bluuebunny/crossref_metadata_2025 huggingface dataset:
Invasive validation of pressure-volume loops derived from cardiovascular magnetic resonance imaging and brachial blood pressure in heart failure patients
Authors: Arvidsson P , Green P G , Watson W D , Shanmuganathan M , Heiberg E , De Maria G L , Arheden H , Herring N , Rider O J
Published: October 2022

Introduction

Left ventricular (LV) pressure-volume (PV) loops provide gold-standard physiological information but require invasive measurements of ventricular intracavity pressure, limiting clinical and research applications. Recent development has seen the introduction of non-invasively computed PV loops from cardiovascular magnetic resonance (CMR) volumetry and a brachial blood pressure measurement. The approach combines LV volumes with a time-varying elastance function to compute time-resolved LV pressures and was validated on invasive pressure data from a porcine model. The method is readily implemented using standard CMR sequences and provides measures of hemodynamic parameters including stroke work, myocardial efficiency, and contractile state. However, the method remains to be validated in patients using invasive left ventricular pressure recordings.

Purpose

To validate for the first time in human patients the performance of non-invasively computed PV loops against invasive measures.

Methods

Four heart failure patients underwent two subsequent sessions of CMR cine imaging and simultaneous brachial blood pressure measurement, with intravenous administration of two different vasoactive drugs, resulting in two different haemodynamic states for each patient. LV catheterization was then conducted with repeat administration of the same infusions. Pressure-volume loops were computed from CMR volumes combined with 1) a time-varying elastance function scaled to brachial blood pressure and temporally stretched to match volume data, and 2) invasive pressures averaged from multiple sampled beats. Method comparison was conducted using linear regression and Bland-Altman analysis.

Results

Figure 1 shows non-invasively derived PV loop parameters compared to invasive data. The non-invasive method demonstrated strong correlations and low bias for stroke work (R2=0.97, bias 4.6%, p<0.0001), potential energy (R2=0.83, bias 1.5%, p=0.001), end-systolic pressure-volume relationship (R2=0.90, bias 5.4%, p=0.0003), energy per ejected volume (R2=0.93, bias 3.5%, p=0.0001), ventricular efficiency (R2=0.99, bias 1.1%, p<0.0001), arterial elastance (R2=0.87, bias −7.8%, p=0.0006), and mean external power (R2=0.89, bias 4.6%, p=0.0005).

Conclusions

Pressure-volume loops can be precisely and accurately computed from cardiovascular magnetic resonance imaging and brachial cuff blood pressure in humans, and is ready for use in research applications.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): Swedish Heart Lung Foundation
The effect of ziltivekimab on the neutrophil-lymphocyte ratio: analysis from RESCUE
Authors: Adamstein N , Cornel J , Davidson M , Libby P , De Remigis A , Jensen C , Rajan S , Ridker P
Published: October 2022

Background

The neutrophil-lymphocyte ratio (NLR), derived from the complete blood count, independently predicts atherosclerotic events and is a potential biomarker for residual inflammatory risk. A previous study showed that interleukin (IL)-1β inhibition reduces the NLR, but whether inhibition with IL-6, a cytokine downstream of IL-1, also lowers the NLR is unknown.

Purpose

To evaluate whether ziltivekimab, a monoclonal antibody targeting the IL-6 ligand, dose-dependently lowers the NLR compared to placebo.

Methods

The phase II RESCUE trial randomized 264 patients with moderate to severe chronic kidney disease (CKD) and high-sensitivity CRP (hsCRP) >2mg/L in a 1:1:1:1 ratio to placebo or ziltivekimab 7.5 mg, 15 mg, and 30 mg subcutaneously once every four weeks. As previously reported, the trial met its primary endpoint as demonstrated by hsCRP reductions of 4% in the placebo group as compared to 77%, 88%, and 92% at 12 weeks in the ziltivekimab 7.5, 15, and 30 mg groups, respectively. Using RESCUE trial data, we further evaluated the percent change from baseline in the NLR at 12 weeks and sought evidence of correlation between any observed changes in the NLR with changes in other measured biomarkers.

Results

Ziltivekimab dose-dependently reduced the NLR starting at week one and sustained through week 12 (Table). The median change in the NLR at 12 weeks, the primary pre-specified endpoint, was −13.5% in the 7.5 mg group, −14.3% in the 15 mg group, and −22.4% in the 30 mg group compared to 1.56% in the placebo group. The estimated treatment difference was −14.6% (p=0.004), −15.3% (p=0.004), and −23.6% (p<0.0001) in the ziltivekimab 7.5, 15, and 30 mg groups respectively. These changes were driven largely by reductions in the absolute neutrophil count with minimal change in lymphocyte count. The change in NLR with ziltivekimab correlated modestly with the changes in hsCRP (R=0.26, p=0.0006), fibrinogen (R=0.18, p=0.02), and haptoglobin (R=0.17, p=0.03), but not serum amyloid A, ApoA1, ApoB, ApoB/ApoA ratio, or traditional risk markers.

Conclusions

IL-6 inhibition with ziltivekimab lowers the NLR. The ongoing ZEUS cardiovascular (CV) outcomes trial will assess whether ziltivekimab can reduce CV event rates among individuals with stage 3 to 4 CKD, known atherosclerotic disease, and elevated hsCRP. If ziltivekimab reduces CV risk, it would provide further evidence for critical inter-relationships between bone marrow function and atherothrombosis.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Novo Nordisk
Increased arterial stiffness predict major adverse cardiovascular events in post-infarcted patients. Do parameters and methods matter?
Authors: Gaszner B , Simor T , Van Der Geest R J , Farkas N , Meiszterics Z
Published: October 2022

Introduction

According to recent 2021 ESC prevention guidelines arterial stiffness (aortic pulse wave velocity – PWV, augmentation index - Aix) predicts future major adverse cardiovascular events (MACE). Both parameters have a prognostic relevance, however due to the various technical approaches the level of high stiffness values show significant differences and resulting an argue against widespread use.

