bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and risk factors of in-hospital mortality of patients with COVID-19 in Germany
Authors: Keller K , Sagoschen I , Barco S , Schmidtmann I , Espinola-Klein C , Konstantinides S , Munzel T , Hobohm L
Published: October 2022

Background

Unselected data of nationwide studies of hospitalized patients with COVID-19 is still sparse, but these data are of outstanding interest not to exceed hospital capacities and to avoid overloading of national health-care systems.

Purpose

Thus, we sought to analyze seasonal/regional trends, predictors of in-hospital case-fatality and mechanical ventilation (MV) in patients with COVID-19 in Germany.

Methods

We used the German nationwide inpatient sample to analyze all hospitalized patients with confirmed COVID-19 diagnosis in Germany between January 1st and December 31st in 2020 (source: RDC of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2020, own calculations). Covid-19-inpatients with MV vs. without MV and survivors vs. non-survivors were compared. Logistic regression models were calculated to investigate associations between patients' characteristics as well as adverse events and i) necessity of MV and ii) in-hospital death.

Results

We analyzed data of 176,137 hospitalizations of patients with confirmed COVID-19-infection. Among those, 31,607 (17.9%) died, whereby in-hospital case-fatality grew exponentially with age. Cardiovascular comorbidities were common in hospitalized patients with confirmed COVID-19-infections: Overall, almost half of the patients (46.8%; n=82,480) had arterial hypertension and 25,574 (14.4%) had a diagnosis of coronary artery disease. In 60.7% (n=106,913) of the hospitalizations, pneumonia was reported, 8.6% (n=15,061) had an acute infection of the upper or lower airways other than pneumonia, and 6.6% (n=11,594) suffered from an acute respiratory distress syndrome (ARDS) during hospitalization

Age ≥70 years (OR 5.91, 95% CI 5.70–6.13, P<0.001), pneumonia (OR 4.58, 95% CI 4.42–4.74, P<0.001) and acute respiratory distress syndrome (OR 8.51, 95% CI 8.12–8.92, P<0.001) were strong predictors of in-hospital death. Most COVID-19-patients were treated in hospitals in urban areas (n=92,971) associated with lowest case-fatality (17.5%) as compared to hospitals in suburban (18.3%) or rural areas (18.8%). MV demand was highest in November/December 2020 (32.3%, 20.3%) in patients between 6th and 8th age-decade. In the first age-decade, 78 of 1861 children (4.2%) with COVID-19-infection were treated with MV and five of them died (0.3%).

Conclusion

The results of our study indicate seasonal and regional variations concerning number of COVID-19-patients, necessity of MV and case-fatality in Germany. These findings may help to ensure flexible allocation of intensive care (human) resources, which is essential for managing enormous societal challenges worldwide to avoid overloaded regional health-care systems.

Funding Acknowledgement

Type of funding sources: None.
Body adiposity estimated with CUN-BAE predicts atrial fibrillation: the SUN cohort
Authors: Diaz-Gutierrez J , Baron-Esquivias G , Martinez-Gonzalez M A , Sayon-Orea C , Bazal P , Almendral J , Barrio-Lopez M T , Amigo-Otero E , Fruhbeck G , Ruiz-Canela M A
Published: October 2022

Background

Obesity is widely recognised as a strong risk factor for atrial fibrillation and recent interest has focused on epicardial fat. Although body mass index is commonly used in the clinical practice, it doesn't precisely estimate adiposity. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) is an equation developed for body fat calculation, that has been previously associated with cardiometabolic disease. Our objective was to assess the association between body fat, as captured by the CUN-BAE index, and the incidence of atrial fibrillation in a prospective cohort.

Methods

The SUN project is a dynamic, prospective cohort of Spanish university graduates. A total of 20.136 participants, free of atrial fibrillation at baseline, were followed-up for a median time of 12 years, with a retention proportion of 91%. CUN-BAE was calculated for each participant taking into account only sex, age and body mass index. Incident cases of atrial fibrillation were confirmed by a cardiologist according to a prespecified protocol. Multivariable Cox regression models were used to estimate hazard ratios (HR) of atrial fibrillation according to calculated body fat.

Results

During follow-up, we identified 128 incident cases of atrial fibrillation. There was a strong direct association between a higher CUN-BAE index at baseline and incident atrial fibrillation during follow-up. In comparison to participants with a lower body fat category (median 21.3%), those with a higher category of body fat (median 34.8%) exhibited a significant 118% higher relative risk of incident atrial fibrillation (adjusted HR=2.18; 95% CI: 1.22, 3.90). For each 2-unit increase in the CUN-BAE index, atrial fibrillation risk significantly increased by 10%. The risk of incident atrial fibrillation remained significantly associated with adiposity even after further adjustment for obesity (body mass index ≥30 kg/m2) and in repeated measures analysis of the CUN-BAE index every other year.

Conclusions

Increased body adiposity, as captured by CUN-BAE index, was strongly and independently associated with a higher risk of atrial fibrillation in a Spanish cohort. These findings support the hypothesis that adiposity is closely related with arrhythmogenic mechanisms that could lead to atrial fibrillation and may be predicted using an equation to estimate body fat.

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Spanish Ministry of Health and European Regional Development Fund (FEDER)
Statins and influenza mortality: systematic review and meta-analysis
Authors: Lobo L M , Masson W , Masson G , Molinero G , Lavalle Cobo A , Huerin M , Delgado J , Benincasa F , Losada P
Published: October 2022

Background

Due to their anti-inflammatory properties, it has been suggested that the use of statins could influence the evolution of influenza virus infection.

