bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of depression in type 2 diabetes patients with and without cardiovascular disease
Authors: Zareini B , Soerensen K K S , Blanche P B , Falkentoft A C F , Fosboel E F , Koeber L K , Torp-Pedersen C T P
Published: November 2023

Background

Information on how subtypes of incident cardiovascular disease (CVD) affect the rate of depression in patients with type 2 diabetes (T2D) can help identity high-risk patients.

Purpose

To compare the incidence of depression among patients with T2D with incident CVD relative to patients with T2D free of CVD but similar duration of T2D.

Methods

Patients diagnosed with incident T2D without CVD or psychiatric disease were identified from the Danish registries between 2000 and 2018. CVD was defined as the first diagnosis of acute myocardial infarction (AMI), heart failure (HF), stroke, or peripheral artery disease (PAD). The patients were followed 90 days after first T2D diagnosis until first occurrence of depression, emigration, death, one year after CVD development, or end of the study (December 31, 2019). We used time-dependent Poisson regression to estimate the incidence rate ratios (IRR) of depression following different types of CVD compared with patients without CVD. The model included age, sex, comorbidities, calendar year, T2D duration, educational level, and living situation as covariates.

Results

Among 175,916 incident T2D patients (median age 61 (IQR:51;70), 59% males) followed for 1,306,228 person-years (py), 34,825 experienced depression. The crude incidence rate of depression per 1000 py (95% confidence interval) in patients without CVD was 25.8 (16.8;37.9). Compared with T2D patients without CVD, adjusted IRR of depression following AMI, stroke, PAD, and HF was: 2.4 (1.8;3.1) 5.7 (5.3;6.2), 2.5 (2.2;2.9), 2.3 (2.1;2.6), respectively.

Conclusions

All CVDs was associated with increased rate of depression, but highest rate was seen in T2D patients with stroke.
Physical exercise as a treatment for persisting symptoms post covid infection
Authors: Kogel A , Machatschek M , Scharschmidt R , Wollny C , Lordick F , Ghanem M , Laufs U , Fikenzer S
Published: November 2023

Background and purpose

Subsequent to the health problems of the acute phase of SARS-CoV-2 infection, the long-term consequences of SARS-CoV-2 infection are affecting large numbers of patients worldwide. To date, no evidence-based treatment is available for the increasing number of patients with persisting symptoms post COVID 19 infection. We hypothesized that physical exercise may represent a safe and effective treatment option post COVID.

Methods

We performed a systematic search of the literature that revealed a lack of randomized training studies in patients post COVID. Based on these findings a prospective randomized controlled study with open-label and blinded endpoint evaluation was designed. 272 patients with symptoms of fatigue persisting over 6 weeks post COVID infection were screened. Patients with cardiovascular findings were excluded. 44 patients consented and were randomized to four weeks of supervised personalized strength endurance training for 4 weeks or usual care (Fig.1). The mean age was 42.7±13.4 years, and 61% were females.

Results

The individualized combined training was very well tolerated by the participants and the exercise compliance (quality of training) was high at 96.7 ± 2.0 %. There were no adverse events related to the training. Spirometric analysis showed a significantly higher increase in VO2peak (exercise: 10.0±12.7% vs. control: 0.1±8.9%, p<0.01) and oxygen-pulse (exercise: 9.8±10.8% vs. control: 0.0±13.9%, p<0.05) indicating the training effects of the intervention (Fig.2). Parameters of the Multidimensional Fatigue inventory-20 (MFI-20), the McGill Quality of Life Questionnaire (MQOL), and the Post-COVID-19 Functional Status (PCFS) were significantly improved after 4 weeks in both groups. The improvements in fatigue and quality of life were not statistically different between the training and usual care groups.

Conclusion

An individualized exercise program is a safe and well-tolerated treatment option in patients with persisting symptoms post-Covid. These patients significantly improve in physical performance after 4 weeks compared to patients without exercise intervention. Fatigue and quality of life improve over time in individuals that are willing to participate in a training study irrespective of allocation to the training group.Fig. 1:Flow diagram of the inclusion process in the PCTS studyFig. 2:Changes in relative oxygen uptake, oxygen pulse, and MFI-20 of the exercise and the control group between T0: baseline visit and T1: after exercise intervention or after the corresponding period in the control group. The red line represents the mean.*: p<0.05; **: p<0.01 ***: p<0.001, ****: p<0.0001, #: p<0.05 percentual change between groups.
The role of preparticipation screening in detecting silent coronary artery disease in master athletes: a way to prevent exercise-related adverse cardiovascular events
Authors: Scarfo' G , Rizza A , Fusi J , Besola L , Colli A , Franzoni F
Published: November 2023

Introduction

Regular exercise reduces morbidity and mortality from cardiovascular diseases through cardiac and systemic adaptations including the increased coronary blood flow, an improved endothelial function, a slower progression of atherosclerotic processes as well as the stabilization of pre-existing lesions. However, long-term exercise is frequently associated with adverse cardiovascular events in 35-year older subjects because of a cardiac remodeling that predisposes to malignant arrhythmias and to an earlier atherosclerosis. Moreover, in athletes, ischemia is often silent with a higher risk of sudden cardiac death.

Purpose

The aim of our observational study was to evaluate the efficacy of preparticipation screening in identifying the presence of coronary artery disease (CAD) in a population of asymptomatic master athletes.

