P3765Low vascular endothelial growth factor-C was a predictor for cardiovascular events in patients with atrial fibrillation and suspected or known coronary artery disease: a subanalysis of the ANOX study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Iguchi ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
High Sensitivity ◽  
Cardiovascular Death ◽  
Vascular Endothelial ◽  
Median Level ◽  
History Of ◽  
Artery Disease ◽  
Factor C ◽  
Endothelial Growth Factor

Abstract Background Lymphatic system has been considered to play an important role in cardiovascular disease. We recently reported that vascular endothelial growth factor-C (VEGF-C), a central player in lymphangiogenesis, predicted all-cause mortality in patients with suspected or known coronary artery disease (CAD). However, relationship between VEGF-C and atrial fibrillation (AF) remains unclear. Methods The ANOX study is a multicenter, prospective cohort study of 2,418 patients with suspected CAD, to determine the predictive value of possible novel biomarkers related to angiogenesis or oxidative stress for major adverse cardiovascular events (MACE) among patients undergoing elective angiography. Blood samples were collected from the arterial catheter sheath at the beginning of coronary angiography. Serum levels of VEGF-C, as well as N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin-I (cTnI), and high-sensitivity C-reactive protein (hsCRP), were measured. The outcome was a MACE defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results Of a total of 2,418 patients, 261 patients had AF at baseline. AF group were older, and had more chronic kidney disease, history of heart failure, and history of stroke, but less diabetes, dyslipidemia, and CAD. The median level of NT-proBNP, cTnI, and hsCRP were higher in AF group [AF vs non-AF: NT-proBNP, 1048 pg/ml vs 162 pg/ml (p<0.0001); cTnI, 0.0003 ng/ml, vs 0.0 ng/ml (p<0.0001); hsCRP, 1.43 ug/ml vs 0.88 ug/ml (p=0.0005)], whereas median level of VEGF-C was lower in AF group [3107 pg/ml vs 3590 pg/ml (p<0.0001)]. AF was associated with lower VEGF-C and higher hsCRP after adjustment for potential confounders. During the 3-year follow-up, 29 (11.1%) patients in AF group and 136 (6.3%) patients in non-AF group developed MACE (p=0.007). Incidence of stroke was higher in AF group (17 (6.5%) vs 52 (2.4%); p<0.0009), despite that the incidence of cardiovascular death and myocardial infarction were similar between the groups. We divided the entire cohort into two groups based on the lowest quartile of VEGF-C or highest quartile of other biomarkers, lowest quartile of VEGF-C (log rank p=0.0004), as well as highest quartile of cTnI (log rank p=0.0009), were significantly associated with MACE in AF group. After adjustment for established risk factors and these biomarkers, both lowest quartile of VEGF-C (HR, 2.73; 95% CI, 1.27–6.06) and highest quartile of cTnI (HR, 2.54; 95% CI, 1.08–6.09) were significantly associated with MACE in AF group. Conclusions AF was associated with lower level of VEGF-C, and low VEGF-C as well as high cTnI might serve as an independent predictor of MACE in patients with AF and suspected or known CAD.

P3639Vascular endothelial growth factor-C and mortality in patients with suspected but no history of coronary heart disease: a subanalysis of the ANOX study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
T Unoki ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
All Cause Mortality ◽  
History Of ◽  
Factor C ◽  
Endothelial Growth Factor

Abstract Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular disease. Recently, we demonstrated that serum levels of vascular endothelial growth factor-C (VEGF-C), a central player of lymphangiogenesis, are inversely and independently associated with the risk of all-cause mortality in patients with suspected or known coronary heart disease (CHD). However, the prognostic value of VEGF-C in patients with suspected but no history of CHD is still unclear. Methods Serum VEGF-C levels were measured in 1,717 patients with suspected but no history of CHD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict cardiovascular events (ANOX) study, and followed up for 3 years. The primary outcome was all-cause death. The secondary outcomes were cardiovascular death, and major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 161 patients died from any cause, 50 died from cardiovascular disease, and 104 developed MACE. After adjustment for established risk factors, VEGF-C levels were significantly and inversely associated with all-cause death (hazard ratio [HR] for 1-SD increase, 0.69; 95% confidence interval [CI], 0.58–0.83) and cardiovascular death (HR, 0.72; 95% CI, 0.52–0.998), but not with MACE (HR, 0.91; 95% CI, 0.74–1.13). Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-C levels further improved the prediction of all-cause death (continuous net reclassification improvement [NRI], 0.282; 95% CI, 0.121–0.443; P<0.001; integrated discrimination improvement [IDI], 0.009; 95% CI, 0.003–0.016; P=0.005), but not that of cardiovascular death (NRI, 0.178; 95% CI, r=−0.103–0.458; P=0.214; IDI, 0.004; 95% CI, r=−0.002–0.009; P=0.194) or MACE (NRI, 0.037; 95% CI, r=−0.162–0.235; P=0.717; IDI, 0.000; 95% CI, r=−0.0004–0.0005; P=0.872). Conclusions In patients with suspected but no history of CHD undergoing elective coronary angiography, a low VEGF-C value may predict all-cause mortality independent of established risk factors and cardiovascular biomarkers. Acknowledgement/Funding The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization

scholarly journals Cardiovascular family history increases the risk of disease recurrence after a first myocardial infarction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Wahrenberg ◽  
P Magnusson ◽  
R Kuja-Halkola ◽  
H Habel ◽  
K Hambraeus ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Family History ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Funding Source ◽  
History Of ◽  
First Time ◽  
Early Family

Abstract Background Despite recent advances in secondary prevention, recurrent cardiovascular events are common after a myocardial infarction (MI). It has been reported that genetic risk scores may predict the risk of recurrent cardiovascular events. Although patient-derived family history is a composite of both genetic and environmental heritability of atherosclerotic cardiovascular disease (ASCVD), it is an easily accessible information compared to genetically based risk models but the association with recurrent events is unknown. Purpose To evaluate whether a register-verified family history of ASCVD is associated with recurrent cardiovascular events (rASCVD) in patients after a first-time MI. Methods We included patients with a first-time MI during 2005 – 2014, registered in the SWEDEHEART SEPHIA registry and without prior ASCVD. Follow-up was available until Dec 31st, 2018. Data on relatives, diagnoses and prescriptions were extracted from national registers. A family history of ASCVD was defined as a register-verified hospitalisation due to MI, angina with coronary revascularization procedures, stroke or cardiovascular death in any parent. Early history was defined as such an event before the age of 55 years in fathers and 65 years in mothers. The association between family history and a composite outcome including recurrent MI, angina requiring acute revascularization, ischaemic stroke and cardiovascular death during follow-up was studied with Cox proportional hazard regression with time from SEPHIA registry completion as underlying time-scale, adjusted for age with splines, gender and year of SEPHIA registry. Regression models were then further adjusted for hypertension, diabetes, smoking and for a subset of patients, LDL-cholesterol (LDL_C) at time of first event. Results Of 25,615 patients, 2.5% and 32.1% had an early and ever-occurring family history of ASCVD, respectively. Patients with early family history were significantly younger than other patients and were more likely to be current smokers and have a higher LDL-C (Median (IQR) 3.5 (1.1) vs 3.3 (1.1) mmol/L). In total, 3,971 (15.5%) patients experienced the outcome. Early family history of ASCVD was significantly associated with rASCVD (Hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.23–1.87), and the effect was sustained when adjusted for cardiovascular risk factors (HR 1.48, 95% CI 1.20–1.83) and LDL-C (HR 1.35, 95% CI 1.04–1.74). Ever-occurring family history was weakly associated with ASCVD (HR 1.09, 95% CI 1.02 – 1.17) and the association remained unchanged with adjustments for risk factors. Conclusions Early family history of cardiovascular disease is a potent risk factor for recurrent cardiovascular events in a secondary prevention setting, independent of traditional risk factors including LDL-C. This is a novel finding and these patients may potentially benefit from intensified secondary preventive measures after a first-time MI. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This work was funded by grants from The Swedish Heart and Lung Association

scholarly journals The Impact of Cytochrome P450 2C19 Polymorphism on Cardiovascular Events in Indonesian Patients with Coronary Artery Disease

2017 ◽  
pp. 18-24
Author(s):  
Muzakkir Amir ◽  
Mirnawati Mappiare ◽  
Paskalis Indra
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Platelet Aggregation ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cyp2c19 Genotype ◽  
Cyp2c19 Polymorphism ◽  
Cytochrome P450 2C19 ◽  
Artery Disease ◽  
The Impact