Objective

To evaluate the effect of statin therapy on mortality from influenza.

Material and methods

A meta-analysis that included studies evaluating the use of statins in patients with influenza and reporting data on mortality, after searching the PubMed/MEDLINE, Embase, and Cochrane Controlled Trials databases, was performed. A random effects model was applied. The risk of bias was analyzed and a sensitivity analysis was performed.

Results

Eight studies (10 independent cohorts), which included a total of 2,390,730 patients, were identified and eligible for analysis. A total of 1,146,995 subjects analyzed received statins, while 1,243,735 subjects were part of the control group. Statin therapy was associated with lower mortality (OR: 0.66; 95% CI: 0.51–0.85). The sensitivity analysis showed that the results were robust.

Conclusions

Our data suggest that, in a population with influenza, the use of statins was associated with a significant reduction in mortality. These results must be confirmed in future clinical trials.

Funding Acknowledgement

Type of funding sources: None.
Cardiovascular mortality risk beyond 10 years in men and women; long-term follow-up from the EPIC-Norfolk prospective population study
Authors: Van Trier T , Jorstad H T , Snaterse M , Scholte Op Reimer W J M , Visseren F L J , Dorresteijn J A N , Wareham N J , Lindeboom R , Peters R J G , Boekholdt S M
Published: October 2022

Introduction

Current primary prevention strategies in cardiovascular (CV) disease focus on initiating preventive interventions in people at high 10-year risk of CV mortality. However, initiating such strategies should be beneficial not only in the first 10 years, but throughout life. Established risk algorithms estimate the risk of 10-year CV mortality, but limited evidence is available about the relationship between 10-year and longer-term CV mortality.

Purpose

To compare cumulative incidence of CV mortality in a population cohort at 10- and 20-years follow-up, stratified by sex.

Methods

We analysed CV mortality at 10-years and 20-years follow-up using Kaplan-Meier estimates among men and women aged 39–70 years without baseline CV disease or diabetes mellitus in the large, prospective population-based EPIC-Norfolk cohort. CV mortality included death with as underlying or contributing cause ischaemic heart disease, heart failure, cerebrovascular disease or peripheral artery disease.

Results

We analysed data from 20,453 participants (56% women), with a mean age of 56±8 years, and median (IQR) follow-up of 22 (21–23) years. At baseline, there were no clinically relevant differences in CV risk factors between men and women. Overall cumulative CV mortality rate was 1.9% (384 deaths) in the first 10 years, and 7.3% (995 deaths) at 20 years follow-up (ratio 3.8). Among men, 10-year CV mortality was 2.9% (249 deaths), and 9.6% (785 deaths) at 20 years follow-up (ratio 3.3). Among women, CV mortality was 1.2% (135 deaths) at 10 year and 5.5% (594 deaths) at 20 years follow-up (ratio 4.6).

Conclusion

We observed an incremental increase in CV mortality beyond the 10-year scope of current established CV risk algorithms. At 20 years follow-up, CV mortality rates were 3–5 times higher compared with the first decade, indicating that 20-year CV mortality risk for both men and women cannot simply be estimated based on extrapolation of 10-year risk.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC-Norfolk is supported by programme grants from the Medical Research Council UK (MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (CRUK 8257).
Impact of sexually transmitted infections on cardiovascular mortality in united states: a nationwide county-level analysis 2011–2019
Authors: Abohashem S , Aldosoky W , Sayed A , Khalid N , Abbasi T , Mir T
Published: October 2022

Background

Sexually Transmitted Infections (STIs) are associated with a significantly increased risk of morbidity and mortality; however, its population-level effect on cardiovascular mortality (CVM), particularly amongst various demographic subgroups, remains unknown.

Purpose

To assess the impact of county STIs levels on CVM rates, in overall and between different patient groups stratified by age, sex and race.

Methods

The CDC WONDER database tool was utilized to retrieve age adjusted county-level CVM rates (ACVM) for U.S. counties between 2011 and 2019. Data on STIs were provided by the County Health Rankings project database. STIs is the number of newly diagnosed chlamydia (the most common STI in north America) cases per 100,000 population in a county. Rates measure the number of events in a given time period (generally one year) divided by the average number of people at risk during that period. The Behavioral risk Factors Surveillance System and County Health Rankings project were used to retrieve county data on demographics, CV risk, socioeconomic, environmental, and health care access factors. 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

Of 3143 U.S. counties, a total of 2890 counties (62.09% white; 50.76% female; 14.12% aged ≥65) with data available on ACVM and STIs levels were analyzed. In a multivariate model adjusted for demographic composition, CV risk, socioeconomic, environmental, and healthcare-access factors, STIs were significantly associated with higher levels of ACVM (IRR: 1.015; 95% CI: 1.007 to 1.022; 3.40 AYD). Additionally, this association was relatively higher in the middle-aged [45–64] (IRR: 1.016; 95% CI: 1.002 to 1.030) compared to the elderly [≥65] (IRR: 1.010; 95% CI: 1.002 to 1.018), males (IRR: 1.013; 95% CI: 1.004 to 1.021) compared to females (IRR: 1.011; 95% CI: 1.002 to 1.020), and non-Hispanic Blacks (IRR: 1.026; 95% CI: 1.011 to 1.040) compared to non-Hispanic Whites (IRR: 1.010; 95% CI: 1.002 to 1.018). Notably, the relative impact of STIs was highest in middle-aged non-Hispanic Blacks (IRR: 1.038; 95% CI: 1.013 to 1.063; AYD: 10.50), and middle-aged males (IRR: 1.021; 95% CI: 1.006 to 1.037; AYD: 4.30), (Figure).

