Daily Cardiology Research Analysis
A randomized trial (CENTURY) showed that an intensive lifestyle-plus-medical program with PET coronary flow capacity guidance reduced death, myocardial infarction, and revascularization in chronic coronary disease. Mechanistic imaging from PROSPECT II linked elevated lipoprotein(a) specifically to focal vulnerable coronary plaques, distinct from LDL-related diffuse atherosclerosis. In Medicare patients >60 years, PFO closure lowered recurrent ischemic stroke versus medical therapy, albeit with s
Summary
A randomized trial (CENTURY) showed that an intensive lifestyle-plus-medical program with PET coronary flow capacity guidance reduced death, myocardial infarction, and revascularization in chronic coronary disease. Mechanistic imaging from PROSPECT II linked elevated lipoprotein(a) specifically to focal vulnerable coronary plaques, distinct from LDL-related diffuse atherosclerosis. In Medicare patients >60 years, PFO closure lowered recurrent ischemic stroke versus medical therapy, albeit with slightly higher early AF/VTE risks.
Research Themes
- Physiology-guided comprehensive management in stable coronary artery disease
- Lipoprotein(a) as a driver of focal vulnerable plaque formation
- Stroke prevention strategies in older patients with patent foramen ovale
Selected Articles
1. Optimal medical care and coronary flow capacity-guided myocardial revascularization vs usual care for chronic coronary artery disease: the CENTURY trial.
In this randomized trial (n=1,028), a comprehensive PET–coronary flow capacity–guided program combining intensive lifestyle modification and aggressive goal-directed medical therapy reduced 11-year all-cause mortality, death/MI, late revascularization, and MACE compared with usual care. Revascularization within 90 days was rare and predominantly reserved for severely reduced CFC.
Impact: It provides randomized evidence that physiology-guided comprehensive care changes hard outcomes over a decade in chronic CAD, supporting a shift toward integrated, goal-based management with selective revascularization.
Clinical Implications: Adopt integrated programs that combine intensive lifestyle intervention and goal-directed pharmacotherapy with PET-based CFC to triage revascularization, aiming to reduce mortality and MI in stable CAD.
Key Findings
- Comprehensive care lowered 11-year all-cause mortality (4.7% vs 8.2%; P=0.023).
- Death or MI was reduced (7.0% vs 11.1%; P=0.024) and late revascularization decreased (9.5% vs 14.8%; P=0.021).
- Major adverse cardiac events were significantly lower (20.5% vs 29.9%; P=0.0006).
- Only 5.4% underwent early revascularization, predominantly guided by severely reduced CFC.
Methodological Strengths
- Randomized design with long-term (up to 11 years) outcomes and repeated PET physiology.
- Comprehensive, protocolized intervention with clear CFC-based revascularization criteria.
Limitations
- Single-center programmatic model may limit generalizability across health systems.
- Open-label comprehensive care with frequent contacts may introduce performance bias.
Future Directions: Multicenter pragmatic trials to test PET-CFC–guided comprehensive care pathways, cost-effectiveness analyses, and implementation frameworks across diverse healthcare settings.
BACKGROUND AND AIMS: The randomized CENTURY trial tested the hypothesis that a comprehensive strategy integrating intense lifestyle modification and aggressive medical management to goals with revascularization reserved for severely reduced coronary flow capacity (CFC) by positron emission tomography (PET) would reduce risk factors, subsequent revascularization, death and myocardial infarction (MI) compared with standard of care in chronic stable coronary artery disease (CAD). METHODS: Participants were randomly assigned to standard or comprehensive care groups. Rest-stress PET quantified CFC for physiological CAD severity at baseline, 2, 5, and up to 11 years. The comprehensive care group reviewed PET results with frequent clinic visits and open 24/7 phone/email support. Standard care lacked supportive contact with blinded PET results that were unblinded only for severely reduced CFC with high mortality risk for potential revascularization. RESULTS: Between 2009-2017, 515 patients were assigned to comprehensive care and 513 to standard care and followed for 5 or more years. Comprehensive vs standard care decreased risk factors and summed 5-year risk score (Δ-1.1 vs + 0.33; 95% confidence interval -1.84 to -0.97; P < .0001), decreased cumulative 11-year all-cause death (4.7% vs 8.2%; P = .023), death or MI (7.0% vs 11.1%; P = .024) late revascularization (9.5% vs 14.8%; P = .021) and major adverse cardiac events (20.5% vs 29.9%; P = .0006). Only 56 of 1028 (5.4%) CENTURY patients with chronic CAD had revascularization within 90 days predominantly guided by CFC severity. CONCLUSIONS: The randomized CENTURY trial demonstrates that comprehensive integrated lifestyle modification and medical management towards goals with revascularization reserved for severely reduced CFC, significantly reduced risk factor scores, death, death or MI, and revascularization. CLINICALTRIALS.GOV: NCT00756379.