Methods

Between 2018 and 2019, 420 35-year older athletes (mean age: 55 + 17) underwent a preparticipation screening at the University of Pisa. None of them reported cardiovascular risk factors or previous cardiovascular diseases. After a physical examination, all subjects were submitted to spirometry and ECG stress test.

Results

The ECG stress test demonstrated signs of myocardial ischemia (ST depression > 1 mm) in 41 subjects; 3 athletes showed a frequency-dependent left bundle-branch block; 24 subjects had exercise-induced premature ventricular complexes during the ECG stress test. These subjects underwent further evaluations (Tc-99 myocardial perfusion SPECT and coronary angio-CT) to detect the presence of perfusion defects or coronary abnormalities: 26 athletes had an important coronary atherosclerosis with significant stenosis in one or more vessels and later subjected to Percutaneous transluminal coronary angioplasty (PTCA) or to coronary artery bypass grafting (CABG). 5 athletes presented a coronary myocardial bridge and 1 subject was demonstrated to have an anomalous origin of the left coronary.

Conclusions

Preparticipation screening in 35-year-older athletes was able to detect the presence of obstructive coronary artery disease (CAD) in the 38% of suspected cases and anomalous origin or intramural coronary course in 8,8% of cases that showed electric abnormalities during the stress test. Despite recent conflicting opinions about the scientific value of the preparticipation screening in young athletes, the present study demonstrated that it was fundamental to early detect silent conditions that could predispose master athletes to adverse cardiovascular events.
Effect of exercise training on cardiorespiratory fitness, quality of life and objectively measured physical activity in patients undergoing anthracycline-based chemotherapy: the Caprice RCT
Authors: Stuetz L , Schneider C , Dierks A , Campbell K , Wilhelm M , Eser P
Published: November 2023

Introduction

Exercise training based cardio-oncologic rehabilitation programmes (ET) were shown to counteract the loss in cardiorespiratory fitness and quality of life (QoL) and reduce cancer fatigue during anthracycline-based chemotherapies (AC). It is unknown whether these changes are due to greater volumes of physical activity (PA) induced by ET and whether ET is associated with greater objectively measured daily PA compared to guideline-based recommendation of PA.

Method

Patients with breast cancer or lymphoma receiving AC were recruited from four cancer centres in Switzerland and randomly assigned to three months centre-based ET during (EXduringAC) or after (EXpostAC) AC. All patients were counselled on guideline directed PA and PA was measured with an activity tracker. Primary endpoints were peak VO2, fatigue and QoL after AC (AC-end) and at 3 months follow-up. PA and steps were compared between days with and without centre-based training session.

Results

Data of 51 patients were available. Neither Intention-to-Treat (ITT) nor Per-Protocol (PP) analyses revealed between group differences with regard to peak VO2, fatigue, and QoL at neither AC-end nor follow-up (Figure 1). There was also no between group difference with regard to PA and steps, however, compared to EXpostAC, in EXduringAC the steep decline in PA and steps in AC cycles 3 and 4 was prevented (PP analysis, Figure 2). PA on days with centre-based training sessions was 28 (95% confidence interval 24-32) min higher and patients performed 4382 (3995-4768) steps more compared to days without centre-based training sessions.

Conclusion

ET performed during or after AC had no additional effect on changes in peak VO2, fatigue, or QoL assessed at AC-end or follow-up compared to using an activity tracker alone, possibly due to the lack of additional PA completed by patients during ET. This is the first study that objectively measured the effect of ET on PA and daily step count during and following AC. While days with centre-based ET had significantly more PA and steps, this surplus was likely to be compensated on days without centre-based ET.Figure 1Figure 2
Typical and atypical chest pain: an equivocal and dangerous definition
Authors: Cosmi D , Tarquini B , Mariottoni B , Bennati M , Morganti M , Cosmi F
Published: November 2023

Background

The traditional classification of stable chest pain into typical, atypical and non anginal1 is equivocal and can lead to doctor's decisions and patient's perception that do not correspond to the real importance of the clinical picture.

Methods

In the last 15 years, 3,588 outpatients, aged >35 years (mean 64±9, female 55%) were evaluated for stable chest pain reported for more than 48 hours. We excluded 290 patients with a history of myocardial infarction or angina pectoris, heart failure, valve diseases or any other major cardiovascular event, or ECG signs of recent ischemia. In the other 3,298 cases we applied the traditional classification of chest pain. All patients were evaluated for the presence of HEART score risk factors² (smoking, obesity, family history of cardiovascular events, hypertension, diabetes, hypercholesterolemia) as well as age. All patients with typical or atypical angina and those with non-anginal pain according to the physician's judgment were evaluated with one or more functional cardiovascular tests (exertion test, nuclear stress tests, stress echo).A follow-up was performed at 6 months and 1 year, for the detection of major cardiovascular events (cardiovascular death, non-fatal heart attack, revascularization, stroke) and non-cardiovascular mortality.

