bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and reclassification value of serum cathepsin S over the GRACE risk score in patients with non-ST-segment elevation acute coronary syndrome
Authors: Sopova K , Georgiopoulos G , Mueller-Hennessen M , Sachse M , Vlachogiannis N , Biener M , Vafaie M , Katus H , Spyridopoulos I , Giannitsis I , Stamatelopoulos K , Stellos K
Published: November 2020

Background

Cathepsin S is an extracellular matrix degradation enzyme that plays an important role in atherosclerotic cardiovascular disease by inducing vasa vasorum development and atherosclerotic plaque rupture.

Purpose

To determine the prognostic and reclassification value of baseline serum cathepsin S after adjustment for the Global Registry of Acute Coronary Events (GRACE) score, which is a clinical guideline recommended risk score in non-ST-segment elevation acute coronary syndrome (NSTE-ACS).

Methods

Serum cathepsin S was measured by ELISA in 1,129 consecutive patients presenting with acute symptoms to the emergency department for whom a final adjudicated diagnosis of NSTE-ACS was made. All-cause mortality or all-cause death/non-fatal myocardial infarction (MI) after a median follow-up of 21 months were evaluated as the primary or secondary study endpoint, respectively. The Net Reclassification Index (NRI) estimated the reclassification predictive value for risk of each end-point of cathepsin S over the GRACE score.

Results

After a median follow-up of 21 months 101 (8.95%) deaths were reported. The combined endpoint of death or non-fatal MI occurred in 176 (15.6%) patients. Dose-response curve analysis adjusted for the effect of age, gender, diabetes mellitus, high-sensitivity-cardiac troponin T, high-sensitivity C-reactive protein, revascularization and index diagnosis revealed a non-linear association of continuous cathepsin S with all-cause death (P=0.036 for non-linearity; adjusted HR=1.60 for 80th vs. 20th percentiles, P=0.038) or with the combined endpoint (P=0.008 for non-linearity, adjusted HR=1.53 for 80th vs. 20th percentiles, P=0.011). Serum cathepsin S maintained its predictive value for all-cause death (adjusted HR=1.70 highest vs. lowest tertile, 95% CI 1.03–2.82, P=0.039) after adjusting for the GRACE Score. Similarly, cathepsin S predicted the combined endpoint of all-cause death or non-fatal MI (adjusted HR=1.67 highest vs. lowest tertile, 95% CI 1.15–2.42, P=0.007) independently of the GRACE Score. When cathepsin S was added over the GRACE Score it correctly reclassified risk for all-cause death in 20% of the population (P=0.004). Similarly, serum Cathepsin S conferred a significant reclassification value over the GRACE score for all-cause death or non-fatal MI in 15.9% of the population.

Conclusions

Serum cathepsin S is a predictor of mortality and improves risk stratification over the GRACE score in patients with NSTE-ACS. The clinical application of cathepsin S as a novel biomarker in NSTE-ACS should be further explored and validated.

Funding Acknowledgement

Type of funding source: Foundation. Main funding source(s): German Heart Foundation
Obesity predicts subclinical myocardial injury in men and women of all ages: the Nord-Trondelag Health Study
Authors: Lyngbakken M.N , Rosjo H , Hveem K , Omland T
Published: November 2020

Background

Obesity strongly associates with subclinical myocardial injury as quantified by concentrations of cardiac troponin. Body mass index (BMI) is the most commonly used index of obesity, but BMI does not take into account the different phenotypes that arise on the basis of age, sex and body composition. We aimed to investigate the influence of these factors on the association of obesity with subclinical myocardial injury.

Methods

We analyzed total body fat and fat-free mass by bioelectrical impedance analysis and cardiac troponin I (cTnI) with a high-sensitivity assay in 30,778 participants of the prospective observational The Nord-Trøndelag Health Study at study visit 4 (2017–2019). All subjects were free from known cardiovascular disease at baseline, and we excluded subjects with BMI <18.5 kg/m2. Subgroup analyses were performed according to sex and age (<45 years, 45–59 years, ≥60 years). Adjustment was made for established cardiovascular risk factors and indices of body composition.

Results

Median age was 52.1 (range 16.5 to 98.9) years and 56% were women. Concentrations of cTnI were detectable in 60.6% of study participants, and were median 1.5 (0.6 to 2.9) ng/L. Median BMI was 26.7 (24.0 to 29.9) kg/m2. There was a strong and linear association between BMI and cTnI in adjusted models, with a 37.3 (95% CI, 27.6 to 46.9) % increase in concentrations of cTnI per 10 units of BMI (Figure 1). When adjusting for body composition, strong associations were observed for both sexes. The association between BMI and cTnI was stronger with increasing age (Table 1).

Conclusion

Obesity is strongly associated with subclinical myocardial injury. The associations are stronger with increasing age and persisted after adjustment for body composition, suggesting a harmful effect of obesity on the myocardium independently of different obesity phenotypes.

