Abstract
In order to determine whether treatment of hyperlipidaemia with simvastatin impairs exercise stress responses and so may contribute to an excess of suicides and violent deaths, the effects of simvastatin 20 mg daily and placebo on exercise physiology were compared in 19 patients. After 6 weeks of treatment there was no evidence of reduced exercise capacity, or of reduced cortisol or catecholamine responses. It is concluded that treatment of hyperlipidaemia with an inhibitor of HMG-CoA reductase does not significantly modify stress responses, and so the explanation for a possible increase in non-cardiac mortality must be sought elsewhere.
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- Azzarito C., Boiardi L., Zini M., Agosti A., Dotti C., Biagi R., Portioli I. Long-term therapy with high-dose simvastatin does not affect adrenocortical and gonadal hormones in hypercholesterolemic patients. Metabolism. 1992 Feb;41(2):148–153. doi: 10.1016/0026-0495(92)90143-x. [DOI] [PubMed] [Google Scholar]
- Borg G. A. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377–381. [PubMed] [Google Scholar]
- Candrina R., Balestrieri G., Salvi A., Di Stefano O., Spandrio S., Giustina G. Cortisol secretion in patients on simvastatin. Lancet. 1990 Jan 6;335(8680):53–53. doi: 10.1016/0140-6736(90)90182-5. [DOI] [PubMed] [Google Scholar]
- Elborn J. S., Stanford C. F., Nicholls D. P. Reproducibility of cardiopulmonary parameters during exercise in patients with chronic cardiac failure. The need for a preliminary test. Eur Heart J. 1990 Jan;11(1):75–81. doi: 10.1093/oxfordjournals.eurheartj.a059596. [DOI] [PubMed] [Google Scholar]
- Engelberg H. Low serum cholesterol and suicide. Lancet. 1992 Mar 21;339(8795):727–729. doi: 10.1016/0140-6736(92)90609-7. [DOI] [PubMed] [Google Scholar]
- Fowkes F. G., Leng G. C., Donnan P. T., Deary I. J., Riemersma R. A., Housley E. Serum cholesterol, triglycerides, and aggression in the general population. Lancet. 1992 Oct 24;340(8826):995–998. doi: 10.1016/0140-6736(92)93009-c. [DOI] [PubMed] [Google Scholar]
- Frick M. H., Elo O., Haapa K., Heinonen O. P., Heinsalmi P., Helo P., Huttunen J. K., Kaitaniemi P., Koskinen P., Manninen V. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987 Nov 12;317(20):1237–1245. doi: 10.1056/NEJM198711123172001. [DOI] [PubMed] [Google Scholar]
- Friedewald W. T., Levy R. I., Fredrickson D. S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499–502. [PubMed] [Google Scholar]
- Jay R. H., Sturley R. H., Stirling C., McGarrigle H. H., Katz M., Reckless J. P., Betteridge D. J. Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia. Br J Clin Pharmacol. 1991 Oct;32(4):417–422. doi: 10.1111/j.1365-2125.1991.tb03924.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan J. R., Manuck S. B., Shively C. The effects of fat and cholesterol on social behavior in monkeys. Psychosom Med. 1991 Nov-Dec;53(6):634–642. doi: 10.1097/00006842-199111000-00005. [DOI] [PubMed] [Google Scholar]
- Kromhout D., Katan M. B., Menotti A., Keys A., Bloemberg B. Serum cholesterol and long-term death rates from suicide, accidents, or violence. Seven Countries Study Group. Lancet. 1992 Aug 1;340(8814):317–317. doi: 10.1016/0140-6736(92)92415-c. [DOI] [PubMed] [Google Scholar]
