bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct measurement of peak oxygen uptake in cardiopulmonary exercise testing as a survival predictor in octogenarians
Authors: Braga F , Milani M , Fachetti A , Espinosa G , Moraes G , Milani J G P O , Mourilhe-Rocha R
Published: June 2024

Background

The direct measurement of peak oxygen uptake (VO2peak) through cardiopulmonary exercise testing (CPET) serves as the gold standard for assessing cardiorespiratory fitness. This measurement is a firmly established indicator of health and holds substantial prognostic value concerning all-cause mortality in both populations with and without cardiovascular diseases. However, due to the scarcity of older individuals in studies employing CPET, its significance in this phase of life is less explored. Existing data on octogenarians primarily relies on the indirect measurement of VO2peak through the estimation of peak metabolic equivalents achieved (MET). It is worth noting that indirect estimation is generally less precise compared to direct measurement through CPET. This gap raises questions about the enduring validity of VO2peak as a robust predictor of mortality and morbidity in this specific demographic, akin to its predictive efficacy among younger individuals.

Purpose

To analyse the role of VO2peak as a predictor of survival in octogenarians.

Methods

Patients aged 80 years or older who underwent CPET assessment at a single centre from Brazil were included in this study. The variable VO2peak was determined as the highest 30-second average sample obtained during the final minute of the effort. The measured value was subsequently compared to predicted values by the Wasserman algorithm to calculate the percent-predicted VO2peak achieved (%VO2peak). The optimal cut-off point for the %VO2peak was determined by receiver operating characteristic (ROC) curve analysis, and this value was used as a cut-off to categorise individuals with %VO2peak higher or lower. Then, Cox regression models were employed to evaluate this dichotomisation to predict survival outcomes.

Results

Among 188 patients assessed, 22 (11.7%) died during the median follow-up of 494 days, with non-survivors being older, having lower VO2peak, and lower %VO2peak (Figure 1). Figure 2A illustrates the ROC curve for mortality prediction by %VO2peak. The area under the ROC curve was 0.699 (95% CI: 0.627 to 0.764; p < 0.001), and the optimal cut-off point was determined to be %pVO2 ≤ 80%. Cox regression models indicated associations between %VO2peak ≤ 80% and mortality: HR=3.19 (95% CI: 1.30 to 7.86, p=0.011) for the unadjusted model (Figure 2B); and HR=3.124 (95% CI: 1.26 to 7.74, p=0.013) for the model with inclusion of age as a covariate to evaluate the impact of %VO2peak while accounting for age-related effects.

Conclusion

Amidst the backdrop of a rapidly aging population, our study highlights the enduring significance of VO2peak as a survival predictor among the elderly. These findings hold profound implications for tailoring healthcare strategies to address the evolving demographic landscape.
Revisiting the peak breathing reserve < 15% criterion to indicate ventilatory limitation to treadmill incremental cardiopulmonary exercise testing in men and women aged 20 to 80 years
Authors: Milani M , Milani J G P O M , Machado F V C , Cipriano G F B , Neder J A , Hansen D , Cipriano G
Published: June 2024

Background

The respiratory system is not the limiting step to humans’ tolerance to dynamic exercise in most physiological circumstances. For instance, minute ventilation at peak exercise (VEpeak) is appreciably lower than the maximal sustained ventilatory capacity (MSVC). Using the estimated (from forced expiratory volume in one second (FEV1)) maximal voluntary ventilation (MVVest) as a surrogate of the MSVC, a peak breathing reserve (BRpeak= [1-(VEpeak /MVVest)] x 100) > 15% has been widely recommended as the decision node to rule out ventilatory limitation. Supportive evidence for this contention, however, stems from small samples tested on a cycle ergometer, an exercise modality associated with lower ventilatory demands than those elicited by treadmill - the commonest ergometer in cardiology.

Purpose

To determine the prevalence of ventilatory limitation to treadmill incremental cardiopulmonary exercise testing (CPET) based on BRpeak≤15% in a large sample of apparently healthy men and women showing a large age span.

Methods

We retrospectively analyzed treadmill CPET data from 3,544 apparently healthy individuals aged 20 to 80 years living in Midwest Brazil. As recommended by current guidelines(1-2), we multiplied FEV1 by 35 or 40. We established the prevalence of BRpeak≤15% in subjects stratified by sex and age (20-39, 40-59, and 60-80 years). Anticipating a high prevalence of low BRpeak using 35 or 40, we aimed to establish which coefficient should be used to multiplying FEV1 to decrease the prevalence of ventilatory limitation to ≤5% and ≤1% in each sex.

Results

BRpeak≤15% was found in 21.7% of women and 48.0% of men when FEV1 was multiplied by 35: corresponding values were 5.8% and 17.4% when the multiplying coefficient was 40, respectively (Figure 1). Regardless of sex, particularly high prevalence of BRpeak≤15% was found in the middle-aged group (Figure 2). Using 40.5 to multiply FEV1 in women and 45 in men resulted in ≤5% prevalence of ventilatory limitation. Further discriminative power (≤1% of BRpeak≤15%) required coefficients as high as 45 and 49 for women and men, respectively (Figure 2).

