ASCVD risk refinement with NT-proBNP for statin allocation among low- and intermediate risk individuals

Background: Statin trials targeting low- to intermediate risk individuals, namely MEGA, JUPITER, and HOPE-3, have demonstrated benefit of statin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD), but are poorly reflected in guideline recommendations for primary prevention of ASCVD. N-terminal pro-B-type natriuretic peptide (NT-proBNP) may refine ASCVD risk in low-to intermediate risk individuals eligible for HOPE-3, JUPITER and MEGA, and aid statin initiation in low- to intermediate risk populations. Methods: 5434 participants, aged 45 years and above from the prospective population-based Rotterdam Study, free of ASCVD, heart failure, and diabetes, were included between 1997 and 2008. Eligibility criteria for MEGA, JUPITER, and HOPE-3 trials were checked for each participant. ASCVD event rates, hazard ratios (HR), 5-year numbers needed to treat (NNT5y), and screen (NNS5y) per trial eligible population and NT-proBNP category (?50, 50-100, and >100 pg/mL) were calculated. Results: Median age was 61.6 years, 58.9% were women, median NT-proBNP was 60 pg/mL. The proportions of participants eligible for MEGA, JUPITER and HOPE-3 were 34.9%, 10.4% and 23.7%. Incidence rates per 1000 person-years for ASCVD were 10.4 (95%CI: 60.1-67.9) for MEGA, 16.8 (95%CI: 13.6-20.6) for JUPITER, and 12.1 (95%CI: 10.3-14) for HOPE-3. Adjusted HR in trial eligible individuals for NT-proBNP >100 pg/mL compared to ?50 pg/mL level were 1.73 (95%CI: 1.21-2.47), 1.46 (95%CI: 0.80-2.66) and 1.50 (95%CI: 0.99-2.26), respectively. Estimated NNT5y among trial eligible individuals with NT-proBNP levels >100 pg/mL based on high-intensity statin treatment, varied from 23 to 34 to prevent one ASCVD event, while NNS5y ranged between 56 and 134. Conclusions: NT-proBNP level >100 pg/mL identifies individuals at the highest ASCVD risk among low- to intermediate risk populations who are likely to benefit from statin treatment at acceptable NNT5y and NNS5y. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The Rotterdam Study is supported by the Erasmus MC and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research (NWO); the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; the Netherlands Genomics Initiative; the Ministry of Education, Culture, and Science; the Ministry of Health, Welfare, and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. Dr Pavlovi? was supported by Erasmus Mundus Western Balkans, a project funded by the European Commission. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Rotterdam Study has been approved by the Medical Ethics Committee of the Erasmus MC (registration number MEC 02.1015) and by the Dutch Ministry of Health, Welfare and Sport (Population Screening Act WBO, license number 1071272-159521-PG). The Rotterdam Study has been entered into the Netherlands National Trial Register (NTR; www.trialregister.nl) and into the WHO International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/network/primary/en/) under shared catalogue number NTR6831. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data supporting the findings of this study are available from the corresponding author upon reasonable request.