Skip Navigation

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Dzau, V.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Dzau, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


Risk assessment in cardiovascular disease: from traditional risk factors to genomics

V. Dzau*

Department of Medicine, Brigham Women's Hospital, Boston, Massachusetts, U.S.A.

* Victor Dzau, MD, Department of Medicine, Brigham Women's Hospital, 75 Francis Street, Tower 1 Room 210, Boston, MA 02115, U.S.A.

Abstract

In addition to the traditional Framingham risk factors, candidate markers for cardiovascular disease are being proposed and their number continues to grow. High-sensitivity C-reactive protein has been validated as a risk factor for both primary and secondary cardiovascular events. Most other protein markers, however, remain incompletely validated. Molecular analysis of the genetic loci associated with monogenic disorders may help to identify polymorphisms that underlie major polygenic disorders, such as essential hypertension. Genomics and proteomics have accelerated the discovery of novel genes, gene expression patterns, proteins and single nucleotide polymorphisms as predictors of disease outcome and drug response, but their validation and characterization in clinical studies remain a challenge. Studies such as The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) Trial Programme are addressing this issue by collecting large numbers of samples for mass pharmacogenomic analysis. In conclusion, novel disease markers and risk factors promise to have a radical impact on cardiovascular medicine in the long term, but their adoption into clinical practice is dependent on widespread validation in patient populations, ease of measurement and extensive physician education.

Key Words: Biomarkers • Cardiovascular disease • Genomics • Pharmacogenomics • Risk factors

