bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal associations of insulin and Lp(a) levels: a Mendelian randomization study
Authors: Lejawa M , Golawski M , Fronczek M , Osadnik T , Pawlas N , Lisik M , Paneni F , Ruscica M , Jozwiak J , Gierlotka M , Banach M 
Published: October 2024

Abstract

Background
Numerous observational studies have demonstrated circulating lipoprotein(a) [Lp(a)] to be inversely related to occurrence of type 2 diabetes [T2D]. However, this is not consistently supported by Mendelian randomization [MR] studies. In vitro studies have shown insulin to downregulate Lp(a) expression, which might be another mechanism behind the correlation observed between Lp(a) and T2D.

Purpose
In this MR study, we investigated the influence of genetically predicted levels of insulin on genetically predicted Lp(a) levels to elucidate the potential causal links between Lp(a) and diabetes.

Methods
Independent genetic variants associated with insulin levels were acquired from a meta-analysis of genome-wide association studies (GWAS, N=151,013). Summary data for Lp(a) were acquired from a GWAS study in the UK Biobank (N=361,194). Inverse-variance-weighted (IVM) method was used to perform a two sample MR study. Sensitivity analysis was conducted via MR Egger, weighted median (WME), as well as leave-one-out analysis.

Results
Genetically predicted insulin levels were negatively associated with Lp(a) levels according to IVM estimate (p=0.003). In sensitivity analysis, WME supported this result (p=0.0002), while MR-Egger was not statistically significant (p=0.11). Leave-one-out analysis did not show the results to depend on any single variant.

Conclusion
This MR study provides robust evidence supporting the association between plasma insulin levels and decreased Lp(a) concentration. These findings suggest that hyperinsulinemia triggered by insulin resistance can be in part responsible for the observed negative correlation between low Lp(a) and T2D risk.
Figure 1. Genetic associations between insulin levels and Lp(a). Each genetic variant included in the analysis is represented as a point + 95% CI. Localization on the horizontal axis represents the correlation of the variant with exposure (plasma fasting insulin, inverse variance normal transformed values). Localization on the vertical axis represents the correlation of the variant with outcome (Lp(a), natural log transformed values). Lines represent estimates of different MR methods.Figure 1.
PCSK9 inhibitors in HIV patients with dyslipidemia
Authors: Datla S , Ali B , Sattouf Z 
Published: October 2024

Abstract

Introduction
Cardiovascular disease has become increasingly prevalent in the HIV (human immunodeficiency virus) population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug-drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring inhibitor of the LDL-receptor pathway. PCSK9 inhibitors offer an alternative in patients who cannot tolerate or need additional therapy in addition to statin for optimal dyslipidemia management.

Purpose
The purpose of this study is to compare major adverse cardiovascular events in HIV patients on a PCSK9 inhibitor (evolucumab, alirocumab, inclisiran) vs patients not on a PCSK9 inhibitor.

Methods
A retrospective cohort study was conducted using electronic medical records from a global federated health research network. The TriNetX network was searched on February 10, 2024, including records from 2020 to 2024. Patients were included based on a diagnosis of HIV status and concomitant dyslipidemia. Patients with HIV and dyslipidemia on a PCSK9 inhibitor were propensity-score matched for age, sex, race, and comorbidities with patients who were not on a PCSK9 inhibitor. The outcomes were mortality, myocardial infarction, heart failure and stroke.

Results
A total of 485 patients were included in the study. PCSK9 inhibitor use associated with 9% lower odds of all-cause mortality (odds radio, .29; 95% CI, 0.18-0.48; p&lt;.0001). PCSK9 inhibitor use was also associated with 8% lower odds of heart failure (odds radio, .63; 95% CI, 0.47-0.85; p&lt;.0023). No significant associations were noted for myocardial infarction (odds radio, .87; 95% CI, 0.63-1.21; p=0.406) or stroke (odds radio, .67; 95% CI, 0.45-1.01; p=0.052).

