LDL-Cholesterin: Von der Hypothese zur Kausalität

Zusammenfassung

Der Begriff der „LDL-Hypothese“ wird häufig verwendet um den Zusammenhang von LDL Cholesterin (LDL-C) und kardiovaskulären Ereignissen zu beschreiben. Im Hinblick auf aktuelle Studienergebnisse stellt sich die Frage, inwieweit dieser Terminus noch adäquat ist. Vor dem Hintergrund der Daten zur kausalen Bedeutung des LDL für die molekulare und zelluläre Pathogenese der Atherosklerose, der Epidemiologie und der klaren genetischen Assoziation von LDL-C und Herzinfarktrisiko sowie der großen Statin-Studien sowie dem Beleg einer Ereignis-Reduktion durch eine nicht Statin-vermittelte LDL Senkung in der IMPROVE-IT Studie erscheint der Terminus „Hypothese“ überholt und der Begriff „LDL-Kausalität“ adäquat.

Abstract

The term „LDL-Hypothesis“ is frequently used to describe the association between LDL cholesterol (LDL-C) and cardiovascular outcomes. In the light of recent results of randomized trials the question arises whether the term hypothesis is still adequate. Considering the causal importance of LDL for the pathogenesis of atherosclerosis, epidemiological evidence and the clear genetic association of LDL-C with cardiovascular risk as well as the large statin trials and the reduction of events by a non-statin intervention in the IMPROVE-IT study, the term “hypothesis” appears to be outdated and should be replaced by “LDL-causality”.

Schlüsselwörter

LDL - Cholesterin - LDL-Hypothese - IMPROVE-IT

Keywords

LDL - Cholesterol - LDL-Hypothesis - IMPROVE-IT

• Literatur

• 1 Baigent C, Keech A, Kearney PM et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005; 366: 1267-1278
• 2 Blazing MA, Giugliano RP, Cannon CP et al. Evaluating cardiovascular event reduction with ezetimibe as an adjunct to simvastatin in 18,144 patients after acute coronary syndromes: final baseline characteristics of the IMPROVE-IT study population. Amer Heart J 2014; 168: 205-212 e201
• 3 Boekholdt SM, Hovingh GK, Mora S et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. JACC 2014; 64: 485-494
• 4 Califf RM, Harrington RA, Blazing MA. Premature release of data from clinical trials of ezetimibe. New Engl J Med 2009; 361: 712-717
• 5 Cannon CP. IMPROVE-IT Trial: A Comparison of Ezetimibe / Simvastatin vs Simvastatin Monotherapy on Cardiovascular Outcomes After Acute Coronary Syndromes. AHA Scientific Session, Chicago: 17.11.2014
• 6 Cannon CP, Giugliano RP, Blazing MA et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial). Amer Heart J 2008; 156: 826-832
• 7 Ference BA, Majeed F, Penumetcha R et al. Effect of Naturally Random Allocation to Lower Low-Density Lipoprotein Cholesterol on the Risk of Coronary Heart Disease Mediated by Polymorphisms in NPC1L1, HMGCR, or Both: A 2 × 2 Factorial Mendelian Randomization Study. J Am Coll Cardiol 2015; Mar 6. pii
• 8 Ference BA, Yoo W, Alesh I et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. JACC  2012; 60: 2631-2639
• 9 Kannel WB, Castelli WP, Gordon T et al. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med 1971; 74: 1-12
• 10 Klose G, Laufs U, Marz W et al. Familial hypercholesterolemia: developments in diagnosis and treatment. Dtsch Arztebl Int 2014; 111: 523-529
• 11 Laufs U, Descamps OS, Catapano AL et al. Understanding IMPROVE-IT and the cardinal role of LDL-C lowering in CVD prevention. Europ Heart J 2014; 35: 1996-2000
• 12 Myocardial Infarction Genetics Consortium. Stitziel NO, Won HH, Morrison AC et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. New Engl J Med 2014; 371: 2072-2082
• 13 Nicholls SJ, Tuzcu EM, Sipahi I et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA 2007; 297: 499-508
• 14 Schulz R, Schluter KD, Laufs U. Molecular and cellular function of the proprotein convertase subtilisin / kexin type 9 (PCSK9). Basic Res Cardiol 2015; 110: 463
• 15 Shepherd J, Cobbe SM, Ford I et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. New Engl J Med 1995; 333: 1301-1307
• 16 Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC / AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology / American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129: S1-45
• 17 Voight BF, Peloso GM, Orho-Melander M et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012; 380: 572-580