Published online before print August 21, 2006, doi: 10.1161/01.HYP.0000238606.74107.26
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2006;48:E19.)
© 2006 American Heart Association, Inc.
Letters to the Editor |
Response to Are the Eutrophic Effects of Angiotensin Receptor Blockers Real?
Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
Kidney Research Center, Ottawa Health Research Institute, Ottawa, Ontario, Canada
Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital and, Hypertension and Vascular Research Unit, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada
Dr. Fuchs’s correspondence1 regarding our article2 questioned "whether the eutrophic effects of angiotensin receptor blockers [ARBs] are real." Extensive and compelling experimental and human studies, using different techniques from independent laboratories, demonstrate that ARB effects on the vasculature are real.3–5
Use of the ß-blocker atenolol as an appropriate comparator drug was also raised. We demonstrated previously that atenolol compared with an ARB did not correct the altered structure and endothelial dysfunction of resistance arteries from patients with essential hypertension,3 despite similar blood pressure (BP) control. Patients in our study2 were already treated with antihypertensive drugs (including angiotensin-converting enzyme inhibitors and calcium channel blockers) with BP control (
144/84 mm Hg), similar to that reached at the end of the United Kingdom Prospective Diabetes Study,6 but had persistent vascular remodeling. Hence the aim of our study to evaluate whether remodeling of resistance arteries could be corrected with better BP control and more complete renin–angiotensin inhibition with the addition of an ARB, valsartan, on top of previous therapy. Atenolol was the logical comparator, because despite reducing BP equally to ARBs in patients of similar age,7 it did not improve structure or function of small arteries,3 thus it was a good negative control. Atenolol was not used as first-line therapy in our study as implied by Fuchs.1
BP during the study was equally well controlled by atenolol and valsartan, contrary to what Fuchs1 states. In double-blind, randomized mechanistic studies, groups are usually small, and it is difficult to achieve exactly the same BPs in both groups, in contrast to large multicenter trials. Even in the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT),8 despite a total of 42 000 patients, some groups had 4-mm Hg higher systolic BP. However, in our study, the systolic BP difference after treatment was not significant. Statistical significance cannot be ignored because it does not fit preconceived ideas. Fuchs1 speculates about ambulatory BP, but in a previous study, we found no difference in 24-hour BP between ARBs and atenolol.3
Regarding Fuchs’s comment1 on the parameters measured, media/lumen ratio is the most useful parameter to evaluate vascular remodeling within and between subjects in these studies.9 Furthermore, media/lumen ratio correlates with prognosis.10 Very rarely have lumen changes in response to antihypertensive treatment achieved statistical significance in most studies.
Fuchs’s1 argument regarding statistics ignores our hypothesis. The study was not a comparison of the degree to which each drug influences remodeling but whether, with similar BP lowering in these diabetic hypertensive subjects, valsartan would result in a smaller media/lumen ratio of small arteries, whereas atenolol would not. In addition, no correlation was found between the media/lumen ratio and possible confounding variables, such as age, duration of diabetes, and hypertension. Finally, contrary to Fuchs’s statement,1 long-term blood glucose control (glycohemoglobin) was identical in both groups.
In conclusion, we disagree with Fuchs1 regarding "his personal doubts on the internal validity" of our study, which may result from lack of understanding of small artery studies or misinterpretation of our statistics and results.
 |
Acknowledgments |
|---|
Disclosures
R.M.T. serves on the advisory boards and speakers’ honoraria for less than $10,000 for Merck, Novartis. E.L.S. serves on a advisory boards and speaker’s honoraria for less than $10,000 for Abbottt BMS, Boehringer-Ingelheim, Glaxo, Merck, Novartis and received research grants of more than $10,000 from Novartis, Pfizer. The remaining author reports no conflicts.
|
References |
|---|
 Top References |
|---|
- Fuchs FD. Are the eutrophic effects of angiotensin receptor blockers real? Hypertension. 2006; 48: e18.[Medline] [Order article via Infotrieve]
- Savoia C, Touyz RM, Endemann DH, Pu Q, Ko EA, De Ciuceis C, Schiffrin EL. Angiotensin receptor blocker added to previous antihypertensive agents on arteries of diabetic hypertensive patients. Hypertension. 2006; 48: 271–277.
[Abstract/Free Full Text] - Schiffrin EL, Park JB, Intengan HD, Touyz RM. Correction of arterial structure and endothelial dysfunction in human essential hypertension by the angiotensin receptor antagonist losartan. Circulation. 2000; 101: 1653–1659.
[Abstract/Free Full Text] - Rizzoni D, Porteri E, De Ciuceis C, Sleiman I, Rodella L, Rezzani R, Paiardi S, Bianchi R, Ruggeri G, Boari GEM, Muiesan ML, Salvetti M, Zani F, Miclini M, Rosei EA. Effect of treatment with candesartan or enalapril on subcutaneous small artery structure in hypertensive patients with noninsulin-dependent diabetes mellitus. Hypertension. 2005; 45: 659–665.
[Abstract/Free Full Text] - Malik RA, Schofield IJ, Izzard A, Austin C, Bermann G, Heagerty AM. Effects of angiotensin type-1 receptor antagonism on small artery function in patients with type 2 diabetes mellitus. Hypertension. 2005; 45: 264–269.
[Abstract/Free Full Text] - UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38). BMJ. 1998; 317: 703–713.
[Abstract/Free Full Text] - Lindholm luteinizing hormone (LH), Ibsen H, Dahlof B, Devereux RB, Beevers G, de Faire U, Fyhrquist F, Julis S, Kjeldsen SE, Kristiansson K, Lederballe-Pedersen O, Nieminem MS, Omvik P, Oparil S, Wedel H, Aurup P, Edelman J, Snapinn S, The LIFE Study Group. Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002; 359: 1004–1011.[CrossRef][Medline] [Order article via Infotrieve]
- The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002; 18: 288:2981–2997.
- Schiffrin EL, Hayoz D. Review: How to assess vascular remodeling in small and medium-sized muscular arteries in humans. J Hypertens. 1997; 15: 571–584.[CrossRef][Medline] [Order article via Infotrieve]
- Rizzoni D, Porteri E, Boari GEM, De Ciuceis C, Sleiman I, Muiesan ML, Castellano M, Miclini M, Agabiti Rosei E. Prognostic significance of small-artery structure in hypertension. Circulation. 2003; 108: 2230–2235.
[Abstract/Free Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||