2. Lipoprotein(a), Cholesterol, Triglyceride Levels, and Vulnerable Coronary Plaques: A PROSPECT II Substudy.
In 865 recent MI patients with 3-vessel NIRS–IVUS imaging, TC, LDL-C, and non-HDL-C tracked pancoronary plaque and lipid burden, whereas Lp(a) uniquely associated with focal vulnerable plaques. This mechanistic distinction provides a rationale for Lp(a)-targeted therapies to reduce MI risk by addressing plaque vulnerability.
Impact: It clarifies that Lp(a) is linked to focal plaque vulnerability rather than diffuse plaque burden, refining pathophysiologic understanding and informing targeted Lp(a)-lowering strategies.
Clinical Implications: Beyond LDL-C lowering for diffuse atherosclerosis, consider Lp(a) assessment to identify patients at risk for focal vulnerability who may benefit from emerging Lp(a)-lowering therapies.
Key Findings
- TC, LDL-C, and non-HDL-C associated with pancoronary plaque volume and lipid core burden (P<0.01).
- Lp(a) was independently associated with focal vulnerable plaques (P=0.01), not with diffuse plaque burden.
- HDL-C and triglycerides were not highlighted as drivers of focal vulnerability in multivariable models.
Methodological Strengths
- Three-vessel, coregistered NIRS–IVUS imaging after culprit treatment enabling whole-coronary assessment.
- Rigorous multivariable analyses defining focal vulnerable plaque by standardized thresholds.
Limitations
- Observational, post-MI cohort; causality cannot be inferred and selection bias possible.
- Single baseline lipid/lipoprotein measurements; generalizability beyond recent MI populations is uncertain.
Future Directions: Prospective studies linking Lp(a) lowering to reduction in imaging-defined vulnerable plaques and clinical MI, and integration with CT/NIRS-IVUS risk modeling.
BACKGROUND: Although lipoprotein(a) (Lp[a]) has been associated with acute myocardial infarction (MI), the relationship between Lp(a) and the presence of high-risk "vulnerable" coronary plaques has not been studied. OBJECTIVES: The aim of this study was to investigate whether specific lipoproteins are associated with pancoronary plaque volume and lipid deposition vs the development of non-flow-limiting high-risk vulnerable plaques. METHODS: In PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) II, 3-vessel coronary artery imaging was performed with a combined near-infrared spectroscopy and intravascular ultrasound catheter after treatment of all flow-limiting lesions in patients with recent MI. The relationships of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), HDL-C, Lp(a), and triglycerides to pancoronary plaque volume, pancoronary lipid core burden index (LCBI), and the presence of focal vulnerable plaques (plaque burden ≥70% and maximum LCBI over any 4-mm segment ≥324.7) were assessed in 865 patients. RESULTS: By multivariable analysis, TC, LDL-C, and non-HDL-C (but not Lp[a]) were associated with pancoronary plaque volume and pancoronary LCBI (P < 0.01 for all), but not with the presence of vulnerable plaque. Conversely, Lp(a) (but not TC, LDL-C, or non-HDL-C) was associated with the presence of focal vulnerable plaques (P = 0.01). CONCLUSIONS: In PROSPECT II, elevated TC, LDL-C, and non-HDL-C were strongly associated with pancoronary atherosclerosis and lipid deposition, whereas elevated Lp(a) was strongly associated with the presence of focal vulnerable plaques. These findings may explain the association between high Lp(a) levels and future MI and suggest a unique role for Lp(a) role in atherosclerosis progression and plaque vulnerability. (PROSPECT II & PROSPECT ABSORB-An Integrated Natural History Study and Randomized Trial; NCT02171065).
