bluuebunny/crossref_metadata_2025_split huggingface dataset:
TCF21 variant is a risk factor for coronary artery disease and will it be a prognostic marker?
Authors: Temtem M , Serrao M , Pereira A , Santos M , Mendonca F , Sousa J.A , Monteiro J , Sousa A.C , Freitas S , Henriques E , Guerra G , Ornelas I , Drumond A , Palma Dos Reis R , Mendonca M.I 
Published: November 2020

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
Does coronary calcium scoring adds value to cardiovascular risk prediction in asymptomatic population?
Authors: Serrao M , Temtem M , Pereira A , Monteiro J , Santos M , Sousa A.C , Henriques E , Freitas S , Ornelas I , Drumond A , Palma Dos Reis R , Mendonca M.I 
Published: November 2020

Abstract

Background
Despite being a controversial subject, multiple guidelines mention the use of Coronary Artery Calcification (CAC) scoring in the cardiovascular risk prediction, in asymptomatic population. The inclusion of CAC scoring in traditional risk models may help in decision-make providing better cardiovascular risk stratification.

Purpose
The aim of our study is to estimate the impact of CAC scoring in cardiovascular events risk prediction in a model based on traditional risk factors (TRFs).

Methods and results
The study consisted of 1052 asymptomatic individuals free of known coronary heart disease, enrolled from GENEMACOR study and referred for computed tomography for the CAC scoring assessment. A cohort of 952 was followed for a mean of 5.2±3.2 years for the primary endpoint of all-cause of cardiovascular events. The following traditional risk factors were considered: (1) current cigarette smoking, (2) dyslipidemia, (3) diabetes mellitus, (4) hypertension and (5) family history of coronary heart disease. Among this population, the extent of CAC differs significantly between men and women in the same age group. Therefore, the distribution of CAC score by age and gender was done by using the Hoff's nomogram (a). According to this nomogram, 3 categories were created: low CAC (0≤CAC&lt;100 and P&lt;50); moderate CAC (100≤CAC&lt;400 or P50–75) and high CAC (CAC≥400 or P&gt;75). Two Cox regression models were created, the first only with TRFs and the second adding the CAC severity categories. When including CAC categories to the TRFs, the higher severity level presented a significant risk of MACE occurrence with an HR of 4.39 (95% CI 1.83–10.52; p=0.001).

Conclusion
Our results point to the importance of the inclusion of CAC in both primary and secondary prevention to an improved risk stratification. Larger prospective multicentre cohorts with longer follow-up should reproduce and validate these findings.

Funding Acknowledgement
Type of funding source: None
Lower levels of low-density lipoprotein cholesterol are associated with lower prevalence of thin-cap fibroatheroma in statin-treated patients with coronary artery disease
Authors: Hashimoto T , Minami Y , Asakura K , Katamine M , Kato A , Katsura A , Muramatsu Y , Sato T , Kameda R , Meguro K , Shimohama T , Ako J 
Published: November 2020

Abstract

Background
Lowering low-density lipoprotein cholesterol (LDL-C) with statins slows progression of atherosclerotic plaques and reduces cardiovascular events. The 2019 European Society of Cardiology guideline for the management of dyslipidaemias recommends the absolute LDL-C treatment target as &lt;55mg/dL for very high-risk patients, &lt;70 mg/dL for high-risk patients and &lt;100 mg/dL for moderate-risk patients. However, the difference in plaque composition of coronary lesions according to these LDL-C levels remains to be elucidated.

Purpose
To investigate plaque morphologies according to LDL-C levels in statin-treated patients with coronary artery disease (CAD).

Methods
A total of 685 consecutive statin-treated patients with CAD, who underwent optical coherence tomography (OCT) imaging of culprit lesions were enrolled. The prevalence of vulnerable compositions in culprit plaques evaluated by OCT was compared among the groups of patients classified by LDL-C levels (&lt;55, 55–70, 70–100, ≥100 mg/dL).

Results
LDL-C levels &lt;55 mg/dL, &lt;70 mg/dL and &lt;100 mg/dL were observed in 6.3%, 21.8% and 63.9% of patients, respectively. The prevalence of thin-cap fibroatheroma was significantly different among the groups (P=0.014, Figure) with a trend toward lower prevalence in the lower two LDL-C groups than in the higher two LDL-C groups. A gradient with lower prevalence of thrombus in lower LDL-C groups was observed, although the statistical significance was not demonstrated (Figure). There was no significant difference in the prevalence of macrophage or cholesterol crystal among the groups.

Conclusions
Lower LDL-C level was associated with a trend toward lower prevalence of thin-cap fibroatheroma and thrombus in statin-treated patients with CAD.