Figure 1. Association between BMI and cTnI

Funding Acknowledgement

Type of funding source: Public Institution(s). Main funding source(s): South-Eastern Norway Regional Health Authority
Risk results from screening for a high cardiovascular disease risk by means of traditional risk factor measurement or coronary artery calcium scoring in the ROBINSCA trial
Authors: Van Der Aalst C , Denissen S.J.A.M , Vonder M , Gratema J.-W.C , Adriaansen H.J , Kuijpers D , Vliegenthart R , Roeters Van Lennep J , Van Der Harst P , Braam R , Van Dijkman P , Van Bruggen R , Oudkerk M , De Koning H.J
Published: November 2020

Aims

Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease (CHD)-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or Coronary Artery Calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial.

Methods and results

Individuals at expected elevated CVD risk were randomized (1:1:1) into the control arm (n=14,519; usual care); screening arm A (n=14,478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n=14,450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. 12,185 participants (84.2%) in arm A and 12,950 (89.6%) in arm B were screened. 48.7% were women, and median age was 62 (InterQuartile Range 10) years. SCORE screening identified 45.1% at low risk (SCORE<10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE≥20%). According to CAC screening, 76.0% were at low risk (Agatston<100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston≥400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%).

Conclusion

We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated.

ROBINSCA flowchart

Funding Acknowledgement

Type of funding source: Public grant(s) – EU funding. Main funding source(s): Advanced Research Grant
The influence of partners on lifestyle-related risk factors in patients after an acute coronary syndrome. Results from the RESPONSE-2 randomized controlled trial
Authors: Verweij L , Jorstad H.T , Minneboo M , Ter Riet G , Peters R.J.G , Scholte Op Reimer W.J.M , Snaterse M
Published: November 2020

Background

Having a partner is associated with better prognosis in patients with cardiovascular disease. However, the influence of partners on modification of patients' lifestyle-related risk factors (LRFs) is unclear. Therefore, we studied the influence of partners and the level of partner participation on LRF modification in patients after an acute coronary syndrome (ACS) or revascularization.

Methods

The RESPONSE-2 trial was a community-based lifestyle intervention trial comparing nurse-coordinated referral to a comprehensive set of lifestyle interventions (physical activity, weight reduction and/or smoking cessation) to usual care. In the current analysis, we investigated the association of having a partner on the improvement in >1 LRF without deterioration in other LRFs at 12 months follow-up. Secondary, the influence of the level of partner participation (participating partner, non-participating partner and no partner) in the intervention group was studied.

Results

In total 824 individuals (411 intervention, 413 control) were included in the analysis. The presence of a partner was comparable in both groups (intervention 74%, control 69%). In the intervention group, 48% of partners participated in the lifestyle interventions. Overall, having a partner was positively associated with improvement in LRFs (odds ratio (OR) 2.57 (95% confidence interval (CI) 1.57–4.21), p<0.001). In the intervention group, having a participating partner was also positively associated with improvement in LRFs compared to patients without a partner (OR 2.45 95% CI 1.25–4.79, p=0.009). When analysed the influence of partners on LRFs separately, patients with a participating partner were most successful in reducing weight compared to patients without a partner (OR 2.71 95% CI 1.16–6.36, p=0.02).

Conclusion

Having a partner is associated with improvement on LRFs in patients after ACS or revascularization. Moreover, patients with participating partners in the lifestyle programs were most successful in LRF modification. Involvement of partners in lifestyle interventions should be considered in routine practice.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Netherlands Organisation for Scientific Research (NWO)
Post-myocardial transitional care in Poland - single centre experience with novel Coordinated Comprehensive Care programme – clinical and laboratory follow-up
Authors: Telec W , Krysztofiak H , Kalmucki P , Baszko A , Szyszka A
Published: November 2020

Background

Cardiac rehabilitation (CR) is an inherent part of the transitional care after acute myocardial infarction (AMI). Polish health care system has created a novel Coordinated Comprehensive Care Program after AMI, which ensures outpatient follow-ups, further invasive treatment and free-of-charge CR for all patients after acute MI.

Purpose

The aim of the study was to analyze the impact of CR on clinical and laboratory characteristics of the patients who completed the recommended programme.

Methods

118 participants were enrolled. They were divided into two groups, depending on the criterium of completion (rehabilitation group) or non-completion (no rehabilitation group) of the CR. The clinical and laboratory data at discharge and after 12 months were collected and analyzed in both groups.

Results

The majority of the patients (n=83, 70,3%) underwent CR. This group was younger in comparison to patients who did not participate in CR (63.0±8.6 vs. 69.8±8.7 years; p<0.01). Index hospitalization was significantly shorter in rehabilitation group (7 vs. 8 days, respectively; p<0,04). LDL-C reduction was observed in both groups, but only rehabilitation group presented statistically significant reduction (median LDL at discharge 108,5 vs. 67,0 mg/dl at follow-up; p<0.01). No rehabilitation group had LDL-C non-significantly decreased (p=0.16). NT-proBNP decreased in both groups over 12 months, but only rehabilitation group had significant reduction (median 590,0 pg/ml at discharge vs. 199,0 at follow-up; p<0.01). Laboratory follow-up is summarized in Figure 1. BMI increased in both groups, with statistical importance in rehabilitation group (p<0,01).

