2. Headache Classiﬁcation Committee of thereport of a patient with triptan responsiveInternational Headache Society The Inter-national Classiﬁcation of Headache Dis-orders. Cephalalgia 2004; 24: 1–160. 3. Relja G, Zorzon M, Locatelli L, Carraro N,istered on an open-label basis; (2) frova-cervical and intracranial vessels and thetriptan was eﬀective only two times; andhistory gave
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Coronary Heart Disease: Reducing The Risk
A Worldwide View
Gerd Assmann, FRCP; Rafael Carmena, MD; Paul Cullen, FRCPI; Jean-Charles Fruchart, PhD; Fabrizio Jossa, MD; Barry Lewis, FRCP; Mario Mancini, MD; Rodolfo Paoletti, MD; for the International Task Force for the Prevention of Coronary Heart Disease Worldwide, cardiovascular diseases are now the most risk increases steeply, approaching that of men after the age common cause of death and a substantial source of chronic disability and health costs. In the light of new datafrom clinical trials and a fuller understanding of risk factors, History of Cardiovascular Disease
the International Task Force for the Prevention of Coronary The risk of further CHD events or stroke is much higher in Heart Disease, in cooperation with the International Athero- persons with a history of myocardial infarction, angina, sclerosis Society, prepared a revised and comprehensive stroke, or intermittent claudication and in those who have statement regarding the scientific basis of the primary and ischemic changes on resting or exercise ECG than in persons secondary prevention of cardiovascular disease. The follow- without such findings. Any of these features confers grade III ing is a short account of the clinical implications of this status (high risk; Table 1) and warrants vigorous reduction of statement. It is best read in conjunction with the full docu- ment, which can be found at http://www.chd-taskforce.com Positive Family History of CHD, Stroke, or Peripheral
Assessing the Global Risk of
Note any reliable cardiovascular family history, and grade its Cardiovascular Disease
severity on the basis of the following.
Assessing a patient’s overall or global risk of cardiovasculardisease is the first step in preventive care, for it enables the ● How early in life relatives were affected (discount events physician to identify and provide the appropriate level of treatment for risk factors. Much can be learned from measur- ● The closeness of the relationships (eg, CHD in a sibling or ing even a few risk factors. The fuller the knowledge of the parent confers greater risk than CHD in an uncle) patient’s risk status, the sounder the treatment decisions.
● What proportion of adult relatives were affected Initial costs may be offset by long-term rational treatment.
The goals of treatment and, hence, the extent of dietary Smoking
change and the need for (and choice and dosage of) drug Note the duration and amount of current and former use of treatment all depend on global risk assessment. Two methods cigarettes and other tobacco products; these are potent but potentially reversible causes of CHD.
Psychosocial Risk Factors
There is increasing evidence that stress, lack of social
Note and tabulate the following risk factors, including those support, depression, and low socioeconomic status are asso- laboratory investigations that are available.
ciated with an increased risk of CHD. Although specific Age, Sex, and Menopausal Status
treatment for these factors is often difficult, assessing them is Risk increases progressively with adult age, and coronary still an important part of the work-up. The psychosocial heart disease (CHD) is most common after the age of 60 profile of the patient also has a large influence on the patient’s years. In premenopausal women, CHD is rare (except in those ability to comply with measures such as lifestyle modifica- who use oral contraceptives and smoke). After menopause, From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Mu¨nster, Germany (G.A., P.C); Faculty of Medicine, University of Valencia, Spain (R.C.); Department for the Study of Lipids and Lipoproteins, Institut Pasteur de Lille, France(J.-C.P.); Department of Clinical and Experimental Medicine, University of Naples, Italy (F.J., M.M.); University of London, UK (B.L.); Faculty ofPharmacy, University of Milan, Italy (R.P.) Correspondence to Gerd Assman, FRCP, Institut fuer Arterioskleroseforschung, Universitaet Muenster, Albert-Schweitzer-Strasse 33, 48149 Muenster, The full version of this document, which was prepared in cooperation with the International Atherosclerosis Society, was published in Nutrition, Metabolism and Cardiovascular Disease 1998;8(3):205–271, and is also available on the Task Force Internet home page at http://www.chd-taskforce.com A complete list of investigators can be found in the full version of this document.