Purpose

We evaluated the cut-off PWV and Aix values for MACE prediction using cardiac magnetic resonance imaging (CMR) and oscillometric methods for validating the prognostic value of high stiffness parameters in post-infarcted patients.

Methods

CMR phase contrast imaging (Siemens Avanto, 1,5 T CMR device) and an invasively validated oscillometric based Arteriograph (AG) method were compared in this 6 years follow-up study, including 49 patients suffered previous ST-elevation myocardial infarction (STEMI). Patients received follow-up for MACE comprising all-cause death, non-fatal MI, ischemic stroke, hospitalization for heart failure and coronary revascularization.

Results

49 patients (37 male, average age: 57±8 years) were investigated. An acceptable agreement and significant correlation (Spearman's rho: 0.332, p<0,01) was found between AG and CMR derived PWV values. Bland Altman plot was created to test for methods' agreement. The bias showed that in general the mean difference between the two measures was 3.6 m/s (upper and lower limit of agreement: –0.2 and 7.5 m/s). The coefficient of variation was 43.9%. Totally 51 MACE events occurred during the 6 years follow-up period. Hospitalisation for coronary revascularisation (55%), all-cause death (15%), non-fatal MI (12%), heart failure (12%) exposed the majority of MACE events. Optimized PWV and Aix cut-off values for MACE prediction were calculated (PWVCMR: 6,47 m/s; PWVAG: 9,625 m/s; AixAG: 34,22%) by receiver operating characteristic analysis (Figure 1). Kaplan-Meier analysis in all parameters showed a significantly lower event-free survival in case of high PWV and Aix values (Figure 2). Multivariate Cox regression analysis revealed PWV and Aix as a predictor of MACE (PWVCMR hazard ratio (HR): 1.31 (CI: 1.1–1.7), PWVAG HR: 1.24 (CI: 1.0–1.5), AixAG HR: 1,043 (CI: 1,01–1,08), p<0,05 respectively).

Conclusions

Arterial stiffness, particularly elevated PWV predicts MACE in postinfarcted patients. Our study showed both CMR and oscillometric techniques are feasible for MACE prediction, however, adjusted cut-off values of PWV are recommended for different methods to improve individual risk stratification. All these findings emphasize the clinical relevance for the future measurement of arterial stiffness might contribute to improved risk stratification after MI, which is crucial for the assessment of prognosis and guidance of secondary prevention treatment.

Funding Acknowledgement

Type of funding sources: None.
Clinical significance of undetectable high sensitivity cardiac troponin I (hs-TnI) in Thai individuals with low cardiovascular risk
Authors: Sabkaewyod P , Vathesatogkit P , Stitara P
Published: October 2022

Introduction

The long term prognosis of individuals who has undetectable hs-TnI is poorly defined in low cardiovascular risk. We aim to examine whether undetectable hs-TnI individuals have better cardiovascular outcomes in low cardiovascular risk population.

Methods

Data of low cardiovascular risk population (<7.5%) who has no established of atherosclerosis cardiovascular disease (ASCVD) was derived from the Electricity Generating Authority of Thailand (EGAT) study in 2007–2009 survey. High sensitivity cardiac troponin I was measured by using the Abbott ARCHITECT i2000 SR assay. We categorized level of hs-TnI into undetectable hs-TnI (<1.9 ng/L), low hs-TnI, intermediate and more hsTnI by gendered specific cut-off. The low cardiovascular risk population was classified into extremely low risk (<5%) and low risk (5–7.5%). Major cardiovascular event (MACE) and all-cause mortality were collected until 31st December 2019. Survival analysis and subgroup analysis were performed.

Results

A total of 3,442 participants were eligible. Mean age was 43.6 years-old, 65.5% male, hs-TnI was detected 79.8%, median hs-cTnI was 2.6 ng/L (2,3.6). During median time followed-up 10.3 years, 52 events (1.5%) of MACE and 60 events (1.7%) of all-cause mortality occurred. After adjusted for conventional risk factors, hs-cTnI significantly associated with incidence of MACE (HR 1.03 95% CI 1.02–1.04, p-value <0.001). Compared with intermediate and more hs-TnI group, undetectable hs-TnI and low hs-TnI had 79% and 52% lower incidence of MACE (HR 0.21, 95% CI (0.05–0.79) and HR 0.48, 95% CI (0.23–1.0), p-value for trend 0.04. Subgroup analysis, incidence of MACE remained higher either extremely low or low CV risk compared with those undetectable hs-TnI. (P for interact 0.83)

Conclusion

Among individuals with low cardiovascular risk, hs-TnI testing can provide risk prognostication. Undetectable hs-TnI could be as a negative risk marker for adverse cardiovascular events.

Funding Acknowledgement

Type of funding sources: None.
Physical activity during adolescence and early adulthood and adult cardiometabolic risk profile: a longitudinal study
Authors: Soendergaard S M , Lynggaard V , Winding T N , Kempel M K
Published: October 2022

Introduction

Physical activity (PA) is important in the prevention of cardiometabolic diseases. However, little is known of the effect of maintaining PA during adolescence and cardiometabolic risk in early adulthood.

Purpose

This 14-year longitudinal prospective cohort study investigated the association of maintaining PA since adolescence and subsequent cardiometabolic risk factors in early adulthood and to what extend adiposity affects this.

