An elderly woman with hypercholesterolaemia but no symptoms

Coronary Health Care (1998) 2, 39~4 9 1998 Harcourt Brace & Co. Ltd

CLINICAL F O R U M

An elderly woman with hypercholesterolaemia but no symptoms E Vallely, G. J. Blauw*, R. G. J. Westendorp*, J. Shepherdt, C. G. Isles~ Senior Dietitian, Department of Dietetics, Royal Infirmary, Glasgow;*Consultant Geriatrician, Section of Gerontology and Geriatrics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands," "/'Professor of Biochemistry, Royal Infirmary, Glasgow," ~.Consultant Physician, Dumfries and Galloway Royal Infirmary, Dumfries, UK

(Department of Health 1992). Many recent studies have included the elderly and it would appear that they are just as likely to benefit from having a healthy balanced diet as their younger counterparts (4S 1994; Shepherd et al 1995). The main dietary goals for this case history are therefore to ensure that her diet does not contain a high proportion of fat, particularly saturated fat. This can be achieved by advising her to avoid flied foods and to use lower fat dairy products. She should also try to decrease her intake of fatty meats and the 'hidden' sources of fat, for example, cakes, pies and biscuits. She should be encouraged to include a variety of fruit and vegetables in her diet and to aim for 5 portions per day. Due to the anti-thrombotic effects of omega 3 fatty acids within oily fish, 2 portions per week would be considerable advisable. A reduction in salt intake is also recommended as part of the healthy guidelines. It is important to remember that, by making these changes, this lady may significantly decrease her calorie intake. This may compromise her health by causing her to become underweight which in old age will pose a far greater risk to health than being overweight (Caroline Walker Trust 1995). To avoid a calorie deficit she should be advised to include more complex carbohydrates such as bread and potatoes to ensure nutritional adequacy. As excess alcohol can be a contributory factor to raised triglycerides, a decrease in intake may be required. There is uncertainty as to the role of dietary calcium in the pathogenesis of osteoporosis. However, because there are few calcium-rich foods, the potential for elderly people to have low dietary calcium intakes is very real. The major source o f calcium in the diet is milk and milk products. It would therefore be prudent to encourage the older adult to try to include the equivalent of a pint of milk daily to achieve the recommended intake o f 700 mg of calcium per day (Department of Health 1992).

INTRODUCTION The Clinical Forum is intended to touch upon an area of medicine or nursing where controversy still exists and consensus has not yet been reached. The theme in our fifth issue concems the management of an elderly woman who was found to have a risky lipid profile at a screening examination. The opinions of a dietitian, two geriatricians and a biochemist were sought.

CASE HISTORY A 74-year-old woman who has always enjoyed good health attends her Practice Nurse for a check-up where she gives the following details. She is a never smoker with no personal or family history of vascular disease, though she freely admits she does not exercise to any great extent. She is not overweight and her blood pressure in the surgery is only 138/86 with normal urinalysis. On the basis of this assessment her Practice Nurse congratulated her on having a low risk of vascular disease. The patient, however, wanted a more detailed assessment and persuaded the nurse to check her blood lipids. A non-fasting cholesterol was then found to be 7.8 mmol/1 with triglycerides 3.2 and high-density lipoprotein (HDL) 0.9 mmol/1. Random blood glucose was 5.2 mmol/1. She was given advice on a healthy diet and review in three months when similar blood results were obtained.

EXPERT

OPINION

-

PAULA VALLELY

The nutritional recommendations for the older adult are essentially the same as for the younger population

Correspondenceto: Dr ChristopherIsles, Department of Medicine, Dumfries and GallowayRoyalInfirmary,Bankend Road, Dumfries DG[ 4AP, UK (Tel:+44 (0) 1387241501; Fax +44 (0) 1387241193) 39

40

Coronary Health Care

Problems can also arise due to p o o r dentition in the elderly. This can have an impact on food choice in that decayed or missing teeth or badly fitting dentures can prevent people from including foods that are harder to chew, such as some fresh fruits and vegetables. Poor dentition m a y therefore have an important effect on the nutritional status of the elderly (Scottish Diet 1993). This advice on healthy eating applies to the majority of older people. There will be some, however, who through being ill or frail will need to be encouraged to eat whatever they can. In these instances appetite stimulation is essential, and drastic reduction of fat and salt or over-enthusiastic inclusion of fruit and vegetables may be detrimental in improving dietary adequacy. FURTHER READING

