The African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT)

Lead Research Organisation: North West University

Abstract

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Technical Summary

Cardiovascular disease (CVD) is the number one cause of death world-wide. But Africa is known for its tremendous burden of infectious diseases. With the introduction of antiretroviral therapy, the scene is starting to change with indicators pointing that dramatic increases in the incidence of hypertension and subsequent CVD, will overtake infectious diseases in the near future. Economic progress in African countries, come at a significant cost to the health burden. Although antihypertensive medication is highly cost-effective, the weak health systems in Africa fail to ensure awareness, treatment and control. The status quo can thus not be maintained in Africa concerning current practices to manage hypertension. It may have significantly greater impact if tailored population- and individual targeted prevention strategies are employed in the whole population, but especially in young individuals to early detect, prevent or delay hypertension onset. Such strategies should be based on (a) a clear understanding of the pathophysiological development of hypertension over time in young black populations; (b) coupled with objectively measured health behaviours. The African-PREDICT study was designed to address both aspects by longitudinally tracking and monitoring hypertension development in 1200 healthy black and white individuals (aged 20-30 years). We include apparently healthy men and women of African and European descent from low/mid/high levels of socio-economic status; with brachial blood pressure (BP) < 140 and 90 mmHg; HIV uninfected; no previous diagnosis or medication for chronic disease; and not pregnant or breastfeeding. Within a Hypertension Clinic at the North-West University in South Africa, we perform a wide range of basic and advanced measurements at each visit. We obtain: (1) Questionnaire data including medical history, social status, traditional risk factors (age, sex, smoking, alcohol intake) and dietary intake (24 hour dietary recall on 3 days within a week), personality, psychological distress and psychosocial profile; (2) Biological samples for biomarker analyses (blood, spot & 24hr urine) are preserved at -80°C. The study was designed to assess a wide range of traditional and novel biomarkers, including (i) the RAS Fingerprint™ covering 10 peptides from the renin-angiotensin system; (ii) pro-inflammatory multiplex biomarker analyses and urinary proteomic profiles; (iii) urinary metabolomics, with targeted genomics to be performed at a later stage; (3) Anthropometric measurements, bio-electrical impedance – body fat% and lean mass, and 7-day accelerometric physical activity monitoring; (4) Blood Pressure: 24-hour BP, central BP, and cardiovascular stress reactivity tests; and (5) Assessments of early target organ damage include albuminuria, carotid wall thickness and distensibility, ECG, echocardiography, pulse wave velocity, and retinal microvasculature. Since the study sample comprises participants in their twenties, we anticipate few hard end points (e.g. stroke) in the 10 years of follow-up. The focus will be on ‘soft’ surrogate end points, including changes in biomarker profiles and early target organ damage. By employing also in Africa the latest cutting-edge research on biomarkers and polyomics proven to predict hypertension and cardiovascular outcome, precision medicine may have the potential to lead to novel strategies in preventing and treating hypertension in Africa.

Publications

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Ahiante BO (2019) Leptin and the vasculature in young adults: The African-PREDICT study. in European journal of clinical investigation

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Ahiante BO (2018) Leptin and its Relation to Autonomic Activity, Endothelial Cell Activation and Blood Pressure in a Young Black and White Population: The African-PREDICT study. in Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme

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Barnard SA (2018) Bioavailable IGF-1 is beneficially associated with biomarkers of endothelial function in young healthy adults: The African-PREDICT study. in Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society

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Botha D (2021) Comparing the associations of clinic vs. ambulatory blood pressure with subclinical organ damage in young healthy adults: the African-PREDICT study. in Hypertension research : official journal of the Japanese Society of Hypertension

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Craig A (2021) Urinary albumin-to-creatinine ratio is inversely related to nitric oxide synthesis in young black adults: the African-PREDICT study. in Hypertension research : official journal of the Japanese Society of Hypertension

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Crouch SH (2020) Inflammation and hypertension development: A longitudinal analysis of the African-PREDICT study. in International Journal of Cardiology. Hypertension

 
Description Contributed to the development of a new Roadmap for Hypertension Management in Africa, as part of the Hypertension Task Force of the Pan African Society of Cardiology (PASCAR).
Geographic Reach Africa 
Policy Influence Type Membership of a guideline committee
URL https://www.ncbi.nlm.nih.gov/pubmed/29042191
 
