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Cardiovascular DiseaseNIMANCT01555294

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

An observational study of Cardiovascular Disease, run by Radboud University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Cardiovascular Disease
How many people
1,960 participants
Where
1 siteNetherlands
Study dates
May 2005to May 2011
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Study population: Participants recruited from a population-based survey aged 50-70 years. Participants from families with Familial Combined Hyperlipidemia.

Who may be able to join

  • aged 50-70 years at inclusion
  • age >18 years

Who cannot join

  • recent symptomatic CV disease (<6 months)
  • Familial Combined Hyperlipidemia:
  • pregnancy

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • Radboud University Nijmegen Medical Centre, Department of General Internal Medicine, Division of Vascular Medicine

    Nijmegen

Other trials in Netherlands

About this study

Official title: Evaluation of Non-invasive Measurements of Atherosclerosis in Cardiovascular Risk Stratification: a Study in a Population-based Cohort and Familial Combined Hyperlipidemia

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.

Read the 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.

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
Medical subject headings
Cardiovascular Diseases, Hyperlipidemia, Familial Combined

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01555294
Study groupRoleWhat they receive
community-based cohortThe 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 HyperlipidemiaFCH 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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cardiovascular events

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

    Measured: 3-7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2012 (estimated)
  2. Study startMay 2005
  3. Primary completionMay 2011
  4. Study completionMay 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Time perspective
Prospective
Enrolment
1,960 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01555294
Sponsor's protocol ID
CMO 2003/174
Acronym
NIMA
Status last verified
Mar 2012
First submitted
6 Sep 2011
Last updated
15 Mar 2012
Results posted
No
Data monitoring committee
No

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, Gottsater A, Gaetani E, Pola R, Wells P, Rodger M, Forgie M, Langlois N, Corral J, Vicente V, Fontcuberta J, Espana F, Grarup N, Jorgensen 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.

    PubMed 20622881
  • ter Avest E, Holewijn S, Stalenhoef AF, de Graaf J. Variation in non-invasive measurements of vascular function in healthy volunteers during daytime. Clin Sci (Lond). 2005 May;108(5):425-31. doi: 10.1042/CS20040300.

    PubMed 15636580
  • ter Avest E, Abbink EJ, Holewijn S, de Graaf J, Tack CJ, Stalenhoef AF. Effects of rosuvastatin on endothelial function in patients with familial combined hyperlipidaemia (FCH). Curr Med Res Opin. 2005 Sep;21(9):1469-76. doi: 10.1185/030079905X61910.

    PubMed 16197666
  • ter Avest E, Holewijn S, Bredie SJ, Stalenhoef AF, de Graaf J. Remnant particles are the major determinant of an increased intima media thickness in patients with familial combined hyperlipidemia (FCH). Atherosclerosis. 2007 Mar;191(1):220-6. doi: 10.1016/j.atherosclerosis.2006.03.025. Epub 2006 May 4.

    PubMed 16677651
  • ter Avest E, Holewijn S, Bredie SJ, van Tits LJ, Stalenhoef AF, de Graaf J. Pulse wave velocity in familial combined hyperlipidemia. Am J Hypertens. 2007 Mar;20(3):263-9. doi: 10.1016/j.amjhyper.2006.09.015.

    PubMed 17324737
  • Ter Avest E, Holewijn S, van Tits LJ, de Wit HM, Stalenhoef AF, de Graaf J. Endothelial function in familial combined hyperlipidaemia. Eur J Clin Invest. 2007 May;37(5):381-9. doi: 10.1111/j.1365-2362.2007.01804.x.

    PubMed 17461984
  • Koenen TB, van Tits LJ, Holewijn S, Lemmers HL, den Heijer M, Stalenhoef AF, de Graaf J. Adiponectin multimer distribution in patients with familial combined hyperlipidemia. Biochem Biophys Res Commun. 2008 Nov 7;376(1):164-8. doi: 10.1016/j.bbrc.2008.08.111. Epub 2008 Aug 30.

    PubMed 18762168
  • Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AF, de Graaf J. The metabolic syndrome and its traits as risk factors for subclinical atherosclerosis. J Clin Endocrinol Metab. 2009 Aug;94(8):2893-9. doi: 10.1210/jc.2009-0084. Epub 2009 May 5.

    PubMed 19417041
  • Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AF, de Graaf J. Brachial artery diameter is related to cardiovascular risk factors and intima-media thickness. Eur J Clin Invest. 2009 Jul;39(7):554-60. doi: 10.1111/j.1365-2362.2009.02152.x. Epub 2009 May 8.

    PubMed 19453648
  • Holewijn S, den Heijer M, van Tits LJ, Swinkels DW, Stalenhoef AF, de Graaf J. Impact of waist circumference versus adiponectin level on subclinical atherosclerosis: a cross-sectional analysis in a sample from the general population. J Intern Med. 2010 Jun;267(6):588-98. doi: 10.1111/j.1365-2796.2009.02192.x. Epub 2009 Nov 4.

    PubMed 20210840
  • Holewijn S, den Heijer M, Swinkels DW, Stalenhoef AF, de Graaf J. Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk. J Intern Med. 2010 Dec;268(6):567-77. doi: 10.1111/j.1365-2796.2010.02277.x.

    PubMed 21091808
  • Holewijn S, Sniderman AD, den Heijer M, Swinkels DW, Stalenhoef AF, de Graaf J. Application and validation of a diagnostic algorithm for the atherogenic apoB dyslipoproteinemias: ApoB dyslipoproteinemias in a Dutch population-based study. Eur J Clin Invest. 2011 Apr;41(4):423-33. doi: 10.1111/j.1365-2362.2010.02426.x. Epub 2010 Dec 3.

    PubMed 21128932
  • Bus BA, Marijnissen RM, Holewijn S, Franke B, Purandare N, de Graaf J, den Heijer M, Buitelaar JK, Voshaar RC. Depressive symptom clusters are differentially associated with atherosclerotic disease. Psychol Med. 2011 Jul;41(7):1419-28. doi: 10.1017/S0033291710002151. Epub 2010 Dec 10.

    PubMed 21144110
  • Holewijn S, den Heijer M, Stalenhoef AF, de Graaf J. Non-invasive measurements of atherosclerosis (NIMA): current evidence and future perspectives. Neth J Med. 2010 Dec;68(12):388-99.

    PubMed 21209464
  • Marijnissen RM, Bus BA, Holewijn S, Franke B, Purandare N, de Graaf J, den Heijer M, Buitelaar JK, Oude Voshaar RC. Depressive symptom clusters are differentially associated with general and visceral obesity. J Am Geriatr Soc. 2011 Jan;59(1):67-72. doi: 10.1111/j.1532-5415.2010.03228.x.

    PubMed 21226677

Questions about this trial

What is this clinical trial studying?

An observational study of Cardiovascular Disease, run by Radboud University Medical Center at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cardiovascular events (time frame: 3-7 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01555294, which also lists 22 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2012.

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