Conclusions

Post-myocardial rehabilitation is more frequently prescribed to younger patients with shorter index hospitalisation. Clinical and laboratory parameters improve more in the group that underwent CR programme and this might warant more effort on increasing CR accessibility and patient enrollement. The phenomenon of weight gain in patients after acute myocardial infarction independently from undergoing rehabilitation program or not needs further research.

Figure 1. 12-month laboratory follow-up.

Funding Acknowledgement

Type of funding source: None
Adherence to guideline-directed medical therapy and its association with re-hospitalization and mortality following coronary artery bypass graft surgery
Authors: Dankner R , Orenstein L , Laufer K , Olmer L , Ziv A , Novikov I , Moshkovitz Y
Published: November 2020

Objectives

We investigated associations with re-hospitalization, and intermediate- and long-term mortality, of cardio-thoracic surgeons' adherence to pharmacological guideline-directed medical therapy (GDMT) in discharge recommendations of coronary artery bypass graft (CABG) surgery patients.

Methods

In this longitudinal multicenter study, 1,131 patients who underwent elective CABG surgery in seven medical centers during 2004–2007 were interviewed in the hospital before surgery. Adherence of cardio-thoracic surgeons to GDMT was considered as prescribing medications from three families: antiplatelet therapy, beta-blockers and statins; and was determined from discharge letters. Patients were interviewed one-year after hospitalization to obtain information on re-hospitalizations and current medications. Mortality information was extracted from the Ministry of Internal Affairs registry and updated until March 2018.

Results

GDMT adherence was evident in the discharge recommendations of 638 patients (56.4%). A propensity score (PS)-weighted multivariate logistic regression showed a 26% lower 1-year risk of re-hospitalization/mortality among patients whose discharge recommendations reflected full adherence than among patients whose recommendations reflected partial adherence (OR=0.74, 95% CI: 0.57–0.97, p=0.03). A PS-weighted Cox proportional hazard model showed 24% lower intermediate (8 year)-term mortality hazard among patients with cardio-thoracic surgeons' adherence to GDMT, compared to other patients (HR=0.76, 95% CI: 0.59–0.98, p=0.03); however the protective effect was attenuated when examining long (14 year)-term mortality. Short- and intermediate-term protective effects were also found when considering only adherence to beta-blockers or statins. Use of GDMT increased 1-year after CABG surgery only in patients who attended cardiac rehabilitation programs after surgery and not in those who did not attend cardiac rehabilitation during that year.

Conclusions

The reference in CABG patients' discharge recommendations to GDMT was associated with a lower 1-y re-admissions/mortality and lower intermediate-term mortality. Cardio-thoracic surgeons should adhere closely to preventive medication guidelines. Cardiac rehabilitation is associated with better post CABG surgery patients preventive treatment.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): Israel National Institute for Health Policy
Managed care improves prognosis in AMI patients irrespectively of the hospital setting. Data from the MAnaged Care for Acute Myocardial Infarction Survivors (MACAMIS) Programme
Authors: Jankowski P , Topor-Madry R , Gasior M , Ceglowska U , Teisseyre P , Ciesla D , Wisniewska A , Gryka P , Wysoczanski W , Zdrojewski T
Published: November 2020

Background

In 2017 a nation-wide system of managed care for MI survivors comprising acute treatment of MI, cardiac rehabilitation and cardiac ambulatory care within one year following MI was implemented in Poland. The managed care programme (MCP) was proved to be related to lower risk of all-cause death. The goal of the analysis was to assess the effectiveness of MCP in patients discharged from university, district, municipal and non-public hospitals.

Methods

The database of survivors of acute MI discharged from hospital from October 1, 2017 to December 31, 2018 was analyzed. Patients who died within 10 days after discharge were excluded from the analysis. The primary end-point was defined as death from any cause. Propensity-Score Matching using nearest neighbor matching was used to form comparable groups of patients participating and not participating in the MCP. The Cox proportional hazard regression analysis was used to assess the relation between MCP and the overall mortality.

Results

MCP was implemented in the first stage in 48 hospitals spread around the country (about 34% of all hospitals treating acute MI patients in Poland). Among them 14 were university, 20 district, 8 municipal and 6 nonpublic hospitals. Out of 34064 patients discharged from hospitals with MCP implemented 10404 patients (30.5%) participated in MCP. They were matched with 10404 patients not participating in the MCP. About 24% of the analyzed patients were discharged from university hospitals, 42% from district hospitals, 20% from nonpublic, 14% from municipal and other hospitals. During 326.3±134.8 days of follow-up 1062 patients died (4.4% vs. 6.5% of patients participating and not participating in the MCP; p<0.001). Hazard ratios related to MCP of patients hospitalized in each hospital categories are presented in the table.