Methods

Data were drawn from an ongoing cohort and consisted of 262 participants with longitudinal information on PA and cardiometabolic risk factors in adulthood. The cardiometabolic risk factors were collected by blood samples, anthropometric measures, and blood pressure in a health examination at the age of 28 years (table 1). Subsequently, the risk factors were clustered in four domains (“Inflammation”, “Lipids”, “Glucose metabolism” and “Blood pressure”) and calculated into z-scores. Further, a composite z-score of all domains was calculated. PA was obtained by questionnaires at age 15, 18, 21 and 28. The participants were categorized into “inactive maintainers”, “fluctuaters” and “active maintainers” and linear regression was used to examine the association between PA groups and the cardiometabolic domains in a crude and two adjusted models 1 and 2.

Results

Increasing z-scores from “active maintainers” to “fluctuaters” to “inactive maintainers” were seen in all domains except in “blood pressure” when adjusted for sex, smoking, parental and own education, and parental cardiovascular medical history, and significantly different when comparing “active maintainers” to “inactive maintainers” (table 2, model 1). In the composite z-score outcome including all domains, a significantly adverse z-score was found for “inactive maintainers” z=0.63, p=0.001 when adjusted for the variables in model 1 (table 2). When also adjusted for body fat percentage (model 2), the z-score became insignificant z=0.19, p=0.198 (table 2).

Conclusion

Maintaining PA from adolescence to early adulthood is associated with a significant lower cardiometabolic risk profile compared to inactive maintainers. However, some of the adverse risk profile is explained by being overweight or obese. Given the increasing prevalence of CVD and diabetes these results highlight the importance of maintaining PA at all stages of life.

Funding Acknowledgement

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Karen Elise Jensen Foundation and The Steno Partner Collaboration between Goedstrup Hospital and Steno Diabetes Center Aarhus.
Fibroblast growth factor 21 is independently associated with long term mortality in metabolic syndrome
Authors: Phrommintikul A , Osataphan N , Sa-Nguanmoo P , Wongcharoen W , Chattipakorn N , Chattipakorn S
Published: October 2022

Background

Metabolic syndrome (MetS), a cluster of interrelated cardiovascular risk factors, is associated with increased risk of cardiovascular and non-cardiovascular disease. Fibroblast growth factor 21 (FGF21) plays an important role in metabolic regulation and has been shown to be elevated in MetS. However, role of FGF21 in pathogenesis of cardiovascular disease is still controversial.

Objective

We aimed to identify the association between plasma FGF21 level and long-term mortality in MetS patients.

Methods

Patients with MetS were enrolled in this study during 2015–2017. Blood samples for FGF21 were collected after 12-hour fasting and plasma FGF21 levels were determined using a human FGF21 enzyme-linked immunosorbent assay (ELISA) at the first time of the enrollment. Clinical parameters, and all-cause mortality were recorded. Cox-proportional hazard regression was used for the analysis of association between plasma FGF21 level and all-cause mortality.

Results

A total of 202 Mets patients (male 44.6%) with mean age of 64.3±8.3 years and BMI of 27.3±5.4 kg/m2 were enrolled. After a median follow up of 80 months, 32 (15.8%) patients died. Multivariable Cox proportional hazard regression showed that FGF21 level was independently associated with all-cause mortality after adjustment for age, established cardiovascular disease, estimated glomerular filtration rate and left ventricular ejection fraction. Patients with FGF21 level above median (240 pg/ml) had higher risk of all-cause death compared to patients with FGF21 ≤240 pg/ml (hazard ratio [HR], 3.66; 95% confidence interval [CI], 1.24–10.82; p=0.019) (Figure 1).

Conclusion

FGF21 level is independently associated with long term mortality in metabolic syndrome.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Thailand research fund
Lp(a) is not associated with arterial stiffness: a Mendelian randomization study
Authors: Simistiras A , Delialis D , Georgiopoulos G , Bampatsias D , Maneta E , Dimoula A , Petropoulos I , Neofytou O , Oikonomou E , Kontogiannis C , Ioannou S , Miliotou A , Kanakakis I , Evangelou E , Stamatelopoulos K
Published: October 2022

Background

Deeper understanding of the potential causal relationship between Lp(a) and vascular injury will provide further insight to related pathways to be monitored and targeted by emerging treatments. Accumulating evidence supports the causal association of lipoprotein(a) [Lp(a)] with cardiovascular disease and calcific aortic valve disease (AVD). Arterial stiffening is mechanistically linked with cardiovascular disease and AVD severity. We hypothesized that Lp(a) may be causally associated with pulse-wave velocity (PWV) as the gold-standard marker of arterial stiffness.

Aim

To investigate the potential causal association of Lp(a) levels with PWV.

Methods

We performed a two sample Mendelian randomization (MR) analysis of LP(a) on PWV by combining the summary data of two independent Genetic-Wide Association Study (GWASs). Genetic variants associated with Lp(a) were retrieved from the UK Biobank (N=220,497). A GWAS based on a cohort in Germany (N=7,000) was used to obtain genetic associations for PWV index (outcome). We assessed two different measures of arterial stiffness, brachial ankle (baPWV) and carotid femoral pulse (cfPWV) wave velocity. In total, we used 170 SNPs as Instrument Variables (IV's) and applied a two sample MR with the main technique of Inverse Variance Weighting method (IVW). We conducted sensitivity analyses (MR-Egger and Median based) to detect pleiotropy of the causal variants and to test for robustness of our findings.

Results

Our analyses based on all 170 SNP's did not find evidence for causal relationship between Lp(a) and PWV for neither measurement [bivw (baPWV) = −0.0005, CI (−0.0043, 0.0034), P=0.8 and bivw (cfPWV) = −0.006, CI (−0.013, 0.002), P=0.16 for brachial ankle and carotid-femoral PWV, respectively]. Sensitivity analyses, including weighted median and mode-based estimation, did not show significant association of Lp (a) with neither baPWV nor cfPWV.

