Journal of the American Society of Hypertension
Volume 2, Issue 4, Supplement , Pages S1-S2, July 2008

Introduction

Article Outline

 

The importance of hypertension as a cardiovascular risk factor has been clearly demonstrated in long-term epidemiological and randomized intervention studies. However, hypertension should no longer be regarded as a static office-based measure; the prognostic importance of out-of-office readings, involving ambulatory and home-based monitoring, has also been demonstrated. More recently, there has been a shift towards out-of-office monitoring, which can assess antihypertensive efficacy over a 24-hour period and highlight blood pressure (BP) control “gray areas,” including the early morning BP surge, which is linked to peak increases in vascular events. In the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) Study, for example, 24-hour BP variability was a greater determinant of cardiovascular mortality than office BP.1

Nevertheless, achieving BP control, particularly over the 24-hour period, is difficult; this is coupled with a need to prevent adverse cardiovascular outcomes in the long-term. Many studies show that optimal BP control, if obtained, can reduce cardiovascular risk. In the Blood Pressure Treatment Trialists' Collaboration, which incorporated data from 29 randomized trials, angiotensin-converting enzyme (ACE) inhibitors, calcium antagonists, diuretics, or beta-blockers all lowered the risk of stroke and coronary heart disease, with no significant differences between treatments.2 A number of other studies suggest that the picture is more complex, and to more fully protect a patient, a physician needs to consider multiple risks and the BP-independent benefits, including target-organ protection, that antihypertensives can offer.

It follows that agents, such as the angiotensin receptor blocker (ARB) telmisartan, which can provide sustained 24-hour BP control, attenuate the early morning BP surge and associated adverse outcomes. ACE inhibitors and ARBs are also associated with a decreased risk of new-onset diabetes, and ARBs are beneficial in the treatment of obese/overweight patients with hypertension and type 2 diabetes; this has most recently been shown in the Study of Micardis in Overweight/Obese patients with Type 2 diabetes and Hypertension (SMOOTH) Study.3

There are also a number of well-designed renal studies, such as Irbesartan in Diabetic NephropaThy (IDNT), Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL), and A trial to compare telMisartan 80 mg vs. losArtan 100 mg, in hypertensive type 2 DiabEtic patients with Overt nephropathy (AMADEO), which highlight the renoprotection properties associated with some ARBs.4, 5, 6 These studies show that ARBs can reduce the time to doubling of serum creatinine levels, prevent the progression of microalbuminuria to overt nephropathy, and delay the development of end-stage renal disease. ARBs can also provide cerebrovascular protection beyond that explained by BP reduction alone. Most notably, the Losartan Intervention For Endpoint (LIFE) Study showed that despite almost identical BP reduction, a losartan-based regimen reduced the relative risk of stroke to a greater extent than an atenolol-based strategy.7

Some of the BP independent properties of antihypertensives are being highlighted in updated guidelines, including the European Society of Hypertension/European Society of Cardiology 2007 recommendations, thus offering physicians a more educated and informed choice on which antihypertensive agent to use. With the advancement of even larger mega-trials, physicians can also identify the type of patient to protect and by which strategy, based on the inclusion criteria of these trials; for example, the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) has enrolled more than 25,000 patients with a broad range of cardiovascular diseases, enabling a evidence-based approach with a view to optimizing patient management.8, 9

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References 

  1. Mancia G, Facchetti R, Bombelli M, Friz HP, Grassi G, Giannattasio C, et al. Relationship of office, home, and ambulatory blood pressure to blood glucose and lipid variables in the PAMELA population. Hypertension. 2005;45:1072–1077
  2. Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:1527–1535
  3. Sharma AM, Davidson J, Koval S, Lacourciere Y SMOOTH Study Investigators. Telmisartan/HCTZ versus valsartan/HCTZ in obese hypertensive patients with type 2 diabetes: the SMOOTH Study. Cardiovasc Diabetol. 2007;6:28
  4. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860
  5. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving H-H, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–869
  6. Bakris G, Burgess E, Davidai G, Koval S, Weir M; the AMADEO Investigators. Influence of glycemic control on proteinuria in patients with type 2 diabetes and overt nephropathy and hypertension: results of the AMADEO trial. A poster presented at the 67th Scientific Sessions of the American Diabetes Association, Chicago, Illinois, June 22–26, 2007.
  7. Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359:995–1003
  8. Sleight P. The ONTARGET/TRANSCEND Trial Programme: baseline data. Acta Diabetol. 2005;42:S50–S56
  9. Teo K, Yusuf S, Sleight P, Anderson C, Mookadam F, Ramos B, et al. 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

PII: S1933-1711(08)00037-5

doi:10.1016/j.jash.2008.03.005

Journal of the American Society of Hypertension
Volume 2, Issue 4, Supplement , Pages S1-S2, July 2008

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