Conclusions

STIs is robustly associated with county-level ACVM, independent from several important confounders. This impact is most prominent in vulnerable demographic subgroups, namely middle-aged, males, and Blacks. Efforts to reduce STIs levels may significantly lower the burden of cardiovascular mortality attributable to STIs, particularly in groups most frequently affected by health disparities.

Funding Acknowledgement

Type of funding sources: None.
Cardiovascular risk factors in patients with and without a history of atherosclerotic cardiovascular disease in the SANTORINI study and estimation of risk
Authors: Ray K K , Manu M C , Burden A , Catapano A L
Published: October 2022

Background

Strategies for the prevention of atherosclerotic cardiovascular disease (ASCVD) are related to individual risk factors, and according to guidelines the higher the risk, the more intense the treatment required. Identifying patients at highest risk who might benefit the most from interventions is central for tailored solutions and ASCVD prevention, and any underestimation of risk may increase the ASCVD burden in these patients.

Purpose

To describe demographics and cardiovascular (CV) risk factors of patients with and without prior ASCVD enrolled in the SANTORINI study, as well as their CV risk as assigned by the investigator at the time of enrolment.

Methods

SANTORINI is an observational study (NCT04271280) conducted in 14 European countries and including patients aged ≥18 years with high- and very-high CV risk, as assessed by the investigator, and requiring lipid-lowering therapy. Patients were recruited between March 2020 and February 2021. The ASCVD status (coronary; cerebral; peripheral/other; polyvascular) of patients was defined based on medical records and the basis for risk classification was documented. For those whose risk was classified by the investigator based on the 2019 ESC/EAS guidelines, the CV risk was re-assessed centrally based on the information present in the study database to assess concordance.

Results

A total of 9044 patients were included in the analysis; of these, 76.9% had documented history of ASCVD (Table 1). Overall, the majority of patients were male (72.6%) and had a mean (SD) age of 65.3 (10.9) years. Mean (SD) LDL-C was 2.3 (1.13) mmol/L and 2.8 (1.37) mmol/L in the with and without ASCVD groups, respectively. Hypertension was common in both groups, whereas diabetes and familial hypercholesterolaemia were more prevalent in those without than those with ASCVD (44.6% vs 30.3% and 18.6% vs 7.2%, respectively). Patients with and without ASCVD had multiple CV risk factors (Table 1). Overall, ESC/EAS guidelines were cited as the most commonly used basis for risk classification (52.0%). Among all patients, the investigator assessed 26.0% and 84.2% of patients without and with ASCVD, respectively, as being very high-risk. However, central re-estimation for those using ESC/EAS guidelines suggested that 54.7% and 100% of those without and with ASCVD were at very high CV risk (Table 2).

Conclusion

Analysis of the SANTORINI baseline data shows that CV risk factors are common even in patients without documented ASCVD, and that the CV risk of patients both with and without ASCVD is underestimated in clinical practice, potentially contributing to clinical inertia in risk factor control.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany
Prevalence of standard modifiable cardiovascular risk factors in patients with ST segment elevation myocardial infarction and its relation with outcomes
Authors: Bergami M , Simovic S , Cenko E , Davidovic G , Kedev S , Zdravkovic M , Vavlukis M , Vasiljevic Z , Mendieta G , Milicic D , Badimon L , Manfrini O , Bugiardini R
Published: October 2022

Background

It has been recently suggested that more than 15% of patients with ST-segment–elevation myocardial infarction (STEMI) lack any of the standard modifiable risk factors (cigarette smoking, diabetes, hyperlipidemia, and hypertension -SMuRFs). This claim implies that other factors play a significant role in development of STEMI and has led to considerable interest in genetic causes of coronary heart disease including family history (FHx)

Purpose

To investigate whether FHx may be a significant driver for STEMI in patients without SMuRFs.

Methods

We analyzed 11,840 patients with ACSs, without evidence of prior cardiovascular disease (CVD) enrolled in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry between January 2010 to January 2021. Main outcome measures were the adjusted rates of STEMI and 30-day mortality from STEMI using multivariable logistic regression models. Patients presenting with non-ST elevation acute coronary syndromes served as controls.

Results

Among patients with STEMI, at least 1 of the 4 conventional risk factors was present in 88.1% of women and 86.7% of men. Overall, 3,194 patients (27.0%) self-reported a FHx of CV disease, defined as a first-degree relative with premature CV events (men, age <55 years; women, age <65 years). There were 261 (8.2%) patients with FHx but without SMuRFs and 2,933 (91.8%) patients with FHx and SMuRFs. After adjusting for age, and standard risk factors, FHx was associated with a significantly lower incidence of STEMI in patients with SMuRFs, but not in those without SMuRFs (ORs: 0.87; 95% Cl: 0.79 to 0.97 vs 0.80; 95% Cl: 0.58 to 1.12). Prior use of evidence-based medications (aspirin, beta-blockers, ACE inhibitors/ARBs and statins) did not consistently change prior estimates on FHx and SMuRFs (OR: 0.82 95% Cl: 0.71 to 0.96 and OR 0.89 95% CI: 0.54–1.47). Patients who presented with STEMI had a 46% excess risk of 30-day mortality (OR: 1.46; 95% CI: 1.11 to 1.91; p<0.001) compared with controls

Conclusions

In direct contrast with recent findings, almost 90% of patients with STEMI have SMuRFs. Self-reported FHx is not a significant risk factor for development of STEMI and related high rate of CV mortality in patients without SMuRFs. Although research on genetic causes of heart disease is important, public health policies, and research efforts should place significant emphasis on the 4 SMuRFs and the lifestyle behaviors causing them to reduce the epidemic of STEMI.

Funding Acknowledgement

Type of funding sources: None.
Serum copper, copper-zinc ratio and the risk of sudden cardiac death and all-cause death: a prospective cohort study
Authors: Isiozor N , Kunutsor S K , Laukkanen J A
Published: October 2022

Sudden cardiac death (SCD) constitutes a major global health burden, contributing to about 20% of deaths in Western countries. In addition to the associated economic and health impacts of SCD, the genetic predispositions to SCD-associated risk factors make identification of biomarkers for screening or therapeutic management of SCD to be crucial. Copper (Cu) and Zinc (Zn) are essential micronutrients and trace elements involved in various homeostatic mechanisms in humans, including inflammation, immunity, and oxidation-reduction reactions. However, the potential association of Cu and Cu/Zn ratio and risk of SCD in a prospective study is not established. We therefore examined the association between serum Cu levels, Cu/Zn ratio and the risk of SCD and all-cause death in Finnish men.

Methods

We used a prospective study from eastern Finland, comprising 1889 men aged 42–60 years without history of coronary heart disease at baseline ((1984–1989). The baseline serum Cu and Zn concentrations were determined using Atomic Absorption Spectrometer. Serum Cu/Zn ratio were categorized into quartiles: ≤1.03; >1.03 to ≤1.18; >1.18 to ≤1.34; and >1.34. Associations of serum Cu, Cu/Zn ratio and risk of SCD and all-cause death were analyzed using multivariable Cox models.

Results

After a median follow-up of 26 years, 147 SCD cases and 848 all-cause deaths were recorded. The hazard ratios (HR, and 95% CI) per unit increase in serum Cu levels for SCD and all-cause death were 2.51 (1.00–6.28) and 2.37 (1.60–3.51) respectively, after adjustment for age, C-reactive protein, total cholesterol, body mass index, systolic blood pressure, smoking status, and history of type 2 diabetes. Using the first quartile of Cu/Zn ratio as the referent, the HR and 95% CIs for SCD and all-cause death in the fourth quartiles were 1.32 (0.84–2.09) and 1.35 (1.11–1.64) respectively. Men in the highest quartile of Cu/Zn ratio, compared with those in the lowest quartile, had higher risk of all-cause death.

Conclusion

Serum Cu level, per unit increment, was directly associated with risk of SCD and all-cause death in middle-aged Finnish men. There was linear association between Cu/Zn ratio and risk of all-cause death. Serum Cu can possibly be a prognostic marker or risk factor for SCD and all-cause death, while Cu/Zn ratio may be a marker for all-cause death. However, the exact mechanisms need further exploration.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): North Savo Regional Fund
Genetic sensitivity to stress modifies the relationship between socioeconomic status and major adverse cardiovascular events
Authors: Abohashem S , Osborne M , Choi K , Liu Z , Zureigat H , Mezue K , Gharios C , Armstrong K , Smoller J , Tawakol A
Published: October 2022

Background

Lower socioeconomic status (SES) associates with major adverse cardiovascular events (MACE), in part through stress-related neural pathways that elicit inflammation. However, it is unknown whether genes that heighten stress sensitivity modify the association between lower SES and MACE.

Purpose

To assess whether genetic predisposition to stress sensitivity would modify the link between low SES and MACE

Methods

13,154 participants (median age 60 yrs, 41% male) from the Mass General Brigham Biobank were studied. A polygenic risk score for neuroticism (nPRS) was used as a measure of genetic predisposition to stress sensitivity (GSS). Using home addresses, SES was evaluated as median income and area deprivation index (ADI). Stress-related neural activity (SNA) was assessed (N=978) using validated FDG PET/CT imaging methods. MACE, and cardiovascular disease (CVD) risk factors were evaluated. Mediation analyses were employed.

Results

Over median (IQR) 4.9 (4.1–5.9) years of follow-up, 1,030 (7.8%) individuals had MACE. Lower SES (as low income, or alternatively as high ADI) associated with incident MACE among individuals with higher GSS (nPRS ≥ median) but not lower GSS (Fig. 1A and 1B). Similarly, lower SES associated with SNA among individuals with higher but not lower GSS (Fig. 1C). SNA mediated the relationship between income and MACE (P<0.05**) among those with higher GSS.

Conclusions

Genetic predisposition to stress sensitivity appears to heighten CVD risk associated with lower SES. This relationship may result from differential activation of stress-related neural pathways.

Funding Acknowledgement

Type of funding sources: None.
Early interventions to promote healthy lifestyle and risk factor control in subjects with elevated cardiovascular risk. A 3-year randomized clinical trial
Authors: Bergum H , Sandven I , Abdelnoor M , Anderssen S , Grimsmo J , Elle Rivrud D , Myhr N E , Vold M B , Stenbakken C , Lidfors B , Dufseth L , Klemsdal T O
Published: October 2022

Background

Cardiovascular risk factor control is suboptimal in Europe, including Norway. The present study examined the efficacy of a multimodal primary prevention intervention program based on the existing Norwegian health care system.

