bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipoprotein(a) levels in acute myocardial infarction patients and their associations with prior events and coronary artery disease severity: a real-world cohort study
Authors: Azevedo S , Da Silva Correia D , Barbosa Sousa R , Amador R , Sousa Paiva M , Gomes D , Certo Pereira J , Carvalho R , Bello R , Fonseca I , Tralhao A , Trabulo M , Figueira J , Sousa Almeida M , Ferreira J 
Published: October 2024

Abstract

Introduction
Circulating lipoprotein(a) [Lp(a)] has been associated with the risk of atherosclerotic coronary artery disease (CAD) and is an emergent therapeutic target.
The objective of this study is to explore the association between serum levels of Lp(a) and previous myocardial infarction (MI) and/or coronary revascularization and the extension of obstructive CAD in patients with acute MI undergoing coronary angiography.

Methods
All consecutive patients with MI who underwent coronary angiography and Lp(a) measurement between May and November 2023 were included. Patient data were either registered prospectively or completed retrospectively using electronic health records. Lp(a) was measured using the Immunoturbidimetric Assay method with reaction intensification by particles, employing the World Health Organization/International Federation of Clinical Chemistry and Laboratory Medicine (WHO/IFCC) International Reference Reagent (SRM2B), on the "Roche Cobas C702" chemistry analyzer.
The number of major coronary arteries (left main, left anterior descending, left circumflex and right coronary arteries) with stenosis &gt;50% on the coronary angiography were registered. In the primary analysis we explored the association between Lp(a) levels using tertiles and previous occurrence of MI/revascularization, as well as the extension of obstructive CAD. In the secondary analysis we compared Lp(a) levels in patients with and without previous MI/revascularization and patients with 3-4 major vessels CAD vs. 0-2 vessels.

Results
A total of 116 patients were enrolled, with a mean age of 62±13 years, 79% males, 29% with known coronary artery disease, 71% with dyslipidemia, 24% with diabetes, 65% with hypertension, and 58% were either active or former smokers. The median Lp(a) level was 72 (20-183) nmol/L.
In the primary analysis (table 1), the number of previous MI/revascularizations was significantly higher in the third tertile of Lp(a) (T3) versus T1 (p=0.044). No significant differences were found for the remaining analyses. In the secondary analysis (figure 1) the level of Lp(a) was significantly higher in patients with 3-4 vessel CAD vs. 0-2 vessel (158.4±145.2 nmol/L vs. 103.16±104.6 p=0.044).

Conclusion
In this small real-world cohort population with acute MI, the number of previous MI or coronary revascularization was higher in patients with increased levels of Lp(a) and this marker of atherosclerotic disease was greater in patients with more extensive CAD.
Sex-specific guideline target value attainment and prognostic value of low-density lipoprotein cholesterol in tertiary care
Authors: Rumora K , Lopez Ayala P , Schaefer I , Durandi V , Walter J E , Leibfarth J P , Hure G , Isayeva G , Zellweger M J , Strebel I , Von Eckardstein A , Pfister O , Mueller C 
Published: October 2024

Abstract

Background
Factors contributing to guideline-target-level-attainment of low-density lipoprotein cholesterol (LDL-C) in countries with high healthcare expenditure are incompletely understood.

Purpose
the primary aim of this study was to test two hypotheses: 1) LDL-C control may be inferior in women versus men; 2) within the secondary prevention group, presence of a previous acute atherothrombotic event (acute myocardial infarction and stroke) may result in superior LDL-C control.

Methods
LDL-C levels and guideline target level attainment were determined in 4090 consecutive patients referred for myocardial perfusion single photon emission tomography (MPI-SPECT) between 2010 and 2016. Findings were validated in an independent cohort (n=1228) of consecutively enrolled patients in an outpatient cardiac rehabilitation program, between 2016 and 2023.

