Pulsed excimer laser versus continuous-wave Nd:YAG laser versus conventional angioplasty of peripheral arterial occlusions: prospective, controlled, randomised trial

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et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group.

14. McKhann G, Drachman D, Folstein M,

Neurology 1984; 34: 939-44. 15. Roth M, Huppert FA, Tym E,

et

al. CAMDEX: the

Cambridge

examination for mental disorders of the elderly. Cambridge:

Cambridge University Press,

1988.

16. Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 189-98. 17. Khachaturian ZS. 42: 1097-105.

Diagnosis of Alzheimer’s disease. Arch Neurol 1985;

18. Anderson JM, Hubbard BM. The effect of advanced old age on the neurone content of the cerebral cortex. Observations with an automatic image analyser point counting method. J Neurol Sci 1983; 58: 235-46. 19. Jernigan TL, Archibald SL, Berhow MT, et al. Cerebral structure on

changes. Biol Psychiat 1991; 29: 55-67. 20. Rocca WA, Hofman A, Brayne C, et al. Frequency and distribution of Alzheimer’s disease in Europe: a collaborative study of 1980-1990 prevalence findings. Ann Neurol 1991; 30: 381-90. 21. Cascino GD, Jack CR, Parisi JE, et al. Magnetic resonance imagingbased volume studies in temporal lobe epilepsy: pathological correlations. Ann Neurol 1991; 30: 31-36. 22. Press GA, Amaral DG, Squire LR. Hippocampal abnormalities in amnesic patients revealed by high-resolution magnetic resonance imaging. Nature 1989; 341: 54-57. 23. Bogerts B, Falkai P, Haupts M, et al. Post-mortem volume measurements in limbic system and basal ganglia structures in chronic schizophrenics—intitial results from a new brain collection. Schizophrenia Res 1990; 3: 295-301. 24. Esiri MM, Oppenheimer DR. Diagnostic neuropathology. Oxford: Blackwell Scientific Publications, 1989: 109. MRI 1. Localization of age-related

Pulsed excimer laser versus continuous-wave Nd:YAG laser versus conventional angioplasty of peripheral arterial occlusions: prospective, controlled, randomised trial

Early clinical studies of coronary and peripheral laser angioplasty showed that arterial occlusions could be recanalised by continuous-wave lasers delivered with contact probes and by pulsed lasers applied with multifibre catheters. However, whether laser-assisted angioplasty improves success rates in reopening occlusions and in long-term patency rates is unclear. We have compared the primary recanalisation and long-term patency rates after laser-assisted and conventional percutaneous transluminal angioplasty (PTA) of femoropopliteal artery occlusions in 116 consecutive symptomatic patients (excimer laser 37, Nd:YAG laser 40, PTA 39). Primary recanalisation was achieved in 81 patients (70%). The primary recanalisation rate achieved with the excimer laser was significantly lower than that with the Nd:YAG laser (49% vs 78%, p<0·01) or with

PTA

(82%,

p<0·003).

The

overall

angiographic recanalisation rate (primary and secondary recanalisation) after laser and PTA was 89%. After 3 months, clinical improvement was recorded in 76% of patients. Clinical long-term results were available in 94 (91%), and angiographic long-term results in 77 (75%), of 103 successfully recanalised patients. Life-table analysis of the longterm results revealed no significant difference of the restenosis rate between the three treatment groups. The 12-month patency rate was 60% as assessed clinically and 39% as judged by angiography. Primary and secondary recanalisation rates and long-term patency rates were significantly correlated with length of the occlusion. Our results suggest that PTA of femoropopliteal artery occlusions is only indicated if the occlusion is short (<8 cm) and that laser-assisted angioplasty should only be used after failure of conventional PTA.

Introduction Percutaneous transluminal angioplasty (PTA) is an established treatment for segmental femoropopliteal artery stenoses.1 However, PTA of femoropopliteal artery occlusions has an initial recanalisation rate of only 26% to 91% (depending upon occlusion length), and a long-term patency rate of about 65%.2,3 The aim of laser-assisted angioplasty was to improve initial and long-term patency rates. Early clinical studies of coronary and peripheral laser angioplasty showed that arterial obstructions could be recanalised by continuous-wave (cw) lasers delivered by contact probes’ and by pulsed lasers delivered by multifibre catheters. 7-9 The various clinical feasibility studies showed similar results for pulsed and cw lasers.1o However, whether laser-assisted angioplasty improves success rates in reopening occlusions and in long-term patency rates is unclear. We did a prospective, randomised trial comparing the pulsed XeCl excimer laser, the cw Nd:YAG (neodymium-yttrium-aluminium-garnet) laser, and conventional PTA in patients with segmental femoropopliteal artery occlusions.