Caroline Walker Trust 1995 Eating Well for Older People. Caroline Walker Trust, 6 Aldridge Road Villas, London Wl 1 1BP Department of Health 1992 The Nutrition of Elderly People. HMSO, London Report of a WorkingParty to the Chief Medical Officerfor Scotland 1993 The Scottish Diet. The Scottish Office,Edinburgh Scandinavian Simvastatin Survival Study Group 1994 Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383-1389 Shepherd J, Cobbe SM, Ford I et al for the West of Scotland Coronary Prevention Study Group 1995 Prevention of coronary heart disease with Pravastatin in men with hypercholesterolaemia.New England Journal of Medicine 333:1301-1307

Furthermore, they appear to have a beneficial effect on the occurrence of stroke, even though total cholesterol is not a risk factor for cerebrovascular disease (Blauw et al 1997). These results suggest that statins have a favourable effect on cardiovascular disease independent of their cholesterol-lowering capacity and may indicate that cholesterol lowering with statins could be efficacious in older age. However, the latter has still to be established from the results of forthcoming clinical trials with statins in elderly subjects. To date, there is hardly any need to measure plasma cholesterol levels in subjects above the age of 70 years. At this age, high cholesterol levels are p o o r discriminators of cardiovascular risk whereas the efficacy of cholesterol-lowering therapy among this age group is not established yet. The cholesterol measurement of this ever-healthy 74-year-old woman illustrates the problems physicians face when such investigations are performed. It may change an independent woman into a patient who fears cardiovascular disease. REFERENCES

Blauw GJ, Lagaay AM, Smelt AHM, Westendorp RG 1997 Stroke, statins and cholesterol. A meta-analysisof randomised, placebo controlled, double blind trials with HMG-CoA reductase inhibitors. Stroke 28:946-950 Weverling-RijnsburgerAWE, Blauw GJ, Lagaay AM, Knook DL, Meinders AE, Westendorp RGJ 1997 Total cholesterol and risk of mortality in the oldest old. Lancet 350:1119-1123

EXPERT EXPERT

OPINION

- GERARD

BLAUW

AND

RUDI WESTENDORP

It is beyond doubt that high cholesterol in plasma challenges a healthy life in middle age. In line with the epidemiological data, various clinical trials have convincingly shown that a new class of cholesterol-lowering drugs, the so-called 'statins', reduces mortality and morbidity from cardiovascular disease by at least 30%. However, the 74-year-old w o m a n presented here does not fit into the classic epidemiological observations, nor into the profile of the subjects who participated in the clinical trials. Above the age of 70 years, the impact of high serum cholesterol as a risk factor of cardiovascular disease is controversial. Above the age of 85 years, the relation between total cholesterol and mortality is even reversed, i.e. high cholesterol is associated with longevity (Weverling Rijnsburger et al 1997). In contrast to these observational data, the experimental data on the effect of cholesterol lowering in elderly subjects are scarce. The favourable results of cholesterol lowering with 'statins' are predominantly obtained a m o n g male subjects younger than 70 years. F r o m the above-mentioned clinical trials, it has become apparent that the efficacy of the statins is largely independent of the basal cholesterol level.

OPINION

- JIM SHEPHERD

In general terms, this lady is remarkably healthy for her age, being a non-obese, normotensive non-smoker with normal urinalysis. In considering her risk of vascular disease we must focus on her plasma lipid abnormality. A total cholesterol concentration of 7.8 mmol/1 is unusual even for a w o m a n of 74. Based on the Lipid Research Clinic's population survey in the USA, her expected total cholesterol would be 5.9 mmolll; her value even exceeds the 95th percentile of 7.5 mmol/1 (Rifkind & Segal 1983). Detailed lipoprotein analysis reveals that her lipid abnormality is not confined to a raised total cholesterol alone. She also has a raised plasma triglyceride and a low H D L cholesterol. Her low-density lipoprotein (LDL) cholesterol, although not measured, may be calculated using the formula of Friedewald shown below: LDL cholesterol (mmol/1) = total cholesterol - HDL cholesterol - 0.45 x triglyceride (mmol/1). The accuracy with which the L D L cholesterol is estimated using this formula is relatively p o o r due to the summation of different analytical errors, but it does provide some useful information. It is important to note, however, that the Friedeweld formula should not be used if the plasma triglyceride is greater than 4.0 mmol/1. In this lady's case, her calculated L D L cholesterol is significantly elevated at 5.5mmol/1

