scholarly journals High-Serum Angiopoietin-Like Protein 3 Levels Associated with Cardiovascular Outcome in Patients with Coronary Artery Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Ming-Chun Chen ◽  
Bang-Gee Hsu ◽  
Chung-Jen Lee ◽  
Ji-Hung Wang

Background. Angiopoietin-like protein 3 (ANGPTL3) plays a pivotal role in lipid metabolism and angiogenesis, and there is growing interest regarding the association between ANGPTL3 and coronary artery disease (CAD). This study aims to investigate whether ANGPTL3 levels can be used to predict the future occurrence of major adverse cardiovascular events (MACEs) in patients with CAD. Methods. Overall, 90 patients with CAD were enrolled between January and December 2012. The study’s primary endpoint was incidence of MACEs. Patient follow-up was completed on June 30, 2017. Results. Following a median follow-up period of 54 months, 33 MACEs had occurred. Patients reporting MACEs had lower statin use (P=0.022) and higher serum C-reactive protein (P<0.001) and serum ANGPTL3 (P<0.001) levels than those without MACEs. Kaplan–Meier analysis revealed higher cumulative incidence of CV events in the high ANGPTL3 group (median ANGPTL3 level ≥ 222.37 ng/mL) than in the low ANGPTL3 group (log-rank P=0.046). Multivariable Cox regression analysis demonstrated that ANGPTL3 levels were independently associated with MACEs in patients with CAD (hazard ratio: 1.003; 95% confidence interval: 1.000–1.005; P=0.026) after adjusted for age, gender, and body mass index, classical risk factors, and potential confounders. Conclusions. Serum ANGPTL3 levels could serve as a biomarker for future occurrence of MACEs in patients with CAD.

2016 ◽  
Vol 48 (11) ◽  
pp. 810-815 ◽  
Author(s):  
A. Pereira ◽  
R. Palma dos Reis ◽  
R. Rodrigues ◽  
A. C. Sousa ◽  
S. Gomes ◽  
...  

Recent genetic studies have revealed an association between polymorphisms at the ADAMTS7 gene locus and coronary artery disease (CAD) risk. Functional studies have shown that a CAD-associated polymorphism (rs3825807) affects ADAMTS7 maturation and vascular smooth muscular cell (VSMC) migration. Here, we tested whether ADAMTS7 (A/G) SNP is associated with cardiovascular (CV) survival in patients with established CAD. A cohort of 1,128 patients with angiographic proven CAD, who were followed up prospectively for a mean follow-up period of 63 (range 6–182) mo, were genotyped for rs3825807 A/G. Survival statistics (Cox regression) compared heterozygous (AG) and wild-type (AA) with the reference homozygous GG. Kaplan-Meier (K-M) survival curves were performed according to ADAMTS7 genotypes for CV mortality. Results showed that 47.3% of patients were heterozygous (AG), 36.5% were homozygous for the wild-type allele (AA) and only 16.2% were homozygous for the GG genotype. During the follow-up period, 109 (9.7%) patients died, 77 (6.8%) of CV causes. Survival analysis showed that AA genotype was an independent risk factor for CV mortality compared with reference genotype GG (HR = 2.7, P = 0.025). At the end of follow-up, the estimated survival probability (K-M) was 89.8% for GG genotype, 82.2% for AG and 72.3% for AA genotype ( P = 0.039). Carriage of the mutant G allele of the ADAMTS7 gene was associated with improved CV survival in patients with documented CAD. The native overfunctional ADAMTS7 allele (A) may accelerate VSMC migration and lead to neointimal thickening, atherosclerosis progression and acute plaque events. ADAMTS7 gene should be further explored in CAD for risk prediction, mechanistic and therapeutic goals.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Temtem ◽  
M Serrao ◽  
A Pereira ◽  
M Santos ◽  
F Mendonca ◽  
...  