Conclusion

The implemented in Poland nation-wide system of managed care for MI survivors is related to improved survival in all hospital settings.

Funding Acknowledgement

Type of funding source: None
Predisposing factors to acute pancreatitis in patients with severe hypertriglyceridemia
Authors: Juliani F.C , Miname M.H , Chacra A.P.M , Salgado W , Maranhao R.C , Santos R.D , Rocha V.Z
Published: November 2020

Severe hypertriglyceridemia (HTG) is a rare condition defined as fasting triglyceride (TG) levels >885 mg/dL. Besides the association between mild-moderate HTG and cardiovascular disease (CVD), severe HTG is a known risk factor for acute pancreatitis (AP). The factors predisposing patients with severe HTG to AP are not completely clear.

Purpose

Compare patients with severe HTG with and without AP and identify factors predisposing to AP.

Methods

We performed a retrospective search of patients with severe, refractory HTG in our hospital database over the last 10 years. Inclusion criteria: at least one TG≥2,000mg/dL and the latest on-therapy TG≥1,000mg/dL.

Results

From 692 patients with at least one TG≥1,000 mg/dL, 27 met the inclusion criteria. Nineteen (70%) were male, mean age 53±14 y-old. The median maximum TG value was 3,384mg/dL and the latest on-therapy TG was 1,791 mg/dL despite fibrate use; 70,4% were diabetics (44% insulin users; 41% had previous CVD). Patients with AP were younger, with higher fasting glucose and lower HDL-C. However, there were no differences between the AP and no AP groups, regarding maximum and latest TG, diagnosis of diabetes and treated HbA1C.

Conclusion

In this cohort of patients with severe, refractory HTG, those with AP were significantly younger, suggesting a greater genetic role for HTG in this group. There were no other relevant diferences between the AP and no AP groups. Conceivably, other unrecognized factors were at play accounting for the AP events.

Funding Acknowledgement

Type of funding source: Public hospital(s). Main funding source(s): Zerbini Foundation, FAPESP (The The São Paulo Research Foundation)
Levels of phospholipids and triacylglycerol-containing omega 3 fatty acids in myocardial tissue of patients with myocardial infarction: analyzed by a lipidomics profiling method
Authors: Shiozawa T , Shimada K , Lee-Okada H , Kadoguchi T , Aikawa T , Hayashi H , Miyazaki T , Matsushita S , Suwa S , Yokomizo T , Amano A , Nakazato Y , Daida H
Published: November 2020

Objective

According to population-based studies, low omega 3 fatty acid (omega3FA) intake and high levels of serum triacylglycerol (TAG) are associated with cardiovascular diseases. Recent advances in mass spectrometry allow molecular lipid (lipidomics) profiling, which may enhance cardiovascular risk prediction. In this study, we assessed the levels of omega3FA-containing phospholipids (PL) and TAG in myocardial tissues of patients with and without myocardial infarction (MI) using a lipidomics profiling method.

Methods

We performed lipidomics profiling of human left atrial appendage (LAA) tissue of 29 consecutive patients receiving off-pump coronary bypass surgery with standard LAA resection. The patients were divided into the MI group (n=7) and an age- and gender-matched non-MI group (n=7).

Results

Lipidomics profiling revealed that the MI group tended to have low levels of phosphatidylcholines (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), and plasmalogen, and high levels of TAG species. Individual molecular species containing omega3FA, such as PC (18:0/20:5; 3,200±1,200 vs. 4,500±910 pmol/g tissue, p=0.04) and plasmalogen (18:1/20:5; 57,000±21,000 vs. 91,000±28,000 pmol/g tissue, p=0.02), were significantly lower in the MI group than in the non-MI group.

Conclusions

To our knowledge, this is the first study to determine the levels of omega3FA-containing PL and TAG in myocardial tissue using lipidomics profiling. We discovered that lower levels of omega3FA-containing PL and higher levels of TAG existed in myocardial tissues of patients with MI than in those of patients without MI. Accordingly, the lipidomics profiling method for human myocardial tissue may be useful for developing therapy targets for cardiovascular diseases.

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): MEXT/JSPS KAKENHI Grant
The new LDL-C target <55 mg/dL is achieved by less than 40% of very high risk patients with familial hypercholesterolaemia despite receiving PCSK9 inhibitors: real world data
Authors: Rallidis L , Vlachopoulos C , Liberopoulos E , Skoumas I , Kiouri E , Koutagiar I , Anastasiou G , Kosmas N , Tousoulis D , Iliodromitis E
Published: November 2020

Background

The recently published ESC/EAS guidelines for the management of dyslipidaemias have lowered the low-density lipoprotein cholesterol (LDL-C) target in the very high risk patients below 55 mg/dL.

Purpose

To examine how achievable is this target in very high risk patients receiving a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) on top of lipid-lowering treatment (LLT).

Methods

The cohort comprised 158 patients who attended the lipid clinic of 3 hospitals in Greece and started treatment with PCSK9i. Patients were requested to attend the lipid clinic 3 months after the initiation of PCSK9i.

