The Impact and Future of Non-traditional Cardiovascular Risk Markers


and by displaying predicted risk in cases and non-cases separately, before and after inclusion of the new risk marker;


• evaluate the accuracy of the new marker by displaying observed versus expected event rates across the range of predicted risk for models without and with the non-traditional risk marker (goodness-of-fit test) and by reporting the number of subjects re-classified and the event rates in the re-classified groups; and


•


demonstrate the clinical importance in a randomised prospective study with analyses of cost-effectiveness.


1. 2.


Conroy RM, Pyorala K, Fitzgerald AP, et al., Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project, Eur Heart J, 2003;24(11):987–1003.


Anderson KM, Wilson PWF, Odell PM, et al., An Updated Coronary Risk Profile. A Statement for Health Professionals, Circulation, 1991;83(1):356–62.


3. Sehestedt T, Jeppesen J, Hansen TW, et al., Risk stratification with the risk chart from the European Society of Hypertension compared with SCORE in the general population, J Hypertens, 2009;27(12):2351–7.


4. Graham IM, Guidelines on cardiovascular disease prevention in clinical practice: the European perspective, Curr Opin Cardiol, 2005;20:430–39.


5.


Mancia G, De Backer G, Dominiczak A, et al., 2007 ESH- ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension, J Hypertens, 2007;25(9):1751–62.


6. Mancia G, Laurent S, Agabiti-Rosei E, et al., Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document, J Hypertens, 2009;18(6):308–47).


7. Sachdeva A, Cannon CP, Deedwania PC, et al., Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines, Am Heart J, 2009;157(1):111–17.


8.


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9.


Lawes CM, Vander Hoorn S, Law MR, et al., Blood pressure and the global burden of disease 2000. Part II: estimates of attributable burden, J Hypertens, 2006;24(3): 423–30.


10.


Akosah KO, Schaper A, Cogbill C, et al., Preventing myocardial infarction in the young adult in the first place: how do the National Cholesterol Education Panel III guidelines perform? J Am Coll Cardiol, 2003;41(9):1475–9.


11.


Ridker PM, Paynter NP, Rifai N, et al., C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction: The Reynolds Risk Score for Men, Circulation, 2008;118;2243–51.


12.


Blankenberg S, Zeller T, Saarela Olli, et al., for the MORGAM Project, Contribution of Thirty Biomarkers to Ten-Year Cardiovascular Risk Estimation in Two Population Cohorts; The MORGAM – Biomarker Project, Circulation, 2009, accepted.


13. 14.


Wang TJ, Gona P, Larson MG, et al., Multiple biomarkers for the prediction of first major cardiovascular events and death, N Engl J Med, 2006;355(25):2631–9. Zethelius B, Berglund L, Sundstrom J, et al., Use of


18. 15. 16. 17. Conclusion


We feel that the best method to find new and better non-traditional cardiovascular risk factors/markers is to acquire a better understanding of the complex process leading from a certain gene combination through traditional and non-traditional cardiovascular risk factors/ markers to subclinical cardiovascular damage and, ultimately, CVD. Through this better understanding it will probably be possible to identify which risk factors/markers are the most important at different time- points in the development of CVD in the hope of finding the right markers with the right cut-off values for the right populations.36


n


multiple biomarkers to improve the prediction of death from cardiovascular causes, N Engl J Med, 2008;358(20): 2107–16.


Danesh J et al., C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease, N Engl J Med, 2004;350(14):1387–97.


Tzoulaki I, Liberopoulos G, Ioannidis JP, Assessment of claims of improved prediction beyond the Framingham risk score, JAMA, 2009;302(21):2345–52.


Olsen MH, Hansen TW, Christensen MK, et al., Cardiovascular risk prediction by N-terminal pro brain natriuretic peptide and high sensitivity C-reactive protein is affected by age and sex, J Hypertens, 2008;26(1):26–34.