Conclusion

To avoid unacceptable high false positive rates for ventilatory limitation to incremental CPET on a treadmill (BRpeak≤15%), pre-exercise FEV1 should be multiplied by higher coefficients than those commonly recommended for cycle ergometer-based tests. This is particularly critical for men who reach high exercise intensities. Ever if appropriate coefficients are employed, BRpeak should be used with caution as the sole criterion to rule in or out a contribution of "the lungs" to exercise limitation in individual subjects(3).
Does peak exercise capacity correlate with aortic stiffness and atrial strain in children with Fontan circulation? - A case-control study
Authors: Tekerlek H , Saglam M , Selcuk S N , Aykan H H , Vardar-Yagli N , Karagoz T
Published: June 2024

Background/Introduction

It is well known that exercise capacity is reduced in Fontan patients. However, more information is needed on exercise capacity, atrial strain, and aortic stiffness in children with Fontan circulation compared to controls and on the relationship of aortic stiffness and atrial strain with exercise capacity.

Purpose

It was aimed to compare peak exercise capacity, aortic stiffness, and atrial strain with controls and to investigate the relationship between peak exercise capacity and aortic stiffness and atrial strain in children with Fontan circulation.

Methods

Demographic and clinical characteristics were recorded. Peak oxygen consumption (VO2peak) was measured using cardiopulmonary exercise test (CPET) with modified Bruce protocol on a treadmill and recorded as ml/min, ml/min/kg, %pred values according to Wasserman’s equations. Atrial strain with speckle tracking echocardiography (STE) and aortic stiffnes with pulse wave velocity (PWV) were assessed using Philips Healthcare EPIQ CVx. The dominant atrium strain was recorded for reservoir phase (εres), conduit phase (εcon), and contractile phase (εact) were recorded as %. Aortic pulse wave velocity (PWV) recorded as m/sec.

Results

Fifteen children with Fontan circulation (median= 12 years, 6 female) and 14 controls (median=12 years, 5 female) were included. VO2peak, εres, and εcon were lower; aortic PWV were higher in patients compared to controls (p<0.05) (Table 1). VO2peak significantly associated with aortic PWV, εres, εcon, and εact in children with Fontan circulation (p>0.05) (Table 2).

Conclusions

Decreased exercise capacity, increased aortic stiffness, and the impaired atrial strain was found in children with Fontan circulation compared to controls in this study.Furthermore, decreased exercise capacity associated with increased aortic stiffness and impaired atrial strain. Further studies with the increased number of participants can provide new insights into determinants of exercise intolerance in children with Fontan circulation.
Optimising screening of intermediate to high-risk asymptomatic sportsmen with exercise electrocardiogram
Authors: Hupin D , Oriol M , Laukkanen J A , Roche F
Published: June 2024

Aims

The importance of exercise electrocardiogram (ECG) is still controversial in the prevention of cardiovascular events among sportsmen. The aim of this study was to assess the relevance of exercise ECG as a screening tool for cardiovascular events when any cardiovascular disease (CVD) risk factors are present.

Methods

The study included leisure time asymptomatic sportsmen evaluated from 2011 to 2016 in a university hospital. Major adverse cardiovascular events (MACE) and atrial fibrillation were collected at 3 years.

Results

Of the cohort of 2457 sportsmen (mean age 50.2 ± 9.4 years), 50 (2%) had a high risk SCORE2. A total of 256 exercise ECGs (10%) were defined as positive, most of them due to silent myocardial ischemia (SMI) (n = 196; 8%). These 196 SMI cases led to 33 coronary angiograms (1%), which revealed 23 significant coronary stenoses requiring revascularization. In multivariate logistic regression analysis, having at least 2 CVD risk factors was independently associated with (1) positive exercise ECG [OR=1.80 (CI 95%: 1.29-2.52), p=0.0006], with (2) suspected SMI [OR=2.57 (CI 95%: 1.10-6.02), p=0.0304], with (3) confirmed SMI [OR=8.20 (CI 95%: 3.46-19.46), p<0.0001] and with (4) cardiovascular events (MACE or atrial fibrillation) [OR=6.95 (CI 95%: 3.49-13.81), p<0.0001] at 3 years.

Conclusions

The study supports the European recommendations for the use of exercise ECG in evaluation of asymptomatic leisure time sportsmen. Having at least 2 CVD risk factors was the best predictors for presence of coronary artery stenosis that may increase the risk for adverse events.
Left ventricular filling pressure correlates with exercise capacity during exercise stress test in cardiovascular disease patients
Authors: Satoto H H , Widiastuti A Z
Published: June 2024

Background

Cardiovascular disease patients with lower exercise capacity have higher risks for cardiovascular mortality and outcomes. Diastolic dysfunction is also correlated with cardiovascular mortality. E/e’ is one of the diastolic dysfunction parameters and it showed left ventricular filling pressure. The previous study showed that diastolic dysfunction correlates with decreased exercise capacity, but not left ventricular ejection fraction.

Purpose

This study aims to determine the relationship between left ventricular filling pressure using E/e’ and exercise capacity in cardiovascular disease patients.

Methods

Cardiovascular patients who underwent exercise stress tests and echocardiography at our hospital in 2022 – 2023 were enrolled in this study. We assessed diastolic dysfunction using E/e’ parameter during the echocardiography examination. We used predicted METs from Bruce protocols treadmill test time to determine each patient’s exercise capacity.

Results

There were 282 patients (Age 54+10 years; 74.8% male; 71.3% with chronic coronary syndrome, 22% with chronic heart failure, 6.7% with hypertensive heart disease). The mean E/e’ was 9.33+3.36 and the mean exercise capacity was 6.3+2.2 METs. Left ventricular filling pressure had a significant negative weak correlation with predicted exercise capacity (r=-0.228; p=0.000) in cardiovascular disease patients. We performed receiver operating characteristic analysis that showed the area under the curve for E/e’ was 8 and found the exercise capacity cut-off was 6 METs. Patients with E/e’ more than 8 were likely to have exercise capacity less than 6 METs (OR= 1.75 (95% CI, 1.07 – 2.84) p=0.032).