1999 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
Assmann et al
Reducing Coronary Heart Disease
Clinical Risk Assessment
Presence of 1 risk factor of moderate degree in a Presence of 1 risk factor of severe degree in a History of myocardial infarction, angina, stroke, or middle-aged man, eg, plasma cholesterol 200 –250 middle-aged man, eg, smokes 20 cigarettes per peripheral vascular disease, ECG evidence of CHD, mg/dL (5.2– 6.5 mmol/L), BP 170/100, or smokes day, plasma cholesterol Ͼ250 mg/dL (Ͼ6.5 or evidence of coronary or carotid plaques mmol/L), diabetes, or family history in a closerelative Presence of 2 risk factors of moderate degree in a Presence of 2 risk factors of severe degree, eg, middle aged man, eg, plasma cholesterol 200–250 plasma cholesterol Ͼ250 mg/dL (Ͼ6.5 mmol/L) mg/dL (5.2–6.5 mmol/L) and HDL cholesterol Ͻ35 and smokes 20 cigarettes a day, diabetes, or Presence of 3 risk factors of moderate degree Familial hypercholesterolemia or remnanthyperlipidemia BP indicates blood pressure.
*Ϸ3 CHD events per 1000 per year in middle-aged men; 3rd quintile of PROCAM algorithm.
†Ϸ7 CHD events per 1000 per year in middle-aged men; 4th quintile of PROCAM algorithm.
‡Ϸ23 CHD events per 1000 per year in middle-aged men; 5th quintile of PROCAM algorithm.
In PROCAM (1978 –1996), more than 30 000 individuals at work in Germany were assessed for Ͼ30 anthropometric and laboratory parameters. Based on PROCAM, a formula for calculating CHD risk in middle-aged men was derived that takes into account age, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglyceride,smoking behavior, presence of diabetes mellitus, positive family history of myocardial infarction, and presence of angina pectoris. It is available as an interactiveprogram at http://www.chd-taskforce.com.
Weight and Height
Plasma Lipids and Lipoproteins
Derive the body mass index (BMI) by nomogram or calcu- The preferred investigation for plasma lipids and lipoproteins lation (BMIϭweight in kg/height in m2). Overweight is is one that measures total cholesterol, triglycerides, HDL defined as a BMIϾ25 and obesity as a BMIϾ30. Excess cholesterol, and LDL cholesterol after a 14-hour fast (water adipose tissue in the truncal region is an important cardio- permitted). If the full profile is unavailable, plasma choles- vascular disease risk factor, and it adversely affects blood terol alone is useful in defining risk and diagnosing some pressure, cholesterol (total, HDL, and LDL), and triglyceride levels and glucose tolerance. Truncal obesity can be assessed Lipid levels are continuously related to risk. Take particular and treatment can be monitored by estimating the weight/hip note of an LDL cholesterol level Ͼ135 mg/dL (Ͼ3.5 mmol/L), ratio (circumference of waist at umbilicus/circumference of a HDL cholesterol level Ͻ35 mg/dL (Ͻ0.9 mmol/L), and a hips at widest part; it is normally Ͻ1.0 in men and Ͻ0.85 in triglyceride level of 150 to 400 mg/dL (1.7 to 4.5 mmol/L).
women) or by measuring girth horizontally at the level of the Lipids can be assessed in a blood sample taken within 24 hours umbilicus (normally Ͻ94 cm in men and Ͻ80 cm in women).
Truncal obesity syndrome is often accompanied by some of the onset of myocardial infarction; thereafter, LDL cholesterol or all of the following features: high plasma triglycerides, low levels often fall and only return to their previous level after Ϸ3 HDL cholesterol, type 2 diabetes, hypertension, and an months. Lipid measurements can also be reduced for 3 months increased risk of CHD. A key mechanism is insulin resis- after a severe illness and for 2 weeks after a minor illness. Levels tance. Reducing overweight is often highly effective against of lipoprotein(s) exceeding 30 mg/dL confer increased risk.
Type 1 and type 2 diabetes confer a markedly increased risk Blood pressure is continuously related to the risks of stroke of CHD; even impaired glucose tolerance is often accompa- and CHD over a wide range, although a systolic pressure of nied by lipid risk factors and elevated blood pressure.
Ն160 mm Hg and/or a diastolic pressure Ն90 mm Hg is used Diabetes should be suspected in persons with diabetic to define hypertension. Isolated systolic hypertension symptoms and random plasma glucose levels Ͼ200 mg/dL (Ͼ160 mm Hg) is an important risk factor in the elderly.
(Ͼ11.1 mmol/L). Diabetes is now defined as a plasma Blood pressure is best measured with the subject seated, after glucose level Ͼ126 mg/dL (Ͼ7 mmol/L) after fasting for 8 hours and/or a plasma glucose level Ͼ200 mg/dL Cardiovascular Examination
(Ͼ11.1 mmol/L) at 2 hours during an oral glucose tolerance The cardiovascular examination may reveal a carotid bruit or a missing peripheral pulse, denoting existing atherosclerotic Other CHD risk factors that are now measured in many disease and conferring grade III risk.
laboratories include fibrinogen and homocysteine.
