bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of unemployment on cardiovascular mortality in united states: a nationwide county-level analysis 2010–2019
Authors: Sayed A , Aldosoky W , Khalid N , Diab M , Elsaiey A , Dar T , Abohashem S
Published: October 2022

Background

Unemployment has been linked with a myriad of adverse health outcomes; however, its population-level impact on cardiovascular mortality (CVM), particularly amongst various demographic subgroups, remains understudied.

Purpose

To determine the impact of county unemployment levels on CVM rates, in overall and between different demographic subgroups.

Methods

We utilized the CDC WONDER database tool to retrieve county-level CVM rates for U.S. counties between 2010 and 2019. The County Health Rankings project was used to retrieve data on unemployment levels in each county as well as other characteristics used in an adjusted multivariate model. Generalized linear mixed models using Poisson regression were used to estimate the impact of unemployment on county-level CVM using relative (incidence rate ratios; IRR) and absolute (additional yearly deaths; AYD) measures.

Results

From 2010 to 2019, a total of 2904 U.S. counties (64.2% white; 50.81% female) with data available on CVM and unemployment levels were analyzed. In a multivariate model adjusted for demographic composition, CV risk, socioeconomic, environmental, and healthcare-access factors, unemployment was significantly associated with higher levels of CVM (IRR: 1.026; 95% CI: 1.018 to 1.033; 6.00 AYD). The relative impact of unemployment was strongest in elderly Blacks (IRR: 1.051; 95% CI: 1.029 to 1.074), middle-aged whites (IRR: 1.050; 95% CI: 1.032 to 1.067), and middle-aged females (IRR: 1.046; 95% CI: 1.018 to 1.075). The absolute impact of unemployment was highest in elderly Blacks (AYD: 94.70), elderly Whites (AYD: 35.30), and elderly females (AYD: 32.70). On a relative basis, the impact was more pronounced in the middle-aged (IRR: 1.030; 95% CI: 1.015 to 1.044) compared to the elderly (IRR: 1.022; 95% CI: 1.014 to 1.030), females (IRR: 1.026; 95% CI: 1.017 to 1.036) compared to males (IRR: 1.022; 95% CI: 1.014 to 1.031), and Blacks (IRR: 1.036; 95% CI: 1.016 to 1.057) compared to Whites (IRR: 1.030; 95% CI: 1.022 to 1.038).

Conclusion(s)

Unemployment is significantly associated with county-level CVM, and this impact is most pronounced in vulnerable demographic subgroups, namely females and Blacks. Efforts to reduce unemployment levels may significantly lower the burden of cardiovascular disease, particularly in groups most strongly affected by health disparities.

Funding Acknowledgement

Type of funding sources: None.
Sex and gender influence on cardiovascular health in sub-saharan Africa: findings from Ghana, Gambia, Mali, Guinea, and Botswana
Authors: Dev R , Favour-Ofili D , Raparelli V , Behlouli H , Azizi Z , Kublickiene K , Kautzky-Willer A , Trinidad Herrero M , Pilote L , Norris C M
Published: October 2022

Background

Sex and gender-based differences in cardiovascular health (CVH) has been explored in the context of high-income countries. However, these relationships have not been examined in low- and middle-income countries. There is an upsurge of cardiovascular diseases (CVDs) in sub-Saharan Africa (SSA). Irrespective of biological sex, gender-related factors could be the precursor of these conditions.

Purpose

To examine the associations between biological sex, gender-related variables, and CVH risk factors in SSA countries.

Methods

We conducted a retrospective analysis of the World Health Organization's “STEPwise approach to surveillance of risk factors for non-communicable disease” or “STEPS” survey, conducted in adults aged 18–69 years from Ghana, Gambia, Mali, Guinea, and Botswana. The surveys were conducted between 2006 and 2014. The main outcome was CVH, as measured by a composite measure of STEPS-HEART health index (smoking, hypertension, diabetes, obesity/overweight, and daily consumption of fruits and vegetables), values ranging from 0 (worst) to 5 (best or ideal). Multivariable logistic regression was applied to determine the gender-related factors related to poorer CVH (index less than 4). Two-way interaction between the sex and gender-related factors were tested by including an interaction term in bivariate models.

