The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study provided extensive data on predisposing factors, consequences, and prevention of atrial fibrillation (AF) in patients with hypertension and left ventricular (LV) hypertrophy. Randomized losartan-based treatment was superior to atenolol-based treatment for reducing new-onset AF and complications, especially stroke, associated with new-onset or pre-existing AF. Potential mechanisms of AF prevention by angiotensin receptor blockade supported by LIFE results include greater reduction in left atrial size and LV hypertrophy. Differential effects of antihypertensive treatment on the left atrium and left ventricle may help prevent AF and reduce risk of stroke associated with hypertensive heart disease.
Benjamin, E.J., D'Agostino, R.B., Belanger, A.J., Wolf, P.A. and Levy, D. (1995) Left atrial size and the risk of stroke and death. The Framingham Heart Study. Circulation92: 835-841.
2.
Dahlöf, B., Devereux, R.B., de Faire, U., Fyhrquist, F., Hedner, T., Ibsen, H. et al. (1997) The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study: rationale, design and methods. Am J Hypertens10: 705-713.
3.
Dahlöf, B., Devereux, R.B., Julius, S., Kjeldsen, S.E., Beevers, G., de Faire, U. et al. (1998) Characteristics of 9194 patients with left ventricular hypertrophy: The LIFE study. Hypertension32: 989-997.
4.
Dahlöf, B., Devereux, R.B., Kjeldsen, S.E., Julius, S., Beevers, G., de Faire, U. et al. (2002) Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet359: 995-1003.
5.
Dahlöf, B., Devereux, R.B. and Kjeldsen, S.E. (2004a) Reply to letter in response to Diuretics in the LIFE study. Lancet364: 413-414.
6.
Dahlöf, B., Burke, T.A., Krobot, K., Carides, G.W., Edelman, J.M., Devereux, R.B. et al. (2004b) Population impact of losartan use on stroke in the European Union (EU): projections from the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. J Hum Hypertens18: 367-373.
7.
De Mello, W.C. and Specht, P. (2006) Chronic blockade of angiotensin II AT1-receptors increased cell-to-cell communication, reduced fibrosis and improved impulse propagation in the failing heart. J Renin Angiotensin Aldosterone Syst7: 201-205.
8.
Devereux, R.B., Dahlöf, B., Gerdts, E., Boman, K., Nieminen, M.S., Papademetriou, V. et al. (2004) Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation110: 1456-1462.
9.
Devereux, R.B. and Dahlöf, B. (2007) Potential mechanisms of stroke benefit favoring losartan in the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) study. Curr Med Res Opin23: 443-457.
10.
Fogari, R., Mugellini, A., Destro, M., Corradi, L., Zoppi, A., Fogari, E. et al. (2006) Losartan and prevention of atrial fibrillation recurrence in hypertensive patients. J Cardiovasc Pharmacol47: 46-50.
11.
Fuster, V., Rydén, L.E., Cannom, D.S., Crijns, H.J., Curtis, A.B., Ellenbogen, K.A. et al. (2006) ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 guidelines for the management of patients with atrial fibrillation) developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Europace8: 651-745. Erratum in: Europace2007;9: 856.
12.
Gerdts, E., Oikarinen, L., Palmieri, V., Otterstad, J.E., Wachtell, K., Boman, K. et al. (2002) Correlates of left atrial size in hypertensive patients with left ventricular hypertrophy. The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. Hypertension39: 739-743.
13.
Gerdts, E., Wachtell, K., Omvik, P., Otterstad, J.E., Oikarinen, L., Boman, K. et al. (2007) Left atrial size and risk of major cardiovascular events during antihypertensive treatment. Losartan Intervention for Endpoint Reduction in Hypertension Trial. Hypertension49: 311-316.
14.
Greenberg, B., Quinones, M.A., Koilpillai, C., Limacher, M., Shindler, D., Benedict, C. et al. (1995) Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy. Circulation91: 2573-2581.
15.
Hart, R.G., Pearce, L.A., Rothbart, R.M., McAnulty, J.H., Asinger, R.W., Halperin, J.L. (2000) Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy. J Am Coll Cardiol35: 183-187.
16.
Healey, J.S., Baranchuk, A., Crystal, E., Morillo, C.A., Garfinkle, M.,Yusuf, S. et al. (2005) Prevention of atrial fibrillation with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: a meta-analysis. J Am Coll Cardiol45: 1832-1839.
17.
Hennersdorf, M.G., Schueller, P.O., Steiner, S. and Strauer, B.E. (2007) Prevalence of paroxysmal atrial fibrillation depending on the regression of left ventricular hypertrophy in arterial hypertension . Hypertens Res30: 535-540.
18.
Ibsen, H., Wachtell, K., Olsen, M.H., Borch-Johnsen, K., Lindholm, L.H., Mogensen, C.E. et al. (2004) Does albuminuria predict cardiovascular outcome on treatment with losartan versus atenolol in patients with hypertension and left ventricular hypertrophy? A LIFE substudy. J Hypertens22: 1805-1811.
19.
Kannel, W.B., Wolf, P.A., Benjamin, E.J. and Levy, D. (1998) Prevalence, incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates. Am J Cardiol82: 2N-9N.
20.
Kizer, J.R., Dahlöf, B., Kjeldsen, S.E., Julius, S., Beevers, G., de Faire, U. et al. (2005) Stroke reduction in hypertensive adults with cardiac hypertrophy randomized to losartan versus atenolol. The Losartan Intervention For Endpoint reduction in hypertension study. Hypertension45: 46-52.
21.
