Partial peroxisome proliferator-activated receptor agonist angiotensin receptor blockers: Potential multipronged strategy in stroke prevention

Cerebrovascular Diseases

Volumn 26, Issue 2, 2008, Pages 106-112

  Towfighi, Amytis ^a   Ovbiagele, Bruce ^b  

^a UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antihypertensive therapy; Atherosclerosis risk factors; Atherothrombotic stroke; Blood pressure management; Cardiovascular prevention; Hyperglycemia; Ischemic stroke; Lipid management; Primary and secondary prevention; Risk factor management

Indexed keywords

ACETYLSALICYLIC ACID; ANGIOTENSIN RECEPTOR ANTAGONIST; CLOPIDOGREL; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIPYRIDAMOLE; EPROSARTAN; GLITAZONE DERIVATIVE; IRBESARTAN; LOSARTAN; NISOLDIPINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PIOGLITAZONE; PLACEBO; RAMIPRIL; ROSIGLITAZONE; TELMISARTAN; VALSARTAN;

CEREBROVASCULAR DISEASE; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; DRUG BLOOD LEVEL; DRUG MECHANISM; DRUG SUBSTITUTION; DRUG WITHDRAWAL; DYSLIPIDEMIA; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; HYPERTENSION; IMPAIRED GLUCOSE TOLERANCE; INSULIN RESISTANCE; INSULIN SENSITIVITY; METABOLIC SYNDROME X; MONOTHERAPY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; PLEIOTROPY; PRIORITY JOURNAL; PROPHYLAXIS; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; RISK ASSESSMENT; SIDE EFFECT; STROKE; WEIGHT GAIN;

ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS; ANIMALS; ANTIHYPERTENSIVE AGENTS; DRUG PARTIAL AGONISM; HUMANS; HYPERLIPIDEMIAS; HYPERTENSION; HYPOGLYCEMIC AGENTS; INSULIN RESISTANCE; ISCHEMIC ATTACK, TRANSIENT; METABOLIC SYNDROME X; OBESITY; PPAR GAMMA; RENIN-ANGIOTENSIN SYSTEM; RISK ASSESSMENT; RISK FACTORS; STROKE;

EID: 50049099439     PISSN: 10159770     EISSN: None     Source Type: Journal    
DOI: 10.1159/000139656     Document Type: Review

References (70)

1. Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schwamm LH, Tomsick T: Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: a statement for healthcare professionals from the American Heart Association/American Stroke Association Council on Stroke: co-sponsored by the Council on Cardiovascular Radiology and Intervention: The American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:577-617.
2. Sowers JR, Frohlich ED: Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am 2004;88:63-82.
3. Watson KE, Peters Harmel AL, Matson G: Atherosclerosis in type 2 diabetes mellitus: the role of insulin resistance. J Cardiovasc Pharmacol Ther 2003;8:253-260.
4. Gorter P, Olijhoek JK, Van Der Graaf Y, Algra A, Rabelink TJ, Visseren FL: Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis 2004;173:361-367.
5. Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M, Taskinen M-R, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-689.
6. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM: Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006;295:1549-1555.
7. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F: Diagnosis and management of the metabolic syndrome - An American Heart Association/National Heart, Lung, and Blood Institute scientific statement: executive summary. Cardiol Rev 2005;13:322-327.
8. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT: The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-2716.
9. Laaksonen DE, Lakka HM, Niskanen LK, Kaplan GA, Salonen JT, Lakka TA: Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am J Epidemiol 2002;156:1070-1077.
10. Gorter PM, Olijhoek JK, van der Graaf Y, Algra A, Rabelink TJ, Visseren FL: Prevalence of the metabolic syndrome in patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease or abdominal aortic aneurysm. Atherosclerosis 2004;173:363-369.
11. Wannamethee SG, Perry IJ, Shaper AG: Nonfasting serum glucose and insulin concentrations and the risk of stroke. Stroke 1999;30:1780-1786.
12. Marroquin OC, Kip KE, Kelley DE, Johnson BD, Shaw LJ, Bairey Merz CN, Sharaf BL, Pepine CJ, Sopko G, Reis SE: Metabolic syndrome modifies the cardiovascular risk associated with angiographic coronary artery disease in women: a report from the Women's Ischemia Syndrome Evaluation. Circulation 2004;109:714-721.
13. Ford ES: Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the US. Diabetes Care 2005;28:2745-2749.
14. Kernan WN, Inzucchi SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI: Insulin resistance and risk for stroke. Neurology 2002;59:809-815.
15. Pyorala M, Miettinen H, Halonen P, Laakso M, Pyorala K: Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki policemen study. Arterioscler Thromb Vasc Biol 2000;20:538-544.
16. UK Prospective Diabetes Study (UKPDS) group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) Lancet 1998;352:854-865.
17. Minamikawa J, Tanaka S, Yamauchi M, Inoue D, Koshiyama H: Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 1998;83:1818-1820.
18. Koshiyama H, Shimono D, Kuwamura N, Minamikawa J, Nakamura Y: Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 2001;86:3452-3456.
19. Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM: Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest 1989;83:1168-1173.
20. Ovbiagele B, Saver JL: Cerebral white matter hyperintensities on MRI: current concepts and therapeutic implications. Cerebrovasc Dis 2006;22:83-90.
21. Golden SH, Folsom AR, Coresh J, Sharrett AR, Szklo M, Brancati F: Risk factor groupings related to insulin resistance and their synergistic effects on subclinical atherosclerosis: The atherosclerosis risk in communities study. Diabetes 2002;51:3069-3076.
22. Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M: Carotid atherosclerosis and coronary heart disease in the metabolic syndrome: prospective data from the Bruneck study. Diabetes Care 2003;26:1251-1257.
23. Bang OY, Kim JW, Lee JH, Lee MA, Lee PH, Joo IS, Huh K: Association of the metabolic syndrome with intracranial atherosclerotic stroke. Neurology 2005;65:296-298.
24. Ovbiagele B, Saver JL, Lynn MJ, Chimowitz M: Impact of metabolic syndrome on prognosis of symptomatic intracranial atherostenosis. Neurology 2006;66:1344-1349.
25. Unger T, Chung O, Csikos T, Culman J, Gallinat S, Gohlke P, Hohle S, Meffert S, Stoll M, Stroth U, Zhu YZ: Angiotensin receptors. J Hypertens Suppl 1996;14:S95-S103.
26. Chung O, Unger T: Angiotensin II receptor blockade and end-organ protection. Am J Hypertens 1999;12:150S-156S.
27. Lucius R, Gallinat S, Rosenstiel P, Herdegen T, Sievers J, Unger T: The angiotensin II type 2 (AT2) receptor promotes axonal regeneration in the optic nerve of adult rats. J Exp Med 1998;188:661-670.
28. Nio Y, Matsubara H, Murasawa S, Kanasaki M, Inada M: Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest 1995;95:46-54.
29. Regitz-Zagrosek V, Friedel N, Heymann A, Bauer P, Neuss M, Rolfs A, Steffen C, Hildebrandt A, Hetzer R, Fleck E: Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts. Circulation 1995;91:1461-1471.
30. Fournier A, Achard JM, Boutitie F, Mazouz H, Mansour J, Oprisiu R, Fernandez L, Messerli F: Is the angiotensin II type 2 receptor cerebroprotective? Curr Hypertens Rep 2004;6:182-189.
31. Malhotra A, Kang BP, Cheung S, Opawumi D, Meggs LG: Angiotensin II promotes glucose-induced activation of cardiac protein kinase C isozymes and phosphorylation of troponin I. Diabetes 2001;50:1918-1926.
32. Nickenig G, Roling J, Strehlow K, Schnabel P, Bohm M: Insulin induces upregulation of vascular AT1 receptor gene expression by posttranscriptional mechanisms. Circulation 1998;98:2453-2460.
33. Velloso LA, Folli F, Sun XJ, White MF, Saad MJ, Kahn CR: Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA 1996;93:12490-12495.
34. Prasad A, Quyyumi AA: Renin-angiotensin system and angiotensin receptor blockers in the metabolic syndrome. Circulation 2004;110:1507-1512.
35. Pollare T, Lithell H, Berne C: A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med 1989;321:868-873.
36. Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg BE, Wester PO, Bjorck JE: Effect of angiotensin-converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: The Captopril Prevention Project (CAPPP) randomised trial. Lancet 1999;353:611-616.
37. Niskanen L, Hedner T, Hansson L, Lanke J, Niklason A: Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/β- blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care 2001;24:2091-2096.
38. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G;Heart Outcomes Prevention Evaluation Study Investigators: Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med 2000;342:145-153.
39. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H: Cardiovascular morbidity and mortality in the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003.
40. Lindholm LH, Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julius S, Kjeldsen SE, Kristiansson K, Lederballe-Pedersen O, Nieminen MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S: Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention for Endpoint Reduction in Hypertension Study (LIFE): a randomised trial against atenolol. Lancet 2002;359:1004-1010.
41. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A, Smith B, Zanchetti A: Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: The VALUE randomised trial. Lancet 2004;363:2022-2031.
42. Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J: Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: The Charm-PRESERVED Trial. Lancet 2003;362:777-781.
43. Berger J, Moller DE: The mechanisms of action of PPARs. Annu Rev Med 2002;53:409-435.
44. Nissen SE, Nicholls SJ, Wolski K, Howey DC, McErlean E, Wang MD, Gomez EV, Russo JM: Effects of a potent and selective PPAR-α agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: two randomized controlled trials. JAMA 2007;297:1362-1373.
45. Investigators TDT: Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006;368:1096-1105.
46. Inzucchi SE: Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287:360-372.
47. Kurtz TW: Treating the metabolic syndrome: telmisartan as a peroxisome proliferator-activated receptor-γ activator. Acta Diabetol 2005;42(suppl 1):S9-S16.
48. Golledge J, Mangan S, Clancy P: Effects of peroxisome proliferator-activated receptor ligands in modulating tissue factor and tissue factor pathway inhibitor in acutely symptomatic carotid atheromas. Stroke 2007;38:1501-1508.
49. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefebvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Koranyi L, Laakso M, Mokan M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J: Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROACTIVE study (Prospective Pioglitazone Clinical Trial in Macrovascular Events): a randomised controlled trial. Lancet 2005;366:1279-1289.
50. Wilcox R, Bousser MG, Betteridge DJ, Schernthaner G, Pirags V, Kupfer S, Dormandy J: Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROACTIVE (Prospective Pioglitazone Clinical Trial in Macrovascular Events 04). Stroke 2007;38:865-873.
51. Insulin Resistance Intervention after Stroke Trial. http://www.iristrial. org/ (accessed June 10, 2007).
52. Fonseca V: Effect of thiazolidinediones on body weight in patients with diabetes mellitus. Am J Med 2003;115(suppl 8A):42S-48S.
53. Larsen TM, Toubro S, Astrup A: PPAR-γ agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord 2003;27:147-161.
54. Guan Y, Hao C, Cha DR, Rao R, Lu W, Kohan DE, Magnuson MA, Redha R, Zhang Y, Breyer MD: Thiazolidinediones expand body fluid volume through PPAR-γ stimulation of ENaC-mediated renal salt absorption. Nat Med 2005;11:861-866.
55. Nissen SE, Wolski K: Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007;356:2457-2471.
56. Gregoire F, Kersten S, Harrington W: PPARS and Obesity. PPAR Research, vol 2007, article ID 78475. http://www.hindawi.com/GetArticle.aspx?doi=10.1155/ 2007/78475&e=cta (accessed June 10, 2007).
57. Benson SC, Pershadsingh HA, Ho CI, Chittiboyina A, Desai P, Pravenec M, Qi N, Wang J, Avery MA, Kurtz TW: Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-γ-modulating activity. Hypertension 2004;43:993-1002.
58. Berger JP, Petro AE, Macnaul KL, Kelly LJ, Zhang BB, Richards K, Elbrecht A, Johnson BA, Zhou G, Doebber TW, Biswas C, Parikh M, Sharma N, Tanen MR, Thompson GM, Ventre J, Adams AD, Mosley R, Surwit RS, Moller DE: Distinct properties and advantages of a novel peroxisome proliferator-activated protein (gamma) selective modulator. Mol Endocrinol 2003;17:662-676.
59. Schupp M, Janke J, Clasen R, Unger T, Kintscher U: Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-γ activity. Circulation 2004;109:2054-2057.
60. Clasen R, Schupp M, Foryst-Ludwig A, Sprang C, Clemenz M, Krikov M, Thone-Reineke C, Unger T, Kintscher U: PPAR-γ-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension 2005;46:137-143.
61. Kurtz TW, Pravenec M: Antidiabetic mechanisms of angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists: beyond the renin-angiotensin system. J Hypertens 2004;22:2253-2261.
62. Fujimoto M, Masuzaki H, Tanaka T, Yasue S, Tomita T, Okazawa K, Fujikura J, Chusho H, Ebihara K, Hayashi T, Hosoda K, Nakao K: An angiotensin II AT1 receptor antagonist, telmisartan, augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes. FEBS Lett 2004;576:492-497.
63. Pershadsingh HA, Kurtz TW: Insulin-sensitizing effects of telmisartan: implications for treating insulin-resistant hypertension and cardiovascular disease. Diabetes Care 2004;27:1015.
64. Michel MC, Bohner H, Koster J, Schafers R, Heemann U: Safety of telmisartan in patients with arterial hypertension: an open-label observational study. Drug Saf 2004;27:335-344.
65. Benndorf RA, Rudolph T, Appel D, Schwedhelm E, Maas R, Schulze F, Silberhorn E, Boger RH: Telmisartan improves insulin sensitivity in nondiabetic patients with essential hypertension. Metabolism 2006;55:1159-1164.
66. Derosa G, Ragonesi PD, Mugellini A, Ciccarelli L, Fogari R: Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study. Hypertens Res 2004;27:457-464.
67. Vitale C, Mercuro G, Castiglioni C, Cornoldi A, Tulli A, Fini M, Volterrani M, Rosano GM: Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome. Cardiovasc Diabetol 2005;4:6.
68. Effect of irbesartan on insulin sensitivity in chronic heart failure. http://clinicaltrials.gov/ct/show/NCT00347087;jsessionid= B8B6AA14296E772D9D750C00A1DA0D98?order=24 (accessed June 10, 2007).
69. Zimmermann M, Unger T: Challenges in improving prognosis and therapy: The Ongoing Telmisartan Alone and in Combination with Ramipril Global End Point Trial programme. Expert Opin Pharmacother 2004;5:1201-1208.
70. Teo K, Yusuf S, Sleight P, Anderson C, Mookadam F, Ramos B, Hilbrich L, Pogue J, Schumacher H: Rationale, design, and baseline characteristics of 2 large, simple, randomized trials evaluating telmisartan, ramipril, and their combination in high-risk patients: The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (ONTARGET/TRANSCEND) trials. Am Heart J 2004;148:52-61.