Prognostic value of suppression of tumorigenesis-2 (ST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus

Abstract Background: Suppression of tumorigenesis-2 (ST2) is implicated in myocardial overload and has long been recognized as an inflammation marker related to heart failure and acute coronary syndromes, but data on the prognostic value of ST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of ST2 in patients with established coronary artery disease and its predictive value in CAD patients with or without type 2 diabetes mellitus (T2DM).Methods: A total of 3641 consecutive patients were included in this prospective cohort study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The association between ST2 and outcomes was investigated using multivariable Cox regression.Results: During a median follow-up of 6.4 years, 775 patients had the occurrence of MACEs and 275 patients died. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p<0.001). Multiple Cox regression models showed that higher level of ST2 was an independent predictor for MACEs developments (HR=1.36, 95% CI 1.17-1.56, p<0.001) and all-cause death (HR=2.01, 95% CI 1.56-2.59, p<0.001). The addition of ST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-statistic, net reclassification index, and integrated discrimination improvement, all p<0.05). Subgroup analyses showed that ST2 remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models.Conclusions: A higher level of ST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. ST2 may provide incremental prognostic value beyond traditional risk factors.

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Prognostic value of soluble suppression of tumorigenesis-2 (sST2) for cardiovascular events in coronary artery disease patients with and without diabetes mellitus

Cardiovascular Diabetology ◽

10.1186/s12933-021-01244-3 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Man Li ◽

Lei Duan ◽

Yulun Cai ◽

Benchuan Hao ◽

Jianqiao Chen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Predictive Value ◽

Cardiovascular Events ◽

Prognostic Value ◽

Cox Regression ◽

Coronary Syndrome ◽

End Point ◽

Artery Disease

Abstract Background Soluble suppression of tumorigenesis-2 (sST2) is implicated in myocardial overload and has long been recognized as an inflammatory marker related to heart failure and acute coronary syndrome, but data on the prognostic value of sST2 in patients with coronary artery disease (CAD) remain limited. This study sought to investigate the prognostic value of sST2 in patients with established CAD and its predictive value in CAD patients with and without type 2 diabetes mellitus (T2DM). Methods A total of 3641 consecutive patients were included in this prospective cohort study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. The association between sST2 and outcomes was investigated using multivariable Cox regression. Results During a median follow-up of 6.4 years, MACEs occurred in 775 patients, and 275 patients died. Multiple Cox regression models showed that a higher level of sST2 was an independent predictor of MACEs development (HR = 1.36, 95% CI 1.17–1.56, p < 0.001) and all-cause death (HR = 2.01, 95% CI 1.56–2.59, p < 0.001). The addition of sST2 to established risk factors significantly improved risk prediction of the composite outcome of MACEs and all-cause death (C-index, net reclassification index, and integrated discrimination improvement, all p < 0.05). In subgroup analysis depending on diabetes status, the diabetes group had a significantly higher level of sST2, which remained a significant predictor of MACEs and all-cause death in patients with and without T2DM in multivariable models. The area under the curve (AUC) of CAD patients with diabetes mellitus was significantly higher than that of those without T2DM. For MACEs, the AUC was 0.737 (patients with T2DM) vs 0.620 (patients without T2DM). For all-cause death, the AUC was 0.923 (patients with T2DM) vs 0.789 (patients without T2DM). Conclusions A higher level of sST2 is significantly associated with long-term MACEs and all-cause death in CAD patients with and without T2DM. sST2 has strong predictive value for cardiovascular adverse events in CAD patients with T2DM, and these results provide new evidence for the role of sST2.