Conclusions

There is a correlation between high left ventricular filling pressure and lower exercise capacity. In cardiovascular disease, patients with higher left ventricular filling pressure were likely to have lower exercise capacity.
Impact of long-term endurance sport on the association between atrial fibrillation and mortality. a prospective cohort study
Authors: Johansen K , Hylen Ranhoff A , Sorensen E S , Heitmann K A , Lochen M L , Morseth B , Myrstad M
Published: June 2024

Introduction

Endurance athletes live longer than non-athletes, however, a high prevalence of atrial fibrillation (AF) has been documented in this population, suggesting that vigorous endurance exercise promotes AF. Moreover, AF is associated with increased mortality in the general population, but it is unclear whether this association is attenuated in athletes. Thus, we aimed to explore the association between AF and mortality in a cohort of veteran endurance athletes and non-athletes.

Method

All 658 veteran endurance athletes aged ≥65 years who completed a 54-kilometer cross-country ski race in 2009/-10 were invited to attend a prospective cohort study. Furthermore, a cohort of non-athletes of the same age attending a population-based study in 2007/-08 was included for comparison. AF and covariates were self-reported with a questionnaire while all-cause mortality was available through linkage with national registries. Athletes also reported prevalence of AF and cardiovascular disease on a follow-up questionnaire in 2014 and 2020, while non-athletes did the same in 2015-2016. Participants with AF were followed from the time they reported AF until death or end of follow-up (participants without AF followed from baseline survey). We analyzed the association between AF and mortality overall and in analyses stratified by athlete status. Cox proportional hazards models (adjusted for age, sex, body mass index, education, smoking, antihypertensive medication, cardiovascular disease and diabetes) were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI).

Result

We included 549 (AF: n=152) athletes (women: n=46) and 3242 (AF: n=469) non-athletes (women: n=1375) (median age: 70, range: 65-92). Athletes annually participated in a 54 km long-distance ski race (median years of participation: 14, range: 1 – 53). Among athletes (n=62) and non-athletes (n=339) with AF, 41 and 72%, respectively, reported at least one concomitant cardiovascular risk factor. During a mean follow-up of 10.9 ± 3.3 years, 20 (13.6%) athletes and 184 (39.2%) non-athletes with AF died. AF was associated with an overall increased risk of mortality (HR: 1.52, 95% CI: 1.28-1.80). We observed no interaction between AF and athlete status (P=.679). In stratified analyses the magnitude of the association with AF was similar for athletes (HR: 1.58, 95% CI: 0.89 – 2.80) and non-athletes (HR: 1.53, 95% CI: 1.28 – 1.84).

Conclusion

Although long-term endurance sport practice is associated with improved survival, the relative increase in mortality associated with AF was not diminished in athletes. Thus, our findings suggest that AF may be a risk marker for mortality, also in an ostensibly healthy cohort of veteran endurance athletes.
Exploring the role of genetics in a family screening program
Authors: Abela M , Debattista J , Scerri J , Felice T , Grech V , Scerri C
Published: June 2024

Introduction

Genetic testing plays a key role in the management of inherited cardiac conditions (ICCs). Personalized medicine in cardiology has evolved substantially, with guidelines now recommending genetic testing in patients with ICC for phenotypic characterisation and risk stratification. It plays a central role in predictive testing, especially in relatives with concealed phenotypes.

Study objective

The main objective of this study is to explore the clinical manifestations and outcomes of gene positive (G+) versus gene negative (G-) family members, complimenting a national cardiac screening program in adolescents.

Methodology

As part of a large nationwide cardiac screening program in adolescents (BEAT-IT), probands with a pre-clinical and clinical phenotype suggestive of an ICC were enrolled into a family screening program. A comprehensive clinical evaluation that also included genetic testing and counselling was offered to these probands. Mutations were classified according to the ACMG criteria. G+ probands included those with a hot variant of unknown significance, likely or definite pathogenic mutation. Relatives were then grouped according to the proband’s genotype (G+/G-).

Results

Eighteen probands (n=1 HCM, n=1 LQTS, n=16 pre-clinical) from the BEAT-IT program were included. A fourth (27.8%) were G+ (n=2 MYH7, n=1 MYBPC3, n=1 ACTC1, n=1 KCNQ1).

Their families were subsequently offered family screening, 87 relatives gave consent to a screen (58.6% female, mean age at evaluation 40.5 ± 17.1 years, 100% Caucasian, 62.1% first degree relatives). A minority (n=3, 3.4%) reported symptoms. A few (n=11, 12.6%) were <18 years at the first evaluation.

Most relatives were in the G- group (n=51, 58.6%). Relatives of G+ probands were more often referred (44.4% vs 9.8%, p<0.001). The presence of an abnormal ECG was also more frequent (36.1% vs 9.8%, p=-0.006). The presence of a definite/possible ICC on echocardiography was also more likely in G+ families (14.3% vs 0.0%, p=0.014).

Most relatives were G- (n=70, 80.5%). The ECG was more frequently abnormal in G+ relatives (n=12/17 [70.6%] vs n=6/70 [8.6%], p<0.001). All relatives given a diagnosis were G+ (n=10, 27.8%) (n=7 LQTS, n=2 HCM, n=1 DCM). Most (n=9, 90.0%) needed lifestyle advice, medical therapy, or a cardiac intervention.