November 2, 1999
Management of CHD Risk Factors
Simple counseling is the first approach in the management of
smoking cessation, and it is often effective. Ask how con-
cerned the smoker is with his or her habit and how much he
or she wants to stop. Reinforce the patient’s desire (verbally
and by providing written materials) to stop smoking by
spelling out the following benefits of smoking cessation.
● How rapidly her or his well being will improve after quitting (eg, food tastes better, effort tolerance improves,and morning cough subsides) ● The risks of continuing to smoke, including the high risk of CHD (including sudden death, stroke, and peripheral vas-cular disease), the several smoking-related cancers, and Estimated risk of a coronary event among men aged 40 to 65 years in the Mu¨nster Heart Study, expressed as quintiles of the ● The progressive decline of the above risks in ex-smokers PROCAM multiple logistic function. Reproduced with permission from Nutr Metab Cardiovasc Dis. 1998;8:205–271 (also availableat http://www.chd-taskforce.com).
Clearly and firmly counsel the patient to stop smoking with apositive, encouraging, and sympathetic attitude. Second or On the basis of the presence, number, and severity of some further attempts are often more successful than the first. Try or all of these 11 groups of risk factors, increased risk is to help arrange for support by others (eg, the patient’s assigned to 1 of 3 grades: I, II, or III, as seen in Table 1.
spouse). Help the smoker identify trigger factors for smoking Appropriate treatment decisions are based on this grading.
(eg, drinking alcohol or coffee, using the telephone, or In asymptomatic patients at increased risk, the precision of driving a car); awareness of the trigger lessens its impact. If risk assessment may be enhanced by imaging methods.
possible, the trigger should be avoided.
Noninvasively, quantitative carotid Doppler ultrasound can If the attempt to stop smoking fails, the next attempt may be used. Increased interomedial thickness is predictive of a be more successful if preceded by a period of “minimum 2-fold increase in CHD risk, and detection of carotid plaques smoking:” when subjects feel the urge to smoke, they ask themselves whether they really need to do so at that moment.
Often, they realize that smoking can be postponed. Another Method II
approach for the unsuccessful quitter is referral to a smoking Quantitative Risk Assessment
cessation class run by a skilled counselor or psychologist.
On the basis of 9 risk factors, data from the Prospective Nicotine dependence can be dealt with by coupling the Cardiovascular Mu¨nster (PROCAM) Study are used to provide above approach with nicotine replacement in patients without a quantitative estimate of risk (Figure) using an algorithm that is CHD. Use nicotine skin patches or nasal spray and progres- currently applicable to men aged 40 to 65 years (Appendix 1).
This is available as an interactive program on the Task Forcewebsite (http://www.chd-taskforce.com).
Treating Overweight and Obesity
The physician’s attitude is important when treating patients
Primary and Secondary Prevention
with weight problems. Encouragement, patience, and enthu- Evidence of a myocardial infarction, stroke, or other athero- siasm are needed. Encourage the patient to combine an sclerotic disease confers a high risk of further cardiovascular exercise program (see below) with changes in diet. Empha- events and has a risk level of grade III. Patients in this size that some elements of lifestyle change will need to be category require vigorous intervention against risk factors, life-long, and spell out the benefits of weight reduction. The and clear evidence exists showing the benefits of such immediate and expected future benefits of weight reduction intervention. Reducing risk in such patients is termed second- ary prevention, whereas risk reduction in persons without such evidence is termed primary prevention. Evidence of CHD is a special case within the high-risk group (ie, among persons with grade III risk). Primary prevention in persons with grade III risk requires equally vigorous intervention against risk factors, and equally cogent evidence exists showing its benefits. Because 30% of patients with a first Lower LDL cholesterol and triglyceride levels and higher manifestation of CHD (such as myocardial infarction) survive for Ͻ3 months and because such first events may lead to prolonged or permanent disability, the potential benefits of Lesser risk of diabetes, certain cancers, accidents, and primary prevention exceed those of secondary prevention.
Assmann et al
Reducing Coronary Heart Disease
Choice of Foods in the Cholesterol-Lowering Diet
breakfast cereals with emphasis onlow-sugar, low-salt brands; porridge;muesli; pasta; rice; crispbread(crackers); matzo All white and oily fish (grilled, poached, oils, (eg, sunflower, corn, walnut,safflower); soft (unhydrogenated)margarines rich in monounsaturated orpolyunsaturated oils; low-fat spreads biscuits (cookies), pies, snacks, andpuddings malted drinks; boiled “Turkish” coffee* Added salt; salad dressings; saladcream (ie, Miracle Whip); mayonnaise *Coffee grounds contain a substance that may increase blood cholesterol; hence, filtered or instant coffee is preferable in patients with hyperlipidemia.
