Cardiovascular risk of carotid atherosclerosis: global consensus beyond societal guidelines
Authors: Jin Hyun Joh, Sungsin Cho
Journal: The Lancet Global Health (2020)

Stroke is one of the leading causes of death and disability globally. More than 80% of strokes are ischaemic and the remainder are haemorrhagic.1Petty GW Brown Jr, RD Whisnant JP Sicks JD O'Fallon WM Wiebers DO Ischemic stroke subtypes: a population-based study of incidence and risk factors.Stroke. 1999; 30: 2513-2516Crossref PubMed Scopus (531) Google Scholar Atherosclerosis of the extracranial carotid artery comprises 15–20% of ischaemic strokes;1Petty GW Brown Jr, RD Whisnant JP Sicks JD O'Fallon WM Wiebers DO Ischemic stroke subtypes: a population-based study of incidence and risk factors.Stroke. 1999; 30: 2513-2516Crossref PubMed Scopus (531) Google Scholar hence most clinical trials have focused on revascularisation, such as carotid endarterectomy and carotid artery stenting. For symptomatic patients, major societal guidelines recommend carotid revascularisation based on the strength of many well designed randomised controlled trials over the past three decades. For asymptomatic patients, in 2011, revascularisation was recommended in those at high risk as long as rates of procedure-related stroke and death were below 3%.2Brott TG Halperin JL Abbara S et al.2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery.Circulation. 2011; 124: 489-532Crossref PubMed Scopus (453) Google Scholar Subsequently, research has indicated that cardiovascular risk in asymptomatic patients with carotid atherosclerosis should be assessed.3Lorenz MW Markus HS Bots ML Rosvall M Sitzer M Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis.Circulation. 2007; 115: 459-467Crossref PubMed Scopus (2399) Google Scholar, 4Naqvi TZ Lee MS Carotid intima-media thickness and plaque in cardiovascular risk assessment.JACC Cardiovasc Imaging. 2014; 7: 1025-1038Crossref PubMed Scopus (385) Google Scholar Several studies have shown associations between carotid plaque and increased intima-media thickness and future cardiovascular disease including stroke and coronary heart disease.3Lorenz MW Markus HS Bots ML Rosvall M Sitzer M Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis.Circulation. 2007; 115: 459-467Crossref PubMed Scopus (2399) Google Scholar, 4Naqvi TZ Lee MS Carotid intima-media thickness and plaque in cardiovascular risk assessment.JACC Cardiovasc Imaging. 2014; 7: 1025-1038Crossref PubMed Scopus (385) Google Scholar In The Lancet Global Health, Peige Song and colleagues5Song P Fang Z Wang H et al.Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study.Lancet Glob Health. 2020; 8: e721-e729Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar report their systematic review, meta-analysis, and modelling study of the prevalence and risk factors of carotid atherosclerosis by means of increased carotid intima-media thickness, carotid plaque, and carotid stenosis, in the general global population. They found that approximately 28% of individuals aged 30–79 years had increased carotid intima-media thickness. Risk factors that significantly contributed to this condition included older age, male sex, smoking, diabetes, and hypertension.5Song P Fang Z Wang H et al.Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study.Lancet Glob Health. 2020; 8: e721-e729Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar This Article contributes to estimations of the global burden of carotid atherosclerosis and the development of effective strategies for primary prevention and management of carotid atherosclerosis. The diagnostic tool used in the articles included in this systemic review was ultrasonography. Duplex ultrasound is most commonly used to assess carotid atherosclerosis. Carotid plaque and carotid stenosis are easily detected with duplex ultrasound because of the superficially positioned carotid artery. However, the method of measurement of intima-media thickness from clinical trials is often different in the precise definition of the investigated carotid segment. Examples of different measurements of intima-media thickness according to the measurement site are shown in the appendix (pp 1–2). Additionally, the method of measuring intima-media thickness is different depending on whether the mean or maximal thickness is measured, the near and far wall or only the thickness of the far wall is measured, scanning is done at a single angle or several different angles, and manual tracking or automated software is used. Furthermore, haemodynamically, the internal carotid artery or carotid bulb has a different atmosphere compared with common carotid artery due to vortex flow and flow separation. Due to these different haemodynamics, differentiating between atherosclerosis (as seen in early plaque formation) and thickening of the carotid wall by use of non-atherosclerotic compensatory remodelling is important. Although the Mannheim carotid intima-media thickness and plaque consensus suggested a standard for image acquisition,6Touboul PJ Hennerici MG Meairs S et al.Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.Cerebrovasc Dis. 2012; 34: 290-296Crossref PubMed Scopus (1046) Google Scholar different techniques are used in daily practice. Advanced carotid atherosclerosis, defined as 50% or more stenosis, increases risk of cardiovascular disease and carotid lesion-derived stroke. Therefore, major societal guidelines recommended carotid revascularisation in patients with asymptomatic stenosis of 70% or more or stenosis of 80% or higher according to the patient's condition.7Abbott AL Paraskevas KI Kakkos SK et al.Systematic review of guidelines for the management of asymptomatic and symptomatic carotid stenosis.Stroke. 2015; 46: 3288-3301Crossref PubMed Scopus (172) Google Scholar Weerd and colleagues8Weerd M Greving JP Jong AWFd Buskens E Bots ML Prevalence of asymptomatic carotid artery stenosis according to age and sex; systematic review and metaregression analysis.Stroke. 2009; 40: 1105-1113Crossref PubMed Scopus (159) Google Scholar reported prevalence estimates for moderate stenosis of 50% or more and severe stenosis of 70% or more through a systematic literature review and meta-regression analysis of 40 studies.8Weerd M Greving JP Jong AWFd Buskens E Bots ML Prevalence of asymptomatic carotid artery stenosis according to age and sex; systematic review and metaregression analysis.Stroke. 2009; 40: 1105-1113Crossref PubMed Scopus (159) Google Scholar The pooled prevalence of moderate stenosis was 4·2% (95% CI 3·1–5·7) and of severe stenosis was 1·7% (0·7–3·9). However, in their study, Song and colleagues showed the prevalence of carotid stenosis of 50% or more was 1·5% (95% CI 1·1–2·1).5Song P Fang Z Wang H et al.Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study.Lancet Glob Health. 2020; 8: e721-e729Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar This discrepancy might be related to differences in lesion definition and inclusion criteria for the meta-analyses. Prevalence data according to the degree of stenosis might be more useful to show the global burden on the health-care system and to develop effective strategies for prevention and management of carotid atherosclerosis. Screening is crucial to detect symptom-free diseases that cause unexpected disability or death. Abdominal aortic aneurysm is a good example to show the clinical benefit and cost-effectiveness of duplex ultrasound-based screening.9LeFevre ML Screening for abdominal aortic aneurysm: U.S. Preventive Services Task Force recommendation statement.Ann Intern Med. 2014; 161: 281-290Crossref PubMed Scopus (197) Google Scholar For the assessment of the balance between benefits and harms of screening, identifying factors associated with an increased risk of disease is more important. Song and colleagues5Song P Fang Z Wang H et al.Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study.Lancet Glob Health. 2020; 8: e721-e729Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar found that smoking, diabetes, and hypertension were significant risk factors for increased carotid intima-media thickness and carotid plaque and that older age was a risk factor for carotid stenosis. Although this study highlighted the lack of information on risk factors for these conditions, it might contribute to future studies to assess the benefit and cost-effectiveness of screening for carotid atherosclerosis. Racial differences in the prevalence of carotid atherosclerosis are an important factor to consider. Rockman and colleagues10Rockman CB Hoang H Guo Y et al.The prevalence of carotid artery stenosis varies significantly by race.J Vasc Surg. 2013; 57: 327-337Summary Full Text Full Text PDF PubMed Scopus (56) Google Scholar showed that the prevalence of carotid stenosis differed by races by analysing the data of vascular screening examinations. They reported that Native American and Caucasian individuals had the highest prevalence of carotid stenosis, whereas African American males and Asian females appeared to have the lowest prevalence.10Rockman CB Hoang H Guo Y et al.The prevalence of carotid artery stenosis varies significantly by race.J Vasc Surg. 2013; 57: 327-337Summary Full Text Full Text PDF PubMed Scopus (56) Google Scholar The racial difference of prevalence of carotid stenosis might be associated with different frequencies of atherosclerotic risk factors in different races. Although Song and colleagues5Song P Fang Z Wang H et al.Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study.Lancet Glob Health. 2020; 8: e721-e729Summary Full Text Full Text PDF PubMed Scopus (168) Google Scholar reported a high prevalence of carotid intima-media thickness and carotid plaque in the Western Pacific region, further epidemiological studies are needed to generate high-level evidence of the potential association between race and the prevalence of carotid atherosclerosis. We declare no competing interests. Download .pdf (.25 MB) Help with pdf files Supplementary appendix Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling studyA substantial global burden of carotid atherosclerosis exists. Effective strategies are needed for primary prevention and management of carotid atherosclerosis. High-quality epidemiological investigations on carotid atherosclerosis are needed to better address the global burden of carotid atherosclerosis at finer levels. Full-Text PDF Open Access