CORRESPONDENCE: LETTERS TO THE EDITOR
Black Pearl in the LIFE Study: Angiotensin-II Receptor Blockade on Atrial Fibrillation for Future Personalized Medicine
Akiyoshi Ogimoto, MD, PhD*,
Yuji Shigematsu, MD, PhD,
Yuji Hara, MD, PhD,
Tomoaki Ohtsuka, MD, PhD,
Tetsuro Miki, MD, PhD and
Jitsuo Higaki, MD, PhD
* The Second Department of Internal Medicine, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan (Email: aogimoto{at}m.ehime-u.ac.jp).
The LIFE study by Wachtell et al. (1) presented evidence indicating that losartan significantly reduces new-onset atrial fibrillation (AF) in comparison to atenolol-based antihypertensive treatment and thereby supports recent studies in this field (2,3). Conversely, the LIFE study revealed that new-onset AF was more frequent in losartan-treated blacks (1.9%) than in atenolol-treated blacks (0.8%). In addition, van der Hooft’s report explained that losartan was one of several drugs that possibly could induce AF (4). Moreover, the occurrence of AF tended to be more frequent in the valsartan group (2.4%) than in the amlodipine group (2.0%) in the VALUE trial (5).
These results surprised and persuaded us to move forward with our own study of AF. We hypothesize that certain types of AF are associated with reduced activation of the renin-angiotensin system (RAS), especially in patients with a small left ventricular cavity (SLVC) due to hypertrophy (6–8). The mechanism of the development of AF in these patients remains unclear. However, we do know that the RAS regulates sodium balance, intravascular volume, and blood pressure. As a result, inhibiting the RAS in patients with an SLVC may induce hypotension, increased heart rate, and hypercontraction due to systolic emptying, which may be related to the autonomic effects on pulmonary venous foci and AF (6–8).
Blacks were reported to have more severe left ventricular (LV) hypertrophy than whites with similar levels of hypertension (9). In addition, multivariable-adjusted LV internal dimensions are smaller in blacks than in whites (9), suggesting that SLVC may be more common in black than white hypertensive patients. Taking these data into consideration, our speculation may be compatible with a part of the LIFE or VALUE study results.
Because of the small percentage (10%) of participants who underwent echocardiographic assessments in the LIFE study (1), the true severity of LV hypertrophy and the LV cavity size are unclear. Commonly used electrocardiographic criteria for detection of LV hypertrophy were reported to have poor sensitivity among both black and white hypertensive patients (10). We suggest that future studies should analyze whether or not the incidence of AF differs in the presence of an SLVC owing to hypertrophy between drug groups.
In conclusion, although an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker may prevent most types of AF, they also may in fact provoke the development of certain types of AF in SLVC patients. Our speculation needs to be confirmed among hypertensive patients with an SLVC due to hypertrophy in a large-scale randomized clinical trial. These analyses may show a more optimal choice for initial pharmacotherapy of hypertension for future personalized medicine.
 |
References
|
|---|
1. Wachtell K, Lehto M, Gerdts E, et al. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenololthe Losartan Intervention For End point reduction in hypertension (LIFE) study. J Am Coll Cardiol 2005;45:712-719.[Abstract/Free Full Text]
2. L’Allier PL, Ducharme A, Keller PF, et al. Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation J Am Coll Cardiol 2004;44:159-164.[Abstract/Free Full Text]
3. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillationa prospective and randomized study. Circulation 2002;106:331-336.[Abstract/Free Full Text]
4. van der Hooft CS, Heeringa J, van Herpen G, et al. Drug-induced atrial fibrillation J Am Coll Cardiol 2004;44:2117-2124.[Abstract/Free Full Text]
5. Julius S, Kjeldsen SE, Weber M, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipinethe VALUE randomised trial. Lancet 2004;363:2022-2031.[CrossRef][Web of Science][Medline]
6. Ogimoto A, Hamada M, Nakura J, Miki T, Hiwada K. Relation between angiotensin-converting enzyme II genotype and atrial fibrillation in Japanese patients with hypertrophic cardiomyopathy J Hum Genet 2002;47:184-189.[CrossRef][Web of Science][Medline]
7. Ogimoto A, Higaki J, Miki T. Polymorphism of inhibitory renin-angiotensin system as a genetic risk factor for atrial fibrillationletter Circulation 2004;110:e329.[Free Full Text]
8. Ogimoto A, Shigematsu Y, Miki T, Higaki J. Angiotensin-converting enzyme inhibitors as a new therapy for atrial fibrillation? Controversyletter Am Heart J 2005;149:566.[Medline]
9. Kizer JR, Arnett DK, Bella JN, et al. Differences in left ventricular structure between black and white hypertensive adultsthe Hypertension Genetic Epidemiology Network study. Hypertension 2004;43:1182-1188.[Abstract/Free Full Text]
10. Lee DK, Marantz PR, Devereux RB, Kligfield P, Alderman MH. Left ventricular hypertrophy in black and white hypertensivesStandard electrocardiographic criteria overestimate racial differences in prevalence. JAMA 1992;267:3294-3299.[Abstract/Free Full Text]
Related Article
-
Reply
- Kristian Wachtell, Mika Lehto, Eva Gerdts, Michael Hecht Olsen, Björn Hornestam, Björn Dahlöf, Hans Ibsen, Stevo Julius, Sverre E. Kjeldsen, Lars H. Lindholm, Markku S. Nieminen, and Richard B. Devereux
J. Am. Coll. Cardiol. 2005 46: 1585-1586.
[Full Text]
[PDF]
|
Top
References