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How best to combat the enemies? Lipid lowering

S.M. Cobbe*

Department of Medical Cardiology, Glasgow Royal Infirmary, University of Glasgow, Glasgow, U.K.

* Correspondence: Stuart M. Cobbe, MD FRCP, Department of Medical Cardiology, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, U.K.

Abstract

The evidence linking elevated plasma low-density lipoprotein cholesterol to atherosclerosis and its clinical consequences is overwhelming. Similarly, there is now compelling evidence that the risk of these complications can be reduced by lipid-lowering therapies. Research reported during the past few years has helped to clarify the apparent paradox of substantial reductions in the risk for cardiovascular events in the presence of minor changes in the extent of coronary artery stenosis. It is clear that lipid reduction results in favourable changes in plaque morphology and composition, reflecting a reduction in the inflammatory content and an increase in the smooth muscle content that favour stability. In addition, changes in endothelial function, platelet adhesiveness and rheology all potentially play a role in the beneficial effects of lipid lowering.

Key Words: Atherosclerosis • lipid lowering • plaque stability

References

  1. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA. 1986;256:2823–2828[Abstract/Free Full Text]
  2. Pekkanen J, Linn S, Heiss G, et al. Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease. N Engl J Med. 1990;322:1700–1707[Abstract]
  3. Jukema JW, Bruschke AVG, van Boven AJ, et al. Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels: the Regression Growth Evaluation Statin Study (REGRESS). Circulation. 1995;91:2528–2540[Abstract/Free Full Text]
  4. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–1389[CrossRef][Web of Science][Medline]
  5. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–1307[Abstract/Free Full Text]
  6. Tonkin A, Alyward P, Colquhoun D, et al. 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[Abstract/Free Full Text]
  7. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001–1009[Abstract/Free Full Text]
  8. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615–1622[Abstract/Free Full Text]
  9. GISSI Prevenzione Investigators (Gruppo Italiano per to Studio della Sopravvivenza nell'Infarto Miocardico). Results of the lowdose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? Ital Heart J. 2000;1:810–820[Medline]
  10. van Boven AJ, Jukema JW, Zwinderman AH, Crijns HJGM, Lie KI, Bruschke AVG. Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. Circulation. 1996;94:1503–1505[Abstract/Free Full Text]
  11. AnonymousThe Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984;251:351–364[Abstract/Free Full Text]
  12. Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: primaryprevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317:1237–1245[Abstract]
  13. Davies M, Thomas A. Plaque fissuring: the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Br Heart J. 1985;53:363–373[Free Full Text]
  14. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995;92:657–671[Free Full Text]
  15. Geng YJ, Henderson LE, Levesque EB, Muszynski M, Libby P. Fas is expressed in human atherosclerotic intima and promotes apoptosis of cytokine-primed human vascular smooth muscle cells. Arterioscler Thromb Vase Biol. 1997;17:2200–2208
  16. Geng YJ, Wu Q, Muszynski M, Hansson GK, Libby P. Apoptosis of vascular smooth muscle cells induced by in vitro stimulation with interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 beta. Arterioscler Thromb Vase Biol. 1996;16:19–27
  17. Boyle JJ, Bowyer DE, Weissberg PL, Bennett MR. Human bloodderived macrophages induce apoptosis in human plaque-derived vascular smooth muscle cells by Fas-ligand/Fas interactions. Arterioscler Thromb Vase Biol. 2001;21:1402–1407
  18. Lendon CL, Davies MJ, Born GV, Richardson PD. Atherosclerotic plaque caps are locally weakened when macrophage density is increased. Atherosclerosis. 1991;87:87–90[CrossRef][Web of Science][Medline]
  19. Shiomi M, Ito T, Tsukada T, et al. Reduction of serum cholesterol levels alters lesional composition of atherosclerotic plaques. Effect of paravastatin sodium on aterosclerosis plaques rabbit. Thromb Vase Biol. 1995;15:1938–1944
  20. Fukumoto Y, Libby P, Rabkin E, et al. Statins alter smooth muscle cell accumulation and collagen content in established atheroma of Watanabe heritable hyperlipidemic rabbits. Circulation. 2001;103:993–999[Abstract/Free Full Text]
  21. Crisby M, Nordin-Fredriksson G, Shah PK, Yano J, Zhu J, Nilsson J. Pravastatin treatment increases collagen content and decreases lipid content, inflammation, metalloproteinases, and cell death in human carotid plaques: implications for plaque stabilization. Circulation. 2001;103:926–933[Abstract/Free Full Text]
  22. Davies MJ. Acute coronary thrombosis: the role of plaque disruption and its initiation and prevention. Eur Heart J. 1995;16:3–7
  23. Treasure CB, Klein JL, Weintraub WS, et al. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. N Engl J Med. 1995;332:481–487[Abstract/Free Full Text]
  24. de Divitiis M, Rubba P, Di Somma S, et al. Effects of short-term reduction in serum cholesterol with simvastatin in patients with stable angina pectoris and mild to moderate hypercholesterolemia. Am J Cardiol. 1996;78:763–768[CrossRef][Web of Science][Medline]
  25. Lacoste L, Lam JY, Hung J, Letchacovski G, Solymoss CB, Waters D. Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. Circulation. 1995;92:3172–3177[Abstract/Free Full Text]
  26. Lowe G, Rumley A, Norrie J, et al. Blood theology, cardiovascular risk factors, and cardiovascular disease: the West of Scotland Coronary Prevention Study. Thromb Haemost. 2000;84:553–558[Web of Science][Medline]

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