Description Extra Mural Unit
Amount R7,000,000 (ZAR)
Organisation Medical Research Council of South Africa (MRC) 
Sector Public
Country South Africa
Start 03/2017 
End 03/2021
 
Description Self-Initiated Research Grant (Dr. LF Gafane-Matemane)
Amount R600,000 (ZAR)
Organisation Medical Research Council of South Africa (MRC) 
Sector Public
Country South Africa
Start 03/2018 
End 03/2020
 
Description South African Research Chair (SARChI)
Amount R15,000,000 (ZAR)
Organisation South African National Research Foundation (NRF) 
Sector Public
Country South Africa
Start 06/2018 
End 06/2022
 
Description Collaboration on Renin Angiotensin System Fingerprint 
Organisation Attoquant Diagnostics GmbH
Country Austria 
Sector Private 
PI Contribution Dr. Marko Poglitsch is contributing towards the study based on funding obtained from the Newton Fund, namely to perform LC-MSMS analyses of several biomarkers related to the blood pressure regulatory RAS system, i.e. the RAS Fingerprint TM.
Collaborator Contribution Although we have to pay for the analyses performed by Dr. Poglitsch, he will also contribute to scientific interpretation of these analyses.
Impact Multi-disciplinary (biochemistry, physiology, cardiology). No output as yet as we have just received the analytical results of the samples in July 2018. Several scientists and postgraduate students are currently analysing the data.
Start Year 2017
 
Description Collaboration on biomarker Marinobufagenin 
Organisation National Institutes of Health (NIH)
Country United States 
Sector Public 
PI Contribution 24-hour Urine samples shipped to the NIH are analysed for the biomarker, Marinobufagenin, based on the collaboration with Dr. Olga V Fedorova and Dr. Alexei Bagrov. Together we focus on how this marker associate with a variety of cardiovascular measures in this unique black and white young and healthy population.
Collaborator Contribution Apart from ensuring accurate analyses of marinobufagenin, especially Dr. Fedorova make consistent scientific contributions and suggestions for statistical analyses in collaborative research publication writing.
Impact This is a multidisciplinary collaboration (biochemistry, physiology, cardiology). Several research manuscripts were published: 1. Strauss M, Smith W, Kruger R, Wei W, Fedorova OV, Schutte AE. Marinobufagenin and left ventricular mass in young adults: The African-PREDICT study. Eur J Prev Cardiol 2018; 25:1587-1595. https://doi.org/10.1177/ 2047487318788140. 2. Strauss M, Smith W, Wei W, Fedorova OV, Schutte AE. Large artery stiffness is associated with marinobufagenin in young adults: The African-PREDICT study. J Hypertension 2018; 36:2333-2339. doi: 10.1097/ HJH.0000000000001866. 3. Strauss M, Smith W, Wei W, Fedorova OV, Schutte AE. Marinobufagenin is related to elevated central and 24 hr systolic blood pressure in young black women: The African-PREDICT study. Hypertens Res 2018; 41:183-192 https://doi.org/10.1038/s41440-017-0009-x. 4. Strauss M, Smith W, Wei W, Fedorova OV, Schutte AE. Autonomic activity and its relationship with the endogenous cardiotonic steroid marinobufagenin: The African-PREDICT study. Nutr Neurosci 2019 https://doi.org/10.1080/1028415X.2018.1564985.
Start Year 2014
 
Description Collaboration on global bio-electrical impedance consortium 
Organisation University of Lisbon
Country Portugal 
Sector Academic/University 
PI Contribution The International Bio-impedance Analysis Multi-centre Collaboration project, is coordinated by Assistant Professor Analiza Silva, Adjunct Faculty Member at Pennington Biomedical Research Center, USA and Assistant Professor at the Faculty of Human Kinetics, University of Lisbon. Global contributions on body composition data - particularly bio-impedance is a unique collaboration where limited data is available from Africa. This is a measurement taken in all participants of the African-PREDICT study.
Collaborator Contribution Consortia data will be collated and global publications on bio-impedance, body composition estimates and predictions of actual body fact are scientific outcomes of the collaboration.
Impact The agreement has recently been established and thus will take a few months to get established. It is multi-disciplinary including anthropometrics, social sciences, physiology, biochemistry.
Start Year 2019
 
