bluuebunny/crossref_metadata_2025_split huggingface dataset:
The workload-indexed blood pressure response predicts cardiovascular events and all-cause mortality in coronary artery disease
Authors: Braganca B , Oliveira I , Cruz I , Lopes R G , Queiros C , Pinto P , Andrade A 
Published: October 2022

Abstract

Background
Abnormal blood arterial pressure response to exercise (BPR) is a cardiovascular (CV) risk factor (CVRF). The concept of pathological BPR, believed to be an excessive raise or decrease, has been challenged. The workload-indexed blood pressure response (WBPR) recently emerged in an attempt to normalize hypertensive responses to exercise. However, it remains to be explored its value in high-risk CV subjects.

Purpose
Evaluation of the predictive value of WBPR in the occurrence of CV events and death in coronary artery disease (CAD) patients.

Methods
A cohort of 318 patients with known CAD, who underwent Bruce protocol treadmill testing between 2009–2010, were retrospectively followed to 11/2021 (9.9±2.3 years) to assess the predictive value of WBPR for the occurrence of death and CV events. The WBPR is the ratio between systolic blood pressure variation from rest to peak exercise (ΔSBP) and metabolic equivalent of task (MET-1). High and low WBPR groups were created based on median value for this sample (5.2 mmHg/MET). Data presented: mean ± standard deviation; 95% confidence interval (CI) for hazard ratios (HR); significance between groups p&lt;0.05.

Results
Low vs high WBPR groups were similar at baseline for sex (88% male, p=0.67), hypertension (63%, p=0.18), diabetes (32%, p=0.34); dyslipidemia (72%, p=0.62), myocardial infarction (75%, p=0.39) and heart failure (HF) (9.9%, p=0.07), with exception for overweight/obesity (90% vs 82%, p=0.009) and age (57±11 vs 61±8 years, p=0.009) that were higher in the high-WBPR group. No significant differences were found between groups for medication at baseline, including anti-hypertensive, anti-thrombotic or anti-ischemic drugs. In the follow-up period occurred 43 deaths (12 CV deaths), 58 reinfarctions, 94 worsening/de novo HF and 29 strokes. A non-linear J-shaped relationship was observed between WBPR and most events. In the event-free survival analyses using Cox regression, the high-WBPR group was associated with all death (HR 2.0 (CI 1.0–3.9, p=0.042), reinfarction (HR 2.3 (CI 1.2–4.1, p=0.008), and worsening/de novo HF (HR 1.7 (CI 1.0–2.9, p=0.043) after adjusting for baseline age, CVRFs and medication. In receiver operating characteristic curves, adding WBPR to a model with other cardiac stress variables (double product, ST-T changes, symptoms, and test positivity) significantly improved the power to predict all death, with an area under curve of 0.73 (CI 0.66–0.80, p=0.037).

Conclusions
Data shows that WBPR is a powerful independent predictor of future cardiovascular events and deaths in CAD patients. This highlights cardiac exercise stress testing as an important risk assessment tool in secondary prevention of cardiovascular disease.

Funding Acknowledgement
Type of funding sources: None.
Cardiac magnetic resonance feature-tracking analysis of left atrial volumes and function in standard vs left-atrial focused images
Authors: Tondi L , Figliozzi S , Badano L P , Torlasco C , Disabato G , Pica S , Camporeale A , Muraru D , Lombardi M 
Published: October 2022

Abstract

Background
Left atrial (LA) volume and function have shown prognostic value in several cardiac conditions. Routine cardiac magnetic resonance (CMR) evaluation of the LA is obtained from standard 2- and 4-chamber long-axis cine images focused on the left ventricle. Previous echocardiographic data showed that LA-focused apical views provide a more accurate estimation of LA maximum volume, as compared to standard apical images. CMR LA-focused imaging could improve the accuracy of LA morpho-functional analysis. CMR feature-tracking (CMR-FT) analysis is emerging as a feasible semi-automatic tool for the evaluation of LA volumes and function.

Purpose
To investigate the potential of LA-focused CMR cine images using LA CMR-FT analysis.

Methods
100 consecutive patients clinically referred to CMR were included in this prospective, observational, multicenter study. LA volumes (LAVmax, LAVmin), emptying fraction (EF), atrial strain reservoir (ɛs), conduit (ɛe), booster (ɛa) and strain rate reservoir (SRɛs) were calculated by CMR-FT analysis on both standard and LA-focused 2- and 4-chamber long-axis cine images. Manual segmentation of a short-axis cine stack covering the LA was used as the reference method (RefMeth) for LA volumes and EF.