Results
About one third of patients (33%) were women, median age was 68 years, 1439 patients had a history of atherothrombosis, 759 patients a history of atherosclerosis without atherothrombosis, and 1892 were in primary prevention. LDL-C levels were higher and guideline target level attainment worse in women than in men in all three strata: age-adjusted difference in atherothrombosis 0.19 mmol/L (95%CI 0.03,0.35 mmol), guideline-target-value-attainment 39.5 % versus 49.4%, p&lt;0.01; in atherosclerosis 0.33 mmol/L (95%CI 0.10-0.57), guideline-target-value-attainment 27.3 % versus 42.2 %, p&lt;0.01; and in primary prevention 0.24 mmol/L (95% CI 0.13-0.38). This was confirmed in the validation cohort. LDL-C levels were higher and guideline-target-value-attainment worse in women versus men: age-adjusted difference age-adjusted difference 0.17 mmol/L (95%CI 0.02-0.33) guideline-target-value-attainment 43.8% versus 49.5%, After multivariate adjustment, female sex remained an independent predictor for higher LDL-C levels. LDL-C concentrations with atherothrombosis was 1.93 mmol/L (IQR 1.48-2.47) versus 2.07 mmol/L (IQR 1.40-2.72, p=0.003) with atherosclerosis and guideline target value attainment 47.5% vs 38.6%, p&lt;0.001, respectively.

Conclusion
Concerning age-adjusted sex-inequalities with higher LDL-C levels and lower guideline-target-value-attainment in women were found in both primary and secondary prevention. Within secondary prevention, a previous atherothrombotic event was associated with lower LDL-C levels and higher guideline-target-value-attainment.
Identification of ischemia with no obstructive coronary arteries using 13N-ammonia positron emission tomography-derived myocardial strain ratio
Authors: Sakai A , Nagao M , Imakado R , Yamamoto A , Nakao R , Arashi H , Momose M , Yamaguchi J 
Published: October 2024

Abstract

Background
Ischemia with no obstructive coronary arteries (INOCA) is a chronic health problem with poor prognosis and remains challenging to diagnose. 13N-ammonia positron emission tomography (NH3-PET) is the most reliable method for detecting INOCA. We recently developed a unique myocardial strain analysis for NH3-PET to detect ischemia-related motion abnormalities.

Purpose
We examined the usefulness of NH3-PET strain analysis to identify patients with INOCA.

Methods
Overall, 98 patients with non-obstructive coronary arteries who underwent adenosine-stress NH3-PET were enrolled. INOCA was defined based on the ESC guidelines. Using an original feature-tracking algorithm dedicated to NH3-PET, the circumferential strain was calculated. Myocardial strain ratio (MSR) was defined as the ratio of strains at stress and rest. In addition, global myocardial flow reserve (MFR) was obtained.

Results
Finally, forty-seven patients were diagnosed with INOCA, and 51 without INOCA. Global MFR were significantly lower in patients with INOCA than in those without INOCA (1.82 ± 0.52 vs. 2.65 ± 0.65, p&lt;0.0001). MSR were significantly lower in patients with INOCA than in those without INOCA (0.94 ± 0.11 vs. 1.04 ± 0.12, p&lt;0.001). Receiver-operating characteristic analysis showed that using the optimal cutoff of the MSR, INOCA could be diagnosed with area under the curve of 0.71. At a median follow-up of 957 days, Kaplan–Meier analysis revealed that the survival rate worsened in patients with INOCA and low MSR (log-rank test, p&lt;0.001).

Conclusions
MSR derived from feature-tracking of NH3-PET is reduced in patients with INOCA. It might suggest a predictive value to identify microvascular dysfunction or related motion abnormalities in patients with INOCA.
High intensity statin-ezetimibe combination therapy reduces mortality in patients with ischaemic heart disease and elevated Lipoprotein(a)
Authors: Loh W J , Koh X H , Mak Y H , Yeo C , Foo R , Heng C K , Watts G F 
Published: October 2024

Abstract

Background
Early and prompt reduction of low-density lipoprotein cholesterol concentrations (LDL-C) using combination lipid-lowering therapy (LLT) is recommended to lower cardiovascular risk in patients with ischaemic heart disease (IHD) and elevated LDL-C. Lowering LDL-C is also an important cardiovascular risk mitigation strategy in patients with elevated lipoprotein(a) [Lp(a)]. However, it is unknown if combination LLT reduces mortality in patients with elevated Lp(a).

