Association of Lipoprotein(a) With Major Adverse Limb Events and All-Cause Mortality Following Revascularization for Chronic Limb-Threatening Ischemia: A Substudy of the BEST-CLI Trial.

Background: The BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia) trial tested the optimal initial revascularization strategy in patients with chronic limb-threatening ischemia. Little is known about the prognostic relevance of Lp(a) (lipoprotein[a]) and its modification by renal function in patients with chronic limb-threatening ischemia. We investigated the relationship between Lp(a) and prespecified cardiovascular outcomes.

Low functional capacity in peripheral artery disease is associated with increased platelet activity and cardiovascular events.

Background And Aims: Low functional capacity is an independent risk factor for cardiovascular (CV) events. Regular physical activity may reduce CV risk through suppression of inflammation and reduced platelet activity. We aimed to investigate the association of functional capacity quantified by the validated Duke Activity Status Index (DASI) with platelet activity and incident major adverse CV and limb events (MACLE) in individuals with peripheral artery disease (PAD) undergoing lower extremity revascularization (LER).

Guideline-Directed Medical Therapy and Outcomes in the ISCHEMIA Trial.

Background: Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain.

Objectives: This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes.

Variation in lipoprotein(a) response to potent lipid lowering: The role of apolipoprotein (a) isoform size.

Background: Lipoprotein(a) [Lp(a)] is a driver of residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) decrease Lp(a) with significant heterogeneity in response. We investigated contributors to the heterogeneous response.

A Platelet Reactivity ExpreSsion Score derived from patients with peripheral artery disease predicts cardiovascular risk.

Platelets are key mediators of atherothrombosis, yet, limited tools exist to identify individuals with a hyperreactive platelet phenotype. In this study, we investigate the association of platelet hyperreactivity and cardiovascular events, and introduce a tool, the Platelet Reactivity ExpreSsion Score (PRESS), which integrates platelet aggregation responses and RNA sequencing. Among patients with peripheral artery disease (PAD), those with a hyperreactive platelet response (>60% aggregation) to 0.

Cardiometabolic Co-morbidity Burden and Circulating Biomarkers in Patients With Chronic Coronary Disease in the ISCHEMIA Trials.

Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity.

A review of air pollution as a driver of cardiovascular disease risk across the diabetes spectrum.

The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes.

Personal Strategies to Reduce the Cardiovascular Impacts of Environmental Exposures.

Ubiquitous environmental exposures increase cardiovascular disease risk via diverse mechanisms. This review examines personal strategies to minimize this risk. With regard to fine particulate air pollution exposure, evidence exists to recommend the use of portable air cleaners and avoidance of outdoor activity during periods of poor air quality.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

Background: ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease.

Methods: Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use.

Baseline characteristics including blood and urine metal levels in the Trial to Assess Chelation Therapy 2 (TACT2).

Background: The reduction in cardiovascular disease (CVD) events with edetate disodium (EDTA) in the Trial to Assess Chelation Therapy (TACT) suggested that chelation of toxic metals might provide novel opportunities to reduce CVD in patients with diabetes. Lead and cadmium are vasculotoxic metals chelated by EDTA. We present baseline characteristics for participants in TACT2, a randomized, double-masked, placebo-controlled trial designed as a replication of the TACT trial limited to patients with diabetes.

Variation in Health Status With Invasive vs Conservative Management of Chronic Coronary Disease.

Background: The ISCHEMIA trial found that patients with chronic coronary disease randomized to invasive strategy had better health status than those randomized to conservative strategy. It is unclear how best to translate these population-level results to individual patients.

Objectives: The authors sought to identify patient characteristics associated with health status from invasive and conservative strategies, and develop a prediction algorithm for shared decision-making.

Platelet RNA Biomarker of Ticagrelor-Responsive Genes Is Associated With Platelet Function and Cardiovascular Events.

Background: Identifying patients with the optimal risk:benefit for ticagrelor is challenging. The aim was to identify ticagrelor-responsive platelet transcripts as biomarkers of platelet function and cardiovascular risk.

Methods: Healthy volunteers (n=58, discovery; n=49, validation) were exposed to 4 weeks of ticagrelor with platelet RNA data, platelet function, and self-reported bleeding measured pre-/post-ticagrelor.

Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials.

Importance: Biomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown.

Objectives: To evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia.

Design And Setting: The ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository.

Timing of Antihypertensive Drug Therapy: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: The timing of antihypertensive drugs administration is controversial. The aim was to compare the efficacy of dosing of antihypertensive drugs in the morning versus evening.

Methods: A PubMed, EMBASE, and clinicaltrials.

Health Status and Clinical Outcomes in Older Adults With Chronic Coronary Disease: The ISCHEMIA Trial.

Background: Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown.

Objectives: The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial.

Methods: One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status).