Protein Biomarkers of Cardiovascular Disease and Mortality in the Community

The discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk-stratification methods and may be informative regarding biological pathways contributing to disease. We used a discovery proteomic platform that targeted high-value proteins for...

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Vydáno v:Journal of the American Heart Association Ročník 7; číslo 14
Hlavní autoři: Ho, Jennifer E., Lyass, Asya, Courchesne, Paul, Chen, George, Liu, Chunyu, Yin, Xiaoyan, Hwang, Shih‐Jen, Massaro, Joseph M., Larson, Martin G., Levy, Daniel
Médium: Journal Article
Jazyk:angličtina
Vydáno: England John Wiley and Sons Inc 17.07.2018
Wiley
Témata:
Aged
Atherosclerosis - blood
Atherosclerosis - epidemiology
Biomarkers - blood
cardiovascular disease risk factors
Cardiovascular Diseases - blood
Cardiovascular Diseases - epidemiology
Cardiovascular Diseases - mortality
Cause of Death
epidemiology
Female
Heart Failure - blood
Heart Failure - epidemiology
Humans
Incidence
Independent Living
Longitudinal Studies
Male
Middle Aged
Mortality
Original Research
Proportional Hazards Models
Proteomics
United States - epidemiology
United States
proteomics
epidemiology
cardiovascular disease risk factors
ISSN:2047-9980, 2047-9980
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Shrnutí:The discovery of novel and highly predictive biomarkers of cardiovascular disease (CVD) has the potential to improve risk-stratification methods and may be informative regarding biological pathways contributing to disease. We used a discovery proteomic platform that targeted high-value proteins for CVD to ascertain 85 circulating protein biomarkers in 3523 Framingham Heart Study participants (mean age, 62 years; 53% women). Using multivariable-adjusted Cox models to account for clinical variables, we found 8 biomarkers associated with incident atherosclerotic CVD, 18 with incident heart failure, 38 with all-cause mortality, and 35 with CVD death (false discovery rate, q<0.05 for all; -value ranges, 9.8×10 to 3.6×10 ). Notably, a number of regulators of metabolic and adipocyte homeostasis were associated with cardiovascular events, including insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 1 (IGFBP1), insulin-like growth factor binding protein 2 (IGFBP2), leptin, and adipsin. In a multimarker approach that accounted for clinical factors, growth differentiation factor 15 (GDF15) was associated with all outcomes. In addition, N-terminal pro-b-type natriuretic peptide, C-reactive protein, and leptin were associated with incident heart failure, and C-type lectin domain family 3 member B (CLEC3B; tetranectin), N-terminal pro-b-type natriuretic peptide, arabinogalactan protein 1 (AGP1), soluble receptor for advanced glycation end products (sRAGE), peripheral myelin protein 2 (PMP2), uncarboxylated matrix Gla protein (UCMGP), kallikrein B1 (KLKB1), IGFBP2, IGF1, leptin receptor, and cystatin-C were associated with all-cause mortality in a multimarker model. We identified numerous protein biomarkers that predicted cardiovascular outcomes and all-cause mortality, including biomarkers representing regulators of metabolic homeostasis and inflammatory pathways. Further studies are needed to validate our findings and define clinical utility, with the ultimate goal of improving strategies for CVD prevention.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.117.008108