Subjects and methods Study design This prospective study was started in June, 1989. The aim was to evaluate the initial recanalisation rate and the restenosis rate after therapy of femoropopliteal artery occlusions by the three procedures. To be able to demonstrate a difference between 65% and 85% in the primary recanalisation rate at 79% power (5% alpha-error, 21% beta-error), the study was initially designed to include 40 patients in each of the three treatment groups. To evaluate the influence of therapy on the restenosis rate, only initially successfully treated patients were assessed. To evaluate clinical ADDRESSES: Departments of Radiology (Prof J. Lammer, MD, G E. Klein, MD), Internal Medicine (E Pilger, MD, M. Decrinis, MD, G Stark, MD), and Medical Computer Sciences (F. Quehenberger, MS), Karl-Franzens University of Graz; and Department of Radiology (J. Lammer), University of Vienna, Austria. Correspondence to Prof Johannes Lammer, Department of Radiology, University of Vienna, AKH-University Hospital, Waehringer Guertel 18-20, A-1090 Wien, Vienna, Austria.

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TABLE ll-LESION CHARACTERISTICS

TABLE I-BASELINE PATIENT CHARACTERISTICS I

Data

are no

of patients unless otherwise stated.

*p=0 15.

occlusions was 7-8 cm (SD 4-3). Arterial calcifications at the site of the occlusion were recorded with plain-film radiographs after angiography. Severity of the vessel-wall calcification was graded (0 no, 1 moderate, 2 severe). Peripheral run-off was documented by angiograms including the total length of the calf. Patency of the crural arteries was scored between 1 and 10.12 77 patients (66%) had a normal run-off (defined as 2-3 patent crural arteries, score < 5), and 39 (34%) had a reduced run-off (0-1 patent crural artery, score>

*Font.lla, SVS/ISCVS 1/2; tFont.llb, SVS/ISCVS 1/3; tFont.111, SVS/ISCVS 11/4; §Font.IV, SVS/ISCVS 11/5; ¶p=0.03. (See ref 12 for SVS/ISCVS stage.)

benefit of the recanalisation procedures, all patients referred for treatment were included in the final analysis (intention-to-treat

concept). Criteria for inclusion were femoropopliteal artery occlusion; clinical symptoms such as limiting claudication, pain at rest, tissue loss, or gangrene; disease suitable for PTA; unsuccessful conservative treatment; symptoms for more than 4 months; length of obstruction between 1 and 20 cm; and anticoagulation therapy feasible. Criteria for exclusion were stenoses without occlusion; thrombotic or embolic occlusions; incomplete angiographic demonstration of run-off arteries; cardiac or renal failure; and insulin-dependent diabetes mellitus. Patients were initially stratified into two groups of occlusion length (11-80 cm and 8.1-19.99 cm) and two groups of peripheral run-off (0-1 patent crural artery and 2-3 patent crural arteries). These subgroups were chosen from the mean occlusion length (8 cm) and the difference in long-term patency rates between patients with normal and reduced outflow in previous laser studies.5,6 Patients were randomised" to receive treatment with the pulsed excimer laser, the cw Nd:YAG laser, or conventional PTA. The study was approved by the ethics committee of the University of Graz and written informed consent was obtained from all acute

patients.

Study population The final

study population consisted of 116 consecutive symptomatic patients. 37 patients were treated with excimer-laserassisted angioplasty, 40 with Nd:YAG-laser-assisted angioplasty, and 39 with conventional angioplasty. Mean age was 65 years (SD 99, range 31-87). Prevalent risk factors were smoking (83 patients, 72%), hypertension (43, 37%), hyperlipidaemia (39, 34%), and diabetes mellitus (29,25%) (table i). Indications for treatment were moderate-to-severe claudication (as judged by treadmill test: speed 4 km/h, ascent 125°, 5 min) in 84 patients (72%) or limbthreatening ischaemia (presence of rest or night pain, ischaemic ulcers, or gangrene) in 32 patients (28%). The occlusion was located in the femoral or femoropopliteal segment in 102 patients and confined to the popliteal segment in 14. Mean length of the

5) (table n).

