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.
Highlights
Cardiovascular disease guidelines recommend strategies that predict and prevent composite endpoints for coronary heart disease and stroke.[1,2,3,4] A rationale for this combined approach is to enhance efficiency of cardiovascular disease screening by capitalising on shared risk factors and preventive interventions, even though coronary heart disease and stroke are aetiologically distinct
Practical advantages of a strategy that integrates heart failure prediction into cardiovascular disease risk assessment could exist since coronary heart disease and stroke risk assessment is already widespread, whereas primary prevention of heart failure is not addressed by current guidelines.[8,9]
We attempted a synthesis of these results in a previous literature-based review, but we found that using published results was insufficiently powered or detailed or both to enable reliable assessment of whether or not NT-proBNP concentration measurement could augment cardiovascular disease risk assessment for coronary heart disease and stroke, and investigators of only few population-based prospective studies reported on associations between NT-proBNP concentration and first-onset heart failure
Summary
Cardiovascular disease guidelines recommend strategies that predict and prevent composite endpoints for coronary heart disease and stroke.[1,2,3,4] A rationale for this combined approach is to enhance efficiency of cardiovascular disease screening by capitalising on shared risk factors and preventive interventions, even though coronary heart disease and stroke are aetiologically distinct. Such a rationale could be extended to heart failure. Statins and antihypertensive treatments might, in addition to their benefits for primary prevention of coronary heart disease and stroke, be effective at reducing the risk of new-onset heart failure.[6,7] Practical advantages of a strategy that integrates heart failure prediction into cardiovascular disease risk assessment could exist since coronary heart disease and stroke risk assessment is already widespread, whereas primary prevention of heart failure is not addressed by current guidelines.[8,9]
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