Learn more about vulnerable plaque

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Science of Atherosclerosis and ASCVD

Lipid Regulation and Atherosclerosis

The lifetime accumulation of cholesterol delivered by LDL within the arterial wall causes atherosclerosis and is a key modifiable factor for the development of ASCVD.1-6

In this section, you will learn more about cholesterol synthesis, regulation via the LDL receptor, and how the accumulation of cholesterol delivered by LDL causes atherosclerosis.

Atherosclerotic Plaque Vulnerability

Atherosclerotic plaques are the hallmark lesion of atherosclerosis.While some plaques remain asymptomatic, some become obstructive causing stable angina, and others elicit acute thrombosis which may lead to an acute coronary syndrome.7,8

This section provides more information about the pathological features of vulnerable plaques and the effect of LDL-C lowering on features of plaque stability.

CV Event Risk and LDL-C

The risk for CV events is related to cumulative exposure and magnitude of LDL-C levels.9-11

Evidence from randomized clinical trials and genetic studies demonstrate that reduction in CV risk is proportional to the absolute reduction in LDL-C levels.1,12-14

Cholesterol Synthesis and Regulation

Learn more about the regulation of circulating cholesterol levels and the role of PCSK9 by watching the video in this section.

Interactive Artery

Check out this interactive artery showing the progression of atherosclerosis and vulnerable plaque.

Clinical Management of Very High-Risk ASCVD

LDL-C Levels in the Real World

Real-world studies consistently demonstrate that the majority of patients with ASCVD at high risk for further CV events do not achieve the recommended LDL-C levels set by current guidelines.1, 9,10

Continue reading to learn more about LDL-C level attainment in the real world.

Risk of Recurrent CV Events

In the USA, CVD is a leading cause of morbidity, with heart disease, stroke, and hypertension ranking among the top causes of morbidity. In addition, 1 in 3 patients with established ASCVD (either MI or stroke) remain at risk for subsequent events.15,16

Learn more about the risk of recurrent events in patients with ASCVD.

Optimizing Lipid Management

Current guidelines recognize that lower is better for patients with ASCVD when it comes to LDL-C reduction, as achieving lower LDL-C levels over time results in further reduction in CV risk.17-19

This section provides an overview of LDL-C thresholds and the current guideline recommendations, as well as additional information on treatment targets, in very high-risk patients.

Read the latest 2022 Expert Consensus Decision Pathway on the role of non-statin therapies for LDL-C lowering in the management of ASCVD risk.

Cholesterol Heat Map

See the proportion of patients in your area with major ASCVD events who have LDL-C levels ≥ 70 mg/dL.

Optimizing LDL-C in Very High-Risk Patients

Click through to hear experts discuss LDL-C goals in patients with recent myocardial infarction.

  1. 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(32):2459-2472. doi:10.1093/eurheartj/ehx144.
  2. Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364(9438):937-952. doi:10.1016/S0140-6736(04)17018-9.
  3. Singh RB, Mengi SA, Xu YJ, Arneja AS, Dhalla NS. Pathogenesis of atherosclerosis: a multifactorial process. Exp Clin Cardiol. 2002;7(1):40-53.
  4. 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. doi:10.1161/CIRCULATIONAHA.106.676890.
  5. Hong YM. Atherosclerotic cardiovascular disease beginning in childhood. Korean Circ J. 2010;40(1):1-9. doi:10.4070/kcj.2010.40.1.1.
  6. Stary HC, Chandler AB, Glagov S, et al. A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1994;89(5):2462-2478. doi: 10.1161/01.cir.89.5.2462.
  7. Stefanadis C, Antoniou C-K, Tsiachris D, Pietri P. Coronary atherosclerotic vulnerable plaque: current perspectives. J Am Heart Assoc. 2017;6(3):e005543. doi:10.1161/JAHA.117.005543.
  8. Grundy SM, Arai H, Barter P, et al. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia – full report. J Clin Lipidol. 2014;8(1):29-60. doi:10.1016/j.jacl.2013.12.005.
  9. Navar-Boggan AM, Peterson ED, D’Agostino RB, Neely B, Sniderman AD, Pencina MJ. Hyperlipidemia in early adulthood increases long-term risk of coronary heart disease. Circulation. 2015;131(5):451-458. doi:10.1161/CIRCULATIONAHA.114.012477.
  10. 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. doi:10.1016/j.jacc.2012.09.017.
  11. Rocha VZ, and Santos RD. Cholesterol inflammation: the lesser the better in atherothrombosis. Eur J Prev Cardiol. 2018;25(9):944-947. doi:10.1177/2047487318772936.
  12. Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670-1681. doi:10.1016/S0140-6736(10)61350-5.
  13. Soran H, Dent R, Durrington P. Evidence-based goals in LDL-C reduction. Clin Res Cardiol. 2017;106(4):237-248. doi:10.1007/s00392-016-1069-7.
  14. 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(9493):1267-1278. doi:10.1016/S0140-6736(05)67394-1.
  15. Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics – 2017 update: a report from the American Heart Association. Circulation. 2017;135(10):e146-e603. doi:10.1161/CIR.0000000000000485.
  16. Bhatt DL, Eagle KA, Ohman EM, et al. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304(12):1350-1357. doi:10.1001/jama.2010.1322.
  17. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2019;139(25):e1046-e1081. doi:10.1161/CIR.0000000000000624.
  18. Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455.
  19. Masana L, Girona J, Ibarretxe D, et al. Clinical and pathophysiological evidence supporting the safety of extremely low LDL levels – the zero-LDL hypothesis. J Clin Lipidol. 2018;12(2):292-299.e3. doi:10.1016/j.jacl.2017.12.018.