Laser angioplasty systems Pulsed laser therapy was given with a 308 nm XeCl excimer laser (MAX 10, Technolas, Grafelfing, Germany) with a pulse width of 60 to 115 ns and a repetition rate of 20 Hz. A 2-2 mm catheter (Ceram Optec, Bonn, Germany) with 30 fibres, 200 µm in diameter, was used. The energy fluence per pulse at the fibre tip was 45-60 mj/mm2. Continuous-wave laser therapy was given with a 1064 nm Nd:YAG laser (CL 60, Surgical Laser Technologies, Malvem, PA, USA) with an exposure time of 0-5-1 s and a repetition rate of 05 Hz. A 2-2 mm single fibre catheter (600 urn) was used with a "sapphire" contact probe (fused silica, 15% surface absorption, spherical configuration).13,14 The energy fluence per pulse at the fibre tip was 35 J/rnm2.

Treatment protocol All procedures were carried out percutaneously through a 7F introducer sheath and with local anaesthesia. Laser catheters were advanced with little forward pressure during laser activation. Angiography was performed after laser recanalisation to assess the degree of residual stenoses. All patients had additional angioptasty with a 4-6 mm balloon. In the control group, recanalisation was done by steerable guide wires in the following sequence: Glidewire (Terumo, Piscataway NJ; USA); Magnum wire (Schneider AG, Biilach, Switzerland); Lunderquist wire (Cook Inc, Bloomington, IN, USA) with a 6F vanAndel catheter (Cook Europe, Bjaerverskov, Denmark). Successful guide-wire recanalisation was followed by balloon angioplasty (5F Match, Schneider AG). All patients underwent fmal angiography including the run-off vessels, and the percentage of improvement and residual stenosis was assessed. During the procedure, patients were given 5000 IU heparin intraarterially. After a successful procedure, intravenous heparin 1000 IU/h was given for 48 h. All patients underwent oral

anticoagulation during follow-up. Definitions and follow-up procedures Success, failure, complications, and long-term patency were according to the standards of the Society of Vascular Surgery (SVS) and the International Society for Cardiovascular Surgery (ISCVS).12 Successful primary recanalisation was defined as recanalisation with 50% or less residual stenosis and antegrade flow immediately after the procedure and restoration of the recorded

1185

popliteal pulse 48 h after the procedure. Failures (inability to cross

the lesion, lack of antegrade flow, early reocclusion without improvement of the pulse status) were regarded as failures for both short-term and long-term calculations. When primary recanalisation failed, a second therapeutic option was chosen. Patients in whom laser recanalisation failed underwent conventional PTA and vice versa. The results of this combination therapy were reported separately as "secondary recanalisation". Complications were rated as minor or major. Minor complications did not influence the clinical state of the patient, whereas major complications prevented the regular therapeutic regimen or required surgical interventions. To compare the influence of the three types of recanalisation on the restenosis rate we initially analysed long-term patency after successful primary recanalisation only. This strategy was chosen to exclude the influence of the primary recanalisation rates of the different methods. Because clinical relief of symptoms is important for the patient but may not correlate with results of the ankle brachial doppler index (ABI) and angiography, patency rates were calculated separately for these three criteria. A clinical failure was defined as deterioration of clinical symptoms by one stage of the Fontaine classification. A decrease in the post-procedure ABI by more than 0-15 was regarded as a sign of reobstruction. Angiographic reobstruction was defined by the criteria of the National Heart, Lung and Blood Institute (NHLBI): increase in diameter stenosis of more than 30% (NHBLI I); an immediate post-PTA diameter stenosis of less than 50% increasing to more than 70% at follow-up (NHLBI II); an increase in stenosis severity to 10% or less of predilatation obstruction (NHLBI III); and a loss of more than 50% of the gain in luminal diameter achieved by PTA

(NHLBI IV).15,16 The patients were followed for a year. Follow-up examinations including clinical status, arterial pulses, and ABI were done at 2 days, and at 3,6,9, and 12 months. Patients underwent angiography after 1 year and when clinical symptoms or doppler values were suggestive of reobstruction. An intraarterial digital subtraction technique was used for computer-assisted quantification of the stenosis by edge detection or videodensitometry. Physicians who were not part of the study team carried out follow-up examinations without knowledge of patient groups. Because the three recanalisation methods did not influence the restenosis rate, all patients referred for treatment were included in the final analysis, to look for other indices that might influence the

restenosis rate.