References

  1. Lowe LP, Greenland P, Ruth KJ, et al. Impact of major cardiovascular disease risk factors, particularly in combination, on 22-year mortality in women and men. Arch Intern Med. 1998;158:2007–2014[Abstract/Free Full Text]
  2. Braunwald E. Shattuck lecture: cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med. 1997;337:1360–1369[Free Full Text]
  3. de Jong SC, Stehouwer CD, van den Berg M, et al. Endothelial marker proteins in hyperhomocysteinemia. Thromb Haemost. 1997;78:1332–1337[Web of Science][Medline]
  4. Cantin B, Despres JP, Lamarche B, et al. Association of fibrinogen and lipoprotein(a) as a conronary heart disease risk factor in men (The Quebec Cardiovascular Study). Am J Cardiol. 2002;89:662–666[CrossRef][Web of Science][Medline]
  5. Nordt TK, Peter K, Ruef J, et al. Plasminogen activator inhibitor type-1 (PAI-1) and its role in cardiovascular disease. Thromb Haemost. 1999;82(suppl 1):14–18
  6. Scanu AM. The role of lipoprotein(a) in the pathogenesis of atherosclerotic cardiovascular disease and its utility as predictor of coronary heart disease events. Curr Cardiol Rep. 2001;3:385–390[Medline]
  7. Austin MA. Small, dense low-density lipoprotein as a risk factor for coronary heart disease. Int J Clin Lab Res. 1994;24:187–192[Web of Science][Medline]
  8. Rifai N, Ridker PM. High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease. Clin Chem. 2001;47:403–411[Abstract/Free Full Text]
  9. Drown DJ. Intercellular adhesion molecule — sICAM-1: an emerging cardiovascular risk factor. Prog Cardiovasc Nurs. 1998;13:30Drown DJ. Intercellular adhesion molecule — sICAM-1: an emerging cardiovascular risk factor. Prog Cardiovasc Nurs. 1998;13:23[Medline]
  10. Marcus AJ, Safier LB, Kaminski WE, et al. Principles of thromboregulation: control of platelet reactivity in vascular disease. Adv Prostaglandin Thromboxane Leukot Res. 1995;23:413–418[Web of Science][Medline]
  11. Tufano A, Coppola A, Loffredo F, et al. Hypercoagulability and atherothrombosis: clinical suggestions and perspectives. Haematologica. 2001;86:8–11[Abstract/Free Full Text]
  12. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2001;342:836–843
  13. Libby P, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice. Circulation. 1999;100:1148–1150[Free Full Text]
  14. Ridker PM, Rifai N, Clearfield M, et al. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;344:1959–1965[Abstract/Free Full Text]
  15. Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999;100:230–235[Abstract/Free Full Text]
  16. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA. 2003;289:2560–2572[Abstract/Free Full Text]
  17. Guidelines Subcommittee. 1999 World Health Organization—International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens. 1999;17:151–183[Web of Science][Medline]
  18. Nicollerat JA. Implications of the United Kingdom Prospective Diabetes Study (UKPDS) results on patient management. Diabetes Educ. 2000;26:8–10 (suppl)
  19. Ridker PM, Cushman M, Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336:973–979[Abstract/Free Full Text]
  20. Marian AJ, Mares A Jr, Kelly DP, et al. Sudden cardiac death in hypertrophic cardiomyopathy. Variability in phenotypic expression of beta-myosin heavy chain mutations. Eur Heart J. 1995;16:368–376[Abstract/Free Full Text]
  21. Marian AJ, Roberts R. The molecular genetic basis for hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2001;33:655–670[CrossRef][Web of Science][Medline]
  22. Lifton RP, Gharavi AG, Geller DS. Molecular mechanisms of human hypertension. Cell. 2001;104:545–556[CrossRef][Web of Science][Medline]
  23. Jeunemaitre X, Gimenez-Roqueplo AP, Celerier J, et al. Angiotensinogen variants and human hypertension. Curr Hypertens Rep. 1999;1:31–41[Medline]
  24. Staessen JA, Kuznetsova T, Wang JG, et al. M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J Hypertens. 1999;17:9–17[Web of Science][Medline]
  25. Sachidanandam R, Weissman D, Schmidt SC, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001;409:928–933[CrossRef][Medline]
  26. Venter JC, Adams MD, Myers EW, et al. The sequence of the human genome. Science. 2001;291:1304–1351[Abstract/Free Full Text]
  27. Mehraban F, Tomlinson JE. Application of industrial scale genomics to discovery of therapeutic targets in heart failure. Eur J Heart Fail. 2001;3:641–650[Abstract/Free Full Text]
  28. Herizi A, Jover B, Bouriquet N, et al. Prevention of the cardiovascular and renal effects of angiotensin II by endothelin blockade. Hypertension. 1998;31:10–14[Abstract/Free Full Text]
  29. Rajagopalan S, Meng XP, Ramasamy S, et al. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest. 1996;98:2572–2579[Web of Science][Medline]
  30. Daley GQ, Cargill M. The heart SNPs a beat: polymorphisms in candidate genes for cardiovascular disease. Trends Cardiovasc Med. 2001;11:60–66[CrossRef][Web of Science][Medline]
  31. Doris PA. Hypertension genetics, single nucleotide polymorphisms, and the common disease: common variant hypothesis. Hypertension. 2002;39:323–331[Abstract/Free Full Text]
  32. Ferrari P, Bianchi G. The genomics of cardiovascular disorders: therapeutic implications. Drugs. 2000;59:1025–1042[CrossRef][Web of Science][Medline]
  33. Lee RT. Functional genomics and cardiovascular drug discovery. Circulation. 2001;104:1441–1446[Free Full Text]
  34. Cook SA, Rosenzweig A. DNA microarrays: implications for cardiovascular medicine. Circ Res. 2002;91:559–564[Abstract/Free Full Text]
  35. Banks RE, Dunn MJ, Hochstrasser DF, et al. Proteomics: new perspectives, new biomedical opportunities. Lancet. 2000;356:1749–1756[CrossRef][Web of Science][Medline]
  36. Kodadek T. Development of protein-detecting microarrays and related devices. Trends Biochem Sci. 2002;27:295–300[CrossRef][Web of Science][Medline]
  37. Nakagawa K, Ishizaki T. Therapeutic relevance of pharmacogenetic factors in cardiovascular medicine. Pharmacol Ther. 2000;86:1–28[CrossRef][Web of Science][Medline]
  38. Edeki T. Clinical importance of genetic polymorphism of drug oxidation. Mt Sinai J Med. 1996;63:291–300[Medline]
  39. Kuivenhoven JA, Jukema JW, Zwinderman AH, et al. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. N Engl J Med. 1998;338:86–93[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
D. P. Basile
Novel Approaches in the Investigation of Acute Kidney Injury
J. Am. Soc. Nephrol., January 1, 2007; 18(1): 7 - 9.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Right arrow Request Permissions
Google Scholar
Right arrow Articles by Dzau, V.
Right arrow Search for Related Content
PubMed
Right arrow Articles by Dzau, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?