European Heart Journal (1992) 13 (Supplement H), 50-53
Lipid screening in aircrew: pros and cons A. KEECH AND P. SLEIGHT
Clinical Trial Service Unit and Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, U.K. KEY WORDS: Aircrew licensing, aviation, lipids, risk screening, national policies, prevention, trials evidence, cholesterol lowering drugs, diet. Introduction
Although aircrew are likely to have a lower risk of coronary heart disease (CHD) than the general population on account of age, social class and lower cigarette consumption, they are not immune. Autopsies on 275 young men who died of trauma (mean age 28-3 years, and including 180 pilots) showed that 25% had at least one coronary artery with greater than 50% obstruction"1. On the other hand, medical standards and pilot incaparitation training have contributed to an extremely low rate of aircraft accidents due to ischaemic heart disease121. Against this background there may be no obvious need to consider risk factor intervention based on blood lipid screening except perhaps for the identification of those few individuals with familial hypercholesterolaemia (FH), where the risk of early myocardial infarction is exceptionally high'31. On the grounds both of passenger safety, notably of single crew aircraft, and also of airline economics, it might be justifiable to screen applicants for aircrew training or employment for FH. It is also rational (on economic grounds) to screen entrants to identify those at higher risk of premature ischaemic heart disease from raised lipids, particularly when associated with other risk factors (hypertension, family history, smoking, central obesity, lack of exercise). Joy has recorded an annual loss rate of U.K. professional flying licences of 1 -5/1000 pilots (mean age 48 years) from ischaemic heart disease, discovered on routine screening*41, an economic loss both to the pilot and his employer. This review will deal with the evidence linking lifestyle, cholesterol and coronary heart disease risk. We will also discuss whether lifestyle changes will reduce risk and whether drug treatment of hyperlipidaemia might adversely affect aircrew during their duties.
density lipoprotein (LDL) receptor leading to FH, and can importantly determine CHD risk'8-91. The relationship of cholesterol levels and CHD
The epidemiological studies provide overwhelming evidence of a strongly positive plasma cholesterol-CHD relationship, documented in both between-population'101 and within-population'"'121 studies. They also show that the relationship is continuous, and with no threshold among Western nations below which a lower cholesterol does not confer a lower risk of CHD. A recent long-term study of urban Chinese extends the graded positive relationship down to levels of cholesterol (about 3-8^-7 mmol. T 1 ) below those commonly found in Western populations, suggesting that biologically normal cholesterol levels (as opposed to Western average levels) may be more like those of the Chinese, with lower risk of CHD eventually coming from sub-Western levels of cholesterol'131. The largest within-population study of cholesterol and outcome, the Multiple Risk Factor Intervention Trial (MRFIT) followed 356 222 men for at least 6 years, and provided powerful evidence of the continuous nature of the relationship. It also drew attention to the importance of CHD risk depending not on the cholesterol level in isolation, but on multiple factors which together determine the probability of a CHD event'"1. Age, gender, blood pressure and smoking status (amongst other things) all, together with cholesterol, influence the probability of a CHD event (see Fig. 1). The British Regional Heart Survey has also shown that, although risk assessment is not highly specific, three out of everyfivecoronary events occurred in those at highest risk'141. Can attention to cholesterol alter CHD risk?
