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Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia
P A Kaufmann1, T Gnecchi-Ruscone, K P Schäfers
1MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Insights
In asymptomatic individuals, elevated low-density lipoprotein (LDL) cholesterol, not total cholesterol (TC), is linked to reduced coronary flow reserve (CFR). This suggests LDL-induced coronary microvascular dysfunction contributes to heart disease development.
Area of Science:
- Cardiology
- Vascular Biology
- Medical Imaging
Background:
- Endothelial dysfunction in coronary microcirculation is observed in asymptomatic hypercholesterolemia.
- Hypercholesterolemia is a risk factor for coronary artery disease.
Purpose of the Study:
- To investigate the relationship between total cholesterol (TC) and its subfractions with coronary flow reserve (CFR) in asymptomatic individuals.
- To determine if lipid profiles impact integrated coronary circulation function.
Main Methods:
- Positron emission tomography (PET) with oxygen-15-labeled water was used to measure myocardial blood flow (MBF) at rest and during adenosine stress.
- 80 asymptomatic, nonsmoking men were divided into normal TC (Group 1) and elevated TC (Group 2) groups.
- Coronary flow reserve (CFR) was calculated as the ratio of stress MBF to rest MBF.
Main Results:
- Elevated TC and LDL cholesterol were observed in Group 2 compared to Group 1 (p < 0.0005).
- No significant differences in rest MBF, stress MBF, or CFR were found between the groups.
- A significant inverse correlation was found between LDL cholesterol and CFR in the hypercholesterolemic group (Group 2, r = -0.61, p < 0.05).
Conclusions:
- Low-density lipoprotein (LDL) cholesterol, but not total cholesterol (TC), is inversely correlated with coronary flow reserve (CFR) in hypercholesterolemic subjects.
- LDL-induced coronary microvascular dysfunction may play a significant role in the pathogenesis of coronary artery disease.
Objectives:
The present study evaluates the impact of total cholesterol (TC) and its subfractions on coronary flow reserve (CFR), an index of the integrated function of the coronary circulation, in asymptomatic subjects.
Background:
Endothelial dysfunction of the coronary microcirculation has been reported in asymptomatic subjects with hypercholesterolemia.
Methods:
Using oxygen-15-labeled water and positron emission tomography, myocardial blood flow (MBF, in ml/min per g) was measured at rest and during intravenous adenosine (140 microg/kg body weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61; age 45 +/- 7 years) had normal TC (< or =6.5 mmol/liter or < or =250 mg/dl) and group 2 (n = 19; age 48 +/- 10 years) had elevated TC.
Results:
Total cholesterol were 5.1 +/- 0.8 and 7.2 +/- 0.7 mmol/liter in groups 1 and 2 (p < 0.0005), respectively; low density lipoprotein (LDL) cholesterol levels were 3.2 +/- 0.8 and 4.9 +/- 0.7 mmol/liter (p < 0.0005); high density lipoprotein (HDL) cholesterol levels were 1.1 +/- 0.3 and 1.0 +/- 0.4 mmol/liter (p = NS); and triglyceride levels were 1.8 +/- 1.3 and 3.0 +/- 1.8 mmol/liter (p < 0.005). Groups 1 and 2 did not differ with regard to MBF at rest (0.87 +/- 0.14 vs. 0.84 +/- 0.14), MBF during adenosine (3.63 +/- 1.02 vs. 3.30 +/- 0.86) or CFR (4.23 +/-1.29 vs. 3.95 +/- 0.93). A significant but weak correlation was found between CFR and HDL in group 1 (r = 0.29, p < 0.05), but not in group 2. In contrast, a significant inverse correlation between LDL and CFR was found in group 2 (r = -0.61, p < 0.05), but not in group 1.
Conclusions:
Low density lipoprotein cholesterol but not TC correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced coronary microvascular dysfunction could play an important role in the pathogenesis of coronary artery disease and its complications.