bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated care using the ABC-stroke pathway improves cardiovascular outcomes and survival in patients with recent ischaemic stroke: a population-based cohort study
Authors: Tsang C T W , Choi S E , Ren Q W , Huang J Y , Gu W L , Guo R , Zhang J N , Chan Y H , Lau G K K , Tse H F , Bucci T , Lam S H M , Abdul-Rahim A H , Lip G Y H , Yiu K H 
Published: October 2024

Abstract

Background
A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed the ABC-stroke pathway, a holistic and integrated care approach to optimise the post-stroke management for patients with recent stroke, and associated heart disease. The ABC-stroke pathway is based on 3 pillars: "A" Appropriate Antithrombotic therapy; "B" Better functional and psychological status; and "C" Cardiovascular risk factors and Comorbidity optimisation (including lifestyle changes). There are limited data on the impact of adherence to the ABC-stroke pathway on post-stroke patient outcomes.

Purpose
We aimed to investigate the potential impact of ABC-stroke pathway adherence in the Clinical Data Analysis and Reporting System (CDARS) database in Hong Kong.

Methods
The analysis included patients with new-onset ischaemic stroke recorded in CDARS between 1st June 2006 and 31st May 2022. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between adherence to the ABC-stroke pathway and the primary outcome. The primary endpoint was a composite outcome of recurrent ischaemic stroke, transient ischaemic attack, haemorrhagic stroke, myocardial infarction, heart failure and all-cause death. Secondary outcomes were the individual components of the composite outcome, and cardiovascular death.

Results
Of the 9,669 included patients with ischaemic stroke (mean age 69.6 ± 13.4 years; 42.5% female), 58.1% were adherent to all 3 main ABC-stroke pillars. After 1 year of follow-up, adherence to the ABC-stroke pathway was associated with a lower risk of the primary composite endpoint (HR: 0.80; 95% CI: 0.72–0.88). Risk reductions increased progressively with a higher number of ABC-stroke criteria obtained (Figure 1). On multivariate analyses of the secondary outcomes, ABC-stroke pathway-adherent care was associated with a reduced risk of all-cause mortality (HR: 0.72; 95% CI: 0.62–0.85), cardiovascular death (SHR: 0.64; 95% CI: 0.45–0.90), haemorrhagic stroke (SHR: 0.50; 95% CI: 0.38–0.67) and heart failure (SHR: 0.771; 95% CI: 0.596-0.998) (Table 1).

Conclusion
In a large cohort of patients with ischaemic stroke, adherence to the ABC-stroke pathway was associated with a reduction of the risk of adverse outcomes.
Long-term continuation to pharmacological treatment for secondary prevention after a myocardial infarction: a register study
Authors: Sakalaki M S , Pivodic A P , Rosengren A R , Fu M F , Bjorck L B 
Published: October 2024

Abstract

Background
Pharmacological treatment for secondary prevention after acute myocardial infarction (MI) is crucial to prevent new events. Several studies report inconsistence and need for improvement of pharmacological treatment. Study follow-up is often less than 10 years and showing that continuation to drug treatment decreases with time.

Objective
To study long-term follow-up of nationally guideline recommended medical therapy (GDMT) for secondary prevention after a myocardial infarction.

Method
The study population consisted of individuals aged 18-84 years, who were hospitalized for a MI between January 2006 and December 2022 and were followed up to 16 years. The study subjects were identified through the National Inpatient Register and linked to the Prescribed Drug Register. Four classes of drugs were analyzed: antiplatelet/anticoagulant therapy, lowering therapy, betablockers and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). Time-updated survival analyses were used to investigate the relationship between continuation of preventive pharmacological treatment and mortality and recurrent MI after an acute MI.

Results
A total number of 139 413 individuals (mean age 69.1±10.6) were included and 33.3% were female. At baseline 51.2% had hypertension, 21.5% diabetes mellitus and 15.2% heart failure. All prescriptions of GDMT were decreased significantly after hospitalization after MI and during first years and remained plateau (figure 1). During follow-up 55487 persons died (39.8%, event rate 5.81 per 100 person years [95% CI 5.76-5.86]). Medication with antiplatelets/anticoagulantia, ACEi/ARB and statins decreased risk of all cause-mortality and myocardial infarction [HR 0.83 [95% CI 0.79-0.86], p-value &lt;0.001, HR 0,79 [95% CI 0.77-0.83], p-value &lt;0.001, HR 0.70 [95% CI 0.67-0.73], p-value &lt;0.001) respectively.