Methods

In this open-label randomized controlled trial, adult patients with elevated cardiovascular risk were randomly assigned to an intervention program including a hospital-based lifestyle course and primary care follow-up or to a control group. The participants were recruited between 2011 and 2015. Primary outcome was change in validated cardiovascular risk scores (NORRISK, NORRISK2, Framingham, PROCAM) between baseline and follow-up. Secondary outcomes included major cardiovascular risk factors.

Results

After 36 months the NORRISK score was significantly improved in patients assigned to the intervention group (IG) compared to patients assigned to the control group (CG); absolute difference in mean delta score in the IG (n=305) compared to mean delta score in the CG (n=296): −0.92, 95% CI: −1.48 to −0.36, p=0.001. The results for NORRISK2, Framingham and PROCAM showed similar significant effects. The secondary endpoints including total cholesterol and blood pressure were only minimally, and non-significantly, reduced in the IG, but the proportion of smokers (p=0.0028) and with metabolic syndrome (p<0.0001) were significantly reduced. A limited number of cardiovascular events were observed, IG (n=9), CG (n=16).

Conclusions

In subjects with elevated cardiovascular risk, a newly developed prevention program, combining a hospital-based lifestyle course and primary care follow-up, significantly reduced cardiovascular risk scores after 36 months. This benefit appeared achievable primarily through improvements in metabolic syndrome characteristics and smoking habits as prominent contributors to the positive results.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The trial is funded in a grant from the Norwegian healthdepartment.
Polygenic risk score associates with atherosclerosis severity at autopsy
Authors: Cornelissen A , Gadhoke N V , Ryan K , Hodonsky C J , Duong T V , Dikongue A , Sakamoto A , Sato Y , Miller C L , Hong C C , Arking D E , Mitchell B D , Guo L , Virmani R , Finn A V
Published: October 2022

Background

Polygenic risk scores (PRS) for coronary artery disease (CAD) are emerging as a potential method to improve cardiovascular risk prediction. Questions remain about their applicability to diverse populations as well as their correlation with coronary histopathology.

Purpose

To assess whether high genetic risk associates with histopathologic coronary plaque morphology.

Methods

We assessed 122 known CAD risk loci in 954 Black and White subjects within our sudden death registry to generate a PRS. The cohort was divided into quintiles according to z-score-standardized PRS, both in a race-stratified fashion and in the pooled sample. Detailed histopathologic examination of the coronary arteries was performed in all subjects.

Results

Subjects in the highest PRS quintile exhibited more severe atherosclerosis compared to subjects in the lowest quintile, with greater mean cross-sectional luminal narrowing (71.5% (95% CI, 66.6%-76.5%) vs. 56.6% (95% CI, 51.1%-62.1%); adjusted p<0.001; Figure 1) and a higher frequency of calcification (adjusted OR 2.19; 95% CI 1.31–3.68; p=0.003) after adjustment for the first 10 principal components, age, sex, and race. Higher z-score-standardized PRS was predictive for the finding of severe atherosclerosis (i.e., ≥75% cross-sectional luminal narrowing) even after additional controlling for traditional CAD risk factors including hypertension, smoking, diabetes mellitus, and hyperlipidemia (adjusted OR 1.39; 95% CI 1.19–1.63; p<0.001; Figure 2). Among Black subjects, higher PRS was associated with higher odds of plaque rupture (adjusted OR 1.31; 95% CI 1.03–1.66; p=0.03) and predicted CAD-associated cause of death among subjects younger than 50 years old (adjusted OR 1.26; 95% CI 1.01–1.58; p=0.04).

Conclusions

This is the first autopsy study investigating associations between PRS and atherosclerotic plaque morphology at a histopathologic level. Our pathological analysis suggests PRS correlates with plaque burden and coronary artery calcification and may be useful as a method for CAD risk stratification, especially in younger subjects.

Funding Acknowledgement

Type of funding sources: Foundation. Main funding source(s): R01 HL141425 Leducq Foundation Grant
Does the quality index of adherence to the evidence-based guidelines predict mortality in patients with myocardial infarction?
Authors: Gudmundsson T , Redfors B , Ramunddal T , Rawshani A , Petursson P , Fischer A R , Erlinge D , Alfredsson J , Mohamman M A , Angeras O , Frobert O , James S , Jernberg T , Omerovic E
Published: October 2022

Background

The SWEDEHEART quality index of hospitals' adherence to the evidence-based (EB) guidelines for myocardial infarction (MI) patients has been continuously used for several decades in Sweden. The grading protocol is based on the consensus among hospitals. The hospitals are awarded points (0, 0.5, 1) for each of the 11 indicators depending on the proportion of patients who received EB treatment and achieved treatment goals. The 11 indicators at present are reperfusion treatment in STEMI (yes/no), time to-reperfusion treatment in STEMI, time to revascularisation in NSTEMI, P2Y12 antagonists at discharge, ACE-inhibitor/ARB at discharge, the proportion of patients at follow-up, smoking cessation at one-year, participation in a physical exercise program, target LDL-cholesterol and target blood pressure at one year.

Purpose

To evaluate whether the SWEDEHEART quality index predicts mortality in patients with MI.

Methods

We used data for all MI patients reported to the SWEDEHEART registry from 72 hospitals in Sweden between 2015–2021. We calculated the difference in quality index between 2021 and 2015. The hospitals were divided into quintiles based on the difference in the score. Logistic regression with log-time offset was used to adjust for confounders (age, gender, diabetes, hypertension, hyperlipidemia, STEMI/NSTEMI, cardiac arrest before admission, occupation status, history of heart failure, prior MI, prior PCI, prior CABG, cardiogenic shock).

Results

We identified 98,635 patients with MI, 32,608 (33.1%) were women and 34,198 (34.7%) had STEMI. The average age was 70.8±12.2 years. The median follow-up time was 2.7 years (IQR 1.06–4.63). The crude all-cause mortality rate was 5.5% at 30-days and 22.3% after long-term follow-up. Most hospitals (72.1%) improved their quality index on average by 3.4% per year (P<0.001). The increase in the quality index continued during COVID-19 pandemic (2020–2021) with average increase of 8.6%, 95% CI, 0.97–1.02; P<0.001. The median change in SWEDEHEART quality index score among the quintiles were −1.5 (Q1), 0,5 (Q2), 2,5 (Q3), 3 (Q4), and 4 (Q5). We found no difference in mortality between the quintiles at 30-days (OR 0.99; 95% CI 0.97–1.02; p=1.02) and long-term (OR 1.01; 95% CI 0,99–1.02; p=0.850).

Conclusion

The SWEDEHEART quality index provides valuable descriptive information about hospitals' adherence to the guidelines. However, the index, in its current form, does not predict mortality in patients with MI.

Funding Acknowledgement

Type of funding sources: None.
Long-term prognostic value of trimethylamine N-oxide in community-based adults and patients with coronary heart disease
Authors: Bjornestad E , Dhar I , Svingen G F T , Pedersen E R , Orn S , Svenningsson M , Tell G S , Ueland P M , Sulo G , Laaksonen R , Nygaard O
Published: October 2022

Background

Trimethylamine N-oxide (TMAO) is an amine oxide generated by gut microbial metabolism. Emerging evidence suggests pro-atherosclerotic and pro-inflammatory properties of TMAO; however, the clinical utility of circulating TMAO in risk stratification is uncertain.

Purpose

We prospectively assessed relationships of plasma TMAO with long-term risk of all-cause, cardiovascular (CV) and non-CV mortality in community-dwelling adults and patients with coronary heart disease.

Methods

By Cox modelling, risk-associations were examined in the Hordaland Health Study (HUSK; 6393 community-based adults) and the Western Norway Coronary Angiography Cohort (WECAC; 4132 patients with suspected chronic coronary syndrome).

Results

Median follow-up time was 11.0 and 10.3 years in HUSK and WECAC, respectively. Following adjustments for established CV risk factors in HUSK, the HRs (95% CIs) comparing the 4th vs. 1st TMAO-quartile were 1.11 (0.88–1.40), 0.97 (0.65–1.46) and 1.17 (0.88–1.54) for all-cause, CV and non-CV mortality, respectively. Corresponding risk estimates in WECAC were 1.07 (0.86–1.32), 1.16 (0.83–1.62) and 1.02 (0.77–1.34). Similar results were observed in patients with angiographically significant coronary artery disease and patients with reduced left ventricular ejection fraction.

Conclusion

Plasma TMAO was not predictive of long-term all-cause, CV or non-CV mortality in patients with or without established coronary heart disease. This large-scale study does not support a role of TMAO for patient risk stratification in primary or secondary prevention.

Funding Acknowledgement

Type of funding sources: None.
Association of fatal and non-fatal adverse health outcomes with urinary peptides reflecting collagen I turnover
Authors: Melgarejo J , Wei D , Latosinska A , Vanassche T , Janssens S , Mischak H , Staessen J A , Verhamme P , Zhang Z Y
Published: October 2022

Background

Imbalance of collagen I (COL1) turnover, featured by increased synthesis and decreased degradation of collagen fibers, is a hallmark of fibrosis in the heart and blood vessels that associates with poor cardiovascular outcomes. Such as imbalance of COL1 turnover could be reflected in urine and serve as fingerprint for future adverse outcomes in general population, and high risk subjects.

Purpose

We hypothesize that imbalance of proteomic signatures of urinary peptides (UPs) reflecting COL1 turnover relate to adverse health outcomes in participants from a general population

Methods

We randomly recruited 776 participants (51.2% women; 50.5 years) from the Flemish Study on Environment, Genes and Health Outcomes cohort and measured UPs proteome by capillary electrophoresis coupled with mass spectrometry. Our analyses focused on 148 peptides of COL1 alpha-1 (COL1A1) chain that retained ≥70% signal in the whole sample. The primary endpoint included fatal and nonfatal cardiovascular endpoints. Secondary endpoints consisted of total mortality, fatal and nonfatal cardiac, coronary, and heart failure endpoints. Multivariate Cox proportional models, partial least squares analysis (PLS), log-likelihood test, and receiver operating characteristics (ROC) curve were applied.

Results

Over a median follow up of 12.4 years, 110 primary endpoints occurred, 61 participants died, 81, 41 and 24 experienced cardiac, coronary, and heart failure endpoints; respectively. In PLS analyses, upregulation of UPs signatures closer to C- and N-terminal locations of the COL1A1 chain whereas downregulation of mid-region UPs were associated with lower risk of adverse health outcomes. This pattern was inverted in subjects with cardiovascular disease, as upregulation of terminal and downregulation of mid region UPs increased risk. Adding UPs to a basic model including sex, age and usual cardiovascular risk factors significantly improved model performance between 2.54% to 4.93% (P≤0.001) for prediction of adverse health outcomes. In ROC plots, adding UPs to the basic model increased the area under the curve up to 4.00% (P<0.012).

Conclusions

UPs reflecting COL1 turnover predicted adverse health outcomes. The inverted up- and down regulations of UPs in between participants with and without previous cardiovascular diseases might be explained by a shift in the UPs signatures of COL1 fragments linked to distinct fibrotic processes. Urinary proteomic might have clinical importance in documenting the extent of collagen accumulation that relates to adverse health outcomes. In patients at high cardiovascular risk, modification of collagen I fibers turnover might be a potential treatment target

Funding Acknowledgement

Type of funding sources: Public grant(s) – EU funding. Main funding source(s): The European Union the European Research Council and the European Research Area Net for Cardiovascular Diseases.
Acute effects of COVID-19 vaccination on inflammatory, macrovasular and microvascular biomarkers
Authors: Terentes-Printzios D , Gardikioti V , Solomou E , Emmanouil E , Gourgouli I , Xydis P , Christopoulou G , Georgakopoulos C , Dima I , Miliou A , Lazaros G , Pirounaki M , Tsioufis K , Vlachopoulos C
Published: October 2022

Purpose

To fight the COVID-19 pandemic, messenger RNA (mRNA) vaccines were the first to be adopted by vaccination programs worldwide. We sought to investigate the short-term effect of mRNA vaccine administration on endothelial function and arterial stiffness.

Methods

Thirty-two participants (mean age 37±8 years, 20 men) that received the BNT162b2 mRNA COVID-19 vaccine were studied in 3 sessions in a sequence-randomized, sham-controlled, assessor-blinded, cross-over design. Primary outcome was endothelial function assessed by brachial artery flow-mediated dilatation (FMD), and secondary outcomes were aortic stiffness, evaluated with carotid-femoral pulse wave velocity (PWV), microvascular function that was estimated with hyperemic mean blood flow velocity (HMBFV) of the brachial artery, and inflammation measured by high-sensitivity C-reactive protein (hsCRP) and interleukins (hsIL-6 and hsIL-1b) in blood samples. The outcomes were assessed prior to, and at 8h, 24h post the 1st dose of vaccination, and 8h, 24h and 48h post the 2nd.

Results

There was an increase in hsCRP that was apparent at 24h after both the 1st dose (−0.60 [95% Confidence intervals [CI]: −1.60 to −0.20], p=0.013) and the 2nd dose (max median difference at 48h −6.60 [95% CI: −9.80 to −3.40], p<0.001) compared to sham. Similarly, interleukins also increased. The vaccine did not change PWV. FMD remained unchanged during the 1st dose but decreased significantly by 1.5% (95% CI: 0.1% to 2.9%, p=0.037) at 24h post the 2nd dose (Figure). FMD values returned towards baseline at 48h. HMBFV remained unchanged during the 1st dose but at 48h post the 2nd dose was numerically lower than the sham procedure but the difference between the 2 sessions was not statistically significant (max mean difference at 48h 8.6 [95% CI: −0.6 to 17.8], p=0.067).

Conclusions

Our study shows that the mRNA vaccine causes a prominent increase in inflammatory markers, especially after the 2nd dose and a transient deterioration of endothelial function at 24h that returns towards baseline at 48h. These results confirm the short-term cardiovascular safety of the vaccine.

Funding Acknowledgement

Type of funding sources: None.
Alirocumab reduces total coronary plaque burden in patients with familial hypercholesterolaemia and no previous clinical atherosclerotic disease
Authors: Perez De Isla L , Diaz Diaz J L , Romero M J , Muniz Grijalvo O , Argueso R , Sanchez Munoz Torrero J F , Mediavilla J D , Ponte P , Fuentes F , Saltijeral Cerezo A , Alvarez Banos P , Rubio P , Cepeda J M , Padro T , Mata P
Published: October 2022

Background

It is well known that statins, ezetimibe and other lipid lowering treatments such as Evolocumab (PCSK9-Inhibitor) reduce cardiovascular events by decreasing LDL-cholesterol (LDL-C) levels and slowing the progression of coronary atherosclerosis. Nevertheless, cardiovascular (CV) risk remains. Alirocumab, a PCSK9 inhibitor has demonstrated a reduction in cardiovascular events but its relationship with coronary atherosclerosis reduction has not been adequately demonstrated.

Purpose

The ARCHITECT trial sought to determine whether Alirocumab 150 mg/2 weeks is able to stop or reverse coronary atherosclerosis progression, by assessing coronary plaque burden (CPB) by serial multidetector computed tomography (MDCT).

Methods

A total of 104 patients with molecularly characterized heterozygous familial hypercholesterolaemia (FH) without clinical cardiovascular disease were enrolled in this trial. Patients had to have CPB >30% as documented by MDCT, be on maximum tolerated statin therapy with or without ezetimibe and LDL-C >100 mg/dL. Patients underwent a MDCT at enrollment and after 18-month treatment with alirocumab and they were analyzed by means of QAngio CT (Medis medical imaging system, the Netherlans). The pre-specified primary endpoint was change in CPB.

Results

Median age was 53.3 (46.2–59.4) years (54, 51.9% woman). Median LDL-cholesterol was 138.9 mg/dL. There was a significant reduction in the primary endpoint as Alirocumab reduced CPB from 34.6 (32.9–36.8)% to 30.4 (27.4–33.4)%. Significant reductions in LDL-C (67%) and atherosclerotic plaque volume were also found. Plaque regression as estimated by CPB was found in 91 (87.5%) patients. Main resuts may be found in figure 1.