In the U18 group (n=11), 3 (27.3%) needed referral (n=2 (18.2%) abnormal ECG, n=1 (9.1%) LQTS diagnosis).

Conclusion

G+ relatives were more likely to be referred and/or given a clinical diagnosis. In the presence of an appropriate infrastructure, phenotyping pre-clinical probands with genetic testing may help identify family members harbouring a pre-clinical or clinical phenotype.
Endurance training protects the heart during maximal exercise in long-distance runners
Authors: Kocic A , Ristanovic L J , Macura M , Mirkovic S , Seman S , Ilic V , Labudovic D , Mrdakovic V , Jakovljevic S , Okwose N , Stojiljkovic S , Jakovljevic D
Published: June 2024

Introduction

Cardiac function (cardiac output) and oxygen extraction (arterio-venous O2 difference) are key physiological determinants of maximal oxygen consumption and endurance performance.

Purpose

The aim of the study was to determine differences in maximal cardiac function represented by cardiac output and cardiac power output and oxygen extraction represented by arterio-venous O2 difference between long-distance runners and age- and gender-matched healthy individuals.

Methods

In a prospective observational study, 63 healthy males were recruited: 47 long-distance (half- and full-marathon) runners (aged 32.6 ± 8.6 years, body mass index 23.4 ± 2.2 kg/m²) and 16 healthy untrained individuals (control group, aged 30.9 ± 11.2 years, body mass index 24.8 ± 2.4 kg/m²). All participants underwent maximal graded cardiopulmonary exercise stress seting using an electromagnetic cycle ergometer with simultanous monitoring of metabolic (gas exchange) and hemodynamic (bioreactance) measurements. Cardiac power output, expressed in watts, as a measure of overall function and pumping capability of the heart, was determined as the product between cardiac output and mean arterial blood pressure. Oxygen extraction (arterio-venous O2 difference) was calculated as the ratio between O2 consumption and cardiac output.

Results

Maximal O2 consumption was significantly lower in the control group compared to runners (absolute values, 3.44 ± 1.12 vs. 3.99 ± 0.52 L/min, p < 0.01; and relative values, 45.3 ± 16.4 vs. 53.6 ± 6.9 ml/kg/min, p < 0.01). However, maximal cardiac output and cardiac power output were significantly higher in the control group compared to runners (21.4 ± 3.9 vs. 18.7 ± 3.0 L/min, p = 0.02; 5.94 ± 1.35 vs. 5.01 ± 1.00 watts, p = 0.01). Maximal stroke volume was significantly higher in control group compared to runners (126 ± 28 vs. 109 ± 21 ml/beat, p = 0.04), whereas maximal heart rate was not significantly different betwen the groups (174 ± 12 vs. 177 ± 22 beats/min, p = 0.70). Arterio-venous O2 difference was significantly higher in runners compared to control group (21.6 ± 3.7 vs. 14.5 ± 3.6 mlO2/100 ml blood, p < 0.01).

Conclusion

During maximal exercise stress testing long-distance runners demonstrate higher cardiorespiratory fitness and oxygen extraction but lower cardiac output and cardiac power output compared to untrained indivuduals. Ability to extract and utilise more oxygen at lower cardiac output during maximal physiogical stress suggests cardiac protective role of endurance training in long-distance runners.
Distribution of cardiovascular risk severity among Egyptian patients with established cardiovascular diseases
Authors: Francis V F , Elshamy S L , Mahgoub A , Shelbaya K , Zarif B
Published: June 2024

Background

The Secondary Manifestations of Arterial Disease (SMART) risk score was recommended by the European Society of Cardiology (ESC) to estimate a 10-year risk for myocardial infarction, stroke, or vascular death in individual patients with clinically manifested atherosclerotic vascular disease (ASCVD).(1) An updated SMART2 algorithm was developed and recalibrated according to the population risks in the different world regions except for Africa. The expected-observed ratio of recurrent ASCVD in the very high-risk region of the SMART2 study was 0.2.(2).

Purpose

Describe the calculated 10-year risk using the SMART score, and the prevalence of contributing risk factors among a sample of Egyptian patients with ASCVD.

Methods

Cross-sectional study included 180 consecutive patients diagnosed with ASCVD and had their first follow-up visit at the Egyptian National Heart Institute. The ESC- certified SMART score web application was used to calculate the estimated 10-year risk of future CV events. The population mean option was used for CRP and serum creatinine as they were not available at the follow-up. All patients were diagnosed within a short duration before the follow-up visit (i.e. 0 years since the first event).

Results

The median and IQR of 10-year risk, using SMART were 17.5 (14-24)%. The percentage of patients who had calculated risk <15% and ≥ 30% were 23% and 13%, respectively. Patients with calculated risk ≥ 30 tend to be older and have more prevalent hypertension, diabetes, and previous statin. Risk factors prevalence and lipid profile medians were elevated in the total study sample (Table).

Conclusion

The calculated risk of recurrent ASCVD among Egyptian patients using the conventional SMART score is beneficial for the individual relative risk assessment but may not reflect the absolute risk among the Egyptian population who have more prevalent risk factors. Large cohort studies are needed in Egypt and other African countries to recalibrate the calculated risk of recurrent ASCVD.
The value of pregnancy-related factors in the prediction of cardiovascular disease and hypertension: a systematic review
Authors: Yang Z , Van Os H , Kist J , Vos R , Vos H , Chavannes N , Petrus A
Published: June 2024

Background/Introduction

Commonly used prediction models for CVD do not consider female-specific risk factors and tend to underestimate the cardiovascular risk in women. Pregnancy-related factors are associated with an increased risk of CVD, hence may improve the performance of prediction models for CVD. Hypertension is one of the most important risk factors for CVD, therefore could be regarded as an intermediate cardiovascular outcome.

