bluuebunny/crossref_metadata_2025_split huggingface dataset:
High discontinuation rate of statins among PCSK9i users: a nationwide study from 2015-2023
Authors: Engebretsen I , Oedegaard K , Halvorsen S , Bugge C , Kristiansen I , Stoevring H , Munkhaugen J 
Published: October 2024

Abstract

Background
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are recommended as additional lipid-lowering drug treatment for high-risk patients if the low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statins and ezetimibe alone. Nationwide data from clinical practice on the use of PCSK9i are lacking. In 2015, PCSK9i became available in Norway with reimbursement restricted to patients with familial hypercholesterolemia (FH) and/or atherosclerotic cardiovascular disease (ASCVD) with LDL-C above certain levels.

Purpose
To investigate the use and adherence of lipid lowering drugs among a nationwide cohort of PCSK9i users, utlizing complete pharmacy dispensation data.

Methods
Information on all PCSK9i users ≤80 years with at least one year of follow-up after the first dispensation were extracted from the Norwegian Prescribed Drug Registry. We evaluated adherence to PCSK9i by calculating the proportion of days covered (PDC) during the initial year of PCSK9i therapy. Poor adherence was defined as PDC &lt;80%, and discontinuation was defined as a gap in treatment ≥180 days during the follow-up period. We analyzed treatment patterns of statins and ezetimibe during the 1-year period before and after PCSK9i initiation by determining the proportion of patients with at least one dispensation of statin and/or ezetimibe treatment.

Results
A total of 2,997 PCSK9i users were identified. Median age at treatment initiation was 62 (IQR: 13) years and 43% were female. Non-adherence to PCSK9i was observed in 16% of the patients, and 18% discontinued treatment (Table). Non-adherence to PCSK9i was more prevalent in females, and in the lowest and highest age quartiles. No significant difference in non-adherence was found among patients with ASCVD compared to patients with FH. In the year preceding PCSK9i initiation, 74% of patients used statins (including combinations with ezetimibe), 11% used ezetimibe monotherapy, and 15% did not use any statin or ezetimibe treatment (Figure). During the year following PCSK9i initiation, 35% used statins (including combinations), 17% used ezetimibe monotherapy, and 48% did not use any statin or ezetimibe treatment. Among patients with ASCVD, 72% used statins prior to PCSK9i initiation, and 22% used statins after. Among patients with FH, 77% used statins prior to PCSK9i initiation, while 51% used statins after.

Conclusion
In this nationwide study of incident PCSK9i users, we observed a substantial decrease in usage of statins and ezetimibe following PCSK9i initiation. Further, almost 1 in 5 patients discontinued treatment with PCSK9i. There is a large potential for optimizing treatment and adherence to PCSK9i and conventional lipid-lowering drugs among Norwegian patients with ASCVD and familial hypercholesterolemia.Adherence and discontinuation to PCSK9iUse of statin and ezetimibe
Lipid goal attainment across baseline socioeconomic and clinical factors comparing an "inclisiran first" implementation strategy and usual care: subgroup analysis of VICTORION-INITIATE
Authors: Koren M , Rodriguez F , Toth P P , Ali Y , Kleeman K , Sarwat S , Abbas C , East C 
Published: October 2024

Abstract

Background
Addressing inequities in cardiovascular care has become a public health priority. Recent results from VICTORION-INITIATE, a pragmatically designed, randomised clinical trial showed the benefit of using inclisiran immediately if patients with atherosclerotic cardiovascular disease (ASCVD) fail to achieve low-density lipoprotein cholesterol (LDL-C) &lt;70 mg/dL (1.8 mmol/L) on maximally tolerated statins.

Purpose
To evaluate effectiveness and safety of an "inclisiran first" implementation strategy (IF) versus usual care (UC) in subgroups that may be associated with healthcare inequities.

Methods
VICTORION-INITIATE was conducted at 45 representative clinical settings across 20 states in the USA. Patients with ASCVD randomised 1:1 (stratified by insurance status) received open-label inclisiran 284 mg at Days 0, 90 and 270) plus UC or UC alone (lipid management directed by treating physicians). Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per lipid guidelines. We compared efficacy and safety endpoints for IF and UC in prespecified subgroups (race, ethnicity, sex, renal function and statin intensity) and by income level (post-hoc analysis).