Abstract Background TCF21 gene, encodes a basic-helix- loop- helix transcription factor, playing a critical action in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Recent data suggest that TCF21 may play a role in the state of differentiation of SMC precursor cells that migrate to vascular lesions and contribute to fibrous cap. Purpose Investigate the association of TCF21 rs12190287G&gt;C variant with coronary artery disease (CAD) in a Portuguese population and its role on the prognosis. Methods Case-control study with 3120 participants, 1687 coronary patients with at least 75% obstruction of a major coronary artery and 1433 controls. Genotyping used the TaqMan technique (Applied Biosystems) and then a univariate and multivariate logistic regression analysis were performed. After a mean follow-up of 5.01±4.2 years (interquartile range 1.96–7.57), the occurrence of the combined Major Adverse Cardiovascular Events (MACE) (Cardiovascular Mortality, non-fatal Myocardial Infarction, new Revascularization, Cerebrovascular Disease and Peripheric Vascular Disease) were registered and analysed by Cox regression. Finally, Kaplan-Meier survival estimate was performed. Results In the total population, GC+CC genotype was found to be associated with CAD with an OR of 1.285; CI: 1.022–1.614; p=0.031. After multivariate logistic regression, adjusted to traditional risk factors, the association with CAD remained significant for this genotype (OR=1.340; CI: 1.042–1.723; p=0.022).After Cox regression adjusted for confounding variables (age and sex, hypertension, diabetes, smoking, dyslipidemia, eGFR, Ejection fraction &lt;55) the mutated genotype remained a significant predictor of MACE (HR=1.420; CI: 1.032–1.953; p=0.031). The individuals carrying the mutated allele (GC+CC) at the mean follow-up showed an event probability of 36.1%, whereas the wild population (GG) presented only 23.4%. The Log-Rank test showed significant differences between the two curves (p=0.019). Conclusion The mutated TCF21 variant can provide a new marker to identify patients at high cardiovascular risk and may representa potential target for gene therapy in future. Figure 1 Funding Acknowledgement Type of funding source: None


2020 ◽  
Author(s):  
Man Li ◽  
Lei Duan ◽  
Yulun Cai ◽  
Benchuan Hao ◽  
Jianqiao Chen ◽  
...  

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.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
B Wang ◽  
J Liu ◽  
S Q Chen ◽  
Q H Luo ◽  
Y Liu ◽  
...  

Abstract Background Lower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. There are currently no studies examining the association of low baseline LDL-C concentration (&lt;1.8 mmol/L) with mortality among patients with CAD and advanced kidney disease (AKD). We aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients. Methods In this observational study, 803 CAD patients complicated with AKD (eGFR &lt;30 mL/min/1.73 m 2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C &lt;1.8 mmol/L, n=138; LDL-C ≥1.8 mmol/L, n=665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality. Results Among 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan–Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (&lt;1.8mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01–1.89). Conclusions Our data demonstrated that among patients with CAD and AKD, a lower baseline LDLC level (&lt;1.8mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This study was supported by the National Natural Science Foundation of China (Grant No. 81670339 and Grant No. 81970311), Cardiovascular Research Foundation Project of the Chinese Medical Doctor Association (SCRFCMDA201216) and Beijing Lisheng Cardiovascular Health Foundation (LHJJ20141751).


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Hendricks ◽  
I Dykun ◽  
B Balcer ◽  
F Al-Rashid ◽  
P Luedike ◽  
...  

