Prognostic benefits of heart rate reduction in cardiovascular disease
a Cattedra di Cardiologia, Universitá di Ferrara, Ferrara, Italy
b Fondazione Salvatore Maugeri, IRCCS, Cardiovascular Pathophysiology Research Centre, Gussago, Brescia, Italy
* Prof. Roberto Ferrari, Cattedra di Cardiologia, University of Ferrara and Fondazione S. Maugeri, IRCCS, Cardiovascular Pathophysiology Research Centre, Corso Giovecca, 203, 44100 Ferrara, Italy.
Abstract
Increased heart rate is associated with high blood pressure and metabolic disturbances that lead to hypertension, atherosclerosis and increased cardiovascular morbidity and mortality. In this respect, elevated heart rate can be considered a marker of risk. Whole body temperature and energy needs are controlled by heart activity, and the language employed by the heart could be considered its rate, which, via the intensity and frequency of shear stress, it uses to regulate endothelial function and vascular tone. A close link between body temperature, metabolism and heart rate has been observed, and so heart rate may determine metabolic demand and control the duration of life. In mammals, the calculated number of heart beats in a lifetime is remarkably constant, despite a 40-fold difference in life expectancy. According to this view, a reduction in heart rate would increase life expectancy also in humans. The heart produces and utilizes approximately 30 kg adenosine triphosphate each day, and slowing its rate by 10 beats/min would result in a saving of about 5 kg in a day. Considering that heart rate is a major determinant of oxygen consumption and metabolic demand, heart rate reduction would be expected to diminish cardiac workload. Clinical studies with beta-blockers have already shown a reduction in mortality and improvement in outcome as a result of reduction heart rate.
Key Words: Cellular energetic needs Heart rate Metabolic rate Life expectancy
References
- Furberg CD, Psaty BM, Meyer JV. Nifedipine. Dose-related increase in mortality in patients with heart disease. Circulation. 1995;92:13261331
[Abstract/Free Full Text] - Gibson RS, Boden WE. Calcium channel antagonists: friend or foe in postinfarction patients? Am J Hypertens. 1996;9:172S176S[CrossRef][Medline]
- The Multicenter Diltiazem Postinfarction Trial Research Group. Effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med. 1988;319:385392[Abstract]
- The Danish Study Group on Verapamil in Myocardial Infarction. Effect of verapamil on mortality and major events after acute myocardial infarction (The Danish Verapamil Infarction Trial II DAVIT II). Am J Cardiol. 1990;66:779785[CrossRef][Web of Science][Medline]
- Beere PA, Glagov S, Zarins CK. Experimental atherosclerosis at the carotid bifurcation of the cynomolgus monkey. Localization, compensatory enlargement, and the sparing effect of lowered heart rate. Arterioscler Thromb. 1992;12:12451253
[Abstract/Free Full Text] - Beere PA, Glagov S, Zarins CK. Retarding effect of lowered heart rate on coronary atherosclerosis. Science. 1984;226:180182
[Abstract/Free Full Text] - Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol. 1986;250:H1145H1149
- Schmidt-Nielsen K. Animal physiology: adaptation and environment. New York: Cambridge University Press; 1975.
- Levine HJ. Rest heart rate and life expectancy. J Am Coll Cardiol. 1997;30:11041106[Abstract]
- Azbel MY. Universal biological scaling and mortality. Proc Natl Acad Sci USA. 1994. p. 1245312457
- Spector WS. Handbook of biological data. Philadelphia: WB Saunders; 1956.
- Coburn AF, Grey RM, Rivera SM. Observations on the relation of heart rate, life span, weight and mineralization in the digoxin-treated A/J mouse. Johns Hopkins Med J. 1971;128:169193[Web of Science][Medline]
- Hjalmarson A, Gilpin E, Kjekshus J, et al. Influence of heart rate on mortality after acute myocardial infarction. Am J Cardiol. 1990;65:547553[CrossRef][Web of Science][Medline]
- Palatini P, Julius S. The physiological determinants and risk correlations of elevated heart rate. Am J Hypertens. 1999;12:3S8S[CrossRef][Web of Science][Medline]
- Gillman M, Kannel W, Belanger A, D'Agostino R. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am Heart J. 1993;125:11481154[CrossRef][Web of Science][Medline]
- Kannel W, Kannel C, Paffenbarger R, Cupples A. Heart rate and cardiovascular mortality: The Framingham Study. Am Heart J. 1987;113:14891494[CrossRef][Web of Science][Medline]
- Bers DM. Excitation-contraction coupling and cardiac contractile force. Dordrecht: Kluwer; 1991.
- Fabiato A. Appraisal of the physiological relevance of two hypotheses for the mechanism of calcium release from the mammalian cardiac sarcoplasmic reticulum: calcium-induced release versus charge-coupled release. Mol Cell Biochem. 1989;89:135140[CrossRef][Web of Science][Medline]
- Tada M, Kadoma M, Fujii J, Kimura Y, Kijima Y. Molecular structure and function of phospholamban: the regulatory protein of calcium pump in cardiac sarcoplasmic reticulum. Adv Exp Med Biol. 1989;255:7989[Medline]
- Opie LH. The Heart: physiology and metabolism. New York: Raven Press; 1991.
- Balaban RS. Regulation of oxidative phosphorylation in the mammalian cell. Am J Physiol. 1990;258:C377C389
- Clausen T, van Hardeveld C, Everts ME. Significance of cation transport in control of energy metabolism in thermogenesis. Physiol Rev. 1991;71:733774
[Free Full Text] - Gudbjarnason S, Mathes P, Ravens KG. Functional compartmentation of ATP and creatine phosphate in heart muscle. J Mol Cell Cardiol. 1970;1:325339[CrossRef][Medline]
- Newsholme EA, Chaliss RAJ, Crabtree B. Substrate cycles: their role in improving sensitivity in metabolic control. Trends Biochem Sci. 1984;9:277280[CrossRef]
- Kjekshus J. Importance of heart rate in determining beta-blocker efficacy in acute and long-term myocardial infarction intervention trials. Am J Cardiol. 1986;57:43F49F[CrossRef][Medline]
- Beta-Blocker Heart Attack Trial Study GroupFurberg CD, Hawkins CM, Lichstein E. Effect of propranolol in postinfarction patients with mechanical or electrical complications. Circulation. 1984;69:761765
[Abstract/Free Full Text] - Ferrari R. Prognosis of PTS with unstable angina or acute myocardial infarction treatment with calcium channel antagonists. Am J Cardiol. 1996;77:2225
- Hjalmarson A. Significance of reduction of heart rate in cardiovascular disease. Clin Cardiol. 1998;21:113117
- Lechat P. Beta-blocker treatment in heart failure. Role of heart rate reduction. Basic Res Cardiol. 1998;93:148155
- Packer M, Colucci WS, Sackner-Bernstein JD, et al. Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. Circulation. 1996;94:27932799
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