Results

Ninety percent of patients had heterozygous familial hypercholesterolaemia (heFH) and 75% had cardiovascular disease (CVD). One hundred forty patients were classified as very high risk because they had either cardiovascular disease (CVD) or heFH with an additional risk factor for whom a target <55 mg/dL is currently recommended. Of those very high risk patients, 105 (75%) were given PCSK9i due to failure to achieve LDL-C targets despite maximum LLT (high intensity statin at maximum tolerated dose + ezetimibe) while in the rest of cases the indication was statin intolerance. The mean reduction of LDL-C at 3 months was 56.2%. Among 105 very high risk patients (all had heFH), LDL-C below 55 mg/dL was achieved by 37.1% while the previously LDL-C target <70 mg/dL was achieved by 60% (Figure 1).

Conclusions

The new LDL-C target <55 mg/dL is achieved by <40% of very high risk patients with heFH despite receiving triple LLT, i.e. PCSK9i + statin + ezetimibe. This therapeutic gap suggests that there is still need for more effective LLT in very high risk heFH patients to maximize their clinical benefit.

Figure 1

Funding Acknowledgement

Type of funding source: None
Do European patients with peripeheral arterial disease receive optimal lipid lowering therapy and achieve LDL-C goals? Results from the DA VINCI study
Authors: Ray K.K , Feudjo Tepie M , Catapano A.L , Giovas P , Bray S , Masana L , Weiss N , Poulter N
Published: November 2020

Background

2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking.

Purpose

Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD.

Methods

The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT).

Results

Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L.

Conclusions

European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Amgen
Baseline triglycerides and non-HDL-C and apoB goal attainment in the ORION-10 and ORION-11 trials
Authors: Ray K.K , Kallend D , Raal F.J , Stoekenbroek R , Koenig W , Leiter L.A , Landmesser U , Schwartz G.G , Wijngaard P.L.J , Kastelein J.J.P , Wright R.S
Published: November 2020

Introduction

Elevated triglyceride (TG) levels contribute to the total burden of circulating atherogenic lipoprotein levels and are associated with increased cardiovascular (CV) risk. LDL-C underestimates risk in patients with elevated TG. Therefore, 2019 ESC/EAS guidelines recommend apoB or non-HDL-C as secondary lipid goals for patients with TG >150mg/dL.

Purpose

To assess the impact of inclisiran on apoB and non-HDL-C goal attainment across a range of TG levels among patients with atherosclerotic CV disease (ASCVD).

Methods

The ORION-10 and ORION-11 trials included 3178 patients with ASCVD and LDL-C >70mg/dl despite maximally tolerated statins randomized to inclisiran or placebo (1:1). Pre-specified secondary endpoints were placebo-corrected changes in lipids at Day 510. For this analysis patients were stratified by TG quartiles at baseline within each trial. The proportion of individuals attaining apoB <55 mg/dL or non-HDL-C <70mg/dl within each trial were assessed across TG strata and the likelihood of goal attainment within TG strata assessed using logistic regression.

Results

In ORION-10, TG quartiles were ≤94, 94 to ≤128, 128 to ≤181 and >181mg/dl respectively and in ORION-11 corresponding values were ≤101, 101 to ≤135, 135 to ≤183 and >183mg/dl. As compared to placebo a significantly greater proportion of patients randomised to inclisiran attained apoB goals within each TG strata (Table). Similar results were observed for non-HDL-C.

Conclusion

Among patients with ASCVD on maximally tolerated statin and high TG levels, attainment of apoB and non-HDL-C secondary lipid targets was more likely with inclisiran than placebo. Inclisiran may be a useful therapeutic option for patients with atherogenic dyslipidaemia.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): The Medicines Company
Adiposity mediates the association between bilirubin, glucose/insulin homeostasis and inflammation
Authors: Mazidi M , Katsiki N , Mikhailidis D.P , Banach M
Published: November 2020

Background and purpose

The exact contribution of adiposity on the link between bilirubin and glucose/insulin homeostasis and inflammatory factors has not been defined. We aimed to quantify the role of adiposity on this association.

Methods

The variables of interest were extracted from the National Health and Nutrition Examination Survey (NHANES 2005–2010). We assessed the role of body mass index (BMI) as an adiposity factor. Analysis of co-variance and causal mediation analysis were conducted based on survey design and sample weights.

Results

Overall, 10,880 men and 11,462 women were included in the present analysis (mean age=47.2 years). Mean circulating bilirubin for the overall population, men and women was 0.74±0.02, 0.83±0.03 and 0.65±0.03 mg/dl, respectively (p<0.001, for the comparison between sexes). In an adjusted model, glucose/insulin homeostasis and inflammatory factors were more favorable for participants with a higher level of bilirubin in both sexes (p<0.001 for all). The extent of the mediation was maximal between the homeostatic model assessment of insulin resistance and bilirubin (men: 45%, women: 58%). In post-menopausal women, 47 and 13% of the changes in insulin and triglyceride-glucose index in response to bilirubin levels could be explained by alterations in BMI. In smokers, BMI could mediate 53% of the association between bilirubin and insulin (p<0.001). Similar results were obtained when participants with normal liver function were analyzed separately (see Figure).