Results

Table 1 shows the results of chest pain classification and positive functional test. Table 2 shows major events at one year of follow-up stratified according to the initial assessment of chest pain. Table 3 stratifies the events according to the extent of the risk factors and age. It is evident that a positive functional test is also present in 10% of patients with atypical pain and in 4% of those with non-anginal pain. Patients with typical pain undergo revascularization more frequently (39%). The peculiarity of our study is that the prognosis and rate of events do not differ in terms of clinical and ischemic burden among the 3 groups at 1 year of follow-up, except when patients are stratified by risk burden and for age (Table 4). About 1% of patients had a clinical event regardless of the type of pain and the presence of ischemia and 87% of the events involved patients with ≥ 3 risk factors or heavy smokers. Nine percent of all heavy smokers aged <65 years had a major event and are the highest risk group with a peak of 12.5% in those with atypical pain.

Conclusions

The traditional classification of stable chest pain should be abandoned, as it does not correlate with actual disease burden and prognosis, that appears to be linked to the burden of cardiovascular risk and above all to smoking in patients < 65 years of age, rather than to the clinical and ischemic burden. It will be necessary to evaluate whether the anatomical burden for the search of high-risk coronary lesions improves the prognosis with added value with respect to the treatment of risk factors³.Picture 1Picture 2
Non-HDL cholesterol and residual risk of myocardial infarction and death in statin-treated patients with and without diabetes
Authors: Hansen M K , Mortensen M B , Olesen K K W , Thrane P , Maeng M
Published: November 2023

Background

Patients with coronary artery disease continue to be at risk of myocardial infarction despite lipid-lowering treatment with statins. However, it is uncertain whether non-high-density lipoprotein (non-HDL) cholesterol identifies increased residual risk in patients with and without diabetes.

Purpose

To test the hypothesis that non-HDL cholesterol identifies residual risk of myocardial infarction and death in statin-treated patients with and without diabetes.

Methods

Contemporary cohort study of consecutive patients undergoing coronary angiography (CAG) for evaluation of coronary artery disease between 2011 and 2020. Analyses were performed in the semi-national Western Denmark Heart Registry. Non-HDL cholesterol was calculated within one year after CAG as total cholesterol minus HDL cholesterol and divided into four groups according to percentile level (<25th, 25th-74th, 75th-94th, and ≥95th percentile). Outcomes were diagnosis of myocardial infarction and all-cause death occurring between one year after CAG and end of follow-up (July 31, 2022). Risk according to non-HDL-C percentile group was estimated as adjusted hazard ratio (95% confidence interval).

Results

A total of 105,804 patients underwent CAG. We included 54,037 statin-treated patients with median duration of follow-up 4.6 years. Among 11,400 patients with diabetes, we observed 587 myocardial infarctions and 2,654 patients died. In 42,637 patients without diabetes, we observed 1,548 myocardial infarctions and 5,842 patients died. The risk of myocardial infarction was similarly increased in patients with and without diabetes. Compared to non-HDL cholesterol <25th percentile, the adjusted hazard ratios were in patients with diabetes 1.2 (95% CI: 0.9-1.5) for 25th-74th percentile, 1.3 (95% CI: 0.9-1.9) for 75th-94th percentile, and 2.2 (95% CI: 1.3-4.0) for ≥95th percentile, and in patients without diabetes 1.0 (95% CI: 0.9-1.2), 1.3 (95% CI: 1.0-1.6), and 2.0 (95% CI: 1.4-3.0). Non-HDL cholesterol was associated with increased risk of death in patients without diabetes with adjusted hazard ratios of 1.0 (95% CI: 0.9-1.1), 1.3 (95% CI: 1.2-1.5), and 2.1 (95% CI: 1.6-2.6), however this association was attenuated in patients with diabetes (0.9 (95% CI: 0.8-1.0), 1.0 (95% CI: 0.9-1.2), and 1.2 (95% CI: 0.9-1.7)). Results were similar when stratifying on presence of obstructive coronary artery disease in both patients with and without diabetes.

Conclusion

In statin-treated patients with and without diabetes, non-HDL cholesterol identified residual risk of myocardial infarction. Further, elevated non-HDL cholesterol was associated with increased risk of all-cause death in patients without diabetes.Figure 1.Figure 2.
Carotid plaque score for stroke and cardiovascular risk prediction in a middle-aged cohort from the general population: the akershus cardiac examination 1950 study
Authors: Ihle-Hansen H , Vigen T V , Berge T B , Walle-Hansen M W H , Hagberg G H , Ihle-Hansen H I H , Thommessen B T , Ariansen I A , Rosjo H R R , Ronning O M R , Tveit A T , Lyngbakken M L
Published: November 2023

Background

Assessment of carotid atherosclerosis with ultrasound may have an unfilled potential in predicting stroke and cardiovascular events.

Purpose

We aimed to explore the predictive value of the carotid plaque score compared to the Systematic COronary Risk Evaluation (SCORE) 2 risk prediction algorithm, on incident stroke and major adverse cardiovascular events (MACE), and establish a prognostic cut-off for the carotid plaque score.

Methods

In the prospective Akershus Cardiac Eexamination (ACE) 1950 cohort study, carotid plaque score was calculated with ultrasound at inclusion in 2012-2015. The largest plaque diameter in each extra cranial segment of the carotid artery both sides was measured and scored from 0-3 points. The sum of each segment provided the carotid plaque score. Incident stroke and composite endpoint MACE (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) was assessed by linkage to national registries throughout 2020.

