bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical application of the HFA/ICOS score in breast cancer women: its added value in the prediction of chemotherapy-related cardiac dysfunction
Authors: Di Lisi D , Madaudo C , Ortello A , Comparato F , Sinagra F P , Damerino G , Gambino G , Novo G , Galassi A R
Published: November 2023

Background

Breast cancer is the most common malignancy in women. It is known that anti-cancer drugs can cause cardiovascular complications. Chemotherapy-related cardiac dysfunction (CTRCD) is the main complication of a treatment with anthracyclines, used to treat breast cancer. Echocardiography is fundamental in the evaluation of the left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) to define CTRCD as mild, moderate or severe, in accordance with 2022 ESC Guidelines on Cardio-Oncology. These guidelines recommend cardiovascular baseline risk stratification using the HFA/ICOS score, in order to plan the most appropriate surveillance program and implement cardioprotective strategies.

Purpose

to assess the usefulness of HFA/ICOS score in patients with breast cancer undergoing treatment with anthracyclines, in predicting the development of CTRCD.

Methods

A retrospective study was carried out enrolling 109 patients with breast cancer treated with anthracyclines. We performed a cardiological visit with an ECG and echocardiogram at baseline (T0), three months (T1), and six months (T2) after starting treatment. Baseline cardiovascular risk was assessed in all patients, using HFA/ICOS score and patients were classified into 4 groups: low-risk patients, medium-risk patients, high and very high risk patients. During the follow-up, we assessed the development of CTRCD analyzing changes in LVEF and in GLS.

Results

At baseline, 61 patients had low risk of developing cardiotoxicity, 34 patients had medium risk, 14 patients had high risk, no patients had very high risk. Analyzing the development of CTRCD, 21 patients (20,5%) developed asymptomatic mild CTRCD at T1 and 13 patients (14%) at T2. 1 patient developed moderate asymptomatic CTRCD at T1 and 1 patient at T2. No patient developed severe CTRCD. We found a significantly higher proportion of CTRCD in the high-risk group (57%, pvalue 0,03) than in the medium (41%) and low risk group (32%). In a subanalysis we found a correlation between the development of asymptomatic CTRCD and the presence of LVEF between 50-54% or arterial hypertension in intermedium/low risk patients.

Conclusion

our study confirms the usefulness of the HFA/ICOS score in the prediction of CTRCD in high risk breast cancer women; however the evidence of a correlation between the presence of LVEF 50-54% or arterial hypertension and the development of asymptomatic CTRCD emphasises the importance of cardiovascular monitoring also in intermediate risk patients, in which chemotherapy plays an additional role of developing CRTD.
Association between cardiac arrhythmia before pregnancy and gestational diabetes: a nationwide population-based study in Korea
Authors: Choi Y , Na J O , Wi W Y , Cho G J
Published: November 2023

Background

Premature extra betas and supraventricular tachyarrhythmias are prevalent in the gestational period. Gestational diabetes mellitus (GDM) complicated a significant proportion of pregnancies worldwide.

Purpose

Given the high prevalence of cardiac arrhythmia (CA) among patients with diabetes, we aimed to investigate the association of CA with GDM.

Methods

This is a nationwide cohort study using the Korean Health Insurance database. We identified 1,113,729 women who gave birth between 2007 and 2015. After excluding subjects who did not undergo the national health screening test within a year before pregnancy, multi-pregnancy, and those with fasting blood glucose ≥126 mg/mL and/or diagnosed with diabetes before pregnancy CA was defined as atrial and ventricular premature beats, paroxysmal tachycardia, and atrial fibrillation. The primary outcome was the incidence of GDM. Subgroup analysis stratified by age and body mass index at pregnancy onset, and a history of hypertension before pregnancy were conducted.

Results

A total of 365,880 women were included in the final analysis. Of them, 3,253 (0.9%) had a diagnosis of CA. Subjects with CA were older at pregnancy onset (mean age 33.3±4.1 vs. 33.0±3.9 years, P<0.001), and had a higher proportion of hypertension (5.2% vs. 1.0%, P <0.001) than in subjects without CA. GDM was detected in 31,938 (8.7%) subjects and more commonly occurred in subjects with CA than those without (14.9% vs. 8.7%, P<0.001). After adjusting for confounding factors, the incidence of GMD was statistically significantly higher in those with CA (adjusted OR 1.78, 95% CI 1.615–1.970, P<0.001). Moreover, the relationship between CA with GDM was statistically significant regardless of age and body mass index (Figure 1). Meanwhile, despite a higher incidence of GDM, the association between CA and GDM was insignificant in subjects with a history of hypertension.

Conclusion

The risk of gestational diabetes was higher in subjects diagnosed with CA before or during pregnancy compared with those without CA.
Genetically determined lipoprotein(a) levels do not cause an increased risk of preeclampsia - a two-sample Mendelian randomization study
Authors: Golawski M , Lejawa M , Osadnik T , Mickiewicz A , Gierlotka M , Jozwiak J , Pawlas N , Banach M
Published: November 2023

Introduction

High blood levels of lipoprotein(a) [Lp(a)] were suggested to increase the risk of preeclampsia. Because excessive coagulation is involved in preeclampsia and Lp(a) is a known pro-coagulative protein, the hypothesis that Lp(a) is causally involved in preeclampsia seems to be consistent. Nevertheless, the exact impact and causal role of Lp(a) on preeclampsia was not well elucidated. Because the levels of Lp(a) are widely recognized to be highly genetics-dependent, we chose Mendelian Randomization [MR] as a tool to determine the impact of Lp(a) on the incidence of preeclampsia.