Results
In comparison to the RefMeth, the standard acquisitions underestimated LA volumes (LAVmax: bias = −8ml, LOA = +20, −35ml; LAVmin: bias = −6 ml, LOA = +15, −27ml) and slightly overestimated EF (bias = +3%, LOA = +17, −11%). Conversely, LA-focused images provided a more accurate estimation (LAV max bias = −1ml, LOA = +11, −9ml; LAV min bias = −2ml, LOA = +12, −7ml) and EF (bias = −2%, LOA = +9, −12%). All three LA strain (εs: bias 7%, LOA = 25, −11%; εe: bias 4%, LOA = 15, −8%; εa: bias 3%, LOA = 14, −8%) and SRεs (bias 0.2 s–1, LOA = 1.13, −0.7 s–1) were significantly higher in standard vs LA-focused images (all p&lt;0.001).

Conclusions
Assessment of LA volumes using CMR-FT applied to dedicated LA-focused long-axis cine images is more accurate than the use of standard acquisitions. LA strain and SRɛs obtained from LA-focused images are significantly lower than those obtained from standard LA acquisitions, possibly due to the inclusion in LA-focused images of LA posterior wall, where pulmonary veins convey and atrial deformation is blunted.

Funding Acknowledgement
Type of funding sources: None.
Cardiovascular disease-wide association study to investigate shared genetics with peak oxygen uptake
Authors: Nordeidet A , Bye A , Langaas M , Klevjer M 
Published: October 2022

Abstract

Introduction
Cardiorespiratory fitness, measured as peak oxygen uptake (VO2peak), is a strong predictor of cardiovascular disease (CVD) morbidity and mortality and is estimated to have a large genetic component (∼60%). However, the genetic determinants are yet to be established. Our research group recently identified novel genetic variants associated with directly measured VO2peak. Interestingly, most were specific to females. Looking into genetic pleiotropy between VO2peak and CVD can help elucidate the biological mechanisms explaining the link between this fitness related trait and disease, and potentially identify new therapeutic targets.

Purpose
The association study aims to investigate if genetic variants found to be associated with VO2peak in women is associated with any cardiovascular disease phenotypes.

Methods
34,188 female participants with genotype data from the Trøndelag Health Study (HUNT) were included in this study. ICD-coded hospital data related to cardiovascular disease was collected on each participant and the ICD codes were mapped to Phecodes, resulting in 100 disease-specific phenotypes. 26 single nucleotide polymorphisms (SNPs) previously found to be associated with directly measured VO2peak (p&lt;5e-6) were included in the analyses, all common variants (minor allele frequency ≥1%). Each of the 26 genetic variants were tested for association with the 100 phenotypes using a logistic mixed model as implemented in SAIGE. The analysis was adjusted for birthyear and ten principal components of ancestry. The Benjamini-Hochberg false discovery rate (FDR) procedure controlling the FDR at 0.05 was used to correct for the number of tested SNPs and phenotypes.

Results
After testing each of the 26 SNPs for association with 100 cardiovascular disease phenotypes, 133 SNP-phenotype associations were nominally significant (p&lt;0.05). The association between rs17066736 and myocarditis had the lowest p-value (1.7e-4). Among the other tested SNP-phenotype pairs were phenotypes related to ischemic heart disease, cardiac conduction disorders, heart failure, cerebrovascular disease, and diseases of arteries and veins. However, when adjusting for multiple testing, none reached overall statistical significance.

Conclusions
The findings showed no statistically significant associations between genetic variants associated with VO2peak and cardiovascular disease phenotypes in women. The role of inborn VO2peak in prediction of CVD (in women) needs further assessment.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): NTNU biotechnology
Combining European Society of Cardiology and American College of Cardiology/American Heart Association risk prediction model with polygenic risk scores to refine cardiovascular prevention
Authors: De La Harpe R , Thorball C W , Redin C , Fournier S , Muller O , Strambo D , Michel P , Vollenweider P , Marques-Vidal P , Fellay J , Vaucher J 
Published: October 2022

Abstract

Introduction
Polygenic risk scores (PRS) predict the risk of developing atherosclerotic cardiovascular disease (ASCVD). However, their utility in combination with existing clinical risk scores remains uncertain.

