LDL-cholesterol – the main risk factor for atherosclerosis

Authors: Branislav Vohnout 1;  Andrea Havranová 2
Authors‘ workplace: Ústav výživy, FO a ZOŠ a Koordinačné centrum pre familiárne hyperlipoproteinémie, Slovenská zdravotnícka univerzita v Bratislave 1;  Ústav experimentálnej endokrinológie – Biomedicínske centrum SAV, Bratislava 2
Published in: AtheroRev 2016; 1(2): 88-92
Category: Reviews


LDL-cholesterol is one of the main risk factors for atherosclerosis. A large number of studies at the bunk and molecular level have described mechanisms whereby it participates in the initiation and development of atherosclerotic lesions. Epidemiological studies have proven the relationship between LDL-C and the risk of cardiovascular diseases. Genetic studies have shown that congenital increased LDL-C levels lead to an increased cardiovascular risk, while genetically determined lowered LDL-C levels reduce the risk. The causal role of LDL-C has been finally confirmed by the results of many clinical trials that have demonstrated the effect of LDL-C reduction on the cardiovascular risk in patients in primary as well as secondary prevention, and the effect was attained through various mechanisms of LDL-C reduction.

Key words:
LDL-cholesterol – atherosclerosis – cardiovascular diseases


1. O’Keefe JH, Cordain L. Cardiovascular disease resulting from a diet and lifestyle at odds with our Paleolithic genome: how to become a 21st-century hunter-gatherer. Mayo Clin Proc 2004; 79(1): 101–108.

2. Allam AH, Thompson RC, Wann LS et al. Atherosclerosis in ancient Egyptian mummies: the Horus study. JACC Cardiovasc Imaging 2011; 4(4): 315–327.

3. Allam AH, Thompson RC, Wann LS et al. Computed tomographic assessment of atherosclerosis in ancient Egyptian mummies. JAMA 2009; 302(19): 2091–2103.

4. Thompson RC, Allam AH, Lombardi GP et al. Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations. Lancet 2013; 381(9873): 1211–1222.

5. Murphy WA Jr, Nedden Dz Dz, Gostner P et al. The iceman: discovery and imaging. Radiology 2003; 226(3): 614–629.

6. Mayerl C, Lukasser M, Sedivy R et al. Atherosclerosis research from past to present – on the track of two pathologists with opposing views, Carl von Rokitansky and Rudolf Virchow. Virchows Arch 2006; 449(1): 96–103.

7. Virchow R. Phlogose und Thrombose im Gefassystem. In: Gesammelte Abhandlungen zur Wissenschaftlichen Medizin. Meidinger Sohn: Frankfurt 1856.

8. von Rokitansky C. Über einiger der wichtigsten Krankheiten der Arterien. Denkshriften der K. Akademie der Wissenschaften (Wien) 1852; 4: 1–72.

9. Ignatowski A. Isvestiya Imperatorshoi Vorenno Medinsinskoy Akademii. St. Petersburg 1908; 16: 154–176.

10. Bacmeister und Henes. Untersuchungen über den Cholesteringehalt des menschlichen Blutes bei verschiedenen inneren Erkrankungen. Deutsche Dtsch Med Wochenschr 1913; 39: 544–546.

11. Anitschkow N. Über die Veranderungen der Kaninchenaorta bei experimenteller Cholesterinsteatose. Beitrage zur pathologishen Anatomie und zur allgemeinen Pathologie 1913; 56: 379–404.

12. Ross R, Glomset JA. Atherosclerosis and the arterial smooth muscle cell: proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science 1973; 180(4093): 1332–1339.

13. Ross R. The pathogenesis of atherosclerosis – update. N Engl J Med 1986; 314(8): 488–500.

14. Ross R. Atherosclerosis – An inflammatory disease. N Engl J Med 1999; 340(2): 115–126.

15. Glass CK, Witztum JL. Atherosclerosis, the road ahead. Cell 2001; 104(4): 503–516.

16. Steinberg D. Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime. Nat Med 2002; 8(11): 1211–1217.

17. Hegele RA, Gidding SS, Ginsberg HN et al. Nonstatin Low-Density Lipoprotein-Lowering Therapy and Cardiovascular Risk Reduction-Statement from ATVB Council. Arterioscler Thromb Vasc Biol 2015; 35(11): 2269–2280.