Results

Data included 15,356 adults (61.4% females, mean age 36.9 years). The prevalence of hypertension (21.6% vs. 13.8%) and overweight/obesity (48.3% vs. 27.5%) was higher among females as compared to males. Females were more likely to be unemployed (17.3% vs. 9.7%) or reported unpaid work (36.8% vs. 15.2%). Overall, females showed worse CVH than males (OR female = 0.95, 95% CI: 0.91–0.99). Being married was associated with better CVH compared with being single, more so for males (OR male = 1.09, 95% CI: 0.96–1.24, p interaction <0.01). Males with unpaid work (OR male = 1.28, 95% CI: 1.12–1.47) had better CVH than their unpaid female counterparts (OR female = 1.08, 95% CI: 1.01–1.17).

Conclusion

This study highlights an alarmingly high prevalence of CVD risk factors, mainly overweight/obesity and hypertension among females in SSA population. Being female was associated with poorer CVH given the disproportionate burden of hypertension and overweight/obesity. Gender-related factors such as marital status and unpaid work were associated with better CVH in males compared to females. With the rising prevalence of CVDs in SSA, it will be important to consider the gender-related factors while implementing preventive programs and creating effective health policies.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): The GENDER– NET Plus ERA-NET Initiative (project ref. number: GNP-78): The Canadian Institutes of Health Research (GNP-161904)
Mortality and predictors of death in women and men with congestive heart failure with preserved, mildly reduced, and reducedejection fraction
Authors: Barretto A , Del Carlo C H , Ramos Neto J A , Abreu A B , Scipioni A R , Mansur A P
Published: October 2022

Background

Congestive heart failure (CHF) is one of the leading causes of death from cardiovascular disease and years lived with disability. Studies showed that women had better survival than men despite higher hospitalizations in women. However, little is known about differences in mortality and predictors of death in women and men with heart failure with preserved (HFpEF), mildly reduced (HFmrEF), and reduced ejection fraction (HFrEF).

Methods

From February 2017 to September 2020, we analyzed the mortality and the predictors of death in women and men with CHF (Framingham criteria). Baseline data included clinical characteristics and echocardiographic findings. Statistical analyses were performed with the Kaplan-Meier (K-M) method and the Cox proportional hazards methods to analyze death rates and search for predictors of death for women and men.

Results

We studied 12,015 patients, mean of 63.8±14.3 years, 6637 (55%) males. Females were older (64.9±14.8 vs. 62.8±13.8 years; p<0.0001), had a higher baseline mean left ventricular ejection fraction (LVEF) (49.8±18.9% vs. 42.6±15.4%; p<0.001), and a lower left ventricular diastolic diameter (LVDD) (54.1±9.0 vs. 60.1±9.6 mm; p<0.001). Over a 3-years follow-up period, 1543 (23.2%) men and 1051 (19.5%) women of the cohort died (K-M: log-rank p<0.0001). Cumulative incidence of death was higher in men (K-M: log-rank p=0.0002) with HFrEF but similar for HFmrEF and HFpEF (Figure 1). Cox regression for death adjusted for age, ischemic, idiopathic, hypertension, Chagas, valve, previous myocardial infarction, diabetes, previous stroke, chronic kidney disease (CKD), atrial fibrillation, and LVEF showed that CKD, previous stroke, and diabetes were the main predictors of death for all phenotypes of LVEF in women and men.

Conclusion

Women had a better prognosis than men inHFrEF but similar mortality for HFmrEF and HFpEF. Control of diabetes and preventing stroke and CKD could significantly reduce the death rate in women and men with all CHF phenotypes.

Funding Acknowledgement

Type of funding sources: None.
Myocardial function and myocardial work in young adults born very preterm or with extremely low birthweight – a regional cohort study
Authors: Engan B , Omdal T R , Greve G , Vollsaeter M , Leirgul E
Published: October 2022

Background

Preterm birth and low birthweight have been associated with increased risk of cardiovascular disease and heart failure at young adult age. However, clinical studies of myocardial function have reported diverging results. Echocardiographic strain analyses allow detection of subclinical early stages of cardiac dysfunction, and non-invasively estimation of myocardial work derived from left ventricular pressure-strain loops provides additional information on cardiac function.

Purpose

We aimed to compare systolic and diastolic myocardial function including measures of myocardial work in young adults born very preterm (<29 weeks of gestation) or with extremely low birthweight (<1000 g) (PB/ELBW) and term-born age-and gender matched controls.

Methods

63 PB/ELBW and 64 controls born in Norway in the periods 1982–1985, 1991–1992, and 1999–2000 were examined with echocardiography. Left ventricular (LV) ejection fraction, LV global longitudinal strain (GLS), traditional diastolic parameters and left atrial longitudinal strain were measured. Myocardial work was estimated by the echocardiographic software from LV pressure-strain loops after determination of GLS and construction of a LV pressure curve derived from brachial cuff pressure recording and timing of mitral valve opening and closure.

