TY - JOUR
T1 - Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population
T2 - a prospective cohort study
AU - Santalahti, K.
AU - Havulinna, A.
AU - Maksimow, M.
AU - Zeller, T.
AU - Blankenberg, S.
AU - Vehtari, A.
AU - Joensuu, H.
AU - Jalkanen, S.
AU - Salomaa, V.
AU - Salmi, M.
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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.
AB - 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.
KW - biomarker
KW - cohort study
KW - death risk
KW - epidemiology
KW - mortality
UR - http://www.scopus.com/inward/record.url?scp=85029711096&partnerID=8YFLogxK
U2 - 10.1111/joim.12648
DO - 10.1111/joim.12648
M3 - Article
C2 - 28682476
AN - SCOPUS:85029711096
VL - 282
SP - 340
EP - 352
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
SN - 0954-6820
IS - 4
ER -