Aim
To undertake an observational study to investigate the effect of combination LLT using high intensity statin with ezetimibe on cardiovascular outcomes in patients with and without elevated Lp(a).

Methods
Serum Lp(a) concentrations were measured in 520 consecutively recruited patients with IHD admitted to hospital, half of whom were admitted for acute myocardial infarction. Patients treated with high intensity statin and ezetimibe within the 1st year from admission to hospital (‘HI statin-ezetimibe group’, n=157) were compared with the rest of patients who had less intensive lipid lowering regimen (‘Others group’, n=363) for cardiovascular outcomes.

Results
During the 2-year follow-up period, 14.6%, 6.5%, and 53.1% of patients had all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE) respectively. Median age was 63.5 years and 82.3% were male. Multivariable Cox regression showed that baseline Lp(a) ≥70 nmol/L was associated with increased risk of all-cause mortality (HR 1.97, 95% CI 1.20-3.22, P=0.007). Compared with a less intensive regimen, HI statin-ezetimibe was associated with reduced risk of all-cause mortality (HR 0.44 [0.21-0.89], P=0.023) and MACE (HR 0.71 [0.52-0.95], P=0.027), with no statistically significant effect on cardiovascular mortality (HR 0.43, P=0.142). Notably, the cardiovascular benefits of HI statin-ezetimibe were more pronounced in patients with elevated Lp(a); a greater reduction in risk of MACE was seen for patients with Lp(a) ≥70 nmol/L (HR 0.51, P=0.007) or Lp(a) ≥100 nmol/L (HR 0.36, P=0.009), and in all-cause mortality risk for those with Lp(a) ≥70 nmol/L (HR 0.24, P=0.025). Although LDL-C reduction &gt;50% was associated with reduced risk of all-cause mortality (p=0.027), this could not fully explain the overall cardiovascular benefit of HI statin-ezetimibe use in patients with or without elevated Lp(a).

Conclusion
Intensification of lipid-lowering therapy with high-intensity statin and ezetimibe improves cardiovascular outcomes in patients at very high cardiovascular risk, particularly those with elevated Lp(a). Larger studies are required to confirm our findings that this cardiovascular benefit is partially independent of LDL-C lowering.
Reduction of triglyceride-rich lipoproteins with retatrutide in type 2 diabetes may be explained by concurrent reduction in ANGPTL3/8 levels
Authors: Wen Y , Lemen D , Chen Y , Lin Y , Thomas M , Hartman M , Coskun T , Milicevic Z , Haupt A , Ruotolo G , Konrad R 
Published: October 2024

Abstract

Background/Introduction
In the recent phase 2 study (NCT04867785) in patients with type 2 diabetes (T2D), retatrutide, an agonist of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon receptors, reduced triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) up to 35.0% and 20.7%, respectively. The angiopoietin-like 3/8 complex (ANGPTL3/8) is the most potent circulating inhibitor of lipoprotein lipase (LPL), and its serum levels have been shown to be directly correlated with TG and low-density lipoprotein cholesterol (LDL-C).

Purpose
In the aforementioned phase 2 study, we examined the effects of retatrutide on circulating ANGPTL3/8 complex concentrations to help understand the mechanism by which retatrutide reduced TG and non-HDL-C.

Methods
Patients with T2D were randomly assigned to receive once-weekly injections of placebo, 1.5 mg dulaglutide, or retatrutide doses of 0.5 mg, 4 mg, 8 mg, or 12 mg. Fasting serum samples were collected at baseline, week 2, week 4, week 8, week 12, week 16, and week 24, and ANGPTL3/8 levels were measured at all time points using a sensitive and selective immunoassay. Plasma PCSK9 levels were also measured at baseline and 24 weeks. Data were analyzed using a mixed model for repeated measures with log-transformation.