Conclusion
Pharmacological treatment as a part of secondary prevention remained greatly underutilized both shortly and during long-term after MI. Usage of antiplatelets or antigulantia, ACEi or ARB and statins decreased the risk of all-cause mortality and recurrent myocardial infarction.
Impact of changes of Achilles tendon thickening on cardiovascular events among patients with familial hypercholesterolemia
Authors: Tada H , Kojima N , Takeji Y , Nohara A , Kawashiri M , Takamura M 
Published: October 2024

Abstract

Backgrounds
Achilles tendon thickening (ATT) can be regressed through LDL-lowering in patients with familial hypercholesterolemia (FH). The Japan Atherosclerosis Society (JAS) determined the threshold of ATT as ≥8.0 mm in male and ≥7.5 mm in female.

Purpose
We aimed to determine clinical impact of changes of ATT in development of major adverse cardiovascular events (MACE).

Methods
Patients with clinically diagnosed FH (N=1,273, male/female=614/659) with ATT data using X-ray were assessed. We divided the patients into 4 groups (group 1: patients without ATT from baseline to their follow-up, group 2: patients without ATT at baseline, but developed ATT at follow-up, group 3: patients with ATT at baseline, but regressed at follow-up, group 4: patients with ATT from baseline to their follow-up). Cox proportional hazards models were used to assess factors associated with MACE, including cardiovascular death and any coronary events.

Results
The median follow-up period was 10.9 years. During the follow-up period, 142 MACEs were observed, and median ATT was regressed from 7.8 to 7.6 mm. We found that there was more significant positive correlation between cholesterol-year score and ATT among patients with and without MACE (p &lt;0.001; Spearman’s r=0.33, and p &lt;0.001; Spearman’s r=0.35, respectively). Under these circumstances, changes of ATT were significantly associated with the occurrence of MACE (hazard ratio (HR): 2.73; 95% confidence interval (CI): 1.33–4.13; p&lt;0.001, HR: 2.18; 95% CI: 1.08–3.28; p&lt;0.001, HR: 6.34; 95% CI: 3.10–9.58; p&lt;0.001, in group 2, group 3, and group 4, respectively when group 1 was considered as reference).

Conclusion
Assessments of ATT condition represent diagnostic values and risk stratification information among patients with FH.
Unveiling homozygous familial hypercholesterolemia in Greece: a comprehensive analysis of baseline traits and LDL goal achievement in adults from the HELLAS-FH Registry
Authors: Anastasiou G , Milionis H , Rizos C , Liamis G , Skoumas I , Vlachopoulos C , Rallidis L , Garoufi A , Kolovou G , Tziomalos K , Sfikas G , Skalidis E , Kotsis V , Doumas M , Liberopoulos E 
Published: October 2024

Abstract

Background
Homozygous familial hypercholesterolemia (HoFH) is a severe genetic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to analyze demographic characteristics, lipid profile, and rate in achieving LDL-C targets in adult HoFH patients in Greece.

Methods
This is a cross-sectional analysis of the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Adults with genetically or clinically diagnosed HoFH were included. Median LDL-C levels were assessed during HoFH diagnosis and enrollment.

Results
Seventeen HoFH adults (mean age 41 years and mean age at diagnosis 31 years, men 58.8%). Genetic confirmation of HoFH was available in 10 patients, while the remaining were diagnosed based on clinical criteria. Family history of atherosclerotic cardiovascular disease was documented in 70.5% of patients. Clinical presentations varied, with 47.0% exhibiting tendon xanthomas, 17.6% xanthelasmas, 23.5% corneal arcus, and 52.9% premature coronary artery disease (CAD). Predominant treatment involved statins (88.2%), ezetimibe (58.8%),PCSK9i (23.5%), lomitapide (29.4%), while LDL apheresis was utilized in 23.5%. Median LDL-C levels were 407 mg/dL (10.53 mmol/L) at diagnosis and 226 mg/dL (5.84 mmol/L) at enrollment. None of the patients achieved the LDL-C target set by the 2019 EAS/ESC Guidelines.

