Cardiovascular Journal of Africa: Vol 28 No 1 (January/February 2016)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 1, January/February 2017

AFRICA

pre-eclampsia, and that this may be the central mechanism

involved in the pathophysiology of both early- and late-onset

pre-eclampsia.

Although some authors have suggested that early-onset

pre-eclampsia is a result of impaired placentation,

while late-

onset pre-eclampsia is as a result of maternal predisposition,

both are associated with endothelial dysfunction. As no one has

as yet discovered the cause of pre-eclampsia, it is difficult to

attach more significance to this attempt to separate early- from

late-onset pre-eclampsia.

An inverse relationship observed between FMD and baseline

vascular dimension has been reported from previous studies,

where peak arterial dilation is a function of baseline vessel

diameter and smaller vessels dilate more than larger ones.

In our

study, we found an inverse correlation between RHI and BPWA

in the entire study population (normotensive and pre-eclamptics

together), as well as within individual groups. Similar results

were recently reported by Carty

and Heffernan

et al

in their

studies on healthy volunteers as well as patients with coronary

artery disease. The authors found that BPWA was positively

related to baseline arterial diameter and in turn, inversely related

to RHI. This means that smaller brachial arteries have low

BPWA and subsequently a high RHI, and vice versa.

It has been suggested that in individuals with variable brachial

geometry, adjusting RHI for brachial artery diameter may be

needed to accurately examine microvascular endothelial function

using PAT.

Although baseline artery diameters were not

measured in our study, several studies have shown no difference

in baseline brachial artery diameters between normotensive

pregnancy and pre-eclampsia.

25-27

In view of these results from

other studies, it can be hypothesised that the inverse relationship

between RHI and BPWA observed in this study could be due to

factors other than the brachial artery diameter. Further studies

will need to be done to determine the factors responsible for the

inverse relationship between RHI and baseline brachial artery

diameter in pregnancy.

An inverse relationship was found between RHI, mean

arterial pressure and diastolic blood pressure in the entire study

population. No relationship was observed between RHI and

systolic blood pressure. Other studies have reported conflicting

relationships between RHI and mean arterial pressure, diastolic

and systolic blood pressure. Truschel

et al

showed a positive

correlation (among men and non-pregnant women) between

RHI and systolic blood pressure, whereas Konttinen

et al

and

Hamburg

et al.

showed no correlation between diastolic, systolic

and mean arterial pressure and RHI. BPWA was, however, found

to be positively correlated with systolic blood pressure.

Hamburg

et al

. suggested that systolic blood pressure may have

a limited effect on the distal microcirculation, whereas it had a

predominant effect on BPWA without additional modification of

the hyperaemic response, when presented as a ratio.

Since RHI

is negatively correlated with BPWA (which in turn is positively

correlated with systolic blood pressure), by extrapolation, RHI

would be negatively correlated with systolic blood pressure.

While assessing racial differences in microcirculatory function,

Morris

et al

. also found mean arterial pressure to be negatively

associated and an independent predictor of RHI.

In pregnancy, a similar correlation between RHI and mean

arterial pressure was found in a study done in Israel assessing the

relationship of pre-eclampsia with sleep-disordered breathing.

This relationship illustrates the impact of blood pressure

on microvascular function. Pre-eclampsia is characterised

by generalised vasoconstriction, an increase in peripheral

resistance, platelet activation, reduced plasma volume and

organ hypoperfusion.

31,32

The aetiology is still unclear, although

evidence suggests that increments in blood pressure may reflect

endothelial dysfunction, with the inability of the endothelial

cells to release relaxing factors that cause vasodilatation.

33,34

Endothelial dysfunction is known to lead to the widespread

clinical features of pre-eclampsia. Results from our study

therefore are in agreement with previous studies that found

endothelial dysfunction in women with pre-eclampsia.

35,36

Traditionally, PAlx is obtained from pressure waveforms

via applanation tonometry of the carotid or radial arteries.

Recently, it has been demonstrated that PAlx measured from

digital pulse-wave volumes by peripheral PAT correlated with

that from applanation tonometry

14,37

in diabetes and idiopathic

scleroderma associated with pulmonary arterial hypertension.

Carty

andNamugowa andMeeme

also reported that EndoPAT

augmentation index correlated with radial artery applanation

augmentation index (measured using the SphygmoCor) in

pregnancy. However, they cannot be used interchangeably since

the actual values do not match, as they are obtained from two

distinct vascular beds via two different methods.

Patvardhan

et al

found that augmentation index derived

from PAT correlated with cardiovascular risk factors. In this

study, we found that heart rate-corrected augmentation index

(Alx@75) was higher in pre-eclampsia compared to that in

normotensive pregnancy, indicating arterial stiffness. Similar

results have been reported by others.

41-45

Normal pregnancy is a profoundly vasodilated state.

This

vasodilated state could be due to the remarkable maternal

cardiovascular adaptation to pregnancy, which is the attenuated

systemic pressor response to vasoconstrictors, including

angiotensin II and norepinephrine.

47,48

A reduction in vascular

compliance in pre-eclampsia is an indication of vascular

stiffness, as is seen in non-pregnant patients with chronic

hypertension, vascular disease or diabetes.

49-52

It may also indicate

vasoconstriction, most likely due to endothelial dysfunction,

since systemic response to vasoconstrictors such as angiotensin

II and norepinephrine is not attenuated but augmented in

pre-eclampsia.

The reactive hyperaemia index, as a measure of endothelial

dysfunction, was lowest in HIV-positive pre-eclamptics (1.67)

and highest in HIV-negative normotensive controls (1.84). In

HIV-positive normotensive controls, the RHI was 1.79 and it

was 1.70 in HIV-negative pre-eclamptic cases. Although these

differences did not achieve statistical significance, a trend

towards a lower reactive hyperaemia index can be seen in the

HIV-positive patients, indicating increasing levels of endothelial

dysfunction. Arterial stiffness, as measured by the augmentation

index was significantly worse (

0.000) in the HIV-positive

pre-eclamptic and normotensive women than in the HIV-negative

pre-eclamptic and normotensive women. Arterial stiffness is also

a measure of endothelial dysfunction, therefore indicating that

HIV infection is indeed associated with endothelial dysfunction

in both normotensive and pre-eclamptic patients.

Considering that vasodilation, upon which the EndoPAT

depends, is influenced by temperature, efforts were made to

conduct the measurements in temperature-controlled rooms for