Advertisement

Antiatherosclerotic effects of β-blockers

      Abstract

      Accumulating data from studies in animals and humans indicate that β-blockade has antiatherosclerotic effects. To date, 2 long-term ultrasound studies provide the strongest evidence. The Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS) trial reported favorable effects with β-blockade on early stages of atherosclerosis in patients with carotid plaque but no symptoms of carotid artery disease. Compared with placebo, metoprolol controlled release/extended release (CR/XL) 25 mg once daily significantly reduced plaque thickness after 18 months of treatment (net difference −0.058 mm/year; p <0.001) and at 3 years’ follow-up (net difference −0.023 mm/year; p = 0.018). The Effects of Long-Term Treatment of Metoprolol CR/XL on Surrogate Variables for Atherosclerotic Disease (ELVA) trial demonstrated that β-blockers and statins affect different mechanisms in the atherosclerotic process and have additive beneficial effects. Patients with hypercholesterolemia were randomized to metoprolol CR/XL 100 mg once daily or placebo once daily and concomitant statin therapy. The metoprolol CR/XL group had a significantly lower rate of progression of the composite carotid bulb intima-media thickness (IMT) plus common carotid IMT than the placebo group, both at 1 year (−0.08 vs −0.01 mm; p = 0.004) and after 3 years’ follow-up (−0.06 vs +0.03 mm; p = 0.011). Several factors may contribute to the mechanism of benefit in these trials, including reduced sympathetic activity, improved hemodynamic parameters, and direct effects on the vascular endothelium.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Scandinavian Simvastatin Survival Study Group
        Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease.
        Lancet. 1994; 344: 1383-1389
        • Wikstrand J.
        • Kendall M.
        • Berglund G.
        Metoprolol versus thiazide diuretics in hypertension: results from the MAPHY study in perspective.
        in: Black H. Clinical Trials in Hypertension. Marcel-Dekker Inc, New York2001: 141-158
        • Wikstrand J.
        • Kendall M.
        The role of β receptor blockade in preventing sudden death.
        Eur Heart J. 1992; 13: 111-120
        • MERIT-HF Study Group
        Effect of metoprolol CR/XL in chronic heart failure.
        Lancet. 1999; 353: 2001-2007
        • Blankenhorn D.H.
        • Selzer R.H.
        • Crawford D.W.
        • Barth J.D.
        • Liu C.R.
        • Liu C.H.
        • Mack W.J.
        • Alaupovic P.
        Beneficial effects of colestipol-niacin therapy on the common carotid artery.
        Circulation. 1993; 88: 20-28
        • Crouse J.R.
        • Byington R.P.
        • Bond M.G.
        • Espeland M.A.
        • Craven T.E.
        • Sprinkle J.W.
        • McGovern M.E.
        • Furberg C.D.
        Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II).
        Am J Cardiol. 1995; 75: 455-459
        • Furberg C.D.
        • Adams Jr, H.P.
        • Appelgate W.B.
        • Byington R.P.
        • Espeland M.A.
        • Hartwell T.
        • Hunninghake D.B.
        • Lefkowitz D.S.
        • Probstfield J.
        • Riley W.A.
        • et al.
        Effects of lovastatin on early carotid atherosclerosis and cardiovascular events.
        Circulation. 1994; 90: 1679-1687
        • Wendelhag I.
        • Wiklund O.
        • Wikstrand J.
        Intima-media thickness after cholesterol lowering in familial hypercholesterolemia.
        Atherosclerosis. 1995; 117: 225-236
        • Lonn E.
        • Yusuf S.
        • Dzavik V.
        • Doris C.
        • Yi Q.
        • Smith S.
        • Moore-Cox A.
        • Bosch J.
        • Riley W.
        • Teo K.
        Effects of ramipril and vitamin E on atherosclerosis.
        Circulation. 2001; 103: 919-925
        • Kaplan J.R.
        • Manuck S.B.
        Status, stress and atherosclerosis.
        Ann N Y Acad Sci. 1999; 896: 145-161
        • Åblad B.
        • Björkman J.A.
        • Gustafsson D.
        • Hansson G.
        • Ostlund-Lindqvist A.M.
        • Pettersson K.
        The role of sympathetic activity in atherogenesis.
        Am Heart J. 1988; 116: 322-327
        • Östlund-Lindqvist A.M.
