Hypertension, Remodelling and Novel Biomarkers in African Subjects

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1 Hypertension, Remodelling and Novel Biomarkers in African Subjects Dike Ojji MBBS, PhD, FWACP, FACP, FESC Senior Lecturer, Department of Medicine, Faculty of Health Sciences, University of Abuja & Honorary Consultant Cardiologist, University of Abuja Teaching Hospital, Gwagwalada, Abuja

2 Map of Nigeria

3 Summary of my PhD work from the Hatter Institute for Cardiovascular Research University of Cape Town ( )

4 Worldwide Prevalence of HT 26.4% in 2000(972million) 333million 639million Others(2008/2025) 1Billion 1.56Billion

5 Worldwide Burden of Hypertension

6 Heart 2013; 19:

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9 Burden of Complications of HT in Nigerians HT HT LVH:40-70% HF:60-75% CKD:25-30% 82% of CVA patients

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12 Vascular Health and Risk Management 2009;5:

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15 Rationale for the Study Because of the enormity of HT-HHD-HHF in our setting, there is the need for faster and cheaper methods of diagnosis compared to ECG and transthoracic echocardiography Although NT-pro BNP levels has been shown to differentiate hypertensive LVH from HHF It has not been very helpful in differentiating HT from HT+LVH(Heart 2008;83: , J Hum Hypertens 1993; 7: ) There is therefore the need to look for other biomarkers that can effectively do this as point-of-care

16 Soluble ST2 We decided to try ST2 which is a novel biomarker of myocardial mechanical stress with exceptional predictive value in HF and MI-related mortality Circulation 2003,107(5): & Circulation 2002,106(23):

17 Soluble ST2 It is a member of the interleukin-1 super family

18 Soluble ST2 ST2 is a soluble protein expressed by the heart in response to disease or injury It is reflective of ventricular remodeling and cardiac fibrosis associated with HF ST2 is not adversely affected by confounding factors such as age, BMI and impaired renal function ST2 levels change quickly in response to changes in the patient s condition

19 Soluble ST2 The 2013 ACC/AHA Guideline For The Management of Heart Failure, recognizes ST2 as not only predictive of hospitalization and death in patients with HF but also additive to natriuretic peptide levels in [its] prognostic value

20 Soluble ST2 Apart from NT-pro BNP only galectin-3 and serum ST2 (sst2) are cleared by the Food and Drug Administration (FDA) for use as aids in assessing prognosis in heart failure. JACC HF 2014; 2:

21 Methodology Recruit subjects in UATH Cardiology Clinic & wards Collected Blood samples for NT-pro BNP & sst2 estimation and Echo the subjects Samples were transported from Nigeria to Hatter Institute for analysis

22 Ultrasound Machine

23 Hypertensive LVH LV RV RA LA

24 Methodology 210 Hypertensive subjects were studied 83-HT without HF&LVH 50- HT+LVH without HF 77-HHF Excluded subjects with DM, CKD and clinical, laboratory, ECG and echocardiography features of CAD

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26 Aim We wanted to know if NT-pro BNP could differentiate hypertensive heart failure from hypertension with or without LVH, and hypertension without LVH from hypertension with LVH.

27 Conclusion NT-pro BNP is a useful biomarker in differentiating HT±LVH from HHF But not a good biomarker in differentiating HT without LVH from HT+LVH

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29 Aim We wanted to know if soluble ST2 could differentiate hypertensive heart failure from hypertension with or without LVH, and hypertension without LVH from hypertension with LVH.

