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  • Sakagami, Satoru  (9)
  • Shinozaki, Tsuyoshi  (9)
  • 2020-2024  (9)
  • 1
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    Abstract 13409: Impact of Smoking on Vascular Endothelial Growth Factor D and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: Smoking is a risk factor for mortality in the general population and in patients with coronary artery disease (CAD). Vascular endothelial growth factor D (VEGF-D) is a secreted glycoprotein that can act as lymphangiogenic and angiogenic growth factors. Recently, we demonstrated that circulating VEGF-D levels are associated with the risk of mortality in patients with suspected or known CAD. However, whether VEGF-D levels differ according to smoking status and whether smoking modifies the relationship between VEGF-D and mortality in those patients are unknown. Methods: Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the association between smoking status and VEGF-D and the impact of smoking status on the association between VEGF-D levels and the risk of all-cause death. VEGF-D was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study. Patients were followed up over 3 years. Results: The mean age (standard deviation [SD]) of the patients was 70.6 (10.4) years; 67.2% were men. Current smokers exhibited significantly higher levels of VEGF-D compared to former smokers and never smokers (median [interquartile range] , 343 [214-556], 312 [201-500] , 291 [182-485] pg/mL, respectively; P =0.006). Stepwise multiple linear regression analysis revealed that the log-transformed VEGF-D level was independently associated with current smoking ( P =0.002), but not with former smoking. After adjusting for potential clinical confounders, the VEGF-D level was significantly associated with all-cause death in never smokers (hazard ratio per 1-SD increase [HR], 1.31; 95% confidence interval [CI] , 1.10-1.55) and in former smokers (HR, 1.22; 95% CI, 1.08-1.37), but not in current smokers (HR, 0.92; 95% CI, 0.65-1.22). Furthermore, VEGF-D provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in former smokers or in current smokers. Conclusions: Current smoking was independently associated with higher levels of VEGF-D. The prognostic value of VEGF-D on mortality was most pronounced in never smokers among patients with suspected or known CAD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13409
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 2
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    Abstract 13417: Impact of Sex on the Prognostic Value of Galectin-3 in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: High circulating levels of galectin-3 are associated with all-cause mortality, cardiovascular (CV) mortality, and/or major adverse CV events (MACE) in patients with CV diseases such as heart failure and coronary artery disease (CAD). However, the impact of sex on the prognostic value of galectin-3 in patients with suspected or known CAD remains unclear. Methods: Using data from a multicenter, prospective cohort of 2418 patients with suspected or known CAD, we assessed the impact of sex on the association between galectin-3 levels and the risks of all-cause death, CV death, and MACE defined as a composite of CV death, nonfetal myocardial infarction, and nonfetal stroke. Galectin-3 was measured in 1624 men and 794 women enrolled in the ANOX Study. Patients were followed up over 3 years. Results: The mean ages (standard deviations) were 69.8 (10.6) years in men and 72.2 (9.9) years in women ( P 〈 0.001). Men exhibited significantly lower levels of galectin-3 compared to women (median [interquartile range], 9.0 [6.9-11.9] versus 9.6 [7.3-12.4] ng/mL, respectively; P =0.004). In the entire patient cohort, the galectin-3 level was significantly associated with all-cause death (hazard ratio per 1 standard deviation increase [HR], 1.28; 95% confidence interval [CI] , 1.16-1.42), CV death (HR, 1.24; 95% CI, 1.04-1.46), and MACE (HR, 1.24; 95% CI, 1.09-1.41) after adjusting for potential clinical confounders. These associations were still significant in women (HR for all-cause death, 1.59; 95% CI, 1.26-1.98; HR for CV death, 1.53; 95% CI, 1.06-2.21; HR for MACE, 1.61; 95% CI, 1.21-2.09), whereas in men, galectin-3 was significantly associated with all-cause death (HR, 1.23; 95% CI, 1.08-1.39), but not with CV death (HR, 1.14; 95% CI, 0.93-1.40) or MACE (HR, 1.15; 95% CI, 0.99-1.35). Furthermore, galectin-3 provided incremental prognostic information for all-cause death, but not for CV death or MACE, to the model with potential clinical confounders and the established CV biomarkers in the entire cohort and in women, but not in men. Conclusions: We identified a significantly stronger prognostic value of galectin-3 in women than in men among patients with suspected or known CAD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13417