Results
The study randomised 450 patients. Baseline demographic and clinical parameters were balanced between study arms (≥65 years of age: IF: 63.1%, UC: 61.3%; non-White: IF: 15.6%, UC: 15.1%; Hispanic: IF: 13.8%, UC: 16.9%; female: IF: 29.8%, UC: 32.0%; income ≤$50,000: IF: 58.7%, UC: 58.2%; estimated glomerular filtration rate ≥30 to &lt;60 mL/min/1.73m2: IF: 20.0%, UC: 17.8%; no statins at baseline: IF: 9.8%; UC: 10.2%). Across all subgroups, more patients achieved LDL-C goals at Day 330 with IF vs UC (Figure 1). Within the UC arm, the proportions of patients achieving LDL-C &lt;70 mg/dL and &lt;55 mg/dL, respectively, were numerically lower for non-White (8.8% and 2.9%) and Hispanic (10.5% and 2.6%) than White (24.6% and 10.2%) and non-Hispanic (24.9% and 10.3%) patients. We did not observe differences in LDL-C goal attainment for these subgroups in patients receiving IF. Compared with UC, IF resulted in greater mean percentage change in other lipids and lipoproteins from baseline to Day 330, irrespective of subgroup (Figure 2). Incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs compared similarly between IF and UC for each subgroup (IF: 35.5−69.2%, UC: 34.2−84.2%, and IF: 3.2−16.9%, UC: 0.0−36.8%, respectively).

Conclusions
VICTORION-INITIATE enrolled a diverse population reflective of "real-world" US clinical practice. The IF strategy consistently resulted in higher rates of LDL-C goal attainment for all subgroups studied and did not lead to differences in lipid outcomes by race or ethnicity as compared to usual care. No additional safety concerns for the IF strategy were identified.
Trajectories of weight and their impact on cardiac remodeling and function 16 years after bariatric surgery
Authors: Piche M , Tremblay X , Blais M , Premont C , Mathieu M A , Auclair A , Pettigrew M , Marin-Couture E , Lajeunesse-Trempe F , Marceau S , Poirier P 
Published: October 2024

Abstract

Introduction
Obesity is a major risk factor for heart failure, particularly heart failure with preserved left ventricular (LV) ejection fraction. Surgical treatment of obesity have significant beneficial short-term effects on weight loss and on cardiac function; its long-term impact on cardiac remodeling and function remains largely unknown.

Purpose
We examine the long-term effect of bariatric surgery on cardiac remodeling and function in adults with preserved LV ejection fraction.

Methods
Forty-four individuals with severe obesity [body mass index (BMI) ≥35kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) were included. Anthropometric measurements and echocardiography were obtained at baseline, 12 months and 16 years follow-up.

Results
Mean age of participants (71% female) was 44 ± 8 years and body mass index (BMI) 49.6 ± 6.1 kg/m2. Bariatric surgery led to marked weight reduction and significant improvements in obesity-related metabolic conditions/comorbidities (hypertension, dyslipidemia, type 2 diabetes). Mean percentage of weight loss at 12 months was 37.1 ± 7.0 %. Percentage of weight regain at 16 years averaged 8.9 ± 35.0 %. Bariatric surgery was associated with a significant reduction in indexed LV mass and LV hypertrophy (p &lt;0.01), and improvement in LV diastolic function parameters (p &lt;0.01) at 12 months. In many participants, cardiac remodeling parameters deteriorated at 16 years follow-up compared to the echocardiographic measurements taken at 12 months post-surgery. Prevalence of LV diastolic dysfunction increased at 16 years (81 vs. 38%; p&lt;0.001), even after adjusting for age. Weight regain at 16 years (regaining &gt;10% of weight lost; n=25; 57%) was not found to be associated with a worsening in cardiac remodeling compared to those who maintained weight loss, except for indexed LV mass (-9.3 ± 10.6 vs. -5.5 ± 7.8 g/m2.7; p=0.04) and LV end-diastolic diameter (-5.4 ± 4.0 vs. -3.5 ± 3.3 cm; p=0.01).

