Clinical trial NCT01555294: Evaluation of Non-invasive Measurements of Atherosclerosis in Cardiovascular Risk Stratification
Official title: Evaluation of Non-invasive Measurements of Atherosclerosis in Cardiovascular Risk Stratification: a Study in a Population-based Cohort and Familial Combined Hyperlipidemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiovascular Disease
Keywords: (subclinical)atherosclerosis
non-invasive measurements
intima-media thickness
flow-mediated dilation
pulse wave velocity and analysis
fatal and non-fatal cardiovascular events
ankle-brachial index (at rest and after exercise)
general population
Familial Combined Hyperlipidemia
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2012-03-15
Enrollment: 1960
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants recruited from a population-based survey aged 50-70 years. Participants from families with Familial Combined Hyperlipidemia.

Brief summary: Multiple risk factors contribute to atherosclerosis, which ultimately results in clinical manifestation of cardiovascular disease. Atherosclerosis results in both functional and morphological changes in the vessel wall, which can be measured by ultrasonography. The current study has been designed to

1. To evaluate whether non-invasive measurements of atherosclerosis are independent predictors of cardiovascular disease and
2. to delineate new biochemical parameters and genetic variations, allowing earlier and more effective preventive therapy
3. The investigators intend to set guidelines for use of NIMA in an outpatient setting to facilitate early detection of increased cardiovascular risk and monitor life-style and pharmaceutical interventions.

In both the general population and in Familial Combined Hyperlipidemia.

Detailed description: Cardiovascular disease (CVD) is the major cause of death in all developed countries. Atherosclerosis is the main cause of CVD. Abundant evidence indicates the 4 major independent risk factors for atherosclerosis and CVD include cigarette smoking, elevated blood pressure, elevated total cholesterol and diabetes mellitus. However, a major problem in clinical medicine is that at every level of risk factor exposure, there is a large inter-individual variation in the amount of atherosclerosis and the development of CVD. Therefore, it is difficult to predict the CVD risk in an individual patient based on risk factor screening alone.

Non-invasive measurements of atherosclerosis (NIMA): An indicator of the overall effect of all known and unknown potential risk factors for atherosclerosis in vivo can be assessed by measuring atherosclerosis directly in the vessel wall. This also provides the opportunity to measure atherosclerosis before developing symptoms of CVD, as changes in the arterial wall precede clinical symptoms of CVD.

Objectives: (1)The main objective is to evaluate whether NIMA are independent predictors of CVD and thus add information to traditional risk factor stratification. (2) Furthermore, we will delineate new biochemical and genetic risk factors, allowing earlier and more effective preventive therapy. (3) We intend to set guidelines for use of NIMA in an outpatient setting to facilitate early detection of increased cardiovascular risk and monitor life-style and pharmaceutical interventions.

We will evaluate 4 different NIMA, based on ultrasound and tonometry techniques, including intima media thickness (IMT), endothelial function by flow mediated dilation (FMD), ankle-brachial index (ABI), Pulse Wave Analyses(PWA) and pulse wave velocity (PWV). The power of NIMA, to predict cardiovascular events will be studied in two available populations, a low risk population cohort, the Nijmegen Biomedical Study (NBS) and a high risk population, families with Familial Combined Hyperlipidemia.

The NBS is a prospective population survey aimed at investigating the frequency of genetic variations in the general population. The study population is recruited as a sex- and age-stratified random sample of all inhabitants of Nijmegen 20 to 90 years old (n=10.000). Recruitment has started in October 2001. The present study is a substudy in the NBS. A follow-up approach will be used to evaluate whether NIMA are related to future cardiovascular events. In total 1517 participants aged 50-70 years were included.

FCH is the most common inherited hyperlipidemia in man. Affected individuals are characterized by elevated cholesterol and/or triglyceride levels and other associated traits including small-dense LDL, insulin resistance, oxidative stress and increased apoB levels, which have been proposed to contribute to the increased risk of CVD. So, this population will be most informative to evaluate the relevance of NIMA in CVD risk assessment as patients exhibit numerous, additive risk factors, which are missed in traditional cardiovascular risk assessment. Our data base contains a unique population of 40 well-characterized FCH families, including 687 patients, relatives and spouses with 5 years follow-up data. These families participate in an ongoing long-term follow-up program with registration of CVD.

All four NIMA's, including IMT, ABI, PWV/PWA, FMD, and both traditional and new biochemical and genetic parameters will be measured in both populations. The relevance of NIMA in identifying subjects at increased risk of CVD will be determined. Furthermore, the effect of risk factors on IMT, ABI, PWV and FMD will be studied, including clinical and traditional risk factors and new biochemical parameters and genetic variations.

Innovative aspects: We will develop an evidence based protocol for NIMA to show the presence of atherosclerosis before clinical manifestation of CVD and to improve cardiovascular risk stratification beyond traditional risk factor screening. Furthermore, we will delineate new risk factors, including both biochemical parameters and genetic variations, contributing to design optimal (new) treatment and to develop new strategies for prevention of CVD in the general population and in a high risk population, FCH.

Clinical relevance: If NIMA turns out to provide powerful information in identifying subjects at increased risk of CVD we will incorporate NIMA into clinical practice guidelines for the purpose of cardiovascular risk stratification and evaluation of risk management strategies. The identification of potential new biochemical and/or genetic risk factors will be very helpful to design optimal treatment and to develop new strategies for identification and prevention of CVD in both the general population and families with FCH.

Eligibility criteria: Population-based cohort:

Inclusion Criteria:

* aged 50-70 years at inclusion

Exclusion Criteria:

* recent symptomatic CV disease (\<6 months)

Familial Combined Hyperlipidemia:

Inclusion Criteria:

* age \>18 years

Exclusion Criteria:

* pregnancy

Primary outcomes:
measure: Cardiovascular events
timeFrame: 3-7 years
Secondary outcomes:
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre, Department of General Internal Medicine, Division of Vascular Medicine
Study officials:
affiliation: Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine
name: Jacqueline de Graaf, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine
name: Anton FH Stalenhoef, MD, PhD
role: STUDY_CHAIR
affiliation: Radboud University Nijmegen Medical Centre, Dept. of Epidemiology and Biostatistics
name: Martin den Heijer, MD, PhD
role: STUDY_CHAIR
affiliation: Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine
name: Suzanne Holewijn, PhD
role: STUDY_CHAIR
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