Determinants of cholesterol levels in the plasma
Cholesterol levels in the plasma are determined both by diet and by genetic factors. A high percentage of calories taken as saturated fat, and excess total calorie intake (with consequent obesity) are the chief dietary factors'561. Migrants can rapidly assume the diet, plasma cholesterol, and CHD pattern of their host country171. Genetic factors also modulate cholesterol level, via defects in the low Correspondence. Anthony Keech, Clinical Trial Service Unit, University of Oxford, Harkness Building, Radcliffe Infirmary, Oxford OX2 6HE, U.K. 0195-668X/92/0H0050 + 04 S08.00/0
More than 20 clinical end-point trials testing dietary change or (one or more) drug therapies to lower serum cholesterol have been conducted over the last 20 years. An overview of published and unpublished randomized studies of cholesterol lowering (R. Peto, personal communication, 1990) shows a highly significant reduction in CHD events (a 10% lowering of cholesterol for only 2 years on average resulting in a 16%+ 3 reduction in all CHD events; 2/'90. cancer1'9'. and duration of cholesterol reduction. However, to date the cholesterol reductions achieved have been small (average around 10%), and for only a short duration (average only 1-3 years for those suffering a CHD event), with often low rates of CHD, and with CHD only contributing to a minority of all deaths. Thus it is not unexpected that even collectively these studies have little power to test reliably whether or not small reductions in CHD will lead to reduced total mortality. Possible adverse effects of lipid lowering
Despite this lack of power, Muldoon et a/.'151 and Oliver1'6' have raised the question of whether the clear benefit of lipid lowering with regard to coronary heart disease is offset by adverse effects on other conditions so that total mortality is not reduced. Meta-analysis of all the unconfounded cholesterol lowering trials has shown no significant effect on total mortality. It is important to understand that this is not the same as proof that there is no effect. It can be calculated that the reduction in CHD mortality observed in the trials should result in a 6% fall in total mortality (since people also die of other conditions). The observed 3% fall in total mortality in the trials, although not statistically significant, is compatible with the 6% expected (R. Peto, personal communication, 1990). Until large cholesterol differences (such as those now achievable with the HMG Coenzyme A reductase inhibitors'171 and the new fibrates) can be tested long-term in subjects where CHD event rates are high, and represent a high proportion of all fatalities, we will not have adequate power to demonstrate effects on total mortality in trials of realistic size. For example, consider the 15% reduction in odds of coronary mortality seen over 5 years in the Muldoon overview of primary prevention trials'131 with the CHD/non-CHD death rates (approximately 1-5% and 31%) observed. To test reliably (i.e. with 90% power) for a conventionally significant (2/" < 0-05)
Morbidity of lowering cholesterol
Some cholesterol lowering regimes such as diet are largely free from side-effects, and may confer other benefits (such as anti-platelet effects offish consumption, anti-oxidant activity of various vitamins, and, together with exercise and the cessation of smoking, elevation of the protective'201 high density lipoprotein cholesterol fraction). The resins such as cholestyramine may not be acceptable to all (aircrew) because of side-effects such as colic or increased bowel frequency. Likewise niacin causes flushing and gastro-intestinal symptoms. Both the fibrates and the statins, apart from rare muscle cramps with raised creatinine kinase and, with the fibrates, occasional gastro-intestinal upset, appear remarkably well tolerated and should not cause problems for aircrew. Identifying lipid risks
On the balance of current evidence it is appropriate to recommend lipid measurement in aircrew at initial entry and thereafter as required, with advice to encourage life-style modification. Drug treatment should be indicated where relevant. Risk factor reduction is the one therapeutic option to reduce the toll from sudden cardiac death, since almost half of community deaths from CHD occur without any medical presence or intervention'21' and neither thrombolysis nor cardiac care units can affect these deaths. In the Second U.K.. Workshop in Aviation Cardiology, Chamberlain'22-23' reviewed the preventive measures taken by individual airlines. Lipids did not figure strongly then, although one airline did measure lipids and give their aircrew a personal multiple risk assessment. As opposed to individual airlines, the current attitudes (1991) of some licensing authorities are given in Table 1. As can be seen, there is no uniform policy yet in the lipid screening of
52 A.KeechandP.Sleight Table 1 Some current* national Civil Aviation regulatory agency licensing practices in relation to blood lipids Published guidelines in relation to serum cholesterol^