Purpose

 This study aims to provide an overview of prediction models for CVD and hypertension which included pregnancy-related factors as predictors, and to evaluate the impact of these factors on the model performance.

Methods

 PubMed and Embase were searched until March 30, 2023. Studies were eligible for inclusion if they i) reported on the development or validation of at least one multivariable model predicting CVD and hypertension in women, ii) were based on a population-based sample of either only parous women or a combination of nulliparous and parous women, iii) included at least one pregnancy-related factor, iv) were available as full-text publications, and v) were originally written in English. The risk of bias was assessed using the prediction model risk of bias assessment tool (PROBAST).

Results

 Seven studies reporting on the development of prediction models for CVD with pregnancy-related factor(s) were included. No models with hypertension as outcome were found. The C-indices of all models ranged between 0.63 and 0.79. In the six studies comparing models with and without pregnancy-related factors, the C-index difference was statistically significant in four studies (point estimate ranging from 0.0033-0.004). The net reclassification improvement for events and non-events was statistically significant in two studies (point estimate: 0.01-0.038) and three studies (point estimate: 0.002-0.02) respectively. The integrated discrimination improvement was statistically significant in three studies (point estimate: 0.0002-0.0013). Only two studies showed low risk of bias and low concern regarding applicability. Subgroup analysis for different age groups were performed in three studies, indicating that prediction models with pregnancy-related factors perform better in younger women.

Conclusion(s)

The addition of pregnancy-related factors results in limited improvements in model performance for the prediction of CVD. Given that improvements appear more pronounced in younger women, pregnancy-related factors may improve prediction especially in women directly after pregnancy. More research should focus on using hypertension as outcome in this group of women, because it requires shorter follow-up to reveal possible cardiovascular risk in an early stage.
Improved sex-specific cardiovascular disease risk prediction using machine learning and explainable artificial intelligence
Authors: Bye A , Wiig-Fisketjon A , De Martin Topranin V , Dalen H , Langaas M
Published: June 2024

Aims

Several risk prediction models are available for determining the 10-year risk of cardiovascular disease (CVD), including the Norwegian NORRISK 2 model. However, the existing models explain only a modest proportion of the incidence. Therefore, this study aimed to develop improved models for predicting the 10-year risk of myocardial infarction (MI) for both sexes.

Methods

Data from 31,946 participants without prior CVD were analyzed. The data set was divided into a training set (for estimation) and a test set (for model evaluation). Prediction models were developed on the training set for each sex using XGBoost and logistic regression, using 96 (men) and 100 (women) variables. The models were evaluated on the test set using Receiver-Operating-Characteristic (ROC) and Precision-Recall (PR) curves. Age and sex-specific thresholds for intervention were explored through cross-validation on the training set. Model performance was compared to the NORRISK 2 model using the test set.

Results

The XGBoost model improved CVD risk prediction for men across all age groups (AUCROC for XGBoost and NORRISK 2, respectively, 0.72 and 0.65 (age 45-54), 0.63 and 0.62 (age 55-64), 0.69 and 0.62 (age 65-74)). For women, NORRISK2 performed better than XGBoost in ROC curve evaluation. However, XGBoost were superior to NORRISK2 when evaluated by PR-curves in women aged 55-64 (PR-AUC for XGBoost and NORRISK 2, respectively, 0.20 and 0.12 compared to 0.06 for a no-skills model). Potential new risk predictors, such as alkaline phosphatase (ALP) for men and thyroid stimulation hormone (TSH) for women, were identified. The results also indicate that the thresholds for intervention should be sex specific.

Conclusion

By employing machine learning and incorporating sex-specific risk factors, we propose improved risk prediction models for CVD, particularly in men. Introducing sex-specific thresholds for intervention could enhance CVD prevention for both women and men.
Prevention of life threating arrythmias in relatives of cardiac arrest survivors; results of family cascade screening in a representative cohort in Czech Republic
Authors: Krebsova A , Kutilkova E , Votypka P , Peldova P , Haskova J , Segetova M , Peichl P , Adamova M , Tavacova T , Macek M , Janousek J , Kautzner J
Published: June 2024

Background

Cardiac arrest (CA) is often the very first sign of an inherited cardiomyopathy or arrhythmic syndrome. The detailed cardiogenetic work up in CA survivors may contribute to individualized therapy in patients and lead to prevention of life threating arrythmias in their relatives.

Purpose

To assess the molecular architecture of non-ischemic CA in a representative cohort in Czech Republic and test the effectiveness of a family cascade screening.

Patients and Methods

Between 2013 and 2023 we ascertained 221 non ischemic SCA survivors (137 M / 84 F), age at cardiac arrest 36±16 years. The initial clinical diagnosis in SCA were mostly idiopathic ventricular fibrillation (iVF 120 – 54%), followed by cardiomyopathy or arrhythmic syndrome. Genetic counselling and next generation sequencing of 100 – 5500 genes (Sophia Genetics, Switzerland) were performed. The family cascade screening was carried out in 514 (2,3 per case) relatives, in order to detect their risk of the disease.

