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Delayed response of myocardial flow reserve to lipid-lowering therapy with fluvastatin
M Guethlin1, A M Kasel, K Coppenrath
1Abteilung für Kardiologie, Klinikum München-Bogenhausen, München, Germany.
Insights
Fluvastatin therapy improved coronary flow reserve (CFR) in coronary artery disease (CAD) patients after six months, indicating a delayed recovery of microvascular function despite rapid lipid reduction.
Area of Science:
- Cardiology
- Nuclear Medicine
- Pharmacology
Background:
- Lipid-lowering therapy improves endothelial function in coronary artery disease (CAD) and hypercholesterolemia.
- Limited data exists on its effects on myocardial microcirculation.
- This study investigated fluvastatin's impact on coronary flow and reserve in CAD patients.
Purpose of the Study:
- To prospectively assess the temporal effects of fluvastatin on coronary flow and flow reserve (CFR).
- To evaluate changes in myocardial microcirculation using positron emission tomography (PET).
Main Methods:
- Open clinical trial with 15 multivessel CAD patients (LDL >160 mg/dL).
- Dynamic 13N-labeled ammonia PET imaging with adenosine to measure regional and global CFR.
- Assessment at baseline, 2 months, and 6 months during fluvastatin treatment (60-80 mg/d).
Main Results:
- Total cholesterol and LDL decreased significantly (29% and 37%, respectively) within 2 months.
- Myocardial blood flow at rest and stress remained unchanged at 2 months.
- By 6 months, stress blood flow and CFR significantly increased (p<0.05).
- Nine patients showed >20% CFR improvement, correlating with better anginal symptoms.
- Improvement was independent of lipid-lowering extent or stenosis severity.
Conclusions:
- Fluvastatin therapy leads to a delayed improvement in stress blood flow and CFR.
- This suggests a slow recovery of the vasodilatory response to adenosine in CAD patients.
- The microvascular benefits emerge later than the lipid-lowering effects.
Background:
Lipid-lowering therapy can improve endothelial function in patients with coronary artery disease (CAD) and hypercholesterolemia. Little is known about induced changes in myocardial microcirculation. This study prospectively investigated the temporal effects of lipid-lowering therapy with fluvastatin on coronary flow and flow reserve (CFR) in patients with CAD assessed by PET.
Methods And Results:
In an open clinical trial, CFR was studied in 15 patients with angiographically documented multivessel CAD and hypercholesterolemia (LDL >160 mg/dL). Dynamic 13N-labeled ammonia PET imaging in conjunction with adenosine was used to assess regional and global CFR at baseline as well as at 2 and 6 months during treatment with fluvastatin (60 to 80 mg/d). Despite a rapid decrease in total cholesterol (29+/-6%) and LDL (37+/-9%), myocardial blood flow at rest and during stress was unchanged after 2 months of treatment (2.7+/-0.9 versus 2.5+/-0.6 mL x g-1 x min-1). At 6 months, stress blood flow as well as CFR increased significantly (3.4+/-1.0 mL x g-1 x min-1). No change in hemodynamic parameters was noted during the entire study. Nine of 15 patients increased CFR by >20%. All responders demonstrated improvement in anginal symptoms, whereas nonresponders stated no change (n=4) or worsening of symptoms (n=2). The improvement in CFR was not related to the amount of lipid lowering and was independent of the severity of stenoses.
Conclusions:
Improvement in stress blood flow and CFR is delayed compared with the lipid-lowering effect of fluvastatin, suggesting a slow recovery of the vasodilatory response to adenosine.