scholarly journals Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease

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 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.


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.


Author(s):  
Mouaz H Al-Mallah ◽  
Kamal Kassem ◽  
Owais Khawaja ◽  
Thomas Song ◽  
Chad Poopat ◽  
...  

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.


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.


2018 ◽  
Vol 47 (04) ◽  
pp. 778-790 ◽  
Author(s):  
Gard Svingen ◽  
Eva Pedersen ◽  
Reinhard Seifert ◽  
Jan Kvaløy ◽  
Øivind Midttun ◽  
...  

AbstractSystemic fibrinogen and neopterin are related to inflammation. We investigated the prognostic utility and possible interactions of these biomarkers in stable coronary artery disease (SCAD) patients undergoing coronary angiography. We included 3,545 patients with suspected stable angina with a median follow-up of 7.3 and 10.2 years for incident acute myocardial infarction (AMI) and all-cause mortality, respectively. Prospective associations were explored by Cox regression. Potential effect modifications were investigated according to strata of fibrinogen, neopterin or high-sensitivity troponin T (hsTnT) below and above the median, as well as gender and smoking habits. During follow-up, 543 patients experienced an AMI and 769 patients died. In a multivariable model, the hazard ratios (HRs; 95% confidence interval [CI]) per 1 SD increase for fibrinogen in relation to these endpoints were 1.30 (1.20, 1.42; p < 0.001) and 1.22 (1.13, 1.31; p < 0.001), respectively. For neopterin, the HRs (95% CI) were 1.31 (1.23, 1.40; p < 0.001) and 1.24 (1.15, 1.34; p < 0.001), respectively. No significant interaction between fibrinogen and neopterin was observed. The prognostic utility of neopterin for incident AMI was improved in patients with an hsTnT above the median, for total mortality in non-smokers, and for both total mortality and AMI in females. In conclusion, both fibrinogen and neopterin were associated with future AMI and total mortality, but had low discriminatory impact. No interaction was observed between these two biomarkers. The prognostic utility of neopterin was improved in patients with hsTnT levels above the median, and in females and non-smokers.


2020 ◽  
Vol 18 (1) ◽  
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.


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 ◽  
Author(s):  
Man Li ◽  
Hongbin Liu ◽  
Lei Duan ◽  
Yulun Cai ◽  
Benchuan Hao ◽  
...  

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.


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


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