bluuebunny/crossref_metadata_2025_split huggingface dataset:
Composition of non-HDL cholesterol and residual cardiovascular risk in secondary prevention
Authors: Hansen M K , Olesen K K W , Thrane P G , Gyldenkerne C , Stoedkilde-Joergensen N , Andersen M H , Maeng M , Mortensen M B 
Published: October 2024

Abstract

Background
Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction.

Purpose
To examine ASCVD risk by composition of non-HDL-C.

Methods
Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides &gt;4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022.

Results
The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups.

Conclusions
The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2
Subgroup analysis of diabetes in COVID-positive revascularized patients: implications for clinical management
Authors: Musayev O , Dashdemirov R , Ibrahimov F , Musayev K , Dadashova G , Gardashova E , Alimli Z , Gasimzade S , Mushtagzadeh N , Aliyeva F 
Published: October 2024

Abstract

Background
The management of revascularized patients with COVID-19, particularly in the presence of diabetes mellitus (DM), presents significant challenges. Understanding the clinical outcomes in this subgroup is essential for optimizing patient care during the pandemic.

Purpose
This study aimed to investigate the clinical outcomes of revascularized COVID-positive patients with and without DM, focusing on revascularization methods, hospitalization rates, mechanical ventilation requirement, mortality, stroke incidence, and presentation of acute coronary syndrome (ACS) subtypes.

Methods
A retrospective analysis was conducted on the cohort of 620 COVID-positive revascularized patients. Among them, 267 patients had diabetes mellitus (DM), while 353 patients did not. Data on revascularization methods, hospitalization rates, mechanical ventilation requirement, mortality, stroke incidence, and ACS presentation were collected and compared between the two groups. Statistical analysis was performed to assess the significance of differences observed.

Results
Among the 620 COVID-positive revascularized patients, 267 (43.1%) had diabetes mellitus, while 353 (56.9%) did not. Demographic analysis revealed that 299 (84.7%) of the COVID-positive patients with diabetes mellitus were male, compared to 181 (67.8%) of those without diabetes mellitus. This difference in gender distribution between the two groups was statistically significant (p &lt; 0.001). Additionally, smoking was more prevalent among COVID-positive patients without diabetes mellitus (38.8%) compared to those with diabetes mellitus (22.5%), with a significant difference observed (p &lt; 0.001) (Table 1). Among the revascularized patients, a higher proportion of patients with diabetes mellitus underwent coronary artery bypass grafting (CABG) compared to those without DM (32.6% vs. 24.1%, p = 0.019). Patients with diabetes exhibited significantly higher hospitalization rates (27.0% vs. 15.6%, p = 0.001) and a trend towards increased mechanical ventilation requirement (11.1% vs. 3.6%, p = 0.121). However, mortality rates, stroke incidence, and ACS presentation did not significantly differ between the two groups (Table2).

Conclusion
This study underscores the heightened vulnerability of revascularized COVID-positive patients with DM, as evidenced by higher hospitalization rates and a trend towards increased mechanical ventilation requirement. These findings emphasize the importance of tailored management strategies for this high-risk subgroup to optimize patient outcomes during the ongoing COVID-19 pandemic.Table 1Table 2
Is the obesity paradox leading to a less stringent secondary prevention strategy in post-acute coronary syndrome patients?
Authors: Moreira M , Frias D , Schmidt C , Alves Dias V , Magalhaes S , Santos M , Torres S 
Published: October 2024

Abstract

Introduction
Patients with acute coronary syndrome (ACS) are at very high risk of recurrent cardiovascular (CV) events. Despite being a major CV risk factor, obesity was associated with best survival in patients with ACS, the so-called "obesity paradox". It is uncertain if this finding is leading to a less stringent secondary prevention strategy in this group of patients, and whether it influences prognosis.

Purpose
To analyze the impact of obesity on outcomes after ACS and on other CV risk factor management.

Methods
Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 cardiac rehabilitation (CR) program in 2017, with a follow-up of 24 months. Patients were classified in 2 groups according to body mass index (BMI) at baseline: Group 1 (G1) were obese patients (BMI≥30 kg/m2), and Group 2 (G2) were non-obese patients (BMI&lt;30kg/m2). Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization.