Description Collaboration on urinary micro-elements 
Organisation University of Lausanne
Country Switzerland 
Sector Academic/University 
PI Contribution I designed the study, and the South African research team perform the recruitment, data collection, participant follow-up, as well as manuscript writing and statistical analyses.
Collaborator Contribution Prof. Murielle Bochud and her research team perform analyses of microelements from urine samples. Contribute also to scientific writing and analyses.
Impact Samples will be analysed early in 2018. Multidisciplinary (physiology, biochemistry, cardiology)
Start Year 2017
 
Description Collaboration on urinary nitrites and nitrates 
Organisation Hannover Medical School
Country Germany 
Sector Academic/University 
PI Contribution For the African-PREDICT study we have designed and conceptualised the study, we also operationalised it by including 1202 research participants and performing detailed measurements from 2013-2017. Apart from advanced cardiovascular measurements performed in our Hypertension Research and Training Clinic we also collected biological samples. For this particular collaboration spot urine samples are crucial and these were correctly collected and stored at -80 degrees Celcius.
Collaborator Contribution Collaborative scientists in Hannover at the Core Unit Proteomics has a GC-MS instrument used to measure particular amino acids and more than 30 other substances. All methods are fully validated and published in peer-reviewing chemical analysis-oriented journals. Amino acids and metabolites including ADMA and SDMA are measured simultaneously in urine (usually 10 µL) after a two-step derivatization and solvent extraction. The NO metabolites nitrite and nitrate, creatinine (indispensable in case of urine not collected over 24 hours), malondialdehyde (MDA) - a biomarker of oxidative stress (i.e., lipid peroxidation) will be measured simultaneously, yet in another urine sample aliquot (usually 100 µL), after one-step derivatization and solvent extraction.
Impact During 2018 arrangements were made to ship the full batch of samples from South Africa to Hannover for analyses. Ethics approval and export permits were obtained, samples were shipped, and all analyses were completed. Early in 2019 the analytical results were sent to the team in South Africa and two PhD students (one in Hannover and one in South Africa) are presently analysing the data.
Start Year 2018
 
Description Collboration on biomarker Uromodullin 
Organisation University Hospital Zürich
Department Zurich Centre for Integrative Human Physiology
Country Switzerland 
Sector Academic/University 
PI Contribution I designed the study, and the South African research team recruit participants, conduct all cardiovascular assessments and collect biological samples.
Collaborator Contribution Professor Oliver DeVuyst, expert on biomarker uromodullin, will perform genetic SNPs and urinary levels of uromodullin in the full study cohort. In partnership scientific papers will be written.
Impact Multidisciplinary (biochemistry, physiology)
Start Year 2017
 
Description Interviews with the media on blood pressure awareness 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact • Was interviewed and cited by News24 news network on the rise of obesity as cardiovascular risk factor in South Africa on 30 April 2019. https://www.news24.com/SouthAfrica/News/health-shock-for-sa-20190430-2
• Interview with Pretoria News on 10 May 2019, discussing awareness of hypertension as part of the South African and global May Measurement Month initiative.
• Appeared in newspapers and websites (Cape Times; Rosebank Killarney Gazette; Mercury; All4women) regarding awareness initiative of May Measurement Month 2019 https://www.pressreader.com/south-africa/cape-times/20190509/281663961445876 ; https://rosebankkillarneygazette.co.za/253076/speakers-raise-awareness-about-hypertension/ ; https://www.iol.co.za/mercury/news/call-to-check-blood-pressure-22974321 ; https://www.all4women.co.za/1746049/health/health-news/get-a-free-test-almost-half-of-south-africans-have-high-blood-pressure

• In the Beeld Newspaper, an article appeared on 17 May 2017 highlighting an interview where blood pressure measurements and hypertension awareness was discussed, along with the International Society of Hypertension's May Measurement Month campaign, titled "Hoë bloeddruk gevaarliker as wat jy mag dink".
Year(s) Of Engagement Activity 2017,2018,2019
URL https://www.all4women.co.za/1746049/health/health-news/get-a-free-test-almost-half-of-south-africans...
 
Description Popular publication 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact • Co-authored a popular paper published online in "The Conversation Africa": Schutte AE, Strauss M. Salt is bad for you: but how it affects your body is still frontier science, 2019. https://theconversation.com/salt-is-bad-for-you-but-how-it-affects-your-body-is-still-frontier-science-112895
Year(s) Of Engagement Activity 2019
URL https://theconversation.com/salt-is-bad-for-you-but-how-it-affects-your-body-is-still-frontier-scien...