Coronary Heart Disease: Reducing The Risk
1999; Lippincott Williams & Wilkins; Volume: 100; Issue: 18 Linguagem: Inglês
10.1161/01.cir.100.18.1930
ISSN1524-4539
AutoresGerd Assmann, Rafael Carmena, Paul Cullen, Jean‐Charles Fruchart, F. Jossa, B. Lewis, Mario Mancini, Rodolfo Paoletti,
Tópico(s)Cardiomyopathy and Myosin Studies
ResumoHomeCirculationVol. 100, No. 18Coronary Heart Disease: Reducing The Risk Free AccessOtherPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessOtherPDF/EPUBCoronary Heart Disease: Reducing The Risk A Worldwide View Gerd Assmann, Rafael Carmena, Paul Cullen, Jean-Charles Fruchart, Fabrizio Jossa, Barry Lewis, Mario Mancini, Rodolfo Paoletti and Gerd AssmannGerd Assmann From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Rafael CarmenaRafael Carmena From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Paul CullenPaul Cullen From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Jean-Charles FruchartJean-Charles Fruchart From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Fabrizio JossaFabrizio Jossa From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Barry LewisBarry Lewis From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Mario ManciniMario Mancini From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) , Rodolfo PaolettiRodolfo Paoletti From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) and From the Institute of Arteriosclerosis Research and Institute of Clinical Chemistry and Laboratory Medicine, University of Münster, 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 of Pharmacy, University of Milan, Italy (R.P.) and for the International Task Force for the Prevention of Coronary Heart Disease Originally published2 Nov 1999https://doi.org/10.1161/01.CIR.100.18.1930Circulation. 1999;100:1930–1938Worldwide, cardiovascular diseases are now the most common cause of death and a substantial source of chronic disability and health costs. In the light of new data from clinical trials and a fuller understanding of risk factors, the International Task Force for the Prevention of Coronary Heart Disease, in cooperation with the International Atherosclerosis Society, prepared a revised and comprehensive statement regarding the scientific basis of the primary and secondary prevention of cardiovascular disease. The following is a short account of the clinical implications of this statement. It is best read in conjunction with the full document, which can be found at http://www.chd-taskforce.comAssessing the Global Risk of Cardiovascular DiseaseAssessing a patient's overall or global risk of cardiovascular disease is the first step in preventive care, for it enables the physician to identify and provide the appropriate level of treatment for risk factors. Much can be learned from measuring even a few risk factors. The fuller the knowledge of the patient's risk status, the sounder the treatment decisions. Initial costs may be offset by long-term rational treatment. The goals of treatment and, hence, the extent of dietary change and the need for (and choice and dosage of) drug treatment all depend on global risk assessment. Two methods for determining global risk follow.Method INote and tabulate the following risk factors, including those laboratory investigations that are available.Age, Sex, and Menopausal StatusRisk increases progressively with adult age, and coronary heart disease (CHD) is most common after the age of 60 years. In premenopausal women, CHD is rare (except in those who use oral contraceptives and smoke). After menopause, risk increases steeply, approaching that of men after the age of 70 years.History of Cardiovascular DiseaseThe risk of further CHD events or stroke is much higher in persons with a history of myocardial infarction, angina, stroke, or intermittent claudication and in those who have ischemic changes on resting or exercise ECG than in persons without such findings. Any of these features confers grade III status (high risk; Table 1) and warrants vigorous reduction of all risk factors.Positive Family History of CHD, Stroke, or Peripheral Vascular DiseaseNote any reliable cardiovascular family history, and grade its severity on the basis of the following. How early in life relatives were affected (discount events presenting after the age of 60 years)The closeness of the relationships (eg, CHD in a sibling or parent confers greater risk than CHD in an uncle)What proportion of adult relatives were affectedSmokingNote the duration and amount of current and former use of cigarettes and other tobacco products; these are potent but potentially reversible causes of CHD.Psychosocial Risk FactorsThere is increasing evidence that stress, lack of social support, depression, and low socioeconomic status are associated with an increased risk of CHD. Although specific treatment for these factors is often difficult, assessing them is still an important part of the work-up. The psychosocial profile of the patient also has a large influence on the patient's ability to comply with measures such as lifestyle modifications