Kizer, J.R., Bella, J.N., Palmieri, V., Liu, J.E., Best, L.G., Lee, E.T. et al. (2006) Left atrial diameter as an independent predictor of first clinical cardiovascular events in middle-aged and elderly adults: The Strong Heart Study. Am Heart J151: 412-418.
22.
Klingbeil, A.U., Schneider, M., Martus, P., Messerli, F.H. and Schmieder, R.E. (2003) A meta-analysis of the effects of treatment on left ventricular mass in essential hypertension. Am J Med115: 41-46.
23.
Kumagai, K., Nakashima, H., Urata, H., Gondo, N., Arakawa, K. and Saku, K. (2003) Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol41: 2197-2204.
24.
Mancia, G., De Backer, G., Dominiczak, A., Cifkova, R., Fagard, R., Germano, G. et al. (2007) 2007 ESH-ESC practice guidelines for the management of arterial hypertension - ESH-ESC task force on the management of arterial hypertension. J Hypertens25: 1751-1762.
25.
Miyasaka,Y., Barnes, M.E., Gersh, B.J., Cha, S.S., Bailey, K.R., Abhayaratna, W.P. et al. (2006) Secular trends in incidence of atrial fibrillation in Olmstead County, Minnesota, 1980 to 2000, and implications on the projections for future prevalence. Circulation114: 119-125.
26.
Miyasaka,Y., Barnes, M.E., Bailey, K.R., Cha, S.S., Gersh, B.J., Seward, J.B. et al. (2007) Mortality trends in patients diagnosed with first atrial fibrillation. A 21-year community-based study. J Am Coll Cardiol49: 986-992.
27.
Okin, P.M., Devereux, R.B., Jern, S., Kjeldsen, S.E., Julius, S., Nieminen, M.S. et al. (2003) Regression of electrocardiographic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Circulation108: 684-690.
28.
Okin, P.M., Wachtell, K., Devereux, R.B., Harris, K.E., Jern, S., Kjeldsen, S.E. et al. (2006) Regression of electrocardiographic left ventricular hypertrophy and decreased incidence of new-onset atrial fibrillation in patients with hypertension. JAMA296: 1242-1248.
29.
Ontarget Investigators, Yusuf, S., Teo, K.K., Pogue, J., Dyal, L., Copland, I., Schumacher, H., et al. (2008) Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med358: 1547-1559.
30.
Rosamond, W., Flegal, K., Furie, K., Go, A., Greenlund, K., Haase, N. et al. (2008) Heart disease and stroke statistics-2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation117: e25-e146.
31.
Schmieder, R.E., Kjeldsen, S.E., Julius, S., McInnes, G.T., Zanchetti, A., Hua, T.A.; VALUE Trial Group. et al. (2008) Reduced incidence of new-onset atrial fibrillation with angiotensin II receptor blockade: the VALUE trial. J Hypertens26: 403-411.
32.
Thom, T., Haase, N., Rosamond, W., Howard, V.J., Rumsfeld, J., Manolio, T. et al. (2006) Heart disease and stroke statistics-2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation113: e85-e151.
33.
Tsai, C.T., Lai, L.P., Lin, J.L., Chiang, F.T., Hwang, J.J., Ritchie, M.D. et al. (2004) Renin-angiotensin system gene polymorphisms and atrial fibrillation. Circulation109: 1640-1646.
34.
Verdecchia, P., Reboldi, G., Gattobigio, R., Bentivoglio, M., Borgioni, C., Angeli, F. et al. (2003) Atrial fibrillation in hypertension: predictors and outcome. Hypertension41: 218-223.
35.
Wachtell, K., Hornestam, B., Lehto, M., Slotwiner, D.J., Gerdts, E., Olsen, M.H. et al. (2005a) Cardiovascular morbidity and mortality in hypertensive patients with a history of atrial fibrillation. The Losartan Intervention for End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol45: 705-711.
36.
Wachtell, K., Lehto, M., Gerdts, E., Olsen, M.H., Hornestam, B., Dahlöf, B. et al. (2005b) Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol. The Losartan Intervention for End Point Reduction in Hypertension (LIFE) study . J Am Coll Cardiol45712-719.
37.
Wachtell, K., Chinali, M., Olsen, M.H., de Simone, G., Gerdts, E., Dahlöf, B. et al. (2006a) Better preservation of left atrial systolic force by losartan may contribute to lower incidence o new-onset atrial fibrillation: the LIFE study. Circulation114: II-791 (abstract 3701).
38.
Wachtell, K., Devereux, R.B. and Lyle, P.A. (2006b) Use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers to prevent atrial fibrillation . Curr Cardiol Rep8: 356-364.
39.
Wolf, P.A., Abbott, R.D. and Kannel, W.B. (1991) Atrial fibrillation as an independent risk factor for stroke: the Framingham study. Stroke22: 983-988.
40.
Wu, E.Q., Birnbaum, H.G., Mareva, M., Tuttle, E., Castor, A.R., Jackman, W. et al. (2005) Economic burden and co-morbidities of atrial fibrillation in a privately insured population. Curr Med Res Opin21: 1693-1699.
41.
Zacks, E., Wachtell, K., Gerdts, E., Dahlöf, B., Ibsen, H., Julius, S. et al. (2005) Association of uric acid level with new-onset atrial fibrillation in treated hypertensive patients. The LIFE study. Circulation112(Suppl II): II-459 (abstract).
42.
Zacks, E., Wachtell, K., Gerdts, E., Dahlöf, B.Ibsen, H., Kjeldsen, S.E. et al. (2007) Association of albuminuria with new-onset atrial fibrillation in treated hypertensive patients: the LIFE study. Circulation116(Suppl II): II-800 (abstract 3536).
