JANUARY – APRIL 2024 VOL 35 NO 1 • Percutaneous coronary intervention facilities in Nigeria • Arterial stiffness assessment in obese black South Africans • Improving adherence to guideline-directed medical therapy • Outcomes of percutaneous balloon mitral valvuloplasty in Tanzania • Surgically treated histologically benign cardiac myxomas • Right atrial strain in an adult African population according to age • Pre-eclampsia: cardiac function in HIV-positive and -negative women • Calcified right ventricular fibroma in an adult CardioVascular Journal of Afr ica (off icial journal for PASCAR) www.cvja.co.za
Pharmaco Distribution (Pty) Ltd. 3 Sandown Valley Crescent, South Tower, 1st Floor Sandton, 2196. PO Box 786522, Sandton, 2146. South Africa Tel: +27 11 784 0077. Fax: +27 11 784 6994. www.pharmaco.co.za ISA _ 21 _ 01 References: 1. Ismo® South African SAHPRA aproved package insert. 2. Ismo 20 Product Monograph(2015). 3. Abshagen,U. 1992. Pharmacokinetics of isosorbide mononitrate. The American Journal of Cradiology, [online] 70 (17),pp.G61-G66 4. Thadani U, Maranda CR, Amsterdam E, et al. Lack of Pharmacological Tolerance and Rebound Angina Pectoris during Twice-daily Therapy with isosorbide-5-mononitrate. Annals of Internal Medicine. 1994.; 120: 353-359. ISMO®-20 R/7.1.4/136. Each Ismo®-20 Tablet contains Isosorbide-5-mononitrate 20mg. S3 For full prescribing information, please refer to the approved package insert R T S Q P R T S Q P P Long term prophylaxis and management of Angina Pectoris1 No first-pass metabolism. 100% bioavalability2,3 Twice-daily dosing regimen shown to avoid withdrawal and tolerance4 Trust the Original!
ISSN 1995-1892 (print) ISSN 1680-0745 (online) Cardiovascular Journal of Afr ica www.cvja.co.za CONTENTS INDEXED AT SCISEARCH (SCI), PUBMED, PUBMED CENTRAL AND SABINET Vol 35, No 1, JANUARY – APRIL 2024 EDITORS Editor-in-Chief (South Africa) PROF PAT COMMERFORD Assistant Editor PROF JAMES KER (JUN) Regional Editor DR A DZUDIE Regional Editor (Kenya) DR F BUKACHI Regional Editor (South Africa) PROF R DELPORT EDITORIAL BOARD PROF PA BRINK Experimental & Laboratory Cardiology PROF R DELPORT Chemical Pathology PROF MR ESSOP Haemodynamics, Heart Failure & Valvular Heart Disease DR OB FAMILONI Clinical Cardiology DR V GRIGOROV Invasive Cardiology & Heart Failure PROF J KER (SEN) Hypertension, Cardiomyopathy, Cardiovascular Physiology DR J LAWRENSON Paediatric Heart Disease PROF A LOCHNER Biochemistry/Laboratory Science DR MT MPE Cardiomyopathy PROF DP NAIDOO Echocardiography PROF B RAYNER Hypertension/Society PROF MM SATHEKGE Nuclear Medicine/Society PROF YK SEEDAT Diabetes & Hypertension PROF H DU T THERON Invasive Cardiology INTERNATIONAL ADVISORY BOARD PROF DAVID CELEMAJER Australia (Clinical Cardiology) PROF KEITH COPELIN FERDINAND USA (General Cardiology) DR SAMUEL KINGUE Cameroon (General Cardiology) DR GEORGE A MENSAH USA (General Cardiology) PROF WILLIAM NELSON USA (Electrocardiology) DR ULRICH VON OPPEL Wales (Cardiovascular Surgery) PROF PETER SCHWARTZ Italy (Dysrhythmias) PROF ERNST VON SCHWARZ USA (Interventional Cardiology) SUBJECT EDITORS Nuclear Medicine and Imaging DR MM SATHEKGE Heart Failure DR G VISAGIE Paediatric DR S BROWN Paediatric Surgery DR DARSHAN REDDY Renal Hypertension DR BRIAN RAYNER Surgical DR F AZIZ Adult Surgery DR J ROSSOUW Epidemiology and Preventionist DR AP KENGNE Pregnancy-associated Heart Disease PROF K SLIWA-HAHNLE 3 FROM THE EDITOR’S DESK P Commerford CARDIOVASCULAR TOPICS 4 Percutaneous coronary intervention facilities in Nigeria OT Olorunda • K Okoro • B Okoh • T Majekodunmi 7 Arterial stiffness assessment in obese black South African patients TL Rasakanya, E Osuch 12 A strategy to improve adherence to guideline-directed medical therapy (GDMT) and the role of the multidisciplinary team in a heart-failure programme W AlHabeeb • F Alayoubi • A Hayajneh • A Ullah • F Elshaer 16 Characteristics and immediate outcomes of patients who underwent percutaneous balloon mitral valvuloplasty at the Jakaya Kikwete Cardiac Institute, Tanzania RK Mutagaywa • MJ Cramer • P Chillo • A Barongo • E Kifai • S Chamuleau • C Eze-Nliam • NB Vera • D Nkya • A Loth • B Alencherry • S Mongella • H Mayala • P Kisenge • S Mwinchete • AB Joseph • G Kwesigabo • A Kamuhabwa • M Albaghdadi • J Ghobrial • M Janabi 27 Clinical characteristics, diagnostic methods and results of surgically treated histologically benign cardiac myxomas DA Görür • H Şaşkin 35 Association between apelin-12 and creatine kinase-MB, depending on success of reperfusion in STEMI patients X Krasniqi • J Vincelj • M Gashi • B Berisha • D Kocinaj 40 Assessment value of the modified early warning score for long-term prognosis of older patients with chronic heart failure Y Yin • J Chen • S Jiang
CONTENTS Vol 35, No 1, JANUARY – APRIL 2024 FINANCIAL & PRODUCTION CO-ORDINATOR ELSABÉ BURMEISTER Tel: 021 976 8129 Fax: 086 664 4202 Cell: 082 775 6808 e-mail: elsabe@clinicscardive.com PRODUCTION EDITOR SHAUNA GERMISHUIZEN Tel: 021 785 7178 Cell: 083 460 8535 e-mail: shauna@clinicscardive.com CONTENT MANAGER MICHAEL MEADON (Design Connection) Tel: 021 976 8129 Fax: 0866 557 149 e-mail: michael@clinicscardive.com The Cardiovascular Journal of Africa, incorporating the Cardiovascular Journal of South Africa, is published 10 times a year, the publication date being the third week of the designated month. COPYRIGHT: Clinics Cardive Publishing (Pty) Ltd. LAYOUT: Jeanine Fourie – TextWrap PRINTER: Tandym Print/Castle Graphics ONLINE PUBLISHING & CODING SERVICES: Design Connection & Active-XML.com All submissions to CVJA are to be made online via www.cvja.co.za Electronic submission by means of an e-mail attachment may be considered under exceptional circumstances. Postal address: PO Box 1013, Durbanville, RSA, 7551 Tel: 021 976 8129 Fax: 0866 644 202 Int.: +27 21 976 8129 e-mail: info@clinicscardive.com Electronic abstracts available on Pubmed Audited circulation Full text articles available on: www.cvja. co.za or via www.sabinet.co.za; for access codes contact elsabe@clinicscardive.com Subscription: To subscribe to the online PDF version of the journal, e-mail elsabe@clinicscardive.com • R500 per issue (excl VAT) • R2 500 for 1-year subscription (excl VAT) The views and opinions expressed in the articles and reviews published are those of the authors and do not necessarily reflect those of the editors of the Journal or its sponsors. In all clinical instances, medical practitioners are referred to the product insert documentation as approved by the relevant control authorities. 44 Right atrial strain in a normal adult African population according to age N Mushitu • R Meel REVIEW ARTICLE 52 Pre-eclampsia: does cardiac function differ in HIV-positive and -negative women? R Bhorat • I Bhorat • OP Khaliq • J Moodley CASE REPORT 64 Calcified right ventricular fibroma in an adult H Gao • S Yuan • Z Hu • Z Zheng • Y Wang • S Wu PUBLISHED ONLINE (Available on www.cvja.co.za and in PubMed)
