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EDITORIALS

Magnetic resonance and therevival of arterial sclerosis

The disease of atherosis was noted in the 1850s,1 but itwas not until 1904 that Marchand recognised theassociation between fatty degeneration of the arteriesand stiffening of the arterial wall and introduced theterm atherosclerosis.2 Since then the fatty componentof the disease (atherosis) has been extensivelyinvestigated, but less attention has been paid to thesclerosis. The elasticity or compliance of an artery isdetermined by the relative amounts of elastin, smoothmuscle, and collagen in the wall; sclerosis arises fromstructural changes, which include loss of elastin and anincrease in collagen.3 Endothelium-derived relaxingfactor (nitric oxide) may also have a dynamic effect.4 4

Although sclerosis is usually widespread and notnecessarily localised to areas of atherosis, both

components of the disease are closely linked and areadversely affected by hypercholesterolaemia,hypertension, and diabetes.The reversibility of atherosis has been shown in

several studies.s Reversal of coronary atherosis hasbeen confirmed in animals6’ but is more difficult toestablish in man. Lesions in the peripheral circulation8and the coronary arteries9 progress less rapidly aftertreatment of hyperlipidaemia, and regression has alsobeen documented.l° Regression is more readilyachieved in early lesions,l1 so early detection andtreatment are important. Nevertheless, atherosis willusually be well advanced before it has a significanteffect on arterial flow or flow reserve, and manypatients present well before this stage with suddendeath from thrombosis superimposed on an active andfissured plaque that is not necessarily flow-limiting.12For this reason, strategies that rely on the detection ofsclerosis may be better suited to identification of

patients at a stage of the disease when reversal of riskfactors could be beneficial.Two reports have lately focused attention on the

ability of magnetic resonance imaging to detect andquantify arterial sclerosis. Behling and colleagues13estimated the compliance of the carotid arteries

(approximately 0-7 mm diameter) of anaesthetised ratsfrom measurements of the cross-sectional area of thearteries at end-diastole and end-systole, and the pulsepressure that distended them. Although dataacquisition to image such small vessels took 5 hours,

these researchers suggested that compliance in humanarteries as small as 3 mm might be measured.Mohiaddin and co-workers used the same method tomeasure regional aortic compliance in man14 and theyalso showed that the lipid content of atheroma couldbe measured with magnetic resonance imaging."Thus, both components of atherosclerosis can beassessed with one technique. That normal aortic

compliance falls with increasing age and with

increasing distance down the aorta is not a new

finding, 16 but Mohiaddin et al also showed that

compliance was abnormally high in athletes and

abnormally low in patients with coronary arterydisease. Over the age of 50 there was overlap betweencompliance in normal volunteers and patients withcoronary disease; below this age there was less overlap,which suggests that compliance might be used as ascreening test for the presence of disease and also tomonitor progression or regression.The velocity at which either the flow or the pressure

wave is propagated along an artery is closely related tocompliance. The flow-wave velocity can be measuredby doppler ultrasound17 or by magnetic resonancevelocity mapping,18 and these techniques provideanother way of assessing arteriosclerosis. Neitherflow-wave velocity nor compliance can be determinedby magnetic resonance in the coronary arteriesbecause of their small size and rapid motion; wideravailability of real-time echo planar imaging mayovercome these difficulties.’9o By contrast, theaorta is an ideal target because it is easy to image andbecause fatty streaks in this vessel progress to raisedlesions at the same place as those in the coronaryarteries.The clinical effects of sclerosis are subtle and we do

not know whether it affects tissue perfusion in thesame way as does a flow-limiting atheroma. 21Variations in compliance along an artery can lead toconnective tissue overgrowth,23 so changes in localcompliance might influence disease progression. Theobservation that normal coronary arteries dilate in

response to increased flow to limit the shear stress onthe walls may be relevant in this context.24

Impairment of this defence mechanism may add to theshear stress that arises from increased velocities over astenotic atheromatous plaque and further damage theendothelium. Arterial sclerosis can influence other

organs. Aortic compliance is an important component

140

of left ventricular afterload and reduced compliancewill not only increase myocardial oxygen demand butmay also reduce oxygen supply through its effect onthe normal aortic diastolic backflow that aids coronaryperfusion.25-27 Similarly, reduced puhnonary arterialcompliance may be a factor in the onset of right heartfailure in patients with chronic lung disease. 28Persistent systolic hypertension following surgicalrepair of aortic coarctation may be the result of morewidespread structural changes in the aorta.29

