Daily Cardiology Research Analysis
Analyzed 201 papers and selected 3 impactful papers.
Summary
Analyzed 201 papers and selected 3 impactful articles.
Selected Articles
1. Digitally Enabled Quality Improvement Intervention and LDL-C Control in Atherosclerotic Cardiovascular Disease: The SAPPHIRE-LDL Cluster Randomized Clinical Trial.
In a pragmatic cluster RCT of 28 clinics and 1,465 patients with ASCVD, a digitally enabled QI strategy reduced mean LDL-C at 6 months by 6.62 mg/dL vs usual care and increased the proportions achieving LDL-C <50 mg/dL and ≥50% reduction. The intervention also increased use of intensive and combination lipid-lowering therapy, without differences in major cardiovascular events over 6 months.
Impact: This CONSORT-aligned, registered cluster RCT demonstrates a scalable, workflow-embedded digital strategy that measurably narrows the LDL-C treatment gap in real-world ASCVD care.
Clinical Implications: Health systems can deploy digitally enabled previsit screening, decision support, and audit-feedback to drive lipid testing and treatment intensification, expecting modest absolute LDL-C gains at 6 months; further steps are needed to reach guideline LDL-C targets broadly.
Key Findings
- Mean LDL-C at 6 months was 76.3 mg/dL (intervention) vs 85.6 mg/dL (control); adjusted mean difference −6.62 mg/dL (95% CI, −11.11 to −2.13; P=.004).
- LDL-C <50 mg/dL achieved in 23.5% vs 13.4% (OR 1.86; 95% CI, 1.30-2.65).
- ≥50% LDL-C reduction achieved in 18.6% vs 13.4% (OR 1.76; 95% CI, 1.27-2.43).
- Higher prescription rates of intensive and combination lipid-lowering therapy in the intervention arm.
- No significant differences in major cardiovascular events over 6 months.
Methodological Strengths
- Pragmatic cluster randomized design with intention-to-treat analysis using GEE accounting for clustering
- Pre-registered trial with clearly defined, objective primary endpoint (LDL-C)
Limitations
- Short 6-month follow-up without demonstrated differences in clinical events
- Modest absolute LDL-C reduction; residual care gap persists despite intervention
Future Directions: Test extended, multi-component implementation bundles and patient-facing tools to further close LDL-C gaps and determine effects on clinical events over longer follow-up.
IMPORTANCE: Bridging the low-density lipoprotein cholesterol (LDL-C) care gap in patients with established atherosclerotic cardiovascular disease (ASCVD) is challenging. Few quality improvement (QI) interventions have successfully improved patient care. OBJECTIVE: To evaluate the impact of a digitally enabled, multifaceted, QI intervention on the control of LDL-C concentration in patients with ASCVD. DESIGN, SETTING AND PARTICIPANTS: This was a pragmatic, 2-arm, cluster randomized clinical trial. A total of 28 clusters (public or private outpatient clinics) in Brazil were randomized to receive a digitally enabled QI intervention or routine practice (control). Adult patients (≥18 years) with established ASCVD were enrolled between November 2023 and December 2024 and followed up for 6 months. INTERVENTION: The intervention comprised a structured, digitally enabled QI strategy integrating previsit screening, electronic clinical decision support algorithms, audit and feedback mechanisms, and targeted clinician and patient engagement tools embedded within routine workflows to support lipid monitoring, treatment intensification, and adherence. MAIN OUTCOMES AND MEASURES: The primary outcome was mean LDL-C level at 6 months.
2. Global, regional, and national prevalence of peripheral arterial disease in 2023: an updated systematic review and modelling study.
Synthesizing 157 studies across 37 countries (>9.7 million participants), the authors estimate a 2023 global PAD prevalence of 6.58% (≈316.5 million adults), rising markedly with age and slightly higher in women. LMICs bear over three-quarters of cases; smoking (OR 2.85), diabetes (1.81), hypertension (1.64), and hypercholesterolemia (1.34) are key correlates. European regions show the highest prevalence, with the Western Pacific region harboring the most cases.
Impact: Provides the most up-to-date, methodologically robust global PAD burden estimates, directly informing screening, prevention, and health system planning.
Clinical Implications: Supports ABI-based and risk-based case-finding in high-risk groups, integration of PAD into broader cardiovascular prevention pathways, and targeted policies in high-burden LMICs.
Key Findings
- Estimated 2023 global PAD prevalence 6.58% among adults ≥25 years, equating to ≈316.54 million cases.
- Prevalence increases with age (4.31% at 25–29 to 22.09% at 90–99) and is slightly higher in women; HICs have higher prevalence but LMICs account for >75% of cases.
- Smoking (OR 2.85), diabetes (1.81), hypertension (1.64), and hypercholesterolemia (1.34) are robust correlates; ~60% of global cases concentrate in ten countries.
Methodological Strengths
- Comprehensive, PROSPERO-registered systematic review with standardized ABI definition and dual independent screening.
