Skip to main content
Top
Published in: Clinical Research in Cardiology 4/2013

01-04-2013 | Original Paper

Prognostic value of NT-pro-BNP and hs-CRP for risk stratification in primary care: results from the population-based DETECT study

Authors: David M. Leistner, Jens Klotsche, Lars Pieper, Sylvia Palm, Günter K. Stalla, Hendrik Lehnert, Sigmund Silber, Winfried März, Hans-Ulrich Wittchen, Andreas M. Zeiher

Published in: Clinical Research in Cardiology | Issue 4/2013

Login to get access

Abstract

Background

There is continuous debate to the use of biomarkers in the general practitioners office and to what degree the established biomarkers N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and high-sensitive C-reactive protein (hs-CRP) might contribute to improved prediction of incident cardiovascular events.

Objective

To evaluate the utility and 5-year predictive value of a single measurement of NT-pro-BNP and hs-CRP for incident cardiovascular events, and its added value beyond the contribution of conventional risk factors in primary care.

Methods

Five year prospective longitudinal clinical epidemiological study in a nationwide sample of 4,775 primary care subjects (mean age 55.8 years, 62 % women) without coronary artery disease at baseline. Main outcome measures were incident major cardiovascular events and all-cause death.

Results

During the 5 years of follow-up, 188 subjects (3.9 %) died or experienced a first major cardiovascular event. The addition of NT-pro-BNP, but not of hs-CRP to a prediction model with established cardiovascular risk factors improved the prediction of major cardiovascular events (increase in C statistic by 0.009; p = 0.008), and was associated with a significant improvement in net reclassification improvement (NRI = 23.6 %; p = 0.003).

