The Role of Angiotensin Receptor Blockers in Cardiovascular Protection Beyond Blood Pressure Control

The Role of Angiotensin Receptor Blockers in Cardiovascular Protection Beyond Blood Pressure Control

Prakash Deedwania
US Cardiovascular Disease 2006
Published: March 2007
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Cardiovascular disorders (CVDs) remain the leading cause of death and disability in the US and the rest of the world. Population, physiological and clinical studies have demonstrated that numerous risk factors contribute to CVD. These include environmental and lifestyle factors (e.g. consumption of high-calorie refined food and decreased levels of physical activity) and several well-established major coronary risk factors including but not limited to hypertension, diabetes and insulin resistance, smoking, and dyslipidemia.

Of these, hypertension is the most prevalent and frequently encountered risk factor in clinical practice and has been listed by World Health Organization as the only medical condition among the ten leading causes of global mortality.

Hypertension is well accepted as the leading risk factor for coronary heart disease (CHD), stroke, congestive heart failure (CHF), and chronic renal failure.1-2 Several large-scale randomized clinical trials have documented that reductions in blood pressure (BP) reduce the increased risk of CV events associated with hypertension.1-4 It is evident from the available data that there is a clear relationship between the magnitude of BP reduction and the degree of cardiovascular protection.1 Although a variety of drugs, or drugcombinations, have been shown to provide such benefit, recent evidence points to the fact that drugs that block renin-angiotensin system (RAS), which include angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) when given alone or in combination with other antihypertensive drugs, might be superior than others due to their cardio-protective effects.1-12

Although ACEIs are well accepted as cardio-protective agents, their utility in treatment of patients with hypertension has been limited due to their side effects and the potential of ACE-escape phenomenon.3-7 In contrast, most ARBs have been shown to have good efficacy and excellent tolerability profile in patients with hypertension. A number of recent clinical trial have demonstrated the clinical efficacy and cardioprotective effects of ARBs.3-7,10,13

Cardio-protective Effects of Angiotens in Receptor Blockers
Blockade of the renin-angiotensin system (RAS) reduces cardiovascular events and decreases the risk of developing diabetes.2-13Cardio-protective effects of agents that inhibit RAS are not dependent on control of hypertension alone. Angiotensin II, the effector peptide of the renin-angiotensin-aldosterone system (RAAS), mediates a variety of effects on BP and body fluid regulation, and has been implicated as a pathogenic factor at many steps along the CVD continuum.2-6,14-16 In addition to the vasoconsrictive effects, angiotensin II-mediated generation of reactive oxygen species (ROS), endothelial dysfunction, vascular and cardiac remodeling, as well as vascular inflammation also contribute to increased risk for cardiovascular events.2-4,14-16

In an experimental model of streptozotocin-induced diabetes, RAS blockade:

  • attenuated production of ROS;
  • reduced oxidative stress;
  • prevented cardiomyocyte hypertrophy and normalized perivascular fibrosis and;
  • the elastin/collagen ratio.14


In an experimental model of myocardial infarction (MI), inhibition of RAS by losartan:

  • improved cardiac function and myocardial antioxidant reserve;
  • reduced cardiac remodeling; and
  • decreased oxidative stress.15
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References:
  1. Chobanian AV, Bakris GL, Black HR, et al., Hypertension (2003);42: pp. 1206–1252.
  2. Dzau V, Braunwald E, Am Heart J (1991);121: pp. 1244–1263.
  3. Burnier M, Brunner HR, Lancet (2000);355: pp. 637–645.
  4. Weir MR, Dzau VJ, Am J Hypertens (1999);12: pp. 205S–213S.
  5. Cohn JN,Tognoni, G N Engl J Med (2001);345: pp. 1667–1675.
  6. Pfeffer MA, McMurray JJ,Velazquez EJ, et al., N Engl J Med (2003);349: pp. 1893–1906.
  7. Julius S, Kjeldsen SE,Weber M, et al., Lancet (2004);363: pp. 2022–2031.
  8. Dahlof B, Sever PS, Poulter NR,Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Ostergren J, Lancet (2005);366: pp. 895–906.
  9. Lindholm LH, Carlberg B, Samuelsson O, Lancet (2005);366: pp. 1545–1553.
  10. 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, Lancet (2002);359: pp. 995–1003.
  11. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med(2000);342: pp. 145–153.
  12. Fox KM, Lancet (2003);362: pp. 782–788.
  13. Ostergren JB, J Hypertens Suppl (2006);24: pp. S3–7.
  14. Fiordaliso F, Cuccovillo I, Bianchi R, Bai A, Doni M, Salio M, De Angelis N, Ghezzi P, Latini R, Masson S, Life Sci. (2006);79: pp. 121–129. Epub 2006 Jan 2030.
  15. Khaper N, Singal PK, J Am Coll Cardiol (2001);37: pp. 1461–1466.
  16. Leiter LA, Lewanczuk RZ, Am J Hypertens (2005);18: pp. 121–128.

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