Endocrinology / General Internal Medicine 1

Pathogenesis, clinical presentation and therapy of arterial and venous vascular disorders

Principal Investigators

Dr M.V. Huisman, Dr J.T. Tamsma, Prof.Dr L.M. Havekes

Aim and focus

Venous and arterial thrombo-embolic disorders:
Diagnosis and treatment of venous and arterial thromboembolic disorders are the focus of research. In venous thromboembolic disease, the value of new diagnostic approaches has been tested in large cohorts of patients, and is ongoing in several studies. Evaluation of innovative treatment strategies has been implemented. In arterial thrombosis evaluation of antithrombotic treatment is being investigated.

Metabolic determinants of atherosclerosis:
The pathophysiology and treatment of metabolic determinants of atherosclerosis are the focus of research. Mechanistic studies regarding obesity, diabetes and hyperlipidemia have been conducted using clinical and preclinical models. Thus, unravelling metabolic pathophysiology in precisely targeted human studies at the clinical research facility on the one hand, joined by series of experiments using unique transgenic mouse models with targeted disruptions of metabolic pathways of lipid metabolism. In the forthcoming period a challenge will be to focus knowledge regarding these metabolic derangements more directly to the pathophysiology, detection, and prevention of early phases of atherosclerosis as will be discussed below.

Position in international context

The research is performed within the context of a network that has been built between the LUMC Departments of General Internal Medicine/Endocrinology, Nephrology, Haematology, Pulmonary Medicine, Cardiology, Vascular Surgery, Neurology and Radiology as well as international institutes with expertise in research on both subthemes. This consortium is optimally equipped to determine the focus of both subthemes.

Content / highlights / achievements

• The optimal diagnostic strategy for pulmonary embolism was studied in a 12 center national study.
• The natural course of catheter related thrombosis was studied and the contribution of genetic abnormalities of coagulation was unravelled.
• The efficacy and safety of a novel antithrombotic agent in patients with proximal vein thrombosis was evaluated in a multicenter study.
• The influence of statin drugs on intima media thickness and vessel wall function in patients with diabetes mellitus was studied.
• Novel aspects of the role of apolipoproteins in plasma and adipose tissue triglyceride metabolism were elucidated

Future themes

• Natural history of deep-vein thrombosis and pulmonary embolism and – early- development and prevention of pulmonary thromboembolic hypertension.
• Optimal diagnosis of recurrent deep-vein thrombosis and pulmonary embolism with MRI direct thrombus imaging.
• Natural history and interventional studies of atherosclerosis as measured and monitored by non-invasive methods (IMT, pulse wave analysis) and using recently developed 3T-MRI technology in large cohorts of patients at high risk for developing atherosclerotic disease.
• The regulation of molecular determinants of dyslipidemia, especially of triglyceride metabolism  in relation to CETP, will be studied in transgenic mouse models with targeted gene alterations.  In addition, translational atherosclerosis research will be implemented in humans in vivo focussing on similar mechanisms like those studied in the mouse models.

Cohesion within the LUMC

This research is conducted with the Departments of Pulmonology, Hematology, Radiology, Nephrology, and Vascular Surgery. Experimental research has now been allocated at the Laboratory of the Department of Internal Medicine and Endocrinology and is performed in collaboration with the TNO-Gaubius institute.

Key publications

Klok FA, Mos IC, Broek L, Tamsma JT, Rosendaal FR, de Roos A, Huisman MV. Risk of arterial cardiovascular events in patients after pulmonary embolism. Blood. 2009 Jun 23. [Epub ahead of print]
IF 10.9

van der Ham RL, Alizadeh Dehnavi R, Berbée JF, Putter H, de Roos A, Romijn JA, Rensen PC, Tamsma JT. Plasma apolipoprotein CI and CIII levels are associated with increased plasma triglyceride levels and decreased fat mass in men with the metabolic syndrome. Diabetes Care. 2009 Jan;32(1):184-6.
IF 7.9

Klok FA, Mos IC, Nijkeuter M, Righini M, Perrier A, Le Gal G, Huisman MV. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Arch Intern Med. 2008 Oct 27;168(19):2131-6
IF 8.4

Eriksson BI, Borris LC, Friedman RJ, Haas S, Huisman MV, Kakkar AK, Bandel TJ, Beckmann H, Muehlhofer E, Misselwitz F, Geerts W; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008 Jun 26;358(26):2765-75.
IF 52.6

Snoep JD, Hovens MM, Eikenboom JC, van der Bom JG, Huisman MV. Association of laboratory-defined aspirin resistance with a higher risk of recurrent cardiovascular events: a systematic review and meta-analysis. Arch Intern Med. 2007 Aug 13-27;167(15):1593-9.
IF 8.4

Agnelli G, Gallus A, Goldhaber SZ, Haas S, Huisman MV, Hull RD, Kakkar AK, Misselwitz F, Schellong S; ODIXa-DVT Study Investigators. Treatment of proximal deep-vein thrombosis with the oral direct factor Xa inhibitor rivaroxaban (BAY 59-7939): the ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients With Acute Symptomatic Deep-Vein Thrombosis) study. Circulation. 2007 Jul 10;116(2):180-7
IF 12.8

Eriksson BI, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Muehlhofer E, Dierig C, Misselwitz F, Kälebo P; ODIXa-HIP Study Investigators. A once-daily, oral, direct Factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement. Circulation. 2006 Nov 28;114(22):2374-81.
IF 12.8

van Belle A, Buller HR, Huisman MV et al.  Clinical Validity of Ruling out Pulmonary Embolism by a Diagnostic Algorithm, Combining Clinical Probability, D-dimer Testing and, Computed Tomography in Patients with Clinically Suspected Pulmonary Embolism. The Christopher Study. JAMA. 2006 Jan 11;295(2):172-9
IF 24.8

Fiessinger JN, Huisman MV, Davidson BL, Bounameaux H, Francis CW, Eriksson H et al. Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial. JAMA 2005; 293:681-689.
IF 24.8