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Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population: a prospective cohort study
Author(s) -
Santalahti K.,
Havulinna A.,
Maksimow M.,
Zeller T.,
Blankenberg S.,
Vehtari A.,
Joensuu H.,
Jalkanen S.,
Salomaa V.,
Salmi M.
Publication year - 2017
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12648
Subject(s) - medicine , hazard ratio , cohort , proportional hazards model , population , cohort study , prospective cohort study , placental growth factor , risk factor , confidence interval , oncology , vascular endothelial growth factor , environmental health , vegf receptors
Abstract Background Circulating levels of growth factors involved in leucocyte production and angiogenesis could be indicative of underlying aberrations of tissue homeostasis and therefore be utilized as predictors of risk for all‐cause cardiovascular disease ( CVD ) or cancer mortality. Methods Baseline plasma levels of a range of growth factors were measured in two cohorts of the population‐based FINRISK study (1997 Discovery cohort, N = 8444, aged 25–74; 2002 Replication cohort, N = 2951, aged 51–74 years) using a multiplexed bead array methodology and ELISA . Participants were followed up by linking them to registry data. Results In the Discovery cohort (653 deaths; 216 CVD ‐related, 231 cancer‐related), fully adjusted Cox proportional hazard regression models showed that increased plasma hepatocyte growth factor ( HGF ) and placental growth factor (Pl GF ) were associated with higher risk of 10‐year mortality ( HR , 1.29 [95% confidence interval ( CI ), 1.18–1.41] and HR , 1.23 [95% CI , 1.14–1.32], respectively). In the Replication cohort (259 deaths; 83 CVD ‐related, 90 cancer‐related), baseline HGF levels also predicted all‐cause mortality ( HR , 1.2 [95% CI , 1.08–1.32]; Pl GF data not available). By including HGF levels in a CVD mortality model, 9% of all CVD deaths were correctly reclassified in the Discovery cohort (categorical net reclassification improvement [ NRI ] for events, P = 4.0 × 10 −4 ). Moreover, adding HGF to all‐cause and CVD mortality models resulted in an overall clinical NRI of 0.10–0.18 in the Discovery cohort and meta‐analyses ( P < 0.05 for all tests). Conclusion Blood levels of HGF and Pl GF may serve as new biomarkers for predicting increased risk of death in the general population.