Daily Cardiology Research Analysis
Analyzed 170 papers and selected 3 impactful papers.
Summary
Analyzed 170 papers and selected 3 impactful articles.
Selected Articles
1. The NOTCH3 extracellular domain is a serum biomarker for pulmonary arterial hypertension.
Across three independent cohorts (341 IPAH; 376 healthy controls), serum NOTCH3-ECD concentrations were significantly higher in idiopathic pulmonary arterial hypertension, supporting its role as a circulating biomarker. The work translates a mechanistic observation—NOTCH3 cleavage in IPAH lungs—into a measurable serum analyte.
Impact: Introduces a mechanistically anchored serum biomarker for IPAH with multi-cohort validation, potentially enabling earlier diagnosis and noninvasive disease monitoring.
Clinical Implications: If validated prospectively and across pulmonary hypertension subgroups, serum NOTCH3-ECD could aid diagnosis, risk stratification, and treatment monitoring of PAH. Implementation would require assay standardization and evaluation versus established markers (e.g., NT-proBNP) and imaging/hemodynamics.
Key Findings
- Serum NOTCH3-ECD levels were significantly elevated in IPAH compared with healthy controls across three geographically distinct cohorts.
- The study leverages constitutive NOTCH3 cleavage in IPAH lungs to identify a circulating extracellular domain as a biomarker.
- Cohorts included 341 IPAH patients and 376 healthy individuals, supporting generalizability for a rare disease setting.
Methodological Strengths
- Multi-cohort validation across geographically distinct populations
- Mechanistic grounding (NOTCH3 cleavage) linked to a measurable serum analyte
Limitations
- Abstract does not report diagnostic accuracy metrics (e.g., ROC/AUC) or longitudinal prognostic data
- Comparative performance versus other PAH etiologies and biomarkers not detailed
Future Directions: Prospective, multi-etiology pulmonary hypertension studies should define diagnostic thresholds, prognostic value, and treatment-response dynamics of NOTCH3-ECD, with standardized assays and head-to-head comparisons versus existing markers.
New biomarkers are needed to detect and follow individuals with World Health Organization group 1.1 pulmonary hypertension (idiopathic pulmonary arterial hypertension (IPAH)). As NOTCH3 cleavage occurs constitutively in the lungs of individuals with IPAH, we investigated whether the NOTCH3 extracellular domain (NOTCH3-ECD) shed into serum could be used as a robust biomarker for IPAH. In three geographically distinct cohorts comprising 341 individuals with IPAH (267 women, 74 men) and 376 healthy individuals (278 women, 98 men), serum NOTCH3-ECD levels were significantly higher in individuals with IPAH (mean ± s.d.: 19.9 ± 5.5 ng ml
2. Associations of biological ageing and genetic risk with incident abdominal aortic aneurysm.
In 350,483 UK Biobank participants, accelerated biological ageing (residual KDMAge and PhenoAge) was associated with higher incident AAA risk (HR 1.29 and 1.63, respectively). Individuals with both accelerated biological age and high polygenic risk had the greatest risk (HR 2.15–2.72), with a significant additive interaction for PhenoAge.
Impact: Links clinically accessible biological age algorithms with AAA risk at population scale and shows synergy with genetic predisposition, informing risk stratification beyond chronological age.
Clinical Implications: Incorporating biological age (e.g., PhenoAge) with polygenic risk could improve AAA screening strategies and preventive targeting. Translation will require calibration of thresholds, external validation, and evaluation of cost-effectiveness and equity.
Key Findings
- Accelerated KDMAge and PhenoAge were independently associated with higher incident AAA risk (HR 1.29 and 1.63).
- Jointly high biological ageing and genetic risk conferred the greatest AAA risk (KDMAge HR 2.15; PhenoAge HR 2.72).
- Significant additive interaction between high genetic risk and accelerated PhenoAge was observed.
Methodological Strengths
- Very large population-based cohort with standardized data and two complementary biological age measures
- Integration of polygenic risk scores with time-to-event modeling
Limitations
- Observational design susceptible to residual confounding and selection bias
- Generalizability beyond UK Biobank demographics and health system context remains to be shown
Future Directions: External validation in diverse cohorts; establish actionable thresholds; test whether biological age-guided screening or interventions reduce AAA events in pragmatic trials.