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Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up

10.21203/rs.3.rs-63605/v1 ◽

2020 ◽

Author(s):

Man Li ◽

Lei Duan ◽

Yulun Cai ◽

Benchuan Hao ◽

Jianqiao Chen ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Prognostic Value ◽

Cox Regression ◽

Major Adverse Cardiovascular Events ◽

Kaplan Meier ◽

Increased Risk ◽

Artery Disease

Abstract Background: Suppression of tumorigenesis-2 is implicated in the myocardial overload and it was long been recognized as an inflammation marker related to heart failure and acute coronary syndromes, but the data on prognostic value of suppression of tumorigenesis-2 on patients with coronary artery disease remains limited. The study ought to investigate the prognostic value of suppression of tumorigenesis-2 in patients with established coronary artery disease.Methods: In this prospective cohort study, a total of 3641 consecutive patients were included. The primary end point was major adverse cardiovascular events. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). The secondary end point was all-cause death. The association between suppression of tumorigenesis-2 and outcomes was investigated using multivariable COX regression.Results: During a median follow up of 6.4 years, there were 775 patients had the occurrence of major adverse cardiovascular events and 275 patients died. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). Multiple COX regression models showed that higher level of suppression of tumorigenesis-2 was an independent predictor in developing major adverse cardiovascular events (HR=1.36, 95% CI 1.17-1.56, p＜0.001) and all-cause death (HR=2.01, 95%CI 1.56-2.59, p＜0.001). The addition of suppression of tumorigenesis-2 to established risk factors significantly improved risk prediction of the composite outcome of major adverse cardiovascular events and all-cause death (c-statistic, net reclassification index, and integrated discrimination improvement, all p＜0.05).Conclusions: Higher level of suppression of tumorigenesis-2 is significantly associated with long-term all-cause death and major adverse cardiovascular events. Suppression of tumorigenesis-2 may provide incremental prognostic value beyond traditional risk factors.

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Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up

10.21203/rs.3.rs-36063/v1 ◽

2020 ◽

Author(s):

Man Li ◽

Hongbin Liu ◽

Lei Duan ◽

Yulun Cai ◽

Benchuan Hao ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Prognostic Value ◽

Cox Regression ◽

Coronary Syndrome ◽

End Point ◽

Increased Risk ◽

Artery Disease

Abstract PurposeST2 has been proved the prognostic value in acute coronary syndrome (ACS), its prognostic value to predict cardiac events in established coronary artery disease (CAD) patients is unknown. The study ought to investigate the prognostic value of ST2 in patients with established coronary artery disease.MethodsA total of 3650 consecutive patients were included in the study. The primary end point was major adverse cardiovascular events (MACEs). The secondary end point was all-cause death. To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models.ResultsDuring a median follow up of 6.4 years, there were 775 patients had the occurrence of MACEs and 275 patients died. Kaplan–Meier survival estimates indicated that the patients with higher level of ST2 (ST2 > 19 ng/ml) had a significantly increased risk of MACEs (log-rank p<0.001)and all-cause death(log-rank p<0.001). After adjustment for potential confounders, multiple COX regression models showed that higher level of ST2 was an independent predictor in developing MACEs(HR 1.31; 95% CI: 1.13–1.52; p<0.001) and all-cause death(HR 1.78; 95% CI: 1.38–2.30; p<0.001). We saw a significant increase of AUC in ROC curve after addition of GDF-15 to a clinical model 0.586 vs 0.619 For MACEs (p<0.001).For long-term all-cause death the increase of AUC 0.766 vs 0.642 (95% CI 0.787–0.846(p<0.001).ConclusionHigher level of ST2 is significantly associated with long-term all-cause death, MACEs and provides incremental prognostic value beyond traditional risks factors.

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Abstract P85: Are Myocardial Bridges Associated With Increased Risk of Death or Myocardial Infarction?