Funding Acknowledgement
Type of funding source: None
Potential determinants of coronary calcium score in a population at intermediate cardiovascular risk
Authors: Brusq C , Bongard V , Berard E , Taraszkiewicz D , Ferrieres J 
Published: November 2020

Abstract

Background
Understanding determinants of coronary calcium score could lead to the development of new preventive actions for reducing cardiovascular risk. Our hypothesis is that major cardiovascular risk factors are linked with coronary calcium score, but the parameters associated with moderate or high scores could be different.

Purpose
The aim of our study was to explore the potential determinants of moderate and high elevation of coronary calcium score in a population of patients at intermediate cardiovascular risk.

Methods
We conducted a cross-sectional analysis, using data from a prospective cohort. Our study population was composed of people presenting with cardiovascular risk factors, who were referred by their attending physician for a complete assessment of their risk factors and for screening for silent cardiovascular disease. People in secondary prevention could also be referred. Coronary calcium score was assessed by cardiac CT scan. We used the following categories for classifying patients according to their coronary calcium score: low (0–100 AU (Agatston units)); moderate (101–300 AU) and high calcium score (greater than 300 AU). We performed a descriptive analysis and then we built a multinomial logistic regression model, using the low calcium score category as reference.

Results
Among the 1585 patients included in the database, we analyzed data from 1402 individuals who beneficiated from coronary calcium scoring. The sample included 714 (51%) men, and 144 (10%) people with a history of cardiovascular disease. Mean age was 59 yrs. Data from the multivariate analysis showed that age (OR=1.07; 95% CI [1.054–1.091] for 1-year increase), gender (OR=0.461; 95% CI [0.330–0.643] for women versus men) and smoking more than 20 cigarettes per day (OR=2.893; 95% CI [1.207–6.935]) were associated with a moderate calcium score. Variables associated with a high calcium score were: age (OR=1.097; 95% CI [1.076–1.119] for 1-year increase), gender (OR=0.221; 95% CI [0.151–0.323] for women vs men), treated dyslipidemia (OR=2.108; 95% CI [1.467–3.027]), treated hypertension (OR=2.199; 95% CI [1.523–3.175]), and history of cardiovascular disease (OR=4.138; 95% CI [2.510–6.823]).

Conclusions
In this study, well-known and modifiable cardiovascular risk factors are associated with calcium score. However, our results highlight that determinants of moderate and high scores may be different. While tobacco is associated with a higher risk of moderate calcium score, hypertension and dyslipidemia appear to be preferentially linked with the highest scores. It is thus appropriate that the 2019 ESC/EAS guidelines for dyslipidemias have classified patients with hypertension and dyslipidemia in the high risk category.

Funding Acknowledgement
Type of funding source: None
Socioeconomic status, secondary prevention activities during the first year after a myocardial infarction and target attainments
Authors: Ohm J , Skoglund P.H , Habel H , Sundstrom J , Hambraeus K , Jernberg T , Svensson P 
Published: November 2020

Abstract

Background
Socioeconomic status (SES) is a strong predictor of recurrent events post-myocardial infarction (MI) with unclear underlying mechanisms. To what extent SES is associated with secondary prevention activities (SPAs) and attainment of quality-of-care treatment goals is unknown.

Purpose
We aimed to assess the association between SES and SPAs during the first year post-MI and attained treatment targets at the 1-year follow-up.

Methods
Nationwide Swedeheart registry-based cohort study on 30,191 18–76 year old 11–15 month survivors of a first MI (8,180 women) 2006–2013. Complementary individual-level clinical data and data on SES (age and gender stratified quintiles of disposable income, level of education, and marital status), were linked from other national registries. Associations between SES and the outcomes were estimated in multivariable logistic regression models with basic adjustment for potential registry-related confounding.

Results
The associations between all indicators of SES and attendance to patient education and physical training programs were strong, moderate for dietary program attendance but absent for participation in smoking cessation program (Table 1). Higher SES was also associated with repeated lipid profile measurements and the highest vs lowest income with intensified statin therapy.
Correspondingly, higher SES was associated with having achieved target levels of LDL-C, blood pressure, and HbA1c as well as with persistence to and being on high intensity statin treatment (Figure 1). Further, higher SES was strongly associated with having quit smoking. No association with income was however observed regarding the weekly physical activity goal.

Conclusions
Higher SES was strongly associated with most SPAs including programs aiming at life style change and risk factor control as well as with attainment of corresponding secondary prevention targets. This may be explanatory for higher long-term risk of recurrent disease.
Figure 1. Target Attainment Forest Plots

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): Stockholm City Council and The Swedish Heart and Lung Association
Non-statin lipid-lowering therapy in coronary atherosclerosis regression: a meta-analysis and meta-regression
Authors: Lobo L.M , Molinero G , Masson W , Siniawski D , Masson G , Huerin M , Nogueira J.P , Benincasa F , Losada P , Suarez F 
Published: November 2020

Abstract

Introduction
Several studies have investigated the association between non-statin lipid-lowering therapy and regression of atherosclerosis. However, the studies were mostly small and their results were not always robust.

