Association of Markers of Hemostasis With Death in HIV-Infected Women

Abstract:In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.

[1]  S. Costanzo,et al.  Association of D-dimer levels with all-cause mortality in a healthy adult population: findings from the MOLI-SANI study , 2013, Haematologica.

[2]  Mardge H. Cohen,et al.  Association of Hepatitis C With Markers of Hemostasis In HIV-Infected and Uninfected Women in the Women's Interagency HIV Study (WIHS) , 2013, Journal of acquired immune deficiency syndromes.

[3]  L. Kuller,et al.  Inflammation, Coagulation and Cardiovascular Disease in HIV-Infected Individuals , 2012, PloS one.

[4]  T. Wakefield,et al.  Biomarkers for the diagnosis of deep vein thrombosis. , 2012, Expert opinion on medical diagnostics.

[5]  L. Kuller,et al.  Does an index composed of clinical data reflect effects of inflammation, coagulation, and monocyte activation on mortality among those aging with HIV? , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  J. Qin,et al.  Pre-ART Levels of Inflammation and Coagulation Markers Are Strong Predictors of Death in a South African Cohort with Advanced HIV Disease , 2012, PloS one.

[7]  M. Yılmaz,et al.  Increased d-dimer levels predict cardiovascular mortality in patients with systolic heart failure , 2012, Journal of Thrombosis and Thrombolysis.

[8]  D. Strachan,et al.  Sex differences in the relationship between inflammatory and hemostatic biomarkers and metabolic syndrome: British 1958 Birth Cohort , 2011, Journal of thrombosis and haemostasis : JTH.

[9]  M. Vacas.  Gender Differences in Thrombogenic Profile Associated to Coronary Obstruction Angiographically Evaluated , 2011 .

[10]  D. Boulware,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. , 2011, The Journal of infectious diseases.

[11]  M. Cesari,et al.  Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions. , 2010, Cardiovascular therapeutics.

[12]  F. Rosendaal,et al.  Venous thrombosis risk associated with plasma hypofibrinolysis is explained by elevated plasma levels of TAFI and PAI-1. , 2010, Blood.

[13]  V. Natarajan,et al.  Traditional risk factors and D-dimer predict incident cardiovascular disease events in chronic HIV infection , 2010, AIDS.

[14]  Richard D Moore,et al.  Early mortality and cause of deaths in patients using HAART in Brazil and the United States , 2009, AIDS.

[15]  Mardge H. Cohen,et al.  Trends in Mortality and Causes of Death Among Women With HIV in the United States: A 10-Year Study , 2009, Journal of acquired immune deficiency syndromes.

[16]  Joseph A. C. Delaney,et al.  Associations of factor VIIIc, D‐dimer, and plasmin–antiplasmin with incident cardiovascular disease and all‐cause mortality , 2009, American journal of hematology.

[17]  J. van der Meer,et al.  Protein S deficiency: a clinical perspective , 2008, Haemophilia : the official journal of the World Federation of Hemophilia.

[18]  Lewis H Kuller,et al.  Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection , 2008, PLoS medicine.

[19]  J. Gilabert-Estellés,et al.  Fibrinolysis: the key to new pathogenetic mechanisms. , 2008, Current medicinal chemistry.

[20]  C. Keenan,et al.  The effects of race/ethnicity and sex on the risk of venous thromboembolism , 2007, Current opinion in pulmonary medicine.

[21]  Y. Aso.  Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis. , 2007, Frontiers in bioscience : a journal and virtual library.

[22]  C. Vigen,et al.  Progressive Prothrombotic State in Women With Advancing HIV Disease , 2006, Journal of acquired immune deficiency syndromes.

[23]  R. White,et al.  Racial and gender differences in the incidence of recurrent venous thromboembolism , 2006, Thrombosis and Haemostasis.

[24]  R. Vasan,et al.  Biomarkers of Cardiovascular Disease: Molecular Basis and Practical Considerations , 2006, Circulation.

[25]  J. Sterne,et al.  Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries , 2006, The Lancet.

[26]  R. Greenblatt,et al.  Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984–2004 , 2005, AIDS.