Olsen MH, Hansen TW, Christensen MK, et al., Impact of the metabolic syndrome on the predictive values of new risk markers in the general population, J Hum Hypertens, 2008;22:634–40.


19.


Olsen MH, Hansen TW, Christensen MK, et al., New risk markers may change the HeartScore risk-classification significantly in one-fifth of the population, J Hum Hypertens, 2008;23(2):105–12.


20.


Nakachi T, Kosuge M, Hibi K, et al., C-reactive protein elevation and rapid angiographic progression of nonculprit lesion in patients with non-ST-segment elevation acute coronary syndrome, Circ J, 2008;72(12): 1953–9.


21.


Kashiwagi M, Tanaka A, Kitabata H, et al., Relationship between coronary arterial remodeling, fibrous cap thickness and high-sensitivity C-reactive protein levels in patients with acute coronary syndrome, Circ J, 2009;73(7): 1291–5.


22. 23.


Zacho J et al., Genetically elevated C-reactive protein and ischemic vascular disease, N Engl J Med, 2008;359(18): 1897–1908.


Olsen MH, Wachtell K, Tuxen C, et al., Opposite Effects of Losartan and Atenolol on Natriuretic Peptides in Patients with Hypertension and Left Ventricular Hypertrophy. A LIFE Study, J Hypertens, 2005;23(5):1083–90.


24.


Olsen MH, Hansen TW, Christensen MK, et al., N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population, Eur Heart J, 2007;28(11):1374–81.


25.


Olsen MH, Wachtell K, Ibsen H, et al., Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study, J Hypertens, 2006;24(4): 775–81.


26.


Ibsen H, Olsen MH, Wachtell K, et al., Reduction in albuminuria translates to reduction in cardiovascular


28. 27.


events in hypertensive patients: losartan intervention for endpoint reduction in hypertension study, Hypertens, 2005;45(2):198–202.


Pearson TA, Mensah GA, Alexander RW, et al., Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association, Circulation, 2003;107(3):499–511.


Ridker PM, Cook N, Clinical usefulness of very high and very low levels of C-reactive protein across the full range of Framingham Risk Scores, Circulation, 2004;109(16): 1955–9.


29.


Koenig W, Lowel H, Baumert J, et al., C-reactive protein modulates risk prediction based on the Framingham Score: implications for future risk assessment: results from a large cohort study in southern Germany, Circulation, 2004;109(11):1349–53.


30.


Ridker PM, Buring JE, Rifai N, et al., Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score, JAMA, 2007;297(6):611–19.


31.


Danesh J, Wheeler JG, Hirschfield GM, et al., C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease, N Engl J Med, 2004;350(14):1387–97.


32.


Olsen MH, Sehestedt T, Lyngbæk S, et al., Urine Albumin/Creatinine Ratio, High Sensitivity C-Reactive Protein and N-Terminal Pro Brain Natriuretic Peptide – Three new Cardiovascular Risk Markers – Do They Improve Risk Prediction and Influence Treatment?, Curr Vasc Pharmacol, 2010;8(1):134–9.


33. 34.


Redon J, Williams B, Microalbuminuria in essential hypertension: redefining the threshold, J Hypertens, 2002;20(3):353–5.


Gustafsson F, Badskjær J, Hansen FS, et al., Value of N-Terminal proBNP in the Diagnosis of Left Ventricular Systolic Dysfunction in Primary Care Patients Referred for Echocardiography, Heart Drug 3, 2003;141–6.


35.


Hlatky MA, Greenland P, Arnett DK, et al., American Heart Association Expert Panel on Subclinical Atherosclerotic Diseases and Emerging Risk Factors and the Stroke Council, Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association, Circulation, 2009;119(17):2408–16


36.


Sehestedt T, Jeppesen J, Hansen TW, et al., Which markers of subclinical organ damage to measure in individuals with high normal blood pressure?, J Hypertens, 2009;27(6):1165–71.


EUROPEAN CARDIOLOGY


13


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