Results

Carotid plaque score was available in 3650 (98.5%) of the participants, with mean age at inclusion was 63.9±0.64 years. Only 462 (12.7%) were free of plaque and the median carotid plaque score was 2 (IQR 1-4). By the end of 2020, 42 (1.2%) subjects had experienced a stroke and 145 (4.0%) a MACE. Carotid plaque score was a predictor of incident stroke (HR 1.25, 95%CI 1.15-1.36) and MACE (OR 1.21, 95%CI 1.14-1.27) after adjustment for SCORE2, and outperformed SCORE2 in predicting stroke (p=0.001). The best cut-off value for carotid plaque score determined by receiver operator characteristics area under the curve was ≥4 with a positive predictive value 2.5% and negative predictive value 99.3%.

Conclusion

Carotid plaque score is a strong predictor of incident stroke and MACE and outperforms SCORE2 for risk prediction in a middle-aged cohort recruited from the general population. A cut-off score of ≥4 seems to be suitable to identify high-risk subjects.Graphical AbstractCarotid plaque score distribution
Rapid access chest pain clinic; insights from 10 years of an australian experience
Authors: Shawki M , Azzopardi R , Al-Fiadh H , Liu F , Lin Y C , Sanders K , Al-Fiadh A
Published: November 2023

Introduction

Rapid Access Chest Pain Clinic (RACPC) has been established in the UK as a safe and cost-effective model for managing low to intermediate Cardiovascular Disease (CVD) risk chest pain patients. In our institute, this service was established in 2012 based on the UK model.

Purpose

This study aimed to assess the safety, efficacy, and cost-effectiveness of the RACPC at a large metropolitan health service in Australia to inform future models of care.

Patients and Methods: We conducted a retrospective analysis of consecutive patients who attended RACPC between 2012 and 2022. Patients aged 25-85 years with low to intermediate CVD risk chest pain and no previously known ischaemic heart disease were included. RACPC staff comprised of a multidisciplinary team of cardiologists, nurse practitioners, and cardiology liaison nurses. The primary outcome was to benchmark our clinic model against national peers. The secondary outcome was to examine the pattern and accuracy of requested cardiac imaging used in RACPC, identify the frequency of incidental findings resulting from imaging and determine the cost-effectiveness of RACPC.

Results

Over the ten-year study period, a total of 4,194 patients were seen. The median waiting time from referral to consultation was 15.5 days (5 - 21.5). Attendance rates gradually increased from 71% to 95% in the clinic's tenth year of operation. Furthermore, the number of missed appointments and cancellations decreased over the years, reaching 1% and 4%, respectively. A total of 1,758 CT Coronary Angiogram (CTCA); 1,629 functional assessments utilising either Transthoracic Stress Echocardiogram (TSE) or Myocardial Perfusion Scan (MPS), and 174 Invasive Angiography (IA) procedures were requested. 1.2% of the cohort had IA without any prior non-invasive cardiac imaging. CTCA was the most frequently requested modality and resulted in the highest rates of incidental findings (24%) such as pulmonary nodules and vascular anomalies, often leading to further investigations. The rate of non-invasive cardiac imaging resulting in IA for CTCA, TSE and MPS were 7.3%, 2.5%, and 6.4%, respectively. Revascularisation rate for positive IA, CTCA, TSE and MPS were 33.3%, 34.6%, 26.7% and 20% respectively. At our health service, and for the purpose of comparison, we encountered an average of 52 patients/year with low to intermediate CVD risk hospitalised for chest pain assessment with an average length of stay of 2.35 days at a cost of 250,000 Australian Dollars ($4808/patient). Whilst at RACPC, an average of 419 patients/year were seen with a total cost of around 62,400 A$ ($149/patient).

Conclusion

RACPC is a safe, efficient, and cost-effective model of care, with CTCA being the preferred modality of imaging due to its high diagnostic accuracy, high negative predictive value and high rate of significant incidental findings.
Pulse wave velocity has an additive prognostic value to SCORE2 in apparently healthy subjects at 6 years of follow up
Authors: Ikonomidis I , Thymis J , Georgiopoulos G , Kolliou G , Katogiannis K , Pavlidis G , Kountouri A , Korakas E , Kostelli G , Lambadiari V , Stamatelopoulos K
Published: November 2023

Backround/Aim: Arterial stiffness is involved in the clinical course of atherogenesis. The purpose of this study was to investigate whether altered arterial wall properties of confers predictively and additively to estimation of cardiovascular risk.

Methods

Pulse wave velocity carotid-femoral (PWVc-f), the gold standard method to assess arterial stiffness, was measured non-invasively by Complior device. Increased PWV(c-f), especially above 10 m/s, indicates increased arterial stiffness. We measured baseline PWV(c-f) in 747 apparently healthy subjects (51.99±13.41 years old, 43.8% males), without established cardiovascular disease and calculated SCORE2 in each subject according to ESC guidelines.We prospectively monitored the occurrence of major cardiovascular events (MACEs-death, myocardial infarction, stroke) during a 6-year follow-up period using electronic records and clinic visits.

Results

Fifty-seven MACEs were documented during follow-up. In univariate analysis, subjects with increased PWV were found to exert greater risk for MACEs (hazard ratio (HR):1.12, 95%CI: 1.09-1.15, p<0.001). PWV remained a significant predictor for MACEs in a model including sex, age, hyperlipidemia, diabetes, hypertension, current smoking, family history of coronary artery disease and treatment with ACEi/ARBs or lipid lowering agents after using backward elimination (HR:1.13; 95% CI: 1.08-1.18, p<0.001). PWV was an independent and additive predictor of outcome when added in a model including solely SCORE2 (HR:1.10; 95% CI: 1.07-1.14,p<0.001; Chi-square change:20.08, p<0.001; C-statistic increase from 0.592 to 0.685) and also in a model encompassing risk factors not included in SCORE2, namely diabetes (HR:1.07; 95% CI: 1.04-1.11,p<0.001; Chi-square change: 43.12, p<0.001; C-statistic increase from 0.613 to 0.698). The HR of PWV for the prediction of MACE remained similar in subjects younger or older than the age of 50 years (p>0.05).

