Clinical Trial
The Role of N-terminal PRO-Brain Natriuretic Peptide and Echocardiography for Screening Asymptomatic Left Ventricular Dysfunction in a Population at High Risk for Heart Failure. The PROBE-HF Study

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Abstract

Background

Screening for asymptomatic left ventricular dysfunction (ALVD) in subjects at risk for heart failure (HF) can affect clinical management. The aim of the present study is to examine the role of NT-pro BNP in the diagnosis of ALVD in subjects with hypertension and diabetes from primary care.

Methods and Results

A total of 1012 subjects with hypertension and/or diabetes and no symptoms or signs of HF were assessed by B-type natriuretic peptide (NT-proBNP) assay and echocardiography. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate-to-severe diastolic dysfunction. Systolic dysfunction was present in 11/1012 (1.1%). NT-proBNP levels were 170 ± 206 and 859 ± 661 pg/mL, respectively, in diastolic and systolic dysfunction and 92 ± 169 in normal subjects (P < .0001). Pooling moderate-to-severe diastolic with systolic dysfunction, a total of 52 subjects (5.1 %) were obtained: best cutoff value of NT-proBNP was 125 pg/mL (males <67 years: sensitivity [Sens] 87.5%, specificity [Spec] 92.7%, negative predictive value [NPV] 99.5%, positive predictive value [PPV] 33.3%; females <67 years: Sens 100%, Spec 84.1%, NPV 100%, PPV 33.3%; males ≥67 years: Sens 100%, Spec 77.1%, NPV 100%, PPV 32.5%; females ≥67 years: Sens 100%, Spec 59.9%, NPV 100%, PPV 23%).

Conclusions

The prevalence of ALVD in subjects at risk for HF is 5.1%. Because of its excellent NPV, NT-proBNP can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.

Section snippets

Methods

From the primary care population database of “Cooperativa Leonardo,” which includes 110 general practitioners for a population of about 130,000 citizens, 1012 consecutive subjects (486 males, 48.0%; 526 females, 52.0%; mean age 66.4 ± 7.8 years, range 36-88) with 1 or both the following risk factors for HF have been selected: type 2 diabetes, on medication at least for the last 6 months or systemic hypertension, on medication at least for the last 6 months with 2 or more drugs. All these

Study Protocol and Definition of Terms

Selected subjects were invited to visit their general practitioner where the following tests were performed in a single blind manner: 1) B-type natriuretic peptide (NT-proBNP) plasma concentration assay was measured in plasma-EDTA samples by noncompetitive immunoassay and electrochemiluminescence detection. The assay was run by a full automatic analyzer (Elecsys Modular E)15—both the reagents and the machine were supplied by Roche Diagnostic (Basel, Switzerland); 2) a complete color-Doppler

Results

Hypertension was present in 929/1012 patients (91.8%); diabetes in 413/1012 (40.8%). A total of 682 of 1012 (67.4%) subjects presented a single risk factor: hypertension in 599/1012 (59.2%) and diabetes in 83/1012 (8.2%). Both risk factors were present in 330/1012 (32.6%) subjects.

A total of 633/1012 (62.5%) subjects had a normal echocardiographic study without evidence of systolic or diastolic dysfunction. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) mild; 41

Discussion

Population studies estimate that the prevalence of ALVD ranges from 0.9% to 5.9%,17 with higher figures in subjects with hypertension or diabetes.18, 19, 20

In the present study, ALVD was documented by echocardiography in 37.5% of population of subjects with hypertension or diabetes: 36.4% showed an isolated LV diastolic dysfunction, whereas 1.1% had a combined systolic and mild diastolic impairment. Pooling moderate-to-severe isolated diastolic dysfunction with systolic dysfunction to achieve a

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    Conflict of interest:

    Partially supported by an unrestricted grant from Roche Diagnostics.

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