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West J Med. Aug 1993; 159(2): 172–179.
PMCID: PMC1022223

Atherosclerosis--reversal with therapy.

Abstract

Evidence for atherosclerosis reversal comes from studies in animals wherein atherosclerosis is induced and then allowed to regress, autopsy studies of starved humans, and angiographic studies testing antiatherosclerosis treatment. Animal models and autopsy studies have provided detailed histologic and biochemical descriptions of regression. Cellular and subcellular information exists on what can occur, but because the same lesions are not re-examined, what actually does occur is unknown. Studies of isolated arterial cell systems and intact lesions indicate that atherogenesis involves at least the following: Increased permeability of the endothelium to macromolecules such as low-density lipoprotein; platelet adherence to areas of functional endothelial injury or denudation; the entrance of monocytes or macrophages and lymphocytes into the subintimal space; and the secretion of growth factors by platelets, injured endothelium, and macrophages. These processes can be initiated or enhanced by various vasoactive agents that induce endothelial cell constriction with the opening of endothelial junctions. These processes also can recruit smooth muscle cells from the media to the subintima where they proliferate. Proliferating smooth muscle cells, along with macrophages, can internalize lipids and lipoproteins to form foam cells. Subintimal smooth muscle cells can also synthesize collagen, elastin, glycosaminoglycans, and other connective tissue elements that trap lipoproteins. Peroxidative injury increases the atherogenic potential of both cholesteryl ester-rich (low-density) and triglyceride-rich (very-low-density and intermediate-density) lipoproteins. Steep oxygen gradients within the arterial wall create local conditions for free radical generation, and any increase in residence time of lipoprotein particles can be atherogenic. In summary, there are many areas where treatment may retard or reverse atherogenesis. Angiographic trials that identify and track individual human lesions have shown that reducing known atherogenic risk factors can lessen coronary and femoral atherosclerosis. But they provide no information on events within arterial wall cells or the intracellular matrix. They deal only with lesions that intrude into the vessel lumen and obtain measurements at infrequent intervals. The weight of evidence is that regression is possible, but there is no consensus on the most effective therapy. The challenge for future trials is to select optimal targets for intervention among the known atherogenic processes.