Conclusion

Arterial stiffness is an independent and additive predictor to conventional risk factors and SCORE2 for adverse outcome at 6 years follow-up.
Prognostic change of adding coronary calcium score and genetic risk score to European SCORE2 in a moderate risk region
Authors: Temtem M , Palma Dos Reis R , Serrao M , Santos M , Sa D , Sousa F , Rodrigues M , Freitas S , Henriques E , Borges S , Guerra G , Ornelas I , Drumond A , Sousa A C , Mendonca M I
Published: November 2023

Introduction

Cardiovascular disease is a public health issue remaining the leading cause of death worldwide. One of its main contributors is coronary artery disease (CAD), a complex multifactorial disease with the influence of hereditary and environmental factors.

It’s crucial to improve cardiovascular risk assessment which is a real challenge in our daily clinical practice. SCORE 2 enhanced the identification of individuals at higher risk of developing CAD, but it remains scanty. Coronary Artery Calcification (CAC) score and Genetic contributions could improve CV risk stratification in primary prevention.

Purpose

Evaluate the impact of including CAC score and Genetic Risk Score (GRS) to the European SCORE2 in MACE prediction and cardiovascular risk stratification in our asymptomatic population.

Methods

945 asymptomatic subjects (mean age 52.9±6.8 years, 74.0% male) selected from the prospective arm of the GENEMACOR study were followed up during 5.4±4.1 years. The population was categorized according to SCORE2 into three risk groups (low-intermediate <5%; high 5-10%; very high >10%). CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff Nomogram in low, moderate and high-risk categories. The GRS was created from 33 genetic variants associated with CAD by GWAS, choosing those with a hazard ratio (HR) higher than 1. Multivariable Cox proportional hazard ratios (HR) with 95% conﬁdence intervals (95% CI) assessed the variables independently associated with CV events occurrence. We evaluated the discriminative ability of the Score2, CAC score and GRS using the Harrel C statistics.

Results

Cox regression analysis showed that the highest categories of SCORE2, CAC and GRS remained in the equation with an HR of 16.6 (p=0.008), HR of 3.6 (p=0.006) and HR of 3.2 (p=0.022), respectively, when compared with the lowest categories.

C-statistic demonstrated that the predictive value for MACE was 0.671 for SCORE2, increased to 0.799 (p=0.002) when adding CAC score and improved to 0.808 (p=0.012) when adding mGRS (Table 1), showing a better discrimination capacity for MACE.

Conclusions

Our results highlight the importance of adding CAC score and GRS to SCORE2 in primary prevention to improve cardiovascular risk stratification and MACE prediction.

Larger prospective multicenter cohorts with longer follow-up should reproduce and validate these findings.
Improving risk stratification of recurrent myocardial infarction in a large real-world dataset using machine learning
Authors: Chodick G , Vered Z , Elgui K , Mathieu T , Trichelair P , Zachlederova M , Rousset A
Published: November 2023

Background

Patient (pt) risk stratification for cardiovascular (CV) events is key to determine the appropriate approach to secondary prevention. Several risk scores have been developed (SCORE2, EUROASPIRE, Thrombolysis in Myocardial Infarction [TIMI] risk score for secondary prevention [TRS 2°P]); these are based on few predictors and have low discriminatory power. Machine learning methods using real-word data (RWD) from electronic health records (EHR) databases and capable of handling a multitude of commonly available variables can serve as powerful tools to improve the discriminatory power and generate efficient and clinically relevant risk scores.

Purpose

This study used a non-linear machine learning model to build an improved risk score for secondary CV events from a large Israeli EHR database.

Methods

Records of pts with a first record of atherosclerotic CV disease (ASCVD) admission or coronary procedure and available follow-up data (mean: 1052 days) from the period of 01/2005–11/2020 were considered (n=77432 [67% coronary artery disease, 21% carotid artery disease, 12% peripheral artery disease], a stratified 1:1 randomization by cause of admission yielding in training set [n=38716] and test set [n=38716]). The model’s performance was assessed by comparison with TRS 2°P score on the test set independent of the training set.

Twenty-six covariates commonly used in clinical routine and widely available in EHR have been selected and a gradient boosting trees algorithm was applied to the pt data at baseline after the original event to predict recurrent myocardial infarction (MI). The ability of the model to discriminate pts was evaluated using the concordance index (c-index), which expresses how well a predicted risk score describes the observed events (1 implies perfect concordance, 0.5 implies random concordance).

Results

Prediction accuracy of our model showed a c-index for a future MI of 0.74 (95% confidence interval [CI]: 0.72, 0.76) which is significantly higher than 0.57 (95% CI: 0.56, 0.58) obtained with TRS 2°P. Our 2-tier risk score has successfully discriminated a low-risk group (74% of cohort) with a 3-year MI prevalence of 5% from a high-risk group (26% of cohort) that had a 5-fold higher prevalence (26.6%) (Figure 1).

