[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia].
BACKGROUND
An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin).


METHODS
Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients.


CONCLUSIONS
An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.
Baller
D
D
Kardiologische Klinik Herzzentrum Nordrhein-Westfalen Klinik der Ruhr-Universität Bochum, Bad Oeynhausen.
Gleichmann
U
U
Notohamiprodjo
G
G
Weise
R
R
Holzinger
J
J
Montanus
H
H
Betker
S
S
Lehmann
J
J
D000328:Adult; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood*; D003131:Combined Modality Therapy; D017023:Coronary Angiography / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D003326:Coronary Circulation / Q000187:drug effects*; D018752:Diet, Fat-Restricted; D004176:Dipyridamole; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects*
D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D004176:Dipyridamole; D019821:Simvastatin
Verbesserung der koronaren Vasodilatationskapazität durch medikamentöse Lipidsenkung bei Patienten im Frühstadium der koronaren Atherosklerose mit eingeschränkter Koronarreserve und mässiggradiger LDL-Hypercholesterinämie.