Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

Abstract

SummaryBackgroundGuidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment.MethodsIn this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure.FindingsWe recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56–1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77–2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010–0·014) and a net reclassification improvement of 0·027 (0·019–0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016–0·022) and a net reclassification improvement of 0·028 (0·019–0·038) for the combination of coronary heart disease, stroke, and heart failure.InterpretationIn people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.FundingBritish Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7.

N-terminal pro-brain natriuretic peptide and associated factors in the general working population: a baseline survey of the Uranosaki cohort study

“…These potential confounding factors should be taken into account when interpreting NT-proBNP values. At present, clinical evidence on whether and how NT-proBNP levels in the general working population should be managed is lacking, although previous studies demonstrated that a small elevation in the NT-proBNP level increased the risk of future CVD even in the general population 11, 31, 70 . Therefore, further clinical studies with long-term observations will be required to assess the clinical utility of measuring NT-proBNP in the general working population and the prognostic value of NT-proBNP for clinical outcomes.…”

Heart Failure Association of the European Society of Cardiology practical guidance on the use of natriuretic peptide concentrations

“…This indication is supported by several diagnostic and randomised controlled studies and is consistently recommended in clinical practice guidelines . NPs also can help in a broad range of other indications, including prognostication of patients with established cardiovascular disorders such as myocardial infarction, valvular heart disease, HF and pulmonary embolism . Overall, BNP and NT‐proBNP have comparable diagnostic and prognostic accuracy; other NPs such as atrial natriuretic peptide (ANP) [or midregional proANP (MR‐proANP)] are also comparable, but less well documented.…”

Sex‐specific associations of obesity and N‐terminal pro‐B‐type natriuretic peptide levels in the general population

“…N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) is a widely used biomarker in diagnosing heart failure (HF), particularly in patients presenting with dyspnoea and other atypical complaints . NT‐proBNP is also used in risk stratification of several cardiovascular (CV) disorders . It is considered to be more stable than BNP because of its relatively long half‐life; however, various factors influence NT‐proBNP levels.…”