designed to reduce risk.ExaminationWeight and HeightDerive the body mass index (BMI) by nomogram or calculation (BMI=weight in kg/height in m2). Overweight is defined as a BMI>25 and obesity as a BMI>30. Excess adipose tissue in the truncal region is an important cardiovascular disease risk factor, and it adversely affects blood pressure, cholesterol (total, HDL, and LDL), and triglyceride levels and glucose tolerance. Truncal obesity can be assessed and treatment can be monitored by estimating the weight/hip ratio (circumference of waist at umbilicus/circumference of hips at widest part; it is normally <1.0 in men and <0.85 in women) or by measuring girth horizontally at the level of the umbilicus (normally <94 cm in men and 160 mm Hg) is an important risk factor in the elderly. Blood pressure is best measured with the subject seated, after he or she has rested for 5 minutes.Cardiovascular ExaminationThe cardiovascular examination may reveal a carotid bruit or a missing peripheral pulse, denoting existing atherosclerotic disease and conferring grade III risk.InvestigationsPlasma Lipids and LipoproteinsThe preferred investigation for plasma lipids and lipoproteins is one that measures total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol after a 14-hour fast (water permitted). If the full profile is unavailable, plasma cholesterol alone is useful in defining risk and diagnosing some major familial hyperlipidemias.Lipid levels are continuously related to risk. Take particular note of an LDL cholesterol level >135 mg/dL (>3.5 mmol/L), a HDL cholesterol level <35 mg/dL ( 200 mg/dL (>11.1 mmol/L). Diabetes is now defined as a plasma glucose level >126 mg/dL (>7 mmol/L) after fasting for 8 hours and/or a plasma glucose level >200 mg/dL (>11.1 mmol/L) at 2 hours during an oral glucose tolerance test using 75 g glucose.Other CHD risk factors that are now measured in many laboratories include fibrinogen and homocysteine.On the basis of the presence, number, and severity of some or all of these 11 groups of risk factors, increased risk is assigned to 1 of 3 grades: I, II, or III, as seen in Table 1. Appropriate treatment decisions are based on this grading.In asymptomatic patients at increased risk, the precision of risk assessment may be enhanced by imaging methods. Noninvasively, quantitative carotid Doppler ultrasound can be used. Increased interomedial thickness is predictive of a 2-fold increase in CHD risk, and detection of carotid plaques indicates a 4-fold increase.Method IIQuantitative Risk AssessmentOn the basis of 9 risk factors, data from the Prospective Cardiovascular Münster (PROCAM) Study are used to provide a quantitative estimate of risk (Figure) using an algorithm that is currently applicable to men aged 40 to 65 years (Appendix 1). This is available as an interactive program on the Task Force website (http://www.chd-taskforce.com).Primary and Secondary PreventionEvidence of a myocardial infarction, stroke, or other atherosclerotic disease confers a high risk of further cardiovascular events and has a risk level of grade III. Patients in this category require vigorous intervention against risk factors, and clear evidence exists showing the benefits of such intervention. Reducing risk in such patients is termed secondary 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 manifestation of CHD (such as myocardial infarction) survive for 40 years, initial training should be gentle (eg, 10 minutes of walking daily). As fitness and tolerance increase, the dose increases in weekly increments, initially by extending the duration. Later, intensity can be increased if suitable, eg, by brisk walking or by alternating walking and jogging or gentle swimming. Young persons and fit middle-aged subjects may ultimately undertake 20 to 30 minutes of aerobic activity 4 to 5 times weekly.Exercise intensity can be judged subjectively; persons should aim for a comfortable intensity, sufficient to extend themselves slightly. Mild shortness of breath during exercise should abate within 4 minutes or less of resting. The subject should be told to stop and to report to a physician if recovery time is prolonged or if chest pain, syncope, or persistent cough occur. Another way to judge intensity requires monitoring pulse rate during exercise; target pulse rates are shown in Table 3. A training effect is obtained at rates of 60% of the maximum rate for age, and this is the initial target rate. With increasing fitness, in persons at low cardiovascular risk, the target may be increased gradually to 75% of maximum, for example, by increasing the speed of walking.Exercise should be supervised, at least initially, and ECG monitoring should be performed in patients at higher risk; this includes those with overt cardiovascular disease, such as angina or silent ischemia, and especially those with high-grade ventricular arrhythmias, low ejection fractions, hypotension on exercise, and inappropriate exercise-induced tachycardia. The type and amount of exercise must also take into account respiratory or