If arterial sclerosis can be detected and monitored

by means of magnetic resonance, is there any evidencethat abnormalities can be reversed in the same waythat atherosis can be reversed? Regression of fibrousplaques has been shown in rabbits,3° but reversal ofsclerosis in man is less well studied. In cholesterol-fed

monkeys sclerosis regresses in parallel with

atherosis,31,32 although alterations in medialarchitecture may persist.As a safe and non-invasive technique, magnetic

resonance imaging has already contributed to theassessment of many diseases. Its role in the detectionand assessment of atherosclerotic vascular diseaseremains to be established, but measurements ofarterial sclerosis are simple and robust, and theyappear to be ideal for longitudinal studies of theprogression and even the regression of disease.

1. Virchow R. Phlogose und Thrombose im Gefaßsystem. Gesammelteabhandlungen zur Wissenschaftlichen Medicin. Frankfurt: MeidingerSohn, 1856: 458.

2. Aschoff L. In: Cowdry EV, ed. Arteriosclerosis: a survey of the problem.New York: MacMillan, 1933: 1-8.

3. Roach MR, Burton AC. The reason for the shape of the distensibilitycurves of arteries. Can J Biochem Physiol 1957; 35: 681-90.

4. Griffith TM, Lewis MJ, Newby AC, Henderson AH. Endothelium-derived relaxation factor. JACC 1988; 12: 797-806.

5. Blankenhom DH, Kramsch DM. Reversal of atherosis and sclerosis.Circulation 1989; 79: 1-7.

6. Armstrong ML, Warner ED, Connor WE. Regression of coronaryatheromatosis in rhesus monkeys. Circ Res 1970; 27: 59-67.

7. Armstrong ML, Megan MB. Lipid depletion in atheromatous coronaryarteries in rhesus monkeys after regression diets. Circ Res 1972; 30:675-80.

8. Duffield RGM, Lewis B, Miller NE Jamieson CW, Brunt JNH,Colchester ACF. Treatment of hyperlipidaemia retards progression ofsymptomatic femoral atherosclerosis: a randomised controlled trial.Lancet 1983; ii: 639-42.

9. Brensike JF, Levy RI, Kelsey SF, et al. Effects of therapy withcholestyramine on progression of coronary arteriosclerosis: results ofthe NHLBI Type II Coronary Intervention Study. Circulation 1984;69: 313-24.

10. Blankenhom DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP,Cashin-Hemphill L. Beneficial effects of combined colestipol-niacintherapy on coronary atherosclerosis and coronary venous bypass grafts.JAMA 1987; 257: 3233-40.

11. Stary HC. Progression and regression of experimental atherosclerosis inrhesus monkeys. In: Goldsmith EF, Morr-Hankowsky J, eds. Medicalprimatology. Basel: Karger, 1972: 356-67.

12. Hackett D, Davies G, Maseri A. Pre-existing coronary stenoses inpatients with first myocardial infarction are not necessarily severe. EurHeart J 1988; 9: 1317-23.

13. Behling RW, Tubbs HK, Cockman MD, Jelinski LW. StroboscopicNMR microscopy of the carotid artery. Nature 1989; 341: 321-23.

14. Mohiaddin RH, Underwood SR, Bogren HG, et al. Regional aorticcompliance studied by magnetic resonance imaging: the effects of age,training, and coronary artery disease. Br Heart J 1989; 62: 90-96.

15. Mohiaddin RH, Firmin DN, Underwood SR, et al. Chemical shift

magnetic resonance imaging of human atheroma. Br Heart J 1989; 62:81-89.

16. Learoyd BM, Taylor MG. Alterations with age m the viscoelasticproperties of human arterial walls. Circ Res 1966; 18: 278-92.

17. Caro CG, Fish PJ, Goss DE. Effect of isosorbide dinitrate on arterialhaemodynamics in man. J Physiol 1985; 365: 93P.

18. Mohiaddin RH, Longmore DB. MRI studies in atherosclerotic vasculardisease: structural evaluation and physiological measurements. Br MedBull 1989; 45: 968-90.