Results
198 patients were included (mean age of 60.3±10.7 years, 82% male) with a mean BMI of 27.7±4.2 kg/m2. Forty-seven patients (23.7%) had a BMI≥30 kg/m2. Patients in G1 were more likely to have hypertension (79% vs 55%; p=0.003) and diabetes (36% vs 20%; p=0.022). CR program was associated with smoking cessation, significant BMI (G1: -0.69 (95%CI: -0.40 to -0.10); G2: -0.39 (95%CI: -0.20 to -0.57) and LDL-Cholesterol (LDL-C) reduction (G1: -38 (95%CI: -25 to -50); G2: -29 (95%CI: -22 to -36), and functional capacity improvement (G1: +1.2 METs (95%CI: +0.9 to +1.5); G2: +1.1 METs (95%CI: +1.0 to +1.4) in both groups at 3 months, with similar magnitude of improvement. At 24 months, BMI had returned to baseline values in both groups, while the improvement in smoking status, LDL-C and functional capacity persisted. At 24 months, MACE occurrence was numerically increased in obese group (G1: 26.1% vs. G2: 17.2%, p=0.182), with a statistically significant higher incidence of non-fatal recurrent ACS in G1 (17% vs. 7.3%, p=0.048).

Conclusions
ACS patients with obesity have worse prognosis, despite the similar improvement in CV risk profile. Our data also suggests that, despite the short-term improvement in BMI, current treatment strategies are not effective at achieving a persistent weight control over 24-months.
Improvement of myocardial lipolysis in iodine-123-beta-methyl-P-iodophenyl-pentadecanoic acid scintigraphy in patients with idiopathic triglyceride deposit cardiomyovasculopathy treated with Tricaprin
Authors: Ono R , Miyauchi H , Iimori T , Hirano K , Kobayashi Y 
Published: October 2024

Abstract

Background
Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare intractable cardiovascular disorder (Orphanet ORPHAcode: 565612) in which defective intracellular lipolysis results in heart failure and coronary artery disease. Myocardial scintigraphy with iodine-123-β-methyl-P-iodophenyl-pentadecanoic acid (BMIPP) is useful for evaluating myocardial TG metabolism and its washout rate (WR) reflects myocardial lipolysis. A decreased WR (&lt;10%) of BMIPP is one of the diagnostic criteria for TGCV. CNT-01, the active ingredient of which is tricaprin, a medium-chain triglyceride, has the potential to facilitate myocardial lipolysis in a mouse model. However, the effects of CNT-01 (tricaprin) on BMIPP scintigraphy in patients with TGCV remain unclear.

Purpose
To evaluate the effects of CNT-01 on BMIPP-WR in patients with TGCV.

Methods
An investigator-initiated, randomized, double-blind exploratory trial (Phase IIa) was conducted. Ten patients with idiopathic TGCV in our hospital were enrolled and orally administered 1.5 g/day of CNT-01 or placebo for 8 weeks. The endpoint was the delta WR on BMIPP scintigraphy. All the participants underwent BMIPP scintigraphy after overnight fasting. Following the protocol recommended by the Japanese Society of Nuclear Cardiology, 111 MBq of BMIPP was intravenously injected at rest after fasting for ≥ 12 h. Early and delayed images were obtained after 20 and 180–210 min, respectively. BMIPP scintigraphy at baseline and 8-week was performed using the same SPECT apparatus. WR is defined as the ratio of the difference between the counts in the early image and time-decay-corrected delayed image divided by the former. We used a recently proposed algorithm for calculating the WR based on the total count and analyzed the WRs (Ann Nucl Cardiol. 2023;9(1):19-25).

Results
A total of 5 patients were assigned to placebo and 5 patients were assigned to CNT-01. During the protocol, delta BMIPP-WRs were -6.18 ± 4.43 and 5.44 ± 2.57 % (95% confidence intervals, -12.33 to -0.03 and 1.88 to 9.00) in the placebo and CNT-01 groups, respectively. The baseline-adjusted difference in delta BMIPP-WR between the two groups was significant (p=0.005) (Picture). No significant changes were observed in clinical parameters.

Conclusion
This study demonstrated that CNT-01 improved myocardial lipolysis in patients with TGCV as measured by BMIPP scintigraphy.
Efficacy of combination therapy with statin and ezetimibe versus high dose statin monotherapy in secondary prevention in high-risk patients
Authors: Halatiu V B , Benedek I , Rodean I P , Benedek T 
Published: October 2024

Abstract

Background
Secondary prevention in patients with acute coronary syndrome focuses on lowering low-density lipoprotein (LDL) cholesterol below 55 mg/dL. In all statin-naïve patients at high risk (LDL-cholesterol target &lt;55 mg/dL), initiation of high-intensity statin monotherapy is recommended by ESC guidelines. Nonetheless, at one month, a significant proportion of patients do not reach their LDL-cholesterol target.

Purpose
The aim of this study was to compare lipid-lowering therapy with statin monotherapy versus statin with ezetimibe in secondary prevention in patients at high risk.