Results

Very likely or certain molecular aetiology (i.e. based on presence of ACMG.net Class 4 to 5 variants) was disclosed in 60/221 (27%) of CASs. Most frequently identified genes were PKP2 (12/60 cases), RYR2 (7/60), KCNH2 (7/60) and SCN5A (7/60). Clinical and/or genetic diagnosis of inherited condition was detected in 134/514 (26%) relatives, where 30/134 were already under medical care for heart failure and/or ventricular arrhythmia of unknown aetiology. ICD was implanted in 3 cases after careful risk stratification.

Conclusion

Relatives of Czech CASs have mostly interest in family cascade screening. It led to identification of potentially lethal condition in 26% of them and allowed so the prevention of cardiac arrest. Our results further underline a role of genetic analysis in diagnostic work up in non-ischemic cardiac arrest and even in iVF as cause of cardiac arrest.
Gender differences in depression after acute coronary syndromes
Authors: Mangas Palma P P , Moreira H M , Rocha M R , Pinho A P , Oliveira C O , Marques C M , Cabrita A C , Rodrigues J R , Afonso Rocha A F , Dias P D , Rodrigues R R
Published: June 2024

Introduction

After an acute coronary syndrome (ACS), a considerable number of patients experience clinically significant depressive symptoms. The prevalence of major depressive disorder ranges from 20 to 30% and is a well-established risk factor for adverse cardiovascular (CV) outcomes and mortality. Depression complicates the optimal management of CV disease by worsening CV risk factors and decreasing adherence to healthy lifestyles and evidence-based medical therapies (1,2).

Purpose

To characterize gender differences in depressive symptoms in patients enrolled in a cardiac rehabilitation program (CRP) after an ACS.

Methods

We performed a retrospective single-centre cohort study which included patients who were referred to our CRP from 2009 to 2018 after an ACS. Evaluation of depressive symptoms was performed using the self-administered Hospital Anxiety and Depression Scale (HADS) before and 12 months after the end of the CRP. Quality of life was evaluated using the EuroQol-5D Questionnaire. We used multiple linear regression to identify variables that made an important contribution for HADS score and to adjust for confounding variables.

Results

A total of 466 patients were included (75.6% male, with a mean age of 54.4 + 9.62 years). Women were more likely to have major depressive disorder (12.7% vs 5.80%, p=0.033) and less likely to have hypertension (60.6% vs 78.2%, p<0.001), diabetes (7.70% vs 16.3%, p=0.024) or to smoke (60.6% vs 78.2%). At the baseline evaluation, women had a higher mean HADS-Depression score (6.60 vs 5.25, p=0.009) and lower EuroQol-5D score (0.85 vs 0.92, p<0.001). Other baseline characteristics were similar between the groups. During the CRP, women were referred more frequently for psychotherapy (50.0% vs 48.5%, p=0.002) and attendance was similar between the groups.

After 1 year of follow-up, women had a mean HADS-Depression score higher than baseline, while men had a decrease on the mean score (0.83 vs -0.24, p=0.03). Multiple linear regression analysis revealed that female gender was a significant predictor of the of HADS-Depression score after adjustment for age, previous diagnosis of major depressive disorder, antidepressant medication and diabetes (β=1.26, 95% confidence interval 0.14-2-38, p=0.027).

Conclusion

Female gender was associated with depression after ACS, independent of all relevant risk factors. New strategies are needed in CRPs, including tailored interventions, mental health support and education, in order to improve quality of life and improve gender disparities.
Does the relationship between time-varying achieved HbA1c and risk of coronary events depend on haptoglobin phenotype within the Action for Health in Diabetes (Look AHEAD) study?
Authors: Carew A , Warren R A , Bancks M P , Espeland M A , Bahnson J L , Lewis C L , Levy A P , Sapp J L , Urquhart R , Wang J L , Rimm E B , Cahill L E
Published: June 2024

Background

Our previous research has identified the haptoglobin (Hp) phenotype as a potential biomarker that could be used to personalize glycemic control in type 2 diabetes mellitus (T2DM) to prevent coronary artery disease (CAD), the most common cardiovascular disease (CVD). We observed that attaining HbA1c ≥8.0% compared with 7.0–7.9% was consistently associated with incident CAD risk among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the Hp2-2 type(1). No similar association was observed among participants without the Hp2-2 type. However, most ACCORD participants were middle-aged and older males who were at high risk of CVD. Therefore, the optimal glycemic target for CAD prevention for the Hp types remains unclear among women, younger adults, and those at lower risk of CVD.

Objective

To explore the relationship between achieving specific clinically relevant HbA1c targets and risk of incident CAD in separate Hp types in a diverse cohort of individuals living with T2DM (the Action for Health in Diabetes (Look AHEAD) study(2)).

Methods

Hp type was measured in 4,539 blood samples from the Look AHEAD study using a validated assay. Cox regression models with time-varying covariables were used to quantify the association between time-varying achieved HbA1c (<6.5%, 6.5-6.9% and ≥8.0% compared to 7.0-7.9%), updated at years 1-4 and biennially thereafter, and incident CAD in the Hp2-2 (n=1,590) and non-Hp2-2 (n=2,949) types separately. Further pre-specified subgroup analyses by age, sex, and history of CVD were performed in each Hp type group separately.

Results

During 16 years of follow-up, 744 incident CAD cases were documented. Compared with HbA1c 7.0-7.9%, having HbA1c <6.5% was associated with a 29% lower CAD risk among participants with the non-Hp2-2 type (adjusted HR 0.71, 95% CI 0.55-0.90). In subgroup analyses, this association was present in participants with the non-Hp2-2 type who were male (0.58, 0.42-0.80), who did not have a history of CVD (0.67, 0.49-0.93), and who were aged ≥65 years at baseline (0.64, 0.43-0.95). HbA1c ≥8.0% was associated with CAD risk among participants with the Hp2-2 type who had a history of CVD (1.81, 1.02-3.21). No associations were observed between the other HbA1c targets and CAD risk when Hp2-2 participants were combined or partitioned into subgroups.

