The predictive value of repeated Non-Invasive Measurements of Atherosclerosis (NIMA) in relation to cardiovascular risk factors and cardiovascular disease stratification: a study in the general population and in Familial Combined Hyperlipidemia (NBS-NIMA 2)

The predictive value of repeated Non-Invasive Measurements of Atherosclerosis
(NIMA) in relation to cardiovascular risk factors and cardiovascular disease
stratification: a study in the general population and in Familial Combined
Hyperlipidemia (NBS-NIMA 2)

This study will unravel the impact of time of exposure to different risk
factors on the development and progression of atherosclerosis, as measured by a
panel of repeated Non-Invasive Measurements of Atherosclerosis (NIMA) and the
incidence of cardiovascular disease (CVD) in both the general population and
families with Familial Combined Hyperlipidemia (FCH). An evidence based
protocol for NIMA to improve cardiovascular(CV) risk stratification in clinical
practice will be developed.

Background & Relevance for cardiovascular diseases:
Despite treatment of classical CV risk factors, considerable risk remains in
both patients with and without CVD. Moreover, it is well-known that at every
level of risk factor exposure there is a large inter-individual variation in CV
risk. By measuring atherosclerosis directly in the arterial wall, the damage
caused by these risk factors can be determined. This provides the opportunity
to measure atherosclerosis before symptomatic CVD develops. Thus, subclinical
disease measurements, representing the final result of risk exposure, may be
useful for improving CV risk prediction, therapeutic strategies and evaluation
of risk factor modification. Therefore, several NIMA have been developed to
measure the amount of atherosclerosis, including flow-mediated dilation (FMD),
intima media thickness (IMT), the presence and thickness of plaques in the
carotid arteries, ankle-brachial index (ABI) at rest and after exercise, pulse
wave velocity (PWV), and pulse wave analysis (PWA). NIMA reflect the result of
exposure to all CV risk factors, leading to structural and functional changes
in the arterial wall, contributing to the process of atherosclerosis and CVD.
During the last few years, evidence has been accumulating that some NIMA have
independent predictive power for CVD, suggesting that NIMA has additive value
in CV risk stratification. However, only ±30% in the variation of NIMA can be
explained by the known CV risk factors, so the major pathophysiological
determinants of NIMA remain to be determined. Furthermore, follow-up data on a
panel of NIMA are lacking and the relevance of repeated NIMA in clinical
practice for the individual patient is unclear.

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Hypothesis:

Changes in NIMA over 5 years, measured by repeated NIMA in both a low and a
high-risk population, in relation to changes in traditional and new CV risk
factors and incidence of CVD will reveal the main determinants of each of the
NIMA. This knowledge will lead to an evidence based protocol for NIMA to
improve CV risk stratification of the individual patient in clinical practice.
Furthermore, the combination of NIMA that predicts CVD best in a cost-effective
way will be identified. Finally, our data may provide more insight in
differences in the development of subclinical atherosclerosis and CVD between
men and women in both populations. The repeated measurements in two weeks in
N=40 participants (N=20 low-risk participants and N=20 FCH patients) will
provide insight in the variability of the measurements and will enable us to
better determine the predictive value of the measurements in our ongoing
prospective follow-up study (NBS-NIMA1).

Methods

In both populations, we evaluated the associations between CV risk factors and
NIMA in NBS-NIMA1. Currently the clinical endpoints are evaluated and based on
these data the predictive value of NIMA for CVD will be evaluated. In the
present study (NBS-NIMA2), repeated measurements of NIMA after 5 years will be
performed in both groups, including FMD, IMT, the presence and thickness of
plaques in the carotid arteries, ABI at rest and after exercise, PWV, and PWA.
Traditional and new clinical and biochemical measurements will be assessed,
including a questionnaire on life style habits and medical history, and
clinical endpoints will be evaluated. Venous blood will be drawn and a urine
sample will be collected. The measurement protocol will be exactly the same as
in our NBS-NIMA 1 study (CMO 2003/174).

Performing NIMA does not cause a risk for the participants, which we have
evaluated by measuring over 1800 participants in NBS-NIMA1 (CMO2003/174). The
amount of burden for the participants mainly is dictated by the fact that we
ask them to come in the fasting state and the time they have to spent (the
visit takes about 1,5 hour). Based on the many participants that were willing
to participate in NBS-NIMA1, this was not a large burden.