Cardiology Research Analysis
April’s cardiology literature coalesced around hypertension control, translational therapeutics, and scalable diagnostics. An individual-patient meta-analysis established ambulatory BP time-in-target (PTTR) as a superior, actionable predictor of mortality and cardiovascular events, while a large cluster RCT showed intensive BP lowering reduced all-cause dementia. Therapeutic innovation spanned aldosterone synthase inhibition (lorundrostat) for resistant hypertension, modified mRNA replacement fo
Summary
April’s cardiology literature coalesced around hypertension control, translational therapeutics, and scalable diagnostics. An individual-patient meta-analysis established ambulatory BP time-in-target (PTTR) as a superior, actionable predictor of mortality and cardiovascular events, while a large cluster RCT showed intensive BP lowering reduced all-cause dementia. Therapeutic innovation spanned aldosterone synthase inhibition (lorundrostat) for resistant hypertension, modified mRNA replacement for inherited cardiomyopathy, and a microbiome–bile acid–platelet TGR5 antithrombotic pathway. Cross-cutting diagnostic advances included AI/opportunistic imaging and pragmatic metrics that enable earlier, data-driven risk stratification and care escalation.
Selected Articles
1. Ambulatory blood pressure monitoring, European guideline targets, and cardiovascular outcomes: an individual patient data meta-analysis.
Across 14 cohorts (n=14,230; median 10.9-year follow-up), the percentage of time ambulatory BP is within ESC 2024 target ranges (PTTR) strongly and independently predicted lower all-cause mortality and cardiovascular events, outperforming office BP classification.
Impact: Introduces PTTR as a practical ABPM-derived metric with robust prognostic discrimination that can reframe hypertension management and guideline implementation.
Clinical Implications: Incorporate PTTR into routine assessment and titration workflows, emphasizing time-in-target rather than single office readings; consider ESC 2024 thresholds to accelerate risk reduction.
Key Findings
- Higher 24-h PTTR was associated with markedly lower mortality (adjusted HR 0.57) and cardiovascular events (adjusted HR 0.30).
- Daytime/nighttime PTTR and cause-specific outcomes showed consistent associations.
- Office BP misclassified many patients compared with PTTR; ESC 2024 targets shortened time needed for relative risk reduction.
2. Blood pressure reduction and all-cause dementia in people with uncontrolled hypertension: an open-label, blinded-endpoint, cluster-randomized trial.
A village-level cluster RCT (n=33,995) in rural China demonstrated that a non-physician–led intensive BP program achieved substantial BP reductions and significantly reduced all-cause dementia and serious adverse events over 48 months.
Impact: Delivers causal, scalable evidence linking intensive BP control to dementia prevention and validates task-shifting strategies in resource-limited settings.
Clinical Implications: Supports adoption of team-based intensive BP targets with clear titration/monitoring protocols; programs should integrate cognitive outcomes and safety surveillance (e.g., electrolytes).
Key Findings
- Net −22/−9.3 mmHg systolic/diastolic BP reduction over 48 months compared with usual care.
- Reduced all-cause dementia (RR 0.85) and serious adverse events (RR 0.94).
3. The gut microbiota-bile acid-TGR5 axis orchestrates platelet activation and atherothrombosis.
Translational work linked reduced deoxycholic acid and Bacteroides vulgatus in CAD patients to heightened thrombosis, showing deoxycholic acid suppresses platelet activation via TGR5; oral DCA or microbiome modulation reduced thrombosis in atherosclerotic mice.
Impact: Reveals a druggable microbiome–bile acid–platelet axis and nominates platelet TGR5 as a novel antithrombotic target with multi-model validation.
Clinical Implications: Motivates early-phase studies of TGR5 agonism and bile-acid/microbiome modulation in thrombosis-prone CAD, with careful safety assessment alongside standard antiplatelet therapy.
Key Findings
- CAD patients showed reduced serum deoxycholic acid and underrepresentation of Bacteroides vulgatus.
- DCA inhibited platelet activation and thrombosis via platelet TGR5; pharmacologic/genetic TGR5 loss abrogated effects.
- Oral DCA, B. vulgatus or healthy stool transfer reduced thrombosis in atherosclerotic mice.
4. Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension.
A double-blind RCT (n=285) showed that the aldosterone synthase inhibitor lorundrostat reduced 24-hour ambulatory systolic BP by ~6.5–7.9 mmHg at 12 weeks vs placebo in patients on 2–5 antihypertensives, with 5–7% hyperkalaemia >6.0 mmol/L.
Impact: Establishes a novel mechanism for resistant hypertension with clinically meaningful ambulatory BP reductions and clear safety monitoring needs.
Clinical Implications: Pending longer-term outcomes, lorundrostat may complement or compete with MRAs; rigorous potassium monitoring protocols are essential.
Key Findings
- Placebo-adjusted 24-h SBP reduction at 12 weeks: −7.9 mmHg (stable 50 mg) and −6.5 mmHg (dose-adjustment arm).
- Hyperkalaemia >6.0 mmol/L occurred in 5–7% of treated patients; none in placebo.
5. Modified mRNA Treatment Restores Cardiac Function in Desmocollin-2-Deficient Mouse Models of Arrhythmogenic Right Ventricular Cardiomyopathy.
From identification of a novel human DSC2 variant to in vivo rescue, modified mRNA replacement restored desmosomal protein expression and improved right ventricular structure/function in Dsc2-deficient ARVC mouse models.
Impact: Provides first-in-class translational evidence for cardiac-targeted mRNA structural protein replacement as a disease-modifying strategy in inherited cardiomyopathies.
Clinical Implications: Supports development of cardiac mRNA replacement (delivery, dosing, immunogenicity) for desmosomal cardiomyopathies with rigorous safety and durability evaluation before human trials.
Key Findings
- Novel pathogenic DSC2 variant identified and functionally validated.
- Modified mRNA restored desmosomal protein levels and improved RV function in mouse models.
- mRNA therapy reduced arrhythmogenic substrate and structural dysplasia, demonstrating disease-modifying potential.