Daily Cardiology Research Analysis
Three impactful cardiology studies stood out today: a massive statin-naïve cohort linked visit-to-visit lipid variability—especially LDL-C variability—to higher coronary calcification and cardiovascular events; a human plaque proteomics study connected glycolytic enzyme abundance to plaque vulnerability with notable sex differences; and a national heart failure registry showed that early implementation of guideline-directed therapy is associated with lower mortality and hospitalization.
Summary
Three impactful cardiology studies stood out today: a massive statin-naïve cohort linked visit-to-visit lipid variability—especially LDL-C variability—to higher coronary calcification and cardiovascular events; a human plaque proteomics study connected glycolytic enzyme abundance to plaque vulnerability with notable sex differences; and a national heart failure registry showed that early implementation of guideline-directed therapy is associated with lower mortality and hospitalization.
Research Themes
- Risk stratification using lipid variability and imaging
- Metabolic drivers of plaque vulnerability in human atherosclerosis
- Real-world implementation of heart failure guideline-directed therapy
Selected Articles
1. Associations of visit-to-visit lipid variability with coronary artery calcification and cardiovascular event in statin-naïve Koreans.
In a very large statin-naïve population, higher visit-to-visit LDL-C variability (variability independent of the mean) was associated with greater coronary artery calcification and a 41% higher risk of cardiovascular events. Variability in total cholesterol, triglycerides, and non-HDL-C also tracked with CAC, underscoring the prognostic value of lipid stability beyond average levels.
Impact: This is one of the largest studies linking lipid variability to both subclinical atherosclerosis and clinical events, providing actionable risk stratification beyond static lipid levels.
Clinical Implications: Consider monitoring lipid variability in addition to absolute levels for statin-naïve patients; stabilizing LDL-C may reduce atherosclerotic burden and events. This supports adherence and therapeutic strategies targeting sustained lipid control.
Key Findings
- Highest quartile of LDL-C variability (VIM) associated with 1.42-fold higher CAC score versus lowest quartile.
- LDL-C variability predicted cardiovascular events (HR 1.41; 95% CI 1.13–1.75) over a median 2.8 years.
- Variability in total cholesterol, triglycerides, and non-HDL-C was positively associated with CAC.
- Design included repeated lipid measures (≥5 tests) and statin-naïve status, minimizing treatment confounding.
Methodological Strengths
- Very large cohorts with repeated lipid assessments and imaging linkage.
- Statin-naïve design reduces therapeutic confounding; use of VIM captures variability independent of mean.
Limitations
- Observational design with potential residual confounding.
- Cardiovascular events partly based on self-report; single-institution setting may limit generalizability.
Future Directions: Test whether interventions that reduce lipid variability (e.g., adherence programs, longer-acting agents) lower CAC progression and clinical events in randomized settings.
2. Proteomic profiling reveals a higher presence of glycolytic enzymes in human atherosclerotic lesions with unfavourable histological characteristics.
In human carotid endarterectomy plaques (n=320), untargeted proteomics identified 240 proteins associated with plaque vulnerability, including upregulation of key glycolytic enzymes (HK3, PKM, LDHA). Associations were driven by macrophage and lipid content, correlated with plaque hemorrhage biomarker BLVRB, and were stronger in women.
Impact: Provides human protein-level evidence linking glycolytic metabolism to plaque vulnerability and hemorrhage, highlighting a sex-specific metabolic axis and potential targets beyond transcriptomics.
Clinical Implications: Suggests metabolic imaging/biomarkers and glycolysis-modulating therapies could refine risk stratification and target plaque stabilization, particularly in women.
Key Findings
- Detected 1,499 proteins; 240 associated with plaque vulnerability (FDR < 0.05).
- Key glycolysis enzymes HK3 (FDR=0.03), PKM (FDR=0.05), LDHA (FDR=0.04) were enriched in vulnerable plaques.
- Associations correlated with macrophage and fat content, pre-operative symptom severity, and BLVRB (plaque hemorrhage biomarker).
- Validation in 120 patients confirmed HK3 and PKM associations with plaque progression and symptoms (P<0.001).
- Sex-specific stronger associations in women suggest metabolic dimorphism in atherosclerosis.
Methodological Strengths
- Large human tissue proteomics with discovery and independent validation sets.
- Integration with pathology, single-cell/bulk transcriptomics, and clinical data.
Limitations
- Cross-sectional tissue analysis cannot infer causality.
- Carotid lesions may not fully generalize to coronary beds; protein–RNA discordance complicates interpretation.
Future Directions: Evaluate glycolysis-targeted interventions and metabolic imaging for vulnerable plaque detection; investigate sex-specific mechanisms and clinical translation across vascular beds.
3. Real-world use of guideline-directed therapy for heart failure: Insights from the Danish Heart Failure Registry.
Among 46,816 incident HFrEF patients, the use of RASi and beta-blockers remained high, while MRA and SGLT2i adoption increased over time. Initiation of GDMT within 4 weeks was associated with significantly lower 1- and 3-year all-cause mortality and hospitalization versus no GDMT.
Impact: Provides strong real-world evidence that early multi-drug GDMT initiation correlates with improved survival and fewer hospitalizations at a national scale.
Clinical Implications: Prioritize rapid, comprehensive GDMT initiation during and immediately after hospitalization for HFrEF; system-level strategies should target early adoption of MRA and SGLT2 inhibitors.
Key Findings
- High RASi and beta-blocker use; increasing MRA and SGLT2i uptake across eras.
- Starting 1–2 or 3–4 GDMT agents within 4 weeks associated with lower 1- and 3-year all-cause mortality (HRs ~0.65–0.75).
- GDMT initiation also linked to reduced 1- and 3-year all-cause hospitalization.
- Rapid adaptation to guideline changes observed over 2008–2022.
Methodological Strengths
- Nationwide registry with very large incident HFrEF cohort and time-updated medication capture.
- Multivariable Cox models across multiple timepoints (4/8/12 weeks) to assess associations with outcomes.
Limitations
- Observational design; potential residual confounding and confounding by indication.
- Medication dosing/titration and adherence not fully captured.
Future Directions: Evaluate implementation strategies (e.g., inpatient initiation bundles, rapid titration pathways) in pragmatic trials to enhance early GDMT uptake and sustainment.