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Prof. Daniel Duprez ,
Our goal is to improve the precision for early detection and treatment of cardiovascular disease by identifying markers for early disease and the response to therapy. The traditional approach to cardiovascular disease prevention involves identifying risk factors that are statistically but not necessarily biologically related to disease. Health care expenditures are overwhelming national and corporate budgets, predominantly because of the escalating costs of advanced disease. Therefore there is an urgent need for early detection and treatment of asymptomatic cardiovascular disease.
The clinical complications of atherosclerosis and atherothrombotic disease represent the major causes of morbidity and mortality worldwide (1). Disorders that shorten life expectancy include myocardial infarction and ischemia, heart failure, stroke, renal failure, peripheral vascular disease, sudden death and dementia, in all of which atherothrombotic disease is the most common cause. Efforts to delay or prevent these morbid events have been the focus of many clinical trials aimed at assessing the efficacy of therapeutic interventions. Furthermore, these events have served as the definition of disease used to establish population risk and risk factors (2).
The underlying disease that eventuates in these morbid events begins in the arterial wall or in the left ventricle and progresses through well-known mechanisms that include endothelial dysfunction, left ventricular hypertrophy, inflammation, plaque formation, plaque rupture and thrombosis. Several major risk factors have been identified for these morbid events. These risk factors may identify or contribute to one or more of the cardiovascular processes that lead to these events, but they do not necessarily identify the disease itself (3).
The traditional risk assessment has been based on the assessment of factors such as age, gender, cholesterol and blood pressure that are associated with cardiovascular morbid events. However, many cases of elevated risk levels reflect an underlying process that has been going for years. Also, many individuals with risk levels below those for which guidelines indicate treatment likely have early evidence of cardiovascular disease. Many may be at above risk for cardiovascular disease based on other factors (e.g., age, gender, smoking). Early reliable identification of such individuals and early treatment for them could have a substantial public health impact.
New insights into mechanisms of progressive cardiovascular disease, innovative technologies to assess it and effective therapy to slow its progression have been prominent research accomplishments over the past decade (4). These advances have now made it possible to detect vascular and cardiac abnormalities in asymptomatic individuals allowing interventions to be used before morbid events occur. By focusing on functional and structural abnormalities of the arteries and heart, it should therefore be possible to identify and track the progression of disease. Since the early abnormalities (e.g. endothelial dysfunction, left ventricular remodeling) are measurable many years before the onset of symptomatic cardiovascular events, these abnormalities should serve as a guide to the need for intervention to slow progression (5). Furthermore, the absence of abnormalities should identify individuals not at risk for progression and thus not in need of intervention.
Cardiovascular morbid events result from progressive vascular disease often complicated by acute events such as plaque rupture or thrombosis. Heart failure begins by structural remodeling of the left ventricle. Assessment of early disease in the arteries or left ventricle likely to progress should be more sensitive and specific predictors of future disease than assessment of risk factors which are not markers for the disease itself. Traditional approach of risk assessment is usually defined as interval risk for a morbid event. Interval risk does not necessarily provide a meaningful index for the individual patient or the health care provider. The goal of risk assessment should be to discriminate between individuals unlikely to sustain a cardiovascular morbid event during their productive lifetime and those in whom therapy should be introduced to protect them from a likely event. Every individual is on a trajectory for a cardiovascular event, since arterial, renal and cardiac disease are inescapable consequences of aging. The slope of that trajectory becomes the major determinant of who needs aggressive intervention. Thus, assessment of the presence or severity of early cardiovascular disease, or even better the slope of its progression with time, would be the optimal means of defining biological risk.
Consequently, our hypothesis is that the burden for appropriate intervention should now be based on the biologic trajectory of key non-invasive markers of early disease. Only by this strategy can we effectively improve the health of our citizens and simultaneously reduce the cost of health care.
In order to quantify the presence and severity of cardiovascular disease in asymptomatic individuals, we developed a screening strategy utilizing a panel of non-invasive tests to establish a score for cardiovascular disease. The score is based on 10 tests: vascular tests are 1.large artery elasticity; 2. small artery elasticity; 3. resting/sitting blood pressure; 4. exercise-induced rise in blood pressure; 5.retinal vascular changes; 6.carotid artery intimal-medial thickness; 7.urine albumin/creatinine ratio and cardiac tests are 8. ECG; 9. left ventricle ultrasound (wall thickness and chamber dimension); 10. BNP
Each of the 10 tests on which the score is based, has been shown to be related with cardiovascular morbidity and mortality. However there has never been a compilation of all of these tests for use in risk assessment. It is reasonable to assume that combining these tests will lead to a better definition of risk. Each of the 10 tests is scored as 0 for normal, 1 for borderline abnormal and 2 for abnormal. The total score for any individual may therefore range from 0 to 20 (6,7). The additional information from the “risk contributors” assessment is then used to for an overall risk assessment.
Noninvasive screening tests to identify vascular and cardiac disease in its early or asymptomatic phase represents a departure from the traditional approach to cardiovascular disease prevention that involves identifying risk factors that are statistically but not necessarily biologically related to disease. Our experience with a panel of 10 screening tests to detect vascular and cardiac functional and structural abnormalities and a composite scoring system has identified a high prevalence of unsuspected disease. Noninvasive testing may eventually replace or supplement risk factor assessment in improving the sensitivity and specificity of efforts to prevent cardiovascular disease morbid events.
1. Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: Global Burden of Disease Study. Lancet 1997;349:1269-1276. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9142060&query_hl=1&itool=pubmed_docsum
2. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM, Hong Y, Miller NH, Lauer RM, Ockene IS, Sacco RL, Sallis JF Jr, Smith SC Jr, Stone NJ, Taubert KA. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 2002;106:388-391. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12119259&query_hl=16&itool=pubmed_docsum
3. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97: 1837-1847. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9603539&query_hl=3&itool=pubmed_docsum
4. Duprez DA, Kaiser DR, Whitwam W, Finkelstein S, Belalcazar A, Patterson R, Glasser S, Cohn JN. Determinants of Radial Artery Pulse Wave Analysis in Asymptomatic Individuals. Am J Hypertens 2004;17:647-653. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15288881&query_hl=5&itool=pubmed_docsum
5. Mancini GBJ, Dahlof B, Diez J. Surrogate Markers for Cardiovascular Disease. Circulation 2004;109: IV 22-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15226248&query_hl=8&itool=pubmed_docsum
6. Cohn JN, Hoke L, Whitwam W, Sommers P, Taylor AL, Duprez D, Roessler R, Florea N. Screening for Early Detection of Cardiovascular Disease In Asymptomatic Individuals. Am J Heart J 2003;146:679-685. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14564323&query_hl=10&itool=pubmed_docsum
7. Cohn JN, Duprez DA, Grandits GA. Arterial Elasticity as Part of a Comprehensive Assessment of Cardiovascular Risk and Drug Treatment. Hypertension 2005;46:217-220. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15867132&query_hl=12&itool=pubmed_docsum
Daniel Duprez, MD, PhD, FACC, FAHA, FESC Professor of Medicine/Cardiology Director Lipid Clinic
Director of Research of the Rasmussen Center for Cardiovascular Disease Prevention Associate Director of the Cardiovascular Clinical Trial Center Cardiovascular Division , University of Minnesota Minneapolis, USA e-mail: firstname.lastname@example.org
Our mission: To reduce the burden of cardiovascular disease.
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