Abstract Background Natriuretic peptides (BNP/NT-proBNP) are routinely used for the diagnosis of heart failure and predicts outcome in patients with both heart failure with preserved and reduced ejection fraction. In addition, natriuretic peptides are associated with incident cardiovascular disease manifestation in primary prevention cohorts. Whether the assessment of BNP/NT-proBNP is of value in patients with coronary artery disease but without heart failure has not been investigated in detail. We here evaluate the association of BNP/NT-pro BNP with mortality patients with coronary artery disease but without known chronic heart failure. Methods The present analysis is based on the ECAD registry of patients undergoing conventional coronary angiography at the Department of Cardiology and Vascular Medicine between 2004 and 2019. For this analysis, we excluded all patients with a diagnosis of heart failure or with elevated BNP/NT-proBNP values at baseline (&gt;100pg/nl for BNP, &gt;400pg/nl for NTproBNP). Moreover, patients with missing follow-up information or without BNP/NT-proBNP levels at admission were excluded. As either BNP or NT-proBNP was available for singular patients, we standardized BNP and NT pro BNP levels based on percentile rank in levels from 0 to 99. Cox regression analysis was used to determine the association of BNP/NT-proBNP with morality in unadjusted and risk factor adjusted models with effect sizes depicted per one standard deviation change in BNP/NT-proBNP rank. Results Overall, 3738 patients (mean age: 62.8±12.6 years, 71% male) were included in our analysis. During a mean follow-up of 2.6±3.5 years, 172 deaths of any cause occurred. Patients without fatal events had significantly lower BNP/NT-prBNP values compared to patients who died (48.4±28.8 vs. 58.4±27.5, p&lt;0.0001). In unadjusted cox regression analysis, BNP/NT-proBNP increase by one standard deviation was associated with a 47% increased risk of morality (HR (95% CI): 1.47 (1.25–1.72), p&lt;0.0001). Upon adjustment for cardiovascular risk factors, the significant link between BNP/NT-proBNP levels and morality remained (HR (95% CI): 1.38 (1.14–1.66). Effect sizes were similar for patients receiving coronary revascularization therapy as part of the coronary angiography (1.32 [1.03–1.70], p=0.03) as well as for patients with purely diagnostic procedures (1.58 [1.28–1.94], p&lt;0.0001). Conclusion In patients without heart failure undergoing coronary angiography, BNP/NT-proBNP levels stratify mortality risk independently of traditional cardiovascular risk factors. Our results support the routine assessment of natriuretic peptides also in patients without heart failure to identify patients at increased risk. Funding Acknowledgement Type of funding source: None


2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Shigeyasu Tsuda ◽  
Ryuji Toh ◽  
Kenta Mori ◽  
Manabu Nagao ◽  
Nobuaki Tanaka ◽  
...  

Objective: Myeloperoxidase (MPO) is known as major leukocyte enzyme that oxidizes lipoproteins. High density lipoprotein (HDL) contains paraoxonase 1 (PON1), which hydrolyzes oxidized phospholipids. HDL requires PON1 to attenuate accumulation of lipid peroxides in LDL. We recently reported that serum MPO/PON1 ratio could be used as a useful marker for dysfunctional HDL and showed elevated ratios in patients undergoing recurrent percutaneous coronary intervention (PCI). However, it remains obscure whether serum MPO/PON1 ratio can predict relapsing coronary atherosclerotic lesions after PCI. Methods and Results: Total 111 patients who had a history of successful PCI were enrolled. Their serum MPO mass and PON1 activities were measured at the time point of enrollment, and they had angiographical follow-up evaluation. Fourteen patients needed repeat-PCI due to restenosis and/or de novo lesions during the follow up period (143±730 days). With the established cut off value of 1.59 based on our previous work, Kaplan-Meier analysis showed significantly higher recurrence rate of coronary lesions which required PCI treatment in patients with higher MPO/PON1 ratio at enrollment than that in patients with lower MPO/PON1 ratio (66.7% vs. 6.0%, p<0.001). High MPO/PON1 ratio was independently associated with recurrent coronary atherosclerotic lesions in multivariate Cox regression analysis after adjusting for age, gender, hypertension, diabetes mellitus, dyslipidemia, and smoking (Hazard ratio 15.8, 95% CI 4.20-59.07, p <0.001), while conventional lipid profiles failed to show any statistical relationships to disease recurrence. In addition, C-index of MPO/PON1 ratio was significantly larger than that of MPO alone, indicating that combination of MPO and PON1 provides greater improvement than single application of MPO in predicting coronary lesions (0.787 vs. 0.719, p<0.05). Conclusions: This study demonstrated that higher MPO/PON1 ratio (>1.59) could predict future recurrence of coronary lesions after PCI. This ratio could be useful marker for secondary prevention of coronary artery disease.