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 AFRICA 3 From the Editor’s Desk I am pleased to be able to offer you in, this issue, an array of articles of interest from Africa and other parts of the world. Olorunda and colleagues (page 4) describe percutaneous coronary intervention facilities (PCI) in Nigeria. They examined the national records and concluded that there is a lack of PCI-capable facilities in Nigeria and that there needs to be an investment from the government and stakeholders in Nigeria to increase the access to PCI, given the paradigm shift from communicable to non-communicable diseases. I applaud the authors but respectfully wish to offer an alternative argument. I am not aware (and await to be informed) of any study that shows that increasing access to PCI would make any impact on mortality, at a population level in Africa. On the contrary, there is excellent evidence that simple measures such as stopping smoking (by increasing taxes on tobacco and reducing illegal cigarette sales), improved primary healthcare (PHC) and improved prescription of simple, cheap medications at PHC level may be more valuable to the future health of the African population than PCI facilities, expensive medications, devices, catheters and highly paid staff. The authors point out that the management of acute coronary syndrome (ACS) inNigeria is limitedby anon-existent prehospital emergency medical services system, delays in presentation and limited capabilities for reperfusion. Decades ago, the ISIS studies showed that the simple administration of aspirin orally, early after onset of symptoms of ACS, improved the prognosis. I would be interested to read a cost/benefit analysis of the value to the population as opposed to implementation of the inexpensive, easily applied measures mentioned above. On a related but different theme, AlHabeeb and co-authors (page 12) describe a retrospective, observational research on patients with heart failure at a cardiac centre in Riyadh, to observe the heart failure patients’ management before (January to December 2014) and after (January to December 2015) the establishment of a programme to manage heart failure. The multidisciplinary heart-failure programme resulted in a positive effect, in the form of improved patient care, after including the clinical pharmacist and nurse specialist. My interpretation of the message is that simple, low-cost interventions improve patient outcomes and we should be exploring them. Pat Commerford Editor-in-Chief Professor PJ Commerford
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 4 AFRICA Cardiovascular Topics Percutaneous coronary intervention facilities in Nigeria Olufemi T Olorunda, Kelechukwu Okoro, Basil Okoh, Tosin Majekodunmi Abstract Background: In Nigeria, the incidence of coronary artery disease has doubled over the last three decades. However, there appears to be a lack of adequate heart catheterisation facilities. Methods: A list of percutaneous coronary intervention (PCI)- capable facilities was compiled for each state in Nigeria and the federal capital territory. Population estimates for 2019 were obtained from the National Bureau of Statistics and this was utilised to calculate the number of PCI facilities per person in each state and the country. Results: There are 12 operational PCI facilities in Nigeria, 11 of which are in the private health sector. Overall, there is one PCI facility per 16 761 272 people in Nigeria. Conclusions: There is a distinct lack of PCI-capable facilities in Nigeria. There needs to be an investment from the government and stakeholders in Nigeria to increase the access to PCI, given the paradigm shift from communicable to noncommunicable diseases. Keywords: percutaneous coronary intervention, acute coronary syndrome, Nigeria Submitted 20/3/22; accepted 27/7/22 Published online 9/2/24 Cardiovasc J Afr 2024; 35: 4–6 www.cvja.co.za DOI: 10.5830/CVJA-2022-041 Thereisaparadigmshiftfromcommunicabletonon-communicable diseases in sub-Saharan Africa.1-3 Cardiovascular disease is the second most common cause of death in Africa and is responsible for 10% of all deaths.4 The World Health Organisation estimated that 361 000 deaths were caused by ischaemic heart disease in Africa and projected that this number will double by 2030.1 In Nigeria, the incidence of coronary artery disease has doubled over the last three decades, and the incidence of acute coronary syndrome (ACS) was reported to be 45.98 per 100 000 hospitalised adults per year.3 The appropriate management of a ST-elevation myocardial infarction (STEMI) requires the prompt identification of the disease process, swift initiation of the pre-hospital system, transport to the appropriate hospital, medication administration, and rapid activation of the heart catheterisation laboratory.4-6 Management of ACS in Nigeria is limited by a non-existent prehospital emergency medical services system, delays in presentation and limited capabilities for reperfusion.3 This has led to a high rate of mortality and major adverse cardiac events.3 In Nigeria, there is a distinct lack of adequate heart catheterisation laboratory facilities.7 The coronary angiography rate for ACS in Nigeria was reported to be 42.4% and percutaneous coronary intervention (PCI) was performed on 28.6% of patients in a study by Isezuo et al.3 The goal of this article was to examine the availability of PCI-capable facilities in Nigeria. Methods A complete list of PCI-capable facilities in Nigeria was compiled by visiting some of the PCI facilities, performing multiple internet searches, and discussion with local physicians and cardiologists. The list of facilities was obtained for each state and the federal capital territory. Every PCI-capable facility was then contacted to verify whether their facility was operational. Facilities that were non-operational as of 28 January 2022 were excluded. The final list of PCI-capable facilities was verified by a local and interventional cardiologist in Nigeria. The population estimate for Nigeria for 2019 was obtained from the National Bureau of Statistics website.8 The number of PCI facilities per persons living in each state where the facility was available was calculated (Fig. 1). The number of PCI facilities per person for the country was also calculated. Results There was a total of 12 operational PCI-capable facilities identified in Nigeria (Table 1). Only six states had functional PCI facilities, with Lagos and Abuja having four each. The list of these PCI facilities is provided in (Table 2). The concentration of PCI facilities per state was the lowest in Rivers State (0.14/ 1 000 000 people) and the highest in Abuja (1.48/1 000 000 people) (Fig. 1). Division of Global Health, Department of Internal Medicine, Rush Medical College, Chicago, IL, USA Olufemi T Olorunda, MD, MPH, olorundaolufemi@gmail.com Department of Cardiology, Marshall University, Huntington, WV, USA Kelechukwu Okoro, MD Evercare Hospital, Lekki, Lagos, Nigeria Basil Okoh, MB BS Euracare Multi-Specialist Hospital, Victoria Island, Lagos, Nigeria Tosin Majekodunmi, MB BS, PhD
