Member SpotlightsDual Focus: Cardiovascular Studies and HIV/AIDS Strategies in Developing Countries Marc Twagirumukiza, M.D. A Science Advisory Board Member Since 2007  Marc Twagirumukiza, a 2008 Steering Committee Member. Marc Twagirumukiza, M.D. is an assistant lecturer and researcher at the National University of Rwanda and a Ph.D. candidate at Ghent University, Belgium. His medical research is primarily cardiovascular, in particular, the effects of arterial stiffness on cardiovascular disease. He is also dedicated to the development of HIV-AIDS public health programs in developing countries. Twagirumukiza has received scholarships and awards from the European Society of Hypertension (ESH), World Heart Federation (WHF), Vlaams Interuniversitair Raad – Belgium (VLIR), and the Swedish International Development Agency - Department of Research Cooperation (Sida/SAREC). He is on the review board of international peer review journals, including “Current HIV Research”, “Annals of Tropical Medicine and Public Health” and the French-edited peer review journals “Médicine d’Afrique Noire” and “Le Pharmacien d’Afrique”. Twagirumukiza belongs to the Pan African Thoracic Society, International Forum for Hypertension Prevention and Control in Africa (IFHA) of which he is Deputy General Secretary and the Africa Health Research Organization, of which he is Executive Secretary and a Scientific Committee Member. In his leisure time, Twagirumukiza enjoys music (choir and piano), cinema and golf. Academic & Professional Background I graduated from the School of Medicine at National University of Rwanda where I got a Doctoral degree in General Medicine in 2000. In 2003 I got a University Diploma in Epidemiology from Université Victor Segalen, Bordeaux 2, France. In 2004, I got a Training Certificate of “Intensive Courses in Multivariate Analysis Applied to Epidemiology” and “Intensive Courses in Epidemiology, Statistics and Applied informatics” from Université Libre de Bruxelles, School of Public Health, Belgium. From September 2004 to July 2005 I completed a training Certificate in "HIV/AIDS Prevention, Treatment Program Monitoring-Evaluation in Developing Countries” organized by the School of Public Health at the National University of Rwanda and Tulane University School of Public Health and Topical Medicine, New Orleans, USA. Since September 2005, I have been a PhD Candidate in clinical pharmacology at Ghent University (Belgium). I am also a physician at the University's teaching hospital of Butare & Kigali (Rwanda) and assistant lecturer/researcher at Faculty of Medicine, National University of Rwanda. Current Research Interests In recent years great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Those cardiovascular diseases (CVD), which are now increasing in developing countries by their morbidity and mortality, are not entirely predicted by classic risk factors, which could hardly explain the burden in poor countries. Besides known risk factors, physio-pathological mechanisms are now focusing, among others, on arterial stiffness (a major determinant of pulse pressure). This has an independent prognostic relevance for all-cause and cardiovascular mortality. A generally accepted mechanistic view is that an increase in arterial stiffness causes a premature return of reflected waves in late systole. A large number of publications and several reviews reported that increased arterial stiffness itself has been suggested to increase cardiovascular morbidity (coronary heart disease, end stage renal diseases and other target organ damage). In contrast to systemic arterial stiffness, which can only be estimated from models of circulation, regional and local arterial stiffness can be measured directly, and non-invasively, at various sites along the arterial tree. A major advantage of the regional and local evaluations of arterial stiffness is that they are based on direct measurements of parameters strongly linked to wall stiffness. Arterial stiffness can therefore be measured easily. What is interesting for further clinical use is that arterial stiffness surrogates can be assessed noninvasively in large populations by measurement of the pulse-wave velocity (PWV), a simple and reproducible method, and central pressures can be obtained noninvasively. According to the Moens-Korteweg equation, the PWV, which is related to the square root of the elasticity modulus, rises in stiffer arteries. The elastic properties of the aorta and central arteries are the major determinants of systemic arterial impedance, and the PWV measured along the aortic and aorto-iliac pathway is the most clinically relevant. Like other surrogates of arterial stiffness, PWV was shown to be associated with cardiovascular risk, as calculated from the Framingham equations. In 2008, an abridged version of an expert consensus document reporting the proceedings of several meetings of the “European Network for Non