Purpose

To determine whether Lp(a) levels have impact on incidence of preeclampsia.

Methods

A two-sample MR study was conducted. Summary statistics were extracted from publicly available datasets. UK Biobank was the source of correlations for Lp(a) levels and FinnGen was used as the source of genetic correlations for preeclampsia. We restricted the variants used to LPA gene region. Inverse-variance-weighted mean was used as a primary analysis. Secondary analyses were performed using weighted median, mode, and MR-Egger methods. Sensitivity analysis was performed by leaving out random 30% of the variants as well as by using previously published variants correlated with Lp(a) levels.

Results

Summary statistics regarding genetic determinants of Lp(a) levels were retrieved for 318922 participants, while data regarding pre-eclampsia were available for 5922 cases and 176113 controls. Genetic associations of included variants with Lp(a) levels (horizontal axis) and with preeclampsia (vertical axis) are presented in Figure. Primary [p=0.562] and secondary analyses [median p=0.825; mode p=0.717; MR-Egger p=0.765] indicated that Lp(a) levels have no impact on the incidence of preeclampsia. Selected variants did not show appreciable pleiotropy as indicated by MR-Egger intercept test [p=0.898]. Sensitivity analysis did not yield statistically significant results [leave-30%-out analysis IVM p-values: 0.313-0.964].

Conclusions

Genetically determined Lp(a) levels were not correlated with and do not appear to have a causal role in preeclampsia. Therefore, Lp(a) screening provides no information as to patients' risk of preeclampsia and Lp(a) reduction is not a promising strategy aimed at preeclampsia prevention. It is nevertheless possible that Lp(a) is involved in the pathogenesis of preeclampsia without a causal, level-dependent role. Irrespectively, the effect of Lp(a) in recurrent pregnancy loss or intrauterine growth restriction needs to be further investigated.
Geographic differences in serious bleeding event rates and clinical profiles among patients with ESKD who receive peritoneal or hemodialysis, 2009-2022
Authors: Bonaca M P , Coyle C , Bash L D , Barash I , Ramey D R , Guedes M , Zhao J , Karaboyas A , Pecoits-Filho R , Atkins G B
Published: November 2023

Background

Patients with end-stage kidney disease (ESKD) have higher rates of bleeding compared to the general population. Therapies to manage risk of thrombosis in patients with ESKD, like anticoagulants, can further increase this risk. Despite these risks, there are limited epidemiological data on bleeding rates in ESKD patients including how this risk varies across geographies. Our aim was to quantify serious bleeding event rates among patients with ESKD who are on dialysis across 5 global regions.

Methods

Data for this analysis come from 21 countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS; 2009-2022) and 8 countries in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS; 2014-2022), both prospective studies among patients treated with hemodialysis (HD) and peritoneal (PD), respectively. Patient characteristics and bleeding rates across 5 regions were analyzed: Australia/New Zealand (ANZ), Europe, Gulf Coast Countries (GCC) (only HD), North America (NA), and Other Asia-Pacific (AP). Counts of first serious bleeding event (i.e., leading to death or inpatient hospitalization) were calculated as event rates per 100 person-years.

Results

In all, 32,396 and 6,068 patients on HD and PD, respectively were included (Table 1). Of patients receiving HD, 3% were from ANZ, 4% were from GCC, 14% were from North America, 28% were from AP, and 51% were in Europe. Of patients on PD, 8% were from ANZ, 7% were from Europe, 26% lived in NA, and 60% were in the AP region. Mean age for HD and PD patients generally ranged from 59-66 with PD patients tending to be a few years younger. GCC patients on HD had a mean age of 55. Both cohorts had similar distribution of sex and race. Anticoagulant use was lowest in AP and highest in NA; with lower use in PD compared to HD.

Serious bleeding rates were highest in ANZ and lowest in AP. Bleeding rates leading to hospitalizations followed a similar trend. Gastrointestinal (GI) bleeding resulted in the highest bleeding event rates for hospitalizations across all regions but was highest in NA. Access bleeding was a more common reason for hospitalization in ANZ and Europe than other regions. The rate of fatal bleeding events was somewhat higher in Europe and AP than other regions with the most common fatal bleeding event being hemorrhagic stroke (Table 2), the highest of which was in AP.

Conclusion

These data highlight the large regional variations and inconsistent patterns in the clinical profiles, treatment patterns, and serious bleeding event rates among patients with ESKD receiving dialysis. Further research is needed to better understand factors that contribute to individual patients’ bleeding risk and to these geographic differences as a mechanism to improve risk management and quality care provided to these patients.Table 1.Patient CharacteristicsTable 2.Bleeding Rates
Glomerular filtration rate predicts pro-vascular progenitor cell depletion: insights from the IPE-PREVENTION and ORIGINS-RCE studies
Authors: Bakbak E , Krishnaraj A , Quan A , Terenzi D C , Puar P , Pan Y , Bakbak A , Bari B , Terenzi K , Rotstein O D , Teoh H , Leiter L A , Bhatt D L , Hess D A , Verma S
Published: November 2023

Background

People living with cardiometabolic disease and impaired renal function are at increased risk of experiencing adverse cardiovascular outcomes(1,2). Recent evidence indicates that individuals living with atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes (T2D) exhibit a reduction in circulating vascular regenerative (VR) cells that are essential for maintaining blood vessel homeostasis(3). However, there is limited data on whether VR cell content changes in response to cardiometabolic and kidney disorders.