Conclusion
The role of dyslipidemia in HIV is challenging due the complex pathophysiology of HIV. There is an apparent increased risk of cardiovascular disease from the infection itself as well current antiretroviral therapies. While current guidelines recommend the use of statins as first line therapy for dyslipidemia in this population, the drug-drug interaction of statins with ARTs, as well as their side effects, limit their use at times. PCSK9 inhibitors are associated with lower odds of all-cause mortality and heart failure. No significant association was seen for myocardial infarction or stroke. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia. Further research should be done for the long term safety and tolerance of this therapy as well as cost-effectiveness and access to PCSK9 inhibitors in this population.
Lipoprotein (a) and lipidemic parameters in PCSK-9 inhibitor patients. Experience from a specialized centre in Greece
Authors: Dima I , Skoumas I , Andrikou I , Grigoriou K , Tsioufis K , Vlachopoulos C 
Published: October 2024

Abstract

Background
Previous studies have reported an association between Proprotein Convertase Subtilsin-kexin type 9 (PCSK-9) inhibition and levels of lipoprotein a [Lp (a)], having a possible effect on the cardiovascular benefit achieved by their use. The purpose of this study was to investigate the effect of PCSK-9 inhibitor use in Lp (a) and other lipidemic parameter levels in the population of a specialized Lipids Clinic during a follow up period of 24 months.

Methods
We enrolled 143 (80 males, mean age 60 years old) patients who were on PSCK-9 inhibitor treatment from the outpatient lipid clinic of our hospital. Information were obtained regarding the presence of coronary artery disease (CAD) and CAD risk factors. CAD was present in 72 patients (63%), Familial Hypercholesterolaemia (FH) in 97 patients (85%) and 20 (18%) patients suffered from statin intolerance. Patients were on triple lipid lowering therapy (statin plus ezetimibe plus PCSK-9 inhibitors) except for those with statin intolerance who were either on dual therapy (ezetimibe plus PCSK-9 inhibitors, N=8) or single PCSK-9 inhibitors therapy (N=10). Lp (a) levels and lipid parameters such as Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglycerides (TG) were measured at baseline, 3 months, 12 months and 24 months of treatment. Additionally, patients were categorized according to baseline Lp (a) levels in two groups, Group 1 (&lt;70mg/dl) (N=62), Group 2 (≥70 mg/dl) (N=26). A comparison of the response in lipid parameters between these two groups was performed.

Results
Mean value for Lp (a) in the whole population was 54mg/dl, 48mg/dl, 44mg/dl, and 45mg/dl at baseline, 3, 12 and 24 months, respectively. T test analysis revealed a significant reduction in Lp (a) levels after 12 months (P&lt;0.05) There was also a significant reduction in LDL levels at all time points (165mg/dl to 78mg/dl, 85mg/dl, 78mg/dl respectively, P&lt;0.05), a reduction in triglyceride levels at 3 and 12 months (125mg/dl to 110mg/dl, 108mg/dl respectively, P&lt;0.05) and an increase in HDL levels after 12 months (50mg/dl to 53mg/dl, P&lt;0.05). Moreover, in Group 1, the response in LDL levels was higher after 12 months of treatment with PCSK-9 inhibitors (158mg/dl to 69mg/dl, P&lt;0.05) compared to Group 2 (155mg/dl to 86mg/dl), indicating that high levels of Lp (a) seem to define the response to treatment.

Colclusions
Besides the detrimental effect in LDL levels, PCSK-9 inhibition has an impact on HDL and TG levels. Lp (a) was also reduced indicating an additional important effect of this inhibition. While higher levels of Lp (a) seem to correlate with poorer response to treatment, our findings enhance the already known importance of Lp (a) as a prognostic factor.
Efficacy and severity of side-effects of rosuvastatin compared to other statins post-heart-transplantation
Authors: Van Dijk B C J , Bos D , Roest S , Goedendorp-Sluimer M M , Brugts J J , Constantinescu A A , Van Der Boon R M A , Taverne Y J H J , De Boer R A , Budde R P J , Caliskan K , Manintveld O M 
Published: October 2024

Abstract

Introduction
The International Society of Heart and Lung Transplantation (ISHLT) 2022 guideline recommends statin therapy in heart transplantation (HTx) patients, with the therapeutic low-density lipoprotein (LDL) target being &lt;2.5 mmol/L. Particularly pravastatin is recommended, given proven beneficial effects on long-term clinical outcome and the low prevalence of side effects. Yet, in the general population, rosuvastatin has been shown to be even more potent.