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 AFRICA 5 Discussion We found that there were 12 functional PCI facilities in Nigeria with one PCI facility per 16 761 272 people. In a study on 10 countries in sub-Saharan Africa, Kakou-Guikahue et al. found that there were only five PCI facilities.1 In Egypt, there was reported to be one PCI facility per 950 000 people after initiation of the Stent for Life programme.9 In South Africa, there were 62 PCI-capable facilities with one PCI facility per 887 096 people.2 Langabeer et al. reported that there were 1 571 PCI-capable facilities in the United States of America, which amounts to about one PCI facility per 199 097 people, based on the 2011 population estimate.10,11 The geographical distribution of the PCI facilities in Nigeria is concerning as they are all in the big cities. An investment from the government in incentivising equitable development of PCI facilities will go a long way. Of the 12 functional PCI facilities in Nigeria, 11 of them are in the private health sector, creating disproportionate access to them in Nigeria’s stark reality of a fee-for-service model.3,12 This needs to be addressed as part of the broader issue of healthcare access and equity. It will be prudent for the government to invest in the infrastructure and provide more publicly accessible PCI facilities with services that are affordable. There remains a significant brain drain in Nigeria, not limited to cardiovascular specialists.13 The economic conditions for physicians in Nigeria and the prospect of an improved quality of life abroad is attractive to local physicians but does come at a cost as it limits the provision of specialised care in Nigeria. There is also a dearth of sub-specialised cardiovascular training programmes in Nigeria, compounding the problem.12 There needs to be an investment from the government and the stakeholders in Nigeria in the training of cardiovascular sub-specialists. A success story that can be mirrored is the advent of an interventional cardiology training programme in Babcock University Teaching Hospital, which is the first of its kind. There is some good news, with two PCI-capable facilities that opened early in 2022 in Lagos. There are also three cardiac catheterisation laboratories that are not currently functional in Akwa Ibom, Bayelsa and Oyo State, which could be refurbished to help provide more access to patients with ischaemic heart disease. Table 2. List of PCI-capable facilities • Afe Babalola University Multi-System Hospital, Ado-Ekiti, Ekiti State • University of Nigeria Teaching Hospital, Enugu • Reddington Hospital, Victoria Island, Lagos • Euracare Multi-Specialist Hospital, Victoria Island, Lagos • First Cardiology Consultants, Ikoyi, Lagos • Evercare Hospital, Lekki Phase 1, Lagos • Babcock University Teaching Hospital, Ilishan-Remo, Ogun State • SaveALife Mission Hospital, Port Harcourt, Rivers • Cardiocare Multispecialty Hospital, Garki, Abuja • Foxglove Multispecialty Hospital, Gwarinpa, Abuja • Nizamiye Hospital, Life Camp, Abuja • Cedarcrest Hospital, Gudu District, Apo, Abuja Table 1. Number of PCI-capable facilities and 2019 population estimate State/territory Number of PCI facilities 2019 population estimate Abia – 3 841 943 Adamawa – 4 536 948 Akwa Ibom – 4 780 581 Anambra – 5 599 910 Bauchi – 7 540 663 Bayelsa – 2 394 725 Benue – 5 787 706 Borno – 5 751 590 Cross River – 4 175 020 Delta – 5 307 543 Ebonyi – 3 007 155 Edo – 4 461 137 Ekiti 1 3 350 401 Enugu 1 4 396 098 Gombe – 3 623 462 Imo – 5 167 722 Jigawa – 6 779 080 Kaduna – 8 324 285 Kano – 14 253 549 Katsina – 9 300 382 Kebbi – 5 001 610 Kogi – 4 153 734 Kwara – 3 259 613 Lagos 4 12 772 884 Nasarawa – 2 632 239 Niger – 6 220 617 Ogun 1 5 945 275 Ondo – 4 969 707 Osun – 4 237 396 Oyo – 7 512 855 Plateau – 4 400 974 Rivers 1 7 034 973 Sokoto – 5 863 187 Taraba – 3 331 885 Yobe – 3 398 177 Zamfara – 5 317 793 FCT (Abuja) 4 2 702 443 Nigeria (Total) 12 201 135 262 PCI facility per 1 000 000 people None 0.1–0.3 0.3–0.5 1.3–1.5 Fig. 1. Concentration of PCI facilities in Nigeria. Map created using mapchart.net
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 6 AFRICA Conclusion There is a paucity of PCI-capable facilities in Nigeria, with only 12 operational facilities, mostly in the private health sector. There needs to be a significant investment by the government and other stakeholders in Nigeria to increase the access to cardiac catherisation, given the increasing burden of ischaemic heart disease and the paradigm shift from communicable to non-communicable diseases. We thank Ayodeji Olorunda for proofreading the manuscript. References 1. Kakou-Guikahue M, N’Guetta R, Anzouan-Kacou J, Kramoh E, N’Dori R, Ba S, et al. Optimizing the management of acute coronary syndromes in sub-Saharan Africa: A statement from the AFRICARDIO 2015 Consensus Team. Arch Cardiovasc Dis 2016; 109(6–7): 376–383. 2. Stassen W, Wallis L, Lambert C, Castren M, Kurland L. Percutaneous coronary intervention still not accessible for many South Africans. Afr J Emerg Med 2017; 7(3): 105–107. 3. Isezuo S, Sani M, Talle A, Johnson A, Adeoye A, Ulgen M, et al. Registry for Acute Coronary Events in Nigeria (RACE‐Nigeria): Clinical characterization, management, and outcome. J Am Heart Assoc 2022; 11(1). 4. Stassen W, Wallis L, Castren M, Vincent-Lambert C, Kurland L. A prehospital randomised controlled trial in South Africa: Challenges and lessons learnt. Afr J Emerg Med 2019; 9(3): 145–149. 5. O’Gara P, Kushner F, Ascheim D, Casey D, Chung M, de Lemos J, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulation 2013; 127(4). 6. Kimeu R, Kariuki C. Assessment of the management of acute myocardial infarction patients and their outcomes at the Nairobi Hospital from January 2007 to June 2009. Cardiovasc J Afr 2016; 27(4): 218–221. 7. Johnson A, Falase B, Ajose I, Onabowale Y. A cross-sectional study of stand-alone percutaneous coronary intervention in a Nigerian cardiac catheterization laboratory. BMC Cardiovasc Disord 2014; 14(1). 8. National Bureau of Statistics. Demographic Statistics Bulletin 2020. https://nigerianstat.gov.ng/elibrary (accessed 2 February 2022). 9. Magdy A, Shawky A, Mohanad A, Shaheen S. Egypt: coronary and structural heart interventions from 2010 to 2015. EuroIntervention 2017; 13(Z): Z21–Z24. 10. Langabeer J, Henry T, Kereiakes D, DelliFraine J, Emert J, Wang Z, et al. Growth in percutaneous coronary intervention capacity relative to population and disease prevalence. J Am Heart Assoc 2013; 2(6). 11. United States Census Bureau. Census Bureau Projects US Population of 312.8 Million on New Year’s Day. https://www.census.gov/newsroom/ releases/archives/population/cb11-219.html (accessed 17 February 2022). 