Blood Pressure Changes During Methotrexate Treatment: Results from a Randomized Placebo-Controlled Trial Among Patients with Cardiovascular Risk.

Objective: Low dose methotrexate (LD-MTX) has been associated with a reduced risk of cardiovascular disease (CVD) among patients with systemic rheumatic diseases but not among the general population. Prior reports suggest that LD-MTX may reduce blood pressure (BP). We studied the effect of LD-MTX on blood pressure.

Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis.

Background: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined.

Methods: A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD).

Lessons Learned from National Heart, Lung, and Blood Institute Covid-19 Clinical Trials.

AbstractIn response to the Covid-19 pandemic, the National Heart, Lung, and Blood Institute launched five multisite clinical trials testing candidate host tissue-directed medical interventions to hasten recovery, improve function, and reduce morbidity and mortality. Speed, flexibility, and collaboration were essential. This article from the Steering and Executive committees describes the Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies (CONNECTS) research program that enrolled 6690 participants and evaluated 18 intervention strategies using 10 molecular agents across the care continuum (outpatient, inpatient, and post discharge), and reports lessons learned from this initiative.

Brief Report: Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.

Background: People with HIV-1 often have chronic inflammation leading to severe non-AIDS morbidity and mortality. The AIDS Clinical Trials Group Study A5314 sought to lower inflammation with low-dose methotrexate (LDMTX). The primary study outcomes were reported previously but here we present the impact of LDMTX on multiple measures of HIV-1 persistence.

ApoA-I Infusions and Burden of Ischemic Events After Acute Myocardial Infarction: Insights From the AEGIS-II Trial.

Background: Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90 days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events.

Apolipoprotein A-I infusions and cardiovascular outcomes in acute myocardial infarction according to baseline LDL-cholesterol levels: the AEGIS-II trial.

Background And Aims: In the AEGIS-II trial (NCT03473223), CSL112, a human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity, did not significantly reduce the risk of the primary endpoint through 90 days vs. placebo after acute myocardial infarction (MI). Nevertheless, given the well-established relationship between higher low-density lipoprotein cholesterol (LDL-C) and plaque burden, as well as greater risk reductions seen with PCSK9 inhibitors in patients with baseline LDL-C ≥ 100 mg/dL on statin therapy, the efficacy of CSL112 may be influenced by baseline LDL-C.

Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women.

Background: High-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels contribute to 5-year and 10-year predictions of cardiovascular risk and represent distinct pathways for pharmacologic intervention. More information about the usefulness of these biomarkers for predicting cardiovascular risk over longer periods of time in women is needed because early-life intervention represents an important risk-reduction method.

Methods: We measured high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels at baseline in 27,939 initially healthy U.

Course of the effects of LDL-cholesterol reduction on cardiovascular risk over time: A meta-analysis of 60 randomized controlled trials.

Background And Aims: Individuals with or at high risk of cardiovascular disease (CVD) often receive long-term treatment with low-density lipoprotein cholesterol (LDL-C) lowering therapies, but whether the effects of LDL-C reduction remain stable over time is uncertain. This study aimed to establish the course of the effects of LDL-C reduction on cardiovascular risk over time.

Methods: Randomized controlled trials (RCTs) of LDL-C lowering therapies were identified through a search in MEDLINE and EMBASE (1966-January 2023).

Lessons from PROMINENT and prospects for pemafibrate.

The neutral result of the PROMINENT trial has led to questions about the future for pemafibrate. This commentary discusses possible reasons for the lack of benefit observed in the trial. There were, however, indicators suggesting therapeutic potential in microvascular ischaemic complications associated with peripheral artery disease, with subsequent analysis showing reduction in the incidence of lower extremity ischaemic ulceration or gangrene.

One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial.

Background: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L.

Mediterranean Diet Adherence and Risk of All-Cause Mortality in Women.

Importance: Higher adherence to the Mediterranean diet has been associated with reduced risk of all-cause mortality, but data on underlying molecular mechanisms over long follow-up are limited.

Objectives: To investigate Mediterranean diet adherence and risk of all-cause mortality and to examine the relative contribution of cardiometabolic factors to this risk reduction.

Design, Setting, And Participants: This cohort study included initially healthy women from the Women's Health Study, who had provided blood samples, biomarker measurements, and dietary information.

IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial.

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l at baseline were randomized to receive clazakizumab (2.

Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

Aims: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals.

Methods And Results: The updated LIFE-CVD (i.