Background: The polymorphism of cytochrome P450 2C19 (CYP2C19) has been documented as the determinant variability in the antiplatelet effect of clopidogrel. The relation between CYP2C19 polymorphism and the antiplatelet efficacy of clopidogrel in Indonesian patients with coronary artery disease (CAD) is unknown. To address this issue, we examined the distribution of CYP2C19 genotypes and platelet aggregation, and assessed the impact of CYP2C19 polymorphism on response to clopidogrel and cardiovascular events. Methods: This observational analytic study with prospective cohort approach was conducted in Wahidin Sudirohusodo and Hasanuddin University Hospital, Makassar. We measured the CYP2C19 genotype by polymerase chain reaction-restriction fragment linked polymorphism (PCR-RFLP) method and platelet aggregation by optical platelet aggregometry with 10 μmol of adenosine diphosphate (ADP) in 69 patients with stable CAD who were treated with clopidogrel. Platelet hyperaggregation was defined as maximal platelet aggregation > 94.3%. The patients were followed up every month at the outpatient department for 6 months or at end point. The end point was acute myocardial infarction, ischemic stroke, or cardiovascular death. Results: Distribution of CYP2C19 alleles were 89.8%, 40.6%, and 11.6%, in CYP2C19*1, CYP2C19*2, and CYP2C19*3, respectively. Distribution of CYP2C19 genotype were 50.7%, 29.0%, 8.7%, 8.7%, and 2.9% in CYP2C19*1/*1, *1/*2, *1/*3, *2/*2, and *2/*3, respectively. Platelet hyper aggregation was more in patients with polymorphism than wild type (p 0.034; OR 3.707) and was associated with cardiovascular events (p 0.030; OR 13.250). There was acute myocardial infarction in 2 patients, ischemic stroke in 1 patient, and cardiovascular death in 1 patient. All of these patients were carrying at least one variant allele of CYP2C19; details of genotype were in two patients with CYP2C19*1/*2, one patient with *2/*2, and one with *2/*3 alleles. Conclusion: CYP2C19*2 and *3 were associated with cardiovascular events due to platelet hyper aggregation.

scholarly journals Impact of chronic kidney disease on the relationship between vascular endothelial growth factor C and mortality in patients with suspected coronary artery disease: a subanalysis of the ANOX study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Wada ◽  
D Takagi ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Funding Source ◽  
Vascular Endothelial ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Cv Disease ◽  
Factor C ◽  
Endothelial Growth Factor ◽  
The Relationship

Abstract Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular (CV) disease. Recently, we demonstrated that serum levels of vascular endothelial growth factor C (VEGF-C), a central player of lymphangiogenesis, are inversely and independently associated with the risk of all-cause mortality in patients with suspected or known coronary artery disease (CAD). However, the impact of chronic kidney disease (CKD) on the relationship between VEGF-C and mortality in patients with suspected CAD is unclear. Methods Serum VEGF-C levels were measured in 1,717 patients with suspected but no history of CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. Patients were divided into 2 groups according to the presence (CKD, n=674) or absence (non-CKD, n=1,043) of CKD. The primary outcome was all-cause death. The secondary outcomes were CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 95 CKD and 66 non-CKD patients died from any cause, 37 CKD and 13 non-CKD died from CV disease, and 61 CKD and 43 non-CKD developed MACE. After adjustment for established risk factors, VEGF-C levels were significantly and inversely associated with all-cause death (hazard ratio [HR] for 1-SD increase, 0.72; 95% confidence interval [CI], 0.57–0.90) and CV death (HR, 0.69; 95% CI, 0.48–0.97), but not with MACE (HR, 0.78; 95% CI, 0.60–1.03) in CKD, while VEGF-C levels were significantly and inversely associated with all-cause death (HR, 0.69; 95% CI, 0.52–0.91), but not with CV death (HR, 0.91; 95% CI, 0.50–1.66) or MACE (HR, 1.09; 95% CI, 0.81–1.44) in non-CKD. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-C levels further improved the prediction of all-cause death (P=0.047 for continuous net reclassification improvement [NRI], P=0.048 for integrated discrimination improvement [IDI]), but not that of CV death (P=0.016 for NRI, P=0.245 for IDI) or MACE (P=0.166 for NRI, P=0.311 for IDI) in CKD, whereas the addition of VEGF-C levels did not improve the prediction of all-cause death (P=0.053 for NRI, P=0.012 for IDI), CV death (P=0.864 for NRI, P=0.602 for IDI) or MACE (P=0.999 for NRI, P=0.154 for IDI) in non-CKD. Conclusions The VEGF-C level inversely and independently predicted all-cause mortality in CKD, but not in non-CKD patients with suspected CAD. The inverse relationship between VEGF-C and all-cause mortality in patients with suspected CAD seems to be remarkable in the presence of CKD. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

scholarly journals Use of sodium glucose cotransporter 2 inhibitors and risk of major cardiovascular events and heart failure: Scandinavian register based cohort study