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31 Concentrations of NT-pro BNP and ST2 in the three Study Groups

32 ROCS Showing the differentiation of the three Hypertensive Groups (ST2) HHF versus HT HT versus HT+LVH HH versus HT+LVH

33 Comparison of ROC S of NT-pro BNP and ST2 in differentiating HT from HHF

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36 Conclusion Serum soluble ST2 does not only differentiate hypertensive subjects with or without heart failure from those with heart failure, but also distinguishes hypertensives without LVH from those with LVH. The use of soluble ST2 therefore extends beyond ischaemic heart disease and cardiomyopathies to hypertensive heart disease and failure

37 Press Release by Critical Diagnostics- SAN DIEGO, CA 14 th January 2014 ST2 IDENTIFIES HYPERTENSIVE PATIENTS LIKELY TO DEVELOP HEART FAILURE The novel biomarker, ST2, once again bests NT-pro BNP, this time in not only distinguishing between the different types of hypertensive heart disease, but also differentiating patients with diastolic dysfunction from systolic dysfunction which can aid in treatment decisions. SAN DIEGO, CA January 14, 2014 Critical Diagnostics announced today that a paper titled, The Effect of Left Ventricle Remodelling On Soluble ST2 in A Cohort of Hypertensive Subjects, published in Journal of Human Hypertension, showed that the Company s biomarker, ST2, was useful in not only differentiating hypertensive heart failure (HHF) patients from those with hypertension (HT) with or without left ventricular hypertrophy (LVH), but also distinguishes hypertensive LVH from hypertension without LVH.

38 Press Release by Critical Diagnostics- SAN DIEGO, CA 14 th January 2014 This study builds on the strong body of evidence we already have showing the powerful predictive value of ST2, declares David M. Geliebter, CEO of Critical Diagnostics. What s particularly interesting is how the investigators identified this subset of patients likely to advance to heart failure or a worsening stage of heart failure, because we know that in half the patients that advance to Stage C, cost of care rises dramatically and 5-year survival rates fall quite precipitously. So having a biomarker that can help health care professionals refine the discrimination within hypertensive patients and those in early stages of heart failure and then treat them accordingly, can save and improve lives and, at the same time, reduce the burden to the healthcare system.

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40 Aim To study the relationship between soluble ST2 and LV geometric pattern in hypertension as the geometric pattern affects prognosis.

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42 Pattern of Left Ventricular Geometry in HT and HT+LVH Subjects CONCENTRIC REMODELLING 14% NORMAL 14% ECCENTRIC HYPERTROPHY 31% CONCENTRIC HYPERTROPHY 41%

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44 ROC showing the sensitivity and specificity of soluble ST2 in differentiating concentric hypertrophy from normal geometry

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48 Conclusion Soluble ST2 level is not only affected by hypertensive LVH but may be a future biomarker in differentiating concentric LVH from normal geometry.

49 FINAL MESSAGE With the results from this study, and with the burden of hypertensive heart disease and hypertensive heart failure in sub-saharan Africa, limited access to echocardiography the use point-of-care ST2 assay in the management of hypertensive heart disease and failure may be a great innovation.

50 Future Publications Right Ventricular Systolic Dysfunction is common in Hypertensive Heart Failure: A Prospective Study in Sub-Saharan Africa (Submitted AHJ) Soluble St2 Correlates with Parameters of Right Ventricular Function in Hypertensive Heart Failure (Under Preparation) AMJC Biomarkers of Remodelling in Hypertensive Heart Disease: Focus on Sub-Saharan African Subjects (Under preparation) Clin Res Card

51 Way Forward Large longitudinal studies on the use of soluble St2 in hypertensive heart disease Ultimately Developing ST2 POC for HHDX There is need for this type of collaborative research between South Africa and sister African countries to be further enhanced

52 Way Forward We found our subjects with hypertensive heart failure to be much younger (mean age of 53) than subjects in the USA and Europe (mean age of 75 years). A possible explanation for this is higher oxidative stress levels in black hypertensive subjects compared to Caucasians. It might therefore be necessary to study the Oxidative Stress levels in our heart failure subjects and compare with similar levels in the Western population.

53 Appreciation God Almighty Prof Karen Sliwa-UCT Prof Falase, Drs Oladapo and Adebiyi Prof Sandrine Lecour-UCT Prof Lionel Opie-UCT Prof Bongani Mayosi Drs Ogah, Adebayo,Aje & Okpechi All My Teachers in UI/UCH Prof John Atherton(Royal Brisbane Hospital, Australia) All staff, Hatter Institute for Cardiovascular Research in Africa Staff, Cardiology Unit, Dept of Medicine, University of Abuja Teaching Hospital

54 THANK YOU VERY MUCH