Cardiovascular drugs that reduce mortality (such as ␤-blockers or diuretics) can also reduce the pulse⫻mass index. Potent vasodilators that increase pulse rate and retain water, do not reduce mortality. 1 *Enrique Sanchez-Delgado, Heinz Liechti 3 2 Laboratorios Solka SA, km16 1/2 Carretera Masaya, PO Box A-02, Managua, Nicaragua (e-mail: solka@ibw.com.ni) Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary heart disease. Lancet 1999; 353: 89–92. 2 Stevens J, et al. The effects of age on the association between body-mass index and mortality. N Engl J Med 1998; 338: 1–7. 3 Finkel E. Piecing together the puzzle of ageing. Lancet 1997; 350: 1150. 4 Sánchez-Delgado E. Presented at the II National Congress of Clinical Specialties, Managua, Nicaragua, 24–27 June 1998, and XIV Central American Congress of Internal Medicine, San Salvador, El Salvador, 18–21 Nov, 1998. 5 Levine HJ. Rest heart rate and life expectancy. JACC 1997; 30: 1104–06. 4 1 Sir—Donald Lloyd-Jones and colleagues assess lifetime risk of coronary heart disease (CHD) on the basis of data from 7733 participants in the Framingham Heart Study. We have modelled cumulative and lifetime risk of CHD for a UK population and estimated the likely effects of risk-factor intervention. Risk of CHD was calculated from the age to 40 to 90 years (in 5 year blocks) with a simple computer programme.2 For each age point, mean systolic and diastolic blood-pressure and cholesterol values for the UK population were obtained from the Health Survey for England (1994),3 and we adjusted for all cause mortality with statistics (1996) from the Office of National Statistics.4 The predicted cumulative and lifetime risk estimates for the UK population show close similarity to those in the Framingham study (data not shown). The calculations were then repeated after adjustment for smoking status, mean blood pressure, or cholesterol (figure). We assessed cumulative and total lifetime risk and the age at which cumulative risk reached 25% (R25). Total lifetime risk was about 20% higher in smokers than in non-smokers. In male smokers R25 was reached by the age of 60 and in non-smokers by the age of 68. The effects of blood pressure reduction of 8 mm Hg and cholesterol lowering by 20% also reduced lifetime risk and R25, although the effects of blood pressure reduction were fairly small (figure). We calculate that, for a general population of symptom-free smoking 40-year-old men, if smoking ceased and mean cholesterol values were reduced by 20%, the burden of THE LANCET • Vol 353 • March 13, 1999 Lloyd-Jones DM, Larson MG, Beiser A, Levy D. Lifetime risk of developing coronary artery disease. Lancet 1999; 353: 89–92. Hingorani AD, Vallance P. A simple computer program for guiding management of cardiovascular risk factor and prescribing. BMJ 1999; 318: 101–05. Colhoun H, Prescott-Clarke P, eds. Joint Health Survey Unit. Health for the Nation. Health Survey for England 1994. London: HM Stationery Office, 1994. Office of National Statistics Mortality Statistics 1996 Cause. Government Statistical Service. Series DH2 no 23. London: HMSO, 1996. Laxatives and the Ice Man Cumulative risk of coronary heart disease (baseline age 40 years) Curves for smokers (—o—) and non-smokers (—䡲—)with UK population mean values for total and HDL-cholesterol and blood pressure (BP). Curves for non-smokers, with systolilc BP 8 mm Hg below population average (— 䊲 —), for non-smokers with total cholesterol 20% below population average (—⽧— ), and non-smokers in whom both systolic BP and total cholesterol are 8 mm Hg and 20% (respectively) below population averages (—●—). Curve for a high-risk individual: smoker with systolic BP of 170 mm Hg, total cholesterol 7·5 mmol/L, and HDLcholesterol 0·8 mmol/L (—□—). coronary heart disease would be nearly halved before retirement age of 65. We also applied the cumulative risk calculations to a high risk 40-year-old individual: a smoker with a systolic blood pressure of 175 mm Hg, total cholesterol of 7·5 mmol/L, HDL cholesterol of 0·8 mmol/L, and left ventricular hypertrophy. The results (figure) indicate a lifetime risk CHD of nearly 100% for a man, and, in this situation, the R25 is reached within 5 years. Our calculations support LloydJones and colleagues’1 suggestion that estimates of lifetime risk could be used to muster support for rational policies to reduce cardiovascular disease burden among the workforce, or the entire population. The R25 value we describe also gives an indication of the speed at which risk accumulates. If applicable to the individual, such calculations might also be useful to guide treatment options and decide the