Scientific Concept of the National Cohort (status ... - Nationale Kohorte

89
A.3 Study design
The device will also be equipped with an ultrasound probe suitable for performing the measurement
of intima–media thickness of the carotid artery.
measurement of arterial stiffness and ankle–brachial index
Arterial stiffness is defined as a reduction in arterial distensibility. The physiological mechanisms
underlying arterial stiffening occurring with age and the accumulation of cardiovascular
risk factors include breaks in elastin fibers, accumulation of collagen, fibrosis, inflammation,
medial smooth muscle necrosis, calcifications, and diffusion of macromolecules
within the arterial wall 567 . These phenomena have been shown to develop simultaneously in
coronary arteries and the aorta 568 . The association of specific measures of arterial stiffness
(such as the augmentation index and central blood pressure) with target-organ damage and
cardiovascular outcome is greater than that of brachial blood pressure 569 , i.e., the increase
in cardiovascular risk can be estimated better from central than from brachial blood pressure
measurements 570 . Recent guidelines for the management of hypertension call for assessment
of arterial stiffness to guide therapeutic decisions 571 .
Moreover, alterations in vascular stiffness may cause diastolic and systolic heart failure, for
example, as a result of left ventricular hypertrophy, and subendocardial ischemia or coronary
artery disease. However, the potential link between measures of vascular stiffness
and ventricular dysfunction (“arterioventriculo coupling”) has not been addressed in large
population-based cohort studies. Furthermore, there is insufficient knowledge on determinants
of arterial stiffness.
The gold standard for measuring arterial stiffness is pulse wave velocity 572 , as measured by
the Sphygmocor device 573 , which has also been used most frequently. However, newer devices
which are easier to use and less observer-dependent have recently become available
(Vascular Explorer, Vicorder) 574 . In practice, pulse wave velocity is calculated as the traveling
time or distance of the pulse wave between two measuring sites 575 . The assessment
of the wave reflection in the arterial system, the pulse wave analysis, gives information on
arterial stiffness, central blood pressure, and subendocardial flow reserve.
The ankle–brachial index is a noninvasive, rapid, and quantitative measure of PAD, derived
from brachial and ankle systolic blood pressure values. The ankle–brachial index is inversely
associated with CVD events, mortality, and the progression to critical leg ischemia,
rest pain, and ulceration 576-579 . It is one of the standard tools for diagnosing lower extremity
PAD and is used for PAD screening and therapeutic efficacy monitoring. Lower extremity
PAD can be symptomatic (intermittent claudication) but is often asymptomatic. The use
of an ankle–brachial index < 0.9 to diagnose PAD has a sensitivity of 0.95 and specificity
of 0.99 and is highly reproducible 580 . However, further information is needed to improve
our understanding of early developments and determinants of progressive reduction in the
ankle–brachial index, and to better assess the predictive ability of reduced ankle–brachial
index for future cardiovascular events.
Procedure of measurement:
Ankle–brachial index, pulse wave analysis, and velocity will be measured at a controlled room
temperature (22°C) after the subject has rested for at least 5–10 min in a supine position.
For these measurements, several devices are available, among them the SpyhgmoCor
device (the current gold standard for measuring pulse wave analysis and velocity) 572 , the
Vascular Explorer, and the Vicorder (the latter two being new multifunctional devices for
measuring ankle–brachial index and pulse wave velocity). To determine the ankle–brachial
A.3