Michael Bestawros1, Takondwa Chidumayo2, Meridith Blevins3, Ashley Canipe4, Jay Bala5, Paul Kelly6, Suzanne Filteau7, Bryan E Shepherd3, Douglas C Heimburger5, John R Koethe8. 1. Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA. 2. University Teaching Hospital, Lusaka, Zambia. 3. Department of Biostatistics, Vanderbilt University, Nashville, TN, USA. 4. Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University, Nashville, TN, USA. 5. Vanderbilt Institute for Global Health, Nashville, TN, USA. 6. University Teaching Hospital, Lusaka, Zambia ; Barts & the London School of Medicine, London, UK. 7. London School of Hygiene & Tropical Medicine, London, UK. 8. Vanderbilt Institute for Global Health, Nashville, TN, USA ; Division of Infectious Diseases, Vanderbilt University, Nashville, TN, USA.
Abstract
INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.
INTRODUCTION: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.
Entities:
Keywords:
HIV; antiretroviral therapy; cardiovascular; inflammation; nutrition; sub-Saharan Africa
Authors: Ronen Rubinshtein; Jeffrey T Kuvin; Morgan Soffler; Ryan J Lennon; Shahar Lavi; Rebecca E Nelson; Geralyn M Pumper; Lilach O Lerman; Amir Lerman Journal: Eur Heart J Date: 2010-02-24 Impact factor: 29.983
Authors: Kathleen V Fitch; Eleni Stavrou; Sara E Looby; Linda Hemphill; Michael R Jaff; Steven K Grinspoon Journal: Atherosclerosis Date: 2011-04-16 Impact factor: 5.162
Authors: Kevin S Heffernan; Jeffrey T Kuvin; Mark J Sarnak; Ronald D Perrone; Dana C Miskulin; Darya Rudym; Priya Chandra; Richard H Karas; Vandana Menon Journal: Nephrol Dial Transplant Date: 2011-02-03 Impact factor: 5.992
Authors: Sidharth A Shah; Thomas Kambur; Cheeling Chan; David M Herrington; Kiang Liu; Sanjiv J Shah Journal: Am J Cardiol Date: 2013-05-16 Impact factor: 2.778
Authors: L Arnoldo Muñoz-Nevárez; Brandon M Imp; Michael A Eller; Francis Kiweewa; Jonah Maswai; Christina Polyak; Omalla Allan Olwenyi; I Elaine Allen; Eric Rono; Benedetta Milanini; Hannah Kibuuka; Julie A Ake; Leigh Anne Eller; Victor G Valcour Journal: J Neurovirol Date: 2019-08-29 Impact factor: 2.643
Authors: Hubaida Fuseini; Ben A Gyan; George B Kyei; Douglas C Heimburger; John R Koethe Journal: Curr HIV/AIDS Rep Date: 2021-02-19 Impact factor: 5.071
Authors: Emily P Hyle; Bongani M Mayosi; Keren Middelkoop; Mosepele Mosepele; Emily B Martey; Rochelle P Walensky; Linda-Gail Bekker; Virginia A Triant Journal: BMC Public Health Date: 2017-12-15 Impact factor: 3.295
Authors: Benson Njuguna; Jepchirchir Kiplagat; Gerald S Bloomfield; Sonak D Pastakia; Rajesh Vedanthan; John R Koethe Journal: J Diabetes Res Date: 2018-05-23 Impact factor: 4.011