Conclusion
The challenges of delayed diagnosis, undertreatment, and unattained LDL-C targets persist in HoFH management in Greece, emphasizing the critical need for effective lipid-lowering interventions to mitigate cardiovascular risk.
Statin use before acute coronary syndrome and coronary risk factors, clinical presentation, interventions, and outcomes: ACC-NCDR-CathPCI Registry in India
Authors: Gupta R , Gupta J B , Sharma K K , Sharma S K , Makkar J S , Khedar R S , Bana A , Sharma S , Guptha S 
Published: October 2024

Abstract

Background
Statins are used for coronary artery disease (CAD) primary and secondary prevention. Limited studies on the association of statin use before acute coronary syndrome (ACS) with clinical presentation and outcomes are available.

Purpose
We compared statin-user and statin-naïve ACS patients for clinical and angiographic findings and in-hospital and 3-year outcomes following percutaneous coronary intervention (PCI).

Methods
Successive patients with ACS who underwent PCI from Sep’17 to Dec’23 were enrolled in the ACC-NCDR-CathPCI registry in India. Details of risk factors, clinical presentation, coronary angiography, interventions and in-hospital were recorded. Follow-up data in a sub-cohort recruited from Apr’19 to Mar’22 were obtained for incident major cardiovascular events (MCE) (cardiovascular deaths, recurrent ACS, PCI and bypass surgery).

Results
8296 ACS patients were enrolled; prior statin use was in 3149 (38%) and statin naïve were 5147 (62%). Statin-user vs statin-naïve patients were older (61.6+10 vs 59.7+11y), with more hypertension (60.1 vs 48.6%), diabetes (35.8 vs 31.8%), pre-existing CAD (PCI 20.9 vs 9.1%; CABG 5.0 vs 2.3%) and lower mean total, LDL, and NHDL cholesterol (p&lt;0.001). Statin users had less ST-elevation myocardial infarction (STEMI) (28.4% vs 45.2%), more non-STEMI (65.2 vs 50.8%), better LVEF (46.3+10 vs 44.5+10%), &gt;2 coronary stents (35.5 vs 29.5%), lower mechanical circulatory support (2.2 vs 3.9%) and lower median hospitalization (66.1 vs 68.5h) (p&lt;0.001). In statin-users incidence of in-hospital CAD deaths was 29 (0.92%) vs 78 (1.52%) (odds ratio, OR 0.61, 95% confidence intervals 0.39-0.93) and all-cause deaths 33 (1.05) vs 91(1.77%) (OR 0.59, 95%CI 0.39-0.88) (p&lt;0.01). ORs attenuated following multivariate adjustments for risk factors, clinical presentation and interventions. In the follow up cohort (n=3813, high-intensity statins 99.6%), among baseline statin-users incident MCE was 98 (6.9%) vs 214 (8.9%) (hazard ratio, HR 0.76, 95%CI 0.59-0.97) and CVD deaths were in 46 (3.2%) vs 113 (4.7%) (HR 0.68, 95%CI 0.48-0.96) with attenuation following adjustment for baseline clinical variables and interventions.

Conclusions
Acute coronary syndrome patients taking pre-admission statins have significantly lower in-hospital and long-term cardiovascular and all-cause mortality following PCI.
Proprotein convertase subtilisin/kexin type 9 levels and the risk of cardiovascular events in statin-treated patients with cardiovascular disease
Authors: Gohbara M , Hibi K , Uemura K , Iwahashi N , Okada K , Fukumoto Y , Ozaki Y , Miyauchi K , Nakagawa Y , Ogawa H , Daida H , Shimokawa H , Kimura T , Kimura K , Nagai R 
Published: October 2024

Abstract

Background
Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events. Although PCSK9 is cleaved by furin and becomes biologically inactive, previous studies have employed measurement methods which cannot distinguish furin-cleaved and uncleaved form of PCSK9.

Methods
This study is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The substudy primary endpoint was a composite of major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In a case-cohort study, sub-cohort was randomly selected samples from the total cohort as tripling the number of cases with MACCE. Serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among participants who subsequently developed MACCE and among randomly selected participants. Their relationships with cardiovascular events were assessed according to the quartiles. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI).

Results
From 1,478 patients in the sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of primary endpoint in patients in the highest quartile of mature PCSK9 concentrations was similar to the lowest quartile (HR 0.809; 95%CI, 0.541-1.209). Similarly, HRs for the highest to lowest quartiles of furin-cleaved PCSK9s was 0.948 [95%CI, 0.645-1.392] (P=0.784). As compared to the lowest quartile, both serum mature and furin-cleaved PCSK9 levels did not predict the cardiovascular events.