[27]  G. Lowe,et al.  Fibrin D-Dimer and Cardiovascular Risk , 2005, Seminars in vascular medicine.

[28]  S. B. Pedersen,et al.  Plasminogen activator inhibitor type 1 (PAI‐1) in plasma and adipose tissue in HIV‐associated lipodystrophy syndrome. Implications of adipokines , 2005, European journal of clinical investigation.

[29]  M. Young,et al.  The Women's Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench , 2005, Clinical Diagnostic Laboratory Immunology.

[30]  R. White,et al.  Effect of ethnicity and gender on the incidence of venous thromboembolism in a diverse population in California in 1996 , 2005, Thrombosis and Haemostasis.

[31]  B. Dezube,et al.  Thrombotic complications in patients infected with HIV in the era of highly active antiretroviral therapy: a case series. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  T. Lindahl,et al.  Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure , 2004, Thrombosis and Haemostasis.

[33]  P. Ridker,et al.  Established and emerging plasma biomarkers in the prediction of first atherothrombotic events. , 2004, Circulation.

[34]  A. Majluf-Cruz,et al.  Venous Thrombosis Among Patients with AIDS , 2004, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[35]  A. Folsom,et al.  Fibrin fragment D-dimer and the risk of future venous thrombosis. , 2003, Blood.

[36]  S. Gorbach,et al.  Lipodystrophy Syndrome in HIV , 2003, Springer US.

[37]  Mary Young,et al.  Causes of death among women with human immunodeficiency virus infection in the era of combination antiretroviral therapy. , 2002, The American journal of medicine.

[38]  Mardge H. Cohen,et al.  Use of highly active antiretroviral therapy in a cohort of HIV-seropositive women. , 2002, American journal of public health.

[39]  J. Danesh,et al.  Fibrin D-Dimer and Coronary Heart Disease: Prospective Study and Meta-Analysis , 2001, Circulation.

[40]  A. Moss,et al.  Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction ∗ , 2000 .

[41]  H. Köhler.  Book Review Comprehensive Clinical Nephrology By Richard J. Johnson and John Feehally. Approximately 700 pp., illustrated. St. Louis, Mosby, 2000. $189. 0-7234-3117-5 , 2000 .

[42]  P. Grant,et al.  Plasminogen-activator inhibitor type 1 and coronary artery disease. , 2000, The New England journal of medicine.

[43]  A. Moss,et al.  Gender-related differences in thrombogenic factors predicting recurrent cardiac events in patients after acute myocardial infarction. The THROMBO Investigators. , 2000, The American journal of cardiology.

[44]  A. Sharrett,et al.  Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[45]  Joseph Feldman,et al.  The Women's Interagency HIV Study , 1998 .

[46]  M. Rondanelli,et al.  Thrombophilic condition in HIV-infected patients. , 1997, Haematologica.

[47]  K. Harjai,et al.  Thrombotic Tendencies and Correlation With Clinical Status in Patients Infected With HIV , 1995, Southern medical journal.

[48]  T. Meade,et al.  Fibrinolytic activity, clotting factors, and long-term incidence of ischaemic heart disease in the Northwick Park Heart Study , 1993, The Lancet.

[49]  J. Gris,et al.  von Willebrand factor antigen, tissue-type plasminogen activator antigen, and risk of death in human immunodeficiency virus 1-related clinical disease: independent prognostic relevance of tissue-type plasminogen activator. , 1992, The Journal of laboratory and clinical medicine.

[50]  M. Prins,et al.  A critical review of the evidence supporting a relationship between impaired fibrinolytic activity and venous thromboembolism. , 1991, Archives of internal medicine.

[51]  C. Dhiver,et al.  Protein S deficiency and HIV infection. , 1991, The New England journal of medicine.

[52]  D. Stern,et al.  Participation of endothelial cells in the protein C-protein S anticoagulant pathway: the synthesis and release of protein S , 1986, The Journal of cell biology.

[53]  M. Alessi,et al.  Correlation between blood fibrinolytic activity, plasminogen activator inhibitor level, plasma insulin level, and relative body weight in normal and obese subjects. , 1986, Metabolism: clinical and experimental.