In comparison, the 3-tier TRS 2°P yielded an unbalanced distribution of group sizes with a disproportionate intermediate risk group (22% low, 67% intermediate, 11% of high-risk) with a limited clinical discriminatory power (7.1%, 10,2% and 15.6% of observed events, respectively) (Figure 2).

Conclusions

Our machine learning based risk score model created on a large set of RWD with a long follow-up seems to offer substantial gain of performance compared to the TRS 2°P. The present 2-tier model shows significant gain of accuracy and clinical discriminatory power paving the way for more individualized prevention strategies.Figure 1Figure 2
Plasma proteomics identify fibroblast growth factor 5 as a biomarker for genetically proven Familial Hypercholesterolemia
Authors: Baragetti A , Mattavelli E , Pellegatta F , Alieva A S , Grigore L , Reutova O , Shlyakhto E V , Catapano A L
Published: November 2023

Background

Subjects affected by genetically proven heterozygous Familial Hypercholesterolemia (FH) present lifelong exposure to high Low Density Lipoprotein Cholesterol ("LDL-C burden") causing premature ACVD. Nevertheless, the diagnosis of FH is still far from being optimal due to shortcomings of the clinical algorithms in detecting this form of severe ACVD since early decades of life (1) and because a significant proportion of FH present comparable LDL-C levels to that of subjects who are hypercholesterolemic but are not diagnosed as FH ("non-FH") (2).

Purpose

We previously demonstrated that targeted proteomics identify subjects at high Atherosclerotic Cardiovascular Diseases (ACVD) risk in the general populations beyond the known risk factors (3). Hence, we now tested whether targeted proteomics may differentiate FH subjects from the general population and from "non-FH".

Methods

We compared the plasma relative abundance of 264 proteins (Proximity Extension Assay; Olink) in 133 genetically proven FH with that of 586 normocholesterolemic subjects ("controls") and that of 55 non-FH (LDL-C between 190-220 mg/dL, not on statins). We trained and validated a Machine Learning (ML) boosting prediction model (4) in these cohorts to identify the protein markers representative of FH (Random Forest classifiers).

Results

Fibroblast Growth Factor 5 (FGF-5) resulted as the most powerful plasma protein in differentiating FH subjects from the controls, with an excellent performance (Area Under the Curve (AUC)=0.995 (0.985-1.000); sensitivity=100%; specificity=99.54%; P<0.0001). FGF-5 also emerged as the top protein in differentiating the FH subjects from non-FH (AUC= 1.000 (0.914-1.000; sensitivity=100%, specificity=100% and P<0.001). Finally, when the two groups were matched for LDL-C, FGF-5 still differentiated the FH from the non-FH subjects, (AUC=1.000 (0.914-1.000), sensitivity=100%, specificity=100%, p<0.001).

Conclusions

FGF-5 allows a clear-cut identification of FH versus controls and, of even more importance, from non-FH with the same LDL-C. The LDL-C burden might be responsible for our findings.
A comprehensive analysis of 30 Biomarkers and their association with cardiovascular outcomes and mortality in the UK Biobank
Authors: Lee C J Y , Honigberg M C , Kany S , Choi S H , Andersson C , Hall A W , Roselli C , Hindy G , Wang M , Khera A V , Natarajan P , Torp-Pedersen C , Elllinor P T
Published: November 2023

Background

The use of a comprehensive panel of circulating biomarkers in risk estimation of cardiovascular disease and mortality in a general healthy population remains uncertain.

Methods

The individual association of 30 clinically available biomarkers with risk of incident heart failure (HF), atrial fibrillation (AF), stroke, myocardial infarction (MI), venous thromboembolism (VTE), and mortality was estimated within 5-years using separate logistic regression models in nearly 500,000 individuals in the UK Biobank; a prospective, population-based cohort recruited between 2006-2010.

Results

A total of 496,415 individuals were included (median age 58 years, 54% female). Higher concentrations of C-reactive protein, gamma-glutamyl transferase, cystatin C, and urate were associated with significantly higher odds, and albumin with lower odds, of all outcomes (Figure 1). Higher levels of sex hormone binding globulin were associated with a higher risk of AF for both sexes (men: Odds ratio [OR] per standard deviation [SD] 1.26, 95% confidence intervals [CI] 1.21-1.31; premenopausal women: OR per SD 1.20, 95% CI 1.09-1.31; postmenopausal women: OR per SD 1.41, 95% CI 1.12-1.77). No significant associations were found among pre- or postmenopausal women between estradiol and cardiovascular outcomes. For men, having estradiol ≥40 pmol/L was associated with a higher risk of mortality, HF and AF.

Conclusions

Several associations were found between multiple biomarkers and cardiovascular disease, and mortality, especially novel associations of hormonal markers associated with both lower and higher odds of cardiovascular disease. Further research is needed to validate these associations and explore the potential clinical applications of biomarker data.
Could a high epicardial adipose tissue volume increase the ability of the calcium score to discriminate cardiovascular events in an asymptomatic population?
Authors: Temtem M , Mendonca M I , Sousa J A , Serrao M , Santos M , Sa D , Sousa F , Freitas S , Borges S , Henriques E , Rodrigues M , Drumond A , Sousa A C , Palma Dos Reis R
Published: November 2023

Background

Evidence indicates that an elevated calcium score (CAC) is a risk marker for subclinical atherosclerosis and cardiovascular (CV) events in the asymptomatic population. Recent research has shown that high epicardial adipose tissue (EAT) volume is associated with coronary calcification and CV events It is unknown whether the association between the two risk markers improved the ability to predict CV events.