Country United Kingdom
no guidelines or limitations
United States124'
no guidelines or limitations
France1251
cholesterol measure required at admission, every 5 years up to 40 years of age, then every 2 years; no target levels stated
Germany
if cholesterol is measured (compulsory in setting of some risk situations e.g. Type II diabetes, established CHD), level should be < 6-5 mmol. 1"'; higher levels considered individually
Canada1*1 CHD established CHD absent
cholesterol level above the 90th percentile for age (2 consecutive measures 1 month apart) disqualifies maintenance of 'normal' cholesterol encouraged. Consideration in context of multiple risk factor assessment advised (Denver Coronary Risk Index — table included in guidelines) — states that cumulative risk 'could be sufficiently high to disqualify pilot', but no cut-point given
Denmark
cholesterol measure required at admission (commercial pilots only), and then 3—4 yearly thereafter; cholesterol > 7 0 mmol. 1"' warrants HDL and LDL measures, and consideration of diet/drug therapy
Sweden
cholesterol measure required at 40 years of age (commercial pilots only); if cholesterol > 7 0 mmol. 1"' HDL and TG measures recommended. Cholesterol > 12 mmol . 1 " ' always disqualifies
Norway
no guidelines or limitations
Australia1271 CHD established CHD absent
risk factors must be controlled; no target levels given for cholesterol assessment of risk factors recommended at 40 years of age, and annual ECG if more than one risk factor present. Cholesterol > 6-5 mmol. I*1 considered to be elevated with need for increased surveillance, and advised to consult family doctor if cholesterol 5-5-6-5 mmol. 1"'
•September 1991, personal communication; | n o country contacted has recommendations for any lipid measurements other than total cholesterol. HDL, LDL = high/low density lipoprotein; TG = tnglycerides.
aircrew, although in Europe, at least, this is in the process of evolution through the European Civil Aviation Conference (ECAC). It is proposed that the ECAC (Joint Aviation Authorities, JAA) licensing standard for professional pilots will include a requirement for regular screening of the plasma cholesterol.
Are aircrew motivated to change?
Aircrew lose financially when grounded for medical reasons and thus should be highly motivated to adopt a lifestyle which will enable them to continue flying. Their regular medical supervision should afford an ideal opportunity to influence lifestyle in a positive way. Motivated people can change their risk of ischaemic heart disease. The best examples come from the medical profession. The surveys of British doctors carried out by Doll and Bradford Hill and by Doll and Peto highlighted the adverse effects of smoking. High lung cancer rates and coronary heart disease rates in doctors subsequently fell much more rapidly than in the general population128'. Second, the US Physicians Health Study1291 demonstrated the benefit of aspirin in reducing the incidence of non-fatal myocardial infarction, but no mortality difference was observed. In part this was because the ischaemic heart disease mortality rate of physicians was very much lower than had been expected from that calculated from the general population.
Hypertension treatment and other risk factors
Hypertension in aircrew is discussed elsewhere in this supplement. Hypertension per se increases the coronary risk threefold. There has been much debate about whether hypotensive drug treatment reduces this risk. Individual hypertension trials are usually too small to answer this question. Collins el a/.1301 have reviewed this evidence in an overview. They concluded that there was a significant (14%) reduction in coronary heart disease after 2-3 years treatment of raised blood pressure (largely thiazide based). This was about half the benefit which might be expected from the epidemiology. We do not know if this shortfall is because the trials were of too short duration to have much effect on a slow process (see the POSCH trial1'81, where benefit appeared only after 2-3 years, but was substantial by 10 years), or whether the drug treatment had some counter-balancing adverse effect (e.g. on lipids). There has been increasing interest in how antihypertensive drug therapy affects other risk factors for CHD such as lipids1311, insulin sensitivity1321 or left ventricular hypertrophy1331. However, in the absence of comparative mortality studies, any recommendations based on these secondary effects must remain speculative, particularly for aircrew, for whom the full range of drug therapy is not an option on account of possible side-effects. Another focus of interest is the confusingly named syndrome 'X' — the association between insulin resistance, hypertension, abnormal serum lipids and central obesity. All
Lipid screening in aircrew
these abnormalities are favourably influenced by nondrug lifestyle change, particularly weight reduction and exercise.
