Journal of Endocrinological Investigation

, Volume 25, Issue 6, pp RC16–RC18 | Cite as

Simvastatin normalizes QTc dispersion and reduces ventricular electrical instability in isolated hypercholesterolemia

  • P. Gualdiero
  • K. Esposito
  • M. Ciotola
  • R. Marfella
  • D. Giugliano
Rapid Communication


This study aimed at evaluating a possible relationship between cholesterol levels and ventricular electrical instability in human beings. Forty subjects (26 males and 14 females, mean age±SD 50.3±3.7 yr) with isolated hypercholesterolemia (≥240 mg/dl) were selected from a population of 250 patients who attended the outpatient department of our institution for symptomatic extrasystolic activity (ventricular premature complexes >3,000/24 h). Subjects were randomly assigned to receive either simvastatin 40 mg/d or placebo for 3 consecutive months. After treatment, subjects in the simvastatin group presented a significant decrease of total cholesterol and LDL-cholesterol (p<0.001) and an increase of HDL-cholesterol levels (p<0.01), associated with a reduction of both QTc dispersion (p<0.001) and ventricular premature complexes (p<0.001). None of these changes were observed in the placebo group. At baseline, there was a relationship between cholesterol levels, ventricular premature complexes (VPC) (r=0.33, p<0.05) and QTc dispersion (r=0.41, p<0.01). After treatment, reductions in serum cholesterol levels correlated with decreases of both VPCs (r=0.37, p<0.01) and QTc dispersion (r=0.49, p<0.01). In subjects with isolated hypercholesterolemia simvastatin may reduce the cardiovascular risk associated with ventricular electrical instability.