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_1.ap85 ◽

2011 ◽

Vol 4 (suppl_1) ◽

Author(s):

Mouaz H Al-Mallah ◽

Kamal Kassem ◽

Owais Khawaja ◽

Thomas Song ◽

Chad Poopat ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Prognostic Value ◽

Cox Regression ◽

Study Cohort ◽

Risk Of Death ◽

Increased Risk ◽

Artery Disease

Background: Myocardial bridging (MB) is frequently seen on coronary CT angiography (CCTA). However, there has been conflicting data on the prognostic value of MB. The aim of this analysis is to determine the prognostic value of MB in patients without obstructive coronary artery disease (CAD) (<50 diameter stenosis). Methods: We included patients with no known prior coronary artery disease (CAD) who underwent CCTA for various clincial reasons. Patients with obstructive CAD on CCTA were excluded. The study cohort was followed for all cause mortality or myocardial infarction (MI) (median follow-up 1.7 years). Group comparisons were made between patients with patients with or without MB. Results: A total of 715 patients were included in this analysis of which 68 patients had MB (10%). 73% of the bridges were in the mid LAD and 22% had bridging in the distal LAD. 48% of the study cohort had normal coronaries, while 52% had evidence of non obstructive CAD. There were no differences in the baseline characteristics, symptomatic status or prevalence of non obstructive CAD between the two groups (all p>0.5). After a median follow-up duration of 1.7 years, 23 patients died and 10 patients experienced myocardial infarction. There were no statistically significant differences in the rate of death/MI between the two groups (figure). Using multivariable Cox regression, the presence of MB was not associated with increased risk for death/MI (Adjusted HR 0.4, 95% confidence interval 0.1 -2.8, p=0.34) Conclusions: In patients with non-obstructive CAD, MB is not associated with increased risk for all cause death or MI.

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Study of effect of diabetes mellitus on classical risk factors for coronary artery disease

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20205318 ◽

2020 ◽

Vol 8 (12) ◽

pp. 4426

Author(s):

Suchitra Garhwal ◽

Anil Kumar Poonia ◽

Veeha Agarwal

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Increased Risk ◽

Classical Risk Factor ◽

Group 2 ◽

Study Association ◽

Artery Disease ◽

Relative Prevalence

Background: Diabetes mellitus (DM) is increasingly prevalent in general population and is associated with increased risk for coronary artery disease (CAD). DM both directly and indirectly increases risk of CAD. Quantum of DM associated increase in classical risk factor for CAD is not exactly described. In present study, association of traditional risk for CAD and DM was analyzed.Methods: Total 150 patients with CAD were enrolled and divided into two group: group 1 with DM (84 patients) and group 2 without DM (66 patients). These two were compared and analyzed for classical risk factors for DM.Results: CAD with DM group had higher prevalence for traditional risk for CAD than CAD alone group: for Hypertension relative prevalence was 67.8 and 36.3% respectively (p<0.05); for Obesity it was 79.7 and 40.9% respectively (p<0.05) and for Dyslipidemia relative prevalence was 75 and 37.8% respectively (p<0.05).Conclusions: DM is major risk for CAD and it is also associated with increased prevalence for hypertension, obesity and dyslipidemia in affected population.

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Abstract 13337: Increased Serum Immunoglobulin G4 Level is a Novel Predictor of Cardiovascular Events Independent of Established Risk Factors: Results From the Real-cad Study

Circulation ◽

10.1161/circ.142.suppl_3.13337 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Aiko Sakamoto ◽

Kenichi Aizawa ◽

Kohei Uemura ◽

Issei Komuro ◽

Yutaka Matsuyama ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Density Lipoprotein ◽