        • Lindqvist P.
        • Brautigam J.
        • Olsson G.
        • Bondjers G.
        • Nordborg C.
        Effect of metoprolol on diet-induced atherosclerosis in rabbits.
        Arteriosclerosis. 1988; 8: 40-45
        • Helin P.
        • Lorenzen I.
        • Garbarsch C.
        • Matthiessen M.E.
        Arteriosclerosis in rabbit aorta induced by noradrenaline.
        Atherosclerosis. 1970; 12: 125-132
        • Vesselinovitch D.
        • Mullan J.F.
        • Wissler R.W.
        • Davis H.R.
        • Brindenstine T.
        Carotid atherogenesis inhibited by sympathectomy, propranolol and nifedipine in rhesus monkeys [abstract].
        Arteriosclerosis. 1986; 6: 561
        • Björk-Skantze H.
        • Kaplan J.
        • Pettersson K.
        • Manuck S.
        • Blomqvist N.
        • Kyes R.
        • Williams K.
        • Bondjers G.
        Psychosocial stress causes endothelial injury in cynomolgus monkeys via β1-adrenoceptor activation.
        Atherosclerosis. 1998; 136: 153-161
        • Pettersson K.
        • Bejne B.
        • Björk H.
        • Strawn W.B.
        • Bondjers G.
        Experimental sympathetic activation causes endothelial injury in the rabbit thoracic aorta via β1-adrenoceptor activation.
        Circ Res. 1990; 67: 1027-1034
        • Kaplan J.R.
        • Manuck S.B.
        • Adams M.R.
        • Weingand K.W.
        • Clarkson T.B.
        Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet.
        Circulation. 1987; 76: 1364-1372
        • Lindén T.
        • Camejo G.
        • Wiklund O.
        • Warnold I.
        • Olofsson S.O.
        • Bondjers G.
        Effect of short term β blockade on serum lipid levels and on the interaction of LDL with human arterial proteoglycans.
        J Clin Pharmacol. 1990; 30: S124-S131
        • Hedblad B.
        • Wikstrand J.
        • Janzon L.
        • Wedel H.
        • Berglund G.
        Low dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness.
        Circulation. 2001; 103: 1721-1726
        • Wiklund O.
        • Hulthe J.
        • Wikstrand J.
        • Schmidt C.
        • Olofsson S.-O.
        • Bondjers G.
        Effect of controlled release/extended release metoprolol on carotid intima-media thickness in patients with hypercholesterolemia.
        Stroke. 2002; 33: 572-577
        • Berglund G.
        • Elmståhl S.
        • Janzon L.
        • Larsson S.A.
        The Malmö Diet and Cancer Study.
        J Intern Med. 1993; 233: 45-51
        • Whittington-Coleman P.J.
        • Carrier O.
        • Douglas B.H.
        The effects of propranolol on cholesterol-induced atheromatous lesions.
        Atherosclerosis. 1973; 18: 337-345
        • Reinis Z.
        • Lojda Z.
        • Heyrovsky A.
        • Horakova D.
        • Reisenaver R.
        Effects of β-blocking agents in experimental atherosclerosis of cocks.
        Rev Czech Med. 1976; 22: 117-126
        • Pettersson K.
        • Hansson G.
        • Björkman J.A.
        • Åblad B.
        Prostacyclin synthesis in relation to sympathoadrenal activation.
        Circulation. 1991; 84: VI38-VI43
        • Pettersson K.
        • Björk H.
        Inhibition of platelet accumulation by β1-adrenoceptor blockade in the thoracic aorta of rabbits subjected to experimental sympathetic activation.
        Cardiovasc Drugs Ther. 1992; 6: 505-511
      1. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure.
        Arch Intern Med. 1997; 157: 2413-2446
        • Teo K.K.
        • Yusuf S.
        • Furberg C.D.
        Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction.
        JAMA. 1993; 270: 1589-1595
        • CIBIS-II Investigators and Committees
        The Cardiac Insufficiency Bisoprolol Study II (CIBIS II).
        Lancet. 1999; 353: 9-13
        • Packer M.
        • Coats J.S.
        • Fowler M.B.
        • Katus H.A.
        • Krum H.
        • Mohacsi P.
        • Rouleau J.L.
        • Tendera M.
        • Castaigne A.
        • Roecker E.B.
        • Schultz M.K.
        • DeMets D.L.
        • Carvedilol Prospective Randomized Cumulative Survival Study Group (COPERNICUS)
        Effect of carvedilol on survival in severe chronic heart failure.
        N Engl J Med. 2001; 344: 1651-1658