CLINICAL STUDIES: ENDOTHELIAL FUNCTION
Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia
Philipp A. Kaufmann, MD*  ,1,
Tomaso Gnecchi-Ruscone, MD*,
Klaus P. Schäfers, MSc*,
Thomas F. Lüscher, MD, FACC, FESC, FRCP and
Paolo G. Camici, MD, FACC, FESC, FRCP*
* MRC Clinical Sciences Centre, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom
Cardiology, University Hospital, Zürich, Switzerland
Manuscript received September 2, 1999;
revised manuscript received December 30, 1999,
accepted February 28, 2000.
Reprint requests and correspondence: Prof. Paolo G. Camici, MRC Cyclotron Unit, Hammersmith Hospital, London W12 ONN, United Kingdom
paolo.camici{at}csc.mrc.ac.uk
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 µg/kg body weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61; age 45 ± 7 years) had normal TC ( 6.5 mmol/liter 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.
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Abbreviations and Acronyms
| | CFR | = coronary flow reserve | | ECG | = electrocardiogram | | H215O | = oxygen-15-labeled water | | HDL | = high density lipoprotein | | LDL | = low density lipoprotein | | MBF | = myocardial blood flow | | PET | = positron emission tomography | | TC | = total cholesterol |
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