Objective

Evaluate whether a high EAT volume added to the CAC score improves the predictive ability to discriminate CV events in an asymptomatic population without apparent cardiovascular disease (CVD).

Methods

A prospective cohort was performed with 1024 participants (mean age 51.6±8.2 years, 75.6% male) selected from controls of the GENEMACOR Study. CAC score was performed by cardiac computed tomography, and CAC severity was reported as an absolute Agatston unit stratified for age and sex- percentile (according to the Hoff Nomogram). EAT volume was measured with a quantitative semi-automated procedure using a postprocessing workstation-TeraRecon Aquarius Workstation (version 4.4.7, TeraRecon, Inc., San Mateo, CA, USA). We evaluated the discriminative ability of the CAC model without (model 1) and with EAT volume (model 2) using the ROC curve along with respective AUC and Harrel C statistics. Categorical free Net Reclassification Improvement (cfNRI) and Integrated Discrimination Index (IDI) reclassified patients.

Results

CAC model showed a C Index of 0.733 (95%CI 0.633-0.833), which increased to 0.756 (95%CI 0.638-0.874) when EAT volume was included in the model. The difference between the two C indexes was significant (delta C statistic=0.023; p=0.020). CfNRI reclassified 63.6% of the population (p=0.0003), and IDI improved the discrimination when EAT was included in CAC model (IDI=0.011; p=0.015).

Conclusion

Our findings displayed that the CAC score associated with a high EAT volume increased the predictive and discriminative ability to event occurrence. Improving the identification of high-risk patients at a subclinical stage could avoid atherosclerosis progression and events occurrence through preventive measures.
Long-term aspirin adherence and risk of cardiovascular events and death after myocardial infarction: A nationwide cohort study
Authors: Kristensen A M D , Pareek M P , Kragholm K , Prescott E
Published: November 2023

Background

Aspirin is mandatory in the acute phase after myocardial infarction (MI); however, the efficacy of aspirin for long-term secondary prevention is less established and may have changed with the addition of modern therapies and diagnostics methods.

Purpose

To investigate the effectiveness of adherence to long term aspirin therapy at different timepoints following MI.

Methods

Using Danish nationwide registries, we included patients ≥40 years with a first time MI undergoing percutaneous coronary intervention from 2004 through 2017, who were alive, not treated with anticoagulants, and had stayed adherent to aspirin at one year after the index event (Figure 1). We evaluated adherence to aspirin therapy as proportion of days covered (PDC) ≤80% and >80% at four landmarks (2, 4, 6, and 8 years after MI, respectively). At each landmark, patients were excluded from the analysis if they had suffered a recurrent MI or stroke, died, emigrated or were on anticoagulant or P2Y12-inhibitor therapy. The absolute and relative risks of a composite of death, recurrent MI, or ischemic stroke at 2 years from each landmark were calculated through multivariable logistic regression analysis with average treatment effect modelling standardized to the distribution of age, sex, diabetes, hypertension, hypercholesterolemia, chronic kidney disease, cancer, peptic ulcer, former bleeding, and chronic obstructive pulmonary disease (as a proxy for smoking). Non-CVD death was used as a neutral comparator.

Results

A total of 40,114 individuals were included in the analysis. Suboptimal adherence to aspirin (PDC≤80%) increased from 10% at first landmark 2 years after MI to 19% at fourth landmark 8 years after MI (Figure 1). The standardized absolute risk of death, recurrent MI, or ischemic stroke was highest at the first landmark 2 years after MI for both PDC-groups (PDC>80%: 8.34%, 95% confidence interval [CI]: 8.04-8.63% and PDC≤80%: 10.75%, 95% CI: 9.80-11.69%) (Figure 2). The standardized relative risk of the composite endpoint was significantly higher for patients with PDC≤80% at all landmarks. A trend towards a diminished protective effect of long-term aspirin therapy appeared from 4 years after the index MI and onwards, decreasing from 1.40 (95% CI: 1.26-1.53) at second landmark 4 years after MI to 1.20 (95% CI: 1.04-1.35) at fourth landmark 8 years after MI. Overall, we found no difference in the relative risk of non-CV death between PDC-groups.

Conclusion

Suboptimal adherence to long-term aspirin therapy following MI was associated with an increased risk of recurrent MI, ischemic stroke, or death, but the relative risk appeared to decrease slightly over time from 4 years after the index MI and onwards.Figure 1Figure 2
The effect of implementing a guideline-based approach to achieve target LDL-C levels in very high risk patients. The PENELOPE study one year follow-up results
Authors: Van Der Brug S J , Khader A O , Atazadah M , Liem A H , Groenemeijer B E , Schut A , Martens F A M , Dunselman P H J M , Alings A M W
Published: November 2023

Background/introduction

Hyperlipidemia is a major modifiable risk factor for developing cardiovascular disease. Lowering LDL-C reduces the risk for coronary heart disease (1,2). The PENELOPE study implemented an ESC-guideline-based, stepwise strategy of lipid-lowering therapy (LLT) to achieve target LDL-C levels in very high-risk patients, with a mean duration of 61 days.