Results
Baseline ANGPTL3/8 levels (mean 26.3 ng/mL, IQR 17.4-33.0 ng/mL) were not different among all study groups. Mean percent changes of ANGPTL3/8 from baseline at week 24 were -1.3%, -12.0%, -48.7% and -51.0% in 0.5 mg, 4 mg, 8 mg and 12 mg retatrutide groups, respectively (Figure). Percent changes of ANGPTL3/8 in 8 mg and 12 mg retatrutide groups were significantly different from placebo group (p &lt; 0.0001). Mean percent changes of PCSK9 levels from baseline to 24 weeks were not different from placebo for any treatment arm (+6.2%, -3.9%, -3.8% and -9.6% for retatrutide 0.5 mg, 4 mg, 8 mg and 12 mg groups, respectively, and -1.5% for dulaglutide and -6.5% for placebo).

Conclusions
In patients with T2D, retatrutide dose-dependently decreased serum concentrations of ANGPTL3/8, the most potent circulating LPL inhibitor. These data suggest that retatrutide may reduce TG-rich lipoproteins by decreasing ANGPTL3/8 levels.
Interleukin-6 signalling, lipoprotein (a) lowering and cardiovascular disease: a mendelian randomisation study
Authors: Brennan S O , Kelly P J , Mccabe J J 
Published: October 2024

Abstract

Background
Elevated lipoprotein(a) (Lp[a]) levels and chronic low-grade inflammation play causal roles in cardiovascular disease (CVD) development, representing promising targets for managing residual risk. CVD prevention trials are currently assessing the efficacy of IL-6 pathway inhibition in ameliorating chronic pro-atherogenic inflammation. Lp(a) increases in response to interleukin 6 (IL-6) and acute inflammatory states, and Lp(a) itself induces an inflammatory response that accelerates atherosclerosis. Recent studies indicate that IL-6-receptor inhibitors may lower Lp(a) levels and reduce inflammation, potentially decreasing CVD risk in an additive manner.

Purpose
This drug-target Mendelian Randomisation (MR) study aims to elucidate the on-target effects of pharmacological IL-6R and LPA inhibition on CVD and explore the relationship between downregulated IL6R signalling and Lp(a) levels.

Methods
Independent genetic variants associated with C-reactive protein levels from around the IL6R gene locus, and Lp(a) lowering variants from around the LPA gene locus were utilised to assess the effect of genetically proxied IL6R and LPA inhibition on CVD risk in large genomic consortia. Two-step cis-MR was then employed to estimate the effect of lower genetically predicted IL6R signalling on CVD, after adjusting for its influence on Lp(a) levels.

Results
Genetically proxied LPA inhibition was associated with reduced odds of coronary artery disease (CAD) (OR 0.88, 95% CI 0.86-0.89), ischaemic stroke (IS) (OR 0.98, 95% CI 0.96-1.00), cardioembolic stroke (OR 0.95, 95% CI 0.92-0.97), heart failure (HF) (OR 0.96, 95% CI 0.92-1.00), and aortic stenosis (OR 0.88, 95% CI 0.85-0.91). IL6R inhibition was associated with reduced odds of CAD (OR 0.76, 95% CI 0.68-0.86), IS (OR 0.89, 95% CI 0.80-0.98), small vessel stroke (SVS) (OR 0.72, 95% CI 0.59-0.89), large artery stroke (LAS) (0.61, 95% CI 0.48-0.78) and atrial fibrillation (OR 0.73, 95% CI 0.65-0.83). Furthermore, downregulated IL6R signalling was associated with lower Lp(a) levels (SD change -0.04, 95% CI -0.08,-0.01). In two-step cis-MR, Lp(a) levels partially mediated the total effect of IL6R inhibition on CAD (proportion-mediated = -11.33%, 95% CI -11.35, -11.31%) and LAS (proportion mediated = -4.19%, 95% CI -4.21, -4.17%), but had little effect on IS (proportion-mediated = -1.78%, 95% CI -1.80, -1.76%), SVS (proportion-mediated = -2.50%, 95% CI -2.52, -2.48%), or atrial fibrillation (proportion-mediated = -0.20%, 95% CI -0.22, -0.18%).