Results

The PB/ELBW with mean age 27 years (standard deviation (SD) 6), mean birthweight 945 g (SD 217) and mean gestational age 27 weeks (SD 2) had LV systolic function mainly within normal range. Only four (<1%) had EF <50%, but 12 (19%) had borderline impaired GLS >−18% or impaired GLS >−16%. Mean GLS in PB/ELBW (−19.7% (95% confidence interval (CI): −20.4, −19.1)) was impaired compared to controls (−20.4% (95% CI: −20.9, −20.0)), p=0.01. Lower birthweight was correlated to more impaired GLS (Pearson correlation coefficient −0.2). Estimated means of EF, measures of diastolic function, left atrial reservoir strain, global constructive and wasted work, global work index and global work efficiency was similar in PB/ELBW and controls.

Conclusions

The young adults born preterm or with extremely low birthweight had LV systolic function mainly within normal range, but GLS was impaired compared to controls, and lower birthweight was associated with more impaired GLS. Diastolic function and global work index were similar compared to controls.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Western Norway Health Authority
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

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<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

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<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

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<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<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

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 >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

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<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<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<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

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<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<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

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<100 or P<50); moderate CAC (100≤CAC<400 or P50–75) and high or severe CAC (CAC≥400 or P>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

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

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.
Comparison of SCORE and SCORE 2 risk prediction tools in contemporary very high risk european population
Authors: Boskovic N , Giga V , Djordjevic-Dikic A , Beleslin B , Stojkovic S , Nedeljkovic I , Aleksandric S , Tesic M , Dedic S , Burazor I , Karadzic T , Paunovic I , Jovanovic I
Published: October 2022

Background

New SCORE 2 algorithm overperformed SCORE algorithm in population with decreasing prevalence of cardiovascular (CV) morbidity and mortality. However, there is limited data in risk stratification with SCORE 2 model in contemporary populations from very high risk countries.

Aim

The aim of this study was to compare risk prediction using SCORE 2 and SCORE model and to compare the proportions of patients requiring statin treatment in primary prevention.

Methods

Our study included 1317 patients (511, 38.8% male gender, average age 54±8) without known CV disease aged 40 to 70 years. Data on CV risk factors were prospectively collected in 20 primary care centers throughout the Serbia from January 2020. to December 2020. Based on the CV risk profile, patients were stratified into 4 categories: low, moderate, high and very high risk according to SCORE model and into 3 categories: low to moderate, high and very high risk according to SCORE 2 model. The number of patients requiring statin treatment was assessed according to the risk category and value of LDL cholesterol in SCORE model and the value of non-HDL cholesterol in SCORE 2 model.

Results

Overall, 589 patients (44.7%) were smokers, mean value of total cholesterol was 6.2±1.1 mmol/L, LDL 3.9±1.1, HDL 1.4±0.5, non HDL 4.8±1.2 mmol/L. Systolic blood pressure was 138.6±19.6, diastolic blood pressure was 85.3±10.4 mmHg and was BMI 26.9±5.2. Based on the SCORE model 166 patients (12.6%) were classified into low risk category, 658 (49.9%) into moderate, 276 (20.9%) into high risk and 217 (16.6%) into very high risk category. Based on the SCORE 2 model 30 (2.8%) patients were classified into low to moderate, 273 (18%) and 1014 (79.2%) into very high risk category. There was significantly less patients in low to moderate group in SCORE 2 model compared to SCORE model (30, 2.8% vs 824, 62.6%, p<0.001 respectively) and significantly more patients with very high risk (1014, 79.2% vs 217, 16.6%, p<0.001), but without significance difference in the high risk group (Figure 1). The use of SCORE 2 model resulted in significantly higher proportion of patients requiring statin treatment 93% vs. 43% using SCORE model (p<0.001).

Conclusion

The use SCORE 2 risk prediction tool, in comparison to SCORE model, results in significant higher proportion of patients being classified as very high risk category with the increase number of patients requiring statin treatment in primary prevention.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Krka Farma
Net clinical benefit of NOAC in Korean atrial fibrillation patients with low to intermediate stroke risk
Authors: Shin S Y , Jung M , Kang K , Byeon K
Published: October 2022

Background

The balance of stroke risk reduction and potential hemorrhagic risk associated with anti-thrombotic treatment (ATT) remain unclear in Korean atrial fibrillation (AF) patients with low to intermediate stroke risk, defined as non-gender CHA2DS2-VASc score 0–1.

