Vascular dysfunction and body mass index in African adults with HIV.

BACKGROUND: Impaired vascular compliance is common among persons with HIV (PWH) and a risk factor for cardiovascular disease (CVD), though many studies documenting this are from regions with a high prevalence of overweight and obesity. The prevalence and characteristics of impaired vascular compliance among PWH with low body mass index (BMI) is not well described, particularly in sub-Saharan Africa (SSA) where the majority of PWH live, a low BMI is more common, and the burden of CVD is rising. AIM: To assess non-invasive vascular compliance measurements, including augmentation index (AIX), pulse wave velocity (PWV) and pulse waveforms, in underweight, normal weight, and overweight PWH on long-term antiretroviral therapy (ART) in SSA. METHODS: A cross-sectional study among PWH on ART at the University Teaching Hospital in Lusaka, Zambia. All participants had been on a regimen of efavirenz, emtricitabine, and tenofovir disoproxil fumarate for five or more years. Carotid-femoral PWV (cfPWV), carotid-radial PWV (crPWV), and the corresponding augmentation indexes (cfAIX and crAIX), were measured in all participants, in addition to aortic pressure waveforms, classified as type A, B, C and D according to reflected wave timings and amplitude. Multiple linear regression assessed relationships between demographic and clinical factors with vascular measurement endpoints. RESULTS: Ninety one PWH on long-term ART were enrolled; 38 (42%) were underweight (BMI < 18.5 kg/m2), 43 (47%) were normal weight (18.5-24.9 kg/m2) and 10 (11%) were overweight (> 25 kg/m2). Median age was 41, 40 and 40 years, among the three groups, respectively, and the proportion of women increased with BMI level. Overweight participants had a 39% higher cfAIX compared to normal-weight participants, while being underweight was associated with 27% lower cfAIX, after adjusting for age, sex and blood pressure (P = 0.02 and P = 0.01, respectively), but measurements of cfPWV, crPWV and crAIX did not differ. CONCLUSION: Underweight PWH in SSA had lower cfAIX measurements compared to normal weight individuals, indicating less arterial stiffness. However, similar cfPWV, crPWV and crAIX values among the underweight and overweight PWH suggest a low BMI may not confer substantial protection against impaired vascular compliance as a contributor to CVD risk among individuals on ART.

May Measurement Month 2019: an analysis of blood pressure screening results from Zambia.

In Zambia, hypertension accounts for the highest proportion of deaths due to cardiovascular diseases causing 3.3% of all deaths, killing an average of 670 people per year. May Measurement Month (MMM) is an annual global screening campaign aiming to improve awareness of blood pressure (BP) at the individual and population level. Adults (≥18 years) recruited through opportunistic sampling were screened at multiple sites within Lusaka during May and June 2019. Ideally, three BP readings were measured for each participant, and data on lifestyle factors and comorbidities were collected. Data were analysed centrally by the MMM project team and multiple imputations were performed where necessary. Of the total of 9232 enrolled, 8.7% of them had never had their BP measured, 2.5% had diabetes mellitus, 1.9% had had a myocardial infarction, 1.5% had had a stroke, 10.6% were current smokers, and 10.0% consumed alcohol once or more per week. Blood pressure fell from a mean of 128.6/82.9 mmHg for the 1st reading to a mean of 123.2/80.0 mmHg for the 3rd reading. The lowest proportion of participants with hypertension was identified by the 3rd reading alone (30.0%). Of all the participants, 30.7% had hypertension, though only 42.6% of them were aware of their diagnosis. Seven hundred and eighty-three (27.6%) were on antihypertensive medication though only 35.0% of them had controlled BP (systolic BP <140 mmHg and diastolic BP <90 mmHg). Compared with MMM17 data, there is deterioration of the monitored parameters calling for urgent and accelerated public health policy and clinical practice interventions. We think that the MMM campaign should continue annually to raise awareness of this treatable condition.

Arterial stiffness is associated with oxidative stress and endothelial activation among persons with treated HIV in Zambia.

BACKGROUND: Cardiovascular disease (CVD) prevalence is rising among persons with HIV (PLWH) in sub-Saharan Africa. Oxidative stress and endothelial activation, resulting in reduced vascular compliance, are contributors to CVD risk. However, there is a paucity of vascular health data in this population. OBJECTIVES: To assess the relationships of oxidative stress and endothelial activation with vascular stiffness among PLWH. METHOD: Fifty-four PLWH on antiretroviral therapy > 5 years and 57 HIV-negative controls, all aged 18-45 years, were enrolled from the University Teaching Hospital, Lusaka, Zambia. Oxidative stress was measured by nitrotyrosine, a peroxynitrite biomarker, and endothelial activation by soluble intercellular adhesion molecule-1 (sICAM-1) plasma levels. Vascular compliance was measured using carotid-radial pulse wave velocity (crPWV) and arterial stiffness index (crASI). RESULTS: PLWH had higher sICAM-1 levels (median 345 ng/mL) compared to controls (275 ng/mL, p < 0.01), as well as higher nitrotyrosine levels (297 versus 182 nM; p = 0.02). Median crPWV was similar between the groups, but PLWH had higher crASI (2.4 versus 2.2 cm/ms; p < 0.05). After adjusting for age, fat mass, and blood pressure, the estimated effect of a one unit increase in nitrotyrosine on crPWV were twofold higher in the PLWH, but neither reached significance. In a model pooling all participants, there were significant differences in the relationship of nitrotyrosine with crPWV and crASI by HIV status. CONCLUSION: PLWH in sub-Saharan Africa had significantly greater oxidative stress and endothelial activation compared to HIV-negative individuals. These factors may contribute to increased arterial stiffness and higher CVD prevalence in this population.