Methods
The current prospective study included 264 consecutive patients admitted with acute ST elevation myocardial infarction who underwent percutaneous coronary intervention. None of the patients had taken lipid-lowering drugs in the previous 12 months. Patients were randomly assigned to one of two treatment groups: Group 1 - rosuvastatin 40 mg (n= 144) and Group 2 - rosuvastatin 40 mg and ezetimibe 10 mg (n= 120). All patients' lipid profiles were assessed upon admission and after one month of lipid-lowering treatment.

Results
At baseline, no patient had LDL cholesterol level lower than 55 mg/dL. There was no significant difference in lipid profile at baseline between the two groups (all p &gt; 0.05). No differences were observed between the two groups in terms of baseline LDL-cholesterol deviation from the target (103.4% versus 99.70%; p= 0.66). As expected, the combination therapy reduced LDL-cholesterol at one month significantly higher compared to high-dose statin monotherapy (-59.65% versus -37.54%; p&lt; 0.0001). After one month of treatment, only 47.92% of patients in Group 1 reached the LDL-cholesterol target (&lt;55 mg/dL) compared to 90.00% of the patients in Group 2 (p&lt;0.0001; R.R.= 0.53).

Conclusion(s)
Our findings show that statin and ezetimibe combination therapy is more effective in reduction in LDL-cholesterol levels and reaching targets compared to statin monotherapy alone. In statin-naïve patients at high risk, early initiation of the statin and ezetimibe combination instead of statin monotherapy should be taken into account in secondary prevention, for an earlier reach of the LDL-cholesterol target and to reduce the overall cardiovascular risk.
Estimate and prognosis of patients who are candidates for treatment with eicosapentaenoic acid after an acute coronary syndrome
Authors: Cordero A , Fernandez Olmo R , Fernandez-Friera L , Manzano S , Bonanad C , Cortez G , Oterino A , Castellano J M , Alvarez-Alvarez B , Flores Blanco P J , Gonzalez-Juanatey J R 
Published: October 2024

Abstract

Background
Treatment with eicosapentaenoic acid (EA) has been shown to reduce the incidence of cardiovascular adverse events (MACE) in patients at high cardiovascular risk with mildly to moderately elevated triglyceride values (&gt;135 mg/dl) and non-elevated (&lt;100 mg/dl) low-density lipoprotein cholesterol (LDLc).

Methods
We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. Patients with LDLc &lt;100 mg/dl and triglycerides &gt;135 mg/dl were analyzed as candidates to EA.

Results
We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women and 30.4% with an ST-elevation ACS. Mean LDLc was 99.8 (38.5) mg/dl and median triglycerides 120.5 (interquartile range 90-197) mg/dl. A total of 3,028 (20.9%) were classified as candidates for EA, and they had the same mean age (p=0.87) but significantly higher prevalence of diabetes (35.1% vs. 21.9%), dyslipidemia (63.5% vs. 50.1%), previous coronary heart disease (CHD) (25.9% vs. 13.9%), or heart failure (HF) (3.6% vs. 2.5%). Candidates less frequently had an ST-elevation ACS (26.6% vs. 34.1%; p=0.02) and the incidence of Killip &gt;1 was equivalent in candidates vs. non-candidates (16.6% vs. 17.7%; p=0.15).
Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE. Candidates for EA had higher mortality (18.4% vs. 14.0%; HR: 1.22 95% CI 1.11-1.35) and MACE (39.0% vs. 33.6%; HR 1.14 95% CI 1.06-1.21) rates. Multivariate analysis (figure), adjusted for age, sex, diabetes (DM), previous coronary heart disease (CHD) or heart failure (HF), and medical treatments at discharge, identified an independently higher risk for all-cause mortality among candidates for EA (HR: 1.15 95% CI 1.04-1.26) [Figure 1] and for MACE (HR: 1.14 95% CI 1.05-1.20). The risk was consistent in all subgroups except for the case of mortality, but not for MACE, and previous ACS (figure 2) were a significant interaction (p=0.01) was observed

Conclusions
Approximately 20% of patients discharged after an ACS could be candidates for EA, and this subset of patients are at higher risk of death or a first MACE.
Effects of lipid-lowering therapies on lipoprotein(a) levels in patients with dyslipidemia: a systematic review and network meta-analysis of 64 randomised controlled trials
Authors: Loh E D W , Koh M Y , Toh K Z X , Teo Y N , Teo Y H , Syn N L X , Tan B Y Q , Yeo L L L , Loh W J , Lim A Y L , Poh K K , Kong W K F , Yeo T C , Chai P , Sia C H 
Published: October 2024

Abstract

Background
Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease. However, there has yet to be a drug approved specifically for lowering Lp(a). There is paucity of studies evaluating the use of current lipid-lowering agents, and their effects, if any, on Lp(a).

