D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda

Objectives:We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda. Methods:We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension. Results:In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio. Conclusion:BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.

[1]  S. Haneuse,et al.  Incidence and predictors of hypertension in adults with HIV-initiating antiretroviral therapy in south-western Uganda , 2015, Journal of hypertension.

[2]  A. Schutte,et al.  Endothelial activation and cardiometabolic profiles of treated and never-treated HIV infected Africans. , 2015, Atherosclerosis.

[3]  M. Lederman,et al.  Gut epithelial barrier dysfunction and innate immune activation predict mortality in treated HIV infection. , 2014, The Journal of infectious diseases.

[4]  Jeffrey N. Martin,et al.  The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy. , 2014, The Journal of infectious diseases.

[5]  M. Suthanthiran,et al.  Hypertension, kidney disease, HIV and antiretroviral therapy among Tanzanian adults: a cross-sectional study , 2014, BMC Medicine.

[6]  Jeffrey N. Martin,et al.  Reversal of the Kynurenine Pathway of Tryptophan Catabolism May Improve Depression in ART-Treated HIV-Infected Ugandans , 2014, Journal of acquired immune deficiency syndromes.

[7]  A. Schutte,et al.  Cardiometabolic changes in treated versus never treated HIV-infected black South Africans: the PURE study. , 2014, Heart, lung & circulation.

[8]  M. Petersen,et al.  Epidemiology and awareness of hypertension in a rural Ugandan community: a cross-sectional study , 2013, BMC Public Health.

[9]  Johanna,et al.  Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis , 2016, International journal of epidemiology.

[10]  A. Miserocchi,et al.  HIV-related mechanisms in atherosclerosis and cardiovascular diseases , 2013, Journal of cardiovascular medicine.

[11]  M. Trøseid,et al.  Markers of microbial translocation predict hypertension in HIV‐infected individuals , 2013, HIV medicine.

[12]  A. Kengne,et al.  Hypertension prevalence and Framingham risk score stratification in a large HIV-positive cohort in Uganda , 2013, Journal of hypertension.

[13]  A. Branch,et al.  Correlates of Hypertension in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy , 2013, Journal of the International Association of Providers of AIDS Care.

[14]  G. Pucci,et al.  Symmetric ambulatory arterial stiffness index and 24-h pulse pressure in HIV infection: results of a nationwide cross-sectional study , 2013, Journal of hypertension.

[15]  M. Trøseid,et al.  Low Nadir CD4 Cell Count Predicts Sustained Hypertension in HIV‐Infected Individuals , 2013, Journal of clinical hypertension.

[16]  J. Brenchley,et al.  Microbial translocation, immune activation, and HIV disease. , 2013, Trends in microbiology.

[17]  T. Bärnighausen,et al.  Hypertension and Obesity in Adults Living in a High HIV Prevalence Rural Area in South Africa , 2012, PloS one.

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

[19]  G. Aldrovandi,et al.  Relationship between Microbial Translocation and Endothelial Function in HIV Infected Patients , 2012, PloS one.

[20]  S. Deeks,et al.  Immunologic basis of cardiovascular disease in HIV-infected adults. , 2012, The Journal of infectious diseases.

[21]  Jeffrey N. Martin,et al.  Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy , 2011, AIDS.

[22]  A. d’Arminio Monforte,et al.  Microbial translocation predicts disease progression of HIV-infected antiretroviral-naive patients with high CD4+ cell count , 2011, AIDS.

[23]  G. Bloomfield,et al.  Hypertension and Obesity as Cardiovascular Risk Factors among HIV Seropositive Patients in Western Kenya , 2011, PloS one.

[24]  P. Libby,et al.  Progress and challenges in translating the biology of atherosclerosis , 2011, Nature.

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

[26]  J. Stasch,et al.  Kynurenine is an endothelium-derived relaxing factor produced during inflammation , 2010, Nature Medicine.

[27]  William M. Tierney,et al.  Creation and evaluation of EMR-based paper clinical summaries to support HIV-care in Uganda, Africa , 2010, Int. J. Medical Informatics.

[28]  M. Lederman,et al.  Plasma levels of bacterial DNA correlate with immune activation and the magnitude of immune restoration in persons with antiretroviral-treated HIV infection. , 2009, The Journal of infectious diseases.

[29]  Steven Wolinsky,et al.  Microbial Translocation Is Associated with Increased Monocyte Activation and Dementia in AIDS Patients , 2008, PloS one.

[30]  N. Crowther,et al.  Metabolic Function and the Prevalence of Lipodystrophy in a Population of HIV-Infected African Subjects Receiving Highly Active Antiretroviral Therapy , 2007, Journal of acquired immune deficiency syndromes.

[31]  P. Libby,et al.  Intertwining of thrombosis and inflammation in atherosclerosis , 2007, Current opinion in hematology.

[32]  J. Brenchley,et al.  Microbial translocation is a cause of systemic immune activation in chronic HIV infection , 2006, Retrovirology.

[33]  P. Price,et al.  Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function. , 2006, Clinical immunology.

[34]  Heidi M Crane,et al.  Antiretroviral medications associated with elevated blood pressure among patients receiving highly active antiretroviral therapy , 2006, AIDS.

[35]  E. Castells,et al.  Impact of highly active antiretroviral therapy on blood pressure in HIV‐infected patients. A prospective study in a cohort of naive patients , 2006, HIV medicine.

[36]  O. Kirk,et al.  Predictors of Hypertension and Changes of Blood Pressure in HIV-Infected Patients , 2005, Antiviral therapy.

[37]  L. Niskanen,et al.  Inflammation, Abdominal Obesity, and Smoking as Predictors of Hypertension , 2004, Hypertension.

[38]  K. Birkeland,et al.  Prevalence of Hypertension in HIV-Positive Patients on Highly Active Retroviral Therapy (HAART) Compared with HAART-Naïve and HIV-Negative Controls: Results from a Norwegian Study of 721 Patients , 2003, European Journal of Clinical Microbiology and Infectious Diseases.

[39]  P. Fratino,et al.  Hypertension among HIV patients: prevalence and relationships to insulin resistance and metabolic syndrome , 2003, Journal of hypertension.

[40]  Jeffrey N. Martin,et al.  T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. , 2003, The Journal of infectious diseases.

[41]  B. Hedblad,et al.  Long-Term Effects of Inflammation-Sensitive Plasma Proteins and Systolic Blood Pressure on Incidence of Stroke , 2002, Stroke.

[42]  D. Levy,et al.  Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. , 1997, Circulation.