Conclusion
Bariatric surgery (BPD-DS) leads to durable long-term weight loss. Weight regain following bariatric surgery does not appear to have adverse effect on cardiac remodeling and function. Surgical treatment of obesity may be an effective and safe way to prevent clinical cardiac dysfunction and heart failure related to obesity.
Left atrial volume in obesity and hypertension: an innovative "ideal human" index allows for weighing their impact - a non-contrast cardiac CT study
Authors: Sosnowski M , Harpula J , Dobrolinska M , Parma Z , Mlynarski R , Wojakowski W 
Published: October 2024

Abstract
Left atrial (LA) enlargement is a common and early feature of cardiac involvement in the natural history of obesity and arterial hypertension (AH). Mechanisms involved in this process are cumulative, and partly shared, thus separating and balancing their contributions is challenging. In a proportion of patients referred for coronary artery calcium (CAC) scoring, these clinical entities are present. The LA volume (LAV) is relatively easy to quantify from a CT scan. Measured LAV values can be misleading unless constitutional parameters (height (h) or body size area (BSA), are considered. We introduced a new indexing parameter, consisting of height and the difference between numerical values of height and BSA. In the "ideal human", the difference is zero. Any deviation from this value determines the share of body mass regardless of height.

Aim
We hypothesize that a novel indexation approach allows for earlier detection of the increased LAV in normotensive and AH patients considering the body mass index.

Method
We retrospectively analyzed CT data from 2535 patients, 1658 w (64±10 ys), and 876 m (aged 6±11ys), with CAC scoring over the last 15 years The LAV was determined by using commercially available software. The raw and indexed (for h, BSA, and the novel parameter [h+ (h-BSA)]) LAV volumes were compared in patients with normal BMI (&lt;25kg/msg), overweight (25-29.9), and obesity (≥30) who with normal blood pressure or with AH.

Results
The LAV was larger in high BMI categories than in normal BMI. In non-AH subjects, the LAV increased from an average of 71 ml (normal) to 80 ml (overweight) and 90 ml (obese). In AH, the LAV increase showed a similar trend of averages (77, 88, 94 ml, F=2.59,p&lt;0.01). Indexing LAVs were non-concordant, as shown in Figure. Thus, one can recognize that LAV normalization for the new index has brought the differences most evident and persuasive. In normal BMI, indexation ways did not significantly affect the LAV estimation. Whilst the body weight increased, no difference could be recognized for values indexing for BSA (red). The LAV indexation for height (blue) cannot help diagnose its increase in obesity. The distinguishing strength can be seen while using the [h-(h-BSA)] denominator (green). It indicates that in any scenario, body mass gain plays a greater role in the LAV increase than AH does.

Conclusions
Body mass is a more important factor that is associated with LAV than AH.. Common methods of LAV indexing, especially referred to as BSA, introduce errors leading to values mimicking normality in non-healthy people and should be forbidden. The proposed indexation way can help overcome the observed discrepancies and support early recognition of the consequences of obesity and hypertension.
Obesity paradox, weight-free anthropometric measures, and major adverse cardiovascular events in the elderly: Insight from the Northern Shanghai Study
Authors: Xu C , Zhao S , Zhang Y 
Published: October 2024

Abstract

Aims
Many studies have investigated the obesity paradox in the elderly. However, besides body mass index (BMI), many other anthropometric measures, such as the waist-to-hip ratio (WHR), provide a better indication of body fat distribution and may be more useful in a geriatric population.

Methods
3285 participants aged over 65 years old from the Northern Shanghai Study were included in this analysis. Eight anthropometric measures, including weight-related measures (BMI, weight-adjusted-waist index, body shape index and body surface area) and weight-free measures (WHR, waist-to-height ratio, body roundness index, relative fat mass) were measured and calculated with standard methods. Major adverse cardiovascular events (MACEs) included the non-fatal myocardial infarction, non-fatal stroke or cardiovascular death.

Results
Participants had an average age of 71.4 years and 1428 (43.47%) were men. The median follow-up was 5.4 years (IQR, 4.4-7.3 years) and 218 events occurred. Participants with obesity (BMI ≥ 28 kg/m2) were associated with a higher risk of MACEs compared with the normal (adjusted Hazard ratio = 1.54, 95% confidence interval (CI): 1.07-2.22, P=0.020). Restricted cubic splines also highlighted the robust correlation between high BMI and high MACEs risk (Pfor overall=0.025, Pfor nonlinear=0.339). Similarly, the aHR for the incidence of MACEs in WHR quartile 4 versus quartile 1 was 1.96 (95% CI: 1.26-3.05, P=0.003). When WHR was examined as a continuous variable, the result remained unaltered (Pfor overall=0.020, Pfor nonlinear=0.353). In adjusted model, all four weight-free measures were significantly associated with increased risk of MACEs (all P&lt;0.05), while only two weight-related measures were related to the risk of MACEs.