18. Vohnout B, de Gaetano G, Donati MB et al. The Relationship between Dyslipidemia and Inflammation. In: M. Mancini, J. Ordovas, G. Riccardi et al (eds). Nutritional and Metabolic Bases of Cardiovascular Disease. Blackwell Publishing 2011: 202–210. ASIN: B005D7EPG0

19. Napoli C, D'Armiento FP, Mancini FP et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions. J Clin Invest 1997; 100(11): 2680–2690.

20. Nakashima Y, Fujii H, Sumiyoshi S et al. Early human atherosclerosis: accumulation of lipid and proteoglycans in intimal thickenings followed by macrophage infiltration. Arterioscler Thromb Vasc Biol 2007; 27(5): 1159–1165.

21. Palinski W, Yamashita T, Freigang S et al. Developmental programming: maternal hypercholesterolemia and immunity influence susceptibility to atherosclerosis. Nutr Rev 2007; 65(12 Pt 2): S182-S187.

22. Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007; 116(16): 1832–1844.

23. Gleissner CA, Leitinger N, Ley K. Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis. Hypertension 2007; 50(2): 276–283.

24. Libby P. Collagenases and cracks in the plaque. J Clin Invest 2013; 123(8): 3201–3203.

25. Steinberg D. Thematic review series: the pathogenesis of atherosclerosis. An interpretive history of the cholesterol controversy: Part I. J Lipid Res 2004; 45(9): 1583–1593 .

26. Keys A, Menotti A, Karvonen MJ et al. The diet and 15 year mortality in the seven contries study. Am J Epidemiol 1986; 124(6): 903–915.

27. Kannel WB, Castelli WP, Gordon T et al. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. Ann Intern Med 1971; 74(1): 1–12.

28. Stamler J, Wentworth D, Neaton JD. Research group MRFIT. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986; 256(20): 2823–2828.

29. Di Angelantonio E, Sarwar N, Perry P et al. Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009; 302(18): 1993–2000.

30. Hovingh GK, Davidson MD, Kastelein JJ et al. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J 2013; 34(13): 962–971.

31. Nordestgaard BG, Chapman MJ, Humphries SE et al. European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: Consensus Statement of the European Atherosclerosis Society. Eur Heart J 2013; 34(45): 3478–3490a.

32. Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial Hypercholesterolemia in the Danish General Population: Prevalence, Coronary Artery Disease, and Cholesterol-Lowering Medication. J Clin Endocrinol Metab 2012; 97(11): 3956–3964. Erratum in J Clin Endocrinol Metab 2014; 99(12): 4758–4759.

33. Cuchel M, Bruckert E, Ginsberg HN et al. European Atherosclerosis Society Consensus Panel on Familial Hypercholesterolaemia. Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society. Eur Heart J 2014; 35(32): 2146–2157.

34. 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. J Am Coll Cardiol 2012; 60(25): 2631–2639.

35. Cohen JC, Boerwinkle E, Mosley TH Jr et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354(12): 1264–1272.

36. Kathiresan S. Myocardial Infarction Genetics Consortium. A PCSK9 missense variant associated with a reduced risk of early-onset myocardial infarction. N Engl J Med 2008; 358(21): 2299–2300.

37. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344(8934): 1383–1389.

38. Shepherd J, Cobbe SM, Ford I et al. for the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333(20): 1301–1307.

39. Cannon CP, Braunwald E, McCabe CH et al. [Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators]. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004; 350(15): 1495–1504. Erratum in N Engl J Med 2006; 354(7): 778.

40. Cannon CP, Blazing MA, Giugliano RP et al. IMPROVE-IT Investigators. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372(25): 2387–2397.

41. Fulcher J, O'Connell R, Voysey M et al. [Cholesterol Treatment Trialists' Collaboration]. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet 2015; 385(9976): 1397–1405.

42. Werner C, Laufs U. Moving beyond the "LDL hypothesis". Vasa 2015; 44(5): 333–340.

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