Zusammenfassung
Die klassischen Risikofaktoren für kardiovaskuläre Erkrankungen haben einen hohen negativen Vorhersagewert, insbesondere in Verbindung mit Scorewerten und Algorithmen, deren Verwendung derzeit in internationalen Konsens-Richtlinien zur primären Prävention dieser Krankheiten befürwortet wird. Da die Kosten im Verhältnis zur geringen Chance, Fälle zu finden, sehr hoch sind, sollten neuartige Risikofaktoren wie C-reaktives Protein, Lipoprotein(a), Homocystein oder genetische Marker nicht wahllos in bevölkerungsweiten Screeningprogrammen eingesetzt werden. Wegen des niedrigen positiven Vorhersagewertes der klassischen Risikofaktoren besteht aber ein klarer Bedarf, die Risikobeurteilung bei Patienten mit hohem und mittlerem Risiko zu verbessern. Dies betrifft 20–25% der Bevölkerung in Deutschland. Diese Personen sind die bevorzugte Zielgruppe für neue Risikofaktoren. Bei Personen mit intermediärem Risiko kann der neue Risikofaktor den Ausschlag geben, ob oder ob nicht mit Blutdruck oder Lipid senkenden Medikamenten behandelt wird. Bei Patienten mit hohem Risiko ergibt sich bei zusätzlichem Vorliegen neuer Risikofaktoren die Motivation zu einer intensivierten Behandlung von Bluthochdruck und Fettstoffwechselstörungen. Beispiele für solche neuen Risikofaktoren sind C-reaktives Protein (CRP), Lipoprotein(a) oder Mikroalbuminurie. Wünschenswert sind neue Risikofaktoren, welche spezifische Behandlungsmodalitäten nach sich ziehen. Dies ist zur Zeit allenfalls für Homocystein der Fall. Letztlich fehlen randomisierte Interventionsstudien, um den klinischen Nutzen neuer Risikofaktoren zu belegen.
Abstract
The established risk factors for cardiovascular disease have a high negative predictive value, especially when combined in scores and algorithms, the use of which is currently advocated by international consensus guidelines for the primary prevention of cardiovascular disease. As the costs are high compared to the small chance of finding cases, novel risk factors such as C-reactive protein, lipoprotein(a), homocysteine or genetic markers should not be used randomly in population-wide screening programs. Due to the low positive predictive value of the established risk factors, there is a clear need to improve risk assessment in patients at high or intermediate risk (20–25% of the male middle-aged German population). These patients are the main target for novel risk factors. A novel risk factor may bring about the decision whether or not a patient at intermediate risk will be treated with blood pressure-lowering or lipid-lowering drugs. Patients at high risk will benefit from novel risk factors because they may justify intensified treatment of high blood pressure or dyslipidemia. Examples of such risk factors are C-reactive protein (CRP), lipoprotein(a) or microalbuminuria. The goal is to find risk factors that will lead to specific treatment. Currently, only homocysteine is fulfilling this requirement. Randomized intervention studies are still needed to prove the clinical relevance of novel risk factors.