Conclusions
Serum mature and furin-cleaved PCSK9 levels did not provide useful information in the assessment of future cardiovascular events in statin-treated patients with stable CAD.Study FlowThe weighted Kaplan-Meier cueves
Remnant cholesterol predicts major cardiovascular events in coronary artery disease patients with NAFLD
Authors: Plattner T , Larcher B , Mader A , Vonbank A , Leiherer A , Muendlein A , Drexel H , Saely C H 
Published: October 2024

Abstract
Remnant cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with non-alcoholic fatty liver disease (NAFLD) is unclear and is addressed in the present study.
We enrolled a high-risk cohort of 913 patients with coronary artery disease (CAD). NAFLD was diagnosed using the validated fatty liver index (FLI). Prospectively, MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a mean follow-up period of 9.5±5.2 years.
At baseline, remnant cholesterol was significantly higher in patients with NAFLD (n=419) than in patients who did not have NAFLD (30±28 mg/dl vs. 18±17 mg/dl; p&lt;0.001). During follow-up, 379 of our patients suffered MACE. Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, diabetes mellitus, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.18 [1.08-1.30], p&lt;0.001), and both in patients with NAFLD as well as in those who did not have NAFLD (standardized adjusted HRs 1.19 [1.05-1.35], p=0.006 and 1.24 [1.03-1.49], p=0.023, respectively).
From our data we conclude that remnant cholesterol is a predictor of MACE in patients with CAD with and without NAFLD.
Effect of triglycerides on cardiovascular risk in patients with a first vs. recurrent acute coronary syndrome
Authors: Cordero A , Fernandez Olmo R , Gonzalez-Juanatey J R , Fernandez-Friera L , Bonanad C , Manzano S , Oterino A , Cortez G , Alvarez-Alvarez A B , Flores Blanco P J , Castellano J M , Bhatt D L 
Published: October 2024

Abstract

Background
Triglyceride (TG) levels have gained increasing interest in the prevention of cardiovascular disease although there is divergent evidence that might be explained by confounding factors.

Methods
We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. TG were measured during the hospitalization, and mortality and major adverse cardiovascular events (MACE) were analyzed through follow-up.

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; 2,378 (16.4%) patients had a previous ACS and were classified as recurrent ACS. Median triglyceride level was 120.5 (interquartile range [IQRS] 90-197) mg/dL and was slightly higher in patients with recurrent ACS (135 IQR 98-186 vs. 129 IQR 95-175; p&lt;0.01). Patients with first vs. recurrent ACS received ticagrelor or prasugrel more frequently at discharge (14.8% vs. 7.4%; p&lt;0.01), but no other differences in medical treatments were observed.
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 during follow-up. Patients with recurrent ACS had higher mortality (32.9% vs. 11.4%; p&lt;0.01) and MACE (46.5% vs. 32.4%; p&lt;0.01) rates. Multivariate analysis, adjusted for age, sex, diabetes, previous heart failure, and medical treatments at discharge showed that TG levels were not associated with higher risk of mortality (p=0.29) but with higher risk of MACE (p=0.04). A significant interaction (p=0.01) was observed for TG and previous ACS for both endpoints and, therefore, analyses were performed separately (Figure 1). As shown in Figure 2, TG were associated with higher risk of death in patients with first ACS (p=0.02) but not in patients with recurrent ACS (p=0.48); in contrast, TG were associated with higher risk of MACE (p=0.024) in patients with a recurrent ACS but not in patients with a first ACS (p=0.25).

Conclusions
Previous ACS modifies the risk of TG on mortality and MACE in patients discharged after an ACS. TG might be considered a target for treatment in patients after a first or recurrent ACS, although the exact impact on outcomes might be different.
Lipoprotein(a) cardiovascular disease risk not captured by low density lipoprotein cholesterol and apolipoprotein B
Authors: Thomas P , Vedel-Krogh S , Kamstrup P R , Nordestgaard B G 
Published: October 2024

Abstract

Background
Elevated lipoprotein(a) affects 1 in 5 individuals and is considered a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and aortic valve stenosis (AVS). However, lipoprotein(a) measurements are not widely implemented in clinical practice. Low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) measurements include contributions from lipoprotein(a), yet whether these measurements can replace measurements of lipoprotein(a) in assessing cardiovascular disease risk from this causal risk factor is unknown.