Purpose

We sought to determine if there is an association between estimated glomerular filtration rate (eGFR) and VR cell content in individuals with ASCVD and/or diabetes. Data were from participants enrolled in the IPE-PREVENTION and ORIGINS-RCE studies.

Methods

IPE-PREVENTION participants had moderately elevated triglycerides (1.5 - 5.65 mmol/L) with established ASCVD and/or T2D. ORIGINS-RCE participants had established ASCVD or T2D and at least one additional cardiovascular risk factor. Circulating mononuclear cells were isolated from peripheral blood and characterized using side scatter properties (SSC) and high aldehyde dehydrogenase activity to quantify pro-angiogenic early myeloid progenitor cells (ALDHhi), and primitive versus lineage-specific cell surface marker co-expression. Participants were stratified according to those with an eGFR <60 mL/min/1.73m², or ≥60 mL/min/1.73m².

Results

Median [IQR] eGFR of the pooled cohort (n=169) was 75 [59, 88] mL/min/1.73m²; 45% had an eGFR that was <60 mL/min/1.73m². The stratum with eGFR <60 mL/min/1.73m² had fewer circulating ALDHhiSSClow progenitor cells (0.037 vs. 0.051%; P<0.01) (Figure 1A) and ALDHhiSSClow cells expressing CD34+ and CD133+ (49 vs. 54%; P=0.03) (Figure 1B) than that with an eGFR ≥60 mL/min/1.73m². The predictive value of eGFR on ALDHhiSSClowCD34+CD133+ frequency was conserved even after controlling for age, sex, LDL-C, BMI, and HbA1c (P<0.01) (Table 1). The frequency of ALDHhiSSCmid monocyte precursor cells did not differ based on eGFR status.

Conclusions

Low eGFR was predictive for the depletion of ALDHhiSSClow primitive progenitor cells that co-express the stem cell markers CD133 and CD34 in individuals with ASCVD and/or T2D suggesting that diminished kidney function is associated with a decrease in vessel reparative pro-angiogenic progenitor cell content. Strategies that improve circulating VR cell content in individuals living with kidney and cardiometabolic disease may provide clinically meaningful benefits.Figure 1Table 1
C-reactive protein in Stroke-Heart-Syndrome: a propensity-matched analysis of a global federated health network
Authors: Bucci T , Sagris D , Harrison S , Pastori D , Ntaios G , Mcdowell G , Buckley B J R , Lip G Y H
Published: November 2023

Introduction

The role of inflammation in the Stroke-Heart-Syndrome is unclear.

Purpose

To assess the predictive role of C-Reactive Protein (CRP) for early cardiovascular complications in patients with stroke.

Methods

Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and CRP levels measured within 24 hours post-stroke, were categorized into three groups: i)<1mg/L, ii)1-3 mg/L and iii)>3mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), atrial fibrillation (AF), ischemic heart disease, ventricular arrhythmias, and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching.

Results

Of the 104,741 patients enrolled, 51% were female and the mean age was 67±2 years. Cardiac complications or death within 30 days occurred in 40.4% patients with CRP>3 mg/L, in 27.6% patients with CRP 1-3 mg/L and in 23.2% patients with CRP<1 mg/L. After propensity score matching, patients with CRP levels of 1-3mg/L and >3mg/L had higher risk of the composite outcome (HR: 1.10, 95%CI: 1.05-1.50;HR: 1.51, 95%CI: 1.45-1.58), death (HR:1.43, 95%CI:1.24-1.64; HR:3.50, 95%CI:3.10-3.96), HF (HR:1.08, 95%CI:1.01-1.16; HR:1.51, 95%CI:1.41-1.61), AF (HR:1.10, 95% CI:1.02-1.18; HR:1.42, 95%CI:1.33-1.52), and ventricular arrhythmias (HR:1.24, 95% CI:1.02-1.52, HR:1.67, 95% CI:1.39-2.01) compared to those with CRP<1 mg/L. Ischemic heart disease was more common only in patients with CRP levels >3mg/L (HR:1.33, 95% CI:1.26-1.40) compared to those with CRP<1mg/L. No association with Takotsubo cardiomyopathy was found. At the sensitivity analysis, these results were also confirmed considering only older patients or excluding those with possible confounding factors.

Conclusion

CRP levels at the admission for an ischemic stroke predict the 30-day risk of cardiac complications or death.
Evaluation of cardiovascular risk in the population with a diagnosis of organic mental illness, a cohort study carried out in South America
Authors: Dulcey L , Theran J , Ciliberti M , Blanco E , Caltagirone R
Published: November 2023

Background

Patients with severe mental illness (SMI), such as schizophrenia or bipolar disorders, are more frequently affected by metabolic syndrome and cardiovascular (CVD) diseases than the general population, with a significant reduction in life expectancy.

Purpose

Beyond metabolic syndrome, quantifying the risk of CVD morbidity in the long-term may help clinicians to put in place preventive strategies. In this study, we assessed 10-year CVD risk in patients with SMI and healthy individuals using an algorithm validated previously.

Methods

Patients aged 35–69 years diagnosed with SMI were consecutively recruited from psychiatric acute care units. Single CV risk factors were assessed, and 10-year CV risk calculated by means of the CUORE Project 10-year CV risk algorithm, based on the combination of the following risk factors: age, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking habit, and hypertensive treatment. Patients’ data were compared with those from the general population. The 10-year CVD risk was log-transformed, and multivariable linear regression was used to estimate mean ratios, adjusting for age, and education.