Purpose
We investigated the lipid-lowering effect and severity of side-effects of rosuvastatin compared to less potent statins in HTx patients.

Methods
In this before-after study, we included all HTx patients whom were prescribed a change from the statin they were using to rosuvastatin, for better cardiovascular risk management and/or because of side-effects, between February 2018 and February 2023. We evaluated the weight, lipid profile and side-effects (including myalgia, cramps, stiffness and weakness) of these patients up to one year prior to and after the statin change. At the same time, side-effects were measured in a visual analogue scale (VAS) ranging from 0-10, with the average score of side-effects utilized for analysis. We compared the differences using a Wilcoxon signed rank test.

Results
Out of 299 HTx patients, we included 114 patients, with a median age of 58 [IQR 50-67] years at switch of whom 31 (27%) were females. Median time since HTx was 9 [IQR 5-15] years. The distribution and dosage of prescribed statins before and after switch can be found in Table 1. Compared to statins used prior to therapy change, rosuvastatin was associated with lower total cholesterol, LDL- and triglyceride levels, with high density lipoprotein (HDL) levels remaining the same (Table 2). No difference in bodyweight was found (Table 2). Before switch, 41 (36%) patients achieved the target of LDL-levels below 2.5 mmol/L. After switch, 86 (75%) patients achieved the target of LDL levels below 2.5 mmol/L. Rosuvastatin shows a trend towards a lower prevalence of side-effects (Table 2).

Conclusion
In HTx patients that were prescribed a change of statin due to better cardiovascular risk management and/or complaints of side-effects, rosuvastatin is related to a more favorable lipid profile, without additional side-effects, compared to other statins. Furthermore, many more patients achieve the guideline recommended LDL-target. Ongoing research should determine whether this translates to a better clinical outcome.
Low-density lipoprotein cholesterol goal attainment with "inclisiran first" versus usual care in patients with atherosclerotic cardiovascular disease
Authors: Rodriguez F , Koren M , East C , Ali Y , Kleeman K , Sarwat S , Abbas C , Toth P P 
Published: October 2024

Abstract

Background
Rapid and sustained attainment of guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals is critical for patients with atherosclerotic cardiovascular disease (ASCVD). In VICTORION-INITIATE, inclisiran administered twice-yearly by a healthcare professional earlier in the treatment pathway allowed more patients with ASCVD to achieve and sustain LDL-C goals vs current usual care (UC).

Purpose
To evaluate cumulative LDL-C exposure in the overall population and LDL-C goal attainment and safety in subgroups of participants (type of ASCVD, timing of ASCVD event, and history of statin intolerance) who received an "inclisiran first" implementation strategy (IF; adding inclisiran immediately on failure to achieve LDL-C &lt;70 mg/dL [1.8 mmol/L] with maximally tolerated statins) compared with UC.

Methods
VICTORION-INITIATE was a 330-day, prospective, pragmatically designed trial that randomised participants 1:1 (stratified by insurance status) to IF (open-label inclisiran 284 mg at Days 0, 90 and 270 plus UC) or UC alone (lipid management directed by treating physician’s discretion). The study took place at 45 sites across 20 states in the USA. Treating physicians had access to LDL-C measurements and were encouraged to intensify treatment per clinical practice guidelines. This prespecified subgroup analysis evaluated LDL-C goal attainment by timing of the most recent ASCVD event (&lt;1 year/≥1 year prior to consent), ASCVD subtype (coronary heart disease [CHD], peripheral arterial disease [PAD], and cerebrovascular disease [CVD]) and statin intolerance status. Cumulative LDL-C exposure over time in the overall population and safety by subgroup were also evaluated.

