Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population: a prospective cohort study

K. Santalahti*, A. Havulinna, M. Maksimow, T. Zeller, S. Blankenberg, A. Vehtari, H. Joensuu, S. Jalkanen, V. Salomaa, M. Salmi

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

12 Citations (Scopus)

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 (PlGF) 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]; PlGF 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 PlGF may serve as new biomarkers for predicting increased risk of death in the general population.

Original languageEnglish
Pages (from-to)340-352
Number of pages13
JournalJournal of Internal Medicine
Volume282
Issue number4
DOIs
Publication statusPublished - 1 Oct 2017
MoE publication typeA1 Journal article-refereed

Keywords

  • biomarker
  • cohort study
  • death risk
  • epidemiology
  • mortality

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