12. Adedinsewo D, Omole O, Oluleye O, Ajuyah I, Kusumoto F. Arrhythmia care in Africa. J Int Cardiac Electrophysiol 2018; 56(2): 127–135. 13. Hagopian A, Thompson M, Fordyce M, Johnson K, Hart L. The migration of physicians from sub-Saharan Africa to the United States of America: measures of the African brain drain. Human Res Health 2004; 2(1). Wake-up call for governments as studies flag high risk of ultra processed foods Experts say the dangers posed by the increasing and alarming global consumption of ultra-processed food – raised blood pressure levels, heart disease and strokes – is threatening a ‘tidal wave of harm’ and should serve as a wake-up call for governments worldwide. In the UK and US, more than half of the average diet now comprises ultra-processed food (UPF) such as cereals, protein bars, fizzy drinks, instant meals and fast foods. For some, especially people who are younger, poorer or from disadvantaged areas, a diet of as much as 80% UPF is typical. Two large studies presented at the world’s largest heart conference showed the devastating impact UPF has on cardiovascular health, reports The Guardian. The first study, which tracked 10 000 women for 15 years, found that those with the highest proportion of UPF in their diet were 39% more likely to develop high blood pressure than those with the lowest. This was the case even after academics adjusted for the effect of salt, sugar and fat. High blood pressure, or hypertension, increases the risk of serious heart conditions including heart disease, peripheral arterial disease, aortic aneurysms, kidney disease and vascular dementia. The second study, a gold-standard meta-analysis of more than 325 000 men and women, showed those who ate the most UPF were 24%more likely to have cardiovascular events including heart attacks, strokes and angina. Increasing daily UPF consumption in calorie intake by 10% was associated with a 6% increased risk of heart disease. And those with UPF making up less than 15% of their diet were least at risk of any heart problems, found the research led by the Fourth Military Medical University in Xi’an, China. The findings were revealed at the annual meeting of the European Society of Cardiology in Amsterdam, where thousands of the world’s leading heart doctors, scientists and researchers were briefed on the studies. The results prompted calls from experts for urgent action. UPF are products that have gone through multiple processes during manufacturing, and are usually high in salt and sugar and may contain additives and preservatives. Often, they are low in fibre and lacking the nutrients present in fresh or minimally processed foods, such as fresh fruit and vegetables, plain yoghurt and homemade bread. Previous studies have linked eating high levels of UPF with a range of health problems including obesity, type 2 diabetes and cancer. One of the researchers behind the first study, Anushriya Pant, of the University of Sydney, said many people were unaware that food they assume is healthy, such as shopbought sandwiches, wraps, soups and low-fat yoghurts, were in fact UPF. Women typically eat more UPF than men, she said, but added that more research was needed to establish whether this was driven by the marketing of ultra-processed diet and low-fat foods at women. Dr Chris van Tulleken, one of the world’s leading UPF experts and author of the book Ultra Processed People, said: ‘The findings of these new papers are entirely consistent with a large and growing body of work showing that increasing consumption of UPF is associated with an increased risk of cardiovascular disease.’ Van Tulleken called for black warning labels to be added to UPF packaging, as is already the case in Chile and Mexico, and said there should be a clampdown on marketing of UPF, and in particular adverts aimed at children. Source: MedicalBrief 2023
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 AFRICA 7 Arterial stiffness assessment in obese black South African patients TL Rasakanya, E Osuch Abstract Introduction: Increased arterial stiffness is a determinant of cardiovascular mortality and an independent marker of cardiovascular disease. The objective of this study was to asses arterial elasticity by determination of pulse-wave velocity (PWV) and augmentation index (Aix) in obese black patients. Methods: PWV and Aix were assessed non-invasively using the AtCor SphygmoCor® system (AtCor Medical, Inc, Sydney, Australia). The study participants were divided into four groups; healthy volunteers (HV) (n = 29), patients with concomitant diseases but normal body mass index (Nd) (n = 23), obese patients without concomitant diseases (OB) (n = 29) and obese patients with concomitant diseases (OBd) (n = 29). Results: The difference in the mean levels of PWV was statistically significant in the obese group with and without concomitant disease. The PWV in the OB group (7.9 ± 2.9 m/s) and in the OBd group (9.2 ± 4.4 m/s) was, respectively, 19.7 and 33.3% higher than in the HV group (6.6 ± 2.1 m/s). PWV was directly correlated with age, glycated haemoglobin level, aortic systolic blood pressure and heart rate. The risk of cardiovascular diseases in the obese patient without additional diseases was increased by 50.7%. The presence of concomitant diseases (type 2 diabetes mellitus and hypertension) in addition to obesity increased arterial stiffness by a further 11.4% and therefore also increased the risk of cardiovascular diseases by a further 35.1%. Aix was increased in the OBd and Nd groups by 8.2 and 16.5%, respectively, however the increase was not statistically significant. Aix was directly correlated with age, heart rate and aortic systolic blood pressure. Conclusion: The obese black patients had a higher PWV, indicating increase in arterial stiffness and therefore a higher risk for cardiovascular disease. In addition, aging, increased blood pressure and type 2 diabetes mellitus contributed further to arterial stiffening in these obese patients. Keywords: arterial elasticity, pulse-wave velocity, augmentation index, blood pressure, body mass index, diabetes Submitted 12/8/21; accepted 23/11/22 Published online 13/2/23 Cardiovasc J Afr 2024; 35: 7–11 www.cvja.co.za DOI: 10.5830/CVJA-2022-064 Arterial stiffening is the ongoing loss and fragmentation of elastin, and an accumulation of stiffer collagen fibres in the arterial wall.1 Arterial stiffness increases with aging and concomitant diseases such as diabetes mellitus, atherosclerosis, hypertension, chronic kidney disease and stroke.2,3 Obesity is linked with a high risk of cardiovascular disease (CVD), particularly when body fat is distributed within the abdominal region. When compared with non-obese subjects, obese subjects have increased arterial stiffness.4,5 Pulse-wave velocity (PWV) and augmentation index (Aix) are gold-standard, non-invasive