Purpose
We tested the hypotheses that lipoprotein(a) risk of ASCVD and AVS is captured by LDL cholesterol or ApoB.

Methods
We included 70,189 individuals from a prospective contemporary cohort study of the general population. Mediated risk by LDL cholesterol and ApoB in the association between lipoprotein(a) and risk of ASCVD and AVS was examined using four-way decomposition analyses stratified by statin treatment at baseline.

Results
During a median follow-up of 10.8 years, 7,127 developed ASCVD and 1,516 AVS. Per 50 mg/dL higher lipoprotein(a), multivariable adjusted hazard ratios were 1.22 (95% CI: 1.18-1.26) for ASCVD and 1.36 (1.28-1.46) for AVS. In individuals without statin use, LDL cholesterol mediated 19% (15%-24%) of the risk of ASCVD from lipoprotein(a) and 7.7% (1.5%-14%) of the risk of AVS from lipoprotein(a) (Figure 1). Corresponding values for ApoB were 14.0% (11%-18%) and 6.6% (2.8%-10%). In statin users (n=9,570), LDL cholesterol did not mediate risk of ASCVD from lipoprotein(a) but mediated 8.0% (0.8%-15%) of the risk of AVS from lipoprotein(a). Correspondingly, ApoB mediated 9.8% (2.2%-17%) of the risk of ASCVD and 4.2% (0.4%-8.0%) of the risk of AVS from lipoprotein(a).

Conclusion
Lipoprotein(a) risk of ASCVD and AVS is not adequately captured by LDL cholesterol and ApoB. Therefore, lipoprotein(a) measurement is needed in all individuals to capture the cardiovascular disease risk from this causal risk factor.
Remnant cholesterol lowering in cardiovascular disease risk reduction in statin trials: meta-regression analyses
Authors: Nordestgaard A T , Nordestgaard B G 
Published: October 2024

Abstract

Background
Remnant cholesterol is a causal risk factor for cardiovascular disease.

Purpose
We tested the hypothesis that remnant cholesterol reduction explains part of the cardiovascular disease risk reduction in statin trials.

Methods
We included statin trials with &gt;1,000 participants and available data on lipid levels. Baseline and follow-up low-density lipoprotein (LDL) and remnant cholesterol levels were extracted. LDL and remnant cholesterol reductions were differences between intervention and reference groups at year one. Risk ratios for any statin use and per 1 mmol/L (39 mg/dL) LDL and remnant cholesterol reductions were estimated using meta-regressions.

Results
We included 29 statin trials with 191,202 participants and 26,639 major cardiovascular events. On an absolute scale when LDL cholesterol was reduced 1 mmol/L (39 mg/dL), remnant cholesterol was reduced 0.17 mmol/L (7 mg/dL) (Figure 1). On a relative scale when LDL cholesterol was reduced 20%, remnant cholesterol was reduced 12%. The risk ratio for statin use versus reference was 0.82 (95% confidence interval: 0.81-0.84) for major cardiovascular events (Figure 2). Risk ratios per 1 mmol/L (39 mg/dL) reductions were 0.82 (0.80-0.83) for LDL cholesterol and 0.37 (0.33-0.41) for remnant cholesterol for major cardiovascular events. Corresponding risk ratios for 1 mmol/L (39 mg/dL) LDL and remnant cholesterol reductions were 0.78 (0.75-0.80) and 0.30 (0.25-0.35) for coronary events, 0.86 (0.82 -0.90) and 0.48 (0.38-0.61) for stroke, and 0.93 (0.91-0.95) and 0.71 (0.62-0.80) for any death, respectively.

Conclusions
Remnant cholesterol lowering likely explain part of the cardiovascular disease risk reduction in statin trials.
Figure 1. Remnant cholesterol reduction as a function of LDL cholesterol reduction.
Regressions were calculated using inverse-variance weighted unadjusted linear regressions. LDL = low-density lipoprotein. LDL-C = LDL cholesterol. R-C = Remnant cholesterol. ∆ = change from baseline to 1 year follow-up.
Figure 2. RR for MACE for statin use and cholesterol reductions.
Risk ratios were calculated using fixed and random effects inverse-variance weighted meta-regressions. CI = confidence interval. LDL = low-density lipoprotein. LDL-C = LDL cholesterol. MACE = major cardiovascular events. R-C = remnant cholesterol. RR = risk ratio.Figure 1Figure 2