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Indices of calcium metabolism and their relationships with arterial structure and function in African women : the PURE study / Lebo Francina Gafane

Motivation - The burden of cardiovascular diseases (CVD) is increasing in developing countries
worldwide, but even more so in sub-Saharan Africa. Due to rapid urbanisation, black
populations experience lifestyle changes (e.g. unhealthy diet, increased access to alcohol
and tobacco) that predispose them to increased obesity and cardiovascular risk. In this
study, attention will be given to cardiovascular alterations, specifically arterial calcification, in
lean and overweight/obese women nearing or already experiencing menopause. These
include elevated blood pressure, large artery stiffness (indicated by increased central pulse
pressure (cPP)) and carotid intima-media thickness (CIMT). Other factors linked to arterial
calcification include the level of obesity as well as low bone mineral density.
Ectopic calcification plays a significant role in cardiovascular morbidity and mortality,
especially in renal failure patients, osteoporotic and elderly women. Factors contributing to
the development and progression of arterial calcification include calciotropic hormones and
altered bone metabolism, particularly in older postmenopausal women. This is due to the
lack of protective effects of oestrogen against vascular alterations and bone loss after
menopause. Previous studies have shown that increased bone resorption indicated by
elevated levels of c-telopeptide of type I collagen (CTX), parathyroid hormone (PTH), low 25-
hydroxycholecalciferol (25(OH)D3) and parathyroid hormone to 25-hydroxycholecalciferol
ratio (PTH:25(OH)D3) are independently linked to arterial stiffening, CIMT and vascular
calcification. Knowledge on the contribution of altered bone metabolism and associated
calciotropic hormones on cardiovascular health in Africans is limited. Previous studies on
ectopic calcification in South Africans focused on men and renal failure patients. This study will explore the possible role of altered calcium regulation and bone metabolism in the
development of arterial calcification and CVD in older African women.
Aim - The aim of this study was to investigate the associations of brachial and central pressures
and CIMT with PTH, PTH:25(OH)D3 and CTX, a marker of bone resorption, in lean and
overweight/obese African women older than 46 years.
Methodology - This sub-study forms part of the Prospective Urban Rural Epidemiology (PURE) study. A
total of 434 urban and rural women older than 46 years were included in the study. Women
infected with the human immunodeficiency virus (HIV) were excluded from the study. The
study was reviewed and approved by the Ethics Committee of the North-West University
(Potchefstroom campus) and all participants signed an informed consent form prior to
enrolment into the project. Field workers administered demographic, general health and
physical activity questionnaires in the participants’ home language. Anthropometric
measurements included weight, height and waist circumference, while body mass index
(BMI) was calculated in kg/m2. Cardiovascular measurements included brachial and central
systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), brachial and central
pulse pressure (PP) as well as CIMT and carotid cross-sectional wall area (CSWA). Blood
pressure measurements were performed on the right arm with the participant in the sitting
position. Blood was drawn after an overnight fasting period. We performed biochemical
analyses from serum and plasma samples for follicle stimulating hormone (FSH), PTH,
25(OH)D3, and CTX. HIV testing was performed according to standardised procedures.
Since interactions existed for BMI with regards to associations of CIMT and cPP with
PTH:25(OH)D3, the study population was divided into the lean (BMI <25 kg/m2) and
overweight/obese (BMI ≥25 kg/m2) groups. We performed independent T-tests to compare
means and used the chi-square test to compare proportions. Single and multiple regression analyses were performed to investigate the associations of markers of vascular structure
and function with CTX and calciotropic hormones.
Results - In this study, 90% of the women displayed an FSH concentration exceeding the cut-off value
of 35 mIu/mL, indicating a postmenopausal state. When comparing lean and
overweight/obese African women, we found that lean women had higher levels of CTX and
25(OH)D3 (both p<0.001), while the overweight/obese group was older (p=0.007) and
presented with higher PTH and PTH:25(OH)D3 levels (both p<0.001). Brachial and central
pressures did not differ between the groups (p≥0.23), except for DBP being higher in the
overweight/obese group (p=0.017). Overweight/obese women had higher CIMT (p<0.001)
and CSWA (p=0.001) as compared to their lean counterparts. A larger proportion of lean
women smoked (63%) and self-reported on alcohol use (37%) than overweight/obese
women (41% and 18%, respectively) (both p<0.001). Forty-one percent of overweight/obese
women used antihypertensive medication, opposed to 25% in the lean group (p=0.001).
In multivariate regression analyses, an independent positive association existed between
CIMT and PTH:25(OH)D3 (R2=0.22; β=0.26; p=0.003) in lean women. In the
overweight/obese group independent positive associations were confirmed between brachial
SBP and PTH (p=0.013) and CTX (p=0.038), and between DBP and PTH (p=0.030).
Brachial PP and central SBP remained positively associated with CTX (p=0.016 and
p=0.024, respectively), while cPP was independently associated with PTH:25(OH)D3
(R2=0.20; β=0.17; p=0.017) and CTX (R2=0.20; β=0.17; p=0.025).
Conclusion - Our results indicate that in older African women, large artery structure and function are
associated with calciotropic hormones and bone resorption, suggesting that altered bone
metabolism and associated calciotropic hormones play a role in the development of vascular
calcification. The different associations in lean and overweight/obese women suggest different mechanisms at work regarding arterial calcification in states of low and high
adiposity. These findings need confirmation in larger prospective and experimental studies. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014

Identiferoai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/11544
Date January 2013
CreatorsGafane, Lebo Francina
Source SetsNorth-West University
LanguageEnglish
Detected LanguageEnglish
TypeThesis

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