Reproduced with permission for Nutr Metab Cardiovasc Dis. 1998;8:205–271 (also available at http://www.chd-taskforce.com).
Examples of suitable aerobic activities include walking (an The reducing diet consists of a maintained or increased excellent exercise), jogging, cycling, and calisthenics, such as intake of low energy-density foods (which help control aerobic classes and rowing; individual preference is impor- appetite), such as green vegetables, salad vegetables, and tant for long-term compliance. Before more strenuous exer- clear soups and a decreased intake of high energy– density cise, a warm-up period of 5 minutes of stretching and other and nonsatiating foods, including alcohol, all fats and oils, gentle activity is advised, as is a final cool-down period of and sugar-containing foods. An example of such a diet is Exercise dosage is determined by its duration, intensity, and frequency. For persons who have been sedentary in Physical Exercise
recent months, those with known cardiovascular disease or A suitable exercise program is recommended for all sedentary with grade III risk, and those aged Ͼ40 years, initial persons; a clear and detailed prescription is needed for training should be gentle (eg, 10 minutes of walking daily).
effectiveness, safety, and personal enjoyment.
As fitness and tolerance increase, the dose increases in 1934
November 2, 1999
Target Pulse Rate During Aerobic Exercise for
Suggested Target Levels for LDL
Persons not at High Cardiovascular Risk*
*Until further information becomes available, a suggested target for triglyc- *Rates listed are inappropriate for patients taking ␤-blockers and other eride lowering is 150 mg/dL (1.7 mmol/L).
Reproduced with permission from Nutr Metab Cardiovasc Dis. 1998;8:205– Adapted from Nutr Metab Cardiovasc Dis. 1998;8:205–271 (also available at 271 (also available at http://www.chd-taskforce.com).
weekly increments, initially by extending the duration.
should know that current dietary guidelines fully maintain the Later, intensity can be increased if suitable, eg, by brisk pleasures of eating and are similar to the habitual diets of walking or by alternating walking and jogging or gentle countries in which mortality from CHD and many cancers is swimming. Young persons and fit middle-aged subjects far lower than in Western countries.
may ultimately undertake 20 to 30 minutes of aerobic Lipid-lowering drugs should be introduced only after a careful trial of conservative management, if indicated by the Exercise intensity can be judged subjectively; persons grade of risk, and always used together with ongoing dietary should aim for a comfortable intensity, sufficient to extend themselves slightly. Mild shortness of breath during exerciseshould abate within 4 minutes or less of resting. The subject Target Levels for Lipid Lowering
Table 4 shows suggested goals for lipid-lowering based on
should be told to stop and to report to a physician if recovery the grade of global risk. Pending the results of further trials to time is prolonged or if chest pain, syncope, or persistent determine optimal goals, Table 4 is consistent with epidemi- cough occur. Another way to judge intensity requires moni- ological studies and with meta-analyses of trials. Treatment is toring pulse rate during exercise; target pulse rates are shown best monitored by LDL cholesterol levels.
in Table 3. A training effect is obtained at rates of 60% of the History and physical examination may reveal the features maximum rate for age, and this is the initial target rate. With of major familial hyperlipidemias. Most are uncommon, but increasing fitness, in persons at low cardiovascular risk, the they require detection because they may confer a particularly target may be increased gradually to 75% of maximum, for high risk of CHD or pancreatitis. These disorders are tabu- example, by increasing the speed of walking.
Exercise should be supervised, at least initially, and ECG A determined effort should be made to reduce or correct monitoring should be performed in patients at higher risk; this even minor degrees of overweight using the means described includes those with overt cardiovascular disease, such as in the section on weight reduction together with those in the angina or silent ischemia, and especially those with high- section on exercise. These measures have a strong favorable grade ventricular arrhythmias, low ejection fractions, hypo- effect on most common plasma lipid disorders.
tension on exercise, and inappropriate exercise-induced Causes of secondary hyperlipidemia should be treated or tachycardia. The type and amount of exercise must also take removed, if possible. Among these causes are medications, into account respiratory or musculoskeletal disease and pe- including corticosteroids, anabolic steroids, thiazides, and retinoids; diabetes mellitus; hypothyroidism; alcohol abuse; Treatment of Hyperlipidemia
chronic renal failure; nephrotic syndrome; and bulimia andanorexia nervosa.