Literatur
1. Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, et al. Prevalence of conventional risk factors in patients with coronary heart disease. J Am Med Assoc2003;290:898–904.10.1001/jama.290.7.898Search in Google Scholar
2. Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, Garside DB, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. J Am Med Assoc2003;290:891–7.10.1001/jama.290.7.891Search in Google Scholar
3. Assmann G, Cullen P, Schulte H. Simple scoring scheme for calculating the risk of acute coronary events based on the 10-year follow-up of the prospective cardiovascular Munster (PROCAM) study. Circulation2002;105:310–5.10.1161/hc0302.102575Search in Google Scholar
4. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation1998;97:1837–47.10.1161/01.CIR.97.18.1837Search in Google Scholar
5. International Task Force for Prevention of Coronary Heart Disease. Pocket Guide to Prevention of Coronary heart disease. http://www.chd-taskforce.de/guide.htmSearch in Google Scholar
6. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001;285:2486–97.10.1001/jama.285.19.2486Search in Google Scholar
7. De Backer G, Ambrosioni E, Borch-Johnson K, Brotons C, Cifkova R, Dallongeville J, et al. European guidelines on cardiovascular disease prevention in clinical practice: Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of eight societies and by invited experts). Eur Heart J2003;24:1601–10.10.1016/S0195-668X(03)00347-6Search in Google Scholar
8. Hense HW, Schulte H, Lowel H, Assmann G, Keil U. Framingham risk function overestimates risk of coronary heart disease in men and women from Germany – results from the MONICA Augsburg and the PROCAM cohorts. Eur Heart J2003;24:937–45.10.1016/S0195-668X(03)00081-2Search in Google Scholar
9. von Eckardstein A, Schulte H, Assmann G. Vergleich internationaler Konsensus-Empfehlungen zur Erkennung des präsymptomatischen Hochrisikopatienten für den Herzinfarkt in Deutschland. Zeitschrift für Kardiologie. 2005;94:52–60.10.1007/s00392-005-0150-4Search in Google Scholar PubMed
10. Hackam DG, Anand SS. Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence. J Am Med Assoc2003;290:932–40.10.1001/jama.290.7.932Search in Google Scholar PubMed
11. Mosca L. C-reactive protein – to screen or not to screen? N Engl J Med2002;347:1615–7.10.1056/NEJMe020127Search in Google Scholar PubMed
12. Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S. Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions. Clin Chem2003;49:1785–96.10.1373/clinchem.2003.023689Search in Google Scholar
13. Marcovina SM, Albers JJ, Scanu AM, Kennedy H, Giaculli F, Berg K, et al. Use of a reference material proposed by the International Federation of Clinical Chemistry and Laboratory Medicine to evaluate analytical methods for the determination of plasma lipoprotein(a). Clin Chem2000;46:1956–67.10.1093/clinchem/46.12.1956Search in Google Scholar
14. Kronenberg F, Neyer U, Lhotta K, Trenkwalder E, Auinger M, Pribasnig A, et al. The low molecular weight apo(a) phenotype is an independent predictor for coronary artery disease in hemodialysis patients: a prospective follow-up. J Am Soc Nephrol1999;10:1027–36.10.1681/ASN.V1051027Search in Google Scholar
15. von Eckardstein A, Schulte H, Cullen P, Assmann G. Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk. J Am Coll Cardiol2001;37:434–9.10.1016/S0735-1097(00)01126-8Search in Google Scholar
16. Strater R, Becker S, von Eckardstein A, Heinecke A, Gutsche S, Junker R, et al. Prospective assessment of risk factors for recurrent stroke during childhood − a 5-year follow-up study. Lancet2002;360:1540–5.10.1016/S0140-6736(02)11520-0Search in Google Scholar
17. Nowak-Gottl U, Junker R, Kreuz W, von Eckardstein A, Kosch A, Nohe N, Schobess R, Ehrenforth S. Childhood Thrombophilia Study Group. Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors. Blood2001;97:858–62.10.1182/blood.V97.4.858Search in Google Scholar PubMed
18. Shlipak MG, Simon JA, Vittinghoff E, Lin F, Barrett-Connor E, Knopp RH, et al. Estrogen and progestin, lipoprotein(a), and the risk of recurrent coronary heart disease events after menopause. J Am Med Assoc2000;283:1845–52.10.1001/jama.283.14.1845Search in Google Scholar PubMed
19. Berg K, Dahlen G, Christophersen B, Cook T, Kjekshus J, Pedersen T. Lp(a) lipoprotein level predicts survival and major coronary events in the Scandinavian Simvastatin Survival Study. Clin Genet1997;52:254–61.10.1111/j.1399-0004.1997.tb04342.xSearch in Google Scholar PubMed
20. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest2003;111:1805–12.10.1172/JCI200318921Search in Google Scholar
21. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation2003;107:363–9.10.1161/01.CIR.0000053730.47739.3CSearch in Google Scholar PubMed
22. Ledue TB, Rifai N. Preanalytic and analytic sources of variations in C-reactive protein measurement: implications for cardiovascular disease risk assessment. Clin Chem2003;49:1258–71.10.1373/49.8.1258Search in Google Scholar PubMed
23. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med2002;347:1557–65.10.1056/NEJMoa021993Search in Google Scholar PubMed
24. Koenig W, Lowel H, Baumert J, Meisinger C. 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. Circulation2004;109:1349–53.10.1161/01.CIR.0000120707.98922.E3Search in Google Scholar PubMed
25. Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr. Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med2001;344:1959–65.10.1056/NEJM200106283442601Search in Google Scholar PubMed
26. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med1997;336:973–9.10.1056/NEJM199704033361401Search in Google Scholar PubMed
27. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, 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. Circulation2003;107:499–511.10.1161/01.CIR.0000052939.59093.45Search in Google Scholar PubMed
28. Assmann, G, Cullen P, Fruchart J-C, Greten H, Naruszewicz M, Olsson A, Paoletti R, Riesen W, Stoll M, Tikkanen M, von Eckardstein A. For the International Task Force for Prevention of Coronary Heart Disease. Implications of emerging risk factors for therapeutic intervention. Nutr Metab Cardiovasc Dis, im Druck.Search in Google Scholar
29. Acevedo M, Pearce GL, Kottke-Marchant K, Sprecher DL. Elevated fibrinogen and homocysteine levels enhance the risk of mortality in patients from a high-risk preventive cardiology clinic. Arterioscler Thromb Vasc Biol2002;22:1042–5.10.1161/01.ATV.0000020007.25154.62Search in Google Scholar
30. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. J Am Med Assoc 2002;288:2015–22.10.1001/jama.288.16.2015Search in Google Scholar PubMed
31. Clark S, Youngman LD, Sullivan J, Peto R, Collins R. Stabilization of homocysteine in unseparated blood over several days: a solution for epidemiological studies. Clin Chem2003;49:518–20.10.1373/49.3.518Search in Google Scholar PubMed
32. Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J, Weger M. DACH-LIGA homocystein (german, austrian and swiss homocysteine society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med2003;41:1392–1403.10.1515/CCLM.2003.214Search in Google Scholar PubMed
33. Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA2002;288:973–9.10.1001/jama.288.8.973Search in Google Scholar
34. Schnyder G, Flammer Y, Roffi M, Pin R, Hess OM. Plasma homocysteine levels and late outcome after coronary angioplasty. J Am Coll Cardiol2002;40:1769–76.10.1016/S0735-1097(02)02481-6Search in Google Scholar
35. Lange H, Suryapranata H, De Luca G, Borner C, Dille J, Kallmayer K, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med2004;350:2673–81.10.1056/NEJMoa032845Search in Google Scholar PubMed
36. Pontremoli R, Leoncini G, Ravera M, Viazzi F, Vettoretti S, Ratto E, et al. Microalbuminuria, cardiovascular, and renal risk in primary hypertension. J Am Soc Nephrol2002;13(Suppl.3):S169–7210.1097/01.ASN.0000032601.86590.F7Search in Google Scholar PubMed
37. Parving HH, Hovind P. Microalbuminuria in type 1 and type 2 diabetes mellitus: evidence with angiotensin converting enzyme inhibitors and angiotensin II receptor blockers for treating early and preventing clinical nephropathy. Curr Hypertens Rep2002;4:387–93.10.1007/s11906-002-0069-3Search in Google Scholar PubMed
38. Hillege HL, Fidler V, Diercks GF, van Gilst WH, de Zeeuw D, van Veldhuisen DJ, Gans RO, Janssen WM, Grobbee DE, de Jong PE; Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation2002;106:1777–82.10.1161/01.CIR.0000031732.78052.81Search in Google Scholar
39. Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, Schroll M, Jensen JS. Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol1999;19:1992–7.10.1161/01.ATV.19.8.1992Search in Google Scholar
40. Houlihan CA, Tsalamandris C, Akdeniz A, Jerums G. Albumin to creatinine ratio: a screening test with limitations. Am J Kidney Dis2002;39:1183–9.10.1053/ajkd.2002.33388Search in Google Scholar PubMed
41. Derhaschnig U, Kittler H, Woisetschlager C, Bur A, Herkner H, Hirschl MM. Microalbumin measurement alone or calculation of the albumin/creatinine ratio for the screening of hypertension patients? Nephrol Dial Transplant2002;17:81–5.10.1093/ndt/17.1.81Search in Google Scholar PubMed
©2004 by Walter de Gruyter Berlin New York
This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