markers of arterial elasticity and predictors of cardiovascular morbidity and mortality.6 PWV is a direct measure of large-artery stiffness. Aix is a surrogate measure of arterial rigidity that could be influenced by the left ventricular ejection fraction and peripheral haemodynamics, as well as the properties of the large arteries.7 PWV values are calculated from the time interval between the estimated forward and reflected waves and are comparable with invasive measurements. Aix values are calculated as the ratio of the augmentation pressure to the pulse pressure.8 A slow PWV indicates good elasticity and a fast PWV, poor elasticity.9 A 1-m/s increase in aortic PWV has been shown to equate to 39% increase in risk of cardiovascular events.10 PWV is an independent predictor of stroke and coronary heart disease in healthy subjects.11 Aix, a measure of pulse-wave reflection, is a more direct measure of arterial stiffness. It calculates how much of the central pulse pressure is accounted for by the reflected pulse wave.12 ElevatedPWVandAix are associatedwithpoor cardiovascular health.13 Increased PWV and Aix indicate damage to the elastic tissue of the arteries.14 Various studies have reported the effects of obesity on arterial elasticity in different ethnic groups.15,16 The aim of this study was to assess arterial stiffness in obese black South African patients. The objectives of the study were to compare the difference in arterial stiffness and to evaluate the effect of hypertension and diabetes on arterial stiffness in obese and non-obese patients using PWV and Aix analysis. This study is the first to assess the effects of obesity on arterial stiffness in obese black South African patients. Methods The study was approved by the Sefako Makgatho University Research and Ethics Committee (SMUREC/M/112/2016:PG). Informed consent was obtained from the participant before entering the study. Full explanation of the procedure was given with the possibility of withdrawal at any time. The study was conducted in accordance with the principles detailed by the Declaration of Helsinki. A comparative study model was used and 110 participants were recruited from the Sefako Makgatho Health Sciences University community. Body mass index (BMI) groups were Department of Pharmacology and Therapeutics, Sefako Makgatho Health Science University, Pretoria, South Africa TL Rasakanya, MSc Pharmacology, tsakani.rasakanya@smu.ac.za Department of Clinical Pharmacology, School of Medicine, Dr George Mukhari Academic Hospital, Sefako Makgatho Health Sciences University, Pretoria, South Africa E Osuch, MD, PhD, ACCP (SA), FCP (ACCP), MSc (Med) Pharmacology, Dip Fam Med
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 8 AFRICA categorised according to the World Health Organisation’s nutrition/BMI guidelines and defined as a person’s weight in kilograms divided by the square of the person’s height in metres. Below 18.5 kg/m2 was defined as underweight, 18.5–24.9 kg/m2 as normal, 25.0–29.9 kg/m2 as pre-obesity, 30.0–39.9 kg/m2 as obese and above 40 kg/m2 as severe obesity. The study participants were divided into four groups; healthy volunteers (HV) (n = 29), patients with concomitant disease (type 2 diabetes mellitus and hypertension) but normal BMI (Nd) (n = 23), obese patients without concomitant disease (OB) (n = 29), and obese patients with concomitant disease (OBd) (n = 29). The eligibility criteria for healthy volunteers were male or female, aged 18–70 years with no abnormalities in the physical examination and no chronic or acute diseases (not on any chronic medication). The eligibility criteria for the study patients were male or female, aged 18–70 years, with type 2 diabetes and with or without hypertension, with a BMI ≤ 25 kg/m2 and on metformin as monotherapy or metformin plus sulfonylurea as a dual combination therapy plus hypertensive therapy (enalapril 10 mg and/or hydrochlorothiazide 12.5 mg) if needed. The obese patients were not on any medications used to treat hyperlipidaemia. No additional medication (and no withholding of medication) was given to the patients with diabetes or other concomitant diseases. The exclusion criteria were patients with type 1 diabetes mellitus, a history of ketoacidosis, current treatment with all types of insulin, patients acutely ill or unstable, and patients with poorly controlled concomitant chronic diseases, such as systolic blood pressure (SBP) ≥ 160 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg. Sample size calculations were based on estimation of the difference in PWV between any two groups. With a sample size of 26 per group, a two-sided t-test at the 5% level would have 80% power to detect a difference of 2 m/s (7–9) in PWV between any two groups, assuming a common standard deviation of 2.5 m/s. Sample size calculation was done on Query Advanced (Statistical Solution Ltd, Cortc, Ireland), version 8.1.1.0. Questionnaires were completed, and vital signs, BMI and fasting glucose levels were measured. After overnight fasting, venous blood was collected via vacupunture and determination of glycated haemoglobin (HbA1c) levels and lipid profiles was done by the National Health Laboratory Services, which is a South African National Accreditation System (SANAS) accredited laboratory. The National Health Laboratories Services handbook on standard operating procedures, version 1, active from 6 March 2015, and document number GPQ0064, was used as a guideline to ensure correct and consistent sample collection and handling. Other variables such as smoking and alcohol consumption were recorded. Validity was maintained by strict adherence to the inclusion and exclusion criteria. The AtCor SphygmoCor®, used for measuring PWV and Aix, was operated by a trained, dedicated user. All of the apparatus used in the laboratory investigations were acquired from reputable suppliers and the procedures were conducted according to the manufacturer’s protocol. PWV and Aix were assessed non-invasively using the AtCor SphygmoCor® system (AtCor Medical, Inc, Sydney, Australia). Electrocardiogram-gated carotid and femoral waveforms were recorded using applanation tonometry. Carotid–femoral path length was measured as the difference between the surface distance joining (1) the suprasternal notch, the umbilicus and the femoral pulse, and (2) the suprasternal notch and the carotid pulse. The carotid–femoral transit time was estimated in eight to 10 sequential femoral and carotid wave forms as the average time difference between the onset of the femoral and carotid waveforms. PWV was calculated as the carotid–femoral path length divided by the carotid–femoral transit time as expressed in metres per second.9 Aix was measured by pulse-wave analysis (PWA). Radial artery waves were recorded non-invasively by applanation tonometry. Twenty waves were captured and PWA was used to derive a central aortic pulse wave and