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 3
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    Distinct Characteristics of VEGF‐D and VEGF‐C to Predict Mortality in Patients With Suspected or Known Coronary Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of the American Heart Association Vol. 9, No. 9 ( 2020-05-05)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 9 ( 2020-05-05)
    Abstract: VEGF‐D (vascular endothelial growth factor D) and VEGF‐C are secreted glycoproteins that can induce lymphangiogenesis and angiogenesis. They exhibit structural homology but have differential receptor binding and regulatory mechanisms. We recently demonstrated that the serum VEGF‐C level is inversely and independently associated with all‐cause mortality in patients with suspected or known coronary artery disease. We investigated whether VEGF‐D had distinct relationships with mortality and cardiovascular events in those patients. Methods and Results We performed a multicenter, prospective cohort study of 2418 patients with suspected or known coronary artery disease undergoing elective coronary angiography. The serum level of VEGF‐D was measured. The primary outcome was all‐cause death. The secondary outcomes were cardiovascular death and major adverse cardiovascular events defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. During the 3‐year follow‐up, 254 patients died from any cause, 88 died from cardiovascular disease, and 165 developed major adverse cardiovascular events. After adjustment for possible clinical confounders, cardiovascular biomarkers (N‐terminal pro‐B‐type natriuretic peptide, cardiac troponin‐I, and high‐sensitivity C‐reactive protein), and VEGF‐C, the VEGF‐D level was significantly associated with all‐cause death and cardiovascular death but not with major adverse cardiovascular events.. Moreover, the addition of VEGF‐D, either alone or in combination with VEGF‐C, to the model with possible clinical confounders and cardiovascular biomarkers significantly improved the prediction of all‐cause death but not that of cardiovascular death or major adverse cardiovascular events. Consistent results were observed within patients over 75 years old. Conclusions In patients with suspected or known coronary artery disease undergoing elective coronary angiography, an elevated VEGF‐D value seems to independently predict all‐cause mortality.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.119.015761
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 4
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    Abstract 13448: Impact of Diabetes on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating growth differentiation factor 15 (GDF-15) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether GDF-15 levels differ according to the diabetic status and whether DM modifies the relationship between GDF-15 and mortality in patients with stable CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between diabetic status and GDF-15 and the impact of DM on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 797 DM and 663 non-DM patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with DM exhibited significantly higher levels of GDF-15 compared to those without DM (median [interquartile range] , 1472 [1049-2258] vs. 1274 [868-1874] pg/mL, respectively; P 〈 0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, DM, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P 〈 0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI] , 1.33-1.71). This association was still significant in patients with DM (HR, 1.52; 95% CI, 1.30-1.79) and in those without DM (HR, 1.57; 95% CI, 1.25-1.96). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with DM, but not in those without DM. Conclusions: Higher levels of GDF-15 were independently associated with DM in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with DM.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13448
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 5
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    Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Journal of the American Heart Association Vol. 9, No. 22 ( 2020-11-17)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 22 ( 2020-11-17)
    Abstract: Whether circulating growth differentiation factor 15 (GDF‐15) levels differ according to smoking status and whether smoking modifies the relationship between GDF‐15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF‐15 and the impact of smoking status on the association between GDF‐15 and all‐cause death. GDF‐15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF‐15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log‐transformed GDF‐15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF‐15 level was significantly associated with all‐cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF‐15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF‐15. The prognostic value of GDF‐15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.120.018217
