Scotts Valley, California CreateSpace 2009 1 9
    [Google Scholar]
  43. Team R.C.R. A language and environment for statistical computing. 2022 Available from: http://www.R-project.org/
    [Google Scholar]
  44. Friis-Møller N. Reiss P. Sabin C.A. Class of antiretroviral drugs and the risk of myocardial infarction. N. Engl. J. Med. 2007 356 17 1723 1735 10.1056/NEJMoa062744 17460226
    [Google Scholar]
  45. Sankatsing R.R. Wit F.W. Vogel M. Increased carotid intima-media thickness in HIV patients treated with protease inhibitors as compared to non-nucleoside reverse transcriptase inhibitors. Atherosclerosis 2009 202 2 589 595 10.1016/j.atherosclerosis.2008.05.028 18599064
    [Google Scholar]
  46. Holmberg S.D. Moorman A.C. Williamson J.M. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet 2002 360 9347 1747 1748 10.1016/S0140‑6736(02)11672‑2 12480430
    [Google Scholar]
  47. Alvi R.M. Neilan A.M. Tariq N. Protease inhibitors and cardiovascular outcomes in patients with HIV and heart failure. J. Am. Coll. Cardiol. 2018 72 5 518 530 10.1016/j.jacc.2018.04.083 30049313
    [Google Scholar]
  48. Kann G. Owasil J. Kuczka K. Evaluation of platelet activation by HIV protease inhibitors – the HIV-PLA II study. HIV AIDS 2021 13 789 800 10.2147/HIV.S262282 34393518
    [Google Scholar]
  49. Turcotte I. El-Far M. Sadouni M. Association between the development of subclinical cardiovascular disease and human immunodeficiency virus (HIV) reservoir markers in people with HIV on suppressive antiretroviral therapy. Clin. Infect. Dis. 2023 76 7 1318 1321 10.1093/cid/ciac874 36346439
    [Google Scholar]
  50. Vemulapalli A.C. Elias A.A. Yerramsetti M.D. The impact of contemporary antiretroviral drugs on atherosclerosis and its complications in people living with HIV: A systematic review. Cureus 2023 15 10 e47730 10.7759/cureus.47730 38021858
    [Google Scholar]
  51. Laurence J. Elhadad S. Ahamed J. HIV-associated cardiovascular disease: Importance of platelet activation and cardiac fibrosis in the setting of specific antiretroviral therapies. Open Heart 2018 5 2 e000823 10.1136/openhrt‑2018‑000823 30018781
    [Google Scholar]
  52. Sukumaran L. Kunisaki K.M. Bakewell N. Association between inflammatory biomarker profiles and cardiovascular risk in individuals with and without. HIV AIDS 2023 37 4 595 603 10.1097/QAD.0000000000003462 36541572
    [Google Scholar]
  53. Mooney S. Tracy R. Osler T. Grace C. Elevated biomarkers of inflammation and coagulation in patients with HIV are associated with higher framingham and vacs risk index scores. PLoS One 2015 10 12 e0144312 10.1371/journal.pone.0144312 26641655
    [Google Scholar]
  54. Triant V.A. Meigs J.B. Grinspoon S.K. Association of C-reactive protein and HIV infection with acute myocardial infarction. J. Acquir. Immune Defic. Syndr. 2009 51 3 268 273 10.1097/QAI.0b013e3181a9992c 19387353
    [Google Scholar]
  55. Baker J.V. Duprez D. Biomarkers and HIV-associated cardiovascular disease. Curr. Opin. HIV AIDS 2010 5 6 511 516 10.1097/COH.0b013e32833ed7ec 20978394
    [Google Scholar]
  56. Subramanya V. McKay H.S. Brusca R.M. Inflammatory biomarkers and subclinical carotid atherosclerosis in HIV-infected and HIV-uninfected men in the Multicenter AIDS Cohort Study. PLoS One 2019 14 4 e0214735 10.1371/journal.pone.0214735 30946765
    [Google Scholar]
  57. Ssinabulya I. Kayima J. Longenecker C. Subclinical atherosclerosis among HIV-infected adults attending HIV/AIDS care at two large ambulatory HIV clinics in Uganda. PLoS One 2014 9 2 e89537 10.1371/journal.pone.0089537 24586854
    [Google Scholar]
  58. Moran C.A. Sheth A.N. Mehta C.C. The association of C-reactive protein with subclinical cardiovascular disease in HIV-infected and HIV-uninfected women. AIDS 2018 32 8 999 1006 10.1097/QAD.0000000000001785 29438198
    [Google Scholar]
  59. Tonelli M. Curhan G. Pfeffer M. Relation between alkaline phosphatase, serum phosphate, and all-cause or cardiovascular mortality. Circulation 2009 120 18 1784 1792 10.1161/CIRCULATIONAHA.109.851873 19841303
    [Google Scholar]
  60. Lai Z. Liu Y. Huang M. Associations between atherosclerosis and elevated serum alkaline phosphatase in patients with coronary artery disease in an inflammatory state. Heart Lung Circ. 2023 32 9 1096 1106 10.1016/j.hlc.2023.05.012 37550157
    [Google Scholar]
  61. Panh L. Ruidavets J.B. Rousseau H. Association between serum alkaline phosphatase and coronary artery calcification in a sample of primary cardiovascular prevention patients. Atherosclerosis 2017 260 81 86 10.1016/j.atherosclerosis.2017.03.030 28371683
    [Google Scholar]
  62. Haarhaus M. Ray K.K. Nicholls S.J. Apabetalone lowers serum alkaline phosphatase and improves cardiovascular risk in patients with cardiovascular disease. Atherosclerosis 2019 290 59 65 10.1016/j.atherosclerosis.2019.09.002 31568963
    [Google Scholar]
  63. Ryu W.S. Lee S.H. Kim C.K. Kim B.J. Kwon H.M. Yoon B.W. High serum alkaline phosphatase in relation to cerebral small vessel disease. Atherosclerosis 2014 232 2 313 318 10.1016/j.atherosclerosis.2013.11.047 24468144
    [Google Scholar]
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Predictive Model for the Detection of Subclinical Atherosclerosis in HIV Patients on Antiretroviral Treatment
Bentham Science Publishers ; https://doi.org/10.2174/011570162X373384250529110832
/content/journals/chr/10.2174/011570162X373384250529110832
/content/journals/chr/10.2174/011570162X373384250529110832
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  • Article Type:     Research Article
Keywords: HIV ; heart disease risk factors ; coronary artery disease ; atherosclerosis ; cardiovascular diseases ; ultrasonography ; carotid arteries ; development of HIV

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