Purpose
We first validated four different PRS in a Swiss population-based cohort. Second, using the PRS with the best predictive capacity, we assessed its benefit when combined with two clinical risk scores: the Systematic COronary Risk Evaluation 2 (SCORE2) and the Pooled Cohort Equation (PCE).

Methods
We used data from a prospective cohort involving 6733 European participants at baseline (2003–2006). The predictive accuracy of the PRS was assessed with discrimination and calibration metrics. For the second aim, subjects with prevalent ASCVD or statin therapy at baseline were excluded. We tested associations between risk prediction models (PRS alone and combined clinical and PRS) and incident ASCVD, using Cox proportional hazard regressions. Net reclassification index (NRI) detected any improvement of ASCVD risk categorisation following the addition of the PRS to clinical risk scores in overall sample and in subgroups (e.g., sex, age, clinical intermediate-risk category)

Results
For the first aim, 4215 subjects (53% women; mean age 53.7±10.7), with 357 prevalent ASCVD, were analysed. The PRS developed by Inouye et al. [1], comprising &gt;6 million variants, presented the best predictive capacity (area under the receiver operating characteristic of 0.77) and was used in the following analyses. For the second aim, 3390 subjects (mean follow-up of 12.0±3.3 years), with 188 incident ASCVD, were analysed. Individuals in the top 20% of the PRS distribution had the same magnitude of association with ASCVD as current smokers or diabetic subjects (see Figure 1). Combining the PRS with SCORE2 led to a reclassification of 17.1% (95% CI, 4.7–29.5) of subjects in the intermediate-risk category (see Figure 2). Likewise, adding the PRS to PCE translated into an NRI of 19.2% (95% CI, 4.8–22.4) in the intermediate-risk category (not shown).

Conclusion
Using a Swiss population-based cohort, PRS presented good predictive capacities for ASCVD. Combining a PRS with clinical risk scores improved reclassification of risk for ASCVD, especially for subjects in the intermediate-risk category. Introducing PRS in clinical practice may refine cardiovascular prevention for subgroups of patients in whom prevention strategies are uncertain.

Funding Acknowledgement
Type of funding sources: None.
Serum uric acid levels significantly improve the accuracy of cardiovascular risk score models
Authors: Moshkovits Y , Tiosano S , Kaplan A , Kalstein M , Bayshtok G , Kivity S , Segev S , Grossman E , Segev A , Maor E , Fardman A 
Published: October 2022

Abstract

Background
This study evaluated the impact of serum uric acid (sUA) on the accuracy of atherosclerotic cardiovascular disease (ASCVD) pooled cohort equations (PCE) model, Systematic Coronary Risk Evaluation score 2 (SCORE2) and SCORE2-Older Persons (OP).

Methods
We evaluated 19,789 asymptomatic self-referred adults aged 40–79 years who were screened annually in a preventive healthcare setting. All subjects were free of cardiovascular disease and diabetes at baseline. sUA levels were expressed as a continuous as well as dichotomous variable (categorized into sex-specific tertiles, with the upper tertiles defined as high sUA). Mortality and cancer data were available for all subjects from nationwide registries. The primary endpoint was the composite of death, acute coronary syndrome and stroke, after excluding subjects diagnosed with lymphatic spread cancer during follow up.

Results
Mean age of study population was 50±8 years and 69% were men. During median follow up of 6 years [2.0–13.1], 1,658 (8%) subjects reached the study endpoint. ASCVD, SCORE2 risk and high sUA were all independently associated with the study endpoint in the multivariable Cox regression model (p&lt;0.001 for all). Continuous net reclassification improvement analysis showed an improvement of 13% in the accuracy of classification when high sUA was added to the PCE and SCORE2 models (p&lt;0.001 for both). sUA remained independently associated with the study endpoint among normal-weight subjects in the SCORE 2 model (HR 1.3, 95% CI 1.1–1.6) but not among overweight individuals (p for interaction = 0.01). Addition of sUA to the models in normal-weight subgroup (N=6,624) resulted in a significant 20% improvement in the model performance for both SCORE2 and ASCVD when sUA was incorporated as dichotomous variable (p&lt;0.001 for ASCVD and p=0.026 for SCORE2 model).

Conclusions
sUA significantly improves classification accuracy of PCE and SCORE 2 models. This effect is especially pronounced among normal weight subjects.

