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The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

ABSTRACT: BACKGROUND:Limited evidence is available on the association of insulin-like growth factors (IGFs) and risk of heart failure in population-based samples. We investigated whether serum IGFs concentrations can predict mortality from heart failure. METHODS:We conducted a nested case-control study of 39,242 subjects aged 40-79 years who participated in the JACC study, a large Japanese prospective cohort study; participants provided serum samples and were followed up for 9 years. In heart failure cases and age-, sex-, community-, and year of blood withdrawal-matched controls, we measured serum concentrations of IGF-I, IGF-II, and IGF binding protein 3 (IGFBP3) and transforming growth factor (TGF-β1). RESULTS:During the follow-up, there were 88 heart failure deaths (44 men and 44 women). Each increment of 1 standard deviation [SD] of IGF-II (120.0 ng/mL in women and 143.7 ng/mL in men) was associated with a 47% reduced risk of mortality from heart failure; multivariable odds ratio was 0.53 (95% confidence interval [CI], 0.30-0.94, P-trend = 0.03). The multivariable odds ratio in the highest quartile of IGFBP3 serum concentrations (≥3.29 µg/mL in women and ≥3.31 µg/mL in men) compared with the lowest (<2.11 µg/mL in women and <2.56 µg/mL in men) was 0.24 (95% CI, 0.05-1.11; P-trend = 0.12). No association was found between serum concentrations of IGF-I or TGF-β1 and risk of heart failure. CONCLUSIONS:Higher serum concentrations of IGF-II were associated with lower mortality from heart failure, which might suggest a possible role of IGF-II in the occurrence or prognosis of heart failure.

SUBMITTER: Eshak ES

PROVIDER: S-EPMC6375814 | biostudies-other | 2019 Mar

REPOSITORIES: biostudies-other

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The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

Eshak Ehab S ES Maruyama Koutatsu K Iso Hiroyasu H Tamakoshi Akiko A

Journal of epidemiology 20180804 3

<h4>Background</h4>Limited evidence is available on the association of insulin-like growth factors (IGFs) and risk of heart failure in population-based samples. We investigated whether serum IGFs concentrations can predict mortality from heart failure.<h4>Methods</h4>We conducted a nested case-control study of 39,242 subjects aged 40-79 years who participated in the JACC study, a large Japanese prospective cohort study; participants provided serum samples and were followed up for 9 years. In hea ...[more]

PMID: 30078811

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Project description:BackgroundThe endogenous lipid molecule sphingosine-1-phosphate (S1P) has received attention in the cardiovascular field due to its significant cardioprotective effects, as revealed in animal studies. The purpose of our study was to identify the distribution characteristics of S1P in systolic heart failure patients and the prognostic value of S1P for long-term prognosis.MethodsWe recruited 210 chronic systolic heart failure patients from June 2014 to December 2015. Meanwhile 54 healthy people in the same area were selected as controls. Plasma S1P was measured by liquid chromatography-tandem mass spectrometry. Patients were grouped according to the baseline S1P level quartiles, and restricted cubic spline plots described the association between S1P and all-cause death. Cox proportional hazard analysis was used to determine the relationship between category of S1P and all-cause death.ResultsCompared with the control group, the plasma S1P in chronic heart failure patients demonstrated a higher mean level (1.269 μmol/L vs 1.122 μmol/L, P = 0.006) and a larger standard deviation (0.441 vs 0.316, P = 0.022). Based on multivariable Cox regression with restricted cubic spline analysis, a non-linear and U-shaped association between S1P levels and the risk of all-cause death was observed. After a follow-up period of 31.7 ± 10.3 months, the second quartile (0.967-1.192 μml/L) with largely normal S1P levels had the lowest all-cause mortality and either an increase (adjusted HR = 2.368, 95%CI 1.006-5.572, P = 0.048) or a decrease (adjusted HR = 0.041, 95%CI 0.002-0.808, P = 0.036) predicted a worse prognosis. The survival curves showed that patients in the lowest quartile and highest quartile were at a higher risk of death.ConclusionsPlasma S1P levels in systolic heart failure patients are related to the long-term all-cause mortality with a U-shaped correlation.Trial registrationCHiCTR, ChiCTR-ONC-14004463. Registered 20 March 2014.