Invasive Investigation of Large Arteries” provided an updated and practical overview of the most relevant methodological aspects and clinical applications in the area of arterial stiffness. This report provides recommendations for the determination of regional, local and systemic causes of arterial stiffness, and for the noninvasive determination of wave reflections. This consensus report "Carotid-femoral PWV" is to be considered as the ‘‘gold-standard’’ measurement of arterial stiffness. My current research is focused on the investigation of the arterial stiffness in hypertensive populations of developing countries (sub-Saharan countries in particular), and the assessment of antihypertensive drug response towards arterial stiffness reduction. The overall topic umbrella is “Arterial Hypertension in Africa: investigation of the problem and treatment strategies”. As a PhD fellow, I am the principal investigator under the supervision of the Heymans Institute of Pharmacology (University of Ghent, Belgium). And last, but not least, besides this large area of research, I am working in the General Cardiology field and am highly interested in public health and the tropical & infectious diseases domain. What were the driving factors that led to your current field of study? I began the research career path at the undergraduate level when I was working on clinical research investigating the prevalence of arterial hypertension at the University Hospital of Butare (Rwanda). The results of this limited survey were surprising: the hypertension was a real public health problem at the hospital in terms of morbidity and severe mortality. The problems seen at the hospital should be more assessed in the general population. At that period I was motivated to pursue research on hypertension and to investigate why the arterial hypertension prevalence is increased in this area of Rwanda, a poor developing country plagued by infectious diseases, HIV/AIDS and nutritional deficiencies. I planned to investigate in three steps; first to carry out the community-based survey to state the real picture of high blood pressure, second to investigate on mechanisms and risk factors, and third to investigate the treatment strategies. Has your profession advanced as expected? The process is more sluggish than expected. The reasons for this slowness are complex. The first one is linked to the developing countries context. Research in sub-Saharan settings, like in other developing places, is a real puzzle: there are existing scientists that are always and unsuccessfully asking for financial and logistic means from a poor government to carry out research. Within this context of the lack of human resources, the government asks those unmotivated available scientists to build up a research environment with the aim to apply for funding from any possible external cooperation. The capacity building in this area needs yet to be addressed. The second reason is linked to the training process. Besides the length of the graduate school and post-graduate training which has greatly increased, particularly in medicine, there’s always a delay to pursue research (from undergraduate to post-graduate or doctoral level) linked to a lack of scholarships for doctoral research. I was blessed to rise from this context and to get funding for my ongoing doctoral research. However this is not yet over since the process for post-doctoral scientist support is nonexistent in African developing countries and the research environment is still poor. What are your future career goals? Within my current doctoral research, I combined three steps of planned research: epidemiology studies, experimental investigation, and pharmacology studies. Currently, my goal is to focus on the third step of the research investigating the effect of drugs on arterial stiffness, in sub-African black hypertensive subjects. Advanced research in this area is also foreseen within a post-doctoral fellowship, focusing the impact of affordable drugs on mechanisms of hypertension in sub-Saharan and developing countries. From this research a couple of antihypertensive drugs should be advocated and monitored in terms of cost-effectiveness, affordability and efficacy. The following questions are specific to Twagirumukiza's research interests: Currently, you are a physician and Ph.D. candidate in clinical pharmacology; how will you integrate the two degrees & and which area will you concentrate in? As a life science, clinical pharmacology is a discipline dedicated to drugs and their clinical use. It is focused on bench-to-bedside studies of drug action through an in-depth knowledge of human pharmacology and therapeutics. It’s a hard process of assessment of drugs in the real world. It has a broad scope, from the discovery of new target molecules, to the effects of drug usage in whole populations; in different areas, including drug metabolizing enzymes & transporters, pharmacokinetics, drug interactions & polypharmacy, drug safety, pharmaco-genetics, pharmaco-economics and pharmaco-epidemiology. Therefore clinical pharmacology connects the gap between medical practice and laboratory science. The main objective is to promote the safety of prescriptions, maximize the drug effects and minimize the side effects. In this world of pharmacology, I am focusing on the vascular response of drugs in the scope of reducing blood pressure. All drugs used in the cardiovascular field are therefore related, but specifically I am concentrating on antihypertensive drugs. In developing countries, the physician working in academic medical institutions is dedicated to three missions: research, clinical work (consultations and hospital work, duties, etc), and teaching. A clinical pharmacologist in an area where health care access is limited is asked to play a big role in rational drug use and this process includes rational prescribing - using the right medication, at the right dose, using the right route and frequency of administration for the patient, and stopping the drug appropriately. Therefore I will be focusing on rational prescribing and treatment optimization, advocating research in areas of drug treatment monitoring (which is nearly nonexistent in developing countries). What drug candidates are you currently investigating to help alleviate cardiovascular diseases? In what stage of the drug discovery process are you involved? Drug development or drug discovery is a long process, which leads through several stages including tests in animal and human clinical trials, to a new medicine. My position in this process is at the end, in clinical trials (Phase I to IV). I am concentrating on antihypertensive drugs, focusing on Hydrochlorothiazide, Atenolol, Amlodipine, Enalapril and Methyldopa. Those are drugs advocated by WHO and are listed on the Essential Drug List. Several surveys has been carried out so far within this research project, including pharmaco-economic aspect investigations, quality of drugs found on the African market (qualitative analysis and in vitro dissolution tests) and influence of tropical conditions on the quality of drugs. Next steps will include the pharmacological response assessment. Although your cardiovascular research involves non-communicable diseases, you also have a strong interest in the public health sector in HIV/AIDS. What research methods have you utilized to investigate this communicable disease? Since 2000, I have been involved as a principal investigator or associate in a couple of surveys within the field of HIV/AIDS: epidemiology, strategic framework development, reviewing and analysis, M&E of HIV/AIDS programs, youth reproductive health and behavioral change. Both quantitative and qualitative methodologies have been used according to the variables to investigate and goals of the survey. Quantitative methods included appropriate design and quantitative approach in analysis. Qualitative approach included in-depth interviews and focus group discussions. All surveys included a review of published and unpublished literature through electronic library searches and/or obtained from the programs that were visited and from interviews with researchers in the different institutions. You're currently involved in strategic planning to combat HIV/AIDS spread & you're also responsible for assessment of current HIV/AIDS programs. What geographic region is part of your analysis & how would you rate progress thus far? All work done in this field was mainly undertaken at the hospital level or national level (in Rwanda) and in East African countries: Mulago (Uganda) and Nairobi, Meru and Kiambu (Kenya). Mainly the assessment is guided by Family Health International’s (FHI) recommended methodology. Most of community-based HIV/AIDS programs are facing the problem of human resources and capacity building coupled to inadequate financial means. The FHI’s “self-evaluation of technical capacity tool” (FACT) and indicator matrix suggest that in rural areas, those programs should increase their teamwork skills in the matter of organizing, monitoring and evaluation, financial accountability, and small project design. At the other hand, at the national level, the resource for ARVs are still scarce, and HIV/AIDS programs are far to meet the challenge in offering ARVs (Antiretroviral Drugs) to all HIV-infected patients. The problem of ARV access, ARV store drop out, ARV rational use and treatment monitoring should be addressed specifically in poor countries. From your experience, what communicable disease programs have been effective & ineffective? What elements contribute to a successful program that curbs the spread of communicable disease, and does success require regional or globally coordinated efforts? In Africa overall, there’s no general statement that this program is performing better than others. There is a large