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

NCT01555294 | Completed

• 1 other identifier: CMO 2003/174
• Study Type: observational
• Target: 1,960
• Locations: 1 country
• Sites: 1

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. 1.To evaluate whether non-invasive measurements of atherosclerosis are independent predictors of cardiovascular disease and
2. 2.to delineate new biochemical parameters and genetic variations, allowing earlier and more effective preventive therapy
3. 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.

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

Outcome Measures

Primary Outcomes (1)

• Cardiovascular events

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

  3-7 years

Study Arms (2)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may not qualify if:

• recent symptomatic CV disease (\<6 months)
• Familial Combined Hyperlipidemia:
• age \>18 years
• pregnancy

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

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

Nijmegen, Netherlands

Location

Related Publications (22)

• 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.

  PMID: 20622881 BACKGROUND

• 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.

  PMID: 15636580 RESULT

• 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.

  PMID: 16197666 RESULT

• 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.

  PMID: 16677651 RESULT

• 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.

  PMID: 17324737 RESULT

• 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.

  PMID: 17461984 RESULT

• 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.

  PMID: 18762168 RESULT

• 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.

  PMID: 19417041 RESULT

• 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.

  PMID: 19453648 RESULT

• 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.

  PMID: 20210840 RESULT

• 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.

  PMID: 21091808 RESULT

• 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.

  PMID: 21128932 RESULT

• 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.

  PMID: 21144110 RESULT

• 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.

  PMID: 21209464 RESULT

• 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.

  PMID: 21226677 RESULT

• Ter Avest E, Stalenhoef AF, de Graaf J. What is the role of non-invasive measurements of atherosclerosis in individual cardiovascular risk prediction? Clin Sci (Lond). 2007 May;112(10):507-16.

  PMID: 17419684 RESULT

• de Graaf J, van der Vleuten GM, ter Avest E, Dallinga-Thie GM, Stalenhoef AF. High plasma level of remnant-like particles cholesterol in familial combined hyperlipidemia. J Clin Endocrinol Metab. 2007 Apr;92(4):1269-75. doi: 10.1210/jc.2006-1973. Epub 2007 Jan 16.

  PMID: 17227806 RESULT

• van der Vleuten GM, Isaacs A, Zeng WW, ter Avest E, Talmud PJ, Dallinga-Thie GM, van Duijn CM, Stalenhoef AF, de Graaf J. Haplotype analyses of the APOA5 gene in patients with familial combined hyperlipidemia. Biochim Biophys Acta. 2007 Jan;1772(1):81-8. doi: 10.1016/j.bbadis.2006.10.012. Epub 2006 Oct 26.

  PMID: 17157483 RESULT

• ter Avest E, Abbink EJ, de Graaf J, Tack CJ, Stalenhoef AF. Effect of rosuvastatin on insulin sensitivity in patients with familial combined hyperlipidaemia. Eur J Clin Invest. 2005 Sep;35(9):558-64. doi: 10.1111/j.1365-2362.2005.01549.x.

  PMID: 16128862 RESULT

• Brouwers MC, de Graaf J, van Greevenbroek MM, Georgieva AM, van der Kallen CJ, Ter Avest E, Stehouwer CD, Stalenhoef AF, de Bruin TW. Parabolic relationship between plasma triacylglycerols and LDL-cholesterol in familial combined hyperlipidaemia: the multiple-type hyperlipidaemia explained? Clin Sci (Lond). 2008 Mar;114(5):393-401. doi: 10.1042/CS20070314.

  PMID: 17953518 RESULT

• van Himbergen TM, van Tits LJ, Ter Avest E, Roest M, Voorbij HA, de Graaf J, Stalenhoef AF. Paraoxonase (PON1) is associated with familial combined hyperlipidemia. Atherosclerosis. 2008 Jul;199(1):87-94. doi: 10.1016/j.atherosclerosis.2007.10.017. Epub 2007 Dec 21.

  PMID: 18096166 RESULT

• Murabito JM, White CC, Kavousi M, Sun YV, Feitosa MF, Nambi V, Lamina C, Schillert A, Coassin S, Bis JC, Broer L, Crawford DC, Franceschini N, Frikke-Schmidt R, Haun M, Holewijn S, Huffman JE, Hwang SJ, Kiechl S, Kollerits B, Montasser ME, Nolte IM, Rudock ME, Senft A, Teumer A, van der Harst P, Vitart V, Waite LL, Wood AR, Wassel CL, Absher DM, Allison MA, Amin N, Arnold A, Asselbergs FW, Aulchenko Y, Bandinelli S, Barbalic M, Boban M, Brown-Gentry K, Couper DJ, Criqui MH, Dehghan A, den Heijer M, Dieplinger B, Ding J, Dorr M, Espinola-Klein C, Felix SB, Ferrucci L, Folsom AR, Fraedrich G, Gibson Q, Goodloe R, Gunjaca G, Haltmayer M, Heiss G, Hofman A, Kieback A, Kiemeney LA, Kolcic I, Kullo IJ, Kritchevsky SB, Lackner KJ, Li X, Lieb W, Lohman K, Meisinger C, Melzer D, Mohler ER 3rd, Mudnic I, Mueller T, Navis G, Oberhollenzer F, Olin JW, O'Connell J, O'Donnell CJ, Palmas W, Penninx BW, Petersmann A, Polasek O, Psaty BM, Rantner B, Rice K, Rivadeneira F, Rotter JI, Seldenrijk A, Stadler M, Summerer M, Tanaka T, Tybjaerg-Hansen A, Uitterlinden AG, van Gilst WH, Vermeulen SH, Wild SH, Wild PS, Willeit J, Zeller T, Zemunik T, Zgaga L, Assimes TL, Blankenberg S, Boerwinkle E, Campbell H, Cooke JP, de Graaf J, Herrington D, Kardia SL, Mitchell BD, Murray A, Munzel T, Newman AB, Oostra BA, Rudan I, Shuldiner AR, Snieder H, van Duijn CM, Volker U, Wright AF, Wichmann HE, Wilson JF, Witteman JC, Liu Y, Hayward C, Borecki IB, Ziegler A, North KE, Cupples LA, Kronenberg F. Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies. Circ Cardiovasc Genet. 2012 Feb 1;5(1):100-12. doi: 10.1161/CIRCGENETICS.111.961292. Epub 2011 Dec 23.

  PMID: 22199011 RESULT

MeSH Terms

Conditions

Cardiovascular Diseases; Hyperlipidemia, Familial Combined

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Jacqueline de Graaf, MD, PhD

  Radboud University Nijmegen Medical Centre, Dept. of General Internal Medicine, Division of Vascular Medicine

  PRINCIPAL INVESTIGATOR

• 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 CHAIR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. J. de Graaf

Study Record Dates

• First Submitted: September 6, 2011
• First Posted: March 15, 2012
• Study Start: May 1, 2005
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: March 15, 2012

Record last verified: 2012-03

Locations

NL (1)