High Dose ◽

Immunoglobulin G4 ◽

End Point ◽

Serum Igg4 ◽

Artery Disease

Background: Inflammation is a mediator of atherosclerosis progression. However, it remains unclear whether immunoglobulin G4 (IgG4)-related immuno-inflammation may play a specific role in cardiovascular disease. Methods: We used a case-cohort design to analyze the association of serum IgG4 levels with future cardiovascular events. The sample included 561 cases of the primary end point, defined as cardiovascular death, myocardial infarction, ischemic stroke, or unstable angina, and a random subcohort of 1688 (1409 males; mean age, 68.1 ± 8.4 years), of whom 73 were also cases, selected from 12413 eligible participants with stable coronary artery disease in the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. Results: This case-cohort study had a median follow-up of 3.9 years (interquartile range [IR] 2.9-4.6). Serum IgG4 levels at baseline were 45.3 mg/dL (IR 37.9-58.9), and 845 (50%) took high-dose statins in the subcohort sample. In Cox regression using age, gender, statin dose, high-sensitivity C-reactive protein (hsCRP), body mass index, estimated glomerular filtration rate (eGFR), hypertension, diabetes, and serum lipid profiles, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides, as covariates, the highest IgG4 quartile was predictive of the primary end point at 4 years (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.03-2.00, P=0.031), compared with the lowest quartile. Similar results were observed for the secondary end point, a composite of the primary end point plus coronary revascularization (HR 1.60, 95% CI 1.16-2.20, P=0.004). Conclusions: Elevated serum IgG4 level at baseline predicted long-term cardiovascular outcomes independent of established risk factors and high-dose statin therapy in patients with stable CAD. Serum IgG4 may reflect residual cardiovascular risk.

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Antithrombotic Therapy for Atherosclerotic Cardiovascular Disease Risk Mitigation in Patients With Coronary Artery Disease and Diabetes Mellitus

Circulation ◽

10.1161/circulationaha.120.045465 ◽

2020 ◽

Vol 142 (22) ◽

pp. 2172-2188

Author(s):

Davide Capodanno ◽

Dominick J. Angiolillo

Keyword(s):

Diabetes Mellitus ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Secondary Prevention ◽

Antiplatelet Therapy ◽

Antithrombotic Therapy ◽

Cardiovascular Events ◽

Thrombotic Risk ◽

Increased Risk ◽

Artery Disease

Patients with diabetes mellitus (DM) are characterized by enhanced thrombotic risk attributed to multiple mechanisms including hyperreactive platelets, hypercoagulable status, and endothelial dysfunction. As such, they are more prone to atherosclerotic cardiovascular events than patients without DM, both before and after coronary artery disease (CAD) is established. In patients with DM without established CAD, primary prevention with aspirin is not routinely advocated because of its increased risk of major bleeding that largely offsets its ischemic benefit. In patients with DM with established CAD, secondary prevention with antiplatelet drugs is an asset of pharmacological strategies aimed at reducing the risk of atherosclerotic cardiovascular events and their adverse prognostic consequences. Such antithrombotic strategies include single antiplatelet therapy (eg, with aspirin or a P2Y 12 inhibitor), dual antiplatelet therapy (eg, aspirin combined with a P2Y 12 inhibitor), and dual-pathway inhibition (eg, aspirin combined with the vascular dose of the direct oral anticoagulant rivaroxaban) for patients with chronic ischemic heart disease, acute coronary syndromes, and those undergoing percutaneous coronary intervention. Because of their increased risk of thrombotic complications, patients with DM commonly achieve enhanced absolute benefit from more potent antithrombotic approaches compared with those without DM, which most often occurs at the expense of increased bleeding. Nevertheless, studies have shown that when excluding individuals at high risk for bleeding, the net clinical benefit favors the use of intensified long-term antithrombotic therapy in patients with DM and CAD. Several studies are ongoing to establish the role of novel antithrombotic strategies and drug formulations in maximizing the net benefit of antithrombotic therapy for patients with DM. The scope of this review article is to provide an overview of current and evolving antithrombotic strategies for primary and secondary prevention of atherosclerotic cardiovascular events in patients with CAD and DM.

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Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-020-01192-4 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Keishi Ichikawa ◽

Toru Miyoshi ◽

Kazuhiro Osawa ◽

Takashi Miki ◽

Hironobu Toda ◽

...

Keyword(s):

Diabetes Mellitus ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Fatty Liver Disease ◽

Cardiovascular Events ◽

Prognostic Value ◽

Suspected Coronary Artery Disease ◽

Alcoholic Fatty Liver ◽

Artery Disease ◽

Alcoholic Fatty Liver Disease

Abstract Background Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. Methods This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. Results Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82–10.44, p < 0.001; 1.56, 1.32–1.86, p < 0.001; 1.23, 1.08–1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). Conclusions NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

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