bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic disparity in cardiovascular disease: a proteomic approach
Authors: Shafi B H , Boettcher M , Ejupi A , Osler M , Lange T , Prescott E 
Published: October 2021

Abstract

Background and purpose
A large unexplained social disparity in the occurrence of cardiovascular disease (CVD) has been documented. The precise mechanism behind these disparities is largely unknown. Biomarkers have improved our understanding of the pathophysiology of CVD. In this study we investigated differences in 184 biomarkers linked to CVD, with the aim of understanding the underlying mechanisms behind socioeconomic disparity in CVD and explore potential preventive measures.

Methods
We included 1144 participants from the Copenhagen City Heart Study, age 55- 64 years, without known CVD. Socioeconomic position (SEP) was defined by educational length in years. Blood samples were obtained and analyzed in two CVD proteomics panels (CVD panel II and III) with a total of 184 protein biomarkers. Associations between biomarkers and SEP were investigated by Pearson correlation coefficient and linear regression with multivariate adjustment for CVD risk factors.

Results
Median educational length was 10 (IQR 7–11) years. Of the measured biomarkers 53 were significantly correlated (p value &lt;0.05) to educational length, 17 positively and 36 negatively (fig. 1). After adjusting for age and gender, 41 biomarkers and after multivariate adjustment 14 biomarkers remained significantly associated with educational length. Some of the strongest negative associations was seen for Leptin (LEP), Von Willebrand factor (vWF), Interleukin-6 (IL6), Fibroblast growth factor 21 (FGF21), Renin (REN) and Growth/differentiation factor 15 (GDF_15) while the strongest positive associations were seen for Growth Hormone (GH), Receptor for advanced glycosylation end products (RAGE) and Myoglobin (MB) (fig. 2).

Conclusion
SEP was associated with elevated levels of multiple biomarkers linked with CVD. The range of biomarkers indicate that pathways involving inflammation (IL6, LEP, RAGE), platelet-activation (vWF, IL6, RAGE), blood pressure (REN, LEP), MAPK cascade (GDF_15, FGF21, LEP, IL6, REN, GH) and weigh (LEP) regulation contribute to the socioeconomic gradient in CVD. Further exploration is needed to identify possible candidates for intervention.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark.
Patients presenting with acute coronary syndromes have unreported coronary artery calcium on historical CT imaging
Authors: Bradley C , Aggarwal A , Goatman K , Jones G , Berry C , Good R 
Published: October 2021

Abstract

Introduction
Ischaemic heart disease (IHD) remains the leading cause of mortality globally1. The presence and extent of coronary artery calcification (CAC) is a strong predictor of cardiovascular events, and CAC scoring has been shown to be more predictive of cardiovascular events than other traditional risk assessment scores2.
Incidental coronary calcification can be detected and quantified on non-gated CT chest scans covering the heart in the field of view3. This finding is typically not reported4 and hence an opportunity to optimise cardiovascular risk assessment and treatment is missed.

Purpose
We sought to investigate whether patients presenting to our centre with an acute coronary syndrome (ACS) event had historical CT imaging demonstrating coronary artery calcification.

Methods
We retrospectively reviewed case records for all patients referred to our centre for an invasive coronary angiogram following their first known admission with an ACS event. ACS were defined according to contemporary guidelines from the European Society of Cardiology. We reviewed a 3 month period prior to the COVID-19 pandemic (01/01/2019–31/03/2019). The national imaging database was interrogated to identify previous CT imaging that includes the heart in the field of view. The presence of coronary calcification was confirmed and quantified using an ordinal scoring method previously described3. The clinical radiology reports for the scans were reviewed to determine the frequency of CAC being reported.
Demographic information was collected from our electronic patient record including the presence of risk factors for IHD. Prescribed medication prior to admission was also recorded using the on-admission medicines reconciliation documented in the electronic patient record.

Results
385 patients with first presentation of ACS were identified. 75 (19%) had a prior non-gated CT chest imaging. The most common indication for CT was for investigation of possible malignancy. The mean interval from CT imaging to ACS admission was 36 months.
CAC was present on 67 (89%) scans. The mean ordinal score was 4.04, corresponding to moderate CAC. The distribution of CAC by coronary artery revealed the majority of disease to involve the left anterior descending artery (Table 1). Only 12/67 (18%) of clinical radiology reports mentioned coronary calcification (Figure 1).
Patients with CAC frequently had additional risk factors for IHD. Despite this only 42% were prescribed antiplatelet therapy, and only 45% prescribed a statin.

Conclusions
A significant proportion of ACS admissions have evidence of CAC on historical CT scans. This finding is often not reported and the majority of patients with demonstrated coronary artery disease are not prescribed appropriate preventative therapies. Systematic reporting of this finding may have a significant impact on the prevention of acute cardiovascular events.

Funding Acknowledgement
Type of funding sources: None. Table 1
Polypill and its association with cardiovascular morbidity and mortality: meta-analysis from randomized controlled trials
Authors: Maraey A , Elsharnoby H , Elzanaty A , Khalil M , Younes A , Salem M 
Published: October 2021

Abstract

Background
Polypill or fixed dose combination pill (containing antihypertensive and cholesterol lowering agents) has shown, in multiple studies, to increase adherence and improve blood pressure and cholesterol measurements in at risk underprivileged populations. However, its long term effect on mortality, cardiovascular and cerebrovascular outcomes in high risk groups is not well-established.

Objective
To assess mortality, cardiovascular and cerebrovascular outcomes in higher risk patients using polypill containing fixed dose of Aspirin, antihypertensive drugs and Statin compared to standard care or placebo.

Methods
We queried MEDLINE, COCHRANE, and EMBASE databases for randomized controlled trials (RCTs) comparing polypill containing Aspirin, Statin and at least 2 antihypertensive medications, to standard care or placebo in patients with increased risk of cardiovascular diseases. We looked for trials including data about mortality, coronary and cerebrovascular events. We excluded trials that did not include outcomes of interest. 5 RCTs matching our criteria were included in our meta-analysis; UMPIRE 2013, IMPACT 2014, Kanyini GAP 2015, PolyIran 2019, and TIPS-3 2021.

Results
12828 patients (6419 in polypill vs 6409 in standard care/placebo groups) with known all-cause mortality, coronary events and cerebrovascular events outcomes were analyzed from 5 RCTs. For cardiovascular mortality outcome, 12205 patients (6108 in polypill vs 6097 in standard care/placebo groups) were analyzed from 4 RCTs since 1 RCT lacked data about cardiovascular mortality outcome. There was no difference between both groups in all four outcomes.
Risk ratio of all-cause morality and cardiovascular mortality in polypill group was 0.89 [95% CI 0.76–1.03, P=0.11, I2=0%] and 0.77 [95% CI 0.48–1.26, P=0.31, I2=59%] respectively (Figure 1).
Risk ratio of coronary events in polypill group was 0.88 [95% CI 0.64–1.20, P=0.41, I2=40%]. Relative risk of cerebrovascular events was 0.73 [95% CI 0.36–1.48, P=0.38, I2=63%] (Figure 2).

Conclusion
Polypill, despite being a practical solution to non-adherence in at risk underprivileged groups, does not improve mortality or major cardiovascular or cerebrovascular outcomes compared to standard care or placebo. Further efforts need to be made towards aggressive preventative measures and encouraging adherence to medications in groups at risk.

Funding Acknowledgement
Type of funding sources: None. Figure 1Figure 2
Lipoprotein(a) levels are not independently associated with endogenous steroid hormone levels, in contrast to other non-genetic and genetic factors: the population-based SKIPOGH study
Authors: Tessitore E , Dobretz K , Dhayat N A , Estoppey S , Kern I , Ponte B , Pruijm M , Vogt B , Vuilleumier N , Bochud M , Mach F , Ehret G 
Published: October 2021

Abstract

Introduction
Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causally related to cardiovascular events. Lp(a) levels are highly variable, by more two orders of magnitude, and most of this variability appears to be of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of the variation of endogenous hormone levels on Lp(a) is unknown.

Purpose
To investigate the association between Lp(a) levels and non-genetic factors, as endogenous steroid hormone levels, in contrast to genetic factors.

Methods
We investigated the association of 28 endogenous steroids with Lp(a) levels and compared the association to other non-genetic and genetic variables in a prospective, population-based sample (N=1,021).

Results
The average age of the participants was 51 years and 53% were female. Median Lp(a) levels were 62 (±204) mg/l and the 90th and 99th percentile of Lp(a) was 616mg/l and 1035 mg/l respectively. The prevalence of a Lp(a) elevation ≥700mg/l was 3.2% and Lp(a) varied greatly from undetectable to 1,690mg/l. Age explained 2.0% of Lp(a) variability (p&lt;0.001), 1% was explained by LDL levels (p=0.001), and 40% by two single nucleotide polymorphisms near the Lp(a) gene that have been previously described. Lp(a) levels were on average almost two times more elevated in secondary prevention and in individuals with very elevated LDL levels (≥4.9 mmol/l). Of the 28 endogenous steroid hormones assessed, 5-androstene-3b,16α,17β-triol, androsterone, 16α-hydroxy DHEA, and estriol were nominatively associated with serum Lp(a) levels and explained 0.4–1% of Lp(a) variability in univariate analyses, but they did not reach significance in multi-variate models.

Conclusion
Our results confirm previous findings demonstrating that the majority of the Lp(a) variation in the general population is of genetic origin. Age and LDL-levels explain a further small part of Lp(a) variability. Endogenous hormone levels do not contribute significantly to the wide range of variability.

Funding Acknowledgement
Type of funding sources: None. Coefficient plot Lp(a) and variables
Imaging-based body fat depots and new-onset atrial fibrillation in general population
Authors: Lu Z , Tilly M J , Aribas E , Bos D , De Knegt R , Ikram M A , De Groot N M S , Voortman T , Kavousi M 
Published: October 2021

Abstract

Background
Obesity is a well-established risk factor for incident atrial fibrillation (AF). Whether different body fat depots differentially associate with AF development remains largely unknown.

Purpose
We aimed to investigate the associations between various body fat depots and the risk of new-onset AF among middle-aged and elderly individuals from general population.

Methods
In the prospective population-based cohort study, body composition was assessed using dual-energy X-ray absorptiometry (DXA) and total body mass, lean mass, fat mass, android and gynoid fat were analyzed (N=3468). Liver fat and epicardial fat were assessed using computed tomography (CT) (N=2145). A body fat score was defined by adding tertiles of each fat depot. All participants were followed for the occurrence of AF until 1st Jan. 2014. Principle component analysis was conducted to identify body fat distribution patterns. Time-to-event analyses were performed using Cox proportional hazards regression analysis. Hazard ratios (HR) and 95% confidence-intervals (95% CI), adjusted for cardiovascular risk factors, were calculated.

Results
Mean (standard deviation) of age for participants in DXA study and CT study was 74.42 (6.85) and 68.66 (6.41) years, respectively. AF incidence rate was 13.1 per 1000 person-years during a median follow-up time of 9.62 years. In the adjusted model, fat mass (HR; 95% CI: 1.33; 1.05–1.68), lean mass (1.40; 1.15–1.72), gynoid fat mass (1.36; 1.12–1.65), and total body mass (1.51; 1.21–1.89) were significantly associated with new-onset AF. Of note, android-to-gynoid fat ratio was inversely associated with incident AF (HR; 95% CI: 0.81; 0.70–0.94). Larger body fat score was associated with increased risk of incident AF (P for trend &lt;0.01). Two fat distribution patterns were identified. Adherence to the fat- and gynoid fat- pattern (P for trend = 0.035), but not muscle- and visceral fat- pattern (P for trend = 0.35), was significantly associated with larger risk of new-onset AF.

Conclusions
Various body fat depots were associated with new-onset AF. Larger values of total body mass carried the highest risk for incident AF. The inverse association between android to gynoid fat ratio with AF presents a novel finding. A significant dose-response relationship between body fat accumulation and risk of new-onset AF was observed, implying a collective impact of fat depots on AF development. Findings also suggest that various fat depots, characterized by different fat distribution patterns, may exert differential combined effect on the risk of incident AF.

Funding Acknowledgement
Type of funding sources: None. Fat depots and atrial fibrillation
Intervention-specific association of weight variability with major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus
Authors: Zhuang X D , Liu M H , Zhang S Z , Christopher O , Liao X X 
Published: October 2021

Abstract

Background
Weight variability is associated with cardiovascular outcomes in diabetic patients. However, the effect of higher weight variability caused by intensive lifestyle intervention (ILI) on cardiovascular outcomes in diabetic patients is not well established. We aimed to evaluate the intervention-specific association between weight variability with major adverse cardiovascular event (MACE) among overweight or obese adults with diabetes.

Methods
In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, multivariate-adjusted Cox regression models were used to evaluate the associations of weight variability measured by variability independent of the mean (VIM) with MACE and secondary outcomes in intensive lifestyle intervention (ILI) and diabetes support & education (DSE) arm, respectively.

Results
During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51–3.30), but not the ILI arm (HR 1.05; 95% CI 0.73–1.50). Moreover, compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were not associated with all secondary outcomes in the ILI arm (all P&gt;0.05) but were associated with the higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20–2.95), all-cause mortality (HR 3.19; 95% CI 1.75–5.82), and myocardial infarction (HR 1.95; 95% CI 1.12–3.37) in the DSE arm.

Conclusions
Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm but not the ILI arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without considering the effect of high weight variability.

Funding Acknowledgement
Type of funding sources: None.
Clinical epidemiology and costs of type 2 diabetic patients with or without prior coronary artery disease or stroke. A longitudinal 5-year claims-data analysis of over 7 million inhabitants
Authors: Maggioni A P , Dondi L , Andreotti F , Ronconi G , Calabria S , Piccinni C , Pedrini A , Esposito I , Martini N 
Published: October 2021

Abstract

Aims
Contemporary, real-world data on type 2 diabetes mellitus (T2DM) are limited. We analysed prevalence, comorbidities, outcomes and costs of T2DM patients with and without coronary artery disease (CAD) or stroke in &gt;7 million inhabitants.

Methods
T2DM patients were identified in 2015 (accrual period) from the Ricerca e Salute (ReS) database linking administrative records to demographics. From 2013–2015 information, four cohorts were considered: #1 with CAD and/or stroke; #2 without CAD and/or stroke; #3 with chronic CAD but no myocardial infarction or stroke; #4 with chronic CAD undergoing percutaneous coronary interventions (PCI). Hospitalizations, drugs and other outpatient care were assessed from 2015 to 2017.

Results
Prevalence of T2DM was 6% (441,085/7,365,954). CAD and/or stroke in the previous 3 years affected 7.5% of T2DM patients (33,153); this cohort was generally older, of male sex, with more comorbidities, prescriptions, and hospital admissions (50% versus 13.4%) compared to cohort #2. Yearly costs were &gt;3-fold for cohort #1 versus #2, main drivers being hospitalizations in the former and drugs in the latter. Unexpectedly, two-year cardiovascular events were significantly higher in cohort #4 compared to any other (Figure). Guideline-recommended therapies were suboptimal in all cohorts.

Conclusions
The present analysis points to three areas of potential improvement in T2DM management: 1) undertreatment of T2DM patients with recommended drugs; 2) three-fold recurrences and costs in T2DM patients with, compared to those without, prior cardiovascular events; 3) highest risk of events in those with chronic CAD and PCI, warranting specific studies aimed at defining more effective preventive strategies.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): This research was partially supported by an unrestricted grant from Astra Zeneca. Astra Zeneca was not involved in data collection, analysis and interpretation, in writing the report, nor in deciding to submit the article for publication.
Clinical benefit of direct oral anticoagulants vs. vitamin-K antagonist in octogenarians with atrial fibrillation
Authors: Bonanad C , Garcia-Blas S , Diez Villanueva P , Ariza A , Tarazona F J , Bertomeu-Gonzalez V , Facila L , Torres J , Nunez J , Cordero A 
Published: October 2021

Abstract

Background
Direct oral anticoagulants (DOACs) have demonstrated to the be more effective and safer than vitamin-K antagonist (VKA) for stroke prevention in patients with atrial fibrillation (AF). AF prevalence increases exponentially with age but octogenarians were underrepresented in clinical trials.

Methods
We performed a metanalysis with currently available studies that assessed the effect of DOACS vs. VKA in patients with age ≥80 and AF after performing a systematic search. The primary endpoints analyzed were stroke and all-cause death. Secondary endpoints were major bleeding, according to each study definitions, intracranial bleeding and gastrointestinal (GI) bleeding. The raw numbers of incident end-points reported in each study were used. A random effects model was selected because significant heterogeneity was observed; sensitivity analyses tested potential sources of heterogeneity, publication bias and the small-study effect.

Results
A total of 147,067 patients from 16 studies were included, 71,913 treated with DOACs and 75,154 with VKA. Inclusion criteria for the study was age ≥80 in 13 studies, ≥85 in two and ≥90 in one. Mean age of patients included all the studies was 86.2 (2.6) years. According to the study drug, 34,448 received rivaroxaban; 20,295 apixaban; 14,641 dabigatran, 492 edoxaban and; 2,037 any DOAC. No difference in mean age was observed according to the study drug.
Stroke incidence was available in the 16 studies. DOACs treatment was associated to 28% reduction of stroke (RR: 0.72 95% CI 0.63–0.82; p&lt;0.001) (figure). All-cause mortality could be assessed in 12 studies and DOACs treatment was associated to 18% in mortality (RR: 0.82, 95% CI 0.70–0.96; p=0.012) (figure). DOACs treatment was not associated to reductions in major bleeding (RR: 0.85, 95% CI 0.69–1.04; p=0.108); in contrast, the highest effect of DOACs treatment was a 43% reduction of intracranial bleeding (RR: 0.47, 95% CI 0.36–0.60; p&lt;0.001) (Figure 4). Finally, DOACs treatment was not associated higher of GI bleeding risk (RR: 1.08, 95% CI 0.76–1.53; p=0.678). Metaregression identified inclusion site in North-America (p&lt;0.001), the ELDERCARE-AF results (p=0.023), control arm different than VKA (p=0.006) and the prevalence of hypertension (p=0.042) were outlined as main sources of heterogeneicity for stroke risk reduction. The type of DOAC was the main source of source of heterogeneicity for all-cause mortality (p&lt;0.001) and major bleeding (p=0.03) risk reduction. No small-study effect was found for any endpoint except for intracranial bleeding (Harbor test p=0.029).

Conclusions
Treatment with DOACs in octogenarians reduces the incidence of stroke, all-cause mortality and intracranial bleeding as compared to VKA.

Funding Acknowledgement
Type of funding sources: None.