haemodynamic measures by a generalised validated mathematical transfer function. Aix measurements were standardised to a pulse rate of 75 beats per min and expressed as a percentage (%).12 Assessment of arterial elasticity by determination of PWV and Aix was done in the obese black patients. Statistical analysis All statistical analyses were done on SAS (SAS Institute Inc, Carey, NC, USA). Continuous variables are summarised as mean values and standard deviations. Mean values of the demographic variables were compared between the four test groups by analysis of variance (ANOVA) followed by pairwise t-test comparison. Median values for both PWV and Aix were calculated. Linear regression analysis was performed with PWV and Aix @75 as outcomes (dependent) variables and the demographic variables as predictors (independent) variables. Results Of the 110 study participants, 29 were healthy volunteers aged 37.2 ± 10 years, 23 patients were non-obese with concomitant disease (type 2 diabetes mellitus and hypertension), aged 58.8 ± 8.4 years, 29 patients were obese without concomitant disease, aged 44.2 ± 14.6 years, and 29 patients were obese with concomitant disease, aged 53.1 ± 9 years. The clinical and haemodynamic characteristics of the study participants are shown in Table 1. The average BMI was 24.82 ± 1.9 kg/m2 for the HV group, 24.7 ± 2.4 kg/m2 for the Nd group, 35.4 ± 4.2 kg/m2 for the OB group and 35.4 ± 4.9 kg/m2 for the OBd group. All the participants in the OBd and Nd groups additionally had type 2 diabetes mellitus, and 65.2% of the Nd group and 75.9% of OBd group had concomitant hypertension (Table 1). The mean PWV levels were statistically significantly different in the obese group with and without concomitant disease. The PWV in the OB group (7.9 ± 2.9 m/s) and in the OBd group (9.2 ± 4.4 m/s) were, respectively, 19.7 and 33.3% higher (p < 0.05) than in the HV group (6.6 ± 2.1 m/s). The risk of CVD in the obese patient without additional disease was 50.7% higher. The presence of concomitant disease (type 2 diabetes mellitus and hypertension) in addition to obesity increased arterial stiffness further by 11.4% and therefore further increased the risk of CVD by 35.1%. Aix was higher in the OBd and Nd groups by 8.2 and 16.5%, respectively, however the increase was not statistically significant. Aix was directly correlated with age, heart rate and aortic SBP. Interestingly, Aix did not differ significantly in the OB group when compared to the HV group (Table 1).
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 AFRICA 9 The results of this study indicated that PWV and Aix increased with increasing age. The values for PWV and Aix for the four groups by age are shown in Figs 1 and 2. To identify the variables that were independently correlated with PWV and Aix, a multivariable linear regression analysis including all studied participants (n = 110) was performed (Table 2). PWV was directly correlated with age, aortic SBP, HbA1c level and heart rate. Aix was directly correlated with age, aortic SBP and heart rate, and inversely correlated with radial SBP and radial DBP (Table 2). The results of this study indicate that age and the presence of concomitant disease was associated with significant differences between PWV and Aix. Interestingly, obese patients without concomitant disease did not show a significant increase in PWV or Aix. Discussion Obesity is a recognised independent predictor of CVD and/or mortality.17,18 Body fat distribution may have an effect on arterial compliance, and increased peripheral artery stiffness is associated with larger abdominal body fat mass.19 Lentferink et al. links obesity with higher arterial pressure and suggests that this might be as a result of an increased preload and afterload due to increased metabolic demand.20 The authors also suggest that in obese populations it can be anticipated that PWV will be higher if the arterial pressure surpasses the physiological adaptations.20 The results of this study indicated that arterial stiffness was increased in these obese patients, however concomitant disease such as hypertension and type 2 diabetes played a major role in arterial stiffness, increasing PWV by 19.7% in the obese patients and by 11.4% in non-obese patients (Table 1). A 1-m/s increase in aortic PWV has been shown to equate to a 39% increase in risk of cardiovascular events.9,10 In this study, the risk of CVD in the obese patient without additional disease was increased by 50.7%, and in obese patients with additional diseases, the risk increased by a further 35.1%. The results of this study show that PWV was directly correlated with HbA1c levels and this is similar to that found Table 1. Characteristic of the study participants (n = 110) Variables HV (n = 29) Nd (n = 23) OB (n = 29) OBd (n = 29) Age, years 37.21 ± 10.19 58.79 ± 8.43* 44.17 ± 14.63* 53.14 ± 9.99*# BMI, kg/m2 24.8 ± 1.9 24.7 ± 2.35 35.41 ± 4.20* 35.41 ± 4.87* Diabetes mellitus, % – 100 – 100 Current smoking, % 10.3 8.7 10.3 13.8 Hypertension, % – 65.2 – 75.9 Heart rate, bpm 68.62 ± 9.66 70.48 ± 14.16 68.86 ± 12.13 73.52 ± 10.63 Aortic PP, mmHg 32.93 ± 9.33 46.17 ± 18.81* 41.24 ± 16.58 45.62 ± 20.46* Radial PP, mmHg 41.241 ± 10.63 60.04 ± 18.50* 50.59 ± 15.11* 56.89 ± 21.23* MAP, mmHg 90.79 ± 11.30 101.13 ± 13.63* 96.89 ± 9.7* 104.83 ± 11.73*# Aortic SBP, mmHg 107.45 ± 16.05 129.00 ± 19.06* 118.28 ± 14.25 128.17 ± 21.28*# Aortic DBP, mmHg 76.48 ± 8.6 80.913 ± 10.32* 79.62 ± 6.68* 84.62 ± 9.52* Radial SBP, mmHg 117.28 ± 17.74 138.87 ± 19.15* 127.52 ± 14.51* 138.66 ± 22.84*# Radial DBP, mmHg 72.69 ± 10.59 79.35 ± 10.52* 78.41 ± 6.29* 83.28 ± 9.28*# HbA1c 5.06 ± 0.32 8.78 ± 2.12* 5.93 ± 1.45 11.25 ± 8.68*# TC 4.61 ± 1.35 5.00 ± 1.28 4.94 ± 1.06 4.56 ± 1.11 LDL-C 3.07 ± 1.41 3.20 ± 1.20 3.14 ± 0.95 2.82 ± 0.86 HDL-C 1.26 ± 0.25 1.28 ± 0.33 1.15 ± 0.18 1.24 ± 0.37 TG 1.07 ± 0.56 1.23 ± 0.64 1.50 ± 1.27 1.81 ± 1.37* Aix, % 24.241 ± 15.14 28.26 ± 10.26 23.48 ± 10.90 26.24 ± 8.52 PWV, m/s 6.59 ± 2.18 7.87 ± 3.61 7.93 ± 2.94 8.80 ± 3.30* BMI, body max index; PP, pulse pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; HbA1c, glycated haemoglobin; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL, high-density lipoprotein cholesterol; TG, triglycerides; Aix, augmentation index; PWV, pulse-wave velocity; HV, healthy volunteers; Nd, non-obese with concomitant disease; OB, obese without concomitant disease; OBd, obese with concomitant disease. *p < 0.05 HV compared with Nd, OB and OBd, #p < 0.05 OB compared with OBd. Age categories (years) HV Nd OB OBd <30 30–39 40–49 50–59 60–70 Median values (m/s) 10 9 8 7 6 5 4 3 2 1 0 Fig. 1. PWV values for the study participants according to age categories and study groups. Age categories (years) HV Nd OB OBd <30 30–39 40–49 50–59 60–70 Median values (m/s) 40 35 30 25 20 15 10 5 0 Fig. 2. Aix values for the study participants according to age categories and study groups.
