Endothelial Dysfunction; a
Barometer of Cardiovascular Health
Endothelial cells line the entire vascular system. They play
critical, complex multi-faceted roles in:
Regulating blood pressure, vascular
smooth muscle tone, local blood flow, vascular growth and repair
Balancing blood clotting and clot
dissolution: maintaining a dynamic barrier between tissue and
bloodstream
Regulating immune function and
inflammation, including inflammatory factors that underlie
plaque formation and instability in occlusive (atherosclerotic)
vascular disease
Traffic through the vascular wall of
immune cells, lipid particles and foreign bodies
Tissue nourishment, ion transport
and electrolyte balance
Endothelial dysfunction impairs vasorelaxation, so that blood flow
fails to meet demand (e.g. in exertional angina); predisposes to
thrombotic events (as in acute coronary syndromes, including
myocardial infarction, and some forms of stroke); promotes
inflammation; and leads to plaque development, progression and
rupture. Many vascular endothelial functions are
mediated by endothelium-derived nitric oxide (NO), and are enhanced
by NO donors such as nitroglycerin (“nitro”) and by inhibitors of NO
breakdown (such as Sildenafil (Viagra ®)). Other important mediators
include prostaglandins (such as prostacyclin), thromboxanes,
endothelin, angiotensins, kinins and hyperpolarizing factors. Many
CV prescription medications, natural products and dietary
supplements enhance endothelial function by design or coincidence.
Endothelial dysfunction results from continued assaults on
the vascular wall by risk factors such as high cholesterol,
diabetes, smoking, hypertension, oxidative stress and others.
Numerous studies have shown that endothelial function is altered in
the presence of established risk factors, as well as emerging risk
factors (such as hyperhomocystenemia, high fibrinogen, and high
CRP). Also several studies have shown strong correlations between
endothelial dysfunction and subclinical markers of atherosclerosis
such as increased carotid intima media thickness (CIMT), increased
coronary calcium score (CSS), and abnormal ankle brachial index (ABI)
all of which are strong predictors of cardiovascular events.
Impaired endothelial function can be detected before the development
of angiographically significant plaque formation (blockage of the
artery) in the coronary and peripheral vasculature. Endothelial
function testing can not only help predict cardiovascular risk but can
also help demonstrate the response to treatment. Pharmacological
therapies and lifestyle changes aimed at improving cardiovascular
risk also improve endothelial function.
How is endothelial function measured? Methods currently used
to measure vascular responsiveness and endothelial function, in
specialist settings, include brachial arterial flow-mediated
dilatation measured but by Doppler Ultrasound; strain gauge plethysmography; peripheral pulse waveform analysis by arterial
tonometry and other methods; LASER-Doppler fluximetry; and invasive
intracoronary provocation tests. The contribution of the endothelium
to the measured response differs between methods. Each of these has
an appropriate research setting, but all are limited to some degree by
difficulties with respect to safety, complexity, operator skill and
bias, cost, the inability to repeat at intervals, meaningless
indices and uncertain predictive value – especially with respect to
the individual patient.
Coronary vs. Brachial Endothelial Function Atherosclerosis is
a systemic metabolic-immune disease that affects the entire vascular
bed. Coronary atherosclerosis due to certain hemodynamic
characteristics seems to pursue a faster trajectory and develops stenotic plaques. However, stenotic plaques are considered only as
the tip of the iceberg. Coronary atherosclerosis has been associated
with brachial artery atherosclerosis and impaired brachial artery
reactivity and strongly correlates with impaired coronary artery
reactivity. Measurement of endothelial function in the brachial artery
with noninvasive techniques provides an opportunity to evaluate
large patient populations.