Conclusion

Achieving HbA1c <6.5% compared with 7.0–7.9% reduced the risk of CAD events in Look AHEAD participants with the non-Hp2-2 type, but not in participants with the Hp2-2 type. HbA1c ≥8.0% was associated with higher CAD risk among participants who had the Hp2-2 type and a history of CVD.
A high level of cardiorespiratory fitness is associated with a stiffer spleen in a population-based cohort study
Authors: Manteufel E , Kaczmarek S , Lehnert K , Markus M , Ewert R , Stubbe B , Ittermann T , Friedrich N , Tzschaetzsch H , Meyer T , Sack I , Doerr M , Bahls M
Published: June 2024

Background

Higher cardiorespiratory fitness (CRF) and muscle strength are independently associated with reduced risk of cardiovascular disease and morbidity. Higher CRF and muscle strength are also associated with an improved immune response. Since the spleen plays an integral role in the innate and adaptive immune system, we hypothesized that CRF and muscle strength would be associated with biophysical characteristics of the spleen. We related CRF and muscle strength with spleen stiffness as measured by shear wave elastography in a large population-based cohort from the Study of Health in Pomerania (SHIP).

Methods

We used cross-sectional data from 677 participants of the population-based, prospective Health Study in Pomerania (SHIP-START-4). A symptom-limited cardiopulmonary exercise test was performed according to a modified Jones protocol. Hand grip strength was determined using a JAMAR dynamometer. Time-harmonic elastography was used to measure splenic shear wave velocity as a surrogate for splenic stiffness. The shear waves in the spleen were generated by a loudspeaker integrated into an examination table, which emitted multifrequency vibrations in the range of 27 to 56 Hz. Tissue strain was encoded from radiofrequency data acquired by an ultrasound system. Shear wave velocity maps covering the entire visible spleen in B-mode were calculated using the k-MDEV method. Finally, mean values were calculated within a manually drawn region of interest. We used linear regression models adjusted for age, sex, and body weight to relate CRF and muscle strength to spleen shear wave velocity.

Results

The median age of the study population was 61 (25th quartile: 52 and 75th quartile: 70) years and 54% were women. A one liter/min higher VO2peak was associated with a 0.05 (95% confidence interval [CI] 0.01 - 0.07; p < 0.01) m/s higher splenic shear wave velocity. A 100 watt higher peak workload was also associated with a 0.05 (95% CI 0.01 - 0.08, p < 0.01) m/s higher splenic shear wave velocity. When CRF was normalized to body weight, a 1 ml/kg/min higher CRF was associated with a 0.007 (95% CI 0.005 - 0.009, p < 0.01) m/s higher splenic shear wave velocity. We found no associations between hand grip strength and splenic shear wave velocity.

Conclusions

In our study, we found that higher VO2peak, VO2peak adjusted for body weight and maximal workload were associated with higher spleen stiffness. As a non-invasive and inexpensive test, time-harmonic shear wave elastography has potential for patient care. Interestingly, there seems to be no correlation between muscle strength and splenic shear wave velocity. It remains unclear why CRF, but not muscle strength, is related to splenic shear wave velocity.
Blood pressure assessment, treatment and control for primary prevention of cardiovascular disease in patients with and without depression
Authors: Ellins E , Summers R , Akbari A , Lloyd K , Osborn D , John A , Gravenor M , Halcox J
Published: June 2024

Background

Patients with depression are at increased risk of future cardiovascular disease (CVD) events compared to those without depression. The reasons for this are not fully understood. Appropriate management of CVD risk factors, including blood pressure (BP) are essential for primary prevention of CVD.

Purpose

To explore whether there are differences in the likelihood of assessment, treatment and attainment of target levels of BP in patients with depression compared to those without.

Methods

A retrospective observational cohort study of patients without a history of depression or CVD was conducted using individual-level linked electronic health record data between 2010 & 2019 using the all-Wales SAIL Databank. Clinical codes were used to identify depression and hypertension diagnoses, BP assessments and antihypertensive therapy (AHT) from general practice (GP) data. Blood pressure assessment is presented as person year rates, and logistic regression was used to identify the likelihood of treatment and control of BP (<140/<90mmHg).

Results

A total of 2,290,075 patients were included (47% female & 7.7% depressed). Depressed patients were younger than non-depressed (mean age 32.0±15.5 vs 40.7±19.3 yrs respectively). Blood pressure assessment rates (BP checks per person per year) were greater in patients with depression 0.813 (0.811-0.815) vs 0.621 (0.620-0.621). Assessment was most frequent in depressed women (0.988 [0.985-0.991]) and least in non-depressed males (0.490 [0.489-0.490]). In patients with a history of HTN, GP diagnosis or high BP reading (n=738,164), 265,232 (35.9%) were on AHT within one year; a smaller proportion of depressed patients with hypertension were receiving AHT than non-depressed (23,808 [34.0%] vs 241,424 [36.1%] p<0.001). However, after multiple logistic regression (adjusting for age, sex, location of residence, deprivation, and comorbidities), depressed patients were more likely to be on AHT (OR 1.22 95%CI 0.12-1.32). In those patients on AHT 235,134 (88.7%) had at least one valid BP measurement during the year. Of these 114,601 (48.7%) achieved a BP <140/90 mmHg. A greater proportion of depressed patients with hypertension on AHT had documented control of BP than non-depressed (11,143 [57.3%] vs 103,458 [48.0%] p<0.001 OR 1.28 95%CI 1.11-1.50). There was a significant interaction between depression and sex, with depressed females being the most likely to achieve control (p<0.001).