Conclusions

Using advanced statistical techniques we analyzed the complex link of bilirubin with inflammation and glucose/insulin homeostasis and identified a role for adiposity. We also suggest that bilirubin has an anti-inflammatory role.

Funding Acknowledgement

Type of funding source: None
Association between insulin resistance and left ventricular diastolic dysfunction in non-diabetic general population
Authors: Kamon T , Kaneko H , Itoh H , Kiriyama H , Koyama K , Fujiu K , Morita H , Uno K , Hayashi N , Komuro I
Published: November 2020

Background

Insulin resistance due to visceral fat accumulation plays a central role in the development of diabetic mellitus and subsequent cardiovascular disease. Abdominal obesity and diabetic mellitus are associated with the progression of left ventricular diastolic dysfunction which is the major structural abnormality in patients with heart failure. However, whether insulin resistance influences left ventricular diastolic dysfunction in non-diabetic subjects is unclear.

Purpose

In this study, we aimed to clarify the association between insulin resistance and left ventricular diastolic dysfunction in non-diabetic general population.

Methods

We examined 2,572 non-diabetic subjects with preserved left ventricular systolic function (ejection fraction ≥50%) and without a past history of diabetic mellitus, heart failure, coronary artery disease, atrial fibrillation, stroke, moderate to severe valvular disease, who underwent medical check-ups at the University of Tokyo Hospital from January 2009 to December 2018. Diabetes mellitus was defined as fasting glucose level ≥126 mg/dL or a subject's use of oral antidiabetic medications or insulin. We calculated the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) score [HOMA-IR = fasting glucose (mg/dL) × insulin (μU/mL) / 405], and defined insulin resistance as HOMA-IR ≥2.5. Left ventricular diastolic function was assessed by echocardiography, using tissue doppler analysis (E/E' ratio in septal and lateral). Visceral adiposity was assessed as visceral fat volume measured by computed tomography scanner.

Results

Mean age was 53.3±9.8 years, and 1,746 subjects (67.9%) were male. Overall, HOMA-IR was 1.1 on average, and HOMA-IR ≥2.5 was observed in 5.0% of study population. BMI and the prevalence of obesity were higher in subjects with HOMA-IR ≥2.5 than in those without. There was no significant difference in left ventricular ejection fraction between HOMA-IR ≥2.5 and ≤2.5. E/E' ratio in septal and lateral were higher in subjects with HOMA-IR ≥2.5 than in those without. Multivariable logistic regression analysis demonstrated that obesity and waist circumference, visceral fat volume were independently associated with HOMA-IR ≥2.5, however, age, hypertension, hypercholesterolemia were not. Further, multiple regression analysis including insulin resistance, age, male gender, obesity, hypertension, hypercholesterolemia, cigarette smoking and visceral fat volume, showed that insulin resistance was an independent determinant of increasing E/E' in both septal and lateral, whereas visceral fat volume was not (Figure 1).

Conclusion

The results of the present study suggest that insulin resistance due to visceral fat accumulation might be associated with the development of left ventricular diastolic dysfunction in non-diabetic general population without overt cardiovascular disease.

Figure 1

Funding Acknowledgement

Type of funding source: None
Estimating cardiovascular disease-free life-years with the addition of semaglutide in people with type 2 diabetes using pooled data from SUSTAIN 6 and PIONEER 6
Authors: Westerink J , Sommer Matthiessen K , Nuhoho S , Fainberg U , Lyng Wolden M , Visseren F , Sattar N
Published: November 2020

Introduction

Cardiovascular disease (CVD) is the leading cause of disability and death in people with type 2 diabetes (T2D). In a post hoc analysis of pooled data (POOLED cohort) from two phase 3, randomized CV outcomes trials, SUSTAIN 6 (NCT01720446) and PIONEER 6 (NCT02692716), the addition of the glucagon-like peptide-1 analogue semaglutide to standard of care (SoC) in people with T2D at high risk of CVD significantly reduced the risk of major adverse CVD events (3-point MACE: CV death, non-fatal stroke and non-fatal myocardial infarction).

Purpose

To estimate the effect of adding semaglutide to SoC on CVD-free life-years and 10-year CVD risk in patients with T2D by predicting individual patient-level risk of CVD events in the POOLED cohort using the DIAL CVD risk model.

Methods

The 3-point MACE hazard ratio from the POOLED cohort (N=6480; HR = 0.76 [95% confidence interval [CI]: 0.62–0.92]) was applied to the patient-level lifetime risk of CVD events derived from the DIAL model. CVD-free life-years and 10-year CVD risk were then calculated based on the age-specific risks of CVD events and non-vascular mortality, using standard actuarial methods. Both new and recurrent CVD events were considered. The DIAL model was validated by comparing the predicted and observed number of CVD events after 1 year. The DIAL model was previously developed using data from people with T2D in the Swedish National Diabetes Registry and validated across geographical regions.