Clinical Forum (acceptable range 2.5-4.0mmol/1, optimal range 2.0-3.3mmol/1). This, together with her elevated triglyceride, would indicate a combined hyperlipidaemia, and would suggest that the L D L particles present in the circulation will be small and dense and susceptible to oxidation making them even more atherogenic. The low level of H D L cholesterol is also relevant since women with this lipid abnormality and a raised plasma triglyceride level have a propensity for atherosclerosis (Assmann & Schulte 1992). It is important to exclude secondary forms of hyperlipidemia before considering the management of an aberrant lipid profile. The most common causes of secondary dyslipidaemia are diabetes mellitus, hypothyroidism, renal disease and alcohol abuse. This lady's random blood glucose does not suggest diabetes and her normal urinalysis would exclude gross renal disease. It would be useful to test her thyroid function as hypothyroidism is notoriously difficult to diagnose clinically, and her alcohol intake should be recorded. Assuming that this lady's hyperlipidaemia is primary, the question of management must first incorporate consideration of diet and lifestyle. These are important management strategies that should never be overlooked (Ornish et al 1990). The question of whether this lady should be offered lipid-lowering drug therapy is most usefully addressed by considering her global risk. The Joint Guidelines of the European Societies of Hypertension and Cardiology and the European Atherosclerosis Society provide a useful risk assessment chart for this purpose (Pyorala et al 1994). Using this chart this lady's risk of a major coronary event over the next 10 years may be calculated at 10-20%, i.e. moderate. Using these criteria, she would not be a candidate for drug therapy at this point and her management should emphasize nonpharmacological therapy. Appropriate exercise advice may be very beneficial to this lady (Berlin & Colditz 1990), raising her H D L cholesterol level and perhaps reducing her triglyceride level. Her diet should be assessed and guidance should be given, if necessary paying particular attention to alcohol intake. REFERENCES

Assman G, SchulteH 1992 Relation of high density lipoprotein cholesteroland triglycerideto incidenceof atherosclerotic coronary artery disease (the PROCAM experience).American Journal of Cardiology70:733-737 Berlin JA, Colditz GA 1990A meta-analysisof physical activity in the preventionof coronary heart disease. AmericanJournal of Epidemiology 132:612-628 Ornish D, Brown SE, ScherwitzLW et al 1990Can lifestyle changes reversecoronary heart disease?The lifestylesheart trial. Lancet 336:129-133 Pyorala K, De BackerG, Graham I, Poole-WilsonP, Wood D 1994Preventionof coronary heart disease in clinical practice. Recommendations of the Task Force of the European Society of Cardiology,European AtherosclerosisSocietyand European Societyof Hypertension.European Heart Journal 15:1300-1331 Rifkind BM, SegalP 1983Lipid Research Clinics Program referencevalues for hyperlipidemiaand hypolipidemia. Journal of the American Medical Association250:1869-1872

COMMENTARY

- CHRISTOPHER

41

ISLES

My first thought on reading this case history was to wish that the nurse had not yielded to the patient's desire to have her lipids checked. This is because measurement of lipids in asymptomatic men and women over 70 years is currently of uncertain value. Such practice cannot therefore be recommended routinely in this age group. Let us start with the epidemiology. Smoking, cholesterol, blood pressure, physical inactivity and diabetes all predict death from coronary heart disease (CHD) in older people (Abrams 1995) with the following necessary qualifications. Relative risk declines with age while attributable risk (the amount by which C H D would be reduced if the risk factor was not present) is increased, simply because C H D is so much more common in the elderly. This point is important when considering treatment of hyperlipidaemia (and hypertension) in the elderly, because it implies that they m a y have just as much to gain by treatment as younger subjects. The observation by Drs Blauw and Westendorp that high serum total cholesterol is associated with longevity in a predominantly female population over 85 years of age in Leiden is an interesting one (Weverling-Rijnsburger et al 1997). There was no relationship between cholesterol and death from cardiovascular disease in this cohort, but a distinct excess mortality from cancer and infectious disease was observed among men and women whose total cholesterol was less than 6.5 mmol/1. A negative association between cholesterol and non-cardiovascular mortality has been noted in other studies (Isles et al 1989). Part of the explanation is that people who are about to die of cancer drop their serum cholesterol (i.e. the low cholesterol is a consequence of the cancer). Other aspects of this association remain incompletely understood. A further difficulty for the clinician is that the cholesterol-lowering drug trials have provided us with only limited data on the benefits of therapy in older subjects. The secondary prevention studies, 4S, CARE and LIPID, randomized around 6000 subjects with pre-existing C H D aged 60-75 years and showed similar benefits when compared to younger patients (4S 1994, Sacks et al 1996, Tonkin 1997). By contrast, the oldest subject in WOSS, a primary prevention study (Shepherd et al 1995) was 65 years at entry to the trial. Risks and benefits of WOSS subjects aged 55-64 were greater than those aged 45-54 years (WOSS 1996). We have good evidence therefore on the benefits of treatment of hypercholesterolaemia for men with no clinical evidence of C H D up to the age of 65 years, and for hypercholesterolaemic men and women with symptomatic C H D up to the age of 70-75 years, but we are clearly short of data on elderly asymptomatic women with hypercholesterolaemia. Paula Vallely makes the case for dietary advice in the elderly and concludes from her review of the

