Daily Cardiology Research Analysis
Analyzed 47 papers and selected 3 impactful papers.
Summary
Mechanistic work shows that non-remnant triglyceride-rich lipoproteins generated by lipoprotein lipase deficiency are directly atherogenic in mice, expanding the paradigm beyond remnant particles. Clinically, a prospective CMR study links thromboaspiration during primary PCI to increased microvascular obstruction in STEMI, while a large biomarker registry identifies 1-month fibrinogen as a strong residual risk predictor after PCI.
Research Themes
- Atherogenicity of non-remnant triglyceride-rich lipoproteins
- Microvascular injury with thromboaspiration in STEMI
- Residual inflammatory/coagulant risk after PCI
Selected Articles
1. Non-remnant triglyceride-rich lipoproteins due to lipoprotein lipase deficiency increase atherosclerosis in mice.
Using induced whole-body LpL deficiency on an LDLR-deficient background, the authors demonstrate that non-remnant, nascent TRLs can drive atherosclerosis in mice fed a Western-type diet. This challenges the remnant-centric view of TRL-driven atherogenesis and implicates lipolysis-independent pathways in vascular injury.
Impact: This study provides in vivo evidence that nascent TRLs are inherently atherogenic, redefining targets for lipid-lowering strategies beyond remnant particles. It advances mechanistic understanding with potential translational implications for therapies aimed at TRL metabolism.
Clinical Implications: Although preclinical, these findings suggest that therapies exclusively lowering remnant cholesterol may be insufficient; interventions targeting TRL production, clearance, or lipolysis-independent pathways could be necessary to reduce atherogenic burden.
Key Findings
- Induced whole-body LpL deficiency on an LDLR-deficient background generates non-remnant, nascent TRLs in vivo.
- Mice with LpL deficiency developed increased atherosclerosis on a Western-type diet, implicating nascent TRLs as atherogenic.
- Findings challenge the remnant-centric paradigm and point to lipolysis-independent mechanisms in TRL-driven atherogenesis.
Methodological Strengths
- Genetically engineered mouse models enabling causal inference on LpL and LDLR pathways.
- In vivo assessment under controlled dietary conditions reflecting high-risk human diets.
Limitations
- Preclinical mouse study limits direct generalizability to humans.
- Abstract truncation limits quantitative details on effect sizes and tissue-specific analyses.
Future Directions: Define molecular pathways by which nascent TRLs induce vascular injury, quantify atherogenicity across TRL subclasses, and test pharmacologic interventions targeting TRL biogenesis and clearance in preclinical and early-phase clinical studies.
Increased fasting and postprandial triglyceride levels are risk factors for cardiovascular disease (CVD). Partially metabolized triglyceride-rich lipoproteins (TRLs) termed remnants are created when intestinally-derived chylomicrons and liver secreted very low density lipoproteins (VLDLs) interact with lipoprotein lipase (LpL) situated on the luminal surface of capillary endothelial cells. Higher circulating remnant levels have been implicated as the reason for the relationship between TRL levels and CVD. We hypothesized that nascent lipoproteins not only remnants are atherogenic. To test this, we created mice with induced whole-body lipoprotein lipase (LpL) deficiency combined with LDL receptor (LDLR) deficiency. On an atherogenic Western-type diet (WD), male and female mice with induced global LpL deficiency (iLpl
2. Selective Use of Thromboaspiration in STEMI: CMR Evidence Against Routine Practice.
In a prospective cohort of 460 STEMI patients undergoing primary PCI, thromboaspiration was associated with higher incidence and extent of CMR-defined microvascular obstruction. The harm signal was strongest with reperfusion beyond 6 hours or non-occlusive thrombus, supporting guideline recommendations against routine TA.
Impact: Provides high-quality imaging evidence that routine thromboaspiration may worsen microvascular injury, refining procedural strategy in STEMI beyond angiographic endpoints.
Clinical Implications: Avoid routine thromboaspiration during primary PCI in STEMI; consider highly selective use only in carefully defined scenarios, particularly avoiding TA in delayed reperfusion or non-occlusive thrombus.
Key Findings
- Thromboaspiration increased the odds of microvascular obstruction (OR 1.52; 95% CI 1.16–1.98) and its extent on CMR.
- Risk amplification was greatest with symptom-to-treatment time >6 hours (OR 3.46) and with non-occlusive thrombus (TIMI thrombus score 1–4; OR 2.23).
- Sex differences were observed: increased MVO risk in men but not in women.
Methodological Strengths
- Prospective design with standardized CMR at two time points (day 6 and 3 months).
- Propensity score-based average treatment effect analysis to address baseline imbalances.
Limitations
- Non-randomized design with potential residual confounding.
- Generalizability may be limited by cohort setting and operator selection of thromboaspiration.
Future Directions: Randomized trials focusing on microvascular endpoints and stratifying by thrombus burden and reperfusion delay; exploration of alternative embolic protection or aspiration strategies that minimize microvascular injury.
