Blood pressure trajectories and the mediated effects of body mass index and HIV‐related inflammation in a mixed cohort of people with and without HIV in rural Uganda

We sought to describe changes in blood pressure and estimate the effect of HIV on blood pressure (BP) over 4 years of observation in a cohort of 155 HIV‐infected adults (≥40 years) on antiretroviral therapy (ART) and 154 sex‐ and age‐quartile‐matched, population‐based, HIV‐uninfected controls for four years in rural Uganda, we compared changes in blood pressure (BP) by HIV serostatus and tested whether body mass index and inflammation (high‐sensitivity C‐reactive protein and interleukin‐6) and immune activation (sCD14 and sCD163) mediated the effects of HIV on BP using hierarchical multivariate and two‐stage parametric regression models. Overall HIV‐uninfected participants had higher mean BP than HIV‐infected counterparts (differences in trend P < 0.0001 for diastolic BP and P = 0.164 for systolic BP). After initial declines in BP in both groups between years 1 and 2, BP moderately increased in both groups through year 4, with greater change over time observed in the HIV‐uninfected group. Body mass index mediated 72% (95%CI 57, 97) of the association between HIV and systolic BP. We found a minimal mediating effect of sCD14 on the relationship between HIV and SBP (9%, 95% CI 5%, 21%), but found no association between other HIV‐related biomarkers. Over four years of observation, HIV‐infected people in rural Uganda have lower BP than HIV‐uninfected counterparts despite having higher levels of inflammation. BMI, rather than measures of HIV‐associated inflammation, explained a majority of the difference in BP observed.

[1]  H. Chu,et al.  Longitudinal increases in waist circumference are associated with HIV-serostatus, independent of antiretroviral therapy , 2007, AIDS.

[2]  D. Harrison The mosaic theory revisited: common molecular mechanisms coordinating diverse organ and cellular events in hypertension. , 2013, Journal of the American Society of Hypertension : JASH.

[3]  A. Roverato,et al.  Premature age-related comorbidities among HIV-infected persons compared with the general population. , 2011, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  D. Hafeman,et al.  American Journal of Epidemiology Practice of Epidemiology Confounding of Indirect Effects: a Sensitivity Analysis Exploring the Range of Bias Due to a Cause Common to Both the Mediator and the Outcome , 2022 .

[5]  A. Schutte,et al.  Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study. , 2012, International journal of epidemiology.

[6]  L. Keele,et al.  A General Approach to Causal Mediation Analysis , 2010, Psychological methods.

[7]  M. Egger,et al.  Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts , 2015 .

[8]  Jeffrey N. Martin,et al.  D-Dimer Levels and Traditional Risk Factors Are Associated With Incident Hypertension Among HIV-Infected Individuals Initiating Antiretroviral Therapy in Uganda , 2016, Journal of acquired immune deficiency syndromes.

[9]  W. Burns,et al.  Angiotensin-converting enzyme 2 is a key modulator of the renin–angiotensin system in cardiovascular and renal disease , 2011, Current opinion in nephrology and hypertension.

[10]  C. Jericó,et al.  Hypertension in HIV-infected patients: prevalence and related factors. , 2005, American journal of hypertension.

[11]  J. Plutzky,et al.  The biology of atherosclerosis: general paradigms and distinct pathogenic mechanisms among HIV-infected patients. , 2012, The Journal of infectious diseases.

[12]  M. Siedner,et al.  Increased Systemic Inflammation and Gut Permeability Among Women With Treated HIV Infection in Rural Uganda , 2018, The Journal of infectious diseases.

[13]  J. Margolick,et al.  Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection. , 2015, The Journal of infectious diseases.

[14]  S. Chatterji,et al.  An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa , 2012, BMC Public Health.

[15]  Hailey R Banack,et al.  From bad to worse: collider stratification amplifies confounding bias in the “obesity paradox” , 2015, European Journal of Epidemiology.

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

[17]  Kuaban Christopher,et al.  Cardiovascular Autonomic Dysfunction in Africans Infected with Human Immunodeficiency Virus , 2002 .

[18]  Mohammed K. Ali,et al.  HIV and Metabolic, Body, and Bone Disorders: What We Know From Low- and Middle-Income Countries , 2014, Journal of acquired immune deficiency syndromes.

[19]  O. Uthman,et al.  Impact of body fat changes in mediating the effects of antiretroviral therapy on blood pressure in HIV-infected persons in a sub-Saharan African setting , 2016, Infectious Diseases of Poverty.

[20]  E. Sobngwi,et al.  Development and validation of a questionnaire for the assessment of physical activity in epidemiological studies in Sub-Saharan Africa. , 2001, International journal of epidemiology.

[21]  A. Feigl,et al.  Population-Level Decline in BMI and Systolic Blood Pressure Following Mass HIV Treatment: Evidence from Rural KwaZulu-Natal , 2016, Obesity.

[22]  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.

[23]  J. Seeley,et al.  Health and functional status among older people with HIV/AIDS in Uganda , 2011, BMC public health.

[24]  T. Bärnighausen,et al.  The Effect of HIV and the Modifying Effect of Anti-Retroviral Therapy (ART) on Body Mass Index (BMI) and Blood Pressure Levels in Rural South Africa , 2014, PloS one.

[25]  Youhua Liu,et al.  Albumin overload activates intrarenal renin–angiotensin system through protein kinase C and NADPH oxidase-dependent pathway , 2011, Journal of hypertension.

[26]  W. Fawzi,et al.  Association between HIV and blood pressure in adults and role of body weight as a mediator: Cross‐sectional study in Uganda , 2017, Journal of clinical hypertension.

[27]  A. Mangili,et al.  Nutrition and HIV infection: review of weight loss and wasting in the era of highly active antiretroviral therapy from the nutrition for healthy living cohort. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[28]  S. Grinspoon,et al.  Inflammation, immune activation, and cardiovascular disease in HIV. , 2016, AIDS.

[29]  M. Petersen,et al.  Population-Based Assessment of Hypertension Epidemiology and Risk Factors among HIV-Positive and General Populations in Rural Uganda , 2016, PloS one.

[30]  P. Singhal,et al.  Absence of age-related increase in systolic blood pressure in ambulatory patients with HIV infection. , 1999, The American journal of the medical sciences.

[31]  M. Egger,et al.  Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis. , 2015, The lancet. HIV.

[32]  L. Sandvik,et al.  Hypertension in an urban HIV-positive population compared with the general population: influence of combination antiretroviral therapy , 2008, Journal of hypertension.

[33]  M. Lederman,et al.  Soluble markers of inflammation and coagulation but not T-cell activation predict non-AIDS-defining morbid events during suppressive antiretroviral treatment. , 2014, The Journal of infectious diseases.

[34]  Jeffrey N. Martin,et al.  Ideal Cardiovascular Health and Carotid Atherosclerosis in a Mixed Cohort of HIV-Infected and Uninfected Ugandans. , 2016, AIDS research and human retroviruses.

[35]  S. Gari,et al.  Access to HIV/AIDS care: a systematic review of socio-cultural determinants in low and high income countries , 2013, BMC Health Services Research.

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

[37]  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.

[38]  Mardge H. Cohen,et al.  Correlates of prevalent hypertension in a large cohort of HIV-infected women: Women's Interagency HIV Study , 2007, AIDS.

[39]  N. Ford,et al.  Causes of hospital admission among people living with HIV worldwide: a systematic review and meta-analysis. , 2015, The lancet. HIV.

[40]  T. Bärnighausen,et al.  In a study of a population cohort in South Africa, HIV patients on antiretrovirals had nearly full recovery of employment. , 2012, Health affairs.