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 10 AFRICA by Elias et al., where type 2 diabetes mellitus status was linked with a significantly higher PWV.21 Studies have shown increased stiffening of arteries in diabetes, and this suggests that it might be due to endothelial dysfunction, low-grade inflammation and oxidative stress, as well as the formation of advanced glycation end-products in the vessel wall, causing cross-linking of collagen molecules and loss of elasticity.22 Continuous increases in blood pressure also stimulate matrix synthesis, causing subsequent elevation in vascular thickness and structural stiffening.23 In addition, chronic hyperglycaemia and hyperinsulinaemia elevate the local activity of the renin–angiotensin–aldosterone system and the expression of angiotensin type I receptors in the vascular tissue, resulting in the development of wall hypertrophy and fibrosis.24 A study by Osuch et al. showed that there was an improvement in arterial elasticity in black patients on angiotensin converting enzyme inhibitors (perindopril 4 mg).9 It would be warranted to investigate further the influence of angiotensin converting enzyme inhibitors on arterial elasticity in obese populations. According to previous studies, Aix can be influenced by an individual’s age, gender and heart rate.21 Our study showed that in obese black participants, Aix was significantly correlated with age, aortic SBP, and radial SBP and DBP, indicating that age and increased BP might lead to an increase in arterial stiffness (Table 2). Increased BP upsurges afterload and the oxygen demand of the myocardium and contributes to left ventricular hypertrophy. This leads to increased arterial stiffness, leading to an imbalance between myocardial oxygen demand and supply.2 A study by Mittchell et al. showed that a healthy individual with no evidence of CVD and low burden of risk factors had age-related increased aortic stiffness.25 Boutouyrie and Vermeersch showed that the enhanced influence of ageing with high BP was gradual, the increase in PWV with BP was more prominent as the subjects got older and that the correlation between PWV and age was highly significant.26 This might be due to the remodelling of the middle tunica, comprising the fragmentation of elastin and its replacement with collagen fibres and calcium deposition, resulting in loss of elasticity and decreased arterial compliance.25,26 The results of this study concur with a number of studies where arterial stiffness increased with increasing age.2,22 The results showed that age was directly correlated with PWV and Aix (Table 2) and that PWV and Aix increased with increasing age (Table 2, Figs 1 and 2). There were limitations to this study. Due to the small sample size, a separate analysis regarding the effect of different antihypertensive and antidiabetic medication on arterial stiffness could not be investigated. The small sample size impacted negatively on the power of the test and therefore it is proposed that the research should be repeated with a larger sample. Anthropometric measurements such as body circumference and waist-to-hip ratio were not done. Conclusion Obese black patients had higher PWV, indicating stiffer arteries and therefore higher risk for CVD. The risk of CVD in the obese patient without additional diseases was increased by 50.7%. Furthermore, aging, increased BP, type 2 diabetes mellitus and increased cholesterol level contributed further to arterial stiffening in these obese patients. The presence of concomitant diseases (diabetes and hypertension) increased arterial stiffness by 11.4% and therefore further increased the risk of CVD by 35.1%. References 1. Yuong OS. Arterial stiffness and hypertension. Clin Hypertens 2018; 24(17): 1–3. 2. De Oliveira AR, Lima Santos PC, Bortolotto LA, Mill JG, da Costa Pereira A. Arterial stiffness: pathophysiological and genetic aspects. Int J Cardiovasc Sci 2017; 30(5): 433–441. 3. O’Rourke MF, Junichiro H. Mechanical factors in mechanical arterial aging: A clinical perspective. J Am Coll Cardio 2007; 50(1): 1–13. 4. Seifalian AM, Filippatos TD, Joshi J, Mikhailidis DP. Obesity and arterial compliance alterations. Curr Vasc Pharmacol 2010; 8: 155–168. 5. Pal S, Radavelli-Bagatini S. Association of arterial stiffness with obesity in Australian women: A pilot study. J Clin Hypertens 2013; 15(2): 118–123. 6. Elias M, Dore A, Davey A, Abhayaratna W, Goodell A, Robbins M. Norms and reference values for pulse wave velocity: one size does not fit all. J Biosci Med 2011; 1(4): 1–9. 7. Obara S, Hayashi SH, Akihirob M, Masahiroa K, Shin-ichirob. Correlation between augmentation index and pulse wave velocity in rabbits. J Hypertens 2009; 27(2): 332–340. 8. Paiva AMG, Mota-Gomes MA, Brandão AA, Silveira FS, Silveira MS, Okawa RTP, et al. Reference values of office central blood pressure, pulse wave velocity, and augmentation index recorded by means of the Mobil‐O‐Graph PWA monitor. Hypertens Res 2020; 43: 1239–1248. 9. Osuch E, Du Plooy WJ, Du Plooy SH, Böhmer L. Effects of perindopril on pulse-wave velocity and endothilin-1 in black hypertensive patients. Cardiovasc J Afr 2012; 23(7): 396–399. 10. Lehman ED, Watts GF, Fateni-Langroudi B, Gosling RG. Aortic compliance in young patients with heterozygous familial hypercholesterolaemia. Clin Sci 1992; 83: 717–721. 11. Naijar S, Scuteri A, Shetty V, Wright GJ, Muler CD, Fleg LJ, et al. Pulse wave velocity is an independent predictor of longitudinal increases in systolic blood pressure and of incident hypertension in the Table 2. Multivariable linear regression analysis for PWV and Aix in the study participants (n = 110) Variables Aix (± SE) p-value PWV (± SE) p-value Age 0.156 ± 0.07 0.04* 0.046 ± 0.021 0.031* Aortic PP 0.11 ± 0.132 0.402 –0.073 ± 0.044 0.101 Radial PP –0.276 ± 0.161 0.089 0.079 ± 0.534 0.15 MAP –0.041 ± 0.170 0.081 –0.067 ± 0.56 0.234 Heart rate 0.398 ± 0.081 < 0.0001* 0.060 ± 0.027 0.03* Aortic SBP 1.595 ± 0.022 < 0.0001* 0.228 ± 0.073 0.003* Aortic DBP 0.920 ± 0.599 0.135 –0.174 ± 0.197 0.383 Radial SBP –1.134 ± 0.214 < 0.0001* –0.097 ± 0.07 0.017 Radial DBP –1.449 ± 0.524 0.009* –0,165 ± 0.178 0.357 BMI –0.045 ± 0.124 0.714 0.07 ± 0.041 0.079 HbA1c –0.013 ± 0.172 0.940 0.192 ± 0.056 0.0009* TC –1.929 ± 1.67 0.251 0.544 ± 0.554 0.329 LDL-C 2.34 ± 1.73 0.183 –0.201 ± 0.577 0.728 TG –1.51 ± 0.827 0.191 –0.124 ± 0.284 0.664 HDL-C 6.92 ± 3.226 0.054 –0.706 ± 1.07 0.512 MAP, mean arterial pressure; PP, pulse pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; BMI, body max index; HbA1c, glycated haemoglobin; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides; SE, standard error; Aix, augmentation index; PWV, pulse-wave velocity. *p < 0.05.