Conclusions
Blood lipid measurement should form an integral part of any serious multi-factorial risk assessment for CHD. The epidemiology is so compelling, and the intervention trial results for rapid benefit on CHD from cholesterol lowering so striking (without any really convincing evidence to date for a downside), that an active screening programme for lipids for pilots and potential pilots should be instituted. Results should be viewed in the context of each individual's complete risk profile, and not in isolation. This may be facilitated by the availability of some form of risk scoring system, such as suggested in the British Regional Heart Study"41. Pilots should be a highly motivated group, and susceptible to health education measures. Emphasis on diet (including diet available at work), exercise and weight reduction are appropriate, with drugs available for situations where absolute CHD risk is high. The formulation and adoption of a uniform approach to licensing guidelines on lipid screening by the JAA throughout Europe should offer major advantages.
References [1] Mason JK. Asymptomatic disease of coronary arteries of young men. BrMedJ 1963; ii: 1234-7. [2] Civil Aviation Authority. World Airline Accident Summary CAP 479. Cheltenham, CAA, 1974. [3] Scientific Steering Committee on behalf of The Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. Br Med J 1991; 303: 893-96. [4] Joy M. The impact of coronary vascular risk factors on professional aircrew licence loss in the United Kingdom. In: Specific Findings in Cardiology and Pulmonary Function with Special Emphasis on Assessment Criteria for Flying. CPP 232, 1977, NATO AGARD, Neuilly-sur-Seine. [5] Keys A, Anderson JT, Grande F. Prediction of serumcholesterol responses of man to changes in fats in the diet. Lancet 1957; n: 959-66. [6] Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res 1990; 31:1149-72. [7] Keys A, Kimura N, Kusakawa A, Bronte-Stewart B, Larsen N, Keys H. Lessons from serum cholesterol studies in Japan, Hawaii and Los Angeles. Ann Int Med 1958; 48: 83-94. [8] Goldstein JL, Hazzard WR, Schrott HG et al. Hyperlipidemia in coronary heart disease. Parts 1-3. J Clin Inv 1973; 52: 1533-77. [9] Brown MS, Faust JR, Goldstein JL. Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts. J Clin Invest 1975; 55: 783-93. [10] Keys A, ed. Coronary heart disease in seven countries. Circulation 1970; 41 (Suppl 1): 186-98. [11] Stamler J, Wentworth D, Neaton J for the MRFIT Research Group. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple
53
Risk Factor Intervention Trial (MRFIT). JAMA 1986; 256: 2823-8. [12] Kannell WB, Castelli WP, Gordon T, McNamara PM. Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham Study. Ann Int Med 1971; 74: 1-12. [13] Chen Z, Peto R, Collins R, MacMahon S, Lu J, Li W. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. Br Med J 1991; 303: 276-82. [14] Shaper AG, Pocock SJ, Phillips AN, Walker M. Identifying men at high risk of heart attacks: strategy for use in general practice. Br Med J 1986; 293: 474-9. [15] Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br Med J 1990; 301: 309-14. [16] Oliver MF. Might treatment of hypercholesterolaemia increase non-cardiac mortality? Lancet 1991; 337: 1529-31. [17] Keech A for the Oxford Cholesterol Study Group. Randomised trial of the effects of cholesterol lowering with simvastatin in patients at increased risk of coronary heart disease. Atherosclerosis 1990; 85:92. [18] Buchwald H, Vargo RL, Matts JP et al. and the POSCH Group. Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. N Engl J Med 1990; 323: 946-55. [19] Tobert JA. Cholesterol lowering and non-cardiac mortality. (Letter) Lancet 1991; 338: 126. [20] Castelli WP, Garrison RJ, Wilson PWF et al. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 1986; 256: 2835-8. [21] Kinlen L. Instanceand presentation of myocardial infarction in an English community. Br Heart J 1973; 35: 616-22. [22] Chamberlain DA. Introduction to Section III Ischaemic heart disease. Eur Heart J 1988; 9 (Suppl G): 69-72. [23] Chamberlain DA. Prevention of cardiovascular disease in airmen. Eur Heart J 1988; 9 (Suppl G): 73-81. [24] Review of Part 67 of the Federal Air Regulations and the Medical Certification of Civilian Airmen, Vol II, 1976. Engelberg AL, Doege TC. American Medical Association, 535 North Dearborn Street, Chicago, Illinois, USA 60610. [25] Arrete du 2 decembre 1988 relatif a l'aptitude physique et mentale du personnel navigant technique de l'aviation civile. Ministere de l'equipment, du logement, des transports et de 1'espace direction generale de l'aviation civile, 246, rue Lecourbe, 75732 Paris, France. [26] Guidelines for the assessment of cardiovascular fitness in Canadian pilots, 1988. Wielgosz AT, Dodge RE, Firor WB el al. Civil Aviation Medicine, Health Advisory Services, Medical Services Branch, Department of National Health and Welfare, Centennial Towers, 200 Kent St., Ottawa, Ontario K1A 0N8. [27] Vohra J, Plowright R. An appraisal of cardiovascular standards for Australian civilian flying licences. Aust NZ J Med 1989; 19: 76-82. [28] Doll R, Peto R. Mortality in relation to smoking: 20 years' observations on male British doctors. Br Med J 1976; 2: 1525-36. [29] Steering Committee of the Physician's Health Study Research Group. Final report on the aspirin component of the ongoing Physicians'Health Study. N Engl J Med 1988; 321: 129-35. [30] Collins R, Peto R, MacMahon S el al. Blood pressure, stroke, and coronary disease. 2. Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990; 335: 827-38. [31] Rosman J, Weidmann P, Ferrari P. Antihypertensive drugs and serum lipoproteins. J Drug Dev. 1990; 3 (Suppl 1): 129-39. [32] Lithell HOL. Effect of antihypertensive drugs on insulin, glucose, and lipid metabolism. Diabetes Care 1991; 14: 203-9. [33] Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561 -6.
Lipid screening in aircrew: pros and cons A. KEECH AND P. SLEIGHT
Clinical Trial Service Unit and Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, U.K. KEY WORDS: Aircrew licensing, aviation, lipids, risk screening, national policies, prevention, trials evidence, cholesterol lowering drugs, diet. Introduction
Although aircrew are likely to have a lower risk of coronary heart disease (CHD) than the general population on account of age, social class and lower cigarette consumption, they are not immune. Autopsies on 275 young men who died of trauma (mean age 28-3 years, and including 180 pilots) showed that 25% had at least one coronary artery with greater than 50% obstruction"1. On the other hand, medical standards and pilot incaparitation training have contributed to an extremely low rate of aircraft accidents due to ischaemic heart disease121. Against this background there may be no obvious need to consider risk factor intervention based on blood lipid screening except perhaps for the identification of those few individuals with familial hypercholesterolaemia (FH), where the risk of early myocardial infarction is exceptionally high'31. On the grounds both of passenger safety, notably of single crew aircraft, and also of airline economics, it might be justifiable to screen applicants for aircrew training or employment for FH. It is also rational (on economic grounds) to screen entrants to identify those at higher risk of premature ischaemic heart disease from raised lipids, particularly when associated with other risk factors (hypertension, family history, smoking, central obesity, lack of exercise). Joy has recorded an annual loss rate of U.K. professional flying licences of 1 -5/1000 pilots (mean age 48 years) from ischaemic heart disease, discovered on routine screening*41, an economic loss both to the pilot and his employer. This review will deal with the evidence linking lifestyle, cholesterol and coronary heart disease risk. We will also discuss whether lifestyle changes will reduce risk and whether drug treatment of hyperlipidaemia might adversely affect aircrew during their duties.