Results

The DIAL model was considered valid for use in the POOLED cohort because the predicted number of CVD events at 1 year was within 5% of the number observed. Adding semaglutide to SoC was associated with a mean reduction in 10-year CVD risk of 20.0% (95% CI: 6.4–32.6%) and a mean increase of 1.72 (95% CI: 0.52–2.96) CVD-free life-years. The number of mean CVD-free life-years gained ranged from 0.62–2.91 years between age groups (Table). For a 60-year-old male with baseline characteristics matched to the average male from the POOLED cohort, adding semaglutide to SoC reduced 10-year CVD risk by 20.8% and provided 2.53 additional CVD-free life-years. The number of CVD-free life-years decreased when baseline age was increased (Figure).

Conclusions

The addition of semaglutide to SoC was associated with a gain in CVD-free life-years. This analysis helps contextualize the results of CV outcomes trials and may help to inform clinical decision-making.

Funding Acknowledgement

Type of funding source: Private company. Main funding source(s): Novo Nordisk A/S
Chronotropic incompetence and exercise capacity after mitral valve surgery: the importance of blood hemoglobin level
Authors: Kanazawa M , Toyoda M , Seki T , Iguchi A , Takahashi S , Kagaya Y , Sato K , Saito H , Ito K , Miura M , Kondo M , Kawatsu S , Endo H , Oda K , Nakamura A
Published: November 2020

Background

Chronotropic incompetence (CI) is sometimes observed during exercise training of cardiac rehabilitation in patients with cardiac surgery, however, little is known concerning the differences between patients with mitral valve (MV) and aortic valve (AV) surgery.

Purpose

Because the possibility exists that cardiac sympathetic nerves might be impaired by left atrium incision, we hypothesized that the incidence of CI was higher in patients with MV surgery (Mitral Valve Replacement and Mitral Valvuloplasty) as compared with patients with AV surgery (Aortic Valve Replacement). And if so, which factor determines the exercise capacity of patients after MV surgery. We thus aimed this study to elucidate the hypothesis with cardiopulmonary exercise testing (CPX).

Methods

We performed CPX by ramp loading with ergometer exercise in total 61 patients who had undergone elective cardiac valve operation (25 patients with MV surgery, age 59.2±9.9 years; 36 patients with AV surgery, age 64.6±12.3 years). We analyzed chronotropic response index (CRI), peak oxygen uptake (peak VO2/W), anaerobic threshold (AT), and peak oxygen pulse (peak VO2/HR) with CPX, and blood hemoglobin concentration (Hb).

Results

The value of CRI was significantly decreased in the patients with MV surgery compared with those with AV surgery (MV; 0.19±0.10 vs. AV; 0.41±0.17, p<0.001). Peak VO2, peak VO2/HR and Hb were not significantly different between patients with MV and those with AV surgery. Patients with MV surgery showed correlations between peak VO2 and Hb (r=0.45, p<0.05), AT and Hb (r=0.52, p<0.01), and a strong correlation between peak VO2 and peak VO2/HR (r=0.63, p<0.001), but not in those with AV surgery.

Conclusions

The present study demonstrated that higher incidence of CI was shown in patients with MV surgery as compared with those with AV surgery. The exercise capacity of patients with MV surgery was determined by peak VO2/HR and Hb. These results suggest that 1) left atrium incision impairs cardiac sympathetic nerves and causes CI, 2) peak VO2/HR which is consisted of arterio-venous oxygen difference and Hb is critical indicator for exercise capacity in patients with MV surgery with CI.

Main results

Funding Acknowledgement

Type of funding source: None
Impact of body mass index on the clinical outcomes in heart failure patients undergoing cardiac rehabilitation
Authors: Kunimoto M , Shimada K , Yokoyama M , Fujiwara K , Honzawa A , Yamada M , Matsubara T , Matsumori R , Abulimiti A , Asai T , Amano A , Morisawa T , Takahashi T , Daida H
Published: November 2020

Background

Increased body mass index (BMI) has recently shown to have a favorable effect on the prognosis in heart failure (HF) patients. However, the impact of BMI on clinical events and mortality in HF patients who underwent cardiac rehabilitation (CR) remains unclear.

Purpose

This study aimed to investigate whether the obesity paradox is present in HF patients who have undergone CR.

Methods

This study enrolled 238 consecutive HF patients who had undergone CR at our university hospital between November 2015 and October 2017. The clinical characteristics and anthropometric data of these patients, including BMI, were collected at the beginning of the CR. The major adverse cardiovascular event (MACE) was defined as a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data regarding the primary endpoints were collected until November 2018.