Results

Three hundred patients and 302 controls were included in the analysis. Among men, the 10-year CVD risk score was very similar between patients with SMI and the general population (mean ratio (MR): 1.02; 95%CI 0.77–1.37), whereas a 39% increase in 10-year CVD risk was observed in women with SMI compared to the general population (MR: 1.39; 95%CI 1.16–1.66).

Conclusions

In our study, women with SMI were consistently more at risk than the general population counterpart, even at younger age.
Sudden cardiac death in people with schizophrenia: higher risk, poorer resuscitation profiles and differing pathologies
Authors: Paratz E , Van Heusden A , Zentner D , Morgan N , Smith K , Thompson T , James P , Connell V , Pflaumer A , Semsarian C , Ingles J , Parsons S , Rauchberger I , Stub D , La Gerche A
Published: November 2023

Background

People with schizophrenia account for approximately 1.0% of the population and appear to experience increased rates of sudden cardiac death (SCD). This study determined characteristics of increased SCD in people with schizophrenia.

Methods

A prospective state-wide registry compared people aged 15-50 years with and without schizophrenia who experienced SCD within a two-year time-period and were referred for forensic evaluation.

Results

579 individuals were identified, of whom 65 (11.2%) had schizophrenia. Patients with schizophrenia were more commonly smokers (46.2% vs 23.0%, p<0.0001), consumed excess alcohol (32.3% vs 21.4%, p=0.05), and used QTc-prolonging medications (69.2% vs 17.9%, p<0.0001). They were less likely to arrest while exercising (0.0% vs 6.4%, p=0.04). Unfavourable arrest-related factors included lower rates of witnessed arrest (6.2% vs 23.5%, p<0.0001), more likely to be found in asystole (92.3% vs 73.3%, p<0.0001), and being more likely to be found as part of a welfare check after a prolonged period of time (median 42 vs 12 hours, p=0.003). There was more frequent evidence of decomposition, and they more commonly underwent autopsy (41.2% vs 26.4%, p=0.04 and 93.8% vs 82.5%, p=0.05), with diagnosis of non-ischaemic cardiomyopathy being more common (29.2% vs 18.1%, p=0.04).

Conclusion

People with schizophrenia account for 11% of young SCD patients referred for forensic investigations, exceeding population rates eleven-fold. They have higher pre-existing cardiac risk factor burden, unfavourable resuscitation profiles and higher rates of non-ischaemic cardiomyopathy. Strategies targeting biopsychosocial support may deliver not only psychological benefits but also help reduce unwitnessed cardiac arrest.
Severe mental illness and symptoms of acute coronary syndrome in emergency calls
Authors: Storgaard Noerskov A , Torp-Pedersen C , Nordgaard J , Bang C F N
Published: November 2023

Background

It can be lifesaving to act fast and correct when acute life-threatening diseases occur. This is, however, challenging in some patients with severe mental illness as they sometimes experience symptoms differently than patients without severe mental illness. This changed perception can affect the patients’ chances of receiving adequate help, as these patients are already stigmatized even by healthcare personnel.

Purpose

We aimed to determine whether patients with severe mental illness reported different symptoms of acute coronary syndrome (ACS) in emergency calls than patients without severe mental illness.

Methods

In this registry-based study, we analyzed symptoms of ACS in emergency calls made from 2014 to 2018 in the Capital Emergency Medical Services, including the Emergency Number (1-1-2) and the Out-of-hours Service (medical helpline). The study population comprised patients with severe mental illness (defined by schizophrenia, bipolar affective disorder, and depression) and a control group of patients without severe mental illness. Additionally, we investigated whether psychotropics (defined by antipsychotics, mood stabilizers, and antidepressants) were associated with altered symptom presentation of ACS. Furthermore, we determined the time from the emergency call to hospitalization. Analyses were performed by logistic regression adjusted for sex and age and t-tests.

Results

In total, 11,113 emergency calls were included; 917 were from patients with severe mental illness (45.4% were female, average age was 64.6 years), and 10,196 were from patients without severe mental illness (35.3% were female, average age was 67.7 years). Severe mental illness was associated with less frequent chest pain in ACS (odds ratio 0.80, 95%CI: 0.70-0.92, p=0.002). Furthermore, treatment with psychotropics was associated with less frequent chest pain in ACS (odds ratio 0.73, 95%CI: 0.64-0.82, p<0.001). The mean time difference from the emergency call to hospitalization was 17 minutes longer for patients with severe mental illness (1 hour 21 minutes vs. 1 hour 4 minutes, p=0.002)

Conclusion

Patients with severe mental illness presented less frequent chest pain in ACS in emergency calls than patients without severe mental illness and had increased time to hospitalization. This calls for increased awareness of symptom presentation in patients with severe mental illness to improve the identification and management of ACS.
Cardiac function in patients with Paget disease of bone: standard and advanced echocardiographic study
Authors: Giaquinto A , Abate V , Muscariello R , Pirrotta F , Merlotti D , Gennari L , Esposito R , Rendina D
Published: November 2023

Background/Introduction

Paget’s disease of bone (PDB) is a common metabolic bone disorder and cardiovascular diseases are considered a possible PDB metabolic complication. Heart complications have only been described anecdotally as high-output heart failure due to high blood flow when skeletal involvement is extensive.

Purpose

Scientific studies that compare the structural and functional characteristics of the heart in this population are few and dated. The aims of this study were to evaluate echocardiographic parameters in PDB patients.

Methods

60 PDB patients and 115 control subjects, matched by age, weight, height and history of arterial hypertension were enrolled. All subjects underwent to standard and advanced echocardiography examination.

