Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein but not cystatin C predict cardiovascular events in male patients with peripheral artery disease independently of ambulatory pulse pressure.
BACKGROUND
Patients with peripheral arterial disease (PAD) are at high risk for cardiovascular (CV) events. We have previously shown that ambulatory pulse pressure (APP) predicts CV events in PAD patients. The biomarkers amino-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cystatin C are related to a worse outcome in patients with CV disease, but their predictive values have not been studied in relation to APP.


METHODS
Blood samples and 24-hour measurements of ambulatory blood pressure were examined in 98 men referred for PAD evaluation during 1998-2001. Patients were followed for a median of 71 months. The outcome variable was CV events defined as either CV mortality or any hospitalization for myocardial infarction, stroke, or coronary revascularization. The predictive values of log(NT-proBNP), log(hs-CRP), and log(cystatin C) alone and together with APP were assessed by multivariable Cox regression. Area under the curve (AUC) and net reclassification improvement (NRI) were calculated compared with a model containing other significant risk factors.


RESULTS
During follow-up, 36 patients had at least 1 CV event. APP, log(NT-proBNP), and log(hs-CRP) all predicted CV events in univariable analysis, whereas log(cystatin C) did not. In multivariable analysis log(NT-proBNP) (hazard ratio (HR) = 1.62; 95% confidence interval (CI) = 1.05-2.51) and log(hs-CRP) (HR = 1.63; 95% CI = 1.19-2.24) predicted events independently of 24-hour PP. The combination of log(NT-proBNP), log(hs-CRP), and average day PP improved risk discrimination (AUC = 0.833 vs. 0.736; P < 0.05) and NRI (37%; P < 0.01) when added to other significant risk factors.


CONCLUSIONS
NT-proBNP and hs-CRP predict CV events independently of APP and the combination of hs-CRP, NT-proBNP, and day PP improves risk discrimination in PAD patients.
Karolinska Institutet, Department of Medicine, Solna, Internal Medicine Unit and Emergency Department, Karolinska University Hospital Solna, Stockholm, Sweden.
Per H
PH
Skoglund
Johannes
J
Arpegård
Jan
J
Ostergren
Per
P
Svensson
D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D002097:C-Reactive Protein / Q000378:metabolism*; D016009:Chi-Square Distribution; D055316:Cystatin C / Q000097:blood*; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D009204:Myocardial Revascularization; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010343:Patient Admission; D010446:Peptide Fragments / Q000097:blood*; D058729:Peripheral Arterial Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000209:etiology / Q000401:mortality; D013548:Sweden; D013997:Time Factors
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein
NT-proBNP; ambulatory blood pressure; blood pressure; cardiovascular disease; cystatin C; hs-CRP; hypertension; peripheral arterial disease; pulse pressure