bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of dapagliflozin on cardiovascular and kidney events by baseline eGFR and UACR in patients with type 2 diabetes mellitus: a patient-level pooled analysis of DECLARE-TIMI 58 and DAPA-CKD trials
Authors: Moura F , Wiviott S , Chertow G , Dwyer J , Gause-Nilsson I , Johansson P , Langkilde A , McMurray J , Mosenzon O , Raz I , Rossing P , Wheeler D , Sabatine M , Heerspink H 
Published: October 2022

Abstract

Background
The sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin reduced the risk of hospitalization for heart failure (HHF) or cardiovascular death (CVD) and the risk of kidney events in patients type 2 diabetes mellitus (T2DM) and high cardiovascular risk or chronic kidney disease in the DECLARE-TIMI 58 and DAPA-CKD trials. These events are more common at lower levels of kidney function. Combining data from the two trials creates an opportunity to examine the effect of dapagliflozin across the spectrum of baseline kidney function.

Purpose
To determine the effects of dapagliflozin on HHF/CVD and kidney endpoints across a broad range of kidney function in the combined dataset.

Methods
We conducted a post hoc analysis of pooled patient-level data from DECLARE and DAPA-CKD. The effects of dapagliflozin compared with placebo on HHF/CVD and kidney endpoints (defined as sustained eGFR decrease ≥40%, end-stage kidney disease, or renal death) were assessed in the combined cohorts and in subgroups of baseline eGFR (&lt;45, 45-&lt;60, 60-&lt;90, ≥90 mL/min/1.73 m2) and urinary albumin:creatinine ratio (UACR) (&lt;30, 30-&lt;300, 300-&lt;1000, ≥1000 mg/g).

Results
A total of 19,748 patients with T2DM were included. Median (IQR) follow up time was 4.1 (3.7–4.4) years. Median eGFR was 85 (65–95) mL/min/1.73 m2 and UACR 18.2 (7–135) mg/g. Overall, dapagliflozin reduced the risk of HHF/CVD by 18% (HR 0.82, 95% CI 0.73–0.92, p&lt;0.001) and kidney endpoints by 40% (HR 0.60, 95% CI 0.52–0.69, p&lt;0.001). Overall rates of HHF/CVD and kidney endpoints were higher with lower eGFR (p&lt;0.001) and with higher UACR (p&lt;0.001). There were consistent relative risk reductions in HHF/CVD and kidney events with dapagliflozin across eGFR (p-interaction 0.25 and 0.32, respectively, Figure 1) and UACR (p-interaction 0.29 and 0.83, respectively, Figure 2) subgroups. The absolute rate difference (ARD) with dapagliflozin for CVD/HHF ranged from 0.1 events per 1000 patient years in patients in normal categories of eGFR and UACR to 1.0–1.7 events in patients in the most abnormal categories. Likewise, the ARD for kidney events ranged from 0.2 events per 1000 patient years in the normal eGFR and UACR groups to 2.5–4.3 events in patients in the most abnormal categories.

Conclusion
In this pooled analysis of pts with T2DM, there was higher risk of HHF/CVD and kidney events with lower eGFR and higher UACR. Dapagliflozin consistently reduced these events regardless of baseline eGFR and UACR, with large absolute risk reductions in patients with lower eGFR and higher UACR.

Funding Acknowledgement
Type of funding sources: None.
Metabolic syndrome and heart failure: 40 years follow up results of the Seven Countries Study
Authors: Parapid B , Simic D V , Stojsic Milosavljevic A , Ristic A , Geleijnse J M , Danchin N , Blackburn H , Jacobs D , Kromhout D , Adachi H , Menotti A , Nissinen A , Moschandreas J , Ostojic M C , Kanjuh V 
Published: October 2022

Abstract

Introduction
Metabolic syndrome (Met Sy) as a highly debatable cluster of traditional risk factors is known to promote cardiometabolic-related morbidity and mortality, but its precise mechanisms remain to be determined.

Purpose
We sought to determine influence of MetSy on heart failure (HF) morbidity and mortality in the Seven Countries' Study as one of the oldest epidemiological studies.

Methods
The Seven Countries Study encompassed 12,763 participants from 3 continents who were all healthy men of over 40 years at baseline and who underwent regular check ups every 5 years throughout over a 4 decades' span. Morbidity and mortality was adjudicated according to valid ICD and LPH coding.

Results
Using the IDF definition of the Metabolic Syndrome, 9,09% of participants were identified (Figure 1). HF was confirmed in 220 patients (16.4% alive at 40y follow up visit), while 8.2% died of HF as well in the same time-frame (Tables 1 & 2). Presence of MetSy has been shown to significantly influence HF mortality (Figures 2) with lowest survival of 22% for 300 months of follow up for patients with both MetSy and HF (Log rank test=4.405, p&lt;0.0001).

Conclusion
Metabolic syndrome treatment remains in the realm of risk factors' control that now we know influence both ischemic heart disease and heart failure of other origins. Historically, just emerging biomarkers' and targeted imaging weren't available to determine such at the time of HF diagnosis. Also, the sample consisted of men only, mainly Caucasian and a modest proportion of Asian and African-American now known to carry ethnic-specific burden of cardiovascular disease. All of the above, emphasizes the importance of more diversity, equity and inclusion-dedicated long term both observational, as well as interventional research.

Funding Acknowledgement
Type of funding sources: None.
Temperature-related chest pain presentations and future projections with climate change
Authors: Dawson L , Andrew E , Nehme Z , Bloom J , Cox S , Anderson D , Stephenson M , Lefkovits J , Taylor A J , Kaye D , Guo Y , Smith K , Stub D 
Published: October 2022

Abstract

Background
Climate change has led to increased interest in studying adverse health effects relating to ambient temperatures. It is unclear whether incident chest pain is associated with non-optimal temperatures and how chest pain presentation rates might be affected by climate change.

Methods
The study included ambulance data of chest pain presentations in Melbourne, Australia from 1/1/2015 to 30/6/2019 with linkage to hospital and emergency discharge diagnosis data. A time series quasi-Poisson regression with a distributed lag nonlinear model was fitted to assess the temperature-chest pain presentation associations, after adjusting for season, day of the week and long-term trend. Future excess chest pain presentations associated with cold and heat were projected under six general circulation models under medium and high emission scenarios.

Results
In 206,789 chest pain presentations, mean (SD) age was 61.2 (18.9) years and 50.3% were female. Significant heat- and cold-related increased risk of chest pain presentations were observed for mean air temperatures above and below 20.8°C, respectively (Figure 1). Excess chest pain presentations related to heat were observed in all subgroups, but appeared to be attenuated for older patients (≥70 years) and patients of higher socioeconomic status (SES). We projected no significant change in net temperature-related chest pain presentations with climate change under medium- and high-emission scenarios, with increases in heat-related chest pain presentations offset by decreases in chest pain presentations related to cold temperatures.

Conclusions
Heat- and cold-exposure appear to increase risk of chest pain presentations, especially among younger patients and patients of lower SES. In Melbourne, Australia, chest pain presentations overall were not projected to increase with climate change, but increases in heat-related chest pain presentations highlight the importance of risk mitigation strategies to minimise adverse health impacts on hotter days.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Alfred Health.
Women and authorship in an international journal dedicated to cardiovascular diseases: analysis of the last decade
Authors: Davo-Jimenez M , Baez Ferrer N , Igareta-Herraiz A T , Gonzalez J , Diaz R , Avanzas P , Dominguez-Gonzalez V , Hernandez-Baldomero I F , Parra-Esquivel P C , Garcia-Baute M C , Hernandez-Vaquero D , Dominguez-Rodriguez A 
Published: October 2022

Abstract

Introduction and purpose
Scientific production has become very important in the progression of the healthcare profession, and the studies made in this field reflect a gender gap in the authorship of such production. In the last decade, a review of the publications made over 35 years in 6 high impact factor journals has evidenced a lesser proportion of women among the first and last signing authors (1,2). Nevertheless, the presence of women as preferential authors is desproportionately low considering the number of female cardiologists in Spain in the year 2017 (40%) (3). The Revista Española de Cardiología (REC) is an international journal dedicated to cardiovascular diseases. Our study investigates the authorship gender differences from publications in the REC.

Methods
A cross-sectional study was made of the REC issues published between January 2011 and December 2020. For each article we recorded the doi identifier, the year of publication, the type of article, the number of authors, the number of female authors, and the number of women with preferential authorship. Preferential authorship was defined as first signing author, corresponding author or last author. A gender-based analysis of the number of authors, the type and year of publication and preferential authorship was carried out. Female participation was calculated from the female/male ratio, with an analysis of the trend observed over the years.

Results
Of 2859 articles documented, 4275 signing authors were women and 12,061 were men.
699, 548 and 481 women were the first, corresponding and the last author, respectively. Table 1 shows the percentage of articles in which a woman was a preferential author, as well as the percentage of women that would have to be present in the general population to cancel statistical significance. The number of articles in which a woman was the first or the corresponding author was seen to increase (p=0.008 and p=0.002, respectively), while no significant changes were observed in relation to last authorship (p=0.09). The percentage of articles in which at least one woman held at least one of the three preferential authorship positions tended to increase over time (p=0.056). In the year 2011, a total of 90 articles out of 252 (35.7%) had at least one woman among the three preferential authors, while in the year 2020 the figure was 123 out of 296 (41.6%) (Figure 1).

Conclusions
Although the participation of female authors in the scientific production of the REC has increased during the last decade, authorship gender inequalities persist.

Funding Acknowledgement
Type of funding sources: None.
Coexistent diabetes is associated with the presence of adverse phenotypic features in patients with hypertrophic cardiomyopathy
Authors: Jex N , Chowdhary A , Thirunavukarasu S , Procter H , Sengupta A , Natarajan P , Kotha S , Poenar A M , Xue H , Cubbon R , Kellman P , Greenwood J P , Plein S , Page S P , Levelt E 
Published: October 2022

Abstract

Background
Type 2 diabetes mellitus (DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. The reasons for this adverse prognostic association are incompletely understood. Although distinct entities both HCM and DM share common features of impaired myocardial energetics and coronary microvascular function.

Purpose
We sought to test the hypothesis that co-existent diabetes is associated with greater reductions in myocardial energetics and perfusion, and higher scar burden in HCM.

Research design and methods
Seventy-five age- and sex-matched participants with concomitant HCM and DM (HCM-DM, n=20), isolated HCM (n=20), isolated DM (n=20) and healthy volunteers (HV, n=15) underwent 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance imaging. The HCM groups were matched for HCM phenotype. The DM groups were matched for diabetes treatment, duration, HbA1c, body mass index and hypertension comorbidity.

Results
ESC sudden cardiac death risk scores were comparable between the HCM groups (HCM: 2.2±1.5%, HCM-DM: 1.9±1.2%; p=NS) and sarcomeric mutations were equally common. HCM-DM had the highest NT-proBNP levels (HV: 42 ng/L [IQR: 35–66], DM: 118 ng/L [IQR: 53–187], HCM: 298 ng/L [IQR: 157–837], HCM-DM: 726 ng/L [IQR: 213–8695]; p&lt;0.0001). Left-ventricular ejection fraction, mass and wall thickness were similar between the HCM groups. HCM-DM displayed a greater degree of fibrosis burden with higher scar percentage, and lower global longitudinal strain compared to the isolated HCM. PCr/ATP was similarly decreased in the HCM-DM and DM (HV: 2.17±0.49, DM: 1.61±0.23, HCM: 1.93±0.38, HCM-DM: 1.54±0.27; p=0.0003). HCM-DM had the lowest stress myocardial blood flow (HV: 2.06±0.42 ml/min/g, DM: 1.78±0.45 ml/min/g, HCM: 1.74±0.44 ml/min/g, HCM-DM: 1.39±0.42 ml/min/g; p=0.004).

Conclusions
We show for the first time that HCM patients with DM comorbidity display greater reductions in myocardial energetics, perfusion, contractile function and higher myocardial scar burden and serum NT-proBNP levels compared to patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and DM.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Diabetes UK
Associations of dietary macronutrient composition with cardiometabolic health: data from the National Health and Nutrition Examination Survey (NHANES) 1999–2014
Authors: Koemel N A , Senior A M , Celermajer D S , Grech A , Gill T P , Raubenheimer D , Simpson S J , Skilton M R 
Published: October 2022

Abstract

Background
Human nutrition is a leading modifiable risk factor for the prevention of cardiometabolic diseases. However, most nutritional research focuses on the role of specific nutrients rather than compositional analysis of the diet.

Purpose
We aimed to assess the association of dietary macronutrient composition with various markers of cardiometabolic health.

Methods
This study was undertaken using 24-hour food recall data from the National Health and Nutrition Examination Survey from years 1999–2014 (n=36,637). Participants included both males and females ≥20 years of age (49.8±18.3 years; 53% Female). Caloric outliers for males (&lt;800 kcal/day or &gt;4200 kcal/day) and females (&lt;600 kcal/day or &gt;3500 kcal/day) were removed from the analysis (n=1844). Cardiometabolic health markers were collected via mobile examination center and included triglycerides (n=16,444), total cholesterol (n=31,155), LDL cholesterol (n=15,798), HDL cholesterol (n=33,435), blood pressure (n=34,121), body fat percentage (n=4269), body mass index (n=35,187), glucose (n=17,208), insulin (n=16,273), oral glucose tolerance test (n=8280), and HbA1c (n=27,288). Associations of dietary macronutrients with cardiometabolic health markers were assessed using 3-dimensional general additive models (Protein; Carbohydrate; Fat) with adjustment for age, sex, misreporting, ethnicity, education level, household income, physical activity, alcohol intake, and smoking. Response surfaces on right-angled mixture triangles were generated as predictions from absolute macronutrient intake at the 50th percentile of total energy intake. Macronutrient intakes were transformed to a percentage of energy to visualize and interpret associations compositionally.

Results
There was a complex 3-way interactive non-linear association of macronutrient composition with lipid profile (Figure A-D; all p&lt;0.04), blood pressure (Figure E-F; all p&lt;0.001), body fat percentage (Figure G; p&lt;0.001), body mass index (Figure H; p&lt;0.001), and all markers of glycemic control (Figure I-L; all p&lt;0.001). Diets comprised of high protein coupled with low fat were associated with higher triglycerides but generally more favorable total cholesterol, blood pressure, and body fatness. Conversely, diets composed of high protein coupled with high fat were associated with higher HDL cholesterol but worse total cholesterol, body fatness, body mass index, and glycemic control.

Conclusions
These findings display a complex relationship between dietary macronutrient composition and cardiometabolic health. Future research is needed to evaluate how dietary source and quality may modify the observed associations.

Funding Acknowledgement
Type of funding sources: Private company.
Effects of omega-3 fatty acid supplementation on the risk of atrial fibrillation (AF) and micro-AF in the OMEMI trial
Authors: Myhre P , Berge T , Kalstad A , Tveit S H , Laake K , Schmidt E B , Solheim S , Arnesen H , Seljeflot I , Tveit A 
Published: October 2022

Abstract

Background
Findings from recent clinical outcome trials have raised concerns regarding potential off target adverse effects from supplementation with n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk.

Purpose
We aimed to assess AF and “micro-AF” in elderly patients with myocardial infarction (MI), randomized to n-3 PUFA or placebo.

Methods
In the OMEMI trial, 70–82 years old patients with a recent MI were randomized to 1.8g/day of eicosapentaenoic/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF was recorded by clinical detection and by screening, also for “micro-AF” (episodes of ≥3 consecutive irregular supraventricular ectopic beats), by two weeks Zenicor thumb ECG (adjudicated by investigators blinded to treatment allocation). Serum phospholipid content of EPA and DHA was determined by gas chromatography at baseline and study end.

Results
Of 1014 patients in the OMEMI trial, 759 (75%) had no history of AF at baseline. These patients were aged 75±4 years and 542 (71%) were male. During the two year follow-up 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or micro-AF. In the n-3 PUFA group 46 (11.9%) had AF/micro-AF (28 AF and 18 micro-AF) while in the placebo group 24 (6.5%) had AF/micro-AF (15 AF and 9 micro-AF); HR 1.90 (95% CI 1.16–3.11, P=0.011; Figure 1, panel A). In both treatment arms combined, EPA increased with a mean of 60% in no-AF, 80% in micro-AF and 110% in AF (P=0.003 for linear trend; Figure 1, panel B). In patients randomized to n-3 PUFA, EPA increased with a mean of 120% in no-AF, 130% in micro-AF and 180% in clinical-AF (P=0.04 for linear trend). There were no significant associations between changes in DHA and new-onset AF.

Conclusion
Supplementation with 1.8 g of n-3 PUFA to post MI patients increased the risk of micro-AF and AF, and there seemed to be a graded association between increases in serum EPA and the risk of micro-AF and AF. Changes in serum DHA was not related to the risk of AF/micro-AF.

Funding Acknowledgement
Type of funding sources: None.
Effects of omega-3 fatty acids on dementia and cognitive Impairment in the ASCEND trial
Authors: Mafham M , Parish S , Offer A , Buck G , Bowman L , Armitage J 
Published: October 2022

Abstract

Background
Observational data suggest that higher fish consumption is associated with a lower risk of dementia and supplementation with omega-3 fatty acid (FA) is associated with better cognition. The aim of this study is to assess the effect of omega-3 fatty acid (FA) supplementation on the risk of dementia and cognitive impairment in a pre-specified secondary analysis, with longer follow-up, of a randomized comparison in the ASCEND trial.

Methods
The study included 15,427 people in the United Kingdom with diabetes and no history of prior cardiovascular disease or recorded dementia randomized in the ASCEND trial between June 2005 and July 2011 randomly assigned to 1g capsules daily containing omega-3 fatty acids or matching placebo for a mean of 7.4 years. The main pre-specified comparison by randomized treatment in this cognitive study was a “broad dementia outcome” of dementia, cognitive impairment or confusion ascertained through participant, carer or general practitioner report or hospital admission diagnosis, by 31 March 2019 (∼2 years beyond the scheduled treatment period).

Results
During a mean follow-up of 7.4 years within the scheduled treatment period and 1.7 years afterwards, the broad dementia outcome occurred in 1146 participants, a similar percentage of participants in the omega-3 FA group and placebo groups: 574 participants (7.4%) vs. 572 (7.4%), rate ratio 1.00 (95% CI, 0.89–1.12) p=0.99. Allocation to omega-3 FA was not associated with any significant effect on measured cognitive function at end of the scheduled treatment period.

Conclusions
Omega-3 FA allocation was not associated with risk of the broad dementia outcome in this population of people with diabetes and the results excluded a proportional impact greater than 11%. Further trials are needed to assess the impact of higher dose omega-3 FA supplementation, but the current evidence does not support supplementation with omega-3 FA for dementia prevention.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): British Heart Foundation, UK Medical Research Council