Results

PBD patients showed a lower values of left ventricular ejection fraction (LVEF) (60,86 ± 4,51 vs 62,79 ± 4,30%, p 0,007), global longitudinal strain (GLS) (21,42 ± 2,20 vs 22,35 ± 2,21%, p 0,021) and myocardial work efficiency (MWE) (94,1 ± 2,0 vs 95,4 ± 2,9%, p 0,021), and higher values of interventricular septum thickness (IVSd) (9,9 ± 1,4 vs 9,1 ± 1,4 mm; p 0,003), and relative wall thickness (RWT) (0,38 ± 0,07 vs 0,35 ± 0,07, p 0,031) compared to controls, while there were no significant difference between the other parameters analyzed (Table 1). Calcification and/or sclerosis of aortic valve was detected in 26 PDB patients (43,3%) compared to 27 subjects (23,5%) in control group (Fisher’s exact test p-value = 0,006). Calcification and/or sclerosis of mitral annulus was detected in 14 PDB patients (23,3%) compared to 12 controls (11,6%) (Fisher’s exact test p-value = 0,022) (Table 2).

Conclusion

The study results support the hypothesis that PDB is a systemic condition, influencing cardiac function and structure, associated with increased cardiovascular risk. Our data showed that myocardial function in PDB patients is impaired. The lower resting values of LVEF, GLS and MWE represent an early subclinical myocardial damage.Table 1Table 2
Gout is associated with increased cardiovascular risk: results from analysis of the CPRD dataset
Authors: Ferguson L , Mcinnes I B , Sattar N , Conrad N
Published: November 2023

Background

Gout, a common crystal arthropathy, has been associated with higher cardiovascular risk. However, the degree to which this risk is potentially mediated by traditional risk factors, and whether this risk differs across individual cardiovascular disorders (CVD), inclusive of heart failure, is unclear.

Purpose

We aimed to determine the risk of incident cardiovascular disease in patients with newly diagnosed gout, whether this varied across a range of cardiovascular disorders, and the potential impact of traditional risk factors.

Methods

We used linked primary and secondary electronic health records from 22 million individuals in the Clinical Practice Research Datalink (CPRD) to assemble a cohort of individuals newly diagnosed with gout between 01/01/2000 and 31/12/2017 and free of cardiovascular disorders (CVD) up to 12 months after diagnosis, and up to five individuals matched on age, sex, socioeconomic status and region, with follow-up until 30/06/2019. We investigated the incidence of twelve cardiovascular outcomes and used Cox-proportional hazards models to examine differences in patients with and without gout. In sensitivity analyses, models were further adjusted for known cardiovascular risk factors (blood pressure, BMI, smoking, cholesterol, and type 2 diabetes).

Results

We identified 153 645 individuals with Gout and 714 192 matched controls. Of these, 31479 people with and 106 520 without gout developed incident CVD during a median of 6.5 years of follow-up. Patients with gout had a higher risk of cardiovascular outcomes than controls: hazard ratio (HR) [95% confidence interval (CI)] 1.57 [1.52, 1.63]. Excess cardiovascular risk disproportionally affected women (HR in women: 1.88 [1.75, 2.02], HR in men: 1.50 [1.40, 1.62]), and was highest in the very young (HR in people aged 45 years or less: 2.20 [1.91, 2.54]) (Figure 1). Excess risk was visible across all 12 cardiovascular diseases investigated, and was particularly pronounced for heart failure, arrhythmias, and valve disease (HR for heart failure: 1.84 [1.73, 1.96], HR for atrial fibrillation and flutter: 1.81 [1.72, 1.91], HR for valve diseases: 1.83 [1.71, 1.97]). Patients with gout presented with on average 3 units higher body mass index than matched controls, and had higher prevalence of chronic kidney disease, dyslipidaemia, and hypertension. In sensitivity analyses, adjusting for known cardiovascular risk factors attenuated the strength of the associations by around half, although gout remained an independent CVD risk factor.

Conclusion

Patients with gout present a higher risk of developing a range of cardiovascular outcomes, in particular heart failure, arrhythmias, and valve disease. These findings suggest patients with gout should have formal CV risk assessment, and stronger attention to lifestyle interventions to mitigate future atherosclerotic and cardiorenal risks.Fig1 CVD rates & HRs in gout vs controls
Impact of pemafibrate on lipid profile and insulin resistance in patients with statin-treated coronary artery disease with metabolic syndrome
Authors: Nakamura A , Kagaya Y , Saito H , Kanazawa M , Sato K , Miura M , Kondo M , Endo H
Published: November 2023

Background

Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor α, a vital modulator of lipid and glucose metabolism. We examined the effects of this drug on lipid markers and insulin resistance in patients with metabolic syndrome (MetS).

Methods

In the randomized, crossover PEBE study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks, followed by crossover of another 24-weeks. Forty-six of 60 patients (77%) enrolled in the PEBE study were founded to have MetS. In the present subanalysis, we compared patients with MetS (MetS group, n = 46) and those without MetS (Non-MetS group, n =14). The primary endpoints were changes from baseline in serum TG, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein A-I (Apo A-I) levels, while the secondary endpoint was change in the homeostasis model assessment of insulin resistance (HOMA-IR).

