Leiden University Scholarly Publications

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Kühnast, S. (2015)

Innovative pharmaceutical interventions in experimental atherosclerosis : focusing on the contribution of non-HDL-C versus HDL-C

Doctoral Thesis
Cardiovascular disease (CVD) is the leading cause of death worldwide despite the successful development of several pharmaceutical interventions of which statin therapy is the dominating lipid-lowering treatment option. Atherosclerosis, a chronic inflammatory disease of multifactorial origin, is a dominant contributor to the development of CVD. The research described in this thesis provides evidence for anti-atherogenic effects of several innovative pharmaceutical interventions that are currently being investigated in clinical trials, targeting hypertension and hypercholesterolemia, more specifically high low-density lipoprotein-cholesterol (LDL-C) and low high-density lipoprotein-cholesterol (HDL-C), as risk factors for CVD. Our results further support additional benefit of these treatment strategies in combination with statin treatment which is currently the __gold standard__ therapy for the treatment of CVD. Most of these lipid-modifying treatment strategies affect both LDL-C and...Show moreCardiovascular disease (CVD) is the leading cause of death worldwide despite the successful development of several pharmaceutical interventions of which statin therapy is the dominating lipid-lowering treatment option. Atherosclerosis, a chronic inflammatory disease of multifactorial origin, is a dominant contributor to the development of CVD. The research described in this thesis provides evidence for anti-atherogenic effects of several innovative pharmaceutical interventions that are currently being investigated in clinical trials, targeting hypertension and hypercholesterolemia, more specifically high low-density lipoprotein-cholesterol (LDL-C) and low high-density lipoprotein-cholesterol (HDL-C), as risk factors for CVD. Our results further support additional benefit of these treatment strategies in combination with statin treatment which is currently the __gold standard__ therapy for the treatment of CVD. Most of these lipid-modifying treatment strategies affect both LDL-C and HDL-C and we demonstrate that the beneficial effects of these treatment strategies predominantly derive from their non-HDL-C/LDL-C-lowering abilities. Nonetheless, results from preclinical studies and clinical trials support the notion that treatment strategies aimed at improving HDL function and raising apolipoprotein A-I may also inhibit the development of atherosclerosis and reduce the prevalence of CVD.Show less
Statins
Alirocumab
Anacetrapib
Niacin
Aliskiren
HDL-cholesterol,
Non-HDL-cholesterol
Hypercholesterolemia
Hypertension
Atherosclerosis
All authors
Kühnast, S.
Supervisor
Jukema, J.W.
Co-supervisor
Princen, J.M.G.; Hoorn, J.W.A. van der
Qualification
Doctor (dr.)
Awarding Institution
Department of Cardiology, Leiden University Medical Center (LUMC), Leiden University
Date
2015-06-11
ISBN (print)
9789461089779

Funding

Sponsorship
The research was in part financially supported by Novartis, Sanofi-Aventis and Regeneron. The printing of this thesis was kindly supported by Daan Traas fonds and TNO, Metabolic Health Research.