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Editorial Comment Desirable Serum Total Cholesterol With Low HDL Cholesterol Levels An Undesirable Situation in Coronary Heart Disease Frank M. Sacks, MD
As awareness of the important effects of serum low density lipoprotein (LDL) and high density lipoprotein (HDL) levels on cardiovascular diseases becomes widespread, concerned physicians are asking for guidance on therapy for the patient with cardiovascular disease who has normal or even belowaverage levels of total cholesterol. It has recently become known that patients classified as having "desirable" total cholesterol levels (240 mg/dl), the accompanying report of Miller et a14 found that over 13 years, 61% experienced a cardiovascular event despite a remarkably favorable mean serum cholesterol level of
See p 1165 175 mg/dl and LDL of 115 mg/dl. In this study,4 two measurements emerged all-important for predicting future events -the serum HDL cholesterol concentration and the left ventricular ejection fraction. These findings, although potentially relevant to many patients in a clinical practice, must be considered tentative and in need of confirmation in a larger population. The small sample size limits generalizability and diminishes the ability of the multiple regression analysis to determine the separate contribution of the intercorrelated risk factors. Nonetheless, these findings are consistent with previous work in patients with a wider range of cholesterol levels.56 Therefore, this study underscores the need to measure the HDL concentration and left ventricular ejection fraction on every patient with CHD. The typical CHD patient in the study of Miller et al,4 in addition to having a low HDL level, is a smoker and has a sedentary lifestyle. Where should therapy be focused? It is axiomatic that every effort should be made to help the patient stop smoking as the intervention of paramount importance. The patient also should be enrolled in a weight-loss program, particularly if The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association. From the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and the Department of Nutrition, Harvard School of Public Health, Boston. Address for correspondence: Dr. Frank M. Sacks, Harvard School of Public Health, Department of Nutrition, 665 Huntington Avenue, Boston, MA 02115.
overweight has produced a paunch, and in a supervised, low-intensity exercise program unless this is contraindicated for cardiological reasons. Although these measures each increase HDL, this effect is small and all too easily lost within the noise of random biological and laboratory variability. However, the physician should keep in mind that the influences of smoking, central adiposity, and inactivity on CHD are likely to be only partly mediated through HDL levels.7'8 Thus, whatever happens to the HDL level, the patient who has made favorable changes in these risk factors should be considered at overall lower risk. Alcoholic beverages, whatever their source and color, and oral estrogen replacement for postmenopausal women each raise HDL9,10 and are associated with decreased risk of CHD.1'12 However, for all too obvious reasons, alcohol, as an intervention, defies general prescription. A reasonable position for physicians is to give reassurance to patients who choose moderate intake that is appropriate to their lifestyle rather than encouragement to teetotalers to begin drinking. Estrogen replacement therapy is associated with reduced risk of fatal coronary events in women with preexisting CHD.12 Although direct information from clinical trials is lacking and the practical use of estrogens is complex, many women, particularly those at high risk of coronary events, would be advised to take estrogen. It is also essential to know whether left ventricular dysfunction exists. It is well established that the left ventricular ejection fraction is a risk factor after myocardial infarction for the development of heart failure and coronary death even in the patient who does not have symptoms of heart failure.13 Knowledge of the ejection fraction after myocardial infarction has gained new importance with the recent demonstration that patients who have ejection fractions of less than 40% and who do not have symptoms of heart failure had improved survival and reduction in major cardiovascular events with long-term therapy with the angiotensin converting enzyme inhibitor captopril.14 Diet therapy is prescribed reflexively, but clinicians rarely consider what type of dietary change will affect HDL. Diet therapy that lowers LDL has an established basis to prevent CHD. But because conventional low fat diets also lower HDL, therapy will be frustrating and of uncertain value when a low HDL is the only lipoprotein abnormality. However, as we noted recently,15 diets that replace saturated animal fats with natural, unhydrogenated, mono-, or polyunsaturated vegetable oils do not
Downloaded from http://circ.ahajournals.org/ at Imperial College London Library on April 21, 2015
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Circulation Vol 86, No 4 October 1992
materially lower HDL. Thus, if diet therapy is prescribed, (and it is not proven that it can benefit coronary atherosclerosis in this type of patient as opposed to the patient with higher levels of LDL), then it should have a moderate content of vegetable oil. Also, diets that are rich in vegetable products including unprocessed vegetable oils have antioxidant vