bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in smoking status after a cardiac rehabilitation program in Spain: description of a smoker's profile
Authors: Sestayo Fernandez M , Alonso Vazquez M , Gonzalez Maestro A , Gonzalez Salvado V , Diaz Balboa E , Neiro Rey M C , Gonzalez Juanatey J R , Pena Gil C
Published: October 2022

Background

Cigarette smoking is a major cardiovascular (CV) risk factor and aids to the development and progression of CV disease.

Purpose

To study the prevalence of smoking in a contemporary Spanish cardiac rehabilitation (CR) cohort, study changes in smoking status over time and define smoker's profile after CR.

Methods

Single-centre, observational retrospective study from all consecutive patients with ischaemic heart disease (n=1379, 6.6% women, age 65.78±11.02 years) that participated in a CR program from 2015 to 2020. Prevalence of smokers was studied over time, from CV event to 6 months after end of CR, including a stratified description of smokers per age group at CV event. Additionally, a comparative analysis of patient profile for those who continued smoking and patients that quitted smoking after CR, was performed.

Results

N=516 patients (37.4%) were active smokers at CV event, including 72 women (31% of all women) and 444 men (38.6% of all men). Highest percentage of smokers was distributed among the youngest age groups: with a 72.6% prevalence among those aged <45 years and 57.9% among those aged 45–55 years. Smoking prevalence decreased with age. Also, there were less female than male smokers in all analysed age groups (Figure 1). At the beginning of CR, the global proportion of active smokers decreased significantly (p<0.01) to a 15.3% (n=210) and continued to significantly decrease at end of CR (10%, n=124), maintaining similar levels at 6 months follow-up (9.9%, n=96). 58% of active smokers at CV event quitted smoking by end of CR. Ongoing smokers were significantly more (p<0.05) depressed (n=20, 16.3%); and had significantly worse (p<0.05) HADS scores at beginning of CR (anxiety: 6.49±3.98, depression: 5.41±4.46), Table 1.

Conclusions

Smoking is nowadays still highly prevalent among CR patients in our setting, especially among young men. Despite a significant fall in the prevalence of smokers after the end of the CR program, there is a non-negligible percentage of patients that keep smoking.

Targeted smoking cessation interventions should be aimed at smokers that have more depression and have worse HADS scores at baseline.

Funding Acknowledgement

Type of funding sources: None.
Altered platelet reactivity, coagulation, endothelial and inflammatory markers early after smoking cessation verified with cotinine plasma concentration
Authors: Ramotowski B , Undas A , Budaj A
Published: October 2022

Background/Introduction

Cigarette smoking is a potent modifiable risk factor for coronary artery disease (CAD) including patients after percutaneous coronary interventions (PCI). Cigarette smoking is associated with major changes in platelet, endothelial, inflammatory, and coagulation responses. The early period after PCI witnesses the highest risk of thrombotic events. However, data regarding alterations of prothrombotic state and platelet reactivity early after smoking cessation are scarce.

Purpose

We investigated alterations to platelet reactivity, coagulation and markers of platelet, endothelial and neutrophil activation in clopidogrel-treated patients with CAD after PCI before and after smoking cessation.

Methods

Patients aged 18 years or older, who smoked at least 10 cigarettes per day, at least 30 days after successful PCI with stent placement, and those treated with 75 mg clopidogrel and 75 mg acetylsalicylic acid (ASA) once daily, were included in the study and were encouraged to quit the habit. Platelet reactivity was measured with VerifyNow system and the concentrations of cotinine, thrombomodulin, P-selectin, platelet factor 4 (CXCL4/PF4), citrullinated histone H3 (H3cit), were assessed in blood samples at baseline and at the 30-day follow-up visit. Smoking cessation was defined as cotinine concentrations of <50 ng/ml.

Results

Among 117 patients, being current smokers, who attended the baseline visit, 84 patients completed a 30-day follow-up. The median [interquartile range] age of patients was 50 [55–65] years, median body mass index was 27.55 [25.2–30.9] kg/m2, and a median load of smoking was 40 [30–47] pack-years. At the follow-up visit, 30 patients stopped smoking as confirmed by cotinine concentrations (study group) and 54 patients continued smoking (control group). Baseline characteristics were similar in both groups. In the study group as compared to the control group, at day 30 a change in platelet reactivity was larger (Δ platelet reactivity units (PRU) 19 [2, 43] vs −6 [−32, 37], p=0.018), along with a change in P-selectin concentration (−11.82 [−23.62, 1.34] vs 7.19 [−14.24, 17.19] ng/ml), p=0.005). The change in the concentrations of thrombomodulin, CXCL4/PF4, and citH3 did not differ significantly between groups.

Conclusion

In the early period after smoking cessation in coronary artery disease patients following PCI treated with clopidogrel and ASA, an increase in platelet reactivity with a decrease in P-selectin levels was observed. No significant changes in other markers were noticed. It might be speculated that the risk of thrombotic complications might be paradoxically enhanced among such patients after smoking cessation despite dual antiplatelet therapy.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Centre of Postgraduate Medical Education
Obesity in young sudden cardiac death: rates, clinical features, and insights into people with body mass index >50kg/m2
Authors: Ashokkumar S , Paratz E , Van Heusden A , Smith K , Zentner D , Morgan N , Parsons S , Thompson T , James P , Connell V , Pflaumer A , Semsarian C , Ingles J , Stub D , La Gerche A
Published: October 2022

Background

Obesity is common in young sudden cardiac death (SCD) victims but it is unclear whether it is more common than in the general population. This study aimed to contextualize young SCD obesity rates, identifying clinical and pathologic features in WHO class II and III obesity.

Methods

A prospective state-wide out-of-hospital cardiac arrest registry included all SCDs in Victoria, Australia from 2019–2021. Body mass indices (BMIs) of patients 18–50 years were compared to age-referenced general population. Characteristics of SCD patients with WHO Class II obesity (BMI ≥30kg/m2) and non-obesity (BMI <30kg/m2) were compared. Clinical characteristics of people with BMI >50kg/m2 were assessed.

Results

504 patients were included. Obesity was strongly over-represented in young SCD compared to the age-matched general population (55.0% vs 28.7%, p<0.0001). Obese SCD patients more frequently had hypertension, diabetes and obstructive sleep apnoea (p<0.0001, p=0.009 and p=0.001 respectively), ventricular fibrillation as their arrest rhythm (p=0.008) and left ventricular hypertrophy (LVH) (p<0.0001). Obese patients were less likely to have toxicology positive for illicit substances (22.0% vs 32.6%, p=0.008) or significant alcohol history (18.8% vs 26.9%, p=0.030). Patients with BMI >50 kg/m2 represented 8.5% of young SCD. LVH (n=26, 60.5%) was their predominant cause of death and only 10 (9.3%) patients died from coronary disease.

Conclusion

Over half of young Australian SCD patients are obese, with all obesity classes over-represented compared to the general population. Obese patients had more cardiac risk factors. Almost two thirds of patients with BMI>50 kg/m2 died with LVH, with fewer than 10% dying from coronary disease.

Funding Acknowledgement

Type of funding sources: None.
Incidence of type 2 diabetes after gastric by-pass surgery in a Swedish controlled cohort study
Authors: Jamaly S , Lundberg C , Adiels A , Lagergren J , Bjorck L , Rosengren A
Published: October 2022

Aims

To assess the long-term risk of developing type 2 diabetes in patients with obesity who have undergone gastric bypass surgery compared to non-operated patients with obesity and the general population.

Methods and results

This study included 55,534 patients aged 20–65 years with a principal diagnosis of obesity in the Swedish Patient Register in 2001–2013. Of these, 23,099 had undergone gastric bypass and 32,435 had not. Each patient was matched by age, sex and geographic region with two population controls from the general population without an obesity diagnosis, i.e., 44,735 controls for the gastric bypass patients and 62,522 controls for the non-operated cohort with obesity. During a median follow-up of 4.2 years (interquartile range [IQR] 2.4, 7.1 years), 3,761 (11.6%) non-operated patients with obesity developed type 2 diabetes (incidence rate 226.0 per 1,000 person-years, confidence interval [CI] 218.8–233.4) compared to 381 (1.6%) among gastric bypass patients (incidence rate 38.7 per 1,000 person-years CI 34.7–43.5). The latter incidence was comparable to population controls incidence rate (34.7 per 1,000 person-years CI 31.7–38.2). Operated and non-operated patients with obesity were also directly compared using Cox regression analysis with adjustment for age, education, and sex, and showed gastric bypass patients had an 85% lower risk of developing diabetes compared to non-operated patients with obesity during the first six years of follow-up (hazard ratio 0.14; 95% CI 0.12–0.17).

Conclusion

Gastric bypass surgery for obesity seems to reduce the risk of developing type 2 diabetes to levels similar to that of the general population during the first six years of follow-up, but not thereafter.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish government and the county councils concerning economic support of research and education of doctorsSwedish Heart and Lung FoundationSwedish Research Council
Low muscle mass is linked with presence of non-alcoholic fatty liver disease irrespective to central obesity: highlights from a prospective epidemiological study in Greece
Authors: Kouvari M , Polyzos S A , Chrysohoou C , Skoumas J , Pitsavos C , Mantzoros C , Panagiotakos D B
Published: October 2022

Background/Introduction

The association between sarcopenia and nonalcoholic fatty liver (NAFL) is highlighted in recent epidemiological studies, although results remain inconsistent.

Purpose

This study aimed to examine the association of low skeletal muscle mass with NAFL as well as the potential mediating effect of waist circumference on the examined association.

Methods

At baseline, 3,042 participants from the Attica region of Greece were recruited. NAFL was assessed through hepatic steatosis index (HSI). Skeletal muscle mass index (SMI) was indirectly calculated using a standard validated procedure.

Results

Ranking from 1st to 3rd SMI tertiles NAFL rate was 45%, 33% and 22%, respectively (p<0.001). Multi-adjusted logistic regression analysis revealed that participants assigned in the 2nd (Odds Ratio (OR): 0.50, 95% Confidence Interval (95% CI): 0.41–0.61)) and 3rd SMI tertile had 50% and 76% (OR: 0.24, 95% CI: 0.19–0.29) lower likelihood to have NAFL compared with their 1st tertile counterparts. This association remained robust after multiple adjustments; however, significance was marginally lost, when waist circumference was added to the model. Subsequently, a multi-adjusted dose-response analysis between SMI and NAFL was performed in the total sample, as well as in the subcategories of normal and abnormal waist circumference. In the total sample, a significant inverse association between SMI and NAFL was observed [OR (per 2 points increase in SMI) = 0.94 (95% CI: 0.92–0.95); p=0.001]. When categorized by waist circumference, participants with moderate/high SMI and normal waist circumference had the lowest NAFL rates (24.3%). Those with low SMI and normal waist circumference and those with moderate/high SMI and abnormal waist circumference had similar rates of NAFL (47.4% and 50.3%, respectively; p=0.25). Participants with both low SMI and abnormal waist circumference presented the highest NAFL rate (60.5%), which was significantly higher compared with the rest subgroups (p<0.001). These findings were confirmed in multi-adjusted analysis to assess NAFL odds per case: participants with adnormal waist, [OR (per 2 points increase in SMI) = 0.97 (95% CI: 0.94–1.00)] vs. participants with normal waist [OR (per 2 points increase in SMI) = 0.89 (95% CI: 0.84–0.95)].

Conclusions

Increasing SMI was associated with lower rates of NAFL independently to abdominal obesity, whereas the two interact as key determinants of NAFL.

Funding Acknowledgement

Type of funding sources: Other. Main funding source(s): Hellenic Society of Cardiology
Metabolically healthy obesity in a young population assisted by the family health strategy LapARC study
Authors: De Souza Mello T , Parente Macedo Moura C , Avelar Mendes De Vasconcellos C , Camara Garcia J , Rossilho Moyses Ushijima N , Rey Costa Tostes F , Brandao Catharina L , Maria Da Costa Muguet C , Do Valle Kangussu F , Dos Santos Ferreira D , Henrique Dos Santos Lemos P , Lopes Monteiro De Barros Junqueira L , Da Silva Guimaraes K , Silaid Muxfeldt E , Tenorio Da Costa Fernandes A C
Published: October 2022

Introduction

Obesity is increasing in younger populations, and is associated with a high cardiovascular (CV) risk, however, it is not clear whether metabolically healthy obesity (MHO) may have a lower CV risk or if it is just an earlier stage of the disease.

Objective

To evaluate the prevalence and cardiovascular (CV) risk factors associated with metabolically healthy obesity (MHO) in a young population assisted by a Family Health Care unit in a large urban center.

Design and method

A cross-sectional population study for CV risk assessment in adults aged 20–50 years old from a Family Health Care unit. Demographic, anthropometric data and CV risk factors were recorded. All underwent office blood pressure (BP) measurements, laboratory evaluation (lipid and glycidic profile). Obesity was defined as a body mass index (BMI) >30 kg/m2 and MHO are those who have less than 3 of the following criteria for metabolic syndrome: office BP higher or equal to 130 x 85 mmHg, hypertension, fasting blood sugar higher or equal to 100 mg/dL, HDL <40 mg/dL (men) and 50 mg/dL (women), triglycerides >150 mg/dL and waist circumference >102 cm (men) and >88 cm (women).

Results

A total of 632 individuals were evaluated (60% female; mean age 37±9 years). The prevalence of obesity was 26%, of which 73% were classified as MHO. Obeses are older, with a higher prevalence of physical inactivity (51% vs 41%, p=0.03), hypertension (44% vs 19%, p<0.001), dyslipidemia (50% vs 36%, p=0.002), and diabetes (7% vs 2%, p=0.001) with higher systolic OBP. MHO compared to unhealthy ones are significantly younger and smoke less. Despite being obese, they have lower BMI (33.6 vs 35.2 kg/m2, p=0.02) and abdominal circumference (102 vs 110 cm, p=0.03), with lower diastolic BP.

Conclusion

MHO was more prevalent in this young population and seems to have a lower CV risk, however it is not clear whether these younger and less obese individuals are only at an earlier stage of the disease. Perhaps the CV diseases onset is postponed for a few years. Even so, these individuals should not be excluded from public health policies as a form of primary prevention.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): CNPQFAPERJ
Effect of diet and lifestyle on the relationship between body mass index and waist circumference and cardiovascular mortality in myocardial infarction patients from the Alpha Omega Cohort
Authors: Cruijsen E , Bonekamp N E , Koopal C , Winkels R M , Visseren F L J , Geleijnse J M
Published: October 2022

Introduction

The associations between measures of body adiposity body mass index (BMI) and waist circumference (WC) and cardiovascular disease (CVD) mortality have been frequently studied and usually follow a J-shaped curve or show a positive relationship. However, less is known about the influence of diet and physical activity on these associations.

Purpose

We aimed to gain insight in potential lifestyle-related effect modifiers of the association of BMI and WC with CVD mortality in myocardial infarction (MI) patients.

Methods

We included 4,837 Dutch patients from the Alpha Omega Cohort with a MI <10 y prior enrolment. BMI and WC were assessed at baseline (2002–2006). Patients were followed through December 2018 for vital status and cause-specific mortality. Continuous associations of BMI and WC with CVD mortality were estimated using Cox proportional hazards models with restricted cubic splines. A BMI of 25 kg/m2 and a WC of 100 cm were used as the references. Age and sex adjusted associations were stratified for diet quality and physical activity level and interaction terms were calculated.

Results

Of the study population (69.0±5.6 y), 17% smoked, 21% had diabetes, 22% were female and >85% used any type of cardiovascular medication. During a median follow-up of 12.4 years [8.5–13.8], 1,010 deaths occurred due to CVD. A J-shaped continuous association was observed between BMI and CVD mortality with inverse associations for a BMI between 25–30 kg/m2, compared to 25 kg/m2. The nadir (HR, 95% CI) was 27.4 kg/m2 (HR: 0.94, 95% CI: 0.88, 1.00) (A). For WC, a non-linear association was observed with CVD mortality with higher mortality risks for a WC above 100 cm (A). Results were similar in patients with low versus high diet quality and in patients with low versus high physical activity (B), interaction terms were not significant (all p>0.55).

Conclusion

In MI patients, a BMI between 25–30 kg/m2 was associated with the lowest risk of CVD mortality. A WC above 100 cm was associated with a higher CVD mortality risk. The observed associations manifested independently of diet quality and physical activity level. Therefore, body adiposity seems to determine CVD mortality risk independently of underlying lifestyle factors.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Regio Deal Foodvalley
Evaluation of cardiac involvement in patients with clinical post-COVID-19 syndrome
Authors: Gorecka M , Jex N , Thirunavukarasu S , Chowdhary A , Poenar A M , Sharrack N , Swoboda P P , Xue H , Vassiliou V , Kellman P , Plein S , Simms A , Greenwood J P , Levelt E
Published: October 2022

Introduction

The underlying pathophysiology of Post-COVID-19 syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus magnetic resonance spectroscopy (31P-MRS) allows non-invasive assessment of the myocardial energetic state.

Purpose

We sought to assess whether Post-COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and tissue characteristics or energetic derangement.

Methods

Prospective case-control study. A total of 20 patients with a clinical diagnosis of Post-COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and ten matching controls underwent 31P-MRS and CMR at 3T at a single time point. (Figure 1) All patients had been symptomatic with acute COVID-19, but none required hospital admission.

Results

Between the Post-COVID-19 syndrome patients and matched contemporary controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes, left ventricular mass), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 and extracellular volume [ECV] fraction mapping, late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with Post-COVID-19 syndrome showed subepicardial hyperenhancement on the late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, ECV, T1, T2 mapping or energetics. This patient was excluded from statistical analyses. (Table 1)

Conclusion

In this study, the overwhelming majority of patients with a clinical Post-COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Welcome Trust Clinical Career Development Fellowship (221690/Z/20/Z);NIHR-UKRI COVID-19 Rapid Response Rolling Call (COV0254)ESC Training Grant
Diabetes and coronary risk equivalency – a population-based cohort study from Western Denmark
Authors: Olesen K , Gyldenkerne C G , Thrane P G , Maeng M M
Published: October 2022

Background

Diabetes is associated with an increased risk of cardiovascular disease. Accordingly, guidelines recommend extensive management of cardiovascular risk factors in patients with diabetes. Diabetes has previously thought to carry the same high cardiovascular risk as already having coronary heart disease. It is, however, unknown if the intensified focus on prophylactic treatment has changed the risk of myocardial infarction and ischemic stroke in contemporary practice.

Aims

We aimed to examine whether diabetes remains a cardiovascular risk equivalent to coronary heart disease under the contemporary treatment regimen.

Methods

We included every person residing in Western Denmark on January 1, 2012, aged 50–89 years. The cohort was stratified by diabetes and coronary heart disease (defined as previous myocardial infarction, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or coronary artery disease documented by coronary angiography). The four groups were followed for up to seven years after inclusion. Outcomes were myocardial infarction, ischemic stroke, cardiac death, and all-cause death. Patients with coronary heart disease only were compared to patients with diabetes only using a multivariable Cox regression model.

Results

We included 1,111,456 persons residing in Western Denmark on January 1, 2012, of whom 86.1% had neither diabetes nor coronary heart disease, 7.5% had diabetes only, 5.0% only had history of coronary heart disease, 1.4% had both diabetes and coronary heart disease. Patients with diabetes only less likely to be in antithrombotic treatment, lipid-lowering treatment, and antihypertensive treatment compared to patients with coronary heart disease only. Compared to patients with diabetes only (Figure 1), coronary heart disease was associated with an increased risk of myocardial infarction (adjusted HR 1.73, 95% CI 1.65–1.82) and cardiac death (adjusted HR 1.40, 95% 1.32–1.48). However, coronary heart disease only was associated with a reduced risk of ischemic stroke (adjusted HR 0.83, 95% CI 0.79–0.87) and all-cause mortality (adjusted HR 0.76, 95% CI 0.74–0.77) compared to diabetes only (Figure 1).