Purpose

The net clinical benefit (NCB) analysis of ATT may be helpful to guide stroke prevention strategy in AF patients with non-gender CHA2DS2-VASc score 0–1.

Methods

This Korean multi-center cohort study retrospectively evaluated the clinical outcomes with single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-vitamin K antagonist oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0–1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/ml], Creatinine clearance [<50 ml/min/1.73 m2], and Dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT including thromboembolic and major bleeding events.

Results

We included 2465 patients (56.2±9.5 years; female, 665 [27.0%]) followed-up for 4.0±2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. In comparison with no treatment, only NOAC demonstrated a positive tendency for stroke prevention (NOAC, NCB 0.47, 95% confidence interval [CI] −0.40 to 2.10; SAPT, NCB −0.31, 95% CI −1.48 to 1.40; and VKA, NCB −1.26, 95% CI −2.97 to 0.67). With detailed risk stratification with ABCD score, NOAC showed a significant NCB for stroke prevention compared with SAPT and VKA (SAPT vs. NOAC, NCB 1.6, 95% CI 0.26–3.50; VKA vs. NOAC, NCB 1.96, 95% CI 0.47–4.16) in patients with ABCD score ≥1. ATT failed to show NCB in patients with truly low stroke risk defined as ABCD score=0.

Conclusion

Korean AF cohort with low to intermediate stroke risk indicates that, in comparison with no ATT, only ATT with NOAC showed marginal NCB. With further risk stratification by ABCD score, NOAC showed significant advantages over other ATTs (VKA or SAPT) in patients with ABCD ≥1.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korean Disease Control and Prevention Agency
A Genetic Risk Score englobing variants associated with coronary artery disease is a good marker for prognosis in an asymptomatic population
Authors: Santos M , Mendonca M I , Sa D , Temtem M , Sousa A C , Freitas S , Rodrigues M , Henriques E , Borges S , Freitas A I , Guerra G , Ornelas I , Drumond A , Palma Dos Reis R
Published: October 2022

Genome-wide association studies have identified several loci linked to coronary artery disease, and coronary atherosclerosis progression. However, the impact of the genetic contribution to MACE occurrence in sub-clinical atherosclerosis is unknown.

Purpose

This study intended to assess the relationship between a set of single nucleotide popymorphism (SNP) associated with CAD by GWAS and the MACE occurrence in an asymptomatic population. After that evaluate whether a wGRS englobing these variants is useful to estimate the prognostic.

Methods

Prospective study performed in an asymptomatic cohort from GENEMACOR population-based sample of 1114 subjects aged 51.7±8.3, 74.2 male, without prior coronary artery disease. Coronary Artery Calcium (CAC) score was assessed by coronary computed tomography (Agatston method), and two categories were considered 1–99 and >100. 33 SNP were evaluate to assess the significantly associated with prognostic. A weighted (wGRS) was constructed as the sum of the risk alleles weighted by the corresponding effect size (HR). Cox regression analysis adjusted for the main risk factors, calcium score (CAC) and wGRS to assess the risk of MACE during follow-up. Kaplan Meier assessed the survival.

Results

Of the studied 33 SNPs previously associated with CAD (GWAS), only 4 presented the significant association with MACE occurrence: CDKN2B-AS1 rs4977574, HNF4A rs1884613,

APOE rs7412/rs429358A and GJA4A rs 618675. After Cox regression analysis the wGRS remained in the equation (HR=2.834); p=0.012, together with CAC score (HR 3.35); p=0.012; diabetes (HR=2.398); p=0.032 and age (HR=1.056; p=0.049. WGRS above the median presented a worst survival rate (p=0.006).

Conclusion

The wGRS englobing: CDKN2B-AS1 rs4977574, HNF4A rs1884613, APOE rs7412/rs429358A and GJA4A rs 618675 is independently associated with cardiovascular events in an asymptomatic population. CDKN2B-AS1 rs4977574 gene expression modulates the progression and severity of vascular calcification in vascular smooth muscle cells (VSMCs), HNF1α-AS1 is an important regulatory molecule in cancer biology and cardiovascular disease (its expression may regulate VSMCs, and high expression promotes atheroprotection). More research is crucial for understand prognosis in asymptomatic population.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): SESARAM EPE
High-sensitivity troponin (hs-cTn) for cardiovascular risk prognostication: a systematic review and meta-analysis
Authors: Sagris M S , Antonopoulos A A , Antoniades C A , Tsioufis K T , Tousoulis D T
Published: October 2022

Background

Chronic low-grade inflammation is involved in coronary atherosclerosis progression whereas recent research efforts suggest that preventative methods should be tailored to the “residual inflammatory risk”. As such, modalities for the early identification of the risk have to be investigated.