Conclusion
IL6R and Lp(a) inhibition are independently associated with reduced risk of CVD. Furthermore, IL6R inhibition is associated with lower Lp(a) and its effect on CVD is independent of its Lp(a)-lowering effects. Targeting the IL6 signalling pathway offers a promising approach to mitigate residual CVD risk in individuals with elevated Lp(a) levels. Future trials should investigate the additive effects of combined IL-6 inhibition and Lp(a) lowering therapies.
Gender differences in the treatment with PCSK9 monoclonal antibodies real world experience from a dedicated prevention clinic
Authors: Hodeda L , Birati E Y , Rotholz A , Eisen A , Gurevitz C 
Published: October 2024

Abstract

Background
Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAb) lower low-density lipoprotein cholesterol (LDL-C) levels and reduce atherosclerotic cardiovascular disease (ASCVD). There are gender differences in PCSK9 biological characteristics, which are not properly addressed in current data.

Purpose
Examining gender differences in treatment with PCSK9 mAb.

Methods
A retrospective study based on data from the Prevention Cardiology Clinic in Rabin Medical Center. Included were patients prescribed with PCSK9 mAb (evolocumab or alirocumab), for primary or secondary prevention. Data included medical background and treatment variables. Response to treatment was evaluated by changes in LDL-C at 3 and 12 months. Data was analyzed by gender.

Results
Study included 246 patients (mean age 67y, ASCVD 78.8%, mean baseline LDL-C 128.2 mg/dL). Women (42% of cohort) prescribed with PCSK9 mAb were older than men (69 vs. 65 years, respectively; p&lt;0.001). The dominant indication for PCSK9 mAb for both genders was secondary prevention, while primary prevention indication was more prevalent in women vs. men (39.4% vs. 16.3%, respectively; p&lt;0.001). Statin intolerance was observed in 82.4% and 58.6% were treated with combination therapy with PCSK9 mAb, without significant gender differences. Baseline mean LDL-C was higher among women vs. men (138.9 vs. 117.3 mg/dL; p&lt;0.001). Overall, high adherence was observed (91.8% and 79.7% at 3 and 12 months, respectively). After 1-year, adherent men had lower LDL-C levels than women (46.8 mg/d and 61.9 mg/dL, respectively; P=0.001), and were more likely to reach their LDL-C therapy goals; below 70 mg/dL (76.1% vs. 62.2%, respectively; P=0.032) and below 55 mg/dL (60.1% vs. 39.8% respectively; P=0.003).

Conclusions
In patients treated with PCSK9 mAb, gender differences exist in prescription age, indications, baseline LDL-C and achieved LDL-C goals. In this study adherence to PCSK9 mAb was higher than reported before, possibly due to surveillance in a dedicated prevention clinic.LDL-C & Non-HDL-C levels under PCSK9 mABSex Differences in acheived LDL-C goals
Heparin does not improve myocardial glucose metabolism suppression in patients with low betahydroxybutyrate level
Authors: Hartikainen S , Tompuri T , Laitinen T M , Hedman M , Laitinen T P 
Published: October 2024

Abstract

Background/introduction
Inadequate myocardial glucose metabolism suppression (GMS) can hamper diagnostic PET/CT imaging with [18F]FDG. β-hydroxybutyrate level (BHB) measurement prior to [18F]FDG injection is a newly proposed method of pre-evaluation of adequate GMS. However, more knowledge is needed, if BHB can be used to guide the preparation protocol (diet, fasting or premedication).

Purpose
The aim of our study was to evaluate if point-of-care measured BHB can be used to guide use of heparin premedication for cardiac [18F]FDG-PET/CT.