Conclusion

In a primary care setting, one single measurement of NT-pro-BNP, but not of hs-CRP significantly improves the prediction of incident cardiovascular events.
Appendix
Available only for authorised users
Literature
5.
go back to reference Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins SJ, Benjamin EJ, D’Agostino RB, Vasan RS (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355(25):2631–2639. doi:10.1056/NEJMoa055373 PubMedCrossRef Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, Jacques PF, Rifai N, Selhub J, Robins SJ, Benjamin EJ, D’Agostino RB, Vasan RS (2006) Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med 355(25):2631–2639. doi:10.​1056/​NEJMoa055373 PubMedCrossRef
6.
go back to reference Melander O, Newton-Cheh C, Almgren P, Hedblad B, Berglund G, Engstrom G, Persson M, Smith JG, Magnusson M, Christensson A, Struck J, Morgenthaler NG, Bergmann A, Pencina MJ, Wang TJ (2009) Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA 302(1):49–57. doi:10.1001/jama.2009.943 PubMedCrossRef Melander O, Newton-Cheh C, Almgren P, Hedblad B, Berglund G, Engstrom G, Persson M, Smith JG, Magnusson M, Christensson A, Struck J, Morgenthaler NG, Bergmann A, Pencina MJ, Wang TJ (2009) Novel and conventional biomarkers for prediction of incident cardiovascular events in the community. JAMA 302(1):49–57. doi:10.​1001/​jama.​2009.​943 PubMedCrossRef
7.
go back to reference Blankenberg S, Zeller T, Saarela O, Havulinna AS, Kee F, Tunstall-Pedoe H, Kuulasmaa K, Yarnell J, Schnabel RB, Wild PS, Munzel TF, Lackner KJ, Tiret L, Evans A, Salomaa V (2010) Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation 121(22):2388–2397. doi:10.1161/CIRCULATIONAHA.109.901413 PubMedCrossRef Blankenberg S, Zeller T, Saarela O, Havulinna AS, Kee F, Tunstall-Pedoe H, Kuulasmaa K, Yarnell J, Schnabel RB, Wild PS, Munzel TF, Lackner KJ, Tiret L, Evans A, Salomaa V (2010) Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation 121(22):2388–2397. doi:10.​1161/​CIRCULATIONAHA.​109.​901413 PubMedCrossRef
8.
9.
go back to reference Zethelius B, Berglund L, Sundstrom J, Ingelsson E, Basu S, Larsson A, Venge P, Arnlov J (2008) Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 358(20):2107–2116. doi:10.1056/NEJMoa0707064 PubMedCrossRef Zethelius B, Berglund L, Sundstrom J, Ingelsson E, Basu S, Larsson A, Venge P, Arnlov J (2008) Use of multiple biomarkers to improve the prediction of death from cardiovascular causes. N Engl J Med 358(20):2107–2116. doi:10.​1056/​NEJMoa0707064 PubMedCrossRef
10.
go back to reference Simon T, Becker R, Voss F, Bikou O, Hauck M, Licka M, Katus HA, Bauer A (2008) Elevated B-type natriuretic peptide levels in patients with nonischemic cardiomyopathy predict occurrence of arrhythmic events. Clin Res Cardiol 97(5):306–309. doi:10.1007/s00392-007-0629-2 PubMedCrossRef Simon T, Becker R, Voss F, Bikou O, Hauck M, Licka M, Katus HA, Bauer A (2008) Elevated B-type natriuretic peptide levels in patients with nonischemic cardiomyopathy predict occurrence of arrhythmic events. Clin Res Cardiol 97(5):306–309. doi:10.​1007/​s00392-007-0629-2 PubMedCrossRef
11.
go back to reference Tang WH, Shrestha K, Van Lente F, Troughton RW, Martin MG, Borowski AG, Jasper S, Klein AL (2008) Usefulness of C-reactive protein and left ventricular diastolic performance for prognosis in patients with left ventricular systolic heart failure. Am J Cardiol 101(3):370–373. doi:10.1016/j.amjcard.2007.08.038 PubMedCrossRef Tang WH, Shrestha K, Van Lente F, Troughton RW, Martin MG, Borowski AG, Jasper S, Klein AL (2008) Usefulness of C-reactive protein and left ventricular diastolic performance for prognosis in patients with left ventricular systolic heart failure. Am J Cardiol 101(3):370–373. doi:10.​1016/​j.​amjcard.​2007.​08.​038 PubMedCrossRef
12.
go back to reference Weber M, Kleine C, Keil E, Rau M, Berkowitsch A, Elsaesser A, Mitrovic V, Hamm C (2006) Release pattern of N-terminal pro B-type natriuretic peptide (NT-proBNP) in acute coronary syndromes. Clin Res Cardiol 95(5):270–280. doi:10.1007/s00392-006-0375-x PubMedCrossRef Weber M, Kleine C, Keil E, Rau M, Berkowitsch A, Elsaesser A, Mitrovic V, Hamm C (2006) Release pattern of N-terminal pro B-type natriuretic peptide (NT-proBNP) in acute coronary syndromes. Clin Res Cardiol 95(5):270–280. doi:10.​1007/​s00392-006-0375-x PubMedCrossRef
13.
