European Journal of Heart Failure 2006 8(7):694-696; doi:10.1016/j.ejheart.2006.05.006
© 2006 European Society of Cardiology
Hypothesis: Correction of low vitamin D status among Arab women will prevent heart failure and improve cardiac function in established heart failure
Hussein F. Saadi,
Elsadig Kazzam,
Bahlul A. Ghurbana and
M. Gary Nicholls*
Department of Internal Medicine, Faculty of Medicine and Health Sciences, UAE University, Al Ain, United Arab Emirates
* Corresponding author. Department of Medicine, Christchurch School of Medicine and Health Sciences, PO Box 4345, Christchurch, New Zealand. Tel.: +64 336 411162; fax: +64 336 41115. E-mail address: gary.nicholls{at}cdhb.govt.nz (M.G.Nicholls).
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Abstract
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Vitamin D deficiency is common in Arab countries particularly
among women. This is the result of a low dietary intake of the
vitamin, limited exposure to sunlight (a paradox in view of
the high sunshine figures), skin colour, obesity and high parity.
Apart from its adverse effects on bone in women and their offspring,
vitamin D deficiency has the potential to cause or exacerbate
heart failure through a number of mechanisms including activation
of the renin–angiotensin system and increased arterial
pressure. Accordingly, we propose that ensuring adequate vitamin
D levels in Arab women will have a much greater impact on health
than just the prevention of bone disease. In particular, we
suggest that prevention and correction of vitamin D deficiency
will reduce the incidence of heart failure and, for Arab women
with established heart failure and vitamin D deficiency, improve
cardiac function.
Key Words: Heart failure • Vitamin D • Renin–angiotensin system • Hypertension
Received January 17, 2006; Revised April 5, 2006; Accepted May 10, 2006
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1. Background
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Women in Arab countries are commonly vitamin D deficient. This
results from low exposure of the skin to sunlight associated
with modest dress codes (including total body clothing) and
skin melanin content, a sparse dietary intake of the vitamin,
a high number of pregnancies
[1-3], and presumably also from
obesity
[4] — a common problem among women in the United
Arab Emirates
[5]. That this deficiency has biological effects
is clear from the frequency with which rickets is observed
[6],
and from the fact that circulating levels of bone resorption
markers are higher
[2,
3] and bone density is lower in women
in Arab countries than in the West
[1,
7-9].
Our hypotheses are first, that widespread vitamin D deficiency amongst Arab women is one contributor to the development and maintenance of hypertension, which is a major risk factor for heart failure [10,11], and second, lack of vitamin D exacerbates heart failure in Arab women with cardiac compromise from whatever cause (hypertension, coronary atherosclerotic disease etc) [12,13]. Since vitamin D deficiency is especially common in Arab women [1-3], we suggest that for them, the effects of avoiding or correcting the deficiency will prove particularly rewarding with regard to the prevention and treatment of heart failure.
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2. Size of the problem
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We are aware of only one systematic study of the prevalence
of heart failure in an Arab country. This was carried out in
the indigenous Arab population in Oman over the years 1992-1994
[14]. The prevalence of symptomatic heart failure (5.17/1000
population) is no less than in Western countries and may be
higher given the high proportion of young people in the population
studied
[14]. The most frequent identified causes of heart failure
in that study were ischaemic heart disease and hypertension
[14] although the role of the latter may have been under-estimated
[10]. Hypertension was considered to be the most common risk
factor for heart failure in Qataris from a survey of hospitalised
patients
[11].
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3. Vitamin D deficiency and hypertension
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As noted above, hypertension is a, and perhaps the, most important
identifiable risk factor for heart failure in Arab populations.
The pathophysiology of primary hypertension is complex and involves
both genetic and environmental factors. Amongst the latter,
there is epidemiological evidence linking the lack of vitamin
D with the prevalence of hypertension
[15] although contrary
evidence can also be quoted
[16]. Exposure to ultraviolet B
irradiation reduced arterial pressure in a cohort of patients
with mild hypertension
[17], and Pfeifer et al reported that
vitamin D supplementation reduced systolic blood pressure in
elderly women with low vitamin D status
[18]. The linkage between
vitamin D and blood pressure may relate, in part, to the fact
that the vitamin is a negative regulator of renin release
[19].
