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Risk factors

What increases the risk of atherosclerosis?

Numerous factors are associated with an increased risk of atherothrombotic disease. Traditional risk factors include:1,2

  • Elevated cholesterol
  • Hypertension
  • Smoking
  • Diabetes
  • Male gender
  • Increasing age


More recently, several additional factors have been associated with an increased risk of cardiovascular (CV) disease. These include:3

  • A family history of early onset CV disease
  • Moderate or severe chronic kidney disease
  • Psychosocial risk factors (such as low socioeconomic status, depression and stress)
  • Inflammatory and autoimmune disease (such as rheumatoid arthritis)


Although atherosclerosis is a systemic disease with overlapping risk factors, the relative importance of different risk factors appears to be subtly different in patients with different manifestations of the disease.4,5 However, modifying these risk factors, both through lifestyle modifications and medication targeted at controlling cholesterol, blood pressure and diabetes, is a cornerstone of prevention in patients with atherosclerotic disease.3,6,7

Who is most at risk of cardiovascular (CV) events?

The risk of CV events is heavily dependent on the extent of atherosclerosis. In the REACH registry, the 1-year risk of CV death, stroke or myocardial infarction (MI) was 7.1% in patients with polyvascular disease (two or more of coronary artery disease, peripheral artery disease or cerebrovascular disease) and 4.1% in patients with atherosclerotic disease in a single bed; the highest risk (9.2%) was in patients with all three conditions.8

Multiple disease locations increase the 1-year risk of cardiovascular events

Multiple disease locations increase the 1-year risk of CV events.

1-year risk of CV death, stroke or MI dependent on the number of symptomatic disease locations

Another analysis of the REACH registry looked at specific risk factors for CV death, stroke or MI. As well as polyvascular disease, significant risk factors were heart failure, prior ischaemic events – with a greater risk for events within 1 year – and diabetes were the most important risk factors.9

Video title

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Peripherial Artery Disease: causes and consequences

Professor Gabriel Steg explains how patient characteristics affect the risk of CV events.
Risk of CV events in patient registries

Which patients can benefit most from vascular protection?

Although the majority of patients with stable atherosclerotic disease stand to benefit from vascular protection, patients with a high baseline risk of ischaemic events stand to benefit the most.10


In the COMPASS study, the high risk of cardiovascular (CV) death, stroke or myocardial infarction in patients with coronary artery disease (CAD) and diabetes, CAD and renal impairment (estimated glomerular filtration rate 15–60 ml/min), CAD and prior myocardial infarction and those with both CAD and peripheral artery disease meant that these patients experienced the highest absolute reductions in the risk of events.10 


Furthermore, because the absolute increase in the risk of bleeding associated with the COMPASS regimen versus an antiplatelet alone was consistent in patients with and without these risk factors, the overall benefit–risk ratio was high.10 

  • Mozaffarian D, Wilson PW, Kannel WB. Beyond established and novel risk factors: lifestyle risk factors for cardiovascular disease. Circulation 2008;117:3031–3038. Return to content
  • Bentzon JF, Otsuka F, Virmani R, Falk E. Mechanisms of plaque formation and rupture. Circ Res 2014;114:1852–1866. Return to content
  • Piepoli MF, Hoes AW, Agewall S et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016;37:2315–2381. Return to content
  • 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;364:937–952. Return to content
  • Fowkes FG, Rudan D, Rudan I et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis. Lancet 2013;382:1329–1340. Return to content
  • Knuuti J, Wijns W, Saraste A et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020;41:407–477. Return to content
  • Aboyans V, Ricco JB, Bartelink MEL et al. 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries. Eur Heart J 2018;39:763–816. Return to content
  • Steg PG, Bhatt DL, Wilson PW et al. One-year cardiovascular event rates in outpatients with atherothrombosis. JAMA 2007;297:1197–1206. Return to content
  • 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;304:1350–1357. Return to content
  • Anand SS, Eikelboom JW, Dyal L et al. Rivaroxaban plus aspirin versus aspirin in relation to vascular risk in the COMPASS trial. J Am Coll Cardiol 2019;73:3271–3280. Return to content

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