Results

There was a significant decrease in serum TG levels (from 266.6 mg/dL to 148.0 mg/dL in MetS group, p < 0.001; from 203.9 mg/dL to 97.6 mg/dL in Non-MetS group, p < 0.001), but %Change was not significantly different between the two groups (−44.1% vs. −51.6%, p = 0.099). Serum HDL-C and Apo A-I levels significantly increased in both groups, but no significant differences in %Change were found between the two groups (p = 0.591 in HDL-C; p = 0.432 in Apo A-I). HOMA-IR significantly decreased in MetS group (from 4.3 ± 4.0 to 3.1 ± 2.2, p = 0.011) but not in Non-MetS group (from 1.7 ± 1.0 to 1.5 ± 1.0, p = 0.553). %Change in liver enzyme levels was markedly decreased in MetS group than in Non-MetS group (alanine aminotransferase, −25.1% vs. −11.3%, p = 0.027; gamma-glutamyl transferase, −45.8% vs. −36.2%, p = 0.020). Although serum adiponectin levels did not change significantly in both groups, leptin levels significantly decreased in MetS group (from 18.5 ng/mL to 16.6 ng/mL, p = 0.004), but not in Non-MetS group (from 9.2 ng/mL to 9.0 ng/mL, p = 0.917).

Conclusion

Pemafibrate is as efficient in patients with MetS as in patients without MetS in improving the lipid and glucose metabolism. In addition, the use in MetS patients may be more effective in improving liver function and insulin resistance.
Improving statins effectiveness by targeting baseline LDL cholesterol in type 2 diabetes mellitus, a systematic review and meta-analysis
Authors: Soroush N , Nekouei Shahraki M , Mohammadi Jouabadi S , Amiri M , Aribas E , Stricker B , Ahmadizar F
Published: November 2023

Background

Although the guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D), it remains controversial whether their cardiovascular effectiveness depends on baseline LDL-Cholesterol (LDL-C) levels at the start of statin use.

Purpose

To determine whether the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality differ according to baseline LDL-C categories.

Methods

This study was registered in the PROSPERO database (CRD42022374004); and was performed according to the PRISMA statement. Through January 2022, Medline, Embase, and Web of science were systematically searched from inception. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to study if the association between statin use and the risk of all-cause mortality and MACE (a composite of myocardial infarction, hospitalization due to heart failure, stroke, and revascularization events) modified by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) <100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) ≥130 mg/dl (3.37 mmol/l) categories.

Results

A total of 11 cohort studies (n= 408,937 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.67 [95% CI 0.57 to 0.79]) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79]), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels of 130 mg/dl or higher had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29, 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and <100 mg/dl categories were respectively (0.66 [95% CI 0.53 to 0.82]) and (0.83 [95% CI [0.68, 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44, 1.02]). Statin use was associated with reductions in HRs of MACE (0.99 [95%CI, 0.98 to 1.00]; P = 0.11) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses.

Conclusion

The results of this study suggest that the greatest cardiovascular protective effects of statin therapy in patients with T2D are attributable to patients with baseline LDL-C levels of 130 mg/dl or higher in real-life settings of observational studies.
Oral anticoagulant therapy and risk of admission to long-term care in patients with atrial fibrillation: a nationwide cohort study
Authors: Teppo K , Airaksinen K E J , Halminen O , Linna M , Jaakkola J , Haukka J , Putaala J , Mustonen P , Langen V L , Kinnunen J , Hartikainen J , Lehto M
Published: November 2023

Background

The impact of oral anticoagulants (OACs) on outcomes in patients with atrial fibrillation (AF) has been a focus of extensive research in the past decades, but there is a complete paucity of information about their effect on the need of long-term care (LTC) in this aging and multimorbid patient group.

Purpose

To assess the hypothesis that OAC therapy is associated with lower need of LTC in patients with AF.

Methods

The registry-based FinACAF cohort study covers all patients with incident AF from all levels of care in Finland from 2007 to 2018, as well as all their OAC purchases, LTC admissions, and information on previous home care acuity. Incidence rate ratios (IRRs) for admission to any type of LTC were estimated with Poisson regression using Lexis-type data structure based on three time scales: follow-up time from AF diagnosis, calendar year, and age. OAC use was treated as a time-varying variable from first OAC purchase onwards.

Results

We identified 188 752 patients (49.0% female; mean age 71.4 years; mean follow-up 3.6 years) with incident AF without prior LTC, of whom 143 534 (76.0%) initiated OAC therapy and 11 775 (6.2%) were admitted to LTC. OAC therapy was associated with a lower rate of LTC admission (adjusted IRR with 95% CI: 0.79 (0.76-0.82)). The association was most evident among patients over 70 years (Kaplan-Meier curve of survival without LTC in Figure). Warfarin and direct oral anticoagulants (DOACs) were both associated with lower need of LTC. Furthermore, when compared to warfarin, DOACs were associated with a lower LTC admission rate (adjusted IRR with 95% CI: 0.69 (0.61-0.79)). No significant disparities were observed between different DOACs. High age and previous need of home care, as well as dementia, psychiatric disorders, and ischemic stroke were the strongest factors associated with the need of LTC.

Conclusions

In this nationwide cohort of patients with incident AF, OAC therapy, particularly with DOACs, was associated with a substantially lower risk of admission to LTC.Survival without LTC. Age over 70 years.
Effectiveness and safety of bempedoic acid in routine clinical practice: 1-year follow-up snapshot of the MILOS German cohort
Authors: Gouni-Berthold I , Koskinas K , Averna M , Stulnig T , Vanassche T , Blackburn C , Smolnik R , Soronen J , Wenz-Poschl K , Pinto X , Parhofer K
Published: November 2023

Background

Low-density lipoprotein cholesterol (LDL-C) has an established role in the development of atherosclerotic cardiovascular disease. The 2019 ESC/EAS dyslipidaemia guidelines recommended more intensive treatment goals, however, many patients do not reach them. Bempedoic acid (BA) is a first-in-class ATP citrate lyase inhibitor that lowers LDL-C levels. There is limited data on the use of BA and BA + ezetimibe (EZE) fixed-dose combination (FDC) in clinical practice.