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Selected References

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  • Ost CR, Sténson S. Regression of peripheral atherosclerosis during therapy with high doses of nicotinic acid. Scand J Clin Lab Invest Suppl. 1967;99:241–245. [PubMed]
  • Thompson GR, Lowenthal R, Myant NB. Plasma exchange in the management of homozygous familial hypercholesterolaemia. Lancet. 1975 May 31;1(7918):1208–1211. [PubMed]
  • Barndt R, Jr, Blankenhorn DH, Crawford DW, Brooks SH. Regression and progression of early femoral atherosclerosis in treated hyperlipoproteinemic patients. Ann Intern Med. 1977 Feb;86(2):139–146. [PubMed]
  • Kuo PT, Hayase K, Kostis JB, Moreyra AE. Use of combined diet and colestipol in long-term (7--7 1/2 years) treatment of patients with type II hyperlipoproteinemia. Circulation. 1979 Feb;59(2):199–211. [PubMed]
  • Duffield RG, Lewis B, Miller NE, Jamieson CW, Brunt JN, Colchester AC. Treatment of hyperlipidaemia retards progression of symptomatic femoral atherosclerosis. A randomised controlled trial. Lancet. 1983 Sep 17;2(8351):639–642. [PubMed]
  • Brensike JF, Levy RI, Kelsey SF, Passamani ER, Richardson JM, Loh IK, Stone NJ, Aldrich RF, Battaglini JW, Moriarty DJ, et al. Effects of therapy with cholestyramine on progression of coronary arteriosclerosis: results of the NHLBI Type II Coronary Intervention Study. Circulation. 1984 Feb;69(2):313–324. [PubMed]
  • Arntzenius AC, Kromhout D, Barth JD, Reiber JH, Bruschke AV, Buis B, van Gent CM, Kempen-Voogd N, Strikwerda S, van der Velde EA. Diet, lipoproteins, and the progression of coronary atherosclerosis. The Leiden Intervention Trial. N Engl J Med. 1985 Mar 28;312(13):805–811. [PubMed]
  • Schettler G. Cardiovascular diseases during and after World War II: a comparison of the Federal Republic of Germany with other European countries. Prev Med. 1979 Sep;8(5):581–590. [PubMed]
  • Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L. Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA. 1987 Jun 19;257(23):3233–3240. [PubMed]
  • Blankenhorn DH, Selzer RH, Mack WJ, Crawford DW, Pogoda J, Lee PL, Shircore AM, Azen SP. Evaluation of colestipol/niacin therapy with computer-derived coronary end point measures. A comparison of different measures of treatment effect. Circulation. 1992 Dec;86(6):1701–1709. [PubMed]
  • Mack WJ, Selzer RH, Pogoda JM, Lee PL, Shircore AM, Azen SP, Blankenhorn DH. Comparison of computer- and human-derived coronary angiographic end-point measures for controlled therapy trials. Arterioscler Thromb. 1992 Mar;12(3):348–356. [PubMed]
  • Cashin-Hemphill L, Mack WJ, Pogoda JM, Sanmarco ME, Azen SP, Blankenhorn DH. Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up. JAMA. 1990 Dec 19;264(23):3013–3017. [PubMed]
  • Blankenhorn DH, Johnson RL, Mack WJ, el Zein HA, Vailas LI. The influence of diet on the appearance of new lesions in human coronary arteries. JAMA. 1990 Mar 23;263(12):1646–1652. [PubMed]
  • Blankenhorn DH, Azen SP, Crawford DW, Nessim SA, Sanmarco ME, Selzer RH, Shircore AM, Wickham EC. Effects of colestipol-niacin therapy on human femoral atherosclerosis. Circulation. 1991 Feb;83(2):438–447. [PubMed]
  • Blankenhorn DH, Johnson RL, Nessim SA, Azen SP, Sanmarco ME, Selzer RH. The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results. Control Clin Trials. 1987 Dec;8(4):356–387. [PubMed]
  • Buchwald H, Varco RL, Matts JP, Long JM, Fitch LL, Campbell GS, Pearce MB, Yellin AE, Edmiston WA, Smink RD, Jr, et al. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH) N Engl J Med. 1990 Oct 4;323(14):946–955. [PubMed]
  • Brown G, Albers JJ, Fisher LD, Schaefer SM, Lin JT, Kaplan C, Zhao XQ, Bisson BD, Fitzpatrick VF, Dodge HT. Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B. N Engl J Med. 1990 Nov 8;323(19):1289–1298. [PubMed]
  • Kane JP, Malloy MJ, Ports TA, Phillips NR, Diehl JC, Havel RJ. Regression of coronary atherosclerosis during treatment of familial hypercholesterolemia with combined drug regimens. JAMA. 1990 Dec 19;264(23):3007–3012. [PubMed]
  • Ornish D, Brown SE, Scherwitz LW, Billings JH, Armstrong WT, Ports TA, McLanahan SM, Kirkeeide RL, Brand RJ, Gould KL. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial. Lancet. 1990 Jul 21;336(8708):129–133. [PubMed]
  • Watts GF, Lewis B, Brunt JN, Lewis ES, Coltart DJ, Smith LD, Mann JI, Swan AV. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS) Lancet. 1992 Mar 7;339(8793):563–569. [PubMed]
  • Lichtlen PR, Hugenholtz PG, Rafflenbeul W, Hecker H, Jost S, Deckers JW. Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). INTACT Group Investigators. Lancet. 1990 May 12;335(8698):1109–1113. [PubMed]
  • Waters D, Lespérance J, Francetich M, Causey D, Théroux P, Chiang YK, Hudon G, Lemarbre L, Reitman M, Joyal M, et al. A controlled clinical trial to assess the effect of a calcium channel blocker on the progression of coronary atherosclerosis. Circulation. 1990 Dec;82(6):1940–1953. [PubMed]
  • Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988 Jul;12(1):56–62. [PubMed]
  • Hackett D, Davies G, Maseri A. Pre-existing coronary stenoses in patients with first myocardial infarction are not necessarily severe. Eur Heart J. 1988 Dec;9(12):1317–1323. [PubMed]

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