- Lindberg G., Råstam L., Gullberg B., Eklund G. A. Low serum cholesterol concentration and short term mortality from injuries in men and women. BMJ. 1992 Aug 1;305(6848):277–279. doi: 10.1136/bmj.305.6848.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lowering cholesterol concentrations and mortality. BMJ. 1990 Sep 15;301(6751):552–555. doi: 10.1136/bmj.301.6751.552-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Luger A., Deuster P. A., Kyle S. B., Gallucci W. T., Montgomery L. C., Gold P. W., Loriaux D. L., Chrousos G. P. Acute hypothalamic-pituitary-adrenal responses to the stress of treadmill exercise. Physiologic adaptations to physical training. N Engl J Med. 1987 May 21;316(21):1309–1315. doi: 10.1056/NEJM198705213162105. [DOI] [PubMed] [Google Scholar]
- McDowell I. F., Smye M., Trinick T., Shortt J. A., Archibald M. P., Trimble E. R., Nicholls D. P. Simvastatin in severe hypercholesterolaemia: a placebo controlled trial. Br J Clin Pharmacol. 1991 Mar;31(3):340–343. doi: 10.1111/j.1365-2125.1991.tb05539.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mol M. J., Stalenhoef A. F., Stuyt P. M., Hermus A. R., Demacker P. N., Van 'T Laar A. Effects of inhibition of cholesterol synthesis by simvastatin on the production of adrenocortical steroid hormones and ACTH. Clin Endocrinol (Oxf) 1989 Dec;31(6):679–689. doi: 10.1111/j.1365-2265.1989.tb01293.x. [DOI] [PubMed] [Google Scholar]
- Muldoon M. F., Manuck S. B., Matthews K. A. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. BMJ. 1990 Aug 11;301(6747):309–314. doi: 10.1136/bmj.301.6747.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oliver M. F. Might treatment of hypercholesterolaemia increase non-cardiac mortality? Lancet. 1991 Jun 22;337(8756):1529–1531. doi: 10.1016/0140-6736(91)93208-q. [DOI] [PubMed] [Google Scholar]
- Pekkanen J., Nissinen A., Punsar S., Karvonen M. J. Serum cholesterol and risk of accidental or violent death in a 25-year follow-up. The Finnish cohorts of the Seven Countries Study. Arch Intern Med. 1989 Jul;149(7):1589–1591. [PubMed] [Google Scholar]
- Prihoda J. S., Pappu A. S., Smith F. E., Illingworth D. R. The influence of simvastatin on adrenal corticosteroid production and urinary mevalonate during adrenocorticotropin stimulation in patients with heterozygous familial hypercholesterolemia. J Clin Endocrinol Metab. 1991 Mar;72(3):567–574. doi: 10.1210/jcem-72-3-567. [DOI] [PubMed] [Google Scholar]
- Stone B. G., Evans C. D., Prigge W. F., Duane W. C., Gebhard R. L. Lovastatin treatment inhibits sterol synthesis and induces HMG-CoA reductase activity in mononuclear leukocytes of normal subjects. J Lipid Res. 1989 Dec;30(12):1943–1952. [PubMed] [Google Scholar]
- Thompson P. D., Gadaleta P. A., Yurgalevitch S., Cullinane E., Herbert P. N. Effects of exercise and lovastatin on serum creatine kinase activity. Metabolism. 1991 Dec;40(12):1333–1336. doi: 10.1016/0026-0495(91)90039-y. [DOI] [PubMed] [Google Scholar]
- Virkkunen M., Penttinen H. Serum cholesterol in aggressive conduct disorder: a preliminary study. Biol Psychiatry. 1984 Mar;19(3):435–439. [PubMed] [Google Scholar]
- Wysowski D. K., Gross T. P. Deaths due to accidents and violence in two recent trials of cholesterol-lowering drugs. Arch Intern Med. 1990 Oct;150(10):2169–2172. [PubMed] [Google Scholar]
- Yusuf S., Wittes J., Friedman L. Overview of results of randomized clinical trials in heart disease. II. Unstable angina, heart failure, primary prevention with aspirin, and risk factor modification. JAMA. 1988 Oct 21;260(15):2259–2263. [PubMed] [Google Scholar]