Immune activation and arterial stiffness in lean adults with HIV on antiretroviral therapy.

BACKGROUND: Greater T-cell activation was associated with reduced vascular compliance amongst persons living with HIV (PLWH) especially among overweight and obese individuals. There is a paucity of data regarding immune activation and arterial stiffness amongst PLWH in sub-Saharan Africa (SSA). OBJECTIVE: To determine the association between immune activation and arterial stiffness in lean PLWH in SSA. METHOD: Forty-eight human immunodeficiency virus positive (HIV+) adults on antiretroviral therapy (ART) >5 years and 26 HIV-negative adults, all with BMI < 25 kg/m2 and no history of CVD, were enrolled. The relationship of vascular compliance with circulating CD4+ and CD8+ naïve, memory, activated and senescent T cells, and serum 8-isoprostane was assessed by HIV status. RESULTS: Increased immune activation was observed in the CD4+ and CD8+ T cells of PLWH, 16.7% vs. 8.9% and 22.0% vs. 12.4% respectively; p < 0.001 (both). Furthermore, a higher proportion of senescent CD4+ T cells were associated with a lower carotid-femoral pulse wave velocity (cfPWV; p = 0.01), whilst a higher proportion of activated CD8+ T cells were associated with a lower carotid-radial pulse wave velocity (crPWV; p = 0.04), after adjustment for BMI and age. However, PLWH also had a higher median carotid-femoral augmentation index (cfAiX) (21.1% vs. 6.0%; p < 0.05) in comparison to their HIV controls. CONCLUSION: Our population of lean PLWH had increased immune activation and higher cfAiX, a marker of arterial stiffness, compared to HIV-negative persons. The negative association between immune activation and arterial stiffness as measured by crPWV in PLHW on long-term treatment needs further elucidation.

Endothelial dysfunction and body mass index: is there a role for plasma peroxynitrite?

BACKGROUND: Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while in underweight persons, oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo). The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15-20 hours post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial dependent and independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. RESULTS: Nitrotyrosine levels in saline-treated rats were similar among the weight-groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, Rmax (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower Rmax in the underweight (106%) compared to the normal weight (112%). Overweight rats had a significant decrease in Rmax (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower Rmax accompanied an increase in peroxynitrite after acetylcholine challenge in all weight-groups. CONCLUSIONS: Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

Haemodynamic responses to tobacco smoke inhalation in male adolescents in Lusaka, Zambia.

BACKGROUND: Tobacco smoke causes changes in the levels of catecholamines in the blood. This leads to an increase in blood pressure and heart rate. This is due to nicotine which has also been noted to cause a decrease in vasodilatory activities leading to an increase in both the blood pressure and heart rate. AIM: To determine the acute effects of tobacco smoke on haemodynamics in black male adolescents in Lusaka, Zambia. STUDY DESIGN: This was an observational study done at the University of Zambia School of Medicine Cardiovascular Research Laboratory in the month of December, 2014. METHODOLOGY: Twenty-two (22) black, male-adolescent (age range 19-25 years), active-smokers, consented to participate in the study. The Diasys Ambulatory Blood Pressure Monitoring system (Novacor, France) was used to obtain the Systolic and Diastolic blood pressures (SBP and DBP) and the heart rate. These were obtained 15 minutes before smoking at 5 minute intervals and averaged to obtain the baseline, during the 15 minutes of smoking and on immediate cessation of smoking and thereafter every 15 minutes up to an hour after smoking. RESULTS: There was a significant rise in SBP (mmHg) during smoking (127.9 ± 13.80 mmHg) from baseline values (113.5 ± 13.15 mmHg) (P = .00). It took 30 minutes for the SBP to return to baseline after cessation of smoking. DBP (mmHg) also increased from baseline (79.5 ± 8.79 mmHg) to 85.6 ± 10.92 mmHg during smoking (P = .01). It returned to baseline values immediately after cessation of smoking. The heart rate (bpm) was also noted to significantly increase during smoking (95.2 ± 16.72 bpm) from the values noted before smoking (74.3 ± 13.75 bpm) (P = .05). The mean value for heart rate returned to baseline value by the 15th minute of recovery. CONCLUSION: The present study demonstrates that smoking may be the cause for the acute increases in SBP, DBP and heart rate in smokers. The smoking caused significant increases in all the haemodynamic indices considered in this study within 15 minutes. Both SBP and DBP increase are indices for stroke and coronary heart disease respectively. The effect of increased SBP was noted to last for 30 minutes while DBP returned to baseline immediately after smoking. A significant increase in heart rate was also noted in the study.