CARDIOVASCULAR JOURNAL OF AFRICA • Volume 35, No 1, January – April 2024 AFRICA 11 Baltimore Longitudinal Study of Aging. J Am Coll Cardiol 2008; 51(14): 1377–1383. 12. Janner JH, Godtfredsen NS, Ladelund S, Vestbo J, Prescott E. Aortic augmentation index: reference values in a large unselected population by means of the SphygmoCor device. Am J Hypertens 2010; 2: 180–185. 13. Stéphane L, Boutouyrie P, Asmar R, Gautier I, Laloux B, Guize L, et al. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension 2001; 37: 1236–1241. 14. Mendes-Pinto D, Rodrigues-Machado MdaG. Applications of arterial stiffness markers in peripheral arterial disease. J Vasc Bassileiro 2019; 18: 1–9. 15. Schutte AE, Kruger R, Gafane-Matemane LF, Breet Y, Strauss-Kruger M, Cruickshank JK. Ethnicity and arterial stiffness. Arterioscler Thromb Vasc Biol 2020; 40: 1044–1054. 16. Pierce GL, Zhu H, Darracott K, Edet I, Bhagatwala J, Huang Y, Dong Y. Arterial stiffness and pulse-pressure amplification in overweight/ obese African-American adolescents: Relation with higher systolic and pulse pressure. Am J Hypertens 2013; 26(1): 20–26. 17. Zahner JG, Gruendl AM, Spaulding AK, Schaller SM, Hills KN, Gasper JW, et al. Association between arterial stiffness and peripheral artery disease as measured by radial artery tonometry. J Cardiovasc Surg 2017; 66(5): 1518–1526. 18. Wilkinson IB, Prasad K, Hall IR, Thomas A, MacCallum H, Webb DJ, et al. Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia. J Am Coll Cardiol 2002; 39(6): 1005–1011. 19. Jani B, Rajkumar C. Aging and vascular ageing. Postgrad Med J 2006; 82: 357–362. 20. Lentferink EY, Kromwijk AJL, van der Aa PM, Knibbe AJC, van der Vorst MJM. Increased arterial stiffness in adolescents with obesity. Childhood Obesity Nutr 2019; 6: 1–8. 21. Elias MF, Crichton GE, Dearborn PJ, Robbins MA, Abhayaratna WP. Associations between type 2 diabetes mellitus and arterial stiffness: A prospective analysis based on the Maine–Syracuse study. Pulse 2017; 5: 88–98. 22. Faqir MI, Born´e Y, Ostling G, Kennback C, Gottsater M, Persson M, et al. Arterial Stiffness and incidence of diabetes: a population-based cohort study. Diabetes Care 2017; 40: 1739–1745. 23. Safar ME, Asmar R, Benetos A, Blacher J, Boutouyrie P, Lacolley P, et al. Interaction between hypertension and arterial stiffness: an expert reappraisal. Hypertension 2018; 72: 796–805. 24. Jankowski P. Value of arterial stiffness in predicting cardiovascular events and mortality. Medicographia 2015; 37(4): 399–403. 25. Mitchell G, Parise H, Benjamin E, Larson M, Keyes M, Vita J, et al. Changes in arterial stiffness and wave reflection with advancing age in healthy men and women. Hypertension 2004; 43: 1239–1244. 26. Boutouyrie P, Vermeersch SJ. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’. Eur Heart J 2010; 31: 2338–2350. New gene-editing treatment cuts dangerous cholesterol in small study The treatment of a handful of patients with severe heart disease, who volunteered for an experimental cholesterollowering treatment using gene editing, has paved the way for the potential transformation of preventive cardiology, say experts. The patients, who suffered from heart attacks and pain, had been unable get their cholesterol as low as cardiologists recommended, despite trying all available medications. So, they volunteered for the experimental treatment that was unlike anything tried in patients before. The New York Times reports that the result, released by the company Verve Therapeutics of Boston at a meeting of the American Heart Association, showed that the treatment appeared to reduce cholesterol levels markedly in patients and that it appeared to be safe. The trial involved only 10 patients, with an average age of 54 years. Each had a genetic abnormality, familial hypercholesterolaemia, that affects around one million people in the United States. But the findings could also point the way for millions of other patients around the world who are contending with heart disease, which remains a leading cause of death. And while more trials in a broader range of patients will need to be carried out, gene-editing experts and cardiologists said the treatment could transform preventative cardiology. ‘Even for seasoned veterans of this field like me, this is a day we will look back on,’ said Fyodor Urnov, a gene editor at the Innovative Genomics Institute in Berkeley, California. ‘It’s like crossing a Rubicon, in a good way. This is not a small step. It is a leap into new territory.’ Impressed with the data and the potential, pharmaceutical giant Eli Lilly has paid $60m to collaborate with Verve Therapeutics and opted to acquire additional rights to Verve’s programmes for an additional $250m. If the editing continues to look promising, Eli Lilly expects to help with larger studies. ‘Until now, we thought of gene editing as a treatment we should reserve for very rare diseases where there is no other treatment,’ said Dr Daniel Skovronsky, Eli Lilly’s chief scientific and medical officer. ‘But if we can make gene editing safe and widely available, why not go after a more common disease?’ The study was led by Dr Sekar Kathiresan, chief executive of Verve. Patients received a single infusion of microscopic lipid nanoparticles containing within them a molecular factory to edit a single gene in the liver, the site of cholesterol synthesis. The gene, PCSK9, raises levels of LDL cholesterol, the bad kind. The plan was to block it. The little lipid spheres were carried through the blood directly to the liver. They entered the liver cells and opened up, revealing two molecules. One instructs the DNA to make a gene-editing tool, and the other is a guide to take the editing tool to the gene that needs editing. continued on page 34…
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