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LDL-C plays an essential role in the development of ASCVD

The process of atherosclerosis development

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Interactive Artery

Check out this interactive artery showing vulnerable plaque.

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Atherosclerosis develops in a multistep process:1-5 

  1. Lipids, including LDL-C, accumulate and are retained in the walls of arteries
  2. Oxidation of accumulated LDLs trigger a chronic maladaptive inflammatory response
  3. Inflammatory response (activated endothelial cells, smooth muscle cells, and infiltrating macrophages) leads to the formation of atherosclerotic plaque
  1. Atherosclerotic plaques can become vulnerable to rupture and acute thrombosis
  2. Arterial thrombosis may lead to an acute coronary syndrome

The link between elevated LDL-C, atherosclerosis, and CVD has been firmly established6,7

At lower concentrations of LDL-C within the arterial intima, there is a lower chance of accumulation and retention in the walls of arteries. As the concentration of LDL-C rises, the probability of retention and risk of atherosclerosis development increases in a log-linear relationship. Epidemiological studies have shown that prolonged hyperlipidemia increases the risk for CV events.

The effect of cumulative exposure to LDL on plaque burden and risk of myocardial infarction8

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Lowering LDL-C in patients who’ve had a prior CV event is critical9

A large registrational study further substantiated the benefit of lowering LDL-C in patients who had a prior myocardial infarction. Patients who achieved a ≥ 50% reduction in LDL-C demonstrated the lowest rates of additional cardiovascular events.

Event rates per LDL-C reduction group9

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The SWEDEHEART registry study included approximately 40,000 Swedish patients admitted for first or recurrent myocardial infarction between January 2006 and December 2016 with a median follow-up of 3.8 years, looking for changes in LDL-C levels and incidence of CV events. LDL-C reduction after the index myocardial infarction event was associated with a reduced incidence of major adverse CV events (defined as the composite of CV mortality, Ml, and IS) and major vascular events (defined as the composite of CV mortality, Ml, IS and coronary revascularization).

ACS = acute coronary syndrome; IS = ischemic stroke; MI = myocardial infarction.

  • References

    1. Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: a multifactorial process. Exp Clin Cardiol. 2002;7:40-53.
    2. Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formulation and rupture. Circ Res. 2014;114:1852-1866.
    3. Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 2007;116:1832-1844.
    4. Maiolino G, Rossitto G, Caielli P, Bisogni V, Rossi GP, Calò LA. The role of oxidized low-density lipoproteins in atherosclerosis: the myths and the facts. Mediators Inflamm. 2013;2013:1-13.
    5. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685-1695.
    6. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38:2459-2472.
    7. Navar-Boggan AM, Peterson ED, D’Agostino RB, et al. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation. 2015;131:451-458.
    8. Ference B, Graham I, Tokgozoglu L, Catapano A. Impact of lipids on cardiovascular health: JACC health promotion series. J Am Coll Cardiol. 2018;72:1141-1156.
    9. Schubert J, Lindhal B, Melhus H, et al. Low-density lipoprotein cholesterol reduction and statin intensity in myocardial infarction patients and major adverse outcomes: a Swedish nationwide cohort study. Eur Heart J. 2021;42:243-252.