Cholesterol simvastatin QTc dispersion ventricular instability 


  1. 1.
    Kannel W.B. Range of serum cholesterol values in the population developing coronary artery disease. Am. J. Cardiol. 1995, 76: 69C–77C.PubMedCrossRefGoogle Scholar
  2. 2.
    Pignone M., Phillips C., Mulrow C. Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials. B.M.J. 2000, 321: 983–986.CrossRefGoogle Scholar
  3. 3.
    Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease. The Scandinavian Simvastatin Survival Study (4S). Lancet 1994, 344: 1383–1389.Google Scholar
  4. 4.
    Sacks F.M., Pfeffer M.A., Moye L.A., et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels (CARE) N. Engl. J. Med. 1996, 335: 1001–1009.CrossRefGoogle Scholar
  5. 5.
    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. N. Engl. J. Med. 1998, 339: 1349–1357.CrossRefGoogle Scholar
  6. 6.
    Takemoto M., Liao J.K. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler. Thromb. Vasc. Biol. 2001, 21: 1712–1719.PubMedCrossRefGoogle Scholar
  7. 7.
    Zipes D.P., Wellens H.J. Sudden cardiac death. Circulation 1998, 98: 2234–2251.CrossRefGoogle Scholar
  8. 8.
    Jouven X., Charles M.A., Desnos M., Ducimetiere P. Circulating nonesterified fatty acids level as a predictive risk factor for sudden death in the population. Circulation 2001, 104: 756–761.PubMedCrossRefGoogle Scholar
  9. 9.
    Barr S.C., Naas A.A., Fenwick M., Struthers A. Enalapril reduces QTc dispersion in mild congestive heart failure secondary to coronary artery disease. Am. J. Cardiol. 1997, 79: 328–333.PubMedCrossRefGoogle Scholar
  10. 10.
    Perkiomäki J., Koistinen M.J., Yli-Mayry S., Huikuri H. Dispersion of the QT interval in patients with and without susceptibility to ventricular tachyarrhythmias after previous myocardial infarction J. Am. Coll. Cardiol. 1995, 26: 174–179.PubMedCrossRefGoogle Scholar
  11. 11.
    Perkiomäki J., Ukaheimo M.J., Pikkujämsä S.M., et al. Dispersion of QT interval and autonomic modulation of heart rate in hypertensive men with and without left ventricular hypertrophy. Hypertension 1996, 28: 16–21.PubMedCrossRefGoogle Scholar
  12. 12.
    Grimm W., Steder U., Menz V., Hoffman J., Grote F., Maisch B. Clinical significance of increased QT dispersion in the 12-lead standard ECG for arrhythmia risk prediction in dilated cardiomyopathy. Pacing Clin. Electrophysiol. 1996, 19: 1886–1889.PubMedCrossRefGoogle Scholar
  13. 13.
    Murray A., McLaughlin N.V., Campbell R.W.F. Measuring QT dispersion: man versus machine Heart 1997, 77: 539–542.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Bazett H. An analysis of time-relations of electrocardiograms. Heart 1920, 7: 353–370.Google Scholar
  15. 15.
    Sen L., Bialecki R.A., Smith E., Smith T.W., Colucci W.S. Cholesterol increases the L-type voltage-sensitive calcium channel current in arterial smooth muscle cells. Circ. Res. 1992, 71: 1008–1014.PubMedCrossRefGoogle Scholar
  16. 16.
    Di Diego J.M., Antzelevitch C. Pinacidil-induced electrical heterogeneity and extrasystolic activity in canine ventricular tissues. Does activation of ATP-regulated potassium current promote phase 2 re-entry? Circulation 1993, 88: 1177–1189.PubMedCrossRefGoogle Scholar
  17. 17.
    Antzelevitch C., Sicouri S., Litovsky S.H., et al. Heterogeneity within the ventricular wall: electrophysiology and pharmacology of epicardial, endocardial and M cells. Circ. Res. 1991, 69: 1427–1449.PubMedCrossRefGoogle Scholar
  18. 18.
    Boineau J.P., Cox J.L. Slow ventricular activation in acute myocardial infarction: a source of re-entrant premature ventricular contractions. Circulation. 1973, 48: 702–713.PubMedCrossRefGoogle Scholar
  19. 19.
    Kimura S., Bassett A.L., Kohya T., Kozlovskis P.L., Myerburg R.J. Simultaneous recording of action potentials from endocardium and epicardium during ischemia in the isolated cat ventricle. Relation of temporal electrophysiologic heterogeneities to arrhythmias. Circulation 1986, 74: 401–409.PubMedCrossRefGoogle Scholar
  20. 20.
    Zeiher A.M., Drexler H., Wolschlager H., Just H. Modulation of coronary vasomotor tone in humans: progressive endothelial dysfunction with different early stages of coronary atherosclerosis. Circulation 1991, 83: 391–401.PubMedCrossRefGoogle Scholar
  21. 21.
    Brown B.G., Zhao X.Q., Sacco D.E., Albers J.J. Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993, 87: 1781–1791.PubMedCrossRefGoogle Scholar
  22. 22.
    Pekkanen J., Linn S., Heiss G., et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without pre-existing cardiovascular disease. N. Engl. J. Med. 1990, 322: 1700–1707.PubMedCrossRefGoogle Scholar
  23. 23.
    Kureishi Y., Luo Z., Shiojima I., et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase AKT and promotes angiogenesis in normocholesterolemic animals. Nat. Med. 2000, 6: 1004–1010.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Rikitake Y., Kawashima S., Takeshita S., et al. Anti-oxidative properties of fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits. Atherosclerosis 2001, 154: 87–96.PubMedCrossRefGoogle Scholar
  25. 25.
    Laufs U., Liao J.K. Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by RHO GTPase. J. Biol. Chem. 1998, 273: 24266–24271.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2002

Authors and Affiliations

  • P. Gualdiero
    • 1
  • K. Esposito
    • 1
  • M. Ciotola
    • 1
  • R. Marfella
    • 1
  • D. Giugliano
    • 1
  1. 1.Department of Geriatrics and Metabolic DiseasesSecond University of NaplesNaplesItaly

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