Clinical trial evidence justifies placing a strong emphasis onplasma lipid-lowering as part of primary and secondary Lipid-Lowering Diet
prevention. Accompanying risk factors are treated at the same A lipid-lowering diet is shown in Appendix 2; it is designed time. Past concerns about the safety of lowering plasma for persons whose habitual diet is Western and requires cholesterol are no longer tenable. The intensity of lipid- adaptation. In the lipid-lowering diet, fat provides up to 30% lowering treatment is determined by the patient’s global risk of food energy; saturated plus hydrogenated fat contributes and by his or her responsiveness to treatment.
no more than 7% to 10% of energy intake, monounsaturated The value of conservative treatment, ie, diet (including the fat 10% to 15%, and polyunsaturated fat up to 7% to 8%. The extremely important element of reduction of overweight) and diet has a high content of complex carbohydrates, and it exercise, cannot be too strongly emphasized; under controlled provides at least 25 g of fiber per day, with an emphasis on conditions, diet even without weight reduction can lower soluble fiber. It contains less than 300 mg of cholesterol per plasma cholesterol by 10% to 25%. Hence, efforts should be day. This is achieved with a generous intake of whole-grain made to maximize skills in dietary counseling. The patient cereal foods, fruit and vegetables, fat-free and low-fat dairy Assmann et al
Reducing Coronary Heart Disease
products, fish, low-fat poultry, moderate amounts of low-fat acid and several concomitantly administered drugs. In a meats and of eggs, and unsaturated vegetable oils as the main larger dose, resins can increase triglyceride levels.
source of fats. Preferred cooking methods include grilling, Fibric acid derivatives are effective triglyceride-lowering steaming, boiling, microwave cooking, and barbecue drugs; they increase HDL cholesterol substantially and (par- ticularly the more recent members of the class) also lower Some patients whose response to this diet is incomplete will plasma cholesterol. Abnormal liver function is a contraindi- achieve satisfactory control when a diet is given that provides cation. Side effects include dyspepsia, rashes, abnormal liver 25% to 27% of energy from fat (6% to 8% of which is from function and (rarely) hepatitis (ALT should be monitored), saturated fat) and 200 to 250 mg of cholesterol per day.
gallstones, impotence, myopathy and rhabdomyolysis, and For patients with hypertriglyceridemia, the standard lipid- sensitivity to warfarin. Great caution is needed in using lowering diet is prescribed, with particular emphasis on controlling overweight and specific advice on moderating or Nicotinic acid in large doses lowers triglyceride and avoiding alcohol consumption and increasing the intake of cholesterol levels and increases HDL cholesterol. Flushing, oily fish. Patients with severe hypertriglyceridemia caused by pruritus, and dyspepsia are common and tend to limit com- excess chylomicron particles need a minimal intake of long- pliance; abnormal liver function may occur. A gradually chain fatty acids but can substitute medium-chain increasing dose schedule is needed. Liver disease, gout, and diabetes are relative contraindications.
Fish oil in large doses effectively lowers triglyceride Lipid-Lowering Drugs
In patients at grade I risk, conservative treatment is usuallyeffective in achieving target lipid levels. In those at grade III Management of Hypertension
risk, a short (eg, 2 month) trial of diet is warranted, during The prevalence of hypertension is about 20% in most coun- which at least 2 sets of lipid measurements should be made tries, rising with age to about 50% by the age of 65 years. In and averaged; if target values are not attained, a drug should the US in 1988, the proportion of hypertensives who were be introduced, with ongoing attention to diet. In those at detected, treated, and achieved good control was 29%; grade II risk, an extended trial of conservative treatment is similarly limited success has been observed in Europe.1 required, with repeated counseling, for a period of at least 6 The usual goal of treatment is to achieve a systolic blood months. Whenever possible, the use and choice of drug pressure Ͻ140 mm Hg and a diastolic blood pressure should be based on clinical trial data. A discussion of Ͻ90 mm Hg. Particular care is directed to patients at highest commonly used lipid-lowering drugs follows.
risk, including the elderly, those with target organ damage Hepatic hydroxymethylglutaryl coenzyme A (HMG CoA) (heart, brain, kidneys, and retina), diabetics, hyperlipidemics, reductase inhibitors offer a major advance in CHD preven- smokers, patients with left ventricular hypertrophy, and those tion. They effectively lower LDL cholesterol, and they have a moderate effect in lowering triglycerides, which may bemore marked with some newer statins. HMG CoA reductase Nonpharmacological Treatment
inhibitors are now the drugs of first choice for familial The following measures are appropriate in all hypertensives.
hypercholesterolemia, and they can be of value in combined ● Reduction of overweight; even a loss of 4 to 5 kg lowers (mixed) hyperlipidemia. Treatment commences at a mini- mum dosage, with dose titration at 6- to 8-week intervals.