density lipoprotein (LDL) receptor leading to FH, and can importantly determine CHD risk'8-91. The relationship of cholesterol levels and CHD
The epidemiological studies provide overwhelming evidence of a strongly positive plasma cholesterol-CHD relationship, documented in both between-population'101 and within-population'"'121 studies. They also show that the relationship is continuous, and with no threshold among Western nations below which a lower cholesterol does not confer a lower risk of CHD. A recent long-term study of urban Chinese extends the graded positive relationship down to levels of cholesterol (about 3-8^-7 mmol. T 1 ) below those commonly found in Western populations, suggesting that biologically normal cholesterol levels (as opposed to Western average levels) may be more like those of the Chinese, with lower risk of CHD eventually coming from sub-Western levels of cholesterol'131. The largest within-population study of cholesterol and outcome, the Multiple Risk Factor Intervention Trial (MRFIT) followed 356 222 men for at least 6 years, and provided powerful evidence of the continuous nature of the relationship. It also drew attention to the importance of CHD risk depending not on the cholesterol level in isolation, but on multiple factors which together determine the probability of a CHD event'"1. Age, gender, blood pressure and smoking status (amongst other things) all, together with cholesterol, influence the probability of a CHD event (see Fig. 1). The British Regional Heart Survey has also shown that, although risk assessment is not highly specific, three out of everyfivecoronary events occurred in those at highest risk'141. Can attention to cholesterol alter CHD risk?
Determinants of cholesterol levels in the plasma
Cholesterol levels in the plasma are determined both by diet and by genetic factors. A high percentage of calories taken as saturated fat, and excess total calorie intake (with consequent obesity) are the chief dietary factors'561. Migrants can rapidly assume the diet, plasma cholesterol, and CHD pattern of their host country171. Genetic factors also modulate cholesterol level, via defects in the low Correspondence. Anthony Keech, Clinical Trial Service Unit, University of Oxford, Harkness Building, Radcliffe Infirmary, Oxford OX2 6HE, U.K. 0195-668X/92/0H0050 + 04 S08.00/0
More than 20 clinical end-point trials testing dietary change or (one or more) drug therapies to lower serum cholesterol have been conducted over the last 20 years. An overview of published and unpublished randomized studies of cholesterol lowering (R. Peto, personal communication, 1990) shows a highly significant reduction in CHD events (a 10% lowering of cholesterol for only 2 years on average resulting in a 16%+ 3 reduction in all CHD events; 2/'90. cancer1'9'. and duration of cholesterol reduction. However, to date the cholesterol reductions achieved have been small (average around 10%), and for only a short duration (average only 1-3 years for those suffering a CHD event), with often low rates of CHD, and with CHD only contributing to a minority of all deaths. Thus it is not unexpected that even collectively these studies have little power to test reliably whether or not small reductions in CHD will lead to reduced total mortality. Possible adverse effects of lipid lowering
Despite this lack of power, Muldoon et a/.'151 and Oliver1'6' have raised the question of whether the clear benefit of lipid lowering with regard to coronary heart disease is offset by adverse effects on other conditions so that total mortality is not reduced. Meta-analysis of all the unconfounded cholesterol lowering trials has shown no significant effect on total mortality. It is important to understand that this is not the same as proof that there is no effect. It can be calculated that the reduction in CHD mortality observed in the trials should result in a 6% fall in total mortality (since people also die of other conditions). The observed 3% fall in total mortality in the trials, although not statistically significant, is compatible with the 6% expected (R. Peto, personal communication, 1990). Until large cholesterol differences (such as those now achievable with the HMG Coenzyme A reductase inhibitors'171 and the new fibrates) can be tested long-term in subjects where CHD event rates are high, and represent a high proportion of all fatalities, we will not have adequate power to demonstrate effects on total mortality in trials of realistic size. For example, consider the 15% reduction in odds of coronary mortality seen over 5 years in the Muldoon overview of primary prevention trials'131 with the CHD/non-CHD death rates (approximately 1-5% and 31%) observed. To test reliably (i.e. with 90% power) for a conventionally significant (2/" < 0-05)
Morbidity of lowering cholesterol