42

CoronaryHealth Care

No D i a b e t e s Non-smoker

Diabetes Non-smoker Smoker

Smoker

Total Cho] :HDL-Chol

Total Chol. :HDL-Chol 4 5 6 7 8

4 5 6 7 8

4 5 6 7 8

180/105 160195 140/85 120175

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120175

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I-I I;:;~::f41 Key to Risk T a b l e s Prognosis:

5yr CVD risk (non-fatal & fatal) >20~ !

Benefit 1:

CVD events prevented per 100 treated for 5 y r s *

Benefit 2:

> T p e r 100

<15

NNT for 5 y r s *

15- 20~ 1~___= 6?_e.r._t0_9- . . . . . . . . . . . . . . . . . -2_0... 1 O- 1 5 ~ ~ = 4 per" 1O0 5 - 10% I?i:)l -'-='-2-g'DerT0i?- . . . . . . . . . . . . . . . 2.5- 5 ~ N - - =~ 1.25 per 1O0

<2.5% L.J

<0.8per 100

s~

starting

= 25 P--b point for discussion "~40--" with patient about = 80 drug treatment.

>120

* assumes BP reduction of about 10-12 I 5 - 6 mmHg in patients with BP > 140-150 / 90, or cholesterol reduction of about 20~ in patients with total cholesterol > 5.0-5.5 mmol/L, produces an approximate 1/3 reduction in CVD risk, whatever the pro-treatment absolute risk o cells with this marker indicate that in patients ~#ith vet9 high levels of cholesterol (> about 8.5-9 mmo]lL) or blood pressure (> about 170-180 t 100-105 mmHg), the risk equations may underestimate the true risk. T h e r e f o r e i t is re 9 that treatme.t considered at l o v e r absolute CYI) r i s k l e v o l s than in o t h e r p a t i e n t s .

Fig. (A)

be

Risk-assessment f o r m for m e n (National Health Committee 1997).

literature that this should be essentially the same as for younger adults. Sensibly, she also cautions against evangelical dietary measures in the frail elderly. The next priority here is to calculate this patient's risk of a major vascular event before deciding whether treatment should be dietary alone or dietary with drugs. Professor Shepherd recommends the use of a risk chart prepared jointly by the European Society of Hypertension, European Society of Cardiology and European Atherosclerosis Society and estimates that the patient's risk of a major coronary event is 10-20% at ten years. An even more user-friendly form of risk assessment, devised in New Zealand, has recently been punished (National Health Committee 1997). This estimates the five-year risk of new angina, myocardial infarction, C H D death, stroke or tran-

sient ischaemic attack according to age, gender, smoking habit, diabetic status, blood pressure and total cholesterol/HDL ratio (Fig.). Keying in the risk profile of the patient in our case history, we find that a woman aged 74 who is a nonsmoker with normal glucose tolerance, blood pressure 138/86 and total cholesterol/HDL ratio 8.7 has a five-year event risk of 10-15%. The New Zealand estimate of risk is slightly higher than that given by the European Guidelines simply because all cardiovascular events and not just major coronary events are included. If our patient had also had a strong family history of premature vascular disease or been morbidly obese with body mass index > 30, then the New Zealand guideline would recommend an increase of one risk category. The guideline goes on to

