Daily Cardiology Research Analysis
Three impactful studies span prevention, precision, and policy. A health-economic analysis from EMPA-KIDNEY shows empagliflozin improves QALYs and likely reduces healthcare costs in chronic kidney disease. A large U.S. cohort indicates “weekend warrior” activity lowers cardiovascular and all-cause mortality in adults with diabetes. Mendelian randomization in South Asians identifies protein targets for dyslipidemia/CVD and suggests a weaker PCSK9–LDL-C relationship than in Europeans, informing an
Summary
Three impactful studies span prevention, precision, and policy. A health-economic analysis from EMPA-KIDNEY shows empagliflozin improves QALYs and likely reduces healthcare costs in chronic kidney disease. A large U.S. cohort indicates “weekend warrior” activity lowers cardiovascular and all-cause mortality in adults with diabetes. Mendelian randomization in South Asians identifies protein targets for dyslipidemia/CVD and suggests a weaker PCSK9–LDL-C relationship than in Europeans, informing ancestry-tailored prevention.
Research Themes
- Cost-effectiveness and QALY impact of SGLT2 inhibitors in CKD
- Physical activity patterns and mortality risk in diabetes
- Ancestry-specific protein targets for dyslipidemia/CVD via Mendelian randomization
Selected Articles
1. Effects of empagliflozin on quality of life and healthcare use and costs in chronic kidney disease: a health economic analysis of the EMPA-KIDNEY trial.
Using randomized trial data with post-trial follow-up, empagliflozin improved QALYs by 0.012 over 2 years and reduced hospital, concomitant medication, and ESKD costs, yielding net healthcare savings over 4 years. The probability of cost-effectiveness at a £20K/QALY threshold rose to 91% by 4 years, with consistent effects across eGFR, albuminuria, and diabetes subgroups.
Impact: Trial-based economic evidence can accelerate implementation of SGLT2 inhibitors in CKD by demonstrating QALY gains and budget impact, directly informing payers and guideline bodies.
Clinical Implications: Supports broader, earlier use of empagliflozin in CKD for both clinical benefit and cost-effectiveness; payers may anticipate reduced hospitalization and ESKD expenditures within 2–4 years.
Key Findings
- QALYs increased by 0.012 per participant over 2 years with empagliflozin versus placebo.
- Healthcare costs decreased for admissions (−£239), concomitant medications (−£130), and ESKD management (−£208) over 2 years.
- Additional ESKD cost savings (−£842) accrued during 2-year post-trial follow-up, with net 4-year healthcare cost −£593.
- Probability of cost-effectiveness at £20K/QALY was 43% over 2 years and 91% over 4 years.
Methodological Strengths
- Randomized, double-blind, placebo-controlled base trial with large, multinational sample
- Detailed micro-costing and post-trial follow-up capturing downstream ESKD costs
Limitations
- Relatively short active treatment and overall follow-up may underestimate long-term cost-effectiveness
- Costs are UK-specific; generalizability to other health systems requires adaptation
Future Directions: Model longer horizons, country-specific costing, and broader CKD phenotypes; evaluate integration with heart failure prevention and health equity impacts.
2. Association of Weekend Warrior and Other Physical Activity Patterns With Mortality Among Adults With Diabetes : A Cohort Study.
Among 51,650 U.S. adults with diabetes followed for 9.5 years, meeting MVPA ≥150 min/week as a weekend warrior or via regular sessions was linked to lower all-cause mortality (HR 0.79 and 0.83, respectively) and reduced cardiovascular mortality (HR 0.67 and 0.81). Insufficiently active individuals had modest benefits; cancer mortality differences were smaller.
Impact: Provides robust, diabetes-specific evidence that accumulating MVPA in 1–2 sessions per week confers mortality benefits comparable to regular distribution, improving feasibility for busy patients.
Clinical Implications: Counseling can emphasize flexibility: patients with diabetes may achieve mortality benefits by concentrating MVPA into 1–2 weekly sessions if regular distribution is impractical.
Key Findings
- Weekend warriors (MVPA ≥150 min/week in 1–2 sessions) had HR 0.79 for all-cause mortality versus inactive peers.
- Cardiovascular mortality was markedly reduced in weekend warriors (HR 0.67) and regularly active (HR 0.81) groups.
- Insufficiently active participants showed smaller or nonsignificant cardiovascular mortality benefits (HR 0.98).
- Cancer mortality differences were modest across activity patterns.
Methodological Strengths
- Large, nationally representative cohort with long median follow-up (9.5 years)
- Clear operationalization of activity patterns and multivariable adjustment
Limitations
- Physical activity was self-reported at one time point, risking misclassification
- Residual confounding is possible in observational design
Future Directions: Use device-based activity tracking and repeated measures; test interventions leveraging weekend-focused programs in diabetes care.
3. Identification of protein targets for dyslipidaemia and cardiovascular diseases among people with South Asian ancestry: a mendelian randomisation study.
Two-sample MR and colocalization across 2,800 plasma proteins identified several causal targets for lipid traits and CVD in South Asians, including CELSR2, ANGPTL3, LPA, and PCSK9. PCSK9’s genetic effect on LDL-C was substantially weaker in South Asians (β 0.16) than Europeans (β 0.37), highlighting ancestry-specific biology relevant to lipid-lowering strategies.
Impact: Defines ancestry-specific therapeutic targets and cautions against extrapolating European-derived pharmacogenetic expectations (e.g., PCSK9 inhibition magnitude) to South Asians.
Clinical Implications: Precision prevention and lipid-lowering strategies in South Asians may require tailored choices (e.g., prioritizing ANGPTL3/LPA pathways or combined approaches) and careful evaluation of PCSK9 inhibitor benefit.
Key Findings
- Identified 29 proteins with putative causal effects on lipid traits; 12 had strong colocalization/GMR support (e.g., ANGPTL3, PCSK9, CELSR2).
- PCSK9 effect on LDL-C: Europeans β=0.37 (95% CI 0.36–0.38) vs South Asians β=0.16 (0.11–0.21), with significant interaction.
- CELSR2 implicated in coronary artery disease in South Asians.
- Findings support ancestry-specific targets for dyslipidaemia and CVD prevention.
Methodological Strengths
- Robust two-sample MR with sensitivity analyses (MR-Egger, weighted median) and colocalization
- Ancestry-stratified comparisons between South Asian and European datasets
Limitations
- Limited South Asian GWAS sample sizes may reduce instrument strength
- MR assumptions (e.g., no horizontal pleiotropy) may not fully hold despite sensitivity analyses
Future Directions: Larger South Asian proteomic/GWAS datasets; pharmacogenetic studies testing PCSK9 and ANGPTL3 modulation; clinical trials powered for ancestry-specific efficacy.