Some cholesterol lowering regimes such as diet are largely free from side-effects, and may confer other benefits (such as anti-platelet effects offish consumption, anti-oxidant activity of various vitamins, and, together with exercise and the cessation of smoking, elevation of the protective'201 high density lipoprotein cholesterol fraction). The resins such as cholestyramine may not be acceptable to all (aircrew) because of side-effects such as colic or increased bowel frequency. Likewise niacin causes flushing and gastro-intestinal symptoms. Both the fibrates and the statins, apart from rare muscle cramps with raised creatinine kinase and, with the fibrates, occasional gastro-intestinal upset, appear remarkably well tolerated and should not cause problems for aircrew. Identifying lipid risks
On the balance of current evidence it is appropriate to recommend lipid measurement in aircrew at initial entry and thereafter as required, with advice to encourage life-style modification. Drug treatment should be indicated where relevant. Risk factor reduction is the one therapeutic option to reduce the toll from sudden cardiac death, since almost half of community deaths from CHD occur without any medical presence or intervention'21' and neither thrombolysis nor cardiac care units can affect these deaths. In the Second U.K.. Workshop in Aviation Cardiology, Chamberlain'22-23' reviewed the preventive measures taken by individual airlines. Lipids did not figure strongly then, although one airline did measure lipids and give their aircrew a personal multiple risk assessment. As opposed to individual airlines, the current attitudes (1991) of some licensing authorities are given in Table 1. As can be seen, there is no uniform policy yet in the lipid screening of
52 A.KeechandP.Sleight Table 1 Some current* national Civil Aviation regulatory agency licensing practices in relation to blood lipids Published guidelines in relation to serum cholesterol^
Country United Kingdom
no guidelines or limitations
United States124'
no guidelines or limitations
France1251
cholesterol measure required at admission, every 5 years up to 40 years of age, then every 2 years; no target levels stated
Germany
if cholesterol is measured (compulsory in setting of some risk situations e.g. Type II diabetes, established CHD), level should be < 6-5 mmol. 1"'; higher levels considered individually
Canada1*1 CHD established CHD absent
cholesterol level above the 90th percentile for age (2 consecutive measures 1 month apart) disqualifies maintenance of 'normal' cholesterol encouraged. Consideration in context of multiple risk factor assessment advised (Denver Coronary Risk Index — table included in guidelines) — states that cumulative risk 'could be sufficiently high to disqualify pilot', but no cut-point given
Denmark
cholesterol measure required at admission (commercial pilots only), and then 3—4 yearly thereafter; cholesterol > 7 0 mmol. 1"' warrants HDL and LDL measures, and consideration of diet/drug therapy
Sweden
cholesterol measure required at 40 years of age (commercial pilots only); if cholesterol > 7 0 mmol. 1"' HDL and TG measures recommended. Cholesterol > 12 mmol . 1 " ' always disqualifies
Norway
no guidelines or limitations
Australia1271 CHD established CHD absent
risk factors must be controlled; no target levels given for cholesterol assessment of risk factors recommended at 40 years of age, and annual ECG if more than one risk factor present. Cholesterol > 6-5 mmol. I*1 considered to be elevated with need for increased surveillance, and advised to consult family doctor if cholesterol 5-5-6-5 mmol. 1"'
•September 1991, personal communication; | n o country contacted has recommendations for any lipid measurements other than total cholesterol. HDL, LDL = high/low density lipoprotein; TG = tnglycerides.
aircrew, although in Europe, at least, this is in the process of evolution through the European Civil Aviation Conference (ECAC). It is proposed that the ECAC (Joint Aviation Authorities, JAA) licensing standard for professional pilots will include a requirement for regular screening of the plasma cholesterol.
Are aircrew motivated to change?
Aircrew lose financially when grounded for medical reasons and thus should be highly motivated to adopt a lifestyle which will enable them to continue flying. Their regular medical supervision should afford an ideal opportunity to influence lifestyle in a positive way. Motivated people can change their risk of ischaemic heart disease. The best examples come from the medical profession. The surveys of British doctors carried out by Doll and Bradford Hill and by Doll and Peto highlighted the adverse effects of smoking. High lung cancer rates and coronary heart disease rates in doctors subsequently fell much more rapidly than in the general population128'. Second, the US Physicians Health Study1291 demonstrated the benefit of aspirin in reducing the incidence of non-fatal myocardial infarction, but no mortality difference was observed. In part this was because the ischaemic heart disease mortality rate of physicians was very much lower than had been expected from that calculated from the general population.