go back to reference Meisinger C, Heier M, von Scheidt W, Kuch B (2010) Admission C-reactive protein and short- as well as long-term mortality in diabetic versus non-diabetic patients with incident myocardial infarction. Clin Res Cardiol 99(12):817–823. doi:10.1007/s00392-010-0193-z PubMedCrossRef Meisinger C, Heier M, von Scheidt W, Kuch B (2010) Admission C-reactive protein and short- as well as long-term mortality in diabetic versus non-diabetic patients with incident myocardial infarction. Clin Res Cardiol 99(12):817–823. doi:10.​1007/​s00392-010-0193-z PubMedCrossRef
15.
go back to reference Wittchen HU, Glaesmer H, Marz W, Stalla G, Lehnert H, Zeiher AM, Silber S, Koch U, Bohler S, Pittrow D, Ruf G (2005) Cardiovascular risk factors in primary care: methods and baseline prevalence rates—the DETECT program. Curr Med Res Opin 21(4):619–630. doi:10.1185/030079905X38187 PubMedCrossRef Wittchen HU, Glaesmer H, Marz W, Stalla G, Lehnert H, Zeiher AM, Silber S, Koch U, Bohler S, Pittrow D, Ruf G (2005) Cardiovascular risk factors in primary care: methods and baseline prevalence rates—the DETECT program. Curr Med Res Opin 21(4):619–630. doi:10.​1185/​030079905X38187 PubMedCrossRef
16.
go back to reference Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, 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 (2002) 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 106(3):388–391PubMedCrossRef Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, 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 (2002) 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 106(3):388–391PubMedCrossRef
17.
go back to reference National Cholesterol Education Program (NCEP) (2002) 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) final report. Circulation 106(25):3143–3421 National Cholesterol Education Program (NCEP) (2002) 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) final report. Circulation 106(25):3143–3421
18.
go back to reference American Diabetes Association (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–20 American Diabetes Association (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–20
19.
go back to reference Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med 342(3):145–153. doi:10.1056/NEJM200001203420301 PubMedCrossRef Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med 342(3):145–153. doi:10.​1056/​NEJM200001203420​301 PubMedCrossRef
20.
go back to reference Klotsche J, Ferger D, Pieper L, Rehm J, Wittchen HU (2009) A novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology. BMC Med Res Methodol 9:63. doi:10.1186/1471-2288-9-63 PubMedCrossRef Klotsche J, Ferger D, Pieper L, Rehm J, Wittchen HU (2009) A novel nonparametric approach for estimating cut-offs in continuous risk indicators with application to diabetes epidemiology. BMC Med Res Methodol 9:63. doi:10.​1186/​1471-2288-9-63 PubMedCrossRef
21.
go back to reference Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27(2):157–172. doi:10.1002/sim.2929 discussion 207–112PubMedCrossRef Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, Vasan RS (2008) Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 27(2):157–172. doi:10.​1002/​sim.​2929 discussion 207–112PubMedCrossRef
22.
go back to reference Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA (1982) Evaluating the yield of medical tests. JAMA 247(18):2543–2546PubMedCrossRef Harrell FE Jr, Califf RM, Pryor DB, Lee KL, Rosati RA (1982) Evaluating the yield of medical tests. JAMA 247(18):2543–2546PubMedCrossRef
23.
go back to reference Pencina MJ, D’Agostino RB (2004) Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med 23(13):2109–2123. doi:10.1002/sim.1802 PubMedCrossRef Pencina MJ, D’Agostino RB (2004) Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation. Stat Med 23(13):2109–2123. doi:10.​1002/​sim.​1802 PubMedCrossRef
24.
go back to reference Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350(7):655–663. doi:10.1056/NEJMoa031994 PubMedCrossRef Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Omland T, Wolf PA, Vasan RS (2004) Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med 350(7):655–663. doi:10.​1056/​NEJMoa031994 PubMedCrossRef
25.
go back to reference Ridker PM, Glynn RJ, Hennekens CH (1998) C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 97(20):2007–2011PubMedCrossRef Ridker PM, Glynn RJ, Hennekens CH (1998) C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 97(20):2007–2011PubMedCrossRef
26.