Project description:ImportanceSeveral lines of evidence support low plasma transthyretin concentration as an in vivo biomarker of transthyretin tetramer instability, a prerequisite for the development of both wild-type transthyretin cardiac amyloidosis (ATTRwt) and hereditary transthyretin cardiac amyloidosis (ATTRm). Both ATTRm and ATTRwt cardiac amyloidosis may manifest as heart failure (HF). However, whether low plasma transthyretin concentration confers increased risk of incident HF in the general population is unknown.ObjectiveTo evaluate whether low plasma transthyretin concentration is associated with incident HF in the general population.Design, setting, and participantsThis study included data from 2 similar prospective cohort studies of the Danish general population, the Copenhagen General Population Study (CGPS; n = 9582) and the Copenhagen City Heart Study (CCHS; n = 7385). Using these data, first, whether low concentration of plasma transthyretin was associated with increased risk of incident HF was tested. Second, whether genetic variants in TTR associated with increasing tetramer instability were associated with lower transthyretin concentration and with higher risk of HF was tested. Data were collected from November 2003 to March 2017 in the CGPS and from November 1991 to June 1994 in the CCHS; participants from both studies were observed for survival time end points until March 2017. Data were analyzed from March to June 2019.ExposuresTransthyretin concentration at or below the 5th percentile, between the 5th and 95th percentile (reference), and greater than the 95th percentile; genetic variants in TTR.Main outcome and measureIncident HF identified using the Danish National Patient Registry.ResultsOf 9582 individuals in the CGPS, 5077 (53.0%) were women, and the median (interquartile range [IQR]) age was 56 (47-65) years. Of 7385 individuals in the CCHS, 4452 (60.3%) were women, and the median (IQR) age was 59 (46-70) years. During a median (IQR) follow-up of 12.6 (12.3-12.9) years and 21.7 (11.6-23.8) years, 441 individuals (4.6%) in the CGPS and 1122 individuals (15.2%) in the CCHS, respectively, developed HF. Baseline plasma transthyretin concentrations at or below the 5th percentile were associated with incident HF (CGPS: hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; CCHS: HR, 1.4; 95% CI, 1.1-1.7). Risk of HF was highest in men with low transthyretin levels. Compared with p.T139M, a transthyretin-stabilizing variant, TTR genotype was associated with stepwise lower transthyretin concentrations for wild-type TTR (-16.5%), p.G26S (-18.1%), and heterozygotes for other variants (p.V142I, p.H110N, and p.D119N; -30.8%) (P for trend <.001). The corresponding HRs for incident HF were 1.14 (95% CI, 0.57-2.28), 1.29 (95% CI, 0.64-2.61), and 2.04 (95% CI, 0.54-7.67), respectively (P for trend = .04).Conclusions and relevanceIn this study, lower plasma and genetically determined transthyretin concentrations were associated with a higher risk of incident HF, suggesting a potential mechanistic association between low transthyretin concentration as a marker of tetramer instability and incident HF in the general population.

Project description:AimsPrevious studies found a relationship between elevated phenylalanine levels and poor cardiovascular outcomes. Potential strategies are available to manipulate phenylalanine metabolism. This study investigated whether increased phenylalanine predicted mortality in critical patients with either acute heart failure (HF) or acute on chronic HF, and its correlation with inflammation and immune cytokines.Methods and resultsThis study recruited 152 subjects, including 115 patients with HF admitted for critical conditions and 37 normal controls. We measured left ventricular ejection fraction (LVEF), plasma concentrations of phenylalanine, C-reactive protein, albumin, pre-albumin, transferrin, and pro-inflammatory and immune cytokines. Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and maximal vasoactive-inotropic scores (VISmax ) were calculated. Patients were followed up until death or a maximum of 1 year. The primary endpoint was all-cause death. Of the 115 patients, 37 (32.2%) were admitted owing to acute HF, and 78 (67.8%) were admitted owing to acute on chronic HF; 64 (55.7%) had ST elevation/non-ST elevation myocardial infarction. An LVEF measured during the hospitalization of <40%, 40-50%, and ≥50% was noted in 51 (44.3%), 15 (13.1%), and 49 (42.6%) patients, respectively. During 1 year follow-up, 51 (44.3%) patients died. Death was associated with higher APACHE II, SOFA, and VISmax scores; higher levels of C-reactive protein and phenylalanine; higher incidence of atrial fibrillation and use of inotropic agents; lower cholesterol, albumin, pre-albumin, and transferrin levels; and significant changes in pro-inflammatory and immune cytokines. Phenylalanine levels demonstrated an area under the receiver operating characteristic curve of 0.80 for mortality, with an optimal cut-off value set at 112 μM. Phenylalanine ≥ 112 μM was associated with a higher mortality rate than was phenylalanine < 112 μM (80.5% vs. 24.3%, P < 0.001) [hazard ratio = 5.07 (2.83-9.05), P < 0.001]. The Kaplan-Meier curves revealed that phenylalanine ≥ 112 μM was associated with a lower accumulative survival rate (log rank = 36.9, P < 0.001). Higher phenylalanine levels were correlated with higher APACHE II and SOFA scores, higher C-reactive protein levels and incidence of using inotropic agents, and changes in cytokines suggestive of immunosuppression, but lower levels of pre-albumin and transferrin. Further multivariable analysis showed that phenylalanine ≥ 112 μM predicted death over 1 year independently of age, APACHE II and SOFA scores, atrial fibrillation, C-reactive protein, cholesterol, pre-albumin, transferrin, and interleukin-8 and interleukin-10.ConclusionsElevated phenylalanine levels predicted mortality in critical patients, phenotypically predominantly presenting with HF, independently of traditional prognostic factors and cytokines associated with inflammation and immunity.

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The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

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The Prospective Association Between Plasma Concentrations of Cellular Growth Factors and Risk of Heart Failure Mortality in Japanese Population.

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