Purpose

This paper demonstrates the legacy effect after one year.

Methods

Nine hundred and ninety-nine (999) patients with a myocardial infarction and a history of atherosclerotic cardiovascular disease and/or diabetes mellitus were included in PENELOPE for stepwise intensified LLT (high intensity statin (HIST) monotherapy, HIST + ezetimibe, HIST + ezetimibe + PCSK9i) until reaching target LDL-C level (≤1.8mmol/L). The primary objective was to assess the prevalence of maintained LDL-C ≤1.8 mmol/L and therapy-adherence after one year.

Results

For the one year follow up visit, 738 patients (73%) were available. Thirty patients had died, 45 were lost to follow up and from 178 patients no signed informed reconsent was obtained. The per protocol cohort included six hundred and seventy-one (671) patients. In this cohort, a non-participation bias cannot be excluded.

After one year, in four-hundred forty-nine (449) patients target LDL-C level (66,9%) was maintained. Mean LDL-C level after one year was 1.67 mmol/L and the adherence rate to LLT was 94,5%. The major treatment regimens were statin monotherapy (61,7%), statin + ezetimibe (28,3%) and PCK9i + ezetimibe (+ statin) (5,8%). Maintained target (LDL-C ≤1.8mmol/L) was 64%, 77% and 82%, respectively. The large percentage loss of patients on target after one year could be explained by the cut-off at 1.8 mmol/L (only 0.28 mmol/L increase in mean LDL-C level), the short-term effect of heart rehabilitation and a treatment change in 20,4% of patients. Therapy adherence was high and did not differ between treatment regimen.

Conclusion

Using an ESC-guideline-based flowchart with quick, stepwise intensification of LLT leads to a 99% success rate (LDL-C ≤1.8mmol/L) within 3 months and 67% after one year. The mean LDL-C level increases with 0.28 mmol/L.
Contribution of Lipoprotein(a) to polygenic risk of coronary artery disease: A prospective UK Biobank analysis
Authors: Arsenault B , Manikpurage H D , Paulin A , Girard A , Eslami A , Mathieu P , Theriault S
Published: November 2023

Background

Lipoprotein(a) (Lp[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown.

Purpose

Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD.

Methods

372,385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using LDpred2. Over the median follow-up of 12.6 years, 13,538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting or coronary angioplasty).

Results

The LPA region contribution to the CAD-PRS-mediated CAD risk was modest (6.5%). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C-statistic 0.751 versus 0.746, difference = 0.005 (95% CI, 0.004-0.006). Compared to participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L (CAD event rate 6.6%), the hazard ratio for incident CAD in participants in the bottom CAD-PRS quintile with Lp(a) levels <25 nmol/L was 0.18 (95% CI, 0.17-0.20, p=6.41e-241, CAD event rate 2.0%).

Conclusions

Compared to individuals with a high genetic risk of CAD (high CAD-PRS and high Lp(a) levels), those with a low genetic risk had an 82% lower CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD should consider blood levels of Lp(a).
Hospitals’ electronic access to information needed to treat COVID-19
Authors: Richwine Chelsea , Everson Jordan , Patel Vaishali
Published: November 2023

Objective

To understand whether hospitals had electronic access to information needed to treat COVID-19 patients and identify factors contributing to differences in information availability.

Materials and methods

Using 2021 data from the American Hospital Association IT Supplement, we produced national estimates on the electronic availability of information needed to treat COVID-19 at US non-federal acute care hospitals (N = 1976) and assessed differences in information availability by hospital characteristics and engagement in interoperable exchange.

Results

In 2021, 38% of hospitals electronically received information needed to effectively treat COVID-19 patients. Information availability was significantly higher among higher-resourced hospitals and those engaged in interoperable exchange (44%) compared to their counterparts. In adjusted analyses, hospitals engaged in interoperable exchange were 140% more likely to receive needed information electronically compared to those not engaged in exchange (relative risk [RR]=2.40, 95% CI, 1.82-3.17, P<.001). System member hospitals (RR = 1.62, 95% CI, 1.36-1.92, P<.001) and major teaching hospitals (RR = 1.35, 95% CI, 1.10-1.64, P=.004) were more likely to have information available; for-profit hospitals (RR = 0.14, 95% CI, 0.08-0.24, P<.001) and hospitals in high social deprivation areas (RR = 0.83, 95% CI, 0.71-0.98, P = .02) were less likely to have information available.

Discussion

Despite high rates of hospitals’ engagement in interoperable exchange, hospitals’ electronic access to information needed to support the care of COVID-19 patients was limited.

Conclusion

Limited electronic access to patient information from outside sources may impede hospitals’ ability to effectively treat COVID-19 and support patient care during public health emergencies.
The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer
Authors: Lammers Senna W M , Geurts Sandra M E , van Hellemond Irene E G , Swinkels Astrid C P , Smorenburg Carolien H , van der Sangen Maurice J C , Kroep Judith R , de Graaf Hiltje , Honkoop Aafke H , Erdkamp Frans L G , de Roos Wilfred K , Linn Sabine C , Imholz Alexander L T , Smidt Marjolein L , Vriens Ingeborg J H , Tjan-Heijnen Vivianne C G
Published: November 2023

Background

Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients.

Methods

Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided.

Results

This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24).

Conclusion

In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.