● Reduction of alcohol intake, if excessive (ie, Ͼ30 mL/d), Lipid levels and alanine transaminase (ALT) levels should be lowers blood pressure in susceptible hypertensives monitored. Severe hypercholesterolemia may require combi- ● Increase in aerobic physical activity nation treatment with a resin. Most statins are not licensed for ● Reduction of salt intake to 4 g (70 mmol) per day use in children, and they are not given to women of ● Increase intake of fruit and vegetables (which provides a child-bearing age unless effective contraception is assured.
substantial intake of potassium) and lower intake of fat and Headache, constipation, flatulence, and dyspepsia are recog- saturated fat; these items are of proven value in lowering nized side effects. Liver function can be impaired, and statins are contraindicated in the presence of active liver disease or ● Deal with coexisting cardiovascular risk factors (eg, smok- elevated ALT levels. Myopathy and potentially fatal rhabdo- myolysis are rare side effects, the risk of which is increasedby drug interactions with erythromycin, fibrates, azole anti- Drug Treatment
fungals, cyclosporin, tacrolimus, nicotinic acid, and some Drug treatment commences with low doses followed by slow dose titration to achieve 24-hour control with once-daily Resins (bile acid sequestrants) are effective cholesterol- medication at a minimum dosage. If systolic pressure lowering drugs. Being nonabsorbable, they are largely free Ͼ160 mm Hg and target organ damage are present, initiate from systemic side effects. They are presented as a powder drug treatment immediately; if diastolic pressure Ͼ90 mm Hg and taken in water or fruit juice with meals. Patient accep- and target organ damage are present, start drug treatment tance is sometimes imperfect. Side effects include constipa- within 1 to 2 weeks if a trial of nonpharmacological measures tion, dyspepsia, abdominal pain, and malabsorption of folic is not promptly effective. Conversely, if hypertension is mild 1936
November 2, 1999
and no target organ damage exists, a trial of nonpharmaco- Suggested Target Lipid Levels in Diabetic Patients
logical management for up to 6 months is warranted. Avail- able clinical trial data suggest that thiazides and ␤-blockersare the preferred initial drugs for uncomplicated hyperten- sives. Nonpharmacological measures are continued after the Initial Drugs
Adapted from Nutr Metab Cardiovasc Dis. 1998;8:205–271 (also available at Low-dose thiazides or ␤-blockers should be the first drugs used for pharmacological management of hypertension, un-less contraindicated. Angiotensin-converting enzyme (ACE) trophy. They are generally well tolerated, but the first dose inhibitors should be prescribed for patients with CHD and may lower blood pressure excessively.
reduced ejection fraction, those with decreased left ventricu- ● Angiotensin II receptor (AT1) antagonists. These drugs lar function due to other causes, diabetics with microalbu- were introduced recently. They do not have adverse meta- minuria or frank proteinuria, and those with impaired renal bolic effects, do not cause cough or angioedema, and are function and heavy proteinuria. For hypertensives who have generally well tolerated. They can worsen renal function in had an uncomplicated myocardial infarction, prescribe patients with bilateral renal artery stenosis.
␤-blockers without intrinsic sympathomimetic activity. Forisolated systolic hypertension, prescribe a low dose of thia- Cardiovascular Risk Reduction in Diabetes
zide, ␤-blocker, ␣-blocker, or long-acting calcium-channel In a trial of patients with type 1 diabetes (ie, insulin- dependent diabetes), careful insulin therapy reduced micro-vascular complications, with a 60% (nonsignificant) reduc- Subsequent Management
tion of macrovascular events. Although trial data in patients If the blood pressure target is not achieved or if side effects with type 2 diabetes are scanty, the consensus is that careful occur, first try substituting a drug from another class. If glycemic control is essential for minimizing diabetic compli- unsuccessful, add a second drug from another class (eg, a diuretic), if not already used, and, if problems still persist, add are correcting overweight to improve control, particularly in a third drug from another class or consider referral to a type 2 diabetics; lowering blood pressure; and controlling lipid abnormalities (Table 5). Frequent aerobic exercise The following is a list of the most commonly used drugs.
facilitates glycemic control and weight control, as does a diet similar to the lipid-lowering diet, but with no sugar other than Thiazides. The use of thiazides is supported by controlled that in fruit and saturated fat (Ͻ7%). Stopping smoking is trial evidence. Low dosage (eg, hydrochlorothiazide 6.25 mg/d up to 12.5 mg/d) lessens the risk of metabolic side Drug treatment may be commenced at the same time as the effects such as potassium depletion, hyperlipidemia, hyper- above measures in patients with severe metabolic abnormal- uricemia, and worsening of glucose tolerance.