Indeed, vitamin D receptor-null mice exhibit increased renal
renin mRNA expression, elevated plasma levels of angiotensin
II, hypertension and cardiac hypertrophy
[20].
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4. Vitamin D deficiency and cardiac failure
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Vitamin D has direct and indirect actions on various components
of the cardiovascular system that are generally seen as protective
[13]. A deficiency of the vitamin can have deleterious effects
on both the heart and vasculature
[13]. There are numerous case-reports
of gross vitamin D deficiency causing heart failure which is
reversible with vitamin D replacement. Furthermore, hypovitaminosis
D is common in patients with established heart failure in the
West
[21,
22], and was considered likely to be a contributor
to cardiac dysfunction in a cohort of 54 Caucasian patients
amongst whom there was an association between the severity of
heart failure and vitamin D status
[12]. We suggest that the
contribution of vitamin D deficiency to the pathogenesis of
heart failure in Arab countries, particularly among females,
is likely to be greater than in the West, whatever the primary
underlying aetiology. Thus, provision of vitamin D through dietary
supplementation or exposure to ultraviolet B light should improve
cardiac function in such patients. Salutary cardiac effects
will be, we suggest, through direct and indirect actions of
vitamin D on the heart
[13], as well as the neurohormonal mechanisms
noted above, together with amplification of type A natriuretic
peptide receptor activity
[23], through which the cardiac natriuretic
peptides exert their various cardioprotective actions.
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5. Testing the hypotheses
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We present here a "broad brush" proposal for testing the hypotheses:
space limitations preclude a more detailed exposition.
The vitamin D status of hypertensive versus matching normotensive Arab subjects can be assessed. Our supposition is that there will be a reciprocal relationship between vitamin D status (serum 25-OH vitamin D) and blood pressure in a cross-sectional study in Arab females. Since vitamin D status is but one factor affecting blood pressure, the cohort will need to be large and a formal power calculation will be necessary. A second study could document the effects of exposure to ultraviolet B irradiation on blood pressure in a cohort of hypertensive, vitamin D deficient Arab women — controlled as in the report by Krause et al [17].
In order to test the hypothesis that vitamin D deficiency exacerbates heart failure, a third study could involve female Arab patients with established heart failure and vitamin D deficiency (serum 25-OH vitamin D<50 nmol/L). Patients would be randomised to receive 50,000 units of vitamin D2 weekly or matching placebo for 6 months [24] in a double-blind, parallel group study. The study end-points (measured at baseline and after 6 months of treatment) would be plasma B-type natriuretic peptide levels (BNP, primary end-point), left ventricular function (echocardiography including tissue Doppler imaging), an objective measure of clinical well-being (visual analogue scale) and the 6-minute walk test. Again, a power calculation would be needed to determine patient numbers. If our hypothesis is correct, those receiving vitamin D will exhibit a fall in plasma BNP, improved left ventricular function, and increased well-being and walking distance.
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6. Implications
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Vitamin D deficiency is demonstrably common among women in Arab
countries. Emphasis on the effects of this deficiency thus far
has been on bone disease. By contrast, adverse effects involving
the cardiovascular system have received scant attention. We
contend that vitamin D deficiency is likely to be one contributor
to the development of heart failure in Arab countries through
protean effects on the cardiovascular and neuroendocrine systems
and via the development of hypertension. Additional benefits
from correcting vitamin D deficiency, not discussed here, might
include protective effects against developing type 1 diabetes
and some neoplasms, as well as correcting muscle aches and pains
and weakness
[24]. Should our hypothesis prove correct, the
public health and financial implications for Arab countries
will be considerable. A relatively simple program to prevent
and treat vitamin D deficiency in Arab women (along with efforts
to prevent obesity and diabetes) would repay the effort and
costs many-fold.
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References
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Abstract
1. Background