Clinical Forum

No Diabetes Non-smoker

180/105 160/95 140/85 120/75

Diabetes

Smoker

Non-smoker

T o t a l Chol. : H D L - C h o l 4 5 6 7 8 4 5 6 7 8

T o t a l Choi. 4 5 6 7 8

Smoker :HDL-Chol 4 5 6 7 8

I

I...~::i::?:~iiii::llii::iili.iiiit

180/105 4) 160195 t"~ 140185 t~ tn 120/75 4~ i. 180/105 Q. "O 160195 O 14 0 / 8 5 120/75 IO 113 1801105 160/95 140/85 120/75

43

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Key to Risk Tables Prognosis: 5 y r CYD risk ( non-fatal & fetal)

Benefit 1 : CYD events prevented per ! 00 treated for 5 tjrs*

>20~I 1 5- 2 0 ~

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= l . Z S p e r 100 < 0 . 8 p e r 100

=80 >120

* assumes BP reduction of about ! O- 12 / 5-6 rnmHcjka patients ~ith BP > 140-150 / 90, o r cholesterol reduction of about 20~ in patkbnts with total cholesterol > 5.0-5.5 retool/L, produces an approximate 113 reduction ~ CVD risk, ~whateverthe we-treatment absolute risk. 9 oells ,with this m~'ker indicate that in patients ~ith vertj high levels of cholesterol (~ about 8.5-9 retool/L) or blood pressure (> about 170-1813 / 1130-105 mml-kj), the risk equations may underestimate the true risk. Tlierefer@ it is reeeisme 9 that t r e a t i e l s t be coastdered at l e v e r a l ~ o l l t e C~q~ r i s k l t v e l s ~ ~ other p a t o i s .

Fig. (]3) Risk-assessment form for women (National Health Committee 1997).

make the assumption that a 20% reduction in total cholesterol (which is what you would expect with a statin) will yield a 33% fall in cardiovascular risk (this approximates to the benefits seen in the West of Scotland Study). It is then an easy task to calculate both the expected absolute benefits of treatment and the number needed to treat for five years to save or delay one event (this is the reciprocal of the absolute risk reduction). The number needed to treat in this particular instance is 25. So what happened to our patient? Thyroid function tests confirmed her euthyroid status. We explained that her risk of a cardiovascular event was 10-15% over five years, recommended a healthy diet and advised that

she continued without drugs. She announced at this point that she was not keen on the idea of taking drugs anyway! Three years later she remains alive and well with no symptoms to suggest CHD. Perhaps most importantly, we have managed to persuade her that further measurements of cholesterol are unnecessary as they are unlikely to influence future management. In summary, the case we have chosen for this Clinical Forum highlights a number o f issues including screening, dietary advice, risk assessment and drug therapy for elderly patients with hyperlipidaemia. It also reminds us that our knowledge of the management of hypercholesterolaemia in asymptomatic elderly women remains incomplete.

44

Coronary Health Care

REFERENCES

Abrams J, Vela SB, Coultas DB, Samaan SA, Malhotra D, Roche RJ 1995 Coronary risk factors and their modification: lipids, smoking, hypertension, oestrogen and the elderly. Current Problems in Cardiology 20:533 612 Isles CG, Hole D J, Gillis CR, Hawthorne VM, Lever AF 1989 Plasma cholesterol, coronary heart disease and cancer in the Renfrew and Paisley Survey. British Medical Journal 298: 920-924 National Health Committee 1997 Guidelines for the management of mildly raised blood pressure in New Zealand. Ministry of Health, PO Box 5013, Wellington, New Zealand (ISBN 0-477-01740-1) Sacks FM, Pfeffer MA, Maye LA et al 1996 The effect of Pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. New England Journal of Medicine 335:1001-1009 Scandinavian Simvastatin Survival Study Group 1994

Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 344:1383-1389 Shepherd J, Cobbe SM, Ford I e t al for the West of Scotland Coronary Prevention Study Group 1995 Prevention of coronary heart disease with Pravastatin in men with hypercholesterolaemia. New England Journal of Medicine 333:1301 1307 Tonkin A 1997 Late breaking clinical trials: LIPID. Program, 70th Scientific Sessions, American Heart Association, November 9th-12th, Orlando, Florida, 629 West of Scotland Coronary Prevention Group 1996 West of Scotland Coronary Prevention Study: Identification of high risk groups and comparison with other cardiovascular intervention trials. Lancet 348:1339-1442 Weverling-Rijnsburger AWE, Blauw GT, Lagaay AM, Knook DL, Meinders AE, Westendorp RGJ 1997 Total cholesterol and risk of mortality in the oldest old. Lancet 350:1119-1123