Purpose
We aimed to identify and compare the effects of lipid-lowering therapies on Lp(a) levels, cardiovascular and safety outcomes, in patients with dyslipidemia.

Methods
A systematic search was performed across four databases (PubMed, Embase, Scopus, Cochrane) for randomised controlled trials (RCTs) published from inception to 3 January 2023. The percentage change of serum Lp(a) levels, cardiovascular and safety outcomes were compared among statins (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin), fibrates, ezetimibe, niacin, PCSK9 inhibitors (alirocumab, evolocumab, bococizumab) and inclisiran, in patients with primary dyslipidemia. Frequentist network meta-analysis was performed to compare the treatment effects among different drug classes, stratified by use of background statin therapy.

Results
A total of 64 RCTs were included, comprising 55,256 patients. In patients on background statin therapy, PCSK9 inhibitors significantly lowered Lp(a) levels, compared with placebo (mean difference [MD] -26.8, 95% confidence intervals [95%CI] -30.8 to -22.7), ezetimibe (MD -21.6, 95%CI -31.4 to -11.8), fibrates (MD -19.4, 95%CI -37.4 to -1.5), and niacin (MD -13.8, 95%CI -25.6 to -2.1). PCSK9 inhibitors were associated with lower risk of major adverse cardiovascular events and similar risk of treatment-related adverse events than placebo. Comparing the PCSK9 inhibitors, evolocumab achieved greater Lp(a)-lowering than alirocumab in patients on background statin therapy (MD -11.4, 95%CI -18.6 to -4.1), including those with heterozygous familial hypercholesterolemia. Niacin also achieved 12.9% (95%CI 1.8 to 24.0) reduction in Lp(a) compared with placebo, but had a higher risk of treatment-related adverse effects than fibrates. Statin monotherapy did not affect Lp(a) levels, regardless of type or intensity of statin therapy. Ezetimibe and fibrate had no effect on Lp(a) levels.

Conclusions
PCSK9 inhibitors produced the greatest effect on Lp(a) levels, compared with other lipid-lowering therapies. Further studies into PCSK9 inhibitors are necessary to characterise their efficacy and safety specifically for Lp(a)-lowering, and elucidate the impact of Lp(a) reduction on cardiovascular risk.% change in Lp(a) levels
Comorbidity neural network model for personalised recommendations in cardiometabolic risk factor management: towards early precision medicine in routine clinical practice
Authors: Dibner Y , Brandt N , Curcin V , Krentz A , Lozhkina A , Luster A , Pere A , Jaun A 
Published: October 2024

Abstract

Background and Aims
Hypertension and hypercholesterolaemia often develop in tandem to confer a risk of cardiovascular disease that may be more than additive. The present study explored early comorbid therapeutic intervention, i.e., beyond individual disease silos, while minimising data bias to provide clinical decision support tools that are portable across clinics.

Methods
A neural network was created to reproduce UK national clinical guidelines with an accuracy higher than 95%. Relying on real-world evidence from the UK primary care Clinical Practice Research Datalink electronic health record resource, a transfer learning methodology was then applied to achieve recommended risk factor goal attainment after two years. Shapley values derived from game theory were used to define similar digital twin cohorts, and to evaluate individualised recommendations that deviated from national clinical guidelines by rejecting a no-benefit hypothesis retrospectively in a classical proportion test. The methodology was ported to an independent hold-out dataset with anonymized records from six primary care clinics in the South of England.

Results
The adult patient population (n=469,496, mean+SD age 61+11yr; M 56% vs F 44%; primary 84% vs secondary prevention 16%) included 101,255 diagnosed for hypertension and 112,180 for cholesterol management. While a majority of the 52,504 therapeutic decisions in a test set agree with single morbidity guidelines, for 4639 deviations from the guidance, a significant minority was identified for whom alternative therapy was recommended. Rejecting a no-clinical benefit hypothesis at the 95% confidence level in a retrospective analysis, 1367 decisions showed statistically significant better outcomes over guidelines, for example by escalating anti-hypertensive therapies for patients receiving statin therapy (1085) or by complementing anti-hypertensive therapy with a statin (158). Similar findings were obtained when tested in a hold-out dataset with 13,725 decisions for 6531 patients.

Conclusions
The results support the contention that machine learning can identify patient subgroups for whom comorbid intervention deviating from clinical guidelines may be appropriate. A novel aspect of the study is the demonstration of clinically portable and actionable application of machine learning in the context of comorbid cardiometabolic diseases. The results represent practical steps towards personalised precision medicine for cardiovascular comorbidity in routine clinical practice.