Why not screen for subclinical atherosclerosis?Literature -
Why not screen for subclinical atherosclerosis?Henrik Sillesen, Erling Falk, Rigshospitalet and University of Copenhagen, Denmark
Published The Lancet, Online March 28, 2011 DOI:10.1016/S0140-6736(11)60059-7
Although preventable, atherosclerotic cardiovascular disease remains a leading global cause of death and disability.1 Despite, or rather because of, major improvements in survival after myocardial infarction and stroke, the prevalence, burden, and costs of the disease continue to rise.2 In high-income countries, cardiovascular disease is the most costly disease—more costly than all cancers combined.3 Furthermore, sudden and unexpected death is still a common first manifestation of cardiovascular disease.3 The only eff ective approach to restrict this undue loss of life, and the health burden and use of resources, is to prevent the disease from developing in the first place ie, primary prevention. Public health initiatives are important but so is personalised prevention for those at highest risk.
Causal risk factors for cardiovascular disease constitute important therapeutic targets, but their usefulness as predictors for developing the disease is limited.4,5 Most heart attacks and strokes occur in people at average risk-factor level who are misclassifi ed by traditional riskfactor scoring, as low or intermediate risk.6 Conversely, others are misclassifi ed as high risk and advised to take drugs to reduce their risk factor(s), drugs that are not needed. These facts remind us that, although exposure to causal factors is important, susceptibility to these factors and the disease in question might be more important. Despite great promise, genetic testing for susceptibility has not proven useful for risk stratification.7 Atherosclerosis develops silently over decades before symptoms eventually occur, off ering unique opportunities for timely detection and personalised prevention. Subclinical atherosclerosis can be detected and quantified non-invasively, to show the cumulative eff ect of all risk and susceptibility factors combined—known and unknown.4,5 Three measures of disease burden have proven useful for risk assessment in clinical practice: coronary artery calcium by CT, intima-media thickness and plaque on carotid ultrasound, and ankle-brachial index.
The 2010 American College of Cardiology Foundation and American Heart Association’s guidelines for cardiovascular risk assessment recommend (class IIa) use of these non-invasive tests for subclinical atherosclerosis in asymptomatic adults at intermediate risk according to traditional risk-factor scoring.8 These tests can correctly reclassify a substantial number of people in this therapeutic grey area to lower or higher risk categories, for which treatments are better defi ned. Tests for subclinical atherosclerosis might also be useful in the management of patients with diabetes, a family history of premature cardiovascular disease, or both (fi gure).8,9 The clinical usefulness of these tests diff ers. For example, only carotid ultrasound can detect early arterial disease in younger individuals whereas measurement of ankle-brachial index depends on the presence of advanced stenotic disease, which is most useful in older patients. Carotid ultrasound and ankle-brachial index measurements are widely available, portable, and safe, whereas cardiac CT is less portable and uses low-dose radiation. On the other hand, CTs are standardised and operator independent, with documented high reproducibility outside research laboratories. What all these non-invasive tests for subclinical atherosclerosis have in common is that they can identify people who, without knowing it, are developing a potentially deadly disease, which off ers the opportunity for timely intervention irrespective of risk-factor status.
So why are we not using the best tools to identify those who need personalised care? Probably because of a misplaced double standard.10 None of the currently recommended risk-assessment algorithms, including the Framingham risk score and the European SCORE system, are supported by evidence from randomised outcome trials. To ask for this kind of evidence from newer and better predictors before using them seems to be more academic than reasonable.5,10
The time has come to change practice. In primary prevention of atherosclerotic cardiovascular disease, we should strive to use the best methods to provide clinically meaningful prognostic information. Several ongoing studies, including the High-Risk Plaque Initiative’s BioImage study,6 are trying to refine and improve the predictive power of recommended tests and explore the incremental value of more advanced and costly technologies, such as magnetic resonance and nuclear imaging.
The burden of cardiovascular disease is increasing despite falling mortality.2 We have inexpensive generic drugs to lower blood cholesterol concentrations and blood pressure, of proven effi cacy and safety. Their wider use will not only reduce the burden of disease but also save money because symptomatic cardiovascular disease is extremely costly.11,12 On this background, non-invasive tests for subclinical atherosclerosis should be implemented to help to target medical prevention to those who need it, and thus limit both undertreatment and overtreatment.
1. Murray CJ, Lauer JA, Hutubessy RC, et al. Eff ectiveness and costs of interventions to lower systolic blood pressure and cholesterol: a global and regional analysis on reduction of cardiovascular-disease risk. Lancet 2003;361: 717–25.
2 Fuster V, Mearns BM. The CVD paradox: mortality vs prevalence. Nat Rev Cardiol 2009; 6: 669.
3 Roger VL, Go AS, Lloyd-Jones DM, et al, on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 2011; 123: e18–209.
4 Naghavi M, Falk E, Hecht HS, et al, for the SHAPE Task Force. From vulnerable plaque to vulnerable patient—part III: executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol 2006; 98: 2H–15H.
5 Shah PK. Screening as ymptomatic subjects for subclinical atherosclerosis: can we, does it matter, and should we? J Am Coll Cardiol 2010; 56: 98–105.
6 Muntendam P, McCall C, Sanz J, Falk E, Fuster V, for the High-Risk Plaque Initiative. The BioImage Study: novel approaches to risk assessment in the primary prevention of atherosclerotic cardiovascular disease—study design
and objectives. Am Heart J 2010; 160: 49–57.
7 Manolio TA. Genomewide association studies and assessment of the risk of disease. N Engl J Med 2010; 363: 166–76.
8 Greenland P, Alpert JS, Beller GA, et al. 2010 ACCF/AHA guideline for assessment of cardiovascular risk in asymptomatic adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2010; 56: e50–103.
9 Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. J Am Coll Cardiol 2010; 56: 1864–94.
10 Hecht HS. The deadly double standard (the saga of screening for subclinical atherosclerosis). Am J Cardiol 2008; 101: 1805–07.
11 Pletcher MJ, Lazar L, Bibbins-Domingo K, et al. Comparing impact and cost-eff ectiveness of primary prevention strategies for lipid-lowering. Ann Intern Med 2009; 150: 243–54.
12 Wisløff T, Nordheim OF, Halvorsen S, Selmer RM, Kristiansen IS. Costs and life year gained with pharmaceutical primary prevention of cardiovascular disease. Dec 18, 2008. http://www.kunnskapssenteret.no/Publikasjoner/ 4786.cms (accessed Jan 3, 2011) (in Norwegian)