CLINICAL RESEARCH: CARDIOVASCULAR DISEASE AND RISK
N-Terminal Pro-B-Type Natriuretic Peptide, Vascular Disease Risk, and Cholesterol Reduction Among 20,536 Patients in the MRC/BHF Heart Protection Study
Heart Protection Study Collaborative Group1,*
Heart Protection Study Collaborative Group, Clinical Trial Service Unit, University of Oxford, Oxford, Oxfordshire, United Kingdom.
Manuscript received February 14, 2006;
revised manuscript received August 22, 2006,
accepted August 28, 2006.
* Reprint requests and correspondence: Heart Protection Study, Clinical Trial Service Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, Oxfordshire OX3 7LF, United Kingdom.
OBJECTIVES: We sought to assess the ability of N-terminal pro-B-type natriuretic peptide (N-BNP) to predict vascular events in high-risk people and to test whether statins benefit people with high levels of N-BNP.
BACKGROUND: The predictive value of N-BNP for occlusive vascular events and the effects of statins in people with high N-BNP levels are uncertain.
METHODS: A total of 20,536 people were assigned randomly to simvastatin 40 mg daily or placebo for an average of 5 years. Five baseline N-BNP groups were defined (<386; 386 to 1,171; 1,172 to 2,617; 2,618 to 5,758; and  5,759 pg/ml).
RESULTS: Baseline N-BNP was strongly predictive of future vascular events independently of other characteristics. Compared with participants with N-BNP <386 pg/ml, those with levels 5,759 pg/ml had adjusted relative risks for major vascular events (MVEs) (i.e., major coronary events [MCE] [nonfatal myocardial infarction or coronary death], stroke, or revascularization) of 2.26, for MCE of 3.09, for stroke of 1.80, and for heart failure (hospitalization or death) of 9.23 (all p < 0.0001). Overall, simvastatin allocation reduced the relative risk of MVE by 24% (95% confidence interval 19 to 28). There was a trend toward smaller (but still significant) proportional reductions in MVE among participants with greater baseline N-BNP levels, but the absolute benefits of simvastatin allocation were similar at all N-BNP levels. Simvastatin allocation was also associated with a 14% (95% confidence interval 0 to 25) proportional reduction in heart failure. No excess risk of other vascular and nonvascular outcomes was observed with simvastatin allocation among participants with greater baseline values of N-BNP.
CONCLUSIONS: In this study, N-BNP levels were strongly predictive not only of heart failure but also of MVEs. In people with high N-BNP levels consistent with heart failure, statin allocation significantly reduced vascular risk, with no evidence of hazard. (Heart Protection Study; http://www.controlledtrials.com/ISRCTN48489393/48489393)
|
Abbreviations and Acronyms
| | BNP = brain-type natriuretic peptide | | CI = confidence interval | | LDL = low-density lipoprotein | | LVEF = left ventricular ejection fraction | | MCE = major coronary event | | MI = myocardial infarction | | MVE = major vascular event | | N-BNP = N-terminal pro-B-type natriuretic peptide |
|
This article has been cited by other articles:
|
|
|
|
 
A. M. Richards and R. W. Troughton
Use of Natriuretic Peptides to Guide and Monitor Heart Failure Therapy
Clin. Chem.,
January 1, 2012;
58(1):
62 - 71.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. G. Gilstrap and T. J. Wang
Biomarkers and Cardiovascular Risk Assessment for Primary Prevention: An Update
Clin. Chem.,
January 1, 2012;
58(1):
72 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Arroll, R. Doughty, and V. Andersen
Investigation and management of congestive heart failure
BMJ,
July 14, 2010;
341(jul14_2):
c3657 - c3657.
[Full Text]
|
|
|
|
|
|
|
P. van der Harst and R. A. de Boer
Statins in the Treatment of Heart Failure
Circ Heart Fail,
May 1, 2010;
3(3):
462 - 464.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. De Caterina, M. Scarano, R. Marfisi, G. Lucisano, F. Palma, A. Tatasciore, and R. Marchioli
Cholesterol-Lowering Interventions and Stroke: Insights From a Meta-Analysis of Randomized Controlled Trials
J. Am. Coll. Cardiol.,
January 19, 2010;
55(3):
198 - 211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Henriksson, S. Palmer, R. Chen, J. Damant, N. K Fitzpatrick, K. Abrams, A. D Hingorani, U. Stenestrand, M. Janzon, G. Feder, et al.