Funding Acknowledgement
Type of funding sources: None.
Comparison between the European SCORE and the updated SCORE2 for cardiovascular outcomes
Authors: Temtem M , Mendonca M I , Serrao M , Santos M , Sa D , Soares C , Sousa A C , Rodrigues M , Freitas S , Henriques E , Borges S , Ornelas I , Drumond A , Palma Dos Reis R 
Published: October 2022

Abstract

Introduction
The European Systematic Coronary Risk Evaluation (SCORE) has predicted a 10-year risk of CVD since 1986. It included only fatal CVD outcomes, underestimating the total CVD burden, especially for younger people. To counteract this issue, a new score was created (SCORE2) to estimate 10-year fatal and non-fatal CVD risk in Europeans without previous CVD or diabetes aged 40–69 years.

Purpose
Establish a comparison between SCORE and SCORE2 in terms of CV outcomes in a moderate-risk population.

Methods
A population of 1,178 individuals without CVD (mean age 53.3±6.9 years; 73.9 male) was stratified into three risk categories for SCORE and SCORE2: low, moderate and high-risk. Using t-test and Chi-square, we compared the two scores in terms of means and risk categories. Kaplan-Meier estimator evaluated MACE occurrence for each category of the two scores during an extended follow-up (mean of 5.2±3.4 years). MACE discriminative capacity of SCORE and SCORE2 was evaluated through C-index methodology.

Results
The means of the two scores were significantly different (p&lt;0.0001): 2.1±2.4 for SCORE and 6.0±3.3 for SCORE2. 51% of the individuals with high-risk SCORE2 presented the lowest value of SCORE (0–5%). Kaplan-Meier curves showed that the highest category had a worst survival for each score. SCORE2 showed a better discriminative capacity for MACE (C-index 0.678) relatively to SCORE (C-index 0.591), with statistical significance (p&lt;0.0001).

Conclusion
SCORE2 enhanced the identification of individuals at higher risk of developing CVD and better discriminated MACE occurrence relatively to SCORE.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
Genetic information or coronary artery calcium score? What is more helpful in today's clinical practice?
Authors: Sa D , Mendonca M I , Temtem M , Santos M , Serrao M , Sousa A C , Borges S , Freitas S , Rodrigues M , Henriques E , Guerra G , Ornelas I , Drumond A , Palma Dos Reis R 
Published: October 2022

Abstract

Introduction
Coronary artery calcium (CAC) score has emerged as the most predictive cardiovascular risk marker in asymptomatic individuals, capable of adding prognostic information beyond the traditional risk factors (TRF). Genetic risk score (GRS) significantly improves cardiovascular genetic risk assessment at the individual level providing a more personalized measure of disease risk.

Purpose
We intend to evaluate which tool, added to TRF, is more valuable in predicting and discriminating cardiovascular events and death (MACE) - GRS or CAC score?

Methods
We performed a prospective study with 1153 participants without CAD history at baseline (74.2% male, age 51.7±8.3 years) during a mean follow-up of 5.4±3.4 years. We selected 14 SNPs previously associated with CAD presenting a risk (HR) for cardiovascular events ≥1. A weighted GRS was calculated, as the sum of these 14 risk alleles weighted by the corresponding effect size in prognostic (HR), and subsequently, subdivided into tertiles. CAC (Agatson) score was calculated in all participants and categorized into: low CAC (0≤CAC&lt;100 or P&lt;50); moderate CAC (100≤CAC&lt;400 or P50–75) and high or severe CAC (CAC≥400 or P&gt;75). Two models were created with TRF baseline (hypertension, smoking, body mass index, dyslipidemia, diabetes, chronic kidney disease, physical inactivity): 1) plus wGRS and 2) plus CAC score categories. Cox Regression Analyses and C-statistic assessed the predictive and discriminative capacity of both models.

Results
For model 1, Cox regression presented an HR of 4.292 for TRF (p=0.007) and 2.713 for 3rd tertile of wGRS (0.036). A modest but statistically significant improvement in MACE discriminative capacity was verified by adding wGRS to TRF, increasing the C-statistic from 0.617 to 0.687 (ΔC=0.070; p=0.013). On the other hand, model 2 better discriminated MACE when the CAC score (C-statistic = 0.765) was added to TRF (ΔC=0.148; p=0.001). Cox regression displayed an HR of 4.42 for TRF (p=0.015) and an HR of 4.55 for high-risk CAC score (p=0.001).