BACKGROUND: Abdominal aortic aneurysm (AAA) is a degenerative cardiovascular disorder prevalent with ageing. While accelerated biological ageing contributes to age-related diseases, its specific role in AAA risk remains unclear. This study investigates the relationships between biological ageing and risk of incident AAA and genetic predisposition to the disease. METHODS: This retrospective study used UK Biobank data from 350,483 participants without AAA at baseline. Biological age was assessed using Klemera-Doubal Method (KDMAge) and phenotypic age (PhenoAge) algorithms.
3. Microvascular Resistance Reserve vs Coronary Flow Reserve to Assess Age-Related Trends in Coronary Microvascular Dysfunction.
In 1,704 patients (2,283 lesions), CMD prevalence by MRR rose with age (37.2% to 78.0%), driven by structural CMD, whereas functional CMD was largely age-stable. CFR classified more patients as CMD than MRR regardless of epicardial disease, suggesting MRR offers more consistent assessment across obstructive and nonobstructive CAD.
Impact: Refines invasive physiologic assessment by distinguishing structural vs functional CMD across age and demonstrates MRR’s greater robustness than CFR when epicardial disease is present.
Clinical Implications: MRR-based classification could better guide diagnosis and stratification of CMD across obstructive/nonobstructive CAD, potentially informing targeted therapy trials and reducing misclassification seen with CFR.
Key Findings
- CMD prevalence by MRR was 48.2% and increased with age from 37.2% (<50 years) to 78.0% (≥80 years).
- Structural CMD rose with age (10.9% to 40.0%), whereas functional CMD remained relatively constant.
- CFR classified more patients as CMD than MRR (53.3% vs 48.2%), indicating potential overestimation by CFR in epicardial disease.
- Age independently predicted both functional (OR/y 1.02) and structural CMD (OR/y 1.05).
Methodological Strengths
- Large, inclusive registry with lesion-level invasive physiology across obstructive and nonobstructive CAD
- Age-stratified analysis distinguishing functional vs structural CMD endotypes
Limitations
- Observational registry without randomized interventions; lacks clinical outcome validation of MRR-guided strategies
- Potential heterogeneity in measurement protocols across centers
Future Directions: Prospective trials to test MRR-guided diagnostic and therapeutic pathways; integration with noninvasive imaging; define thresholds linked to patient-centered outcomes.
BACKGROUND: Advancing age is associated with epicardial atherosclerosis and coronary microvascular dysfunction (CMD), complicating reliable assessment of CMD using coronary flow reserve (CFR). Whether prevalence of functional and structural CMD varies with age remains unclear. OBJECTIVES: The authors sought to evaluate the prevalence of CMD endotypes by age strata and compare CFR with microvascular resistance reserve (MRR) for diagnosis and stratification. METHODS: Data from 1,704 patients (2,283 lesions) with stable angina in the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry) were analyzed, including obstructive (fractional flow reserve ≤0.80) and nonobstructive (fractional flow reserve >0.80) lesions. CMD was classified as no CMD (MRR ≥3.0), functional CMD (MRR <3.0, normal resistance), or structural CMD (MRR <3.0, abnormal resistance). CMD classification was repeated using CFR (<2.5 abnormal). Patients were stratified per age decade: <50, 50-59, 60-69, 70-79, and ≥80 years. RESULTS: CMD prevalence by MRR was 48.2%, and increased across age strata (37.2% to 78.0%; P < 0.001), driven by structural CMD (10.9% to 40.0%; P < 0.001), while functional CMD prevalence remained unchanged (26.3% to 38.0%; P = 0.220). Age independently predicted functional (OR/y: 1.02; P < 0.001) and structural CMD (OR/y: 1.05; P < 0.001). In obstructive lesions, age predicted structural CMD (OR/y: 1.03; P = 0.0055); in nonobstructive lesions, age predicted functional (OR/y: 1.02; P = 0.0032) and structural CMD (OR/y: 1.06; P < 0.001). Overall CMD prevalence by CFR exceeded MRR across groups (53.3% vs 48.2%; P < 0.001), irrespective of epicardial disease. CONCLUSIONS: Structural CMD increases with age regardless of obstructive CAD, while functional CMD prevalence increases only in nonobstructive CAD. CFR may overestimate CMD in epicardial disease, whereas MRR provides a more consistent assessment regardless of obstructive CAD, underscoring the need for prospective studies on their clinical relevance.