Purpose

The purpose of this snapshot of 1-year follow-up data from the MILOS study is to evaluate the effectiveness and safety of BA and its FDC in routine clinical practice in Germany.

Methods

MILOS is a European, prospective, observational, non-interventional study in adult patients with primary hypercholesterolaemia or mixed dyslipidaemia. Patients were recruited from 126 sites in Germany between January 2021 and January 2022, and are followed up for 1–2 years after baseline measurements. Here, we summarise 1-year follow-up data from a snapshot taken on January 13th, 2023.

Results

Of 992 patients enrolled in Germany, 714 had either completed their 1-year follow-up or discontinued the study prematurely, and 524 of these 714 patients attended their 1-year follow-up visit. For this snapshot, 714 patients are used when determining cardiovascular (CV) outcomes and safety endpoints, and 524 patients are used when reporting efficacy data. The overall mean (SD) age of the population (n=524) was 64.7 (10.0) years, and 60.7% were male.

Patients treated with BA/BA+EZE FDC had an overall mean LDL-C level of 2.18 mmol/L (84.1 mg/dL) at 1 year compared with 3.20 mmol/L (123.6 mg/dL) pre-treatment, representing a mean relative LDL-C reduction of 27.3%. Overall, 25.8% (135/524) of patients had reached their LDL-C goal after 1 year of treatment compared with 4.0% (21/524) pre-treatment (Figure 1A and 1B). The overall incidence rate of the composite endpoint of major adverse cardiovascular event (4-component MACE) including CV death, non-fatal myocardial infarction, non-fatal stroke, and coronary revascularisation (n=714) was 3.36%. At 1-year follow-up, 19% (136/714) of patients had an adverse drug reaction (ADR) suspected to be related to BA/BA+EZE FDC, and 0.8% (6/714) had serious ADRs, as deemed by the investigator.

Conclusion

This snapshot analysis of 1-year follow-up data suggests that the addition of BA to other lipid-lowering therapies increases the proportion of patients at LDL-C goal by ∼6-fold in the observed cohort. The safety and tolerability profile of bempedoic acid are in line with data from randomised controlled trials.
The renal outcome post contrast exposure in patient with diabetes and SGLT2 inhibitor
Authors: Chen C , Yi-Cheng Lin Y C L , Chih-Chin Kao C C K , Chun-Yao Huang C Y H
Published: November 2023

Introduction

Contrast-induced nephropathy (CIN) is increasingly prevalent as the increased age and comorbidities. Though most CIN can be reversible, some may progress to acute kidney disease (AKD) and subsequent chronic kidney disease (CKD)1-3. Sodium–glucose cotransporter-2 (2SGLT) inhibitor has been known to bring better renal outcomes 4-7. However, whether it affect contrast-induced kidney injury is not known well. we

Purpose

We aimed to investigate the renal outcomes post-contrast exposure in patients with diabetes and SGLT2 inhibitor.

Materials and methods

We used the Taipei Medical University Clinical Research Database (TMUCRD), composed of clinical data from 3 teaching hospitals. which stores electronic health data of 3 million patients. Patients with diabetes and exposure to contrast in CT-imaging studies or catheter-based angiography from 2016 to 2020 were included. The primary outcome was major kidney adverse event (MAKE), which included acute kidney disease (AKD), chronic kidney disease (CKD), renal replacement therapy (RRT), new onset of urinary albumin-creatinine ratio (uACR), eGFR decline ≥ 40% and all-cause mortality. We used overlap weighting to reduce confounding factors, as in observational studies.

Results

A total of 12,421 patients were included in this study, of them, 920 and 11501 patients were categorized to SGLT2 inhibitor users and non SGLT2 inhibitor users, respectively. SGLT2 inhibitor user had lower MAKE risk as compared with non-SGLT2 inhibitor i user (incidence rate: 37.9 v.s. 53.4 per 1,000 person months, P value = 0.0002) after exposure to contrast media. The incidence rate of AKD, CKD, and eGFR decline ≥ 40% were significantly lower in SGLT2 inhibitor user. However, there were no significantly different in the risk of RRT, new onset of uACR or all-cause mortality.

Conclusions

In this retrospective cohort study, we found that SGLT2 inhibitor user was associated with lower MAKE comparing with non-SGLT2 inhibitor user after contrast exposure in patients with diabetes.Outcomes of DM patients with PCI or contKaplan-Meier plot of major adverse kidne
Empagliflozin suppresses the differentiation/maturation of human epicardial preadipocytes and improves paracrine secretome profile
Authors: Kondo H , Takano M , Miyamoto S , Takahashi N
Published: November 2023

Aims

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the epicardial adipose tissue (EAT) in human, which could enhance the cardioprotective effect in heart failure and atrial fibrillation. However, the precise mechanism of EAT reduction remains unclear. We investigated the direct effect of SGLT2 inhibitor, empagliflozin, on human primary epicardial adipocyte and preadipocyte.