Methods
139 patients [78 male, median age 58 (19-78) years] with clinical indication for cardiac [18F]FDG PET/CT were recruited. All patients had followed a high fat, low carbohydrate diet for one day and fasted for at least twelve hours. For the first 64 patients, BHB was measured, but it was not used to guide premedication. For the next 75 patients, iv. heparin 50 IU/kg was injected 15-20 minutes before FDG injection, if BHB was low (less than 0.35 mmol/l), whereas those with high BHB (more than 0.35 mmol/l) continued without heparin. [18F]FDG uptake pattern was evaluated visually using grades "no uptake", "focal uptake", "isolated lateral wall uptake", "basal ring", "diffuse uptake" and "focal on diffuse". "No uptake" and "focal uptake" were considered as adequate GMS. Statistical significance of the difference in uptake patterns was evaluated using the Pearson’s chi-square test.

Results
Median BHB was 0.4 (0.1-5.8) mmol/l. Half of the patients (76, 55 %) reached BHB higher than 0.35 mmol/l. Still, 102 patients (74 %) had adequate GMS. In high BHB group, 65 patients (86 %) had adequate GMS, whereas of those with low BHB, only 37 patients (59 %) had adequate GMS (p&lt;0.001). In low BHB group prevalence of inadequate GMS was comparable in patients with and without heparin (42 % vs. 41 %, p=0.941) Results for the whole scale of visual distribution patterns can be seen in figure 1.

Conclusion(s)
Patients with high BHB have a high percentage of adequate GMS, whereas in patients with low BHB the probability of adequate GMS is significantly lower. Unfractionated heparin does not seem to improve myocardial GMS in patients with low BHB. Thus, high BHB should be pursued, and a longer diet might be needed for those with low initial BHB.
BMI shift and associated cardiometabolic risk factors in people with type 2 diabetes and obesity and/or overweight: a post hoc analysis from SURMOUNT-2
Authors: Sattar N , Lee C J , Wang H , Grant G , Zhang X M , Plat A 
Published: October 2024

Abstract

In SURMOUNT-2 (SM-2), treatment with once weekly GIP and GLP-1 receptor agonist tirzepatide (TZP) resulted in superior body weight reductions relative to placebo in people living with obesity and T2D. This post hoc analysis assessed whether participants with obesity (body mass index [BMI] ≥30 kg/m2) or overweight (BMI ≥27 kg/m2 with at least one weight-related comorbid condition) who shifted to a lower BMI category had improved cardiometabolic factors.
Change in BMI category (&lt;25 kg/m2, 25 to &lt;30 kg/m2, 30 to &lt;35 kg/m2, 35 to &lt;40 kg/m2, and ≥40 kg/m2) from baseline to week 72 was assessed in participants from SM-2 treated with TZP 10 or 15 mg (N=623) or placebo (PBO)(N=315). BMI shifts were grouped into "improved" (shift to lower BMI category) or "non-improved" (stable or shift to a higher BMI category). Cardiometabolic parameters examined included waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, and lipid profile. A mixed model with repeated measures was performed to estimate the mean change from baseline to week 72 for these parameters.
In this post hoc analysis a total of 484 (52.1%) participants had improved BMI at week 72. For those whose BMI did not improve, most had stable BMI and only 11 (1.2%) had worsened BMI. Nine participants had no post-baseline BMI measurements and were excluded from analysis. Most participants demonstrated improved BMI with TZP treatment (N=418, 67%) vs PBO (N=66, 21%)(Table). Furthermore, 21% (N=129) of participants on TZP improved by ≥2 BMI categories compared to only 1 participant with PBO. Compared to those with non-improved BMI, participants with improved BMI demonstrated greater improvement in cardiometabolic risk factors, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, systolic and diastolic blood pressure, triglycerides, and cholesterol (non-HDL-c, and LDL-c) and increases from baseline in HDL-c (Figure). Greater improvements to cardiometabolic risk factors were seen in participants on TZP vs PBO.
Shifts to lower BMI categories were greater among TZP-treated people living with obesity or overweight and T2D in SM-2 and were associated with improved cardiometabolic risk factors, in this post hoc analysis. SURMOUNT-mortality and morbidity and cardiovascular outcome trials are ongoing to examine the impact of TZP treatment on CVD and mortality.