Results

Patients (mean age 68.7 years, male 61%) were divided into four groups as per BMI quartiles. More patients in the highest BMI group were women, were significantly younger, and had a higher prevalence of hypertension, dyslipidemia, and diabetes mellitus; however, no significant differences were observed in the prevalence of chronic kidney disease, left ventricular ejection fraction, and brain natriuretic peptide levels of the four groups. During a median follow-up duration of 583 days, 28 patients experienced all-cause mortality, and 42 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the highest BMI quartiles had lower rates of MACE (Log-rank P<0.05) (Figure 1). After adjusting for confounding factors, Cox regression multivariate analysis revealed that BMI was negatively and independently associated with the incidence of MACE (hazard ratio: 0.89, 95% confidence interval: 0.83–0.96, P<0.05).

Conclusion

Increased BMI was associated with better clinical prognosis even in HF patients who have undergone CR Therefore, BMI assessment may be useful for risk stratification in HF patients who have undergone CR.

Figure 1. Kaplan-Meier survival curve

Funding Acknowledgement

Type of funding source: None
National quality indicators to promote cardiac rehabilitation service effectiveness in Australia
Authors: Gallagher R , Astley C , Thomas E , Zecchin R , Ferry C , Woodruffe S
Published: November 2020

Background/Introduction

Comprehensive exercise-based cardiac rehabilitation (CR) has well-established efficacy and effectiveness for improving patients' outcomes. There is substantial variability in terms of clinical effectiveness and quality measurement of CR programs internationally which limits service improvement initiatives. In Australia in 2018 a the Australian Cardiovascular Health and Rehabilitation Association (ACRA) and the National Heart Foundation of Australia (NHFA) combined forces to develop nationally-agreed, internationally-consistent, locally-relevant quality indicators (QI).

Purpose

To provide a minimum set of standardised national-level QI that should be collected and reported on by CR programs to determine the quality of delivery and associated outcomes, benchmark performance and support improvement processes.

Methods

We formed the National Cardiac Rehabilitation Measurement (NCRM) Taskforce led by ACRA and NHF and used the National Institute for Health and Care Excellence (NICE) UK guidelines to develop high quality QIs. The process included topic overview, prioritising areas for quality improvement, drafting and consultation, validation and consistency checking.

Results

Eleven preliminary QIs were circulated for ranking and comment to all ACRA members (predominately multidisciplinary CR providers) (68 responses), and to leading national multidisciplinary CR experts from cardiology, research, physiotherapy, nursing, epidemiology and register backgrounds (7 responses). Ratings, comments and suggestions were collated and discussed by the NCRM Taskforce, and the indicators rated most important, useful and feasible were retained, resulting in 10 QIs. These 10 QIs were presented at the ACRA national conference and then discussed at a workshop (55 participants) for this purpose. Ten QIs and accompanying data dictionary with definitions, evidence and allowable values is the final product.

Conclusions

A minimum set of locally relevant, internationally recognised, national QIs for CR is now available for CR providers, health service managers and researchers in Australia, which may be relevant internationally. The QIs will best serve national interests incorporated within a national cardiac registry but will also be useful for site audits and have strong potential to be aggregated across sites, health districts and states. The definitive test of the QIs will be how useful they are for CR program coordinators and funders of such programs; a key consideration for building sustainable business models and ensuring long-term implementation.

Funding Acknowledgement

Type of funding source: None
Impact of cardiac remodelling on physical fitness measured by VO2 max in preadolescent and adolescent endurance athletes
Authors: Bjerring A.W , Landgraff H.E.W , Leirstein S , Haugaa K.H , Hallen J , Edvardsen T , Sarvari S.I
Published: November 2020

Background

Endurance training is associated with both physiological cardiac remodelling and increased maximal oxygen uptake. The relationship between VO2 max and cardiac dimension has not been described in young athletes or in longitudinal studies.

Aims

This study aims to explore the impact of cardiac remodelling on VO2 max in a cohort of young athletes assessed at age 12, 15 and 18.

Methods

Seventy-six promising young cross country skiers were examined at age 12 with echocardiography, including 3D and cardiopulmonary exercise test (CPX). Forty-six (61%) participated in the first follow-up at age 15 and 36 (47%) athletes completed the second follow-up at age 18. The impact of left ventricular (LV) mass and LV end-diastolic volume (EDV) on VO2 max at each time point was assessed using mixed model analysis. Correlation coefficients were calculated at each time point.

Results

There were moderate to very strong correlations between the cardiac parameters and VO2 max at all time points (Figure). In the full model, each improvement in VO2 max of 1000 mL/min at age 15 was associated with an increase in LV mass of 18 g (p<0.001) and an increase in LV EDV of 36 mL (p<0.001), while each improvement in VO2 max of 1000 mL/min at age 18 was associated with an increase in LV mass of 19 g (p<0.001) and LV EDV of 31 mL (p<0.001).

Conclusion

Physical fitness measured by VO2 max is strongly correlated to LV mass and volume in adolescent athletes, suggesting a strong link between cardiac adaption and VO2 max in young athletes.

Figure 1

Funding Acknowledgement

Type of funding source: Public grant(s) – National budget only. Main funding source(s): South-Eastern Norway Health Authority