Methods and Results

In Arm1, human EAT biopsies obtained during surgery and isolated preadipocyte/adipocytes were used for evaluating SGLT2 expression. In Arm2 and Arm3, we investigated the direct effect of empagliflozin on the differentiation/maturation and secretome profile of human preadipocyte/adipocyte. We validated the effect of empagliflozin on paracrine effect of EAT using co-culture with human iPS-derived atrial cardiomyocytes and empagliflozin-treated human epicardial adipocyte in Arm4. The validity of findings obtained from Arm1-4 were verified in view of clinical perspective in Arm5 and Arm6. SGLT2 was mainly expressed in the human pre-adipocyte in EAT. The expression levels of SGLT2 significantly diminished when the pre-adipocyte terminally differentiated. The formation of lipid droplets and fatty acid binding protein 4 (FABP4) expression in adipocyte were attenuated by empagliflozin treatment without affecting cell proliferation. mRNA levels of IL1α, IL1β, IL6, TGFβ and MCP1 in empagliflozin-treated adipocyte were significantly decreased. Of these, secreted protein levels of IL6 and MCP1 were significantly downregulated in supernatant of empagliflozin-treated cells. Co-culture of human iPS-derived atrial cardiomyocytes and adipocyte pre-treated with or without empagliflozin revealed that empagliflozin had striking suppressive effects on myocardial oxidative stress. Only IL6 mRNA expression in human EAT showed the clinically relevant association in terms of the difference of AF prevalence, anti-diabetic drug and N-terminal pro-brain natriuretic peptide.

Conclusions

We demonstrated that empagliflozin suppresses human epicardial pre-adipocyte differentiation/maturation, possibly leading to the reduction of EAT volume, and improves paracrine secretome profile of EAT. IL6 might be a key adipokine regulated by SGLT2 inhibitors.
Factor XI inhibitors in early clinical trials: a meta-analysis
Authors: Galli M , Laborante R , Ortega-Paz L , Franchi F , Rollini F , D'amario D , Capodanno D , Tremoli E , Gibson C M , Mehran R , Angiolillo D J
Published: November 2023

Background

Phase II randomized controlled trials (RCTs) on factor(F)XI inhibitors have shown promising results but they were burdened by low statistical power for clinical outcomes.

Methods

We performed a systematic review and meta-analysis of RCT comparing FXI inhibitors versus other anticoagulants (enoxaparin or direct oral anticoagulants, DOACs) or versus placebo on top of antiplatelet therapy.

Results

Eight RCTs testing FXI inhibitors (ISIS 416858, osocimab, abelacimab, milvexian, asundexian) and enrolling 9,216 patients were included. Compared with enoxaparin, FXI inhibitors were associated with reduced any-bleeding (RR 0.49, 95% CI 0.31-0.77), no difference in major bleeding (RR 0.96, 95% CI 0.41-2.28) and reduced trial-defined efficacy endpoint (RR 0.62, 95% CI 0.49-0.79), the latter driven by the high dose regimens. Compared with DOACs, FXI inhibitors were associated with a trend towards reduced any-bleeding (RR 0.66, 95% CI 0.31-1.38) and no difference in major bleeding (RR 1.03, 95% CI 0.22-4.78) or in trial-defined efficacy endpoint (RR 1.23, 95% CI 0.88-1.70). Compared with placebo, FXI inhibitors were associated with increased any-bleeding (RR 1.25, 95% CI 1.08-1.43) and a trend towards increased major bleeding (RR 1.21, 95% CI 0.75-1.93), both driven by high dose regimens, with no difference in trial-defined efficacy endpoint (RR 1.02, 95% CI 0.92-1.13).

Conclusions

Results of this meta-analysis on FXI inhibitors suggest increased safety and efficacy compared with enoxaparin and modest increased safety compared with DOACs. The use of FXI inhibitors in adjunct to antiplatelet therapy versus placebo appears to be associated with a dose-dependent increase in bleeding without any difference in efficacy.
Mortality with bivalirudin plus a high-dose infusion versus heparin in patients with acute coronary syndrome
Authors: Galli M , Gargiulo G , Benenati S , Mehran R , Angiolillo D J
Published: November 2023

Background

The use of bivalirudin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has been downgraded by recent international guidelines. The reason for this downgrade lies above all on the excess of acute stent thrombosis (ST) associated with bivalirudin, but subsequent studies have suggested that a post-PCI high-dose bivalirudin infusion may mitigate the risk of acute ST related to the short half-life of bivalirudin.

Methods

We performed an updated meta-analysis of RCTs comparing bivalirudin followed by a post-PCI high-dose infusion versus UFH in ACS. Four RCTs accounting for a total of 16,920 patients were included. Odds ratios (OR) with 95% confidence intervals (CIs) using random effect models were calculated. Number needed to treat (NNT) were also calculated. Clinical outcomes at 30 days were included in the analysis.

Results

Four RCTs accounting for a total of 16,920 patients were included. We found that bivalirudin is associated with a non-significant reduction of 30-day all-cause death (OR 0.81, 95% CI 0.56-1.16, NNT 250, I2 53%), compared with UFH. Results were consistent at a subgroup analysis of STE-ACS versus NSTE-ACS and in a sensitivity analysis excluding the VALIDATE-SWEDEHEART, the only study using a shorter post-PCI bivalirudin infusion (mean 57 min) that was not used in the totality of patients (65%). Moreover, bivalirudin followed by a high-dose infusion was associated with a significant reduction of net adverse clinical events (NACE) (OR 0.62, 95% CI 0.42-0.90, NNT 31, I2 87%) as defined in each trial and of ST (OR 0.47, 95% CI 0.31-0.71, NNT 200, I2 1%), compared with UFH. Finally, BARC 3-5 bleeding was non-significantly reduced (OR 0.36, 95% CI 0.12-1.02, NNT 143, I2 82%) with bivalirudin compared with UFH.

Conclusion

We conclude that bivalirudin followed by a high-dose infusion is associated with reduced ST and NACE compared with UFH, but whether it may reduce all-cause mortality requires further investigations.