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Exploring risk markers for incident heart failure using a targeted proteomics chip

Session Poster Session 1

Speaker John Molvin

Event : Heart Failure 2017

  • Topic : coronary artery disease, acute coronary syndromes, acute cardiac care
  • Sub-topic : Acute Coronary Syndromes: Biomarkers
  • Session type : Poster Session

Authors : J Molvin (Malmoe,SE), M Pareek (Odense,DK), O Melander (Malmö,SE), L Rastam (Malmö,SE), U Lindblad (Gothenburg,SE), B Daka (Gothenburg,SE), M Leosdottir (Malmoe,SE), PM Nilsson (Malmö,SE), MH Hecht Olsen (Odense,DK), M Magnusson (Malmoe,SE)

J Molvin1 , M Pareek2 , O Melander3 , L Rastam3 , U Lindblad4 , B Daka4 , M Leosdottir1 , PM Nilsson3 , MH Hecht Olsen2 , M Magnusson1 , 1Lund University, Department of Cardiology, Skåne University Hospital - Malmoe - Sweden , 2Odense University Hospital, Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases (CIMA) - Odense - Denmark , 3Department of Clinical Sciences, Lund University, Skåne University Hospital - Malmö - Sweden , 4University of Gothenburg, Institute of Medicine, Department of Public Health and Community Medicine, Sahlgrenska Academy - Gothenburg - Sweden ,

European Journal of Heart Failure ( 2017 ) 19 ( Suppl. S1 ), 131


Background: The evolving use of multiplex proteomic platforms provides excellent tools for investigating associations between multiple proteins and risk of incident cardiovascular disease (CVD). In this study, we evaluated the impact of 92 proteins, included in a multiplex panel, on incident heart failure (HF).

Methods: All 92 proteins from the OLINK CVD III panel were analyzed in 1,734 participants from a subsample of the population-based Malmö Preventive Project. Only one protein was below detectable limits in >15% samples, i.e., N-terminal pro-brain natriuretic peptide (Nt-proBNP). Therefore, Nt-proBNP was analyzed separately using a competitive enzyme immunosorbent assay. Exclusion of subjects with prevalent HF and missing covariates at baseline examination rendered a final study population of 1,705 subjects. Standardized hazard ratios (HR) for logarithmic values of protein concentrations were reported. A two-sided Bonferroni corrected P-value of 0.05/92=5.4x10-4 was considered statistically significant.

Results: Mean age was 67 years, 29% were women, and 28% had prevalent diabetes. During a mean follow-up time of 8.9±1.5 years, 91 incident HF cases were detected. In age- and sex-adjusted analyses, four proteins were associated with incident HF: Nt-proBNP (hazard ratio (HR): 2.55, 95% CI, 2.07-3.15; P=3.4x10-18), Galectin-4 (GAL-4) (HR 1.60, 1.26-2.01; P=8.4x10-5), Azurocidin (AZU-1) (HR 1.43, 1.17-1.74; P=4.0x10-4) and Growth-differentiation factor 15 (GDF-15) (HR 1.58, 1.27-1.97; 3.8x10-5). When adjusting for traditional risk factors (age, sex, height, systolic blood pressure, anti-hypertensive medication use, diabetes mellitus, prevalent atrial fibrillation and previous myocardial infarction), only Nt-proBNP (HR 2.1, 1.53-2.85; P=4.0x10-6) and GDF-15 (HR 1.37, 1.01-1.84; P=0.042) remained significantly associated with incident HF.

Conclusion: In a community sample of 1,705 elderly individuals without HF, we used an immunoassay designed to analyze 92 proteins with proposed involvement in immunity/inflammation, CVD, and metabolism to explore potential biomarkers for incident HF, and found Nt-proBNP and GDF-15 to be independently associated with future HF development.

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