Conclusions

In contemporary practice in Denmark, patients with diabetes only have a lower risk of myocardial infarction or cardiac death than observed in non-diabetic patients with verified coronary heart disease. On the contrary, patients with diabetes only have a greater risk ischemic stroke and al–cause mortality than coronary heart disease only. Thus, diabetes is not a uniform cardiovascular risk equivalent to coronary heart disease, but depends on the given outcome.

Funding Acknowledgement

Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
Association of hepatic steatosis with subclinical cardiac dysfunction in asymptomatic people with type 2 diabetes
Authors: Yeo J L , Gulsin G S , Dattani A , Brady E M , Bilak J M , Ayton S L , Moss A J , Pang W , Boulos S , House M J , St Pierre T G , McCann G P
Published: October 2022

Introduction

Non-alcoholic fatty liver disease is highly prevalent among people with type 2 diabetes (T2D) and is an emerging risk factor for heart failure with preserved ejection fraction (HFpEF). Whether excess liver adiposity is simply a marker of the coexisting adverse cardiometabolic risk profile or independently contributes to the development of HFpEF is unclear.

Purpose

To assess the association between liver fat fraction and subclinical cardiac dysfunction in adults with T2D.

Methods

Prospective cross-sectional study. Two-hundred and thirty-eight adults with T2D (mean age 63±7 years, 62% males, HbA1c 7.2±1.5%, diabetes duration 10±8 years) with no signs, symptoms, or evidence of cardiovascular disease and 40 age-, sex-, and ethnicity-matched non-diabetic controls (mean age 61±8 years, 63% males, HbA1c 5.2±1.2%) underwent comprehensive phenotyping with echocardiography and multiparametric cardiac MRI including adenosine stress and rest perfusion. Volumetric liver fat fraction (VLFF) was measured using a histologically validated, proprietary MRI technique blinded to all participant details. Inter-study reproducibility was assessed in participants (n=28) who underwent a repeat MRI within two weeks. Linear regression analysis was performed to assess any independent associations between VLFF and identified markers of subclinical cardiac dysfunction in subjects with T2D.

Results

People with T2D had evidence of concentric left ventricular (LV) remodelling (higher LV mass/volume), extracellular matrix expansion (higher ECV fraction), both systolic and diastolic dysfunction (lower global longitudinal systolic strain and E/A ratio, respectively), and coronary microvascular dysfunction (lower myocardial perfusion reserve) (Table 1). VLFF demonstrated excellent inter-study reproducibility with an intra-class correlation coefficient (ICC) of 0.988 (0.974–0.994). T2Ds had higher VLFF compared to controls [7.5 (3.8–13.7)% vs 2.9 (1.7–4.7)%, p<0.001]. In multivariable regression analysis adjusting for age, sex, ethnicity, body mass index, ambulatory systolic blood pressure, HbA1c, and low-density lipoprotein, VLFF (β=−0.161, p=0.027) was independently associated with E/A, but not other imaging measures of subclinical cardiac dysfunction.

Conclusion

Liver fat fraction is elevated in people with T2D and is independently associated with early LV diastolic dysfunction. These results add to the growing evidence that ectopic fat plays an important role in the pathogenesis of HFpEF and may be a potential target for intervention.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): National Institute for Health Research (NIHR) United Kingdom through a Research Professorship award (RP-2017-08-ST2-007).British Heart Foundation through a Clinical Research Training Fellowship (FS/16/47/32190).
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

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 (<45, 45-<60, 60-<90, ≥90 mL/min/1.73 m2) and urinary albumin:creatinine ratio (UACR) (<30, 30-<300, 300-<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<0.001) and kidney endpoints by 40% (HR 0.60, 95% CI 0.52–0.69, p<0.001). Overall rates of HHF/CVD and kidney endpoints were higher with lower eGFR (p<0.001) and with higher UACR (p<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

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<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

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

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

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<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

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 (<800 kcal/day or >4200 kcal/day) and females (<600 kcal/day or >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<0.04), blood pressure (Figure E-F; all p<0.001), body fat percentage (Figure G; p<0.001), body mass index (Figure H; p<0.001), and all markers of glycemic control (Figure I-L; all p<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

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

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