Statistical analysis Cross-tabulations were analysed with chi-squared tests. A Kruskal-Wallis test was done to see whether patient characteristics differed between the groups. To compare treatment effects and to assess the influence of prognostic factors on the recanalisation rate, a logit model was fitted, first comparing treatments alone and then adding each factor separately. Statistical significance was assessed with Wald-test. Long-term patency rates were calculated by life-table analysis. (Detailed formulae, especially for the standard deviation of the survival distribution function, are given in SAS Technical Report P-179). Screening for prognostic factors in long-term patency was done with the Cox proportional hazard model stratified by therapy. p < 0-05 was regarded as statistically significant. Calculations were done with statistical software programs (SAS; JMP SAS Institute; Inc., Cary, NC).17,18

Results

Primary recanalisation Primary recanalisation of the femoropopliteal artery was achieved in 81 patients (70%). The primary recanalisation rate afforded by the excimer laser (18/37 patients, 49%) was significantly lower than that achieved by the Nd:YAG laser (31/40 patients, 78%; p<001) or PTA (32/39 patients, 82%; p < 0-003). There was no significant difference between Nd:YAG laser therapy and PTA. After excimerlaser-assisted angioplasty, there was no residual stenosis in 8

TABLE III-COMPLICATIONS DURING RECANALISATION THERAPY

*p=O 005

of the 37 patients, a less than 50% stenosis in 9, and a 50% stenosis in 1. The data for Nd:YAG-laser-assisted angioplasty are 21/40, 9/40, and 1/40, respectively, and for conventional PTA 25/39, 5/39, and 2/39, respectively. The primary recanalisation rates within the two stratification groups for short occlusions ( 8 cm, n = 57) were excimer 49%, Nd:YAG 84%, and PTA 91%, and for long occlusions (>8 cm, n = 59) excimer 50%, Nd:YAG 72%, and PTA 67%. Successful primary recanalisation depended on type of recanalisation therapy (p < 0-004), length of occlusion (p < 009), and grade of calcification (p < 0-07) but was independent of clinical stage, ABI, localisation of the lesion, and run-off score. The total energy for recanalisation averaged 299 J with the excimer laser (range 2-2736, SD 472) and 977 J with the Nd:YAG laser (11-2404, SD 617). In the Nd:YAG group there was a significant correlation between the total energy and the length of the lesion (p < 0-01). However, there was no correlation between length and energy in the excimer laser group or between calcification and energy in both laser groups.

Secondary recanalisation PTA was successful in 13 of 19 patients in whom excimer laser angioplasty failed and in 5 of 9 patients in whom Nd:YAG laser angioplasty failed. Laser angioplasty was successful in 4 of 7 patients in whom PTA failed. Thus, the primary and secondary recanalisation rate with PTA followed by Nd:YAG laser angioplasty was 92 %. If excimer or Nd:YAG laser angioplasty was done before guide-wire recanalisation, the success rate was 85% or 90%, respectively. The primary and secondary recanalisation rate for all patients was 89% (103/116). After primary and secondary recanalisation, no residual stenosis was present in 65 patients, 29 patients had less than a 50% stenosis, and 9 patients had a 50% stenosis. The secondary recanalisation rate tended to decrease with length of occlusion (p 0-06). =

Complications Minor complications were seen in 40 of 116 patients (34%) (table III). Peripheral emboli were treated successfully by suction and fibrinolysis (3 patients) or left untreated (2). If dissection occurred, an attempt was made to redirect the laser catheter or guide wire; if this failed the primary procedure was terminated. If perforation occurred, the recanalisation procedure was stopped and heparin was reversed by protamine sulphate. Spasm was treated with intraarterial prostaglandin El (002 mg). There were no complications requiring emergency surgery. The complication rate positively correlated with length of lesion (p < 0 05), but not with localisation, grade of calcification, or type of therapy. None of the patients died within 30 days of treatment.

1186

▾ Excimer 0 Nd-YAG P1A

TABLE IV-FOLLOW-UP DATA BY CLINICAL OUTCOME FOR ALL PATIENTS

Clinical improvement

Time

Clinical improvement cannot be assessed 2 days after the recanalisation procedure. However, ABI improved by at least 0-15 within 48 h in 15 patients (40 %) after excimer laser therapy, in 26 patients (65%) after Nd:YAG laser therapy, and in 26 patients (66%) after conventional PTA. After primary and secondary recanalisation, 89 of the 116 patients (77%) showed an improved ABI. Clinical improvement (relief from pain at rest, reduction in gangrene, or improvement of claudication by at least one stage) at 3 months was seen in 88 of 116 patients (76%).

