Short summary

Arteriosclerosis is a slowly progressing illness process, which happens over many years. The precise mechanism for the formation of arteriosclerosis is not known but a number of risk factors are unambiguously identified. This project will be:

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1.    A screening study of risk factors for developing a cardiovascular disease with asymptomatic 50-60 year old men and women

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2.    A randomized study with treatment of magnyl and statin versus placebo for asymptomatic 50-60 year old men and women with coronary calcium

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Rationale

The study consists of three sub projects, which all aim to prevent cardiovascular events as well as to optimize effect, security and cost-effectiveness of treatment. In a cohort of randomly selected asymptomatic 50- to 60-year old men and women, it is planned:

Subproject 1: \n

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• for subsequent impact calculation for subproject 2
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• to identify unknown hypertension, diabetes mellitus or hypercholesterolemia which requires treatment, this is done partly to reveal the extend of the problem and partly to initiate treatment.
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• to clarify the variation in coronary calcium linked to the above mentioned risk factores.
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Subproject 2: \n

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• to survey if treatment with Magnyl and Statin-inhibitor is a risk factor for patients with coronary calcium.
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Subproject 3: \n

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• to establish a biobank with biological material for later analyzation in order to find genetic markers for both known risk factors and for the formation of coronary calcium.
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Description of the cohort

2000 randomly selected men and women, 50-60 years of age, all from the Region of Southern Denmark are invited to be screened. 50 % of these are expected to accept the offer. The patients will be screened within 2009 and there will be collected one blood sample from each person.

Data and biological material

At the screening session there will be tested for: Calcium score (heart CT), blood pressure, ankle-arm index, height, weight, waist size and lung function test (patients who smoke). Furthermore, blood samples will be collected in order to analyze for: Blood glucose, HgbA1C, cholesterol, lipid profile and CRP.

Collaborating researchers and departments

Department of Cardiology and Cardiovascular, Odense University Hospital

• Acting Senior Hospital Physician Axel Diederichsen, PhD 
• 1. registrar Niels C. F. Sandgaard, PhD 
• Senior Hospital Physician Hans Mickley, DMSc 
• Medical Director Mogens Lytken Larsen, DMSc 

Department of Clinical Physiology and Nuclearmedicin, Odense University Hospital

• Senior Hospital Physician Henrik Petersen
• Acting Medical Director and Clinical Associated Professor Allan Johansen
• Senior Hospital Physician and Professor Poul F. Højlund-Carlsen, DMSc 

Department of Biostatistics, Institute of Public Health, University of Southern Denmark

• Professor Werne Vach

Department for Research and MTV, Odense University Hospital

• Head of Department and Professor Mickael Bech, PhD, MSc

Clinic of Cardiology and Radiology, Hospital of South Vest Jutland, Esbjerg

• Senior Hospital Physician Majed Husain, MSc 
• Senior Hospital Physician Niels Peter Rønnow Sand, PhD
• Senior Hospital Physician Karen Fyhring

Medical Department, The Cardiology Section, Hospital Lillebaelt, Vejle

• Senior Hospital Physician Jesper Møller Jensen, PhD
• Senior Hospital Physician Bjarne Linde Nørgaard, PhD

Medical Department, Odense University Hospital, Svendborg

• Senior Hospital Physician Jess Lambrechtsen, PhD
• Senior Hospital Physician and Professor Kenneth Egstrup, DMSc 

Publications associated with the project

Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular-specific serological biomarker. / Vassiliadis E, Melholt Rasmussen L, Byrjalsen I, Larsen DV, Chaturvedi R, Hosbond S, Saabye L, Diederichsen AC, Genovese F, Duffin KL, Zheng Q, Chen X, Leeming DJ, Christiansen C, Karsdal MA. Journal of Translational Medicine 2012 Jul 6;10(1):140

Acute Myocardial Infarction and Pulmonary Diseases Result in Two Different Degradation Profiles of Elastin as Quantified by Two Novel ELISAs. / Skjøt-Arkil, Helene; Clausen, Rikke E; Rasmussen, Lars M; Wang, Wanchun; Wang, Yaguo; Zheng, Qinlong; Mickley, Hans; Saaby, Lotte; Diederichsen, Axel C P; Lambrechtsen, Jess; Martinez, Fernando J; Hogaboam, Cory M; Han, Meilan; Larsen, Martin R; Nawrocki, Arkadiusz; Vainer, Ben; Krustrup, Dorrit Hellebek; Bjørling-Poulsen, Marina; Karsdal, Morten A; Leeming, Diana Julie. I: PloS one, Vol. 8, Nr. 6, e60936, 2013.