Methods

We performed a systematic review and meta-analysis according to the PRISMA guidelines. Any study that presented the prognostic value of high sensitivity troponin (hs-cTn) of vascular inflammation in stable patients without known cardiac heart disease was considered to be potentially eligible. The Medline (PubMed) database was searched up to April 22, 2021. The main endpoint was the difference in c-index (Δ[c-index]) with the use of hs-cTn for major adverse cardiovascular events (MACEs), cardiovascular and all-cause mortality. We calculated I2 to test heterogeneity.

Results

In total, 44 studies and 112,288 stable patients without known coronary heart disease were included in this meta-analysis. The mean follow-up duration of the whole cohort was 6.8±1.1 years. 77,004 (68.5%) of the patients presented in low cardiovascular risk while 35,284 (31.5%) in high. The overall pooled estimated of Δ[c-index] for MACE was 1.4% (95% CI: 0.7–2.1, I2=0%) and for cardiovascular death 1.3% (95% CI: 0.3–2.3, I2=0%). Finally, the overall pooled estimate of Δ[c-index] for all-cause mortality was 3% (95% CI: 1.9–3.9, I2=86%), while high heterogeneity was observed between the studies.

Conclusion

The predictive usefulness of changes in hs-cTn measures in stable individuals with either high or low cardiovascular risk, demonstrating that assessing vascular inflammation in addition to clinical risk factors enhances risk prediction for cardiovascular events and all-cause mortality. Further prospective studies are necessary to confirm these findings and assist clinical decision-making regarding the most optimal prevention strategy.

Funding Acknowledgement

Type of funding sources: None.
Ultra-sensitive troponin-I and incident coronary heart disease, stroke, heart failure, cardiac arrhythmias, arterial aneurysms and venous thromboembolism hospitalizations
Authors: Empana J P , Lerner I , Perier M C , Jabre P , Andrieu M , Climie R E , Van Sloten T , Vedie B , Geromin D , Marijon E , Danchin N , Thomas F , Boutouyrie P , Jouven X
Published: October 2022

Background

Cardiac troponin I (cTnI) as measured by high-sensitive assays has been related to incident cardiovascular disease events (CVD) in the community. With the advent of ultra-sensitive assays, it is now possible to detect troponin I at very low concentration, far below the classical threshold of 1.9 pg/mL. However, the clinical relevance of these low concentrations for predicting CVD is largely unknown.

Purpose

To examine the association of cTnI as low as 0.013 pg/mL with incident cardiovascular disease events (CVDs) in the primary prevention setting.

Methods

cTnI was analyzed in the baseline plasma (2008–2012) of CVD free volunteers from the Paris Prospective Study III using for the first time a novel ultra-sensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection (LOD) of 0.013 pg/mL. Incident CVD hospitalizations for coronary heart disease, stroke, arrhythmias, venous thromboembolism, arterial aneurysms and heart failure were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed standard deviation (SD) increase of cTnI in Cox models using age as the time scale. The added value (gain in discriminatory capacity) of cTnI for CVD risk prediction was examined by calculating the Harell's C-index boostraped difference of the SCORE 2 risk model with and without cTnI.

Results

There were 9503 CVD free participants (40% women) aged 59.6 (6.3) years at baseline. cTnI was detected in 99.6% of the participants (median value = 0.63 pg/mL, interquartile range [IQR] 0.39–1.09). After a median follow-up of 8.34 years (IQR, 8.0–10.07), 516 participants suffered 612 events. In fully-adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (n=516, HR= 1.21; 1.06; 1.39). In univariate Cox analysis and compared to each single established risk factor, cTnI had the highest discrimination capacity for incident CVD events (C-index=0.6349) (Figure 1). Adding log cTnI to the SCORE 2 algorithm increased significantly albeit moderately discriminatory capacity (C-index 0.698 vs. 0.685; boostraped C index difference: 0.0135 (95% CI: 0.0131; 0.0138)).

Conclusion

cTnI concentrations as measured by a novel ultra-sensitive immunoassay is associated with a significant increased risk of incident CVD events in the primary prevention setting.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): ANR: French National Research AgencyEurope: Horizon 2020