Lung function and atherosclerosis: a cross-sectional study of multimorbidity in rural Uganda.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure. METHODS: We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status. RESULTS: Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (ß = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT. CONCLUSIONS: Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.

Prevalence and correlates of carotid plaque in a mixed HIV-serostatus cohort in Uganda.

BACKGROUND: The extent to which the risk of atherosclerotic cardiovascular disease (ACVD) is increased among people living with HIV (PLWH) in sub-Saharan Africa remains unknown. SETTING: Cross-sectional analysis nested within the Ugandan Noncommunicable Diseases and Aging Cohort, including PLWH in rural Uganda > 40 years taking antiretroviral therapy (ART) for at least 3 years, and a population-based control group of HIV-uninfected age- and sex-matched persons. METHODS: We conducted carotid ultrasonography and collected ACVD risk factor data. Our outcome of interest was carotid plaque, defined as > 1.5 mm thickness from the intima-lumen interface to the media-adventitia interface. We fit multivariable logistic regression models to estimate correlates of carotid plaque including HIV-specific and traditional cardiovascular risk factors. RESULTS: We enrolled 155 (50.2%) PLWH and 154 (49.8%) HIV-uninfected comparators, with a mean age of  51.4 years. Among PLWH, the median CD4 count was 433 cells/mm3 and 97.4% were virologically suppressed. Carotid plaque prevalence was higher among PLWH (8.4% vs 3.3%). HIV infection (aOR 3.90; 95% CI 1.12-13.60) and current smokers (aOR 6.60; 95% CI 1.22-35.80) had higher odds of carotid plaque, whereas moderate (aOR 0.13, 95% CI 0.01-1.55) and vigorous intensity of physical activity (aOR 0.34, 95% CI 0.07-1.52) were associated with decreased odds of carotid plaque. CONCLUSION: In rural Uganda, PLWH have higher prevalence of carotid plaque compared to age- and sex-matched HIV-uninfected comparators. Future work should explore how biomedical and lifestyle modifications might reduce atherosclerotic burden among PLWH in the region.

Treated HIV Infection and Progression of Carotid Atherosclerosis in Rural Uganda: A Prospective Observational Cohort Study.

Background Although ≈70% of the world's population of people living with HIV reside in sub-Saharan Africa, there are minimal prospective data on the contributions of HIV infection to atherosclerosis in the region. Methods and Results We conducted a prospective observational cohort study of people living with HIV on antiretroviral therapy >40 years of age in rural Uganda, along with population-based comparators not infected with HIV. We collected data on cardiovascular disease risk factors and carotid ultrasound measurements annually. We fitted linear mixed effects models, adjusted for cardiovascular disease risk factors, to estimate the association between HIV serostatus and progression of carotid intima media thickness (cIMT). We enrolled 155 people living with HIV and 154 individuals not infected with HIV and collected cIMT images at 1045 visits during a median of 4 annual visits per participant (interquartile range 3-4, range 1-5). Age (median 50.9 years) and sex (49% female) were similar by HIV serostatus. At enrollment, there was no difference in mean cIMT by HIV serostatus (0.665 versus 0.680 mm, P=0.15). In multivariable models, increasing age, blood pressure, and non-high-density lipoprotein cholesterol were associated with greater cIMT (P<0.05), however change in cIMT per year was also no different by HIV serostatus (0.004 mm/year for HIV negative [95% CI, 0.001-0.007 mm], 0.006 mm/year for people living with HIV [95% CI, 0.003-0.008 mm], HIV×time interaction P=0.25). Conclusions In rural Uganda, treated HIV infection was not associated with faster cIMT progression. These results do not support classification of treated HIV infection as a risk factor for subclinical atherosclerosis progression in rural sub-Saharan Africa. Registration URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02445079.

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.