Daily Cardiology Research Analysis
Three cardiology studies stand out today: a mechanistic discovery showing SIRT6 regulates angiogenesis by demyristoylating VEGFA; a large two-cohort analysis demonstrating continuous preoperative eGFR (with age interaction) is among the strongest predictors of perioperative cardiac events; and a meta-analysis of finerenone across major RCTs showing fewer heart failure hospitalizations and lower all-cause mortality but higher hyperkalemia risk.
Summary
Three cardiology studies stand out today: a mechanistic discovery showing SIRT6 regulates angiogenesis by demyristoylating VEGFA; a large two-cohort analysis demonstrating continuous preoperative eGFR (with age interaction) is among the strongest predictors of perioperative cardiac events; and a meta-analysis of finerenone across major RCTs showing fewer heart failure hospitalizations and lower all-cause mortality but higher hyperkalemia risk.
Research Themes
- Epigenetic enzyme control of angiogenesis via protein demyristoylation
- Perioperative cardiac risk prediction using kidney function (eGFR) as a continuous predictor
- Mineralocorticoid receptor antagonism (finerenone) in HF/CKD: benefits and risks
Selected Articles
1. SIRT6 promotes angiogenesis by enhancing VEGFA secretion via demyristoylation in endothelial cell.
Endothelial SIRT6 promotes angiogenesis by demyristoylating VEGFA, thereby enhancing its secretion under hypoxia and improving endothelial migration and tube formation. Loss of SIRT6 reduces angiogenic responses, and SIRT6 overexpression rescues ALK14-induced defects, highlighting demyristoylation (not deacetylation) as the key activity.
Impact: This study uncovers a previously unrecognized post-translational mechanism—SIRT6-mediated demyristoylation of VEGFA—linking epigenetic enzyme activity to angiogenesis, suggesting a new therapeutic axis for ischemic cardiovascular disease.
Clinical Implications: Targeting SIRT6 demyristoylase activity could modulate therapeutic angiogenesis in ischemic heart disease and peripheral ischemia. It also raises caution that broad SIRT6 modulation may affect VEGFA biology.
Key Findings
- Endothelial SIRT6 knockout attenuated angiogenesis in mice; SIRT6 promoted endothelial migration and tube formation in vitro.
- SIRT6 regulates intracellular VEGFA levels and global protein myristoylation under hypoxia; knockdown or ALK14 reduced VEGFA secretion.
- CLICK-IT assays identified VEGFA as a myristoylated substrate of SIRT6; SIRT6 enhances VEGFA secretion via demyristoylation, not deacetylation.
- SIRT6 overexpression rescued endothelial angiogenic defects induced by ALK14 treatment.
Methodological Strengths
- In vivo endothelial-specific knockout with phenotypic angiogenesis assessment
- Mechanistic validation using CLICK-IT labeling and functional rescue with SIRT6 mutants
Limitations
- Preclinical study without human validation
- Extent of in vivo models and long-term safety of targeting SIRT6 not addressed
Future Directions: Translate findings to human tissues and ischemic models; develop selective SIRT6 demyristoylase modulators; evaluate therapeutic angiogenesis and safety in large-animal models.
2. Preoperative estimated glomerular filtration rate to predict cardiac events in major noncardiac surgery: a secondary analysis of two large international studies.
Across VISION (n=35,815) and POISE-2 (n=9,219), lower continuous preoperative eGFR strongly predicted 30-day perioperative cardiac events, with attenuation at older ages. Adding eGFR (and its age interaction) improved model discrimination and net benefit over common clinical predictors.
Impact: Provides robust, generalizable evidence that continuous eGFR is one of the strongest predictors for perioperative cardiac risk and should be incorporated into risk calculators.
Clinical Implications: Incorporate continuous eGFR and its age interaction into perioperative cardiac risk assessment to better stratify patients and guide monitoring, optimization, and resource allocation.
Key Findings
- In both VISION and POISE-2, lower preoperative eGFR showed a strong, graded association with 30-day cardiac events.
- The predictive association was attenuated in older patients, indicating an age interaction.
- Adding continuous eGFR improved multivariable model C-statistics and net benefit beyond common predictors.
Methodological Strengths
- Very large combined sample size across two international studies
- Evaluation of continuous nonlinear predictor with age interaction and decision-analytic net benefit
Limitations
- Secondary analysis with potential residual confounding despite multivariable adjustment
- Abstract truncation limits detailed reporting of effect sizes and calibration
Future Directions: Implement and prospectively validate eGFR-integrated risk calculators; assess clinical utility in diverse surgical populations and evaluate intervention thresholds.
3. Effect of Finerenone in Cardiovascular and Renal Outcomes: A Systematic Review and Meta-analysis.
Across three RCTs (n=19,027), finerenone reduced heart failure hospitalizations (HR 0.80) and all-cause mortality (RR 0.86), without significant reduction in cardiovascular death, and increased hyperkalemia risk (RR 2.31). Renal failure rates were similar to placebo.
Impact: Synthesizes high-level evidence that finerenone confers important clinical benefits in HF/CKD populations, informing guideline updates while quantifying safety trade-offs.
Clinical Implications: Consider finerenone to reduce HF hospitalizations and all-cause mortality in appropriate HF/CKD patients, with proactive monitoring and management of hyperkalemia.
Key Findings
- Finerenone reduced heart failure hospitalization risk by 20% (HR 0.80, 95% CI 0.72–0.90).
- All-cause mortality was reduced by 14% (RR 0.86, 95% CI 0.77–0.97).
- No significant reduction in cardiovascular death (HR 0.91, p=0.06); renal failure rates were similar to placebo.
- Hyperkalemia risk was significantly increased (RR 2.31, 95% CI 1.98–2.69).
Methodological Strengths
- Meta-analysis restricted to randomized controlled trials with large total sample size
- Prespecified cardiovascular and renal endpoints with standard effect measures (HR, RR, CI)
Limitations
- Heterogeneity across trials in populations (CKD severity, HF phenotype) and follow-up
- Increased hyperkalemia requires careful monitoring; effects on cardiovascular death remained borderline
Future Directions: Clarify cardiovascular mortality effects in dedicated HF phenotypes; define potassium management protocols and patient selection to optimize benefit-risk.