contrast between communicable diseases itself but also between countries. The success of a program has been reported to be linked to internal situations (a country's political situation, security, literacy level of the country, human resources, etc.) than external situations. Most of the time financial means are available to build up basic actions, but not enough to deal with program-linked expenses. Whereas in malaria fighting programs real progress is homogeneously recorded, in the HIV/AIDS domain results are very heterogenic and not really spectacular. However, in some countries programs reduced the HIV prevalence spectacularly, like in Uganda (2007 prevalence dropped at 10% in urban areas vs 5.7% in rural areas), and Rwanda (2007 prevalence dropped to 3%) (DHS 2005). Some regions in Rwanda noted a spectacular reduction such as Rwamagana (from 13% to 4% between 1998 and 2005) and Gikondo in Kigali city (14% to 8%) (Ministry of Health, Rwanda, 2005). In Kenya the over all prevalence shifted from 14% (mid-1990) to 5% in 2006 (Ministry of Health Kenya, 2005). The high reductions were observed in regions of Busia, Meru, Nakuru and Thika (2007 HIV Updates, UNAIDS). Even if the drop in prevalence could not be considered as exclusively linked to the HIV/AIDS programs, those programs noted a good management and output in the respected areas. To discuss cardiology research, HIV/AIDS programs, and other topics with fellow Science Advisory Board members, please visit our community forum. Websites Lab Research at Heyman's Institute of Pharmacology API DPM Santé Tropicale Twagirumukiza is a representative of Tropical Health in Rwanda for this organization and is also Editor Team Coordinator for the organization's website. Publications S. Laurent, P. Boutouyrie, R. Asmar, I. Gautier, B. Laloux and L. Guize et al., Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients, Hypertension 37 (2001), pp. 1236–1241. L.M. Van Bortel, H.A. Struijker-Boudier and M.E. Safar, Pulse pressure, arterial stiffness, and drug treatment of hypertension, Hypertension 38 (2001), pp. 914–921. M.F. O'Rourke, J.A. Staessen, C. Vlachopoulos, D. Duprez and G.E. Plante, Clinical applications of arterial stiffness: definitions and reference values, Am J Hypertens 15 (2002), pp. 426–444. Nichols WW, O’Rourke MF. McDonald’s Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles. 3rd ed., London, England: Oxford University Press; 1990:77–142,216–269, 283–359,398–37. Benetos A, Rudnichi A, Safar m, Guize L. Pulse pressure and cardiovascular mortality in normotensive and hypertensive subjects. Hypertension. 1998;32:560–564. Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac AM, Target R, Levy B. Assessment of arterial distensibility by automatic pulse wave velocity measurement: validation and clinical application studies. Hypertension. 1995;26:485–490. S. Laurent, J. Cockcroft, L. Van Bortel, P. Boutouyrie, C. Giannattasio and D. Hayoz et al., Expert consensus document on arterial stiffness: methodological issues and clinical applications, Eur Heart J 27 (2006), pp. 2588–2605. P. Boutouyrie, A.I. Tropeano, R. Asmar, I. Gautier, A. Benetos and P. Lacolley et al., Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients: a longitudinal study, Hypertension 39 (2002), pp. 10–15. T. Shokawa, M. Imazu, H. Yamamoto, M. Toyofuku, N. Tasaki and T. Okimoto et al., Pulse wave velocity predicts cardiovascular mortality: findings from the Hawaii-Los Angeles-Hiroshima study, Circ J 69 (2005), pp. 259–264. T. Willum-Hansen, J.A. Staessen, C. Torp-Pedersen, S. Rasmussen, L. Thijs and H. Ibsen et al., Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population, Circulation 113 (2006), pp. 664–670. F.U. Mattace-Raso, T.J. van der Cammen, A. Hofman, N.M. van Popele, M.L. Bos and M.A. Schalekamp et al., Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study, Circulation 113 (2006), pp. 657–663. L. Van Bortel, E.J. Balkestein, J.J. van der Heijden-Spek, F.H. Vanmolkot, J.A. Staessen and J.A. Kragten et al., Non-invasive assessment of local arterial pulse pressure: comparison of applanation tonometry and echo-tracking, J Hypertens 19 (2001), pp. 1037–1044. J.M. Dijk, A. Algra, Y. van der Graff, D.E. Grobbee, M.L. Bots and SMART study group, Carotid stiffness and the risk of new vascular events in patients with manifest cardiovascular disease. The SMART study, Eur Heart J 26 (2005), pp. 1213–1220. T. Weber, J. Auer, M.F. O'Rourke, E. Kvas, E. Lassnig and G. Lamm et al., Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions, Eur Heart J 26 (2005), pp. 2657–2663. C. Vlachopoulos, I. Dima, C. Aznaouridis, C. Vasiliadou, N. Ioakeimidis and C. Aggeli et al., Acute systemic inflammation increases arterial stiffness and decreases wave reflections in healthy individuals, Circulation 112 (2005), pp. 2193–2200. ### << Previous Next >> [ View All Member Spotlights ] |
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