BMJ ◽  
2019 ◽  
pp. l4772 ◽  
Author(s):  
Björn Pasternak ◽  
Peter Ueda ◽  
Björn Eliasson ◽  
Ann-Marie Svensson ◽  
Stefan Franzén ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Cardiovascular Events ◽  
Sglt2 Inhibitor ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Major Cardiovascular Events ◽  
Hazard Ratios ◽  
History Of

Abstract Objective To investigate the cardiovascular effectiveness of sodium glucose cotransporter 2 (SGLT2) inhibitors in routine clinical practice. Design Cohort study using data from nationwide registers and an active-comparator new-user design. Setting Denmark, Norway, and Sweden, from April 2013 to December 2016. Participants 20 983 new users of SGLT2 inhibitors and 20 983 new users of dipeptidyl peptidase 4 (DPP4) inhibitors, aged 35-84, matched by age, sex, history of major cardiovascular disease, and propensity score. Main outcome measures Primary outcomes were major cardiovascular events (composite of myocardial infarction, stroke, and cardiovascular death) and heart failure (hospital admission for heart failure or death due to heart failure). Secondary outcomes were the individual components of the cardiovascular composite and any cause death. In the primary analyses, patients were defined as exposed from treatment start throughout follow-up (analogous to intention to treat); additional analyses were conducted with an as-treated exposure definition. Cox regression was used to estimate hazard ratios. Results Mean age of the study cohort was 61 years, 60% were men, and 19% had a history of major cardiovascular disease. Of the total 27 416 person years of follow-up in the SGLT2 inhibitor group, 22 627 (83%) was among patients who initiated dapagliflozin, 4521 (16%) among those who initiated empagliflozin, and 268 (1%) among those who initiated canagliflozin. During follow-up, 467 SGLT2 inhibitor users (incidence rate 17.0 events per 1000 person years) and 662 DPP4 inhibitor users (18.0) had a major cardiovascular event, whereas 130 (4.7) and 265 (7.1) had a heart failure event, respectively. Hazard ratios were 0.94 (95% confidence interval 0.84 to 1.06) for major cardiovascular events and 0.66 (0.53 to 0.81) for heart failure. Hazard ratios were consistent among subgroups of patients with and without history of major cardiovascular disease and with and without history of heart failure. Hazard ratios for secondary outcomes, comparing SGLT2 inhibitors with DPP4 inhibitors, were 0.99 (0.85 to 1.17) for myocardial infarction, 0.94 (0.77 to 1.15) for stroke, 0.84 (0.65 to 1.08) for cardiovascular death, and 0.80 (0.69 to 0.92) for any cause death. In the as-treated analyses, hazard ratios were 0.84 (0.72 to 0.98) for major cardiovascular events, 0.55 (0.42 to 0.73) for heart failure, 0.93 (0.76 to 1.14) for myocardial infarction, 0.83 (0.64 to 1.07) for stroke, 0.67 (0.49 to 0.93) for cardiovascular death, and 0.75 (0.61 to 0.91) for any cause death. Conclusions In this large Scandinavian cohort, SGLT2 inhibitor use compared with DPP4 inhibitor use was associated with reduced risk of heart failure and any cause death, but not with major cardiovascular events in the primary intention-to-treat analysis. In the additional as-treated analyses, the magnitude of the association with heart failure and any cause death became larger, and a reduced risk of major cardiovascular events that was largely driven by the cardiovascular death component was observed. These data help inform patients, practitioners, and authorities regarding the cardiovascular effectiveness of SGLT2 inhibitors in routine clinical practice.

Cardiac outcomes of raltitrexed in the treatment of colorectal cancer patients with 5-fluorouracil (5-FU) cardiotoxicity.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14607-e14607
Author(s):  
Aryan Firouzbakht ◽  
Daniel John Renouf ◽  
Leo Chen ◽  
Winson Y. Cheung
Keyword(s):  
Colorectal Cancer ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Cancer Patients ◽  
Cardiovascular Events ◽  
Regression Analyses ◽  
History Of ◽  
Artery Disease ◽  
Colorectal Cancer Patients