Results
Of 450 patients randomised to IF or UC, 11.1% and 84.2% had an ASCVD event &lt;1 year or ≥1 year prior to consent, respectively; 91.8%, 18.2% and 14.7% had a history of CHD, CVD or PAD, and 25.8% were statin intolerant. Cumulative exposure to LDL-C to Day 330 was lower in patients treated with IF vs UC (mean time-adjusted LDL-C: 42.4 mg/dL vs 90.7 mg/dL, Figure). Significantly more patients who received IF achieved LDL-C goals of &lt;70 mg/dL and &lt;55 mg/dL at Day 330 vs UC, irrespective of subgroup (Table). Across subgroups, the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs were similar between IF and UC (IF: 52.6−71.2%, UC: 46.2−66.0% and IF: 10.7−28.3%, UC: 11.4−22.2%, respectively).

Conclusions
Participants with ASCVD and LDL-C &gt;70 mg/dL who received IF had lower cumulative LDL-C exposure over the study period than those treated with UC. IF resulted in rapid and sustained achievement of LDL-C goals regardless of ASCVD subtype, event timing and statin intolerance. The safety profile of IF was consistent across the subgroups analysed.
Safety and Efficacy of Moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis
Authors: Alves Kelly F , Oliveira Macena Lobo A , Aquino De Moraes F C , Morbach V , Kendi Tsuchiya Sano V , Menegaz De Almeida A , Marciano Consolim-Colombo F , Laurinavicius A , Goncalves De Sousa M , Batista Souza J 
Published: October 2024

Abstract

Background
Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide, poses an important healthcare challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear.

Purpose
This meta-analysis seeks to assess the impact of moderate-intensity statin plus ezetimibe (MIS+EZT) versus high-intensity statin monotherapy (HIS) on LDL &lt; 70mg/dl; Total Cholesterol; LDL; High Density Cholesterol (HDL) and triglycerides levels. Our goal is to synthesize the existing evidence and pinpoint areas that warrant further investigation.

Methods
A thorough literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients.

Results
In the 13 included studies, involving 8,592 patients, of which 4,525 (52.67%) received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 12 to 219 weeks, with participant ages varying from 66 to 76.5 years in the MIS+EZT group and from 67 to 75.9 years in the HIS group. Analysis revealed significant MIS+EZT-associated with greater percentages in Low Density Lipoprotein (LDL) &lt; 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p&lt;0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p&lt;0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p&lt;0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78 ; 95% CI [0.32; 1.92]; p=0.584; I²=35%).

Conclusions
This meta-analysis underscores the effectiveness of MIS+EZT in enhancing significant clinical outcomes for ASCVD patients, as evidenced by improvements in a greater percentage of patients achieved the LDL &lt;70 target, LDL, Total Cholesterol and Triglycerides levels . Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.
The upfront lipid-lowering combination therapy of statins and ezetimibe vs statin monotherapy in the reduction of cardiovascular outcomes. A meta-analysis.
Authors: Banach M , Jaiswal V , Ang S P , Sawhney A , Deb N , Penson P , Toth P 
Published: October 2024

Abstract

Background
Despite some data in last few years, there is still some inconsistency concerning the effectiveness and safety of the upfront intensive lipid lowering combination therapy (LLT; of moderate to high intensity statin therapy and ezetimibe) in comparison to high intensity statin therapy and recommended by some guidelines stepwise therapy approach.

Purpose
We sought to evaluate the efficacy of combination LLT compared with statin monotherapy for cardiovascular outcomes, LDL-C reduction, and associated adverse events.

Methods
A systematic literature search was conducted using PubMed, Embase, and ClinicalTrial.gov to identify relevant articles published from inception until 29th December 2023. The outcomes were assessed using pooled odds ratio (OR) for categorical data and mean difference (MD) for continuous data, with corresponding 95% confidence intervals (95% CI).