Conclusions

Lp(a) is not causally associated with arterial stiffness. These findings suggest that arterial stiffening is not involved Lp(a)-mediated cardiovascular and aortic valve disease.

Funding Acknowledgement

Type of funding sources: None.
Time series clustering of left atrial strain curves for risk stratification in the general population
Authors: Ntalianis E , Sabovcik F , Cauwenberghs N , Daels Y , Kuznetsova T
Published: October 2022

Objective

Currently, only the peak reservoir left atrial (LA) strain has been in use while a huge amount of useful information during different phases of cardiac cycle has been ignored. In this study, therefore, we tested the hypothesis that an unsupervised time series analysis utilizing the whole LA deformation curves will identify distinct clusters associated to risk factors and improve cardiovascular (CV) risk prediction over the traditionally used covariables in the general population.

Design and method

We prospectively studied 929 community-dwelling individuals (mean age, 51.6 years; 52.9% women), in whom we acquired clinical and echocardiographic data including LA strain traces at baseline and collected cardiac events on average 7.2 years later. We employed two unsupervised time series techniques such as Self-Organizing map and Variational Autoencoder (VAE) with Convolutional Neural Network as building block to cluster spatiotemporal patterns of LA strain curves. Clinical characteristics and cardiac outcome were used to evaluate the validity of the clusters (k).

Results

According to the quantization error value for every k, the optimal number of clusters was 5 for applied methods. Figure 1 (left panel) illustrates the centroids of the clusters using the proposed VAE network. The first three clusters had differences in sex distribution and heart rate, but had similar low CV risk profiles. On the other hand, cluster 5 had the worst CV risk factors combination, and higher prevalence of left ventricular remodelling and diastolic dysfunction (ie, lowest e' velocity and highest E/e') compared to other clusters. We also observed an increase in the risk for incidence of adverse events between cluster 5 and other clusters (Figure 1, right panel). After adjustment for traditional risk factors, cluster 5 had the highest risk of cardiac events as compared to cluster 1, 2 and 3 (HR: 1.36; 95% CI: 1.10–1.69); P=0.0046).

Conclusion

Unsupervised Machine/Deep Learning algorithms employed on time series LA strain curves identifies clinically meaningful clusters of LA deformation, and provides incremental prognostic information over traditional risk stratification.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): KU Leuven
Radial artery calcification in predicting coronary calcification and atherosclerosis burden
Authors: Achim A , Kakonyi K , Nagy F , Jambrik Z , Varga A , Nemes A , Sk Chan J , Toth G , Ruzsa Z
Published: October 2022

Background

Atherosclerosis is a systemic arterial disease with heterogeneous involvement in all vascular beds, however studies examining the relationship between coronary and radial artery calcification are lacking.

The purpose of this study was to assess the relationship between the two sites and the prognostic value of radial artery calcification (RC) for coronary artery disease.

Methods and results

This is a single-center, retrospective cross-sectional study based on doppler ultrasound of radial artery (RUS) and coronary artery angiography (CAG). We included a total of 202 patients undergoing RUS during distal radial access and CAG at the same procedure, between December 2020 and May 2021, from which 103 were found having RC during RUS (RC-group) and 99 without (NRC-group). Coronary calcifications were evaluated either by angiography examination (moderate and severe), positive CT (>100 Agatson units) or intracoronary imaging (IVUS, OCT). A significant correlation was observed between radial calcification and coronary calcification variables (67.3%, vs 32.7% – p=0.001). The correlation between risk factors such as age, smoking, chronic kidney disease and diabetes mellitus was higher while sex did not play a role. The need of PCI and/or CABG was higher in the RC-group (60% vs 44%, p=0.02). RC therefore predicts the extent and severity of coronary artery disease.

Conclusion

RC may be frequently associated with calcific coronary plaques. These findings highlight the potential beneficial examination of radial arteries whenever CAD is suspected.

Funding Acknowledgement

Type of funding sources: None.
Prognostic implications of cardiac 82-rubidium positron emission tomography in angina patients with no perfusion defects
Authors: Rauf M , Hansen K , Galatius S , Wiinberg N , Brinth L , Hojstrup S , Talleruphus U , Prescott E
Published: October 2022

Background

Myocardial perfusion imaging with 82-Rubidium positron emission tomography (82Rb-PET) is increasingly used in the assessment of stable coronary artery disease (CAD). Among other variables, it provides quantitative measures of myocardial blood flow (MBF) which has shown the prognostic significance of coronary microvascular dysfunction (CMD), also in patients without perfusion defects. However, other 82Rb-PET variables may also be of prognostic significance in these patients.

Purpose

The purpose of this study was to evaluate the prognostic value of 82Rb-PET in patients with symptoms suggestive of CAD but no perfusion defects.

Methods

A study was conducted with 3726 consecutive patients who underwent 82Rb-PET on the suspicion of stable CAD between January 2018 and August 2020. After exclusion of patients with regional perfusion defects, we examined the association of 82Rb-PET derived parameters with a composite endpoint: all-cause mortality, hospitalization for unstable angina pectoris, acute myocardial infarction, heart failure or ischemic stroke in 2175 patients. CMD was defined as myocardial blood flow reserve (MBFR) <2. Analyses were further stratified to assess differences across gender.