Conclusion
In the elderly, BMI and alternative anthropometric measures showed no evidence of an "obesity paradox". Weight-free measures were more relevant to a risk of MACEs.Take home message
Long-term changes in cardiac geometry and mechanics after bariatric surgery- insights from the FatWest study
Authors: Grymyr L M D , Gerdts E , Nadirpour S , Nedreboe B G , Cramariuc D 
Published: October 2024

Abstract

Background
Patients with severe obesity have a high prevalence of subclinical cardiac organ damage including impaired longitudinal and radial cardiac mechanics. Previous studies on the impact of bariatric surgery on cardiac remodeling, most of them with short patient follow-up, have yielded inconsistent results.

Purpose
To assess progressive changes in cardiac geometry and mechanics up to five years following bariatric surgery.

Methods
In the prospective Bariatric Surgery on the West Coast of Norway (FatWest) study, cardiac remodeling was assessed by 2D echocardiography preoperatively and at six months, one year and five years after Roux-en-Y gastric bypass in a cohort of 97 patients (44±10 years, 72% women, body mass index [BMI] 41.8±4.8 kg/m²). Excess weight loss (EWL) was calculated as: absolute weight loss/(initial weight-ideal weight)x100. Left ventricular (LV) size was assessed by the LV mass/ height^2.7, LV longitudinal mechanics by the peak global longitudinal strain (GLS) and radial mechanics by the midwall shortening (MWS). LV myocardial oxygen demand was estimated from the LV mass-wall stress-heart rate product. Right ventricular diameter was measured in the basal one-third of the ventricular cavity. Left atrial (LA) reservoir function was assessed by the LA emptying fraction.

Results
After a mean follow-up of 63±13 months, the average postoperative EWL was 66%. Overall, both right ventricular diameter, LV mass index, LV GLS, myocardial oxygen demand and LAEF (68% vs. 64%) improved significantly at the 5-year follow-up (all p&lt;0.05), while MWS remained unchanged (Figure). Prevalence of normal LV geometry increased gradually from 56% to 80%, while that of LV hypertrophy fell from 36% to 16% (p&lt;0.001). Analyses of temporal trends showed that improvement in BMI, LV mass and LV GLS occurred during the first postoperative year (Figure).
In Cox regression analysis, a low 5-year GLS was associated with preoperative hypertension after adjustment for age, sex, preoperative diabetes mellitus, and postoperative changes in BMI, mean blood pressure and myocardial oxygen demand (p&lt;0.01). In a similar linear model, after adjustment for the same covariates, LV mass index at the 5-year follow-up was independently related to the magnitude of the postoperative BMI reduction (R² = 0.58, p&lt;0.001).

Conclusion
Ventricular size and longitudinal mechanics are significantly improved 5 years after bariatric surgery, with the reverse remodeling occurring during the first postoperative year. Residual abnormal 5-year LV geometry and mechanics are related to preoperative hypertension and suboptimal BMI reduction.Figure
Sex-biased proteomic regulation in obesity
Authors: Halland H , Vitorino R , Gerdts E , Meyer K , Kararigas G 
Published: October 2024

Abstract

Background
Obesity is a major risk factor for heart failure with preserved ejection fraction, particularly in women. Obesity-associated inflammation is thought to contribute to this relationship. However, the role of biological sex in the regulation of circulating inflammatory proteins in obesity is not well understood.

Purpose
We aimed to explore sex differences in the plasma inflammatory protein profile in obese subjects.

Methods
Clinical data and samples were collected from 450 women and men with a body mass index (BMI) &gt;27 kg/m² without known cardiovascular disease participating in the FAT associated CardiOvasculaR dysfunction study. Obesity was defined as BMI≥30 kg/m². Olink’s Target 96 inflammation panel, which profiles 92 proteins using proximity extension assay technology, was analysed in biobank samples. A comprehensive correlation analysis was performed to describe relationships between protein biomarkers and clinical variables. Gene enrichment analysis was performed to shed light on biological pathways associated with differentially expressed proteins (DEPs). To determine the functional significance of the DEPs, we used the repositories Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Pearson correlation coefficients were calculated to assess linear associations between the DEPs and relevant clinical variables.