Objectives
(1) to define if a dual lipid-lowering therapy (statin ± non-statin drugs) is associated with coronary atherosclerosis regression, estimated by intravascular ultrasound (IVUS); (2) to assess the association between dual lipid-lowering-induced changes in LDL-C and non-HDL-C levels and atherosclerosis regression.

Methods
We performed a meta-analysis including trials of non-statin lipid-lowering therapy, reporting C-LDL, non-HDL-C and total atheroma volume (TAV) with a minimum of 6 months of follow-up. The primary endpoint was defined as the change in TAV measured from baseline to follow-up, comparing groups of subjects on statins alone versus combination of statin and non-statin drugs. The random-effects model and meta-regression were performed.

Results
Eight eligible trials of non-statin lipid-lowering drugs (1759 patients) were included. Overall, the dual lipid-lowering therapy was associated with a significant reduction in TAV [−3.5 mm3 (95% CI: −4.5 to −2.6)]; I2=11%]. In the analysis stratified according to the lipid-lowering drug class (ezetimibe or PCSK9 inhibitors), the findings were similar. In a meta-regression, a 10% decrease in LDL-C or non-HDL-C levels, was associated, respectively, with 0.92 mm3 and 1.05 mm3 regressions in TAV.

Conclusion
Our data suggest the addition of ezetimibe or PCSK9 inhibitors to statin therapy results in significantly increased regression of TAV. When the LDL-C and non-HDL-C levels reached were lower, the observed effect was also greater.
Forest Plot by Drugs Group

Funding Acknowledgement
Type of funding source: None
Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease
Authors: Munkhaugen J , Sverre E , Kristiansen O , Fagerland M.W , Peersen K , Bergan S , Gullestad L , Husebye E , Vethe N.T 
Published: November 2020

Abstract

Background
There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment.

Purpose
We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease.

Methods
This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C.

Results
Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had &lt;50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C.

Conclusions
There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response.

Funding Acknowledgement
Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award
The impact of the revised ESC Dyslipidaemia Guidelines on lipid-lowering therapy: simulating the need for PCSK9 inhibition in a contemporary ASCVD cohort
Authors: Blaum C , Brunner F.J , Kroeger F , Braetz J , Bay B , Graef A , Gossling A , Lorenz T , Zeller T , Karakas M , Schnabel R.B , Westermann D , Blankenberg S , Seiffert M , Waldeyer C 
Published: November 2020

Abstract

Introduction
The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors.

Purpose
We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients

Methods
We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C &gt;140 mg/dl or &gt;100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017).

Results
We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively).

Conclusion
The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently.

Funding Acknowledgement
Type of funding source: None
Reduction of epicardial adipose tissue thickness with PCSK9 inhibitors
Authors: Rivas Galvez R.E , Morales Portano J.D , Trujillo Cortes R , Gomez Alvarez E.B , Sanchez Cubias S.M , Zelaya S.M 
Published: November 2020

Abstract

Introduction
Epicardial adipose tissue (EAT) is clinically related to atherosclerosis and increased cardiovascular risk. The proprotein convertase subtilisin/kexin type 9 inhibitors (IPCSK9) are a novel group of effective drugs for lowering LDL cholesterol and cardiovascular events, however their effect on EAT has not yet been determined.

Objective
To assess the effect of treatment with PCSK9 inhibitors on epicardial adipose tissue.

Methods
The study enrolled 41 patients under treatment with PCSK9 inhibitors. At the end of the study only 24 patients were included, who were measured thickness of epicardial adipose tissue (TEAT) by transthoracic echocargiogram (just an echocardiographer using Siemens Acuson SC 2000 Prime with two-dimensional 4V1c transducer in two projections: long parasternal axis in the pericardial space of the outer edge of the myocardium above the right ventricle and in a short parasternal axis at the height of papillary muscles on the right ventricle, in telesystole and averaging three measurements; It was measured in millimeters.) using in 2 times before and after 6 months of initiation of treatment.

Results
Of 24 patients, 16 patients recieved evolocumab and 8 alirocumab patients; the mean TEAT pre-treatment and post-treatment was 6.84 mm (1.97) and 5.41 mm (1.86), respectively (p=0.0001); The mean percentage of change of the TEAT after 6 months of treatment was −20.39 (17.20). The mean serum LDL cholesterol levels pre-treatment and post-treatment were 188.04 mg/dL (144.0) and 94.96 mg/dL (106.04), respectively (p=0.0001); The mean change in LDL cholesterol was −51.89 (22.81). Just one patient had myocardial infarction. There was no difference between the means of reducing the percentage of change in epicardial adipose thickness between evolocumab and alirocumab. There was no correlation between lipid decrease and TEAT.

Conclusion
There is a significant reduction after 6 months of treatment with PSCK9 inhibitors in thickness of epicardial adipose tissue.
Effect of IPCSK9 in TEAT and Lipids

Funding Acknowledgement
Type of funding source: None