bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt;55 years; women, age &lt;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&lt;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

Abstract

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; &gt;1.03 to ≤1.18; &gt;1.18 to ≤1.34; and &gt;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

Abstract

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&lt;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

Abstract

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&lt;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

Abstract

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&lt;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&lt;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

Abstract

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&lt;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&lt;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.