Abstract
Background
Statins improve endothelial functioning in patients with coronary artery disease and hypercholesterolemia, while substantially little is known about induced changes in myocardial microcirculation. However, although previous studies have suggested that microvascular abnormalities and endothelial dysfunction is responsible for slow coronary flow (SCF), there is no study investigating possible effects of statins on coronary microvascular function in patients with SCF.
Hypothesis
We prospectively investigated the effects of short‐term lipid‐lowering therapy with atorvastatin on coronary flow reserve (CFR) reflecting coronary microvascular function in patients with SCF assessed by transthoracic Doppler echocardiography (TTDE).
Methods
In an open clinical trial, CFR was studied in 20 subjects with SCF. TTDE was used to assess CFR at baseline as well as after 8 weeks of atorvastatin therapy. Coronary flow was quantified according to TIMI frame count (TFC). Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities.
Results
CFR was independently correlated with TFC. After 8 weeks of atorvastatin therapy, CFR values increased significantly (1.95 ± 0.38 vs. 2.54 ± 0.56, (p < 0.001). No change in hemodynamic parameters was noted during the entire study. The improvement in CFR was not correlated to the amount of lipid‐lowering effect of atorvastatin.
Conclusions
These findings suggest that short‐term lipid‐lowering therapy with atorvastatin improved CFR, which reflects coronary microvascular functioning in patients with SCF. Copyright © 2007 Wiley Periodicals, Inc.
Keywords: slow coronary flow, coronary flow reserve, echocardiography, atorvastatin
Full Text
The Full Text of this article is available as a PDF (237.6 KB).
References
- 1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–1389. [PubMed] [Google Scholar]
- 2. Sever PS, Dahlof B, Poulter NR, Wedel H, Beevers G, et al.: ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower‐than‐average cholesterol concentrations, in the Anglo‐Scandinavian Cardiac Outcomes Trial‐Lipid Lowering Arm (ASCOT‐LLA): a multicentre randomised controlled trial Lancet 2003; 361: 1149–1158. [DOI] [PubMed] [Google Scholar]
- 3. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, et al.: CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo‐controlled trial. Lancet 2004; 364: 685–696. [DOI] [PubMed] [Google Scholar]
- 4. The Long‐Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group: Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. New Engl J Med 1998; 339: 1349–1357. [DOI] [PubMed] [Google Scholar]
- 5. Takemoto M, Liao JK: Pleiotropic effects of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21: 1712–1719. [DOI] [PubMed] [Google Scholar]
- 6. Tambe AA, Demany MA, Zimmerman HA, Mascarenhas E: Angina pectoris and slow flow velocity of dye in coronary arteries. A new angiographic finding. Am Heart J 1972; 84: 66–71. [DOI] [PubMed] [Google Scholar]
- 7. Mangieri E, Macchiarelli G, Ciavolella M, Barilla F, Avella A: et al. Slow coronary flow: clinical and histopathological features in patients with otherwise normal epicardial coronary arteries. Cathet Cardiovasc Diagn 1996; 37: 375–381. [DOI] [PubMed] [Google Scholar]
- 8. Caiati C, Zedda N, Montaldo C, Montisci R, Iliceto S: Contrast‐enhanced transthoracic second harmonic echo Doppler with adenosine: a noninvasive, rapid and effective method for coronary flow reserve assessment. J Am Coll Cardiol 1999; 34: 122–130. [DOI] [PubMed] [Google Scholar]
- 9. Britten MB, Zeiher AM, Schachinger V Microvascular dysfunction in angiographically normal or mildly diseased coronary arteries predicts adverse cardiovascular long‐term outcome. Coron Artery Dis 2004; 15: 259–264. [DOI] [PubMed] [Google Scholar]
- 10. Caiati C, Montaldo C, Zedda N Bina A, Iliceto S New noninvasive method for coronary flow reserve assessment: contrast‐enhanced transthoracic second harmonic echo Doppler. Circulation 1999; 99: 771–778. [DOI] [PubMed] [Google Scholar]
- 11. Gibson CM, Cannon CP, Daley WL, Dodge JT Jr, Alexander B Jr, et al. TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 1996; 93: 879–888. [DOI] [PubMed] [Google Scholar]
- 12. Erdogan D, Gullu H, Caliskan M, Yildirim I, Tok D, et al.: Coronary flow reserve is preserved in white‐coat hypertension. Heart 2006; 92: 1109–1112. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. De Bruyne B, Hersbach F, Pijls NH, Bartunek J, Bech JW, et al.: Abnormal epicardial coronary resistance in patients with diffuse atherosclerosis but “Normal” coronary angiography. Circulation 2001; 104: 2401–2406. [DOI] [PubMed] [Google Scholar]
- 14. Mosseri M, Yarom R, Gotsman MS, Hasin Y Histologic evidence for small‐vessel coronary artery disease in patients with angina pectoris and patent large coronary arteries. Circulation 1986; 5: 964–972. [DOI] [PubMed] [Google Scholar]
- 15. Kayikcioglu M, Payzin S, Yavuzgil O, Kultursay H, Can LH, et al.: Benefits of statin treatment in cardiac syndrome‐X. Eur Heart J 2003; 24: 1999–2005. [DOI] [PubMed] [Google Scholar]
- 16. Baller D, Notohamiprodjo G, Gleichmann U, Holzinger J, Weise R, et al.: Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol‐lowering therapy in patients with early stages of coronary atherosclerosis. Circulation 1999; 99: 2871–2875. [DOI] [PubMed] [Google Scholar]
- 17. Kaesemeyer WH, Caldwell RB, Huang J, Caldwell RW Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol‐lowering actions. J Am Coll Cardiol 1999; 33: 234–241. [DOI] [PubMed] [Google Scholar]
- 18. Ling MC, Ruddy TD, deKemp RA, Ukkonen H, Duchesne L, et al. Early effects of statin therapy on endothelial function and microvascular reactivity in patients with coronary artery disease. Am Heart J 2005; 149: 1137. [DOI] [PubMed] [Google Scholar]
- 19. Hinoi T, Matsuo S, Tadehara F, Tsujiyama S, Yamakido M Acute effect of atorvastatin on coronary circulation measured by transthoracic Doppler echocardiography in patients without coronary artery disease by angiography. Am J Cardiol 2005; 96: 89–91. [DOI] [PubMed] [Google Scholar]