Long-term results 3, 6, and 12 month long-term results based on clinical data and ABI were available for 103 (89%) of 116 patients; 94 (91 %) of the 103 were treated successfully. 13 patients were lost to follow-up (lack of cooperation or change of address). 7 patients died (2 cardiac failure, 3 myocardial infarction, 1 stroke, 1 cancer). Follow-up angiography within 14 months was done in 80 (69%) of 116 patients, and in 77 (75%) of the 103 successfully recanalised patients. 26 of those patients had no angiography because of clinically evident reocclusion (5 patients), death (6), lack of follow-up (8), amputation (1), refusal of angiography because of lack of symptoms (3), and less than 12 months’ follow-up (3). Details of clinical symptoms before treatment and

at

3, 6, and 12 months are

(mo)

Fig 2-long-term patency rates by therapy based on ABI of successfully recanalised patients (life-table analysis), Error bars= SE of patency rates; numbers at curves=% of patency

shown in table IV. 1 patient had below-knee amputation 4 weeks after unsuccessful treatment (0-9%), 13 patients had femoropopliteal bypass surgery after primary failure or reocclusion, and 8 patients had PTA of a recurrent stenosis at the site of recanalisation. Life-table analysis based on clinical symptoms revealed a 12-month patency rate of 64% (SE 13) for patients treated successfully with excimer-laser-assisted angioplasty, 70% (9) after successful Nd:YAG-laser-assisted angioplasty, and 71 % (9) after successful conventional PTA (fig 1). 12month patency rates from life-table analysis based on the ABI were 17% (15), 43% (9), and 38% (9) (fig 2). On angiography 32 patients had reocclusions, 14 restenosis ( > 70% or > 50% loss of gain), and 31 patency. Life-table analysis revealed a 12-month patency rate after successful primary recanalisation with excimer laser, Nd:YAG laser, and conventional PTA of 45% (14),36% (9), and 50% (9), respectively (fig 3). For short occlusions ( 8 cm) the angiographic 12-month patency rates were: excimer 50%, Nd:YAG 47%, and PTA 68%. For long occlusions (> 8 cm) laser-treated patients had better 12month patency rates (excimer 42%, Nd:YAG 24%) than did conventionally treated patients (PTA 12%).

▾ Excimer 0 Nd-YAG

▾ Examer

8PTA

0 Nd-YAG

0 PTA

v

.......

v

Time (mo)

....... J

1It:. L

0

3

b

9

12

rates

Time (mo) Fig 3-Angiographic long-term patency rates by therapy of successfully recanalised arteries (life-table analysis).

Error bars= SE of patency rates; numbers at curves=% of patency.

Error bars=SE of patency rates; numbers at curves=% of patency

by therapy based on clinical criteria of successfully recanalised patients (life-table analysis).

Fig 1-Long-term patency

1187

A Symptoms OABI

V Sogapy

Time (mo)

Fig 4-Long-term results of 116 patients referred for treatment, based

on

clinical criteria, ABI, and

angiography

(life-table analysis). Error bars= SE of patency rates; numbers at

curves = %

of patency.

The clinical patency rate for all patients referred for treatment was 60% (5) after 12 months (fig 4). The clinical patency rate was positively correlated to length of occlusion but was (Cox proportional hazard model, p<0-01) independent of the extent of calcification and run-off score. The ABI of all patients was 0-54 (SD 0 18) before

recanalisation, 0-82 (SD 0-20) 2 days after, and 0-74 (SD 023) after 12 months. Life-table analysis based on the ABI revealed a 12-month patency rate of 34% (SE 5%) (fig 4). Life-table analysis of all 116 patients based on the angiographic results revealed a 12-month patency rate of 39% (SE 5%) (fig 4). The angiographic patency rates were significantly influenced by the length of the occlusion (Cox proportional hazard model, p < 0003) but independent of calcification and run-off.

Discussion Restenosis

seriously limits long-term efficacy of

PTA.