Plasma concentrations of extracellular matrix protein fibulin-1 are related to cardiovascular risk markers in chronic kidney disease and diabetes. / Scholze, Alexandra; Bladbjerg, Else-Marie; Sidelmann, Johannes J; Diederichsen, Axel Cp; Mickley, Hans; Nybo, Mads; Argraves, W Scott; Marckmann, Peter; Rasmussen, Lars M. I: Cardiovascular Diabetology, Vol. 12, Nr. 1, 07.01.2013, s. 6.

Localization of Microfibrillar-Associated Protein 4 (MFAP4) in Human Tissues : Clinical Evaluation of Serum MFAP4 and Its Association with Various Cardiovascular Conditions. / Wulf-Johansson, Helle; Lock Johansson, Sofie; Schlosser, Anders; Trommelholt Holm, Anne; Melholt Rasmussen, Lars; Mickley, Hans; Diederichsen, Axel Cosmus Pyndt; Munkholm, Henrik; Poulsen, Tina Svenstrup; Tornøe, Ida; Nielsen, Vicki; Marcussen, Niels; Vestbo, Jørgen; Sækmose, Susanne Gjørup; Holmskov, Uffe; Sorensen, Grith Lykke.  I: PloS one, Vol. 8, Nr. 12, 2013, s. e82243.

Plasma proteome profiling of atherosclerotic disease manifestations reveals elevated levels of the cytoskeletal protein vinculin. / Kristensen, Lars P; Larsen, Martin R; Mickley, Hans; Saaby, Lotte; Diederichsen, Axel Cosmus Pyndt; Lambrechtsen, Jess; Rasmussen, Lars M; Overgaard, Martin. I: Journal of Proteomics, 22.12.2013

Plasma copeptin as marker of cardiovascular disease in asymptomatic type 2 diabetes patients. / Bar-Shalom D, Poulsen MK, Rasmussen LM, Diederichsen AC, Sand NP, Henriksen JE et al. Diabetes and Vascular Disease Research. 2014;11(6):448-50.

Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic manifestations. / Hosbond SE, Diederichsen ACP, Pedersen L, Rasmussen LM, Munkholm H, Gerke O et al. Scandinavian Journal of Clinical & Laboratory Investigation. 2014;74(3):219-227.

Can osteoprotegerin be used to identify the presence and severity of coronary artery disease in different clinical settings? / Hosbond SE, Diederichsen ACP, Saaby L, Rasmussen LM, Lambrechtsen J, Munkholm H, Sand NPR, Gerke O, Poulsen TS, Mickley H.  Atherosclerosis 2014 Jul 21;236(2):230?236.

Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects. / Sørensen MH, Gerke O, Eugen-Olsen J, Munkholm H, Lambrechtsen J, Sand NP, Mickley H, Rasmussen LM, Olsen MH, Diederichsen A. Atherosclerosis. 2014 Sep 2;237(1):60-66

Coronary calcification among 3477 asymptomatic and symptomatic individuals. Øvrehus KA, Jasinskiene J, Sand NP, Jensen JM, Munkholm H, Egstrup K, Lambrecthsen J, Mickley H, Diederichsen AC. Eur J Prev Cardiol. 2016 Jan;23(2):154-9.

Association between high-sensitive troponin I and coronary artery calcification in a Danish general population. / Olson F, Engborg J, Grønhøj MH, Sand NP, Lambrechtsen J, Steffensen FH, Nybo M, Gerke O, Mickley H,, Diederichsen AC. Atherosclerosis. 2016; 245:88-93.

The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study. Nicoll R, Wiklund U, Zhao Y, Diederichsen A, Mickley H, Ovrehus K, Zamorano P, Gueret P, Schmermund A, Maffei E, Cademartiri F, Budoff M, Henein M. . Int J Cardiol. 2016 Mar 15;207:13-9.

Associations between calcium-phosphate metabolism and coronary artery calcification; a cross sectional study of a middle-aged general population. Grønhøj MH, Gerke O, Mickley H, Hald F, Lambrechtsen J, Sand NP, Rasmussen LM, Olsen MH, Diederichsen A. Atherosclerosis. 2016 Jun 2;251:101-108

Gender and age effects on risk factor-based prediction of coronary artery calcium in symptomatic patients: A Euro-CCAD study; Nicoll R, Wiklund U, Zhao Y, Diederichsen A, Mickley H, Ovrehus K, Zamorano J, Gueret P, Schmermund A, Maffei E, Cademartiri F, Budoff M, Henein M. Atherosclerosis. 2016 Sep 17;252:32-39.