musculoskeletal disease and peripheral vascular disease.Treatment of HyperlipidemiaClinical trial evidence justifies placing a strong emphasis on plasma lipid-lowering as part of primary and secondary prevention. Accompanying risk factors are treated at the same time. Past concerns about the safety of lowering plasma cholesterol are no longer tenable. The intensity of lipid-lowering treatment is determined by the patient's global risk and by his or her responsiveness to treatment.The value of conservative treatment, ie, diet (including the extremely important element of reduction of overweight) and exercise, cannot be too strongly emphasized; under controlled conditions, diet even without weight reduction can lower plasma cholesterol by 10% to 25%. Hence, efforts should be made to maximize skills in dietary counseling. The patient should know that current dietary guidelines fully maintain the pleasures of eating and are similar to the habitual diets of countries in which mortality from CHD and many cancers is far lower than in Western countries.Lipid-lowering drugs should be introduced only after a careful trial of conservative management, if indicated by the grade of risk, and always used together with ongoing dietary measures.Target Levels for Lipid LoweringTable 4 shows suggested goals for lipid-lowering based on the grade of global risk. Pending the results of further trials to determine optimal goals, Table 4 is consistent with epidemiological studies and with meta-analyses of trials. Treatment is best monitored by LDL cholesterol levels.History and physical examination may reveal the features of major familial hyperlipidemias. Most are uncommon, but they require detection because they may confer a particularly high risk of CHD or pancreatitis. These disorders are tabulated in Appendix 3.A determined effort should be made to reduce or correct even minor degrees of overweight using the means described in the section on weight reduction together with those in the section on exercise. These measures have a strong favorable effect on most common plasma lipid disorders.Causes of secondary hyperlipidemia should be treated or removed, if possible. Among these causes are medications, including corticosteroids, anabolic steroids, thiazides, and retinoids; diabetes mellitus; hypothyroidism; alcohol abuse; chronic renal failure; nephrotic syndrome; and bulimia and anorexia nervosa.Lipid-Lowering DietA lipid-lowering diet is shown in Appendix 2; it is designed for persons whose habitual diet is Western and requires adaptation. In the lipid-lowering diet, fat provides up to 30% of food energy; saturated plus hydrogenated fat contributes no more than 7% to 10% of energy intake, monounsaturated fat 10% to 15%, and polyunsaturated fat up to 7% to 8%. The diet has a high content of complex carbohydrates, and it provides at least 25 g of fiber per day, with an emphasis on soluble fiber. It contains less than 300 mg of cholesterol per day. This is achieved with a generous intake of whole-grain cereal foods, fruit and vegetables, fat-free and low-fat dairy products, fish, low-fat poultry, moderate amounts of low-fat meats and of eggs, and unsaturated vegetable oils as the main source of fats. Preferred cooking methods include grilling, steaming, boiling, microwave cooking, and barbecue cooking.Some patients whose response to this diet is incomplete will achieve satisfactory control when a diet is given that provides 25% to 27% of energy from fat (6% to 8% of which is from saturated fat) and 200 to 250 mg of cholesterol per day.For patients with hypertriglyceridemia, the standard lipid-lowering diet is prescribed, with particular emphasis on controlling overweight and specific advice on moderating or avoiding alcohol consumption and increasing the intake of oily fish. Patients with severe hypertriglyceridemia caused by excess chylomicron particles need a minimal intake of long-chain fatty acids but can substitute medium-chain triglycerides.Lipid-Lowering DrugsIn patients at grade I risk, conservative treatment is usually effective in achieving target lipid levels. In those at grade III risk, a short (eg, 2 month) trial of diet is warranted, during which at least 2 sets of lipid measurements should be made and averaged; if target values are not attained, a drug should be introduced, with ongoing attention to diet. In those at grade II risk, an extended trial of conservative treatment is required, with repeated counseling, for a period of at least 6 months. Whenever possible, the use and choice of drug should be based on clinical trial data. A discussion of commonly used lipid-lowering drugs follows.Hepatic hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors offer a major advance in CHD prevention. They effectively lower LDL cholesterol, and they have a moderate effect in lowering triglycerides, which may be more marked with some newer statins. HMG CoA reductase inhibitors are now the drugs of first choice for familial hypercholesterolemia, and they can be of value in combined (mixed) hyperlipidemia. Treatment