Results
A total of 11 studies (8 randomized controlled trials and 3 cohort studies) with 106,358 were involved in the analysis. The mean age of the patients in the combination LLT and statin monotherapy group was 65.3 and 65.7 years, respectively. Pooled analysis shows that combination LLT significantly reduces the LDL-C level from the baseline (MD, -12.13 mg/dl [0.31 mmol/l] (95%CI: -18.26 to -5.99 mg/dl), p&lt;0.001), all-cause mortality (ACM) (OR, 0.75, 95%CI: 0.62 to 0.92, p=0.01), cardiovascular mortality (CVM) (OR 0.75, 95%CI: 0.66 to 0.84, p&lt;0.001), major adverse cardiovascular events (MACE) (OR, 0.72 95%CI: 0.63 to 0.82, p&lt;0.001), non-significant reduction in the incidence of stroke (OR 0.82, 95%CI: 0.66 to 1.01, p=0.06) when compared with statin monotherapy alone. Similarly, the therapy discontinuation rate was comparable between combination LLT and statin monotherapy groups (OR, 0.87 (95%CI: 0.53 to 1.40), p=0.56). The risk of adverse events related to the gastrointestinal tract (OR, 1.12 (95%CI: 0.93 to 1.36), p=0.23) and musculoskeletal system (OR, 0.88 (95%CI: 0.52 to 1.50), p=0.65) was comparable between both the groups of patients.

Conclusion
Combination LLT was associated with an overall greater reduction in LDL-C, a lower risk of ACM, MACE, and CVM compared to statin monotherapy alone.Forest Plot of desired outcomes.Central illustration with key findings.
Score-2 in heavy smokers: are we underestimating the risk?
Authors: Cosmi D , Mariottoni B , Tarquini B , Cosmi F 
Published: October 2024

Abstract

Background
The shared diagnostic decision-making process in patients with atypical chest pain is challenging, especially when functional tests are negative. SCORE2 (1) can help in making decisions. In this score, the risk is assessed based on geographical origin, age, sex, current smoking, systolic blood pressure, cholesterol values.
However, it does not take into account the quantity of cigarettes smoked but only the current binary value, yes or no. In our study we wanted to evaluate the impact of smoking on prognosis, considering the number of cigarettes smoked and in particular focusing on heavy smokers.

Methods
In the last 15 years we evaluated 3,588 outpatients aged &gt;35 years (average 64±9, women 55%) for the presence of stable chest pain. We excluded 290 patients who had ECG changes compatible with recent ischemia, history of myocardial infarction or any other major cardiovascular event, evidence of heart failure, left ventricular dysfunction, or cardiomyopathies. In the other 3,298 cases we applied the traditional classification of typical, atypical angina and non-anginal pain. A functional test was performed in all patients. In 2,774 patients with atypical chest pain and negative functional test we evaluated the extent of cardiovascular risk based on SCORE2 and the number of cigarettes currently smoked. One year follow-up was carried out to evaluate vital status and any fatal and non-fatal cardiovascular events.

Results
Table 1 shows the events in patients classified according to the degree of cardiovascular risk of SCORE2 and in heavy smokers (≥ 20 cigarettes per day) aged &lt;70 years as a cathegory in itself. In moderate smokers (&lt;20 cigarettes/day) of any age, the risk was considered binary as in the conventional assessment. Tables 2 and 3 show the risk stratification in male and female patients. SCORE2 is unable to intercept the extremely high risk of heavy smokers aged &lt;70 years.
This happens both in males, considered at moderate risk in 76% of cases but with a rate of fatal events of 2.4% and as many non-fatal events, both in women with a risk considered moderate in 80% of cases but with a 12% rate of fatal events (as seen in Table 1).

Conclusions
SCORE2 does not consider the quantity of cigarettes smoked per day, so if we rely on it heavy smokers seem to have a moderate risk. On the contrary, based on our analysis, they all have an extremely high risk, regardless of other risk factors, and in any case higher than non-smoking or moderately smoking patients. Especially heavy smoking women aged &lt;70 years with atypical chest pain and negative functional tests have an extreme risk of fatal cardiac events (12% at one year). Probably these patients (male and female), regardless of the outcome of functional tests, should be sent for an anatomical evaluation for the detection of high-risk stenosis, as well as firmly urged to improve lifestyles and treat risk factors .