go back to reference Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstrom M, Mattisson I, Berglund G (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499PubMedCrossRef Manjer J, Carlsson S, Elmstahl S, Gullberg B, Janzon L, Lindstrom M, Mattisson I, Berglund G (2001) The Malmo Diet and Cancer Study: representativity, cancer incidence and mortality in participants and non-participants. Eur J Cancer Prev 10(6):489–499PubMedCrossRef
27.
go back to reference Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, Ibsen H, Torp-Pedersen C, Hildebrandt PR (2007) N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population. Eur Heart J 28(11):1374–1381. doi:10.1093/eurheartj/ehl448 PubMedCrossRef Olsen MH, Hansen TW, Christensen MK, Gustafsson F, Rasmussen S, Wachtell K, Ibsen H, Torp-Pedersen C, Hildebrandt PR (2007) N-terminal pro-brain natriuretic peptide, but not high sensitivity C-reactive protein, improves cardiovascular risk prediction in the general population. Eur Heart J 28(11):1374–1381. doi:10.​1093/​eurheartj/​ehl448 PubMedCrossRef
28.
go back to reference Wannamethee SG, Welsh P, Lowe GD, Gudnason V, Di Angelantonio E, Lennon L, Rumley A, Whincup PH, Sattar N (2011) N-terminal pro-brain natriuretic Peptide is a more useful predictor of cardiovascular disease risk than C-reactive protein in older men with and without pre-existing cardiovascular disease. J Am Coll Cardiol 58(1):56–64. doi:10.1016/j.jacc.2011.02.041 PubMedCrossRef Wannamethee SG, Welsh P, Lowe GD, Gudnason V, Di Angelantonio E, Lennon L, Rumley A, Whincup PH, Sattar N (2011) N-terminal pro-brain natriuretic Peptide is a more useful predictor of cardiovascular disease risk than C-reactive protein in older men with and without pre-existing cardiovascular disease. J Am Coll Cardiol 58(1):56–64. doi:10.​1016/​j.​jacc.​2011.​02.​041 PubMedCrossRef
30.
go back to reference Blankenberg S, McQueen MJ, Smieja M, Pogue J, Balion C, Lonn E, Rupprecht HJ, Bickel C, Tiret L, Cambien F, Gerstein H, Munzel T, Yusuf S (2006) Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 114(3):201–208. doi:10.1161/CIRCULATIONAHA.105.590927 PubMedCrossRef Blankenberg S, McQueen MJ, Smieja M, Pogue J, Balion C, Lonn E, Rupprecht HJ, Bickel C, Tiret L, Cambien F, Gerstein H, Munzel T, Yusuf S (2006) Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study. Circulation 114(3):201–208. doi:10.​1161/​CIRCULATIONAHA.​105.​590927 PubMedCrossRef
31.
go back to reference Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359(21):2195–2207. doi:10.1056/NEJMoa0807646 PubMedCrossRef Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFadyen JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359(21):2195–2207. doi:10.​1056/​NEJMoa0807646 PubMedCrossRef
33.
go back to reference McKie PM, Cataliotti A, Lahr BD, Martin FL, Redfield MM, Bailey KR, Rodeheffer RJ, Burnett JC Jr (2010) The prognostic value of N-terminal pro-B-type natriuretic peptide for death and cardiovascular events in healthy normal and stage A/B heart failure subjects. J Am Coll Cardiol 55(19):2140–2147. doi:10.1016/j.jacc.2010.01.031 PubMedCrossRef McKie PM, Cataliotti A, Lahr BD, Martin FL, Redfield MM, Bailey KR, Rodeheffer RJ, Burnett JC Jr (2010) The prognostic value of N-terminal pro-B-type natriuretic peptide for death and cardiovascular events in healthy normal and stage A/B heart failure subjects. J Am Coll Cardiol 55(19):2140–2147. doi:10.​1016/​j.​jacc.​2010.​01.​031 PubMedCrossRef
35.
go back to reference Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, Popma JJ, Stevenson W (2006) The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part II: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation 114(25):2871–2891. doi:10.1161/CIRCULATIONAHA.106.655761 PubMedCrossRef Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, Popma JJ, Stevenson W (2006) The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part II: clinical trial evidence (acute coronary syndromes through renal disease) and future directions. Circulation 114(25):2871–2891. doi:10.​1161/​CIRCULATIONAHA.​106.​655761 PubMedCrossRef
Metadata
Title
Prognostic value of NT-pro-BNP and hs-CRP for risk stratification in primary care: results from the population-based DETECT study
Authors
David M. Leistner
Jens Klotsche
Lars Pieper
Sylvia Palm
Günter K. Stalla
Hendrik Lehnert
Sigmund Silber
Winfried März
Hans-Ulrich Wittchen
Andreas M. Zeiher
Publication date
01-04-2013
Publisher
Springer-Verlag
Published in
Clinical Research in Cardiology / Issue 4/2013
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-012-0530-5

Other articles of this Issue 4/2013

Clinical Research in Cardiology 4/2013 Go to the issue