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Imaging cardiovascular risk

ESC Congress 2010

Risk Factors, Epidemiology, Rehabilitation and Sports Cardiology

Risk scores and biomarkers (G De Baker, Belgium)
Assessing cardiovascular risk using established risk factors does not fully explain the incidence and appearance of cardiovascular disease in the general population(N Engl J Med 2006;355:2631-2639). In spite of the introduction of several new biomarkers reported to be associated with elevated risk of cardiovascular events independently of established risk factors, these new biomarkers have not clearly contributed to risk stratification of the individual patient(N Engl J Med 2008;358:2107). The presenter stressed the intrinsic difficulties of predicting the future beyond the established risk scores citing a famous sentence of N Bohr “prediction is difficult but predicting the future is even more difficult”. He cited and went partially through over 300 functional and morphologic potential biomarkers and underlined the limited value of single emerging risk factors such as hs-CRP, citing and expanding the results of the ARIC study (Arch Int Medicine 2006;166:1368), the MALMO Diet and Cancer Study (JAMA 2009;302:49-57), the Multi-marker Women’s Health (JACC 2010;55:2080). The UPPSALA study (N Engl J Med 2008;358:2107) has clearly indicated that by simultaneously adding several biomarkers of cardiovascular and renal abnormalities, risk stratification for death from cardiovascular causes substantially improves beyond that of a model that is based only on established risk factors Globally, the added value of single novel biomarkers is deceiving (including hs-CRP); the use of a combination of several biomarkers may add a modest but significant improvement in risk assessment.

Identify the first stage of atherosclerosis (J Lekakis, Athens)
The presenter went through the different role of endothelial function- centered methodologies which may predict atherosclerosis in its preclinical as well as in advanced stages of disease (amongst others: FMD, pulse-amplitude plethysmography, coronary endothelial function assessment of the epicardial and microcirculation, PWA-augmentation index, Laser Doppler flow-metry). Endothelial dysfunction is implicated in and frequently perpetuates crucial aspects of atherosclerosis, such as inflammation and thrombosis of the vessel wall, that are relevant in the early and late stages of the disease. A systemic inflammatory reaction that includes negative influence of C-reactive protein on the endothelium may enhance endothelial dysfunction. There is increasing evidence of the prognostic implications of the degree of coronary and peripheral endothelial dysfunction, as measured in response to acetylcholine or flow-dependent dilation (FDD). As recently observed, endothelial dysfunction seems to represent an independent predictor of CV events integrating most causes beyond conventional CV risk factors and potentially other not-yet-identified factors(Circulation. 2004;109:II-27 ).
The role of endothelial progenitor cells and endothelial microparticles remains elusive and has yet to be established. A novel target to assess integrity of the vessel wall may be represented by glycocalyx, an exclusion zone for circulating red cells adjacent to the endothelial surface in which plasma motion is significantly retarded, an "endothelial surface layer" with a thickness of 0.4 to 0.5 µm in microvessels which contains fluid and plasma proteins in dynamic equilibrium with the flowing plasma(Circ Res. 1996; 79: 581–589; Pflugers Arch Eur J Physiol. 2000; 440: 653–666). There is evidence in animals and humans that glycocalyx plays a protective role of the endothelium during ischemia and reperfusion procedures (Circulation. 2007;116:1896-1906.).

Coronary atherosclerosis: anatomy or ischemia? (M Vannan, Columbus,US)
Asymptomatic subjects: morphological screening: role of Coronary Calcium Calcification(CAC) Population studies show that CAC scores increase with advancing age, reflecting the natural progression of atherosclerosis (Circulation 2007;115:402-426). Men generally have higher CAC scores than women of similar age. CAC scores are often reported as percentiles of calcification in a reference population according to age and sex. The Framingham risk score does not put most young adults at high risk, since in this age group, overt coronary artery disease is unlikely within 10 years, even when multiple risk factors are present.
A CAC score of zero is corresponds to a very low risk of coronary events (J Cardiovasc Comput Tomogr 2007;1:155-159) while high CAC scores are associated with a progressive increase in the risk of events. The Multi-Ethnic Study of Atherosclerosis (MESA) ( number, NCT00005487), a cohort study of 6722 initially asymptomatic adults (38.6% white, 27.6% black, 21.9% Hispanic, and 11.9% Chinese), has shown clear evidence of the incremental prognostic information provided by the CAC score. Although MESA showed an obvious gradient of risk as CAC scores increased, the absolute risk was low (= 1% per year, even in participants with high scores). However it remains unknown whether CAC scanning has a favorable effect on clinical outcomes.
Uncertainties exist as to how, when, and in whom the test should be performed and which CAC-score threshold should trigger a more aggressive prevention t of risk factors. In persons categorized as having a low risk of coronary events according to the CRF accepted criteria, the presence of coronary calcium increases the risk of future CV events, but even subjects in this group with a high CAC score, will have a low likelihood of coronary events (see Figure N Engl J Med 2008;358:1336-1345) In the same way, in those subjects who are in the high-risk category according to classic RF criteria, a low CAC score does not eliminate the risk of worse outcome. Probably the group of subjects who might benefit most from CAC risk stratification would be persons initially identified as having an intermediate Framingham score (10-year risk of 10 to 20%). A low CAC score in these patients might put them to a low-risk category, whereas a high CAC score might indicate a higher risk .