e14607 Background: Both 5-FU and raltitrexed are thymidylate synthase inhibitors, but the latter has a toxicity profile that is distinct from 5-FU. Therefore, it is commonly used as an alternative to 5-FU in the treatment of colorectal cancer patients who have a history of cardiac problems or prior 5-FU cardiotoxicity. To date, the population-based risk of cardiac effects from raltitrexed is uncertain. Our aim was to characterize the patterns of treatment and outcomes of patients receiving raltitrexed-based chemotherapy. Methods: We conducted a retrospective study of all patients diagnosed with colorectal cancer from 1988 to 2012, evaluated at 1 of 5 regional cancer centers in British Columbia, Canada and treated with raltitrexed at any point during their disease. At the institutions in our province, raltitrexed use is limited to those in whom 5-FU is contraindicated. Using chi-squared tests and logistic regression analyses, we evaluated the associations between use of raltitrexed and various cardiovascular events, such as angina, myocardial infarction, hypertension and arrhythmias, as well as other toxicity outcomes, including nausea, vomiting and diarrhea. Results: A total of 186 patients were included: median age was 63 years (IQR 55-70), 97 (52%) were men, and 21 (11%) experienced at least one cardiovascular outcome. Only 4 (2%) patients had a documented cardiac history prior to receipt of any systemic therapy. Among the 21 cases of cardiovascular events, 10 reported angina, 1 suffered a myocardial infarction, 6 had hypertension, and 6 experienced arrhythmias. A significant number of patients also presented with other general toxicities: 25 (13%) reported fever, 11 (6%) suffered mucositis, 75 (40%) had nausea, and 51 (27%) experienced diarrhea. On regression analyses, patients with a previous history of coronary artery disease had a higher risk of cardiovascular events than those without (50 vs 11%, p=0.01). Exposure to 5-FU before raltitrexed did not increase cardiovascular outcomes (p=0.81). Conclusions: Raltitrexed is associated with a low risk of cardiovascular events, but its use should be monitored closely in those with prior coronary artery disease.

scholarly journals Vorapaxar in the treatment of cardiovascular diseases

2020 ◽  
Vol 16 (5) ◽  
pp. 373-384
Author(s):  
Udaya S Tantry ◽  
Kevin P Bliden ◽  
Rahul Chaudhary ◽  
Marko Novakovic ◽  
Amit Rout ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Peripheral Artery Disease ◽  
Coronary Revascularization ◽  
Bleeding Risk ◽  
Cardiovascular Death ◽  
Severe Bleeding ◽  
Peripheral Artery ◽  
Primary Hemostasis ◽  
History Of ◽  
Artery Disease

Vorapaxar specifically and effectively inhibits protease activated receptor-1 and may reduce thrombin-mediated ischemic events without interfering primary hemostasis. In the TRA-2P-TIMI 50 trial, vorapaxar reduced the risk of primary ischemic outcome but with increased bleeding risk. In the post hoc analysis, in patients with a history of myocardial infarction, peripheral artery disease, the net clinical outcome favored vorapaxar therapy with 10% reduction in cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization and moderate or severe bleeding. Based on these favorable results, vorapaxar was approved for the reduction of thrombotic cardiovascular events in patients with prior myocardial infarction or with peripheral artery disease on top of standard antiplatelet therapy. A careful patient selection is needed to balance efficacy versus safety.

Impact of anemia on the relationship between vascular endothelial growth factor C and mortality in patients with suspected or known coronary artery disease: a subanalysis of the ANOX study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Iguchi ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Vascular Endothelial Growth Factor ◽  
Funding Source ◽  
Vascular Endothelial ◽  
Artery Disease ◽  
Cv Disease ◽  
Factor C ◽  
Endothelial Growth Factor ◽  
The Relationship

