Investigating prevalence, progression and histologic characteristics of atherosclerosis in intracranial arteries of black Malawian population: A post-mortem study

Nyasa, Charles

Investigating prevalence, progression and histologic characteristics of atherosclerosis in intracranial arteries of black Malawian population: A post-mortem study

Date

2021-12-10

Authors

Nyasa, Charles

Publisher

Kamuzu University of Health Sciences

Abstract

Type of study This will be a cross-sectional anatomical study involving brain arterial samples obtained from 60 recently-deceased adult black Malawians. The study will be conducted within a period of 1 year in the laboratories of the Division of Anatomy at the Kamuzu University of Health Sciences. Statement of problem The past few decades have seen development of high-performance imaging modalities invaluable at diagnosing atherosclerotic changes in the brain’s arterial tree and subsequent stratification of patient groups at-risk. Similarly, research in intracranial atherosclerosis has increased over the years. However, studies on patho-anatomical characteristics in this area have stagnated, and this is partly due to the rigor often associated with gathering human cadaveric specimens coupled with the relative inaccessibility of brain arteries. The lag of anatomical knowledge in this area presents a missing link as various vessel imaging parameters need to be validated against pathologically-observed phenomena to adequately inform clinical decisions. This makes arrival at definite diagnosis using imaging data a challenge. Meanwhile, the prevalence of intracranial atherosclerosis is reportedly high among Africans, Asians and Hispanics but less so among Caucasians, yet there has been scanty research on atherosclerosis in Africa in general. To date, the prevalence of intracranial atherosclerosis and mechanisms of atherogenesis in Malawians not well known. Aim and objectives The proposed study aims at investigating the prevalence of atherosclerosis and mechanisms of atherogenesis in intracranial arteries of adult black Malawian population. The study’s broad objectives are: • To evaluate the prevalence of atherosclerosis in intracranial arteries of adult black Malawians at systematically selected portions of the cerebral arterial tree (carotid syphon, basilar arteries, cerebral arterial circle and cerebral arteries) To describe the pattern of vessel involvement, histologic characteristics and progression of atherosclerosis in intracranial arteries of adult black Malawians, with respect to known risk factors, intracranial plague location, and populational diversity. The specific objectives of the study are: • To screen for the presence of atherosclerotic plaques in intracranial arteries of adult black Malawians at systematically-selected portions of the cerebral arterial tree using a system described by Resch and Baker • To analyse the pattern of vessel involvement and histologic characteristics of observed atherosclerotic plagues through phenotypic classification and morphological analyses • To assess the intensity and progression of intracranial atherosclerosis among known risk-stratified patient groups (i.e. individuals with HTN, Diabetes or HIV), as well as across varying portions of the cerebral arterial tree through AHA staging • To compare the intensity of histologic characteristics and progression of intracranial atherosclerotic plaques observed among Malawians with those observed in other diverse population groups. Methodology In this proposed study, arteries will be extracted from brains of conveniently-sampled autopsy candidates. Participants will be grouped into four categories (trauma, diabetes, hypertension, and HIV/AIDS) based upon their respective medical histories. For each category, samples will be obtained from 22 designated sites in the region of the interpeduncular fossa of the brain, washed with isotonic saline, glossed and classified based upon a systematic method by Resch and Baker. After that, the harvested segments will be decalcified overnight in 10% formic acid, before perfusion fixing in 4% formaldehyde and stored at 25°C until the time of histological processing. Routine staining and immunofluorescence techniques for CD68 will be applied in order to identify intimal damage and macrophage infiltration respectively. Analysis will involve semi-quantitative classification of plaque components, luminal narrowing, and degree of macrophage infiltration. This research conforms to the Declaration of Helsinki on the use of human subjects as well as the Malawi Anatomy Act of 1990 (amended version) and will be conducted after the approval of COMREC.Expected findings and their dissemination This study will provide insights on the prevalence, progression and pathological mechanisms of intracranial atherosclerosis in adult black Malawian population. The knowledge will assist in promoting effective assessment and management of risk factors for the disease and its attributable sequelae, ischaemic stroke. An understanding of the histologic profile of atherosclerosis vis-a-vis mechanisms of atherogenesis in this population group will adequately inform design of clinical trials and allow identification of biomarkers for use in screening, diagnosis, risk-stratification and pathological validation of vessel wall imaging (VWI) parameters. Moreover, a study of this calibre, carried out in varying patient categories, will shed light on presence of salient plaque characteristics (such as degree of intra-plaque haemorrhage, calcification and inflammatory cell infiltration) that contradistinct plaque vulnerability and ICAS progression across established risk-stratified patient groups. Lastly, investigating variations in patterns of atherogenesis among varying portions of the intracranial arterial tree may allow researchers to comment on the role of variations in anatomical configuration of the cerebral arterial circle in the development of atherosclerosis. This may partly give explanations to observed differences in prevalence of ICAD and ischaemic stroke among Asians, Caucasians and Blacks. Findings of the study will be presented in various research dissemination forums, published in referred journals, and shared with the university and the COMREC

Description

Type of study This will be a cross-sectional anatomical study involving brain arterial samples obtained from 60 recently-deceased adult black Malawians. The study will be conducted within a period of 1 year in the laboratories of the Division of Anatomy at the Kamuzu University of Health Sciences.