BACKGROUND: Arterial stiffness and endothelial dysfunction are implicated in the
pathogenesis of atherosclerosis. Both are present in patients with
hypercholesterolaemia and diabetes mellitus, and are markers of future
cardiovascular events in patients with coronary artery disease (CAD), hypertension
and end-stage renal failure. The structural components, elastin and collagen, which
influence skin elasticity are also responsible for the elasticity of arteries.
AIMS: To investigate: 1. The association between skin elasticity and arterial
elasticity in healthy subjects. 2. The determinants of arterial stiffness in patients with
CAD, particularly renal function. 3. The determinants of endothelial dysfunction in
patients with CAD. 4. The association between arterial stiffness and endothelial
dysfunction in patients with CAD. 5. The survival of subjects from cardiovascular
morbidity and mortality as determined by the severity of CAD, renal function,
arterial stiffness and endothelial function.
METHODS: Skin elasticity was measured in the arm, leg and back using a suction
device which measures the vertical deformation of skin. Arterial stiffness was
assessed using pressure pulse wave velocity (PWV), pulse wave analysis (PWA) and
digital volume pulse (DVP) analysis. Endothelial function was determined noninvasively using PWA with the administration of glyceryl trinitrate (endotheliumindependent vasodilator) and salbutamol (endothelium-dependent vasodilator). The
study in CAD was a cohort study with longitudinal follow up for a median of 18
months. Adverse clinical events were determined through the Information and
Statistics Division of the NHS and the General Register Office in Scotland. Renal
function was assessed using serum creatinine concentration ([creat]sr) and estimated
glomerular filtration rate (eGFR) by using creatinine clearance calculated using the
Cockcroft & Gault equation. Subjects with a history of renal disease were excluded.
The primary-endpoint was a composite of hospitalisation and mortality due to
RESULTS: 1. Arterial elasticity and skin elasticity were only weakly associated. 2.
Arterial stiffness was determined by age, heart rate, central systolic blood pressure
and [creat]sr (R2=0.38, P < 0.001). Arterial stiffness was negatively associated with
eGFR (R2=0.30, P < 0.001), even within the normal range. 3. Endotheliumindependent changes in the augmentation indices (AIs) were determined by age,
body mass index and mean blood pressure (R2=0.09, P < 0.001). Endotheliumdependent changes in AIs were weakly explained by mean blood pressure (R2=0.02,
P < 0.001) but not associated with hypercholesterolaemia, as previously reported, or
renal function. However, the presence or severity of CAD did not explain the
variance in arterial stiffness or endothelial function measures. 4. Endotheliumindependent and dependent changes in AIs were positively correlated. In addition,
endothelium-independent changes in AIs were lower in subjects with stiffer arteries
(r = 0.20, P < 0.01). 5. Subjects with a high number of diseased coronary vessels (P <
0.001), a low eGFR (P < 0.01), or a PWV above the median (P < 0.05) had a higher
risk of developing adverse clinical events. Endothelial function, however, did not
appear to predict a poor outcome.
CONCLUSION: In healthy subjects, skin elasticity is an unreliable marker of arterial
elasticity. An important finding in the CAD study was that renal function was a
determinant of arterial stiffness in patients without a history of renal disease. In this
treated group of subjects, traditional cardiovascular risk factors did not determine
arterial stiffness or endothelial dysfunction and there was no association between
arterial stiffness and endothelial dysfunction. Moreover, endothelial function
measured using PWA, with the administration of GTN and salbutamol, is not a
useful test in patients with CAD on drug treatment. However, the presence and
severity of CAD, renal function, as well as the stiffness of arteries, are predictive of a
shorter time to fatal and non-fatal cardiovascular outcomes.