Investigating prevalence, progression and histologic characteristics of atherosclerosis in intracranial arteries of black Malawian population: A post-mortem study
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Date
2021-12-10
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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.