ities, CHD, or diabetic complications; in patients with mild -blockers. Use of ␤-blockers without intrinsic sympatho- diabetes, it may be deferred pending the outcome of a 2- to mimetic activity is supported by clinical trial data. Side 4-month trial of diet and exercise. Drug options include effects include severe asthma in predisposed patients, insulin, metformin, sulfonylureas, acarbose, and the new worsening of intermittent claudication, aching of the legs, cardiac failure, and an increased grade of heart block Hypertriglyceridemia and low HDL cholesterol may be (possibly less frequent with cardioselective and vasodilator␤ fully corrected by diabetic control and the measures listed above. However, lipid-lowering drugs should be considered if ACE inhibitors. The indications for the use of these drugs hyperlipidemia persists; the main options are a statin if LDL are listed above. Side effects include a cough. ACEinhibitors should be avoided in patients with bilateral renal elevation predominates or a fibrate if triglycerides remain artery stenosis (which should be suspected in patients with elevated (the risk of fibrate myopathy is increased in the peripheral vascular disease or abdominal aortic aneurysm), presence of renal failure or diabetic nephropathy).
because renal failure may be precipitated.
Management of Thrombogenic Risk Factors
Calcium-channel blockers. Long-acting formulations of To manage thrombogenic risk factors, health-related behavior these drugs should be chosen because short-acting ones is important. Such behavior includes the following.
have precipitated ischemic events. Evidence of reducedcardiovascular events was found in 1 trial using calcium- channel blockers for systolic hypertension in the elderly.
These drugs do not have metabolic side effects, but other untoward effects include headache and dependent edema.
● Increased intake of polyunsaturated fatty acids from the ● ␣-blockers. These drugs are useful in older patients with omega-6 and omega-3 classes (from seed oils and oily fish) systolic hypertension; they have a small favorable effect onplasma lipids and lipoproteins, do not worsen glucose Drug therapy can also be used. The 3 main drugs used and tolerance, and lessen symptoms of benign prostatic hyper- their doses are as follows. Acetylsalicylic acid (75 to 160 mg Assmann et al
Reducing Coronary Heart Disease
per day), preferably enteric-coated, is often used; the risk of (HDL cholesterol in mg/dLϫϪ0.045)ϩ(log [triglyceride level in gastrointestinal bleeding is least with lower dosages. Ticlo- mg/dL]ϫ0.3346)ϩ(smoking behavior [noϭ0, yesϭ1]ϫ0.9266)ϩ pidine (250 mg per day) is an alternative; it does carry a risk (diabetes mellitus [noϭ0, yesϭ1]ϫ0.4015)ϩ(positive family historyof myocardial infarction [noϭ0, yesϭ1]ϫ0.4193)ϩ(angina pectoris of neutropenia, so monitoring white cell count is important.
Clopidogrel (75 mg per day) may be more effective than This algorithm was derived from a population of white men aged acetylsalicylic acid, and warfarin dosage should be adjusted 35 to 65 years and, therefore, its applicability to women, men outside to maintain an International Normalized Ratio (INR) in the this age range, and other ethnic groups has yet to be established. The output of the PROCAM algorithm is expressed as the risk of acoronary event (definite fatal myocardial infarction, definite nonfatalmyocardial infarction, or sudden coronary death) in percentage over CHD Prevention in the Elderly
8 years. In the German population of middle-aged men, the output of After the age of 60 years, risk factors such as plasma the algorithm may be divided into quintiles with the following cholesterol, systolic blood pressure, smoking, and low HDL cut-off points: first quintile, Յ0.91% in 8 years (Յ0.11% per cholesterol confer an increased absolute risk of CHD to at annum); second quintile, 0.92% to 1.40% in 8 years (0.12% to 0.18% least the same extent as in younger persons. Clinical trial data per annum); third quintile, 1.41% to 3.65% in 8 years (0.18% to0.46% per annum); fourth quintile, 3.66% to 7.60% in 8 years on risk factor reduction in older persons are few, but some (0.46% to 0.95% per annum); and fifth quintile, Ͼ7.60% in 8 years evidence exists that cholesterol lowering by diet or by statin Risk factor reduction is appropriate in older persons in Appendix 2
good general health who have reasonable life expectancy andthe capacity to enjoy life. Diets must take eating difficulties, Recommended Foods
food preferences, and nutritional soundness into account.
The following foods may be given as generous helpings in meals Drug interactions are of particular concern, and untoward (preferably as a first course) or as snacks. Table 2 has a morecomplete list.
effects can be sources of difficulty.