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 6
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    Impact of Chronic Kidney Disease on the Associations of Cardiovascular Biomarkers With Adverse Outcomes in Patients With Suspected or Known Coronary Artery Disease: The EXCEED‐J Study
    Ovid Technologies (Wolters Kluwer Health) ; 2022
    In:  Journal of the American Heart Association Vol. 11, No. 3 ( 2022-02)
    Details
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 11, No. 3 ( 2022-02)
    Abstract: The impact of chronic kidney disease (CKD) on the prognostic utility of cardiovascular biomarkers in high‐risk patients remains unclear. Methods and Results We performed a multicenter, prospective cohort study of 3255 patients with suspected or known coronary artery disease (CAD) to investigate whether CKD modifies the prognostic utility of cardiovascular biomarkers. Serum levels of cardiovascular and renal biomarkers, including soluble fms‐like tyrosine kinase‐1 (sFlt‐1), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin‐I (hs‐cTnI), cystatin C, and placental growth factor, were measured in 1301 CKD and 1954 patients without CKD. The urine albumin to creatinine ratio (UACR) was measured in patients with CKD. The primary outcome was 3‐point MACE (3P‐MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all‐cause death, cardiovascular death, and 5P‐MACE defined as a composite of 3P‐MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. After adjustment for clinical confounders, sFlt‐1, NT‐proBNP, and hs‐cTnI, but not other biomarkers, were significantly associated with 3P‐MACE, all‐cause death, and cardiovascular death in the entire cohort and in patients without CKD. These associations were still significant in CKD only for NT‐proBNP and hs‐cTnI. NT‐proBNP and hs‐cTnI were also significantly associated with 5P‐MACE in CKD. The UACR was not significantly associated with any outcomes in CKD. NT‐proBNP and hs‐cTnI added incremental prognostic information for all outcomes to the model with potential clinical confounders in CKD. Conclusions NT‐proBNP and hs‐cTnI were the most powerful prognostic biomarkers in patients with suspected or known CAD and concomitant CKD.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    URL: Article
    DOI: 10.1161/JAHA.121.023464
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 7
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    Abstract 13423: Impact of Anemia on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: Growth differentiation factor 15 (GDF-15) is a stress responsive cytokine of the transforming growth factor superfamily. Circulating levels of GDF-15 are elevated in various conditions including anemia and stable coronary artery disease (CAD), and associated with the risk of mortality in patients with stable CAD. However, whether anemia modifies the relationship between GDF-15 and mortality in patients with stable CAD is unknown. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between anemic status and GDF-15 and the impact of anemia on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 564 anemic and 896 non-anemic patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with anemia exhibited significantly higher levels of GDF-15 compared to those without anemia (median [interquartile range] , 1953 [1302-3110] vs. 1175 [838-1579] pg/mL, respectively; P 〈 0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, diabetes, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P 〈 0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI] , 1.33-1.71). This association was still significant in patients with anemia (HR, 1.71; 95% CI, 1.44-2.05) and in those without anemia (HR, 1.44; 95% CI, 1.21-1.71). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with anemia, but not in those without anemia. Conclusions: Higher levels of GDF-15 were independently associated with anemia in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with anemia.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.13423
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 8
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    Abstract 10838: Impact of Diabetes on Soluble Fms-Like Tyrosine Kinase-1 and Cardiovascular Events in Patients with Suspected or Known Coronary Artery Disease: The EXCEED-J Study
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Circulation Vol. 144, No. Suppl_1 ( 2021-11-16)
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    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 144, No. Suppl_1 ( 2021-11-16)