One suggestion is that laser angioplasty might reduce the

rates

of 68-82% for thermal laser-assisted and conventional

angioplasty.25-27 To prove clinically the hypothesised superiority of laser angioplasty there was an obvious need for a randomised trial comparing pulsed and cw laser angioplasty with conventional PTA.28 In the present study the primary recanalisation rates of conventional PTA and Nd:YAG laser angioplasty (82% vs 78%) were almost identical and accorded with other published work.3no.s-z Because peripheral artery occlusions consist of both stenosing plaque and thrombotic material, guide-wire passage with subsequent balloon dilatation is usually possible. About 20% of peripheral artery occlusions are impenetrable for guide wires and balloons because of totally obstructing plaque tissue. However, these are patients who can be treated successfully by laser ablation. That Nd:YAGlaser-assisted angioplasty did not recanalise all obstructions (thrombotic or non-thrombotic) in this series can be explained by the stiffness and lack of steerability of laser catheters. Improved laser catheter technology will probably improve the ability to cross occluded arteries. The significant lower recanalisation rate of excimer-laserassisted angioplasty is more difficult to explain. The unfocused tissue destruction in front of the catheter and the mechanical shock waves due to explosive tissue vaporisation caused a significantly higher percentage of dissections which prevented successful recanalisation. The relatively low energy fluence of 45 to 60 mj/mm per pulse at the fibre tip caused slow recanalisation, another factor favouring the development of dissections due to mechanical advancement of the catheter. Finally, because we did not use an over-the-wire catheter system so as not to cause results of mixed techniques, the recanalisation rate of the excimer laser in the present study was less than that in other studies. The secondary recanalisation rate of 92% after combined guide wire passage and Nd:YAG laser recanalisation was impressive. Belli et ap6 reported a secondary recanalisation rate of 91 % of guide-wire/laser combination therapy. Thus, the sequence of guide-wire recanalisation first followed by Nd:YAG laser ablation when guide-wire recanalisation is unsuccessful seems to be the treatment of choice. Lesion length and calcification reduced the probability of successful recanalisation by all methods. These results suggest that calcified and long ( > 8 cm) femoropopliteal artery occlusions are not suitable for endovascular recanalisation

restenosis rate by producing a better lumen geometry, fewer a smoother inner surface of the artery.19 Whereas some studies have suggested that additional thermal destruction of smooth muscle cells may reduce the anatomic substrate for intimal proliferation,20,21 other laboratory investigations have reported an identical arterial response to mechanical and thermal laser angioplasty22 or increased intimal proliferation after laser recanalisation 23 Pulsed lasers such as the excimer laser cause less thermal injury but more fractures and dissections due to mechanical shock waves, which may cause intimal

rate of 68% after conventional PTA of short occlusions accords with the results of bypass surgery. 29-31 However, since recanalisation and patency rates ofendoluminal therapy in long occlusions (> 8 cm) decrease significantly, bypass surgery should be the preferred treatment if possible and if conservative therapy fails.

proliferation.22,24 Initial success rates of laser recanalisation of peripheral artery occlusions ranged from 72 to 85 % with cw lasers and

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Detection of premature atherosclerosis by

high-resolution ultrasonography in symptom-free hypopituitary adults

Retrospective analysis suggests that there is increased mortality from vascular disease in hypopituitary adults, but vascular status before death is unknown. High resolution B-mode ultrasonic imaging of both carotid and femoral arteries was therefore done in 34 adult hypopituitary patients on routine replacement therapy and was compared with that in 39 matched controls. Changes were related to risk factors for vascular disease. Carotid intima-media thickness was greater in patients than in controls (mean [SD] 0·74 [0·16] vs 0·65 [0·13] mm, p< 0·02). This difference was seen in middle-aged and elderly patients. More patients than controls had one or more atheromatous plaques (65% vs 41%, p < 0·05). The percentage of individual arteries with a plaque was also higher in patients (32% vs 18%, p<0·005). In multiple regression analysis, patients’ age was the dominant factor determining carotid intima-media thickness.

Symptom-free adults with hypopituitarism show an

increased prevalence of atherosclerosis. Lancet 1992; 340:1188-92.

Introduction

Retrospective studies from Sweden and Germany’ have shown that hypopituitary patients on routine replacement treatment have a higher mortality rate, mostly from vascular disorders, and higher life-time incidence of arteriosclerotic events than the general population. The cause of deaths from vascular disorders is uncertain, although growth hormone deficiency or endocrine replacement therapy may ADDRESSES: Unit of Metabolic Medicine (V. Markussis, Dip Med, S Beshyah, MRCP, D. G. Johnston, FRCP), and Irvine Laboratory (C Fisher, FRACS, A. N. Nicolaides, FRCS), Academic Surgical Unit, St Mary’s Hospital Medical School, London, UK; and Northwick Park Hospital, Harrow (P. Sharp, MRCP). Correspondence to Dr S A Beshyah, Unit of Metabolic Medicine, St Mary’s Hospital Medical School, London W2 1 PG, UK. A.