Hypertension treatment and other risk factors
Hypertension in aircrew is discussed elsewhere in this supplement. Hypertension per se increases the coronary risk threefold. There has been much debate about whether hypotensive drug treatment reduces this risk. Individual hypertension trials are usually too small to answer this question. Collins el a/.1301 have reviewed this evidence in an overview. They concluded that there was a significant (14%) reduction in coronary heart disease after 2-3 years treatment of raised blood pressure (largely thiazide based). This was about half the benefit which might be expected from the epidemiology. We do not know if this shortfall is because the trials were of too short duration to have much effect on a slow process (see the POSCH trial1'81, where benefit appeared only after 2-3 years, but was substantial by 10 years), or whether the drug treatment had some counter-balancing adverse effect (e.g. on lipids). There has been increasing interest in how antihypertensive drug therapy affects other risk factors for CHD such as lipids1311, insulin sensitivity1321 or left ventricular hypertrophy1331. However, in the absence of comparative mortality studies, any recommendations based on these secondary effects must remain speculative, particularly for aircrew, for whom the full range of drug therapy is not an option on account of possible side-effects. Another focus of interest is the confusingly named syndrome 'X' — the association between insulin resistance, hypertension, abnormal serum lipids and central obesity. All
Lipid screening in aircrew
these abnormalities are favourably influenced by nondrug lifestyle change, particularly weight reduction and exercise.
Conclusions
Blood lipid measurement should form an integral part of any serious multi-factorial risk assessment for CHD. The epidemiology is so compelling, and the intervention trial results for rapid benefit on CHD from cholesterol lowering so striking (without any really convincing evidence to date for a downside), that an active screening programme for lipids for pilots and potential pilots should be instituted. Results should be viewed in the context of each individual's complete risk profile, and not in isolation. This may be facilitated by the availability of some form of risk scoring system, such as suggested in the British Regional Heart Study"41. Pilots should be a highly motivated group, and susceptible to health education measures. Emphasis on diet (including diet available at work), exercise and weight reduction are appropriate, with drugs available for situations where absolute CHD risk is high. The formulation and adoption of a uniform approach to licensing guidelines on lipid screening by the JAA throughout Europe should offer major advantages.
References [1] Mason JK. Asymptomatic disease of coronary arteries of young men. BrMedJ 1963; ii: 1234-7. [2] Civil Aviation Authority. World Airline Accident Summary CAP 479. Cheltenham, CAA, 1974. [3] Scientific Steering Committee on behalf of The Simon Broome Register Group. Risk of fatal coronary heart disease in familial hypercholesterolaemia. Br Med J 1991; 303: 893-96. [4] Joy M. The impact of coronary vascular risk factors on professional aircrew licence loss in the United Kingdom. In: Specific Findings in Cardiology and Pulmonary Function with Special Emphasis on Assessment Criteria for Flying. CPP 232, 1977, NATO AGARD, Neuilly-sur-Seine. [5] Keys A, Anderson JT, Grande F. Prediction of serumcholesterol responses of man to changes in fats in the diet. Lancet 1957; n: 959-66. [6] Grundy SM, Denke MA. Dietary influences on serum lipids and lipoproteins. J Lipid Res 1990; 31:1149-72. [7] Keys A, Kimura N, Kusakawa A, Bronte-Stewart B, Larsen N, Keys H. Lessons from serum cholesterol studies in Japan, Hawaii and Los Angeles. Ann Int Med 1958; 48: 83-94. [8] Goldstein JL, Hazzard WR, Schrott HG et al. Hyperlipidemia in coronary heart disease. Parts 1-3. J Clin Inv 1973; 52: 1533-77. [9] Brown MS, Faust JR, Goldstein JL. Role of the low density lipoprotein receptor in regulating the content of free and esterified cholesterol in human fibroblasts. J Clin Invest 1975; 55: 783-93. [10] Keys A, ed. Coronary heart disease in seven countries. Circulation 1970; 41 (Suppl 1): 186-98. [11] Stamler J, Wentworth D, Neaton J for the MRFIT Research Group. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple
53
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