THE LANCET
another recent editorial5 you suggest
they may contain some crumb of
plausibility.
*Fausto Avanzini, Claudio Alli,
Gianni Tognoni
Cardiovascular Research Department, Istituto
di Ricerche Farmacologiche Mario Negri,
20157 Milan, Italy
e-mail: Avanzini@irfmn.mnegri.it
1 Staessen JA, Fagard R, Thijs L, et al.
Randomised double-blind comparison of
placebo and active treatment for older
patients with isolated systolic hypertension.
Lancet 1997; 350: 757–64.
2 SHEP Cooperative Research Group.
Prevention of stroke by antihypertensive drug
treatment in older persons with isolated
systolic hypertension: final results of the
Systolic Hypertension in the Elderly Program
(SHEP). JAMA 1991; 265: 3255–64.
3 MRC Working Party. Medical research trial
of treatment of hypertension in older adults:
principal results. BMJ 1992; 304: 405–12.
4 Editorial. The ethics industry. Lancet 1997;
350: 897.
5 Editorial. Good manners for the
pharmaceutical industry. Lancet 1997; 349:
1635.
Authors’ reply
SIR—As Caroline Nabel and colleagues
suggest, we planned to test the a priori
hypothesis that Syst-Eur patients would
benefit from antihypertensive treatment
irrespective of pre-existing
cardiovascular risk. Of 1402 patients
with earlier cardiovascular
complications, 58 (4·1%) and 163
(11·6%) had a history of stroke or
myocardial infarction, respectively. 412
other patients had symptoms or signs
suggestive of coronary heart disease
and 45 of cerebrocascular disease,
614 had electrocardiographic changes
compatible with left-ventricular hyper-
trophy, or a combination of these or
other conditions (n=110). In patients
with cardiovascular complications at
entry, total and cardiovascular mortality
and major endpoints occurred at nearly
twice the rate of that in other par-
ticipants. In multiple Cox regression,
with adjustments applied for significant
covariates (sex, age, entry systolic blood
pressure, smoking), the interaction
terms between treatment and previous
cardiovascular complications were not
significant. Thus, nitrendipine-based
treatments reduced all endpoints
irrespective of previous cardiovascular
complications.
In reply to John Coope and Malcolm
Aylett, antihypertensive drug treatment
in the Syst-Eur trial prevented stroke and
other cardiovascular endpoints. In frail
elderly patients, these complications are
the main determinants of quality of life.
Balanced against the prevention of such
vital complications, side-effects are of
lesser clinical significance and are easily
remediable. Adverse effects of the drugs
1634
used in the Syst-Eur trial were explored
in an elaborate quality of life substudy,1
in which over 800 patients were enrolled
and which is soon to be reported.
With respect to external validity
(generalisability), Syst-Eur recruited
patients in both eastern and western
Europe. The participants were drawn
from population screening, family
practices, or primary or secondary
referral centres. Patients with major
cardiovascular complications and
individuals unlikely to comply with long-
term follow-up and treatment were
excluded. Such circumstances are
bound to limit extrapolation of the Syst-
Eur to all patients with isolated systolic
hypertension. However, 52·6% of
8926 patients were randomised. By
comparison, in the SHEP trial,2 447 921
individuals were contacted mainly by
mass mailing and community screening,
of whom 1·1% (n=4736) were
randomised.
The Syst-Eur trial was not meant to
compare diuretics and calcium-channel
blockers. After publication of the SHEP
results,2 the Syst-Eur study continued in
view of the remaining uncertainty with
respect to its primnary research
question.3 The controversy about
possible adverse effects of calcium-
channel blockers arose only in 19954 and
was not considered by the ethics
committee or by the review boards of the
participating centres in 1991 or 1992.
In response to Fausto Avanzini and
colleagues’ points, in fact, the second of
four planned interim analyses by
intention-to-treat showed that active
treatment had reduced total stroke, the
primary endpoint, by 52% (p=0·0004),
and total and cardiovascular mortality by
27% (p=0·03) and 37% (p=0·01),
respectively. On Feb 14, 1997, the ethics
committee stopped the trial according to
predefined rules, and recommended that
the final report should include all
endpoints that had occurred before this
date. The trial terminating forms
requested after this date increased the
number of patient-years by 17·2%, but
concerned mainly patients without
endpoints because major events had
already been reported to the co-
ordinating office. Thus, the final results
by intention-to-treat showed only a
slight reduction of cardiovascular
mortality (⫺27%; p=0·07) and no
change in total mortality (⫺14%;
p=0·22). The subsequent per-protocol
analysis of the final data showed a
significant reduction of total mortality in
patients randomised to active treatment.
*Jan A Staessen, Willem H Birkenhäger,
Colin T Dollery, Robert Fagard
Syst-Eur Coordinating Office, Campus
Gasthuisberg, B-3000 Leuven, Belgium
1 Fletcher A, Bulpitt C, Amery A, et al. The
assessment of quality of life in the Syst-Eur
Trial. High Blood Press 1993; 2: 45–50.
2 SHEP Cooperative Research Group.
Prevention of stroke by antihypertensive drug
treatment in older persons with isolated
systolic hypertension: final results of the
Systolic Hyperytension in the Elderly
Program (SHEP). JAMA 1991; 265:
3255–64.
3 Flecher A, Spiegelhalter D, Staessen J,
Thijs L, Bulpitt C. Implications for trials in
progress of publication of positive results.
Lancet 1993; 342: 653–57.
4 Furberg CD, Psaty BM, Meyer JV.
Nifedipine. Dose-related increase in mortality
in patients with coronary heart disease.
Circulation 1995; 92: 1326–31.
Obesity
S IR —We have examined the
prevalence of eating disorders and
obesity in a sample of Austrian
women,1 and believe that our findings
confirm and supplement the report by
Per Björntorp (Aug 9, p 423)2 on
obesity.
1000 women (age 15–85 years,
mean 39·6) were interviewed on the
telephone by female dietitians on
topics related to weight, eating
behaviour, and sociodemographic
data. Of the entire sample, 115 were
underweight (body-mass index [BMI]
<19 kg/m2), more than the half (516)
were of normal weight (BMI 19–24
kg/m2), 321 were overweight (BMI
25–30 kg/m 2), and 48 were obese
(BMI >30 kg/m 2). There were
significant weight differences between
the age groups, with a monotonic
increase in the prevalence of
overweight throughout the entire age
range, reaching a peak of 100 (55%) in
women older than 65 years.
Although no women under 25 years
were obese, the highest rate of obesity
was found in women between 45 and
54 years (n=16, 10%). It seems highly
likely that the decrease of prevalence
rate to 6·6% in women over 65 years
may be attributed to the high risk of
mortality in obese individuals.
The low prevalence of obesity
in Tyrolean women is certainly
multicausal. Besides the lower avail-
ability of high-energy nutrition and the
increased physical activity in the rural
population in Tyrol, the non-accep-
tance of obesity in this region is
important.
Johann F Kinzl
Department of Psychiatry, Innsbruck
University Clinics, A-6020 Innsbruck,
Austria
1 Björntorp P. Obesity. Lancet 1997; 350:
423–26.
2 Kinzl JF. Traweger C, Trefalt E,
Mangweth B, Biebl W. Binge eating
disorder in females: a population-based
investigation. Int J Eat Disord (in press).
Vol 350 • November 29, 1997