High prevalence of ST-elevation, early repolarization, and left ventricular hypertrophy during the eligibility assessment for an HIV vaccine trial in young, healthy Tanzanians

BACKGROUND: Vaccinia based immunizations have caused myo/pericarditis and vaccine study volunteers are monitored by ECG. We report ECG outcome obtained during the screening period for an HIV vaccine trial. METHODS: ECG was performed in healthy Tanzanian volunteers. ECG abnormalities and findings interfering with the interpretation of myo/pericarditis were subject to study ineligibility. We determined the prevalence of left ventricular hypertrophy (LVH) defined by the Sokolow-Lyon (SL) or the Cornell index, ST-elevations and early repolarization (ERP) in association with gender, age, BMI and body height by regression analysis adjusted for gender and age. RESULTS: In 257 volunteers (median age 23 years, 63% males) overall positivity for LVH defined by SL or Cornell criteria was seen in 20.6% and 3.5%, ST-elevations ≥ 0.1 mV or ≥ 0.2 mV in 77.8% and 38.1%, and ERP in 23.4%. Positive SL criteria were associated with male gender (PR 7.84, p < 0.001) and lower age (PR 0.70, p = 0.002), and associated with increased body height and lower BMI in univariate analysis. Positive Cornell criteria were only associated with lower age (PR 0.44, p = 0.010). ST-elevations ≥ 0.2 mV were associated with male gender (PR 8.05, p < 0.001) and lower age (PR 0.81, p = 0.003), and ERP with male gender (PR 2.86, p < 0.001). Vaccine study ineligibility due to ECG findings was concluded in 22.1% of the screening population. CONCLUSIONS: High prevalence of LVH according to SL in association with ST-elevation and ERP is especially found in young and male Africans. ECG variations need to be considered for eligibility criteria in studies investigating potential cardiotoxic agents in Africa

Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study

Background: PrEP literacy is influenced by many factors including the types of information available and how it is interpreted. The level of PrEP literacy may influence acceptability and uptake. Methods: We conducted 25 in-depth interviews in a HIV vaccine trial preparedness cohort study. We explored what participants knew about PrEP, sources of PrEP knowledge and how much they know about PrEP. We used the framework approach to generate themes for analysis guided by the Social Ecological Model and examined levels of PrEP literacy using the individual and interpersonal constructs of the SEM. Results: We found that PrEP awareness is strongly influenced by external factors such as social media and how much participants know about HIV treatment and prevention in the local community. However, while participants highlighted the importance of the internet/social media as a source of information about PrEP they talked of low PrEP literacy in their communities. Participants indicated that their own knowledge came as a result of joining the HIV vaccine trial preparedness study. However, some expressed doubts about the effectiveness of the drug and worried about side effects. Participants commented that at the community level PrEP was associated with being sexually active, because it was used to prevent the sexual transmission of HIV. As a result, some participants commented that one could feel judged by the health workers for asking for PrEP at health facilities in the community. Conclusion: The information collected in this study provided an understanding of the different layers of influence around individuals that are important to address to improve PrEP acceptability and uptake. Our findings can inform strategies to address the barriers to PrEP uptake, particularly at structural and community levels. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04066881

Examining oral pre-exposure prophylaxis (PrEP) literacy among participants in an HIV vaccine trial preparedness cohort study

Background PrEP literacy is influenced by many factors including the types of information available and how it is interpreted. The level of PrEP literacy may influence acceptability and uptake. Methods We conducted 25 in-depth interviews in a HIV vaccine trial preparedness cohort study. We explored what participants knew about PrEP, sources of PrEP knowledge and how much they know about PrEP. We used the framework approach to generate themes for analysis guided by the Social Ecological Model and examined levels of PrEP literacy using the individual and interpersonal constructs of the SEM. Results We found that PrEP awareness is strongly influenced by external factors such as social media and how much participants know about HIV treatment and prevention in the local community. However, while participants highlighted the importance of the internet/social media as a source of information about PrEP they talked of low PrEP literacy in their communities. Participants indicated that their own knowledge came as a result of joining the HIV vaccine trial preparedness study. However, some expressed doubts about the effectiveness of the drug and worried about side effects. Participants commented that at the community level PrEP was associated with being sexually active, because it was used to prevent the sexual transmission of HIV. As a result, some participants commented that one could feel judged by the health workers for asking for PrEP at health facilities in the community. Conclusion The information collected in this study provided an understanding of the different layers of influence around individuals that are important to address to improve PrEP acceptability and uptake. Our findings can inform strategies to address the barriers to PrEP uptake, particularly at structural and community levels. Trial registration https://clinicaltrials.gov/ct2/show/NCT0406688