optimum age at which to institute drug therapy. Silvia Ulrich, Aroon D Hingorani, John Martin, *Patrick Vallance Centre for Clinical Pharmacology and Therapeutics, Department of Medicine, University College London Medical School, London W1P 9LN, UK Sir—In his report on the Ice Man’s use of natural laxatives and antibiotics, Luigi Capasso (Dec 5, p 1864) 1 should have cited better references to substantiate his statements about the field of natural product chemistry and pharmacology. We have not been able to find any relevant data from the standard databases (Medline, International Pharmaceutical Abstracts, Biological Abstracts, and NAPRALERT) to confirm a purgative or antibiotic effect of Piptoporus betulinus. The available pharmacological data on antibacterial effects are from the mycelia and culture liquids, and not from the fruit body.2 We were also unable to find any information in Chemical Abstract, NAPRALERT, or standard textbooks to confirm that P betulinus contains agaric acid or toxic oils. Furthermore, agaric acid is a name used for various compounds.3 Capasso claims that “The discovery of the fungus suggests that the Ice Man was aware of his intestinal parasites and fought them with measured doses of Piptoporus betulinus”. The fungus has rarely been used in European traditional medicine and only as a remedy against wounds. Ethnobotanical data from preindustrial Northern Europe show that the fungus has had several non-medical uses, such as to protect metal blades from rust, to sharpen razors, as toys, floats or pincushions. So it is odd that Capasso concludes that the fungi kept by the Ice Man were used to treat a worm infection and not for any other purpose. In some places worm infestation is so common it is regarded as a normal state. Indeed, infestation with Trichuris trichiura “does not usually cause problems except in heavily infected young children, who may exhibit mild toxicity and some degree of anemia”.4 In contradiction to what Capasso claims, there are many medicinal plants 925 its fruitbodies induced the production of interferon. that were used against intestinal worms long before the introduction of chenopod oil to Europe. We find it astonishing that Capasso draws so many conclusions from such a limited amount of data. Institut für Mikrobiologie, Leopold Franzens Universität Innsbruck, A-6020 Innsbruck, Austria *Håkan Tunón, Ingvar Svanberg 1 Swedish Biodiversity Centre, Box 7007, SE-750 07 Uppsala, Sweden (e-mail: hakan.tunon@pharmacog.uu.se) 1 2 3 4 Capasso L. 5300 years ago, the Ice Man used natural laxatives and antibiotics. Lancet 1998; 352: 1864. Coletto MAB, Labollita A. Antibiotic activity in Basidiomycetes: XI. Antibacterial and antifungal activity of 25 new strains. Allionia 1997; 35: 95–101. Budavari S, O’Neil MJ, Smith A, Heckelman PE. The Merck Index, 11th edn. Rahway, NJ. Merck & Co Inc, 1989. Webster LT. Chemotherapy of parasitic infections. In: Goodman Gilman A, Rall TW, Nies AS, Taylor P, eds. The pharmacological basis of therapeutics. New York: Pergamon Press, 1990. Sir—Luigi Capasso1 suggests “the Ice Man was aware of his intestinal parasites and fought them with measured doses of Piptoporus betulinus”. This statement is not supported by the current body of evidence on the pharmaceutical properties of the “birch polypore”.2 In addition to this risky conclusion, Capasso’s statement that P betulinus contains agaric acid (2-hydroxynonadecantricarbonic acid) is simply wrong.3 The latter is a typical product of Laricifomes officinalis, another bracket fungus already used by the ancient Greeks and Romans for medical purposes. This fungus has been used as a purgative or as medicine against pulmonary diseases right up to the 20th century. In our studies, agaricine was not detected in the two fungal fruitbody fragments of the Ice Man or in recent material of P betulinus.2 The pharmacologically active substances of P betulinus are fungisterol, ergosta-7,22-dien-3-␤-ol, ergosterol, tumulosic acid, and a group of triterpenes. Among the latter, polyporenic acid A, B, and C were separated.4 Animal studies have shown polyporenic acid A to have antimicrobial and antiphlogistic activities, whereas polyporenic acid C was highly active against species of Mycobacterium. The five-cyclic triterpenes obtained from the “birch polypore” inhibit the growth of plants and malignant neoplastic cells. Furthermore, P betulinus acts on spontaneous tumours in dogs including cancers of the vagina and on sarcoma S37 and S180 in mice. P betulinus prevents poliomyelitis in white mice and monkeys, and RNA isolated from 926 *Reinhold Pöder, Ursula Peintner Capasso L. 5300 years ago, the Ice Man used natural laxatives and antibiotics. Lancet 1998; 352: 1864. 