    Abstract: Background: Whether diabetes mellitus (DM) modifies the relationship between soluble fms-like tyrosine kinase-1 (sFlt-1), a vascular endothelial growth factor (VEGF) antagonist, and cardiovascular (CV) events in patients with suspected or known coronary artery disease (CAD) are unclear. Methods: Using data from a multicenter, prospective cohort of 3255 patients with suspected or known CAD undergoing elective coronary angiography, we assessed the impact of DM on the prognostic values of sFlt-1 and other biomarkers. Heparin-free fasting serum levels of sFlt-1, VEGF, placental growth factor, cystatin C, N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), and high-sensitivity C-reactive protein (hs-CRP) were measured in 1281 DM and 1974 non-DM patients enrolled in the EXCEED-J study. The primary outcome was 3-point major adverse CV events (3P-MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, CV death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. Results: After adjusting for potential clinical confounders, serum levels of sFlt-1, NT-proBNP, hs-cTnI and cystatin C, but not other biomarkers, were significantly associated with 3P-MACE in the entire cohort. These associations were still significant for sFlt-1, NT-proBNP, and hs-cTnI, but not for cystatin C, in non-DM patients. In contrast, NT-proBNP, hs-cTnI and cystatin C, but not sFlt-1, were significantly associated with 3P-MACE in DM patients. The sFlt-1 level was also significantly associated with all-cause death and CV death in the entire cohort and in non-DM patients, but not in DM patients. It was not significantly associated with 5P-MACE in the entire cohort, non-DM patients, or DM patients. Furthermore, sFlt-1 provided an incremental prognostic information for 3P-MACE and CV death to the model with potential clinical confounders in non-DM patients, but not in DM patients. Conclusions: Serum levels of sFlt-1 were independently associated with 3P-MACE and CV death in patients with suspected or known CAD. These associations were attenuated in DM patients.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.144.suppl_1.10838
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
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  • 9
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    Abstract 14103: Impact of Chronic Kidney Disease on the Association of Cardiovascular and Renal Biomarkers With the Presence and Severity of Coronary Artery Disease in Patients With Suspected Coronary Artery Disease: The EXCEED-J Study
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 142, No. Suppl_3 ( 2020-11-17)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. Suppl_3 ( 2020-11-17)
    Abstract: Background: The impact of chronic kidney disease (CKD) on the association of cardiovascular (CV) and renal biomarkers with the presence and severity of coronary artery disease (CAD) in patients with suspected CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 2324 patients with suspected but no history of CAD undergoing elective coronary angiography, we assessed the impact of CKD on the association of CV and renal biomarkers with the presence and severity of CAD. Heparin-free fasting serum levels of soluble vascular endothelial growth factor (VEGF) receptor-1 (sFlt-1), VEGF, placental growth factor (PlGF), N-terminal pro-brain natriuretic peptide (NT-proBNP), contemporary sensitive cardiac troponin-I (cTnI), high-sensitivity CRP (hs-CRP), cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) were measured in 887 CKD and 1437 non-CKD patients enrolled in the EXCEED-J study. The severity of CAD was quantified using the Gensini score. Results: The mean age (standard deviation) of the patients was 69.8 (10.8) years; 65.6% were men. Serum levels of all biomarkers except PlGF were significantly higher in CKD than in non-CKD patients. In the entire patient cohort, only natural log-transformed (Ln-) cTnI was significantly associated with CAD, multi-vessel or left main trunk disease (MVD/LMTD), and Ln-Gensini score after adjustment for potential confounders. These associations were still significant in non-CKD, but not in CKD: Ln-cTnI was significantly associated with MVD/LMTD and Ln-Gensini score, but not with CAD. Stepwise regression analyses including potential confounders and all biomarkers revealed that Ln-cTnI was independently associated with CAD, MVD/LMTD, and Ln-Gensini score in the entire cohort and in non-CKD, but not in CKD: Ln-cTnI was independently associated with MVD/LMTD and Ln-Gensini score, but not with CAD. No other biomarker exhibited an independent association with CAD, MVD/LMTD, or Ln-Gensini score in the entire cohort, in non-CKD, or in CKD. Conclusions: Among CV and renal biomarkers measured in this study, only Ln-cTnI was independently associated with the presence and severity of CAD in patients with suspected CAD. These associations were attenuated in patients with CKD.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.142.suppl_3.14103
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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