Asymptomatic subjects: functional screening: role of stress tests
Acute myocardial infarction and sudden death are often the first manifestations of coronary artery disease. Thus, it has been suggested that screening strategies to detect ischemia before the appearance of symptoms are imperative. This conclusion would imply that such testing could detect ischemia in totally asymptomatic subjects where an acute infarction or sudden death would soon occur.
ECG stress test has definitely lost its value in this context after the publication of the seminal paper of S. E. Epstein in 1988 (N Engl J Med 1988; 318:1038); whereas the other stress tests such as stress echocardiography, nuclear tests and stress cardiac MRI are approaching a reasonable threshold in this context, never achieving an ideal goal given the unpredictability of a plaque complication using a functional test.

Symptomatic CAD subjects: role of functional screening
The value of exercise echocardiography and nuclear testing were elegantly clarified in the seminal paper by L.J. Shaw et al, who examined prognosis and cost-effectiveness of exercise echocardiography (n=4884) vs. SPECT (n=4637) imaging in stable, intermediate risk, chest pain patients. They defined ischemia extension as the number of vascular territories with echocardiographic wall motion or SPECT perfusion abnormalities.
They found similar risk-adjusted 3-year death or MI rates , ranging from 2.3 to 8.0% for echocardiography and from 3.5 to 11.0% for SPECT. Cost-effectiveness ratios for echocardiography were <$20 000/LYS when the annual risk of death or MI was <2%. However, when yearly cardiac event rate were >2%, cost-effectiveness ratios for echocardiography vs. SPECT were in the range of $66 686–$419 522/LYS. For patients with established coronary disease (i.e. ≥2% annual event risk), SPECT ischaemia was associated with earlier and greater utilization of coronary revascularization (P<0.0001) resulting in an incremental cost-effectiveness ratio of $32 381/LYS. They concluded that a goal strategy of cost-effective testing would support using echocardiography in low-risk patients with suspected coronary disease, whereas patients at higher risk should be referred to SPECT imaging.

Symptomatic CAD subjects: role of anatomic screening (Multidetector computed tomography= MDCT) in acute coronary syndrome:
Multidetector computed tomography (MDCT) has a high diagnostic capacity for detecting or excluding coronary artery stenosis. MDCT is a valuable diagnostic method in emergency department (ED) patients with chest pain of uncertain origin, providing early direct noninvasive visualization of coronary anatomy. ED MDCT had a high positive predictive value for diagnosing acute coronary syndrome, whereas a negative MDCT study predicted a favorable outcome during follow-up (Eur Heart J. 2006; 27: 976). MDCT permits visualization of coronary atheromatous disease and the assessment of coronary obstructions in native vessels, grafts, and stents, though with slightly lower predictive accuracy for in-stent restenosis. (J Am Coll Cardiol. 2005; 46: 1573). MDCT also has a high positive predictive value for diagnosing acute coronary syndrome; conversely, a negative MDCT predicts a favorable outcome(Circulation. 2007;115:1762).
MDCT has the potential to change clinical approach with respect to ED triage in patients with chest pain of unknown origin. Despite the well established benefits of clinical and noninvasive testing with the use of stress testing and myocardial scintigraphy , the straightforward anatomic information obtained by MDCT scanning may have a major influence on ED decision making, especially in patients where other tests performed given equivocal results (Circulation. 2007;115:1762).

Identifiying the vulnerable patient: incremental value by imaging (V. Fuster, NY )
Prof Fuster presented the first follow-up results of the large HRP study, a joint research and development effort to improve the understanding, recognition and management of high-risk plaque for the benefit of all stakeholders in the healthcare system.
The HRP Initiative aims to discover and develop methods to find atherosclerosis at an early stage - before the first heart attack or stroke. Scientists are confident that if individuals with this condition can be identified early, they can be effectively treated. Early diagnosis and treatment could prevent many instances of heart attack and stroke.
The HRP Initiative is led by many of the foremost scientists in the field of cardiovascular disease, radiology and other medical disciplines. The Scientific Program Board is led by co-chairs Dr. Valentin Fuster of Mount Sinai University New York and Dr. Erling Falk of Aarhaus University Hospital in Denmark.
Doctor Fuster presented the preliminary data of the formidable impact of the HRP initiative where in a cohort of > 6000 subjects at risk for near-term atherothrombotic events, the authors use a novel and proactive examination approach, by bringing the necessary research facilities, experienced staff, and advanced imaging equipments to the study participants rather than the other way round. The mobile facility consists of 2 dedicated trailers, one containing a 64-slice CT scanner and the other, a 3.0T MRI scanner. In addition, a fixed building is used for the other baseline study procedures, including blood sampling and ultrasound imaging.
The results are best illustrated in the self-explanatory slides from Dr. Fuster’s presentation, which constitute on their own one of the most important highlights of the ESC 2010 meeting and do not need any commentary.




Imaging cardiovascular risk
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.