3. PFO Device Closure in Patients >60 Years of Age With Ischemic Stroke: Results From U.S. Medicare Beneficiaries.
In Medicare beneficiaries >60 years with ischemic stroke and PFO/ASD, propensity-matched analysis showed PFO closure reduced recurrent ischemic stroke (HR 0.62) compared with medical therapy, with acceptable safety but higher early venous thromboembolism and atrial fibrillation/flutter.
Impact: Expands real-world evidence supporting PFO closure beyond age 60, a population not addressed by prior RCTs, with implications for guideline refinement and shared decision-making.
Clinical Implications: For selected older patients with ischemic stroke and PFO, device closure may be considered to reduce recurrent stroke, with counseling on early AF/VTE risks and post-procedure monitoring.
Key Findings
- PFO closure reduced recurrent ischemic stroke vs medical therapy (HR 0.62; P=0.007).
- No difference in 30-day mortality; higher VTE (1.86% vs 0.37%) and AF/flutter (1.41% vs 0.64%) after closure.
- Median follow-up 2.58 years in a matched cohort of 5,508 beneficiaries (median age 71).
Methodological Strengths
- Large, national Medicare cohort with device registry linkage and 1:4 propensity score matching.
- Evaluation of both efficacy (recurrent stroke) and 30-day safety endpoints.
Limitations
- Observational design with potential residual confounding and selection bias.
- Generalizability limited to U.S. Medicare population; device-specific effects not randomized.
Future Directions: Prospective studies or pragmatic trials in older patients, optimized antithrombotic strategies post-closure, and risk models to balance stroke reduction vs AF/VTE.
BACKGROUND: Transcatheter closure of patent foramen ovale (PFO) is a recommended stroke reduction option in patients ≤60 years of age with cryptogenic ischemic stroke, but data on clinical outcomes following PFO closure in patients >60 years of age are scarce. OBJECTIVES: The aim of this real-world evidence study was to evaluate the clinical outcomes of PFO closure in patients >60 years of age in the United States. METHODS: Medicare fee-for-service data from 2016 to 2022 were used to identify patients >60 years of age who were hospitalized with ischemic stroke and diagnosed with PFO or atrial septal defect and also had ≥6 months of prior fee-for-service coverage. Patients who were implanted with the Amplatzer or Talisman PFO occluder (device group) were identified by linkage to a manufacturer device-tracking database and were propensity score matched (1:4) to those who did not undergo device implantation (control group). Acute safety events through 30 days and recurrent ischemic stroke through 3 years were evaluated. RESULTS: A total of 20,999 Medicare beneficiaries (device group, n = 1,132; control group, n = 19,867) met the inclusion criteria. The matched cohort included 5,508 Medicare beneficiaries (device group, n = 1,132; control group, n = 4,376), with 45% women, a median age of 71 years (Q1-Q3: 67-75 years), and median follow-up of 2.58 years (Q1-Q3: 1.17-3.97 years). The risk for recurrent ischemic stroke was significantly lower in the device group (1.65 [95% CI: 1.18-2.13] events per 100 patient-years) than the control group (2.66 [95% CI: 2.33-3.00] events per 100 patient-years) (HR: 0.62; 95% CI: 0.44-0.88; P = 0.007). Rates of 30-day safety events were not different for death, but venous thromboembolism (1.86% vs 0.37%; P < 0.001) and atrial fibrillation or flutter (1.41% vs 0.64%; P = 0.01) were more common in the device group. CONCLUSIONS: In a real-world U.S. cohort of patients >60 years of age, PFO closure was associated with a reduced risk for recurrent ischemic stroke compared with medical therapy alone, while maintaining a clinically acceptable safety profile.