- Multilevel mixed-effects meta-regression with age–sex splitting; random-effects meta-analysis for correlates and factor-based distribution modeling.
Limitations
- Geographic under-representation and heterogeneity across studies may limit national precision.
- Cross-sectional prevalence and modeling assumptions preclude causal inference and may under-detect PAD with non-compressible arteries.
Future Directions: Standardized, population-based PAD surveillance in underrepresented regions; implementation studies for ABI/risk-based screening and access to vascular care in LMICs.
BACKGROUND: Peripheral arterial disease is a growing public health concern. We aimed to provide updated estimates of peripheral arterial disease prevalence and case numbers at the global, regional, and national levels in 2023, and synthesise evidence on factors associated with peripheral arterial disease. METHODS: In this systematic review and modelling analysis, we searched PubMed, Embase, MEDLINE, CINAHL, Global Health, AMED, and ProQuest Dissertations and Theses Global for articles and grey literature published between April 30, 2019, and Dec 9, 2024, reporting peripheral arterial disease prevalence in the general population. This search was supplemented by eligible studies identified through relevant systematic reviews and manual reference screening. Studies were eligible if peripheral arterial disease was defined as an ankle-brachial index (ABI) lower than or equal to 0·90. Studies using hospital-based or clinical samples and studies conducted exclusively in populations with specific characteristics (eg, diabetes) were excluded. Two reviewers independently screened records for eligibility, extracted study-level data, and assessed the study quality using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. An age-sex splitting procedure was applied to disaggregate prevalence data. A multilevel multivariable mixed-effects meta-regression approach was used to examine the associations between age and peripheral arterial disease prevalence, stratified by sex and income level (high-income countries [HICs] and low-income and middle-income countries [LMICs]). Pooled odds ratios (ORs) for factors associated with peripheral arterial disease were estimated through a random-effects meta-analysis. Peripheral arterial disease prevalence at regional and national levels was derived using an associated factor-based distribution model. The study protocol was registered in PROSPERO (CRD420261290434).
3. A loss-of-function polymorphism in the propeptide of lysyl oxidase exacerbates atherosclerosis.
Using a Pcsk9-AAV8/high-fat mouse model and single-cell RNA sequencing, the LOX-PP R158Q polymorphism aggravated atherosclerosis by driving proliferative and calcification programs in plaque macrophages and smooth muscle cells despite unchanged LOX enzymatic activity. The data reveal an enzymatically independent, proatherogenic role of the LOX propeptide, nominating it as a potential therapeutic target.
Impact: This work uncovers a previously unappreciated, enzyme-independent mechanism by which a human LOX-PP variant promotes atherogenesis and maps cell-type–specific programs underlying the phenotype.
Clinical Implications: While preclinical, these findings prioritize LOX-PP biology—and not just LOX enzymatic cross-linking—as a tractable axis for anti-atherosclerotic therapies, potentially enabling genotype-informed interventions.
Key Findings
- LOX-PP R158Q polymorphism increased atherosclerotic burden in a Pcsk9-AAV8/high-fat diet mouse model.
- Macrophage and vascular smooth muscle cell proliferation was enhanced without altering LOX enzymatic activity.
- Single-cell RNA-seq showed enrichment of proliferation- and calcification-related gene programs in plaques from R158Q mice.
- Findings support an enzymatically independent proatherogenic role for LOX-PP.
Methodological Strengths
- Integrated in vivo atherosclerosis model with single-cell transcriptomics for mechanistic resolution
- Genotype-specific interrogation demonstrating phenotype independent of LOX enzymatic activity
Limitations
- Preclinical mouse model without human cohort validation
- Therapeutic tractability of LOX-PP requires targetability and safety testing
Future Directions: Validate LOX-PP pathways in human vascular tissues and test LOX-PP–directed modulation in preclinical therapeutic studies, including genotype-stratified approaches.
A single-nucleotide missense polymorphism (rs1800449, R158Q) in the propeptide domain of lysyl oxidase (LOX-PP) is associated with increased risk of coronary artery disease (CAD) independent of changes in plasma lipid levels. Although the enzymatic function of LOX has an essential role for the cross-linking of extracellular matrix proteins in connective tissues, whether and how LOX-PP R158Q contributes to the development of atherosclerosis has not been clearly established. Here, hypercholesterolemia was induced in mice that were WT or homozygous for the LOX-PP R158Q polymorphism by adeno-associated virus-8-mediated overexpression of Pcsk9 followed by high-fat diet feeding for 16 weeks. We found that the R158Q polymorphism promoted atherosclerosis and induced proliferation of macrophages and vascular smooth muscle cells without altering LOX enzymatic activity. Using single-cell RNA sequencing, we found the transcriptional program of atherosclerotic plaques from mice harboring R158Q was strongly enriched for proliferation- and calcification-related genes in a regionally distinct manner. Together, these results establish an enzymatically independent proatherogenic role for the LOX-PP and suggest its potential as a novel therapeutic target.