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

TY - JOUR

T1 - Plasma levels of hepatocyte growth factor and placental growth factor predict mortality in a general population: 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

N1 - © 2017 The Association for the Publication of the Journal of Internal Medicine.

PY - 2017/10

Y1 - 2017/10

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 - Adult

KW - Aged

KW - Biomarkers/blood

KW - Cardiovascular Diseases/mortality

KW - Female

KW - Hepatocyte Growth Factor/blood

KW - Humans

KW - Male

KW - Middle Aged

KW - Mortality

KW - Neoplasms/mortality

KW - Placenta Growth Factor/blood

KW - Predictive Value of Tests

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Factors

U2 - 10.1111/joim.12648

DO - 10.1111/joim.12648

M3 - SCORING: Journal article

C2 - 28682476

VL - 282

SP - 340

EP - 352

JO - J INTERN MED

JF - J INTERN MED

SN - 0954-6820

IS - 4

ER -