NIMA: Evaluation of Non-invasive Measurements of Atherosclerosis in Cardiovascular Risk Stratification

• Sponsor: Radboud University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01555294
• Collaborator: (none)
• Enrollment: 1,960
• Location: 1
• Duration (Months): 72
• Patients Per Site Per Month: 27.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 1960 participants
• Time Perspective: Prospective
• 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 Start Date: May 1, 2005
• Actual Primary Completion Date: May 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
community-based cohort The present study is a substudy in the Nijmegen Biomedical Study (NBS). 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. In the current study 1517 participants aged 50-70 years were included from 2005 to 2008, from whom baseline characteristics were obtained. All visited our hospital and during the visit venous blood was drawn, height and weight were measured, a questionnaire about medical history, life style habits, and family history was completed and non-invasive measurements of atherosclerosis were performed.
Familial Combined Hyperlipidemia FCH is the most common inherited dyslipidemia in man. Affected individuals are characterized by elevated cholesterol and/or triglyceride levels and an increased risk of CVD. Our data base contains a unique population of 40 well-characterized FCH families, including 687 patients, relatives and spouses. These families were recruited in 1994 and extensively studied, including information on an extensive panel of biochemical and genetic parameters. In total 343 participants were included in the NIMA study; 103 FCH patients and 240 unaffected relatives from whom baseline characteristics were obtained.

Outcome Measures

Primary Outcome Measures

1. Cardiovascular events [3-7 years]

   Fatal and non-fatal cardiovascular events will be evaluated by questionnaire and validated using hospital records and records from general practitioners.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Radboud University Nijmegen Medical Centre, Department of General Internal Medicine, Division of Vascular Medicine	Nijmegen		Netherlands

Sponsors and Collaborators

• Radboud University Medical Center

Investigators

• Principal Investigator: Jacqueline de Graaf, MD, PhD, Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine
• Study Chair: Anton FH Stalenhoef, MD, PhD, Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine
• Study Chair: Martin den Heijer, MD, PhD, Radboud University Nijmegen Medical Centre, Dept. of Epidemiology and Biostatistics
• Study Chair: Suzanne Holewijn, PhD, Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

• Gretarsdottir S, Baas AF, Thorleifsson G, Holm H, den Heijer M, de Vries JP, Kranendonk SE, Zeebregts CJ, van Sterkenburg SM, Geelkerken RH, van Rij AM, Williams MJ, Boll AP, Kostic JP, Jonasdottir A, Jonasdottir A, Walters GB, Masson G, Sulem P, Saemundsdottir J, Mouy M, Magnusson KP, Tromp G, Elmore JR, Sakalihasan N, Limet R, Defraigne JO, Ferrell RE, Ronkainen A, Ruigrok YM, Wijmenga C, Grobbee DE, Shah SH, Granger CB, Quyyumi AA, Vaccarino V, Patel RS, Zafari AM, Levey AI, Austin H, Girelli D, Pignatti PF, Olivieri O, Martinelli N, Malerba G, Trabetti E, Becker LC, Becker DM, Reilly MP, Rader DJ, Mueller T, Dieplinger B, Haltmayer M, Urbonavicius S, Lindblad B, Gottsäter A, Gaetani E, Pola R, Wells P, Rodger M, Forgie M, Langlois N, Corral J, Vicente V, Fontcuberta J, España F, Grarup N, Jørgensen T, Witte DR, Hansen T, Pedersen O, Aben KK, de Graaf J, Holewijn S, Folkersen L, Franco-Cereceda A, Eriksson P, Collier DA, Stefansson H, Steinthorsdottir V, Rafnar T, Valdimarsson EM, Magnadottir HB, Sveinbjornsdottir S, Olafsson I, Magnusson MK, Palmason R, Haraldsdottir V, Andersen K, Onundarson PT, Thorgeirsson G, Kiemeney LA, Powell JT, Carey DJ, Kuivaniemi H, Lindholt JS, Jones GT, Kong A, Blankensteijn JD, Matthiasson SE, Thorsteinsdottir U, Stefansson K. Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm. Nat Genet. 2010 Aug;42(8):692-7. doi: 10.1038/ng.622. Epub 2010 Jul 11.

• Responsible Party: Jacqueline de Graaf, Prof. Dr. J. de Graaf, Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT01555294
• Other Study ID Numbers: CMO 2003/174
• First Posted: Mar 15, 2012
• Last Update Posted: Mar 15, 2012
• Last Verified: Mar 1, 2012

• Keywords provided by Jacqueline de Graaf, Prof. Dr. J. de Graaf, Radboud University Medical Center: (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
• Additional relevant MeSH terms: Cardiovascular Diseases; Atherosclerosis

Study Results

No Results Posted as of Mar 15, 2012