Assessing the cost effectiveness of using prognostic biomarkers with decision models: case study in prioritising patients waiting for coronary artery surgery
BMJ,
January 19, 2010;
340(jan19_1):
b5606 - b5606.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. C.M. Linssen, S. J.L. Bakker, A. A. Voors, R. T. Gansevoort, H. L. Hillege, P. E. de Jong, D. J. van Veldhuisen, R. O.B. Gans, and D. de Zeeuw
N-terminal pro-B-type natriuretic peptide is an independent predictor of cardiovascular morbidity and mortality in the general population
Eur. Heart J.,
January 1, 2010;
31(1):
120 - 127.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Di Angelantonio, R. Chowdhury, N. Sarwar, K. K. Ray, R. Gobin, D. Saleheen, A. Thompson, V. Gudnason, N. Sattar, and J. Danesh
B-Type Natriuretic Peptides and Cardiovascular Risk: Systematic Review and Meta-Analysis of 40 Prospective Studies
Circulation,
December 1, 2009;
120(22):
2177 - 2187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland, J. J.V. McMurray, J. Kjekshus, J. H. Cornel, P. Dunselman, C. Fonseca, A. Hjalmarson, J. Korewicki, M. Lindberg, N. Ranjith, et al.
Plasma Concentration of Amino-Terminal Pro-Brain Natriuretic Peptide in Chronic Heart Failure: Prediction of Cardiovascular Events and Interaction With the Effects of Rosuvastatin: A Report From CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure)
J. Am. Coll. Cardiol.,
November 10, 2009;
54(20):
1850 - 1859.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. B. Daniels and E. Barrett-Connor
Can Natriuretic Peptides Help Identify Heart Failure Patients for Whom Statins Are Beneficial?
J. Am. Coll. Cardiol.,
November 10, 2009;
54(20):
1860 - 1861.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C. Korngold, J. L. Januzzi Jr, M. L. Gantzer, M.V. Moorthy, N. R. Cook, and C. M. Albert
Amino-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity C-Reactive Protein as Predictors of Sudden Cardiac Death Among Women
Circulation,
June 9, 2009;
119(22):
2868 - 2876.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland, I. Squire, and L. Ng
Interpretation of Amino-Terminal Pro-Brain Natriuretic Peptide Levels in the HPS and the CORONA Study
J. Am. Coll. Cardiol.,
September 23, 2008;
52(13):
1104 - 1105.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Winkler, C. Wanner, C. Drechsler, J. Lilienthal, W. Marz, V. Krane, and for the German Diabetes and Dialysis Study Investi
Change in N-terminal-pro-B-type-natriuretic-peptide and the risk of sudden death, stroke, myocardial infarction, and all-cause mortality in diabetic dialysis patients
Eur. Heart J.,
September 1, 2008;
29(17):
2092 - 2099.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. C H J Michielsen, J. A Bakker, R. R J V. Kimmenade, Y. M Pinto, and M. P V. Dieijen-Visser
The diagnostic value of serum and urinary NT-proBNP for heart failure
Ann Clin Biochem,
July 1, 2008;
45(4):
389 - 394.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Paulsen, C. Holm, J. N. Bech, J. Starklint, and E. B. Pedersen
Effects of statins on renal sodium and water handling: Acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans
Nephrol. Dial. Transplant.,
May 1, 2008;
23(5):
1556 - 1561.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Sanz, P. R. Moreno, and V. Fuster
The Year in Atherothrombosis
J. Am. Coll. Cardiol.,
March 4, 2008;
51(9):
944 - 955.
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Pitt
N-terminal pro-B-type natriuretic peptide concentrations >=100 ng/l increased risk of all-cause mortality
Evid. Based Med.,
February 1, 2008;
13(1):
26 - 26.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. G.F. Cleland, A. P. Coletta, A. T. Abdellah, D. Cullington, A. L. Clark, and A. S. Rigby
Clinical trials update from the American Heart Association 2007: CORONA, RethinQ, MASCOT, AF-CHF, HART, MASTER, POISE and stem cell therapy
Eur J Heart Fail,
January 1, 2008;
10(1):
102 - 108.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Lehman
Evidently...
Evid. Based Med.,
August 1, 2007;
12(4):
103 - 103.
[Full Text]
[PDF]
|
|
|
|
|
|
|
Other articles noted
Evid. Based Med.,
August 1, 2007;
12(4):
127 - 128.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Shadman, M. A. Allison, and M. H. Criqui
Glomerular Filtration Rate and N-Terminal Pro-Brain Natriuretic Peptide as Predictors of Cardiovascular Mortality in Vascular Patients
J. Am. Coll. Cardiol.,
June 5, 2007;
49(22):
2172 - 2181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Statins in High-Risk Patients with High NT-proBNP Levels
Journal Watch Cardiology,
February 7, 2007;
2007(207):
3 - 3.
[Full Text]
|
|
|
|