Conclusion

Patients with depression are more likely to have BP assessed and to have hypertension treated and controlled than patients without depression within Welsh primary care. This maybe due to more frequent interaction with their GP, but further research is required to investigate reasons and impact on outcomes.
Heterogeneous associations of traditional atherosclerotic risk factors and long-term complications in different arterial territories: the EPIC Norfolk prospective population cohort
Authors: Van Den Bogaart M , Van Trier T J , Snaterse M , Martens F M A C , Peters R J G , Boekholdt S M , Jorstad H T
Published: June 2024

Background

Atherosclerotic risk factors have been associated with cardiovascular disease (CVD) complications in specific arterial territories. However, these observations are limited by relatively short-term follow-up (i.e. ten years) We therefore investigated longer-term associations between atherosclerotic risk factors and specific cardiovascular complications in a large cohort with ≥20 years follow-up.

Methods

We included participants from the EPIC Norfolk prospective population cohort without a history of CVD. The strength of associations between CVD risk factors (smoking, low-density lipoprotein cholesterol (LDL-c), and systolic blood pressure (SBP)) and CVD events were evaluated using a competing risks regression model. CVD events were defined as hospitalization or death due to ischemic heart disease (IHD), ischemic stroke, hemorrhagic stroke or peripheral arterial disease (PAD) including abdominal aortic aneurysm (AAA). Patients were followed-up until the first event, death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, diabetes, HDL-c, kidney function and body mass index. LDL-c and SBP were analysed by comparing highest versus lowest quartiles. Smokers (at baseline) were compared to never-smokers. For 10.1% of participants with missing risk factor data, median imputation was used.

Results

We included 23,581 participants (56% women) with a mean baseline age of 58 (IQR 51-66). During mean follow up of 22.4 years (IQR 19-23), occurrence of any CVD event was observed in 29.4% (6,926) individuals. Of these, 55.3% (4,449) were IHD, 15.0% (1,211) were ischemic stroke, 5.9% (471) were hemorrhagic stroke and 23.8% (1,920) were PAD or AAA. LDL-c was strongly associated with IHD [adjusted hazard rate (aHR) 1.67, 95% CI 1.50 - 1.85], but not significantly with hemorrhagic stroke (aHR 1.07, 95% CI 0.78 – 1.47). SBP was significantly associated with ischemic stroke (aHR 1.94, 95% CI 1.53 – 2.46), but not with hemorrhagic stroke (aHR 1.39 95% CI 0.97 – 2.00). Smoking was strongly associated with PAD/AAA (aHR 2.49, 95% CI 2.13 - 2.92), but not with ischemic stroke (aHR 1.20, 95% CI 0.95 – 1.51) and hemorrhagic stroke (aHR 1.20 95% CI 0.83 – 1.73) (Figure 1).

Conclusions

There is considerable heterogeneity in the associations between atherosclerotic risk factors and long-term cardiovascular complications in different arterial territories. Knowledge of these differences may assist in personalised treatment decisions and risk communication. Hazard Ratios for CVD events.
Statin therapy eligibility in a large primary prevention cohort according to European Society of Cardiology Guidelines
Authors: Hauguel-Moreau M , Mansencal D , Miliani K , Beauchet A , Rodon C , Dubourg O , Mansencal N
Published: June 2024

Background

2016 European Society of Cardiology (ESC) guidelines on statin therapy eligibility in primary prevention were updated in 2021, with significant differences and particularly the use of a new estimation of 10-year fatal and nonfatal CVD risk with Systematic Coronary Risk Estimation 2 (SCORE2).

Purpose

The aim of the study was to compare the proportion of subjects aged 40 to 69 years eligible to statin therapy according to the 2016 and 2021 ESC recommendations in a large primary prevention cohort.

Methods

We conducted a screening campaign between January 2007 and December 2022 for cardiovascular risk factors in large urban cohort of subjects aged 40-69 (the CARVAR 92 study). We systematically calculated the individual cardiovascular risk for all our subjects. We thus estimated the proportion of subjects eligible for statin therapy based on 2021 ESC guidelines versus 2016 ESC guidelines. Costs relating to statin therapy were also estimated.

Results

27,807 subjects were included in the CARVAR 92 study: 13.7% were eligible to statin therapy according to the 2016 ESC guidelines versus 32.2% according to the 2021 guidelines (p < 0.0001). The proportion of subjects eligible to statin therapy increased by a factor 2.3 between the 2016 and 2021 ESC guidelines for the whole cohort, and increased by a factor 12 in men aged 40 to 50 (from 3.8% of individuals eligible to statin therapy for 2016 recommendation to 45.7% [p < 0.0001] for 2021 recommendation). Costs associated with statin therapy for the whole cohort increased by a 2.7 factor between 2016 and 2021 recommendations.

Conclusion

In a large primary prevention cohort, we observed a strong increase in the number of subjects eligible to statin therapy with the new 2021 ESC recommendations (versus 2016) and therefore in statin costs, particularly in men between 40 and 50 years old. The clinical and economic impact on the occurrence of cardiovascular events of these new recommendations in a real life remains to be evaluated. Eligibilty to statin therapy.