Results
Women and men did not differ by age (49±9 vs 48±9 years), BMI (32.3±4.6 vs 31.6±3.7 kg/m²) or in prevalences of diabetes (both 11%) or obesity (65% vs 62%) (all p&gt;0.05). However, hypertension was more common in men than women (74% vs 52%, p&lt;0.001). In men (n=188), obesity was associated with downregulation of monocyte chemotactic protein 3, tumor necrosis factor (ligand) superfamily member 12, interleukin 10 and protein S100-A12 and with upregulation of neurotrophin-3 (all p&lt;0.05), thereby suggesting a mechanism for the observed impaired inflammatory response and insulin resistance. In women (n=262), obesity was associated with the downregulation of interleukin 7, interleukin 12 subunit beta, interleukin 6, and C-X-C motif chemokine 11, suggesting a state of persistent low-grade inflammation. In addition, the upregulated sulfotransferase 1A1 and SIR2-like protein 2 proteins indicate a physiologic adaptation to oxidative stress and the metabolic excess endemic to obesity.

Conclusion
We found that the abundance of several circulating inflammatory proteins was altered in presence of obesity, and that the plasma proteomic profile differed by sex. Interestingly, there was no overlap in the DEPs between women and men in the presence of obesity. These findings support the hypothesis that the pathophysiological mechanisms driving obesity-associated inflammation and immune dysregulation differ by sex. In turn, this may aid in the pursuit of discovering sex-specific biomarkers to identify obese individuals at particular risk of heart failure.
HFpEF and glycemic variability: GHIDD Trial
Authors: Fazio G 
Published: October 2024

Abstract

Background
Recently the guidelines of European Association of Preventive Cardiology reported that the prevalence of diabetes mellitus in patients with diastolic heart failure (HFpEF) is around 31%. Glunovo® is a transdermal device capable of detecting and storing the concentration of glucose in the abdominal interstitial fluid 480 times a day for up to 14 consecutive days.

Purpose
In our study we evaluated the non diabetic patients with HFpEF with Glunovo to evaluate the glycaemic variability in this population

Methods
100 patients with HFpEF admitted to cardiology units of 4 Italian centres on the major islands were enrolled consecutively. Glunovo® was applied to each enrolled patient for 7 days. At the end of the glycaemic monitoring were calculated for each patient the glycaemic variability and the incidence of hyperglycaemia and hypoglycaemia. Glycaemic variability refers to a blood glucose value of ≥ 200 mg / dL or ≤ 59 mg / dL detected more than 3 times in a day for at least 4 days. The inclusion criterion was the presence of diastolic heart failure while the only exclusion criterion was the presence of diabetes diagnosis. Overall, 43 males and 57 females were enrolled with a mean age of 69.3 years (39-87 years). All patients underwent a timely glucose measurement at admission which excluded the presence of hyperglycaemia. No potentially hyperglycaemic drugs were added to the treatment during the hospital stay. Continuous glucose monitoring was performed as an integral part of the hospitalization diagnostic routine.

Results
In 94 of the 100 patients enrolled it was possible to conclude the analysis, detecting the glycaemic variability, the point glycaemia values and the estimated glycated haemoglobin value. A glycaemia ≥200 mg/dL was found in 53 patients (56%) while a high glycaemic variability was found in 51 patients (54%). A blood glucose value &lt;59 mg / dl was found in 48 patients (51%). Only 5 times the estimated glycated Hb values were&gt; 7%. 32 of the patients who had at least 3 punctual glucose values ≥200 mg/dL were prescribed an oral glucose load curve, which in 100% of cases confirmed the diagnosis of diabetes.No statistically significant differences were found based on age group or sex. In the control group, consisting of 10 patients without DHF undergoing continuous glucose monitoring at one of the participating cardiology units, an unknown hyperglycaemia was found in only 1 patient (10%) and a glycaemic variability in only 1 patient (10%).

Conclusions
Our experience suggests an incidence of hyperglycaemia and glycaemic variability more then 65% in patients affected by HFpEF. If our data were reproducible on a large scale, a so high prevalence of diabetes in patients with HFpEF cold explain the efficacy of SGLT-2 inhibitor and GLP-1 Agonist in this class of patients.