Conclusions

Alirocumab demonstrated significant regression of CPB on MDCT over 18 months. ARCHITECT provides crucial mechanistic clues on coronary plaque behavior under the use of Alirocumab and its results could link and explain ODYSSEY-OUTCOMES results.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Sanofi
Coronary CT angiography derived pericoronary inflammation and bespoke cardiovascular risk prediction in the lipid clinic: beyond the calcium score
Authors: Graby J , Sellek J , Khavandi A , Loughborough W , Hudson B J , Shirodaria C , Downie P , Antoniades C , Rodrigues J C L
Published: October 2022

Background

Dyslipidaemia promotes atherosclerosis. Genetic dyslipidaemias, Familial Hypercholesterolaemia (FH) being the most common, are associated with heightened risk of coronary artery disease (CAD) and premature major adverse cardiovascular events (MACE). However, this risk is both heterogeneous and modifiable with treatment.

CT coronary imaging can identify subclinical atherosclerosis, enabling personalised risk stratification and treatment targets. Coronary artery calcium scoring (CACS) is current first-line in European guidelines for asymptomatic patients. However, calcification occurs late in CAD pathogenesis and CACS has low specificity in young patients with severe FH. CT coronary angiography (CTCA) assesses non-calcific plaque and high-risk plaque (HRP) features unappreciable with CACS. Additionally, the pericoronary fat attenuation index (FAI) measures inflammation on routine CTCA and is the strongest non-invasive imaging biomarker of risk of fatal MI.

Purpose

To quantify and compare the reclassification of subclinical atherosclerosis burden in Lipid Clinic patients assessed via CACS vs CTCA with FAI analysis.

Methods

Analysis of a prospectively maintained clinical database of asymptomatic Lipid Clinic patients with both CACS and CTCA imaging from May 2019 to December 2020. CACS was reported with the standardised Agastston criteria and compared with (i) the CTCA-derived Coronary Artery Disease – Reporting and Data System (CAD RADS) grading of anatomical stenosis, including a modifier for HRP features, and (ii) FAI analysis. Significance was defined as two-tailed p75th percentile vs age and sex matched controls) was seen in 6/27 (22%) patients with none to mild calcification on CACS and 6/28 (21%) patients with none to mild CAD on CTCA, of whom 3/7 (43%) had HRP. High FAI was seen in all groups of calcification severity and CAD RADS score (Figure 2). The proportion with high FAI was higher in CAD RADS 0 vs CAD RADS 4, and CACS severity was not associated with level of inflammation (p=0.94).

High FAI was observed in 16% of patients on treatment, suggesting treatment failure. This included patients with CACS ranging from 0 to severe (>400), and CAD RADS of minimal (1) to severe (4).

Conclusion

CTCA re-stratifies CAD presence and severity vs CACS in a high-risk, asymptomatic patient group and identified a high proportion of patients with HRP features. FAI provides incremental value in identification of patients at risk of future MACE regardless of CACS grade, including patients without evidence of overt CAD. Identifying high FAI on treatment may imply treatment failure.

Funding Acknowledgement

Type of funding sources: None.
Impact of antihypertensive medication regimens on blood pressure control in individuals with established coronary heart disease
Authors: Brennan S , Costigan O , McEvoy J W
Published: October 2022

Background and purpose

Hypertension is a major risk factor for coronary heart disease (CHD) development and progression, with pharmacological control of blood pressure reducing the risk of CHD events and death [1].

Treatment and control of blood pressure in CHD is suboptimal, with many patients failing to achieve guideline-directed targets [1,2]. This study aims to assess the relationship between antihypertensive medication regimens and blood pressure control in patients with hypertension and established coronary heart disease.

Methods

The iASPIRE study recently evaluated secondary prevention in an Irish cohort with coronary heart disease [2]. Based on a method used in a similar study [3], we calculated the average percentage daily dose of each prescribed antihypertensive agent. We then assessed the relationship between dose and number of antihypertensive agents with blood pressure control.

Results

540 (75.5%) of iASPIRE participants had an underlying diagnosis of hypertension, and at the study examination, 56% of these had a blood pressure ≥140/90 mmHg, while 83% had a blood pressure ≥130/80 mmHg. The median number of antihypertensive agents prescribed was 2 (IQR 1–2), with 88% of those with hypertension on at least one blood pressure medication. In participants with hypertension on treatment, the median percentage daily medication dose was 29% (IQR 14–50). After adjustment for age and sex, the addition of further antihypertensive medications increased the odds of achieving a blood pressure target of <130/80 mmHg (OR 1.3, 95% CI 1.07–1.69, p=0.012). The average percentage daily dose of each antihypertensive agent was lower in both participants with a medication-controlled blood pressure of <130/80 mmHg and <140/90 mmHg compared to those without blood pressure control (30% versus 37% p=0.006 and 33% versus 38% p=0.028 respectively).

Conclusion

Many patients with hypertension and coronary heart disease currently fail to achieve blood pressure control. This analysis found that an increasing number of antihypertensive medications but not increasing dose was associated with better blood pressure control. Combination therapy is superior to sequential monotherapy in the treatment of hypertension [1], and an approach that emphasises the initiation of several antihypertensive agents would likely lead to better blood pressure control in individuals with coronary heart disease.

Funding Acknowledgement

Type of funding sources: None.