Overview
Cross-system analysis of cardiovascular biology has generated several testable hypotheses about drug response, combination therapy, and treatment optimization. Building on the vast foundation of cardiology research, these hypotheses identify potential patterns that may improve treatment selection.
The Hypotheses
1
Statin Response Heterogeneity
Observation: Different statins show distinct response patterns despite targeting the same enzyme.
Prediction: Patients who respond exceptionally well to rosuvastatin may also respond well to PCSK9 inhibitors and SGLT2 inhibitors.
Testable: Correlate rosuvastatin response with alirocumab or canagliflozin response.
2
GLP-1 Agonist Clustering
Observation: Semaglutide and dulaglutide show remarkably similar efficacy profiles.
Prediction: Patients who respond to one will likely respond to the other.
Testable: Compare head-to-head response rates; patients switching should maintain CV protection.
3
Inflammation-CV Convergence
Observation: Multiple inflammation markers (CRP, NLRP3, VCAM1) show coordinated elevation.
Prediction: Patients with concordant elevation of all three will have higher CV event rates.
Testable: Measure all three markers in prospective CV cohorts.
4
LDLR-Statin Connection
Observation: The LDL receptor and lovastatin appear biologically linked.
Prediction: Patients with certain LDLR variants may show differential response to lovastatin vs other statins.
Testable: Correlate LDLR genotype with statin-specific LDL response.
5
Triple CV Drug Optimization
Observation: Rosuvastatin, alirocumab, and canagliflozin may share response predictors.
Prediction: A subset of patients will show exceptional response to all three.
Testable: Identify whether response to one predicts response to the others.
6
PCSK9-Inflammation Axis
Observation: PCSK9 appears linked to inflammatory pathways.
Prediction: PCSK9 inhibitors may show CV benefit beyond LDL reduction in high-inflammation patients.
Testable: Stratify PCSK9i trial results by baseline inflammation status.
7
APOE as Dual-Risk Marker
Observation: APOE is the major risk gene for both CV disease and Alzheimer's.
Prediction: APOE variants show coordinated effects on vascular and neuroinflammation.
Testable: Correlate CV inflammatory markers with brain imaging in APOE4 carriers.
8
Cross-Class Synergy
Observation: Certain drug combinations show better-than-additive benefits.
Prediction: Drugs sharing biological characteristics will show synergistic effects.
Testable: Look for interaction effects in factorial CV trials.
Potential Impact
CV disease kills 18 million people annually.
If these hypotheses improve treatment by 5%:
- 900,000 deaths prevented annually
- 26 million patients with improved outcomes
Related: Microbiome & Cardiovascular Disease
The TMAO pathway—where gut bacteria convert dietary choline/carnitine into an atherosclerosis-promoting metabolite—represents a major microbiome-CV connection. See our Microbiome & Immunity hypotheses for testable predictions on TMAO stratification and metabolic endotoxemia.