2 Peintner U, Pöder R. The Iceman’s fungi. Mycol Res 1998; 102: 1153–62. 3 Pöder R. Ice Man’s Fungi: discussion rekindled. Science 1993; 262: 1956. 4 Cross LC, Eliot CG, Heilbron IM, Jones ERH. Constituents of the higher fungi. Part 1. The triterpene acids of Polyporus betulinus Fr. J Chem Soc 1940: 632–36. Author’s reply Sir—The discovery, 8 years ago, that the Ice Man had two pieces of bracket fungus among his personal effects has resulted in lively debate among specialists as to the purpose of the fungus. Archaeologists have proposed many explanations, for example, that these woody growths were used as tinder, a practice that continued until the past century in the Alps.1 When it was shown by anthropologists that the Ice Man was familiar with some ancient forms of popular medicine, for example the use of tattoos as a therapy for joint pain or as primitive acupuncture,2 some researchers suggested the presence of the bracket fungus might be related to the fungus’s pharmacological effects.3 Although there is little experimental data about these effects, we know that bracket fungi were widely used in ancient Roman and Greek medicine,4 and were empirically linked by ancient and popular physicians to “drastic” effects and to disinfecting properties.3 For these reasons, archeologists and myocologists have suggested that the Ice Man may offer a view of the dawn of European medicine. Indeed, he provides the earliest known example of direct proof of human medical knowledge by the possession of fungi to which ancient physicians assigned some pharmacological effects.3 The discovery that the Ice Man had intestinal worms adds further archaeological evidence to this picture, namely that human trichuriasis has existed in Europe since neolithic times; unfortunately, we do not yet know how serious the disease was in neolithic man or in the neolithic ecosystem, nor do we have any data on the prevalence of the disease in neolithic populations. Many medicinal plants could have been used in ancient times to treat intestinal worms and they were theoretically already in use by the time of the Ice Man, though we have no direct archeological evidence of the practice in Europe during neolithic times. The Eber’s papyrus gives a preparation to combat intestinal verminoses with pomegranate, but we believe the pomegranate was not introduced into continental Europe until many centuries later. There is also direct evidence for anthelmintic therapy in North America in ancient times. Kliks5 identified chenopodium oils in human coprolites dating to precontact time from Utah and Nevada. Other than these two examples, no further direct evidence of medicinal plants used in ancient times to combat intestinal verminoses has emerged from archaeological contexts to date, nor do we have other direct evidence for Europe. The Ice Man fits into this context with his diseases, but also with the earliest evidence of the most ancient European medical knowledge. We believe this ancient knowledge must be investigated, even if it goes beyond the bounds of our current experimental data. Luigi Capasso Department of Anthropology, National Anthropological Museum, 66100 Chieti, Italy 1 Spindler K. Der mann im eis. Munich: C Bertelsmann, 1993. 2 Dorfer L, Moser M, Spinder K, Bahr F, Egarter-Vigl E, Dohr G. 5200-year-old acupuncture in Central Europe? Science 1998; 282: 242–43. 3 Pöder R, Peintner U, Pümpel T. Mykologishe untersuchungen an den pilzbeifunden der gletschermumie vom hauslabjoch. Veröffentlichungen der Universität Innsbruck 1993; 187: 313–20. 4 Buller AHR. The fungus lore the Greeks and Romans. Trans Br Mycol Soc 1914; 5: 21–66. 5 Kliks M. Paleoepidemiological studies on Great Basin Coprolites: estimation of dietary fiber intake and evaluation of the ingestion of anthelmintic plant substances. Occasional paper-archaeological research facilities. Berkley: University of California, 1975. Trandolapril and human diabetic neuropathy Sir—Rayaz Malik and colleagues (Dec 19/26, p 1978)1 claim that the angiotensin-converting enzyme (ACE) inhibitor trandolapril may improve peripheral neuropathy in normotensive patients with diabetes. However, there are two major sources of bias in the trial. First, they do not provide information on the upper limit of blood pressure, defined as normotensive, they only give mean (SD) systolic blood pressure in the placebo group of 139·2 mm Hg (11·2) and 139·8 mm Hg (12·9) at 6 and 12 months, respectively. Therefore, one would expect that almost half the patients had systolic blood pressure THE LANCET • Vol 353 • March 13, 1999