commences at a minimum dosage, with dose titration at 6- to 8-week intervals. Lipid levels and alanine transaminase (ALT) levels should be monitored. Severe hypercholesterolemia may require combination treatment with a resin. Most statins are not licensed for use in children, and they are not given to women of child-bearing age unless effective contraception is assured. Headache, constipation, flatulence, and dyspepsia are recognized side effects. Liver function can be impaired, and statins are contraindicated in the presence of active liver disease or elevated ALT levels. Myopathy and potentially fatal rhabdomyolysis are rare side effects, the risk of which is increased by drug interactions with erythromycin, fibrates, azole antifungals, cyclosporin, tacrolimus, nicotinic acid, and some calcium-channel blockers.Resins (bile acid sequestrants) are effective cholesterol-lowering drugs. Being nonabsorbable, they are largely free from systemic side effects. They are presented as a powder and taken in water or fruit juice with meals. Patient acceptance is sometimes imperfect. Side effects include constipation, dyspepsia, abdominal pain, and malabsorption of folic acid and several concomitantly administered drugs. In a larger dose, resins can increase triglyceride levels.Fibric acid derivatives are effective triglyceride-lowering drugs; they increase HDL cholesterol substantially and (particularly the more recent members of the class) also lower plasma cholesterol. Abnormal liver function is a contraindication. Side effects include dyspepsia, rashes, abnormal liver function and (rarely) hepatitis (ALT should be monitored), gallstones, impotence, myopathy and rhabdomyolysis, and sensitivity to warfarin. Great caution is needed in using fibrates together with statins.Nicotinic acid in large doses lowers triglyceride and cholesterol levels and increases HDL cholesterol. Flushing, pruritus, and dyspepsia are common and tend to limit compliance; abnormal liver function may occur. A gradually increasing dose schedule is needed. Liver disease, gout, and diabetes are relative contraindications.Fish oil in large doses effectively lowers triglyceride levels.Management of HypertensionThe prevalence of hypertension is about 20% in most countries, rising with age to about 50% by the age of 65 years. In the US in 1988, the proportion of hypertensives who were detected, treated, and achieved good control was 29%; similarly limited success has been observed in Europe.1The usual goal of treatment is to achieve a systolic blood pressure <140 mm Hg and a diastolic blood pressure 30 mL/d), lowers blood pressure in susceptible hypertensivesIncrease in aerobic physical activityReduction of salt intake to 4 g (70 mmol) per dayIncrease intake of fruit and vegetables (which provides a substantial intake of potassium) and lower intake of fat and saturated fat; these items are of proven value in lowering blood pressureDeal with coexisting cardiovascular risk factors (eg, smoking and hyperlipidemia)Drug TreatmentDrug treatment commences with low doses followed by slow dose titration to achieve 24-hour control with once-daily medication at a minimum dosage. If systolic pressure >160 mm Hg and target organ damage are present, initiate drug treatment immediately; if diastolic pressure >90 mm Hg and target organ damage are present, start drug treatment within 1 to 2 weeks if a trial of nonpharmacological measures is not promptly effective. Conversely, if hypertension is mild and no target organ damage exists, a trial of nonpharmacological management for up to 6 months is warranted. Available clinical trial data suggest that thiazides and β-blockers are the preferred initial drugs for uncomplicated hypertensives. Nonpharmacological measures are continued after the start of drug treatment.Initial DrugsLow-dose thiazides or β-blockers should be the first drugs used for pharmacological management of hypertension, unless contraindicated. Angiotensin-converting enzyme (ACE) inhibitors should be prescribed for patients with CHD and reduced ejection fraction, those with decreased left ventricular function due to other causes, diabetics with microalbuminuria or frank proteinuria, and those with impaired renal function and heavy proteinuria. For hypertensives who have had an uncomplicated myocardial infarction, prescribe β-blockers without intrinsic sympathomimetic activity. For isolated systolic hypertension, prescribe a low dose of thiazide, β-blocker, α-blocker, or long-acting calcium-channel blocker.Subsequent ManagementIf the blood pressure target is not achieved or if side effects occur, first try substituting a drug from another class. If unsuccessful, add a second drug from another class (eg, a diuretic), if not already used, and, if problems still persist, add a third drug from another class or consider referral to a specialist.The following is a list of the most commonly used drugs. Thiazides. The use of thiazides is supported by controlled trial evidence. Low d
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