BACKGROUND: Thromboaspiration (TA) has been proposed as an adjunct to primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) to reduce thrombus burden. However, its effect on microvascular perfusion remains uncertain, and concerns have been raised about its potential to aggravate microvascular injury. AIMS: This study aimed to evaluate the impact of TA on microvascular obstruction (MVO) using cardiac magnetic resonance (CMR) imaging in a large cohort of STEMI patients. METHODS: We prospectively enrolled 460 STEMI patients treated with primary PCI within 12 hours of symptom onset. TA was performed in 193 patients (42%). CMR was performed at day 6 and 3 months to assess infarct size and MVO. A propensity score-based average treatment effect (ATE) analysis was used to adjust for baseline differences. Subgroup analyses were conducted according to symptom-to-treatment time, thrombus burden (TIMI thrombus score (TTS)), and sex. RESULTS: TA was independently associated with higher MVO incidence (OR 1.52; 95% CI: 1.16-1.98; p=0.0024) and greater MVO extent (SMD 0.42; 95% CI: 0.02-0.72; p=0.041). The association was particularly significant in patients reperfused beyond 6 hours (OR 3.46; 95% CI: 1.92-6.23; p<0.0001) and those with non-occlusive thrombus (TTS "1-4") (OR 2.23; 95% CI: 1.29-3.85; p=0.004). Sex-stratified analysis showed increased MVO risk in men (OR 1.52; 95% CI: 1.14-2.05; p=0.005) but not in women. CONCLUSION: TA during primary PCI was associated with increased occurrence and extent of MVO, particularly in patients with delayed reperfusion or non-occlusive thrombus. These findings reinforce current ESC guidelines against routine TA use and suggest that its application should be restricted to carefully selected patients.
3. Residual Cardiovascular Biomarkers After Medical Therapy and Their Prognostic Implications Following Percutaneous Coronary Intervention.
In 2,789 PCI patients, most biomarkers improved at 1 month except fibrinogen, which increased and emerged as the strongest independent predictor of major adverse cardiovascular events over up to 4 years. The correlation between 1-month hs-CRP and fibrinogen was moderate, highlighting residual inflammatory/coagulant risk.
Impact: Identifies fibrinogen as a practical, incremental prognostic marker post-PCI despite contemporary medical therapy, informing risk stratification and potential therapeutic targeting.
Clinical Implications: Consider incorporating 1-month fibrinogen into post-PCI risk assessment to identify high-risk patients for intensified secondary prevention and exploration of anti-inflammatory/antithrombotic strategies.
Key Findings
- At 1 month post-PCI, most biomarkers decreased, but fibrinogen increased (329 ± 86 to 359 ± 92 mg/dL; P < 0.001).
- Higher quartiles of 1-month fibrinogen predicted major adverse cardiovascular events with adjusted HR up to 2.23.
- 1-month hs-CRP and fibrinogen were moderately correlated (r = 0.426), indicating overlapping but distinct residual risk pathways.
Methodological Strengths
- Large prospective registry with serial biomarker assessments including inflammation and coagulation pathways.
- Longitudinal follow-up up to 4 years with clinically meaningful composite endpoints.
Limitations
- Observational design precludes causal inference and is susceptible to residual confounding.
- Single-country registry; fibrinogen may reflect intercurrent conditions influencing levels.
Future Directions: Test whether targeting fibrinogen-linked pathways or intensified secondary prevention based on 1-month fibrinogen reduces events; validate thresholds across diverse populations.
BACKGROUND: Despite medical therapy, atherothrombotic events remain common in high-risk patients with coronary artery disease. OBJECTIVES: The purpose of this study was to evaluate the association between atherothrombotic biomarkers and outcomes in patients with coronary artery disease who are undergoing percutaneous coronary intervention (PCI). METHODS: Biomarkers including lipid profile (low-density lipoprotein cholesterol and triglycerides), inflammation (high-sensitivity C-reactive protein [hs-CRP]), platelet reactivity (P2Y12 reaction unit), and coagulation (fibrinogen) were measured on admission and at 1 month following medical therapy post-PCI (n = 2,789). The primary endpoint was major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, or stroke, occurring between 1 month and 4 years post-PCI. RESULTS: Biomarker levels decreased significantly (all P values ≤ 0.001), except for fibrinogen levels (329 ± 86 vs 359 ± 92 mg/dL; P < 0.001). The median follow-up of the participants was 2.2 years (IQR: 1.3-4.0 years). Covariate-adjusted HRs for the lowest to highest quartiles were 1.00 (referent) (95% CI), 1.37 (0.78-2.41), 1.89 (1.11-3.21), and 1.71 (1.01-2.91) for 1-month hs-CRP; and 1.00 (referent), 1.49 (0.83-2.67), 1.83 (1.03-3.26), and 2.47 (1.40-4.36) for 1-month fibrinogen. Among these biomarkers, hs-CRP and fibrinogen levels at 1 month showed the highest correlation (r = 0.426). After adjusting for covariates and biomarkers, the 1-month fibrinogen level was the strongest incremental predictor of major adverse cardiovascular event (HRs: 1.00 [referent], 1.45 [0.80-2.62], 1.65 [0.91-2.98], and 2.23 [1.20-4.12], P < 0.001). CONCLUSIONS: Among medically treated patients following PCI, elevated fibrinogen levels were associated with adverse outcomes. Further studies are warranted to clarify these associations and to determine whether adjunctive therapies can improve outcomes in this high-risk group. (Gyeongsang National University Hospital [GNUH] Registry; NCT04650529).