Conclusion
Our results suggest that adding a polygenic risk score to conventional risk factors provides a modest improvement in the discrimination of first-onset MACE. However, the CAC score added to the traditional model allows better discrimination of MACE compared to wGRS. CAC score could be helpful for MACE prediction, at least in individuals belonging to the higher genetic risk group. However, further investigation is required before clinical implementation.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPERAM
Prediction of lifetime cardiovascular risk and individual lifetime treatment benefit in four European risk regions: geographic recalibration of the LIFE-CVD model
Authors: Hageman S H J , Lu W , Kaptoge S , Lall K , Bobak M , Pikhart H , Kubinova R , Pajak A , Tamosiunas A , Stang A , Schmidt B , Schramm S , Di Angelantonio E , Visseren F L J , Dorresteijn J A N 
Published: October 2022

Abstract

Background
The life expectancy free of cardiovascular disease (CVD) in individuals without previous CVD can be estimated with the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model, as recommended by the 2021 ESC CVD prevention guidelines. Our aim was to systematically recalibrate the LIFE-CVD model to four European risk regions using contemporary and representative registry data.

Methods and results
The LIFE-CVD model was systematically recalibrated to four distinct risk regions within Europe, using representative aggregate data on age- and sex-specific expected CVD and non-CVD mortality incidences and risk factor distributions. For external validation, 1,451,077 individuals without previous CVD were included from seven European cohorts, with 53,721 CVD events and 62,902 non-CVD deaths during follow up. After applying the recalibrated risk prediction models to external validation cohorts, C-indices (figure 1) ranged from 0.670 (95% CI 0.650–0.690) to 0.787 (95% CI 0.785–0.789). Predicted risks matched the observed risks in the CPRD data. With the recalibrated LIFE-CVD model, the estimated gain in CVD-free life expectancy from preventive therapy differed per region, for example a 50-year-old smoking women with a systolic blood pressure of 140mm Hg was estimated to gain 0.4 years of CVD-free life from 10 mm Hg SBP reduction in the low risk region, whereas this would be 1.5 years in the very high risk region (figure 2).

Interpretation
By taking into account geographical differences in CVD incidence, the recalibrated LIFE-CVD model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making in cardiovascular prevention options as recommended by the 2021 European Prevention Guidelines.

Funding Acknowledgement
Type of funding sources: None.
The value of additional risk factors for improving 10-year cardiovascular risk prediction in apparently healthy people
Authors: Hageman S H J , Pennells L , Pajouheshnia R , Tillmann T , Blaha M J , McClelland R L , Matsushita K , Nambi V , Van Der Schouw Y T , Verschuren W M M , Lehmann N , Jockel K H , Di Angelantonio E , Visseren F L J , Dorresteijn J A N 
Published: October 2022

Abstract

Background
In clinical practice, factors known to be associated with cardiovascular disease (CVD) like albuminuria, education level, or coronary calcium score are not directly incorporated in cardiovascular risk prediction models. The aim of the current study was to quantify the added value of potential risk modifying characteristics when added to the SCORE2 algorithm for individuals without diabetes mellitus (DM) or prior CVD.

Methods and results
Individuals without previous CVD or DM were included from the ARIC, MESA, EPIC-NL and HNR studies (n=46,285) in whom 2,177 CVD events and 2,062 non-cardiovascular deaths were observed over exactly 10.0 years of follow-up. The effect of each possible risk modifying characteristic was derived using Fine and Gray models that included an offset term for the SCORE2 linear predictor. The risk modifying characteristics were applied to individual predictions using the “naïve approach”, which modifies predicted risks based on the population prevalence and the SHR of the relevant predictor. Subdistribution hazard ratios are presented in the table. External validation was performed in the CPRD cohort (UK, n=518,015, 12,675 CVD events). In the external validation, adjustment of SCORE2 predicted risks with both single and with all available risk modifiers did not negatively affect calibration (see figure) and led to a modest increase in discrimination (C-index 0.742 [95% CI 0.737–0.746] versus unimproved SCORE2 risk C-index 0.737 [95% CI 0.732–0.741]). The net reclassification index or adding all these predictors was +0.032 (95% CI 0.025; 0.028) for future events and −0.008 (95% CI −0.009; −0.007) for future non-events. The coronary calcium score was found to the single strongest added predictor.

Interpretation
The current analysis presents a method on how to integrate possible risk modifying characteristics that are not included in existing CVD risk models for the prediction of CVD event risk in apparently healthy people. This flexible methodology improves the accuracy of predicted risks and increases applicability of prediction models for individuals with additional risk known modifiers

Funding Acknowledgement
Type of funding sources: None.