Author(s):  
Mustafa Umut Somuncu ◽  
Belma Kalayci ◽  
Ahmet Avci ◽  
Tunahan Akgun ◽  
Huseyin Karakurt ◽  
...  

AbstractBackgroundThe increase in soluble suppression of tumorigenicity 2 (sST2) both in the diagnosis and prognosis of heart failure is well established; however, existing data regarding sST2 values as the prognostic marker after myocardial infarction (MI) are limited and have been conflicting. This study aimed to assess the clinical significance of sST2 in predicting 1-year adverse cardiovascular (CV) events in MI patients.Materials and methodsIn this prospective study, 380 MI patients were included. Participants were grouped into low sST2 (n = 264, mean age: 60.0 ± 12.1 years) and high sST2 groups (n = 116, mean age: 60.5 ± 11.6 years), and all study populations were followed up for major adverse cardiovascular events (MACE) which are composed of CV mortality, target vessel revascularization (TVR), non-fatal reinfarction, stroke and heart failure.ResultsDuring a 12-month follow-up, 68 (17.8%) patients had MACE. CV mortality and heart failure were significantly higher in the high sST2 group compared to the low sST2 group (15.5% vs. 4.9%, p = 0.001 and 8.6% vs. 3.4% p = 0.032, respectively). Multivariate Cox regression analysis concluded that high serum sST2 independently predicted 1-year CV mortality [hazard ratio (HR) 2.263, 95% confidence interval (CI) 1.124–4.557, p = 0.022)]. Besides, older age, Killip class >1, left anterior descending (LAD) as the culprit artery and lower systolic blood pressure were the other independent risk factors for 1-year CV mortality.ConclusionsHigh sST2 levels are an important predictor of MACE, including CV mortality and heart failure in a 1-year follow-up period in MI patients.


2011 ◽  
Vol 27 (7) ◽  
pp. 1407-1413 ◽  
Author(s):  
Loukianos S. Rallidis ◽  
Christos Varounis ◽  
Vassilios Sourides ◽  
Athanasios Charalampopoulos ◽  
Christos Kotakos ◽  
...  

2020 ◽  
Author(s):  
Yan Zhang ◽  
Jing-Lu Jin ◽  
Ye-Xuan Cao ◽  
Hui-Hui Liu ◽  
Hui-Wen Zhang ◽  
...  

Abstract Background: Elevated lipoprotein(a) [Lp(a)] and fibrinogen (Fib) are both associated with coronary artery disease (CAD). The atherogenicity of Lp(a) can be partly due to the potentially antifibrinolytic categories. We hypothesize that patients with higher Lp(a) and Fib may have worse outcomes. Methods: In this prospective study, we consecutively enrolled 8,417 Chinese patients with stable CAD from March 2011 to March 2017. All subjects were divided into 9 groups according to Lp(a) (Lp(a)-Low, Lp(a)-Medium, Lp(a)-High) and Fib levels (Fib-Low, Fib-Medium, Fib-High) and followed up for CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed.Results: During a median of 37.1 months’ follow-up, 395 (4.7%) CVEs occurred. The occurrence of CVEs increased by Lp(a) (3.5% vs. 5.3% vs. 5.6%, p=0.001) and Fib (4.0% vs. 4.4% vs. 6.1%, p<0.001) categories. When further classified into 9 groups by Lp(a) and Fib levels, the CVEs were highest in the 9th (Lp(a)-High and Fib-High) compared with the 1st (Lp(a)-Low and Fib-Low) group (7.2% vs. 3.3%, p<0.001). The highest risk of subsequent CVEs was found in the 9th group (HRadjusted 2.656, 95% CI 1.628-4.333, p<0.001), which was more significant than Lp(a)-High (HRadjusted 1.786, 95% CI 1.315-2.426, p<0.001) or Fib-High (HRadjusted 1.558, 95% CI 1.162-2.089, p=0.003) group. Moreover, adding the combined Lp(a) and Fib increased the C-statistic by 0.013.Conclusion: Combining Fib and Lp(a) enhance the prognostic value for incident CVEs beyond Lp(a) or Fib alone.


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