Low-calorie vegetables (fresh or frozen, not canned); use cooked, in salad, and as crudite´s. These include: artichokes, asparagus, CHD Prevention in Postmenopausal Women
cabbage, cauliflower, carrot, celery, chicory, cress, cucumber, Most CHD risk factors operate in both sexes. In women, eggplant, endive, French (green) beans, green pepper, leek, let- plasma cholesterol, low HDL cholesterol, and blood pressure tuce, marrow, mushroom, onion (boiled), pumpkin (boiled), rad- are related to risk; diabetes, triglyceride levels, and cigarette Soup: broth, consomme´, and other clear soups.
smoking confer greater risks than in men. Limited data from Beverages: coffee or tea with skim milk, sugar-free soft drinks, and clinical trials in women suggest that cholesterol lowering mineral water; use aspartame and saccharine as sweeteners.
lowers CHD incidence and promotes regression of coronaryartery disease.
Foods Permitted in Controlled Quantities
Estrogen replacement therapy lowers LDL cholesterol and The following foods are permitted in controlled quantities.
increases HDL cholesterol, effects that are attenuated by those progestogens that have androgenic activity. Progesto- Vegetables: 1 small boiled or baked potato.
Cereal foods: 5 U per day. 1 Uϭ1 thin slice of wholemeal bread cut gens such as medroxyprogesterone have only small effects in from a large loaf, 1 cup of sugar-free breakfast cereal, 1⁄2-cup reducing the favorable influence of estrogens. Many obser- vational studies suggest that postmenopausal estrogen re- Fish, chicken, turkey, very lean meat: 120 to 180 g per day.
placement may reduce CHD incidence,2 but such data are Dairy foods: 2 U per day. 1 Uϭ1 cup skim milk, 1⁄2-cup low-fat milk, inconclusive and controlled trial evidence is needed to clarify 1 cup very-low-fat yogurt without added sugar, 30 g of skim milk– based cottage cheese, or 30 g of fat-free fromage frais; 2eggs per week are allowed.
Legumes (pulses): 1⁄2-cup serving, 3 to 4 times per week. These Appendix 1
include boiled lentils, mung beans, chick peas, butter beans, The multiple logistic function from PROCAM has the form: Oils and fats: 10 g (2 to 3 teaspoons) per day. These include olive oil, canola oil, corn oil, and sunflower oil, plus 10 g per day of where yϭϪ12.3199ϩ(age in yearsϫ0.1001)ϩ(systolic blood pres- sure in mm Hgϫ0.0118)ϩ(LDL cholesterol in mg/dLϫ0.0152)ϩ 1 cupϭ200 mLϭ7 fluid ounces; 30 gϭ1 ounce 1938
November 2, 1999
Classification of the Primary Hyperlipidemias
CHD indicates coronary heart disease; HDL, high density lipoprotein; IDL, intermediate density lipoprotein; PVD, peripheral vascular disease; VLDL, very low density lipoprotein; ϩ, slight to moderate increase; ϩϩ, moderate to marked increase; and ϩϩϩ, marked to extreme increase.
*Depending on which lipoprotein class is present in excess, the primary hyperlipidemias may manifest as predominantly elevated levels of cholesterol or of triglyceride, or both lipids may be involved (see below).
†The prevalence of genetic hyperlipidemias varies from population due to genetic drift, founder effects, and selection bias. The data shown in Appendix2 apply to most Caucasian populations.
Reproduced with permission from Nutr Metab Cardiovasc Dis. 1998;8:205– 271 (also available at http:///www.chd-taskforce.com).
1. Brown MS, Goldstein JL. Drugs used in treatment of hyperlipopro- teinemias. In: Gilman AG, Rall TW, Nies AS, Taylor P, eds. Goodmanand Gilman’s The Pharmacological Basis of Therapeutics. 8th ed. NewYork: McGraw-Hill; 1990:874.
2. Assmann G, Schulte H, von Eckardstein A. Hypertriglyceridemia and elevated levels of lipoprotein (a) are risk factors for major coronaryevents in middle-aged men. Am J Cardiol. 1996;74:1179 –1184.
KEY WORDS: cardiovascular diseases Ⅲ risk factors Ⅲ hyperlipidemia
TIMOTHY K MELLOR BDS MBBCh FDSRCS FDSRCPS FRCS EDUCATION 1. Undergraduate The University of Liverpool 1974-78 BDS (Bachelor of Dental Surgery) The University of Wales 1987-91 MB BCh (Bachelor of Medicine & Surgery) 2. Postgraduate The Royal College of Physicians & Surgeons of Glasgow 1983 FDSRCPS (Fellowship in Dental Surgery) The Royal Colle