Abstract Background The lymphatic system has been suggested to play an important role in cholesterol metabolism and cardiovascular (CV) disease. Recently, we demonstrated that serum levels of vascular endothelial growth factor C (VEGF-C), a central player of lymphangiogenesis, are inversely and independently associated with the risk of all-cause mortality in patients with suspected or known coronary artery disease (CAD). However, the impact of anemia on the relationship between VEGF-C and mortality in those patients is unclear. Methods Serum VEGF-C levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. Anemia was defined as a hemoglobin level of less than 13 g/dL in men and &lt;12 g/dL in women. Patients were divided into 2 groups according to the presence (anemic, n=882) or absence (non-anemic, n=1,536) of anemia. The primary outcome was all-cause death. The secondary outcomes were CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 164 anemic and 90 non-anemic patients died from any cause, 64 anemic and 24 non-anemic patients died from CV disease, and 96 anemic and 69 non-anemic patients developed MACE. After adjustment for established risk factors, VEGF-C levels were significantly and inversely associated with all-cause death (hazard ratio [HR] for 1-SD increase, 0.71; 95% confidence interval [CI], 0.59–0.84), CV death (HR, 0.60; 95% CI, 0.44–0.79), and MACE (HR, 0.76; 95% CI, 0.60–0.95) in anemic, while VEGF-C levels were not significantly associated with all-cause death (HR, 0.87; 95% CI, 0.69–1.11), CV death (HR, 1.32; 95% CI, 0.85–1.93), or MACE (HR, 1.12; 95% CI, 0.87–1.42) in non-anemic patients. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of VEGF-C levels further improved the prediction of all-cause death (P&lt;0.001 for continuous net reclassification improvement [NRI], P=0.006 for integrated discrimination improvement [IDI]) and CV death (P&lt;0.001 for NRI, P=0.005 for IDI), but not that of MACE (P=0.021 for NRI, P=0.059 for IDI) in anemic, whereas the addition of VEGF-C levels did not improved the prediction of all-cause death (P=0.234 for NRI, P=0.415 for IDI), CV death (P=0.190 for NRI, P=0.392 for IDI) or MACE (P=0.897 for NRI, P=0.128 for IDI) in non-anemic patients. Conclusions The VEGF-C level was inversely and independently associated with all-cause and CV mortality in anemic, but not in non-anemic patients with suspected or known CAD. The inverse relationship between VEGF-C and mortality may depend on the presence of anemia. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

Abstract 12898: Serum Vascular Endothelial Growth Factor-C Levels are Inversely Associated With Major Adverse Cardiovascular Events in Patients With Arteriosclerotic Obliterans

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Nobutoyo Masunaga ◽  
Hiromichi Wada ◽  
Masaharu Akao ◽  
Shuichi Ura ◽  
Akira Yamada ◽  
...  
Keyword(s):  
Risk Factors ◽  
Vascular Endothelial Growth Factor ◽  
Cardiovascular Events ◽  
Serum Levels ◽  
Vascular Endothelial ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Factor C ◽  
Endothelial Growth Factor

Background: Vascular endothelial growth factor-C (VEGF-C), a homologue of VEGF family, plays a key role in lymphangiogenesis. Recently, we demonstrated that VEGF-C is closely associated with dyslipidemia and atherosclerosis. However, the relationship between serum VEGF-C levels and cardiovascular events in patients with atherosclerotic disease is unknown. Methods and Results: We performed a prospective cohort study involving a total of 209 patients with arteriosclerotic obliterans (ASO) (age, 73±8 y [SD]; male, 75%; hypertension, 88%; diabetes, 69%; dyslipidemia, 72%; history of smoking, 76%; Fontaine class, 2.1±0.8). Serum levels of VEGF-C, VEGF-A and high-sensitivity C-reactive protein (hsCRP) were determined employing specific enzyme-linked immunosorbent assays. The primary outcome was major adverse cardiac events (MACEs) defined as all-cause mortality, hospitalization due to acute coronary syndrome, stroke, congestive heart failure, aortic disease, and coronary/peripheral revascularization. Patients were followed up over a 4 year period. The median follow-up was 484 (IQR, 220-955) days. During the follow-up period, MACEs developed in a total of 86 patients (41.1 %). Patients were divided into two groups based on the median of each biomarker. In Kaplan-Meier analyses, low-VEGF-C (P=0.014, by log-rank test), but not high-hsCRP or high-VEGF-A, was significantly associated with MACEs. Multivariate Cox proportional hazard analyses revealed that serum levels of VEGF-C (hazard ratio [HR], 0.79 [per 1-SD increase]; 95% confidence interval [CI], 0.63-0.99; P=0.04), but not hsCRP or VEGF-A, were inversely and significantly associated with MACEs after adjustment for age, gender, and established risk factors. Finally, we performed stepwise Cox proportional hazard analysis including data on age, gender, established risk factors, Fontaine class and serum levels of hsCRP, VEGF-A and VEGF-C. Notably, Fontaine class (HR, 1.4; 95% CI, 1.1-1.8; P=0.002) and the VEGF-C level (HR [per 1-SD increase], 0.80; 95% CI, 0.64-0.99; P=0.045), but not other parameters, were independent predictors of MACEs. Conclusions: A low VEGF-C value may serve as a predictive marker of cardiovascular events in patients with ASO.

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