Distinct association of VEGF-C and VEGF-D with prognosis in patients with chronic heart failure: the PREHOSP-CHF study
| Autor: | Yujiro Ono, Masaharu Akao, Mitsuru Abe, Masahiro Suzuki, Yoichi Ajiro, Tsuyoshi Shinozaki, Kazuhiko Kotani, Akihiro Koike, Masatoshi Shimizu, Tomomi Koizumi, Takashi Takenaka, Moritake Iguchi, Hiromichi Wada, Morihiro Matsuda, Koji Hasegawa, Prehosp-Chf investigators |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | European Heart Journal. 42 |
| ISSN: | 1522-9645 0195-668X |
| Popis: | Background The lymphatic system has been suggested to play an important role in cardiovascular (CV) diseases including heart failure (HF). Vascular endothelial growth factor C (VEGF-C) and VEGF-D are key regulators of lymphoangiogenesis. Purpose To investigate the association of VEGF-C and VEGF-D with prognosis in patients with chronic HF (CHF). Methods The PREHOSP-CHF study is a multicenter prospective cohort study to determine the predictive value of angiogenesis-related biomarkers in CHF. A total of 1,024 patients (mean age, 75.5±12.6 years; male, 58.7%) admitted to acute decompensated HF were included in the analyses. The primary outcome was MACE defined as a composite of CV death or HF hospitalization. The secondary outcomes were all-cause death, CV death, and HF hospitalizations. Serum levels of VEGF-C and VEGF-D, as well as N-terminal pro B-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin-I (hs-cTnI), high sensitive C reactive protein (hs-CRP), VEGF, and soluble VEGF receptor-2 (sVEGFR-2) were measured at the time of discharge. Patients were followed-up over two years. Results Median [interquartile range] of VEGF-C and VEGF-D levels were 4821 [3633–6131] pg/ml and 404 [296–559] pg/ml, respectively. In multivariate stepwise regression analysis, independent determinants of VEGF-C levels were younger age, female gender, absence of prior HF hospitalization, chronic kidney disease, and anemia, lower ejection fraction, lower NT-proBNP levels, higher VEGF levels, and higher sVEGFR-2 levels, while those of VEGF-D levels were lower body mass index, presence of diabetes and atrial fibrillation, and higher NT-proBNP levels. During the follow-up, a total of 209 (20.4%) all-cause deaths, 112 (10.9%) CV deaths, and 309 (30.2%) HF hospitalizations occurred. After adjusting for established risk factors and CV biomarkers, VEGF-C levels were significantly and inversely associated with the incidence of MACE and non-CV death (Fig.1, model 4). On the other hand, VEGF-D levels were significantly and positively associated with the incidence of HF hospitalization (Fig. 1, model 4). When we divided the patients into 4 groups based on the median of VEGF-C and VEGF-D levels, patients with low VEGF-C and high VEGF-D showed significantly higher incidence of MACE, all-cause death, CV death, and HF hospitalization compared to those with high VEGF-C and low VEGF-D (Fig. 2). Conclusions Among patients with CHF, VEGF-C and VEGF-D had different characteristic and association with the incidence of adverse events. VEGF-C levels were inversely associated with the incidence of MACE and non-CV death, and VEGF-D levels were positively associated with the incidence of HF hospitalization. These results suggests different effects of VEGF-C and VEGF-D in CHF. Combination of VEGF-C and VEGF-D enables us to make good risk stratification in patients with CHF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Clinical Research from the National Hospital Organization Figure 1Figure 2 |
| Databáze: | OpenAIRE |
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