Effect of previous exposure to malaria on blood pressure in Kilifi, Kenya: A Mendelian randomization study

Background Malaria exposure in childhood may contribute to high blood pressure (BP) in adults. We used sickle cell trait (SCT) and α+thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24‐hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with −2.4 (95% CI, −4.7 to −0.2) mm Hg lower 24‐hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30‐ to 59‐year‐old participants, among whom it was associated with −6.1 mm Hg (CI, −10.5 to −1.8) lower 24‐hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24‐hour systolic BP in Kilifi was −3.5 mm Hg (CI, −6.9 to −0.1), increasing to −5.2 mm Hg (CI, −9.5 to −0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 (CI, 0.76–0.98) for SCT and 0.89 (CI, 0.80–0.99) for α+thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets

[PP.01.13] Marked BP distribution shift from casual to ambulatory measurement in Kenya

Objective: Few studies have used ambulatory blood pressure monitoring (ABPM) to describe blood pressure (BP) patterns in sub-Saharan Africa (sSA). We conducted a population-based study in Kilifi, Kenya to determine the usefulness of ABPM in this setting. Methods: Design and method: An age-stratified sample of 1248 individuals were randomly selected from our Demographic Surveillance Area. Of these, 986 underwent casual BP measurement at their homes using an automated Omron™ M10-IT monitor. All individuals with casual BP above 140/90mmHg (mean of 2 out of 3 readings) and a random subset with BP below 140/90mmHg were invited to undergo 24-hour ABPM within one week of screening. ESH defined cutoffs were used to define hypertensive status. Results: Of 415 individuals who underwent both casual and ABPM measurement, 162 (39%) had sustained hypertension, 161 (39%) were normotensive, 58 (14%) had whitecoat hypertension and 34 (8%) had masked hypertension. Population BP was markedly higher when using casual BP compared to ABPM (11mmHg 95% CI [9–13] systolic and 9mmHg [7–11] diastolic). If casual BP measurement only had been used, age standardized population prevalence of hypertension would have been 26.5% (19.3–35.6). ‘True’ prevalence by ABPM was 17.1% (11.0–24.4), masked hypertension 7.6 (2.8–13.7)% and white coat hypertension 3.8% (1.7–6.1) of the population. The sensitivity and specificity of casual BP measurement for ‘diagnosing’ hypertension were 80% (73–86) and 84% (79–88) respectively. The positive and negative predictive values were 80% (74–85) and 84% (79–89). BP indices and validity measures showed strong age related trends; for example sensitivity of casual BP was 9.7% (2.5–24.9) in 30–39 year olds but 91% (83–97) in 60–69 year olds. Non-dipping was present in 9% (3–15) of the population and was strongly associated with masked hypertension (OR 10, [4–27]). Conclusions: Casual BP measurement methods substantially overestimated hypertension prevalence, while failing to identify a significant proportion who were hypertensive on ABPM. Whether ABPM identifies those at risk of future vascular events better than casual methods and is justified on cost effectiveness in sSA are key research questions.</p

Clinical and epidemiological implications of 24-Hour ambulatory blood pressure monitoring for the diagnosis of hypertension in Kenyan adults: A population-based study

Background The clinical and epidemiological implications of using ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension have not been studied at a population level in sub‐Saharan Africa. We examined the impact of ABPM use among Kenyan adults. Methods and Results We performed a nested case–control study of diagnostic accuracy. We selected an age‐stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP ≥140/90 mm Hg and a random subset of those with screening BP &lt;140/90 mm Hg were invited to undergo ABPM. Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, “white coat” hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM. Screening BP ≥140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5–31.5%). Age standardized prevalence of screening BP ≥140/90 mm Hg was 26.5% (95% CI 19.3–35.6%). On ABPM, 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4–23.1%) and age‐standardized prevalence of 17.1% (95% CI 11.0–24.4%). Age‐standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8–13.7%) and 3.8% (95% CI 1.7–6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73–86%) and 84% (95% CI 79–88%), respectively. BP indices and validity measures showed strong age‐related trends. Conclusions Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM. Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults

Blood pressure and arterial stiffness in Kenyan adolescents with the sickle cell trait

The potential association between sickle cell trait (SCT) and increased arterial stiffness/blood pressure (BP) has not been ev aluated in detail despite its association with stroke, sudden death, and renal disease. We performed 24-hour ambulatory BP monitoring and arterial stiffness measurements in adolescents raised in a malaria-free environment in Kenya. Between December 2015 and June 2016, 938 randomly selected adolescents (ages 11-17 years) who had been continuous residents of Nairobi from birth were invited to participate in the study. Standard clinic BP measurement was performed, followed by 24-hour ambulatory BP monitoring and arterial stiffness measurement using an Arteriograph24 (TensioMed Ltd., Budapest, Hungary) device. SCT status was determined using DNA genotyping in contemporaneously collected blood samples. Of the 938 adolescents invited to participate, 609 (65%) provided complete data for analysis. SCT was present in 103 (15%). Mean 24-hour systolic and diastolic BPs were 116 (standard deviation (SD), 11.5) mm Hg and 64 (SD, 7) mm Hg, respectively, in children with SCT and 117 (SD, 11.4) mm Hg and 64 (SD, 6.8) mm Hg, respectively, in non-SCT children. Mean pulse wave velocity (PWV) was 7.1 (SD, 0.8) m/second and 7.0 (SD, 0.8) m/second in SCT and non-SCT children, respectively. We observed no differences in PWV or in any clinic or ambulatory BP-derived measures between adolescents with and without SCT. These data suggest that SCT does not independently influence BP or PWV

Blood pressure and arterial stiffness in Kenyan adolescents with the Sickle Cell Trait

The potential association between sickle cell trait (SCT) and increased arterial stiffness/blood pressure (BP) has not been evaluated in detail despite its association with stroke, sudden death and renal disease. We performed 24-hour ambulatory BP monitoring and arterial stiffness measurements in adolescents raised in a malaria free environment in Kenya. Between December 2015 and June 2016, 938 randomly selected adolescents that had been continuous residents of Nairobi from birth were invited to participate in the study. Standard clinic BP measurement was performed followed by 24-hour ambulatory BP monitoring and arterial stiffness measurement using an Arteriograph device. SCT status was determined using DNA genotyping on contemporaneously collected blood samples. Of 938 invited, 609 (65%) provided complete data for analysis. SCT was present in 103 (17%). Mean 24-hour systolic and diastolic BP, SD was (116, 11.5) and (64, 7) mmHg respectively in SCT; and (117, 11.4) and (64, 6.8) in non-SCT. Mean pulse wave velocity (PWV), SD was (7, 0.8) and (7, 0.8) ms-1 respectively in SCT and non-SCT. No differences were observed in PWV and any clinic or ambulatory BP derived measures between those with and without SCT. These data suggest that SCT does not independently influence BP or PWV

Blood pressure and arterial stiffness in Kenyan adolescents with α+thalassemia

Background Recent studies have discovered that α‐globin is expressed in blood vessel walls where it plays a role in regulating vascular tone. We tested the hypothesis that blood pressure (BP) might differ between normal individuals and those with α+thalassemia, in whom the production of α‐globin is reduced. gMethods and Results The study was conducted in Nairobi, Kenya, among 938 adolescents aged 11 to 17 years. Twenty‐four‐hour ambulatory BP monitoring and arterial stiffness measurements were performed using an arteriograph device. We genotyped for α+thalassemia by polymerase chain reaction. Complete data for analysis were available for 623 subjects; 223 (36%) were heterozygous (−α/αα) and 47 (8%) were homozygous (−α/−α) for α+thalassemia whereas the remaining 353 (55%) were normal (αα/αα). Mean 24‐hour systolic BP ±SD was 118±12 mm Hg in αα/αα, 117±11 mm Hg in −α/αα, and 118±11 mm Hg in −α/−α subjects, respectively. Mean 24‐hour diastolic BP ±SD in these groups was 64±8, 63±7, and 65±8 mm Hg, respectively. Mean pulse wave velocity (PWV)±SD was 7±0.8, 7±0.8, and 7±0.7 ms−1, respectively. No differences were observed in PWV and any of the 24‐hour ambulatory BP monitoring‐derived measures between those with and without α+thalassemia. Conclusions These data suggest that the presence of α+thalassemia does not affect BP and/or arterial stiffness in Kenyan adolescents