19. Stehling M, Howseman A, Chapman B, et al. Real-time NMR imaging ofcoronary vessels. Lancet 1987; ii: 964-65.

20. Firmin DN, Klipstein RH, Hounsfield GN, Longmore DB. Echo-planarhigh resolution flow velocity mapping. Proceedings of the seventhannual meeting of the Society of Magnetic Resonance in Medicine,Berkeley, 1988: 122 (abstr).

21. Atherosclerosis of the aorta and coronary arteries in five towns. BullWHO 1976; 53: 485-645.

22. Pickering G. Arteriosclerosis and atherosclerosis: the need for clearthinking. Am J Med 1963; 34: 7-18.

23. Hasson JE, Megerman J, Abbott WM. Increased compliance nearvascular anastomoses. J Vasc Surg 1985; 2: 419-23.

24. Vita JA, Treasure CB, Ganz P, Cox DA, Fish RD, Selwyn AP. Control ofshear stress in the epicardial coronary arteries of humans: impairmentby atherosclerosis. JACC 1989; 14: 1193-99.

25. Klipstein RH, Firmin DN, Underwood SR, Rees RSO, Longmore DB.Blood flow patterns in the human aorta studied by magnetic resonance.Br Heart J 1987; 58: 316-23.

26. Bogren HG, Klipstein RH, Firmin DN, et al. Quantitation of antegradeand retrograde blood flow in the human aorta by magnetic resonance.Am Heart J 1989; 117: 1214-22.

27. Bogren HG, Mohiaddin RH, Klipstein RH, et al. The function of theaorta in ischemic heart disease: a magnetic resonance and angiographicstudy of aortic compliance and blood flow patterns. Am Heart J 1989;118: 234-37.

28. Bogren HG, Klipstein RH, Mohiaddin RH, et al. Pulmonary arterydistensibility and blood flow patterns: a magnetic resonance study ofnormal subjects and of patients with pulmonary arterial hypertension.Am Heart J 1987; 118: 990-99.

29. Rees RSO, Somerville J, Ward C, et al. Magnetic resonance imaging inthe late postoperative assessment of coarctation of the aorta. Radiology1989; 173: 499-502.

30. Kramsch DM. Calcium antagonists and atherosclerosis. In: KritchevskyD, Holmes WL, Paoletti R, eds. Drugs affecting lipid metabolismVIII. London: Plenum, 1985: 323-47.

31. Farrar DJ, Bond MG, Sawyer JK, Green HD. Pulse wave velocity andmorphological changes associated with early atherosclerosis

progression in the aortas of cynomolgus monkeys. Cardiovasc Res 1984;18: 107-18.

32. Farrar DJ, Green HD, Wagner WD, Bond MG. Reduction in pulse wavevelocity and improvement of aortic distensibility accompanyingregression of atherosclerosis in the rhesus monkey. Circ Res 1980; 47:425-32.

WHAT’S UP WITH THE ENZYMES?

Patients with persistently raised liver enzymes are

frequently encountered in clinical practice; such increasesare also found in symptom-free individuals during blooddonation or routine health checks. What is the nature of theliver disease and how many of these lesions are treatable?Will non-invasive tests help, or is a liver biopsy required inevery case? These issues have now been addressed in two

studies, from Sweden,l and Bethesda, Maryland.2 Thecommonest abnormality was fatty liver, in 21-63% of cases.Other disorders included non-cirrhotic alcoholic liverdisease (18%), chronic active (viral) hepatitis (10-20%);chronic persistent hepatitis (10%); cirrhosis (6-9%);haemochromatosis (3%); granulomatous liver disease

(2-4%); and autoimmune liver disease (2-3%). Drug-induced hepatitis was rare.An accurate diagnosis is essential to establish the

prognosis, but the main aim is to identify disorders forwhich there are treatments of proven value---g,haemochromatosis, Wilson’s disease, severe autoimmunechronic active hepatitis, and tuberculous liver disease.3 VanNess and Diehl2 found that only 18 % of their cohort fell intothese categories, but their patients were not offered any ofthe promising, if still experimental, treatments now