Results

Resting and stress MBF were higher in women, while MBFR was lower and CMD more prevalent (30.5% among women versus 25.3% among men, p=0.008). Over a median follow-up of 1.7 years (IQR 1.1–2.5 years) a total of 148 events were observed. In unadjusted analyses, MBF during stress, MBFR, left ventricular ejection fraction (LVEF), LVEF-reserve, heart rate reserve and Ca-score were associated with adverse outcomes in both genders (Figure 1). A joint multivariable Cox model, for both genders, adjusted for patient characteristics, cardiovascular risk factors and 82Rb-PET variables showed reduced MBFR <2 (HR 1.75, 95% CI 1.24–2.48), resting LVEF (HR 1.38 per 10% decrease, 95% CI 1.24–1.54) and LVEF-reserve (HR 1.19 per 5% decrease, 95% CI 1.07–1.31) to be significant predictors of outcomes (Figure 2). Results were consistent in subgroups defined by gender, previous history of ischemic heart disease (IHD), reduced LVEF and atrial fibrillation.

Conclusion

MBFR, LVEF and LVEF-reserve derived from 82Rb-PET are predictors of adverse outcome and provide prognostic information in patients with no perfusion defects. This may aid in identifying patients at risk and provide opportunity of prevention.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Bispebjerg Frederiksberg Hospital, Copenhagen
Inflammation and risk of recurrent cardiovascular events according to prior vascular disease location
Authors: Burger P M , Ridker P , Dorresteijn J , Koudstaal S , Mosterd A , Pradhan A , Visseren F
Published: October 2022

Background

In recent years, anti-inflammatory drugs have been shown to reduce the risk of recurrent cardiovascular disease (CVD) events in patients with coronary artery disease (CAD), but have not yet been tested in patients with other vascular disease locations. Whether the relation between inflammation and recurrent CVD is modified by prior vascular disease location is unknown.

Purpose

This study aimed to establish the relation between low-grade inflammation and recurrent CVD according to prior vascular disease location.

Methods

Inflammation was measured by plasma concentrations of high-sensitivity C-reactive protein (CRP). Patients from the UCC-SMART cohort with CAD (n=4,517), cerebrovascular disease (CeVD; n=2,154), peripheral artery disease (PAD, n=1,154), or abdominal aortic aneurysm (AAA, n=424), and CRP ≤10 mg/L were included in the main analysis (combined n=8,249). Patients with CRP >10 mg/L (n=756) were analysed separately. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes included the primary outcome components, major adverse limb events (MALE), and all-cause mortality. The relation between CRP and outcomes was assessed using Cox proportional hazard models stratified by prior vascular disease location, and adjusted for potential confounders.

Results

During a median follow-up of 9.5 years (interquartile range 5.1–13.9) 1,877 CVD events, 887 MALE events, and 2,341 deaths were observed. In the total population, CRP was related to recurrent CVD (hazard ratio [HR] per 1 mg/L 1.08; 95% confidence interval [CI] 1.05–1.10), and all secondary outcomes except for ischemic stroke (HR 1.03; 95% CI 0.99–1.08). Compared to the first quintile of CRP, HRs for recurrent CVD were 1.66 (95% CI 1.41–1.96) for the last quintile ≤10 mg/L, and 1.97 (95% CI 1.64–2.36) for the subgroup with CRP >10 mg/L. CRP was related to recurrent CVD in patients with CAD (HR per 1 mg/L 1.08; 95% CI 1.04–1.11), as well as CeVD (HR 1.05; 95% CI 1.01–1.10), PAD (HR 1.08; 95% CI 1.03–1.13), and AAA (HR 1.08; 95% CI 1.01–1.15; p for interaction 0.815). The relation between CRP and all-cause mortality was stronger for patients with CAD (HR 1.13; 95% CI 1.09–1.16) compared to other locations (HRs 1.06–1.08; p=0.002).

Conclusion

Inflammation is an independent risk factor of recurrent CVD and mortality, irrespective of prior vascular disease location. Trials of anti-inflammatory drugs in patients with CeVD, PAD, and AAA are warranted.

Funding Acknowledgement

Type of funding sources: None.
Antiplatelet therapy and risk of adverse cardiovascular events in peripheral artery disease
Authors: Kamil S , Sehested T S G , Blanche P , Houlind K , Lassen J F , Gislason G , Dominguez H
Published: October 2022

Background

Antiplatelet therapy has been shown to reduce adverse cardiovascular (CV) events in patients with PAD, but despite the well-established medication benefit, large-scale epidemiological data evaluating antiplatelet agent of choice with low bleeding risk and high antithrombotic effect is sparse.

Purpose

We explored Danish healthcare registers to examine guideline-recommended antiplatelet therapy and associated risk of adverse CV outcomes in patients with PAD.

Methods

All patients with a first-time diagnosis of PAD between January 1, 1997 and December 31, 2016 were identified. Patients alive six months after diagnosis were divided into four treatment groups: aspirin, clopidogrel, dual therapy (DAPT), and no antiplatelet therapy. Logistic regression models were used to estimate 1-year risk of myocardial infarction (MI), stroke, CV death, all-cause mortality, and gastrointestinal (GI) bleeding.

Results

We identified a total of 85,771 PAD patients [median age 70.6 (IQR 63–77 years), 52% male]. The results suggest that compared to no antiplatelet therapy, use of clopidogrel alone significantly decreased 1-year risk of incident MI, stroke, CV death and all-cause mortality with odds ratios 0.56 (CI 0.46–0.68), 0.69 (CI 0.59–0.81), 0.72 (CI 0.56–0.94), and 0.79 (CI 0.65–0.97) respectively. Likewise, aspirin monotherapy was associated with only a marginal reduction in 1-year risk of stroke by 11% and all-cause mortality by 7%. Odds ratios for GI bleeding were estimated to be 1.18 (CI 1.04–1.34), 1.34 (CI 0.94–1.91), and 1.54 (CI 1.05–2.26) for aspirin, clopidogrel, and DAPT groups, respectively.

Conclusion

In this nationwide study, clopidogrel is associated with significantly reduced risk of MI, stroke, CV death and all-cause mortality with low risk of bleeding and appears to support clopidogrel as antiplatelet agent of choice for CV risk reduction in patients with PAD.

Funding Acknowledgement

Type of funding sources: None.
Identification of factors associated with smoking cessation in patients with coronary artery diseases. Findings from a large nationwide cohort of smoking cessation services
Authors: Allagbe I , Marianne Z , Thomas D , Limosin F , Chague F , Le Faou A L
Published: October 2022

In patients with coronary artery diseases (CAD) (i.e. prior myocardial infarction (MI) or angina), smoking cessation (SC) is a major prevention goal. From a large French national database of SC services, we aimed to describe social, medical and smoking characteristics, as well as predictive factors of SC in men and women with CAD.

Methods

We conducted a retrospective study of smokers with CAD who visited a SC service and were included in the nationwide database of SC services (CDTnet). Endpoint was the abstinence rate, defined as SC maintained for at least 28 consecutive days, confirmed by an exhaled carbon monoxide <10 ppm.

Results

Among the 4,532 smokers with CAD (myocardial infarction and angina), 21% (948) were women. The mean age was 55 years in both sexes. Two-thirds had consulted after a hospital contact and nearly half (45%) smoked more than 20 cigarettes per day. Compared to men, women presented more often with anxio-depression symptoms (57% vs 41%) and respiratory diseases (38% vs 28%), were less educated (65% vs 73% had at least one degree), suffered less often from other cardiovascular diseases such as stroke or peripheral arterial disease (16% vs 21%) and much lower rate of alcohol misuse (9% vs 25%). Finally, 82% of smokers received Nicotine Replacement Therapy (NRT) at the first consultation. The abstinence rate achieved was similar in women and men (54%). Factors positively associated with SC in women were: having more than one previous quit attempt, having a level of education ≥ first secondary school diploma) (OR=1.42; CI95% [1.04–1.95]) and using an electronic cigarette at the first consultation (OR=2.74; CI95% [1.22–6.58]). In men, these factors were: being employed (OR=1.25; CI95% [1.08–1.45]), declaring high confidence in quitting (OR=1.24; CI95% [1.07–1.44]) and using NRT (OR=1.41; CI95% [1.13–1.74]). Psychiatric or respiratory diseases were negatively associated with SC in both men and women. In men, the factors negatively associated with SC were: smoking at home, having diabetes, using cannabis and presenting with high nicotine dependence. Among women, living with a smoker hampered SC.

Conclusion

Our findings on a large nationwide cohort from SC services showed that in smokers with prior MI or angina, it is important to take into account comorbidities, particularly psychiatric and respiratory disorders, in order to improve smoking cessation rates.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): This work was supported by IReSP and INCa through a call for doctoral grants launched in 2019
Does low glycemic index diet superior than routine diet to control blood inflammation state and lipid parameters in patients with coronary artery disease?
Authors: Alyavi A L , Alyavi B A , Uzokov J , Payziev D D , Orziev D Z , Mukhamedova M G , Majidov I H
Published: October 2022

Background and aims

Low glycemic index diet has been shown several benefits in terms of reduction in atherosclerotic biomarkers in patients with coronary artery disease (CAD).

Objective of the study

To demonstrate superiority of the low glycemic index diet in patients with CAD in terms of blood inflammation state and lipid parameters.

Methods

One hundred and sixty patients aged 38–76 years established with CAD entered as 12 week dietary intervention either with low glycemic index (n=80) or routine diet (n=80) together with standard therapy from 2016 to 2019 (male=48%; 58.2±12.0 years). Laboratory (including hs-CRP, pro-inflammatory interleukins, IL-1β, IL-6, TNF-α, lipid parameters TC, TG, LDL-Cholesterol, HDL-Cholesterol) and instrumental data were obtained at baseline and in 12 weeks of the intervention.

Results

There were no statistically differences in biochemical data between two groups at their baseline characteristics. Low glycemic index diet positively influenced on hs-CRP (from 252.4±40.6 mg/dL to 161.9±28.5 mg/dL vs. from 237.8±35.6 mg/dL to 202.4±23.8 mg/dL; P<0.05), HbA1c (from 6.95±1.95% to 4.78±1.18% vs. 6.80±1.65% to 6.25±1.45%; P<0.05), TG (from 5.2±2.2 to 3.1±1.8 vs. from 5.8±2.8 to 4.9±2.0, P<0.05), TNF-α (from 1.48±0.91 to 0.88±0.19 vs. from 1.55±1.35 to 1.12±0.35, P<0.05), IL-6 (from 8.2 pg/mL to 4.9 pg/mL vs. from 8.2 pg/mL to 4.9 pg/mL, P<0.005) than routine diet. Although reduction in IL-1β were observed in both groups (from 32.5±17.2 pg/ml to 28.9±16.8 pg/ml, P>0.05; vs. 33.6±21.6 pg/ml to 29.8±20.4, P>0.05;), however there were no statistically significant from baseline and between groups (P>0.05).

Conclusions

Low glycemic index diet demonstrated superiority to routine diet to improve inflammatory state and lipid parameters in patients with CAD.

Funding Acknowledgement

Type of funding sources: None.
Prognostic impact of suboptimal adherence to statin therapy after STEMI: results from the FAST-STEMI registry
Authors: Annone U , Giammaria M , D'Ascenzo F , Gallone G , Gaido L , Della Valle A , Del Nevo F , Guagliumi G
Published: October 2022

Introduction

Patterns and prognostic impact of suboptimal adherence to statin therapy, after STEMI, remains understudied

Purpose

To identify predictors and to estimate the prognostic impact of low statin adherence after STEMI

Method

We evaluated real-world purchase of statins and typical cardiovascular drugs, after STEMI, in a large regional database that enrolled patients from 2012 to 2017; adherence was defined as the ratio of bought tablets divided by the number of expected tablets in the follow-up period. Cox regression was used for multivariate analysis; Kaplan Meier and Cox proportional hazard models were performed to evaluate cumulative event rates of all-cause mortality at follow-up

Results

A total of 4062 patients were enrolled, of which 12.6% died after a median of 4.7 years of follow up (IQR 3.7–5.7). Statin adherence lower than 80%, identified as the best cutoff at Youden's analysis, was identified in 42% of the registry population; statin adherent patients were more likely younger, with known dyslipidemia at enrollment, discharged with ACE inhibitors and a potent P2Y12 inhibitor (ticagrelor or prasugrel), and with a statin diverse from atorvastatin. After multivariate adjustment for in-study outcome predictors, low statin adherence was independently associated with all cause mortality (HR 0.57; 95% CI 0.46–0.70; p<0.001), along with older age, not known dyslipidemia at enrollment and clopidogrel at discharge after STEMI

Conclusions

In the contemporary real-world setting, statin adherence following STEMI remains poor, especially in high risk patients, and is still a crucial independent predictor of all-cause mortality. Effective strategies to improve statint adherence remain an unmet clinical need.

Funding Acknowledgement

Type of funding sources: None.
Jena auf Ziel: get all patients with ST-elevation myocardial infarction on EAS/ESC-LDL-C targets
Authors: Makhmudova U , Samadifar B , Maloku A , Haxhikadrija P , Otto S , Schulze P C , Weingaertner O
Published: October 2022

Background and aims

Low-density lipoprotein cholesterol (LDL-C) reduction is an essential part of the 2019 ESC/EAS dyslipidemia guidelines [1]. Only 18% of patients achieve 2019 ESC/EAS LDL-C target goal in secondary prevention [2]. “Jena auf Ziel – JaZ” (“Jena on target”) is a prospective study that aims at LDL-C target attainment in all patients with ST-elevation myocardial infarction (STEMI) and determination of reasons for failed target attainment.

Methods

All STEMI patients were started on atorvastatin 80 mg/ezetimibe 10 mg on admission. LDL-C levels were monitored during the hospital stay and a 12 months follow-up period. Patients were educated about cardiovascular risk factor optimization. Individual patient cards to document LDL-C levels over time were used to enforce LDL-C target attainment.

Results

In the first 50 consecutive patients, LDL-C levels were 3.39±1.23 mmol/L on admission, 1.84±0.86 mmol/L on discharge and 1.30±0.65 mmol/L during the first follow-up visit (6–8 weeks). On atorvastatin 80 mg/ezetimibe 10 mg 14 out of 50 patients (28%) reached the LDL-C goal on discharge, 36 out of 50 patients (72%) after 6–8 weeks. After addition of bempedoic acid or PCSK9-inhibitors all patients which were followed up in our lipid clinic reach the EAS/ESC-LDL-C target. Only two patients reported myalgias of which one patient refused to continue with lipid-lowering drugs. One patient had elevated liver enzymes, which resolved after switching to a lower statin dose.

Conclusions

One out three STEMI patients reached the EAS/ESC-LDL-C target during the initial hospital stay on atorvastatin 80 mg/ezetimibe 10 mg. Adding bempedoic acid or PCSK9 inhibitors resulted in LDL-C target attainment of all patients during follow-up. EAS/ESC-LDL-C target attainment is feasible and well-tolerated in empowered, well-educated patients.

Funding Acknowledgement

Type of funding sources: None.
The effect of trehalose administration on miRNA-10a expression in patients with history of myocardial infarction (MI) and systemic inflammation
Authors: Ganjali S , Jamialahmadi T , Banach M , Sahebkar A
Published: October 2022

Background

MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of endothelial function, inflammatory cells, and cholesterol homeostasis, may cause the onset of vascular inflammation which plays an important role in the development of cardiovascular disease. Trehalose is a nonreducing disaccharide which anti-inflammatory properties have been indicated in different experimental models.

Purpose

This study aimed to evaluate the effectiveness of intravenous (IV) trehalose administration on the circulating level of miRNA-10a as a biomarker of coronary inflammation in patients with history of myocardial infarction (MI) and elevated C-reactive protein (CRP).

Methods

This was a randomized, double-blind trial comprised 15 men (aged 18–80) with history of MI and evidence of systemic inflammation. The patients were randomly allocated to 2:1 ratio and respectively underwent the injection of either IV trehalose (15 g/week) or placebo for 12 weeks. At baseline and at the end of study, the serum level of miRNA-10a was measured by SYBR Green qPCR, quantified by the comparative method, and normalized to U6 expression. Relative expression software tool (REST) was used to analyze the miRNA-10a fold change (FC) expression level.

Results

At the baseline, patients in trehalose group showed slightly lower level of miRNA-10a relative to the placebo group (FC: 0.272, P=0.052), while it was not statistically significant. Within-group analysis showed that miRNA-10a had a significantly lower level in placebo group at the end of the study in comparison with the baseline (FC; 0.19, P=0.029). Albeit, miRNA-10a level increased after trehalose administration in relation to the baseline, while it was not statistically significant (FC: 1.963, P=0.114), Moreover, these changes in miRNA-10a levels were statistically significant in trehalose group related to the placebo group (P=0.047).

Conclusions

Together these findings demonstrate that trehalose administration could effectively increase the circulating level of miRNA-10a and may contribute to the regulation of coronary inflammation in patients with a history of MI and elevated CRP levels. This anti-inflammatory effect of trehalose can be confirmed in the large-scale studies or by evaluating other miRNAs related to the vascular inflammatory processes.

Funding Acknowledgement

Type of funding sources: None.
Differences in aerobic capacity evolution and cardiovascular risk factors between diabetic and non-diabetic patients at different stages of a cardiac rehabilitation
Authors: Uribe Heredia N G , Balaguer Recena J , Piccone Saponara L G , Benitez Peyrat J , Solorzano Guillen C , Jimenez Martinez M E , Toran Martinez C , Castillo Sandoval A , Perez Sanchez A , Casas Sanchez B , Novo Garcia E
Published: October 2022

Introduction

Type 2 diabetes mellitus (DM) is an important factor that is associated with increased cardiovascular morbidity, producing disorders in different devices and systems whose mechanisms are not entirely known. This study was conducted in order to understand the evolution of aerobic capacity and the different cardiovascular risk factors (CVRF) in diabetic patients compared to non-diabetic patients.

Methodology

Prospective observational study. A total of 301 patients were included consecutively in a conventional cardiac rehabilitation program from January 2017 to March 2020, after one month of having had acute coronary syndrome, phase II of which lasted 2 months, who had an analysis, ergometry with spire gas analysis, and anthropometric characteristics were included. Those who had signs of ischemia in ergometry were excluded from the study. The tests were conducted as recommended by the ATS/ACCP.

Results

301 patients were included, with an average age of 57.6±9.1 years, diabetics 92 (30,6%), LVEF average 56.9±9.6%, women 13.6%. Among the basal characteristics, diabetic patients had the highest prevalence of dyslipemia (89.1% vs 68.4% p s <0.001), HTA (62% vs 47.8% p x 0.03) and lower FEVI (55.1±10.26 vs 57.8±8.9 p-0.03), in addition to lower peak oxygen consumption (VO2 ml/kg/min) (18.8±5.0 vs 22.9±6.3 p-<0.001); DM being an independent predictor to obtain a lower VO2 with an OR 1.25 [IC (95%) 1.31–1.19 p<0.001] (Table 1). At the end of Phase II, both groups gained better control of CVRF (Table 2) including an improvement in VO2; but in the DM group the gain rate was significantly lower (0.08±0.14 Vs 0.13±0.17 p=0.02). In phase III (average follow-up 7.3 months) the benefits in the control of CVRF (Table 2) were maintained in both groups with the highest rate of increase in VO2 in patients with DM (0.07±0.2 Vs 0.02±0.13 p=0.05) (Image 1).

Conclusions

In our study, patients with DM undergoing an RHC program achieve better control of FRCV and aerobic capacity in a similar way to non-diabetic patients, which is maintained at 7 months of follow-up in phase III, although initially the aerobic capacity gain in diabetics is slower, achieve a higher increase in VO2 in Phase III.

Funding Acknowledgement

Type of funding sources: None.
The impact of statin on post-operative atrial fibrillation after discharge from cardiac surgery: secondary analysis of the SEARCH-AF CardioLink-1 randomized trial
Authors: Hibibo M , Verma S , Pandey A , Quan A , Verma A , Bisleri G , Ha A , Mazer C D
Published: October 2022

Background

There is conflicting evidence regarding the use of statins to reduce the risk of post-operative atrial fibrillation (POAF) in patients undergoing cardiac surgery.

Purpose

We sought to determine the effects of statin use on the burden of new-onset post-discharge POAF in the Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation (SEARCH-AF) CardioLink-1 randomized controlled trial.

Methods

In the SEARCH-AF trial, 336 patients with risk factors for stroke (CHA2DS2-VASc score ≥2) and no history of preoperative AF were randomized to usual care or continuous cardiac rhythm monitoring for 30 days after discharge from cardiac surgery with a wearable, patched-based device. The primary endpoint was the occurrence of cumulative atrial fibrillation/flutter (AF/AFL) lasting for ≥6 minutes detected by continuous monitoring or AF/AFL documented by a 12-lead electrocardiogram within 30 days of randomization. Using time-to-event analysis and Cox regression, we evaluated the association between the risk of post-operative AF in relation to statin use and dosing intensity (low, moderate, high) at the time of discharge. We excluded patients who experienced post-operative AF during hospitalization in this analysis.

Results

In the overall cohort (n=336), 260 (77.4%) patients were treated with statins at the time of hospital discharge. There were 18 (5.4%) patients who experienced post-operative AF during hospitalization. Patients prescribed with statins were more likely to be male (p=0.018), had lower CHA2DS2-VASc scores (p=0.011), and were more likely to undergo isolated coronary artery bypass grafting (CABG) (p=0.083). Baseline characteristics were otherwise similar between the 2 groups. Patients treated with statins at discharge had a 2-fold lower rate of post-operative AF than those who were not treated with statins in the overall cohort (17.6% vs. 8.2%, Log-Rank p=0.017) and among those who were randomized to continuous cardiac rhythm monitoring (31.6% vs. 16.0%, Log-Rank p=0.027) (Figure). After adjusting for surgery type (CABG vs. valve surgery) and the CHA2DS2-VASc score, statin use at discharge was associated with a lower risk of post-operative AF within 30 days after surgery (hazard ratio 0.48, 95% CI 0.24–0.97). Furthermore, increasing intensity of statin therapy was associated with lower risk of POAF (ptrend=0.0012) (Figure 1)

Conclusion

Among cardiac surgery patients with risk factors for stroke and no history of pre-operative AF, the use of statins was associated with a reduction in post-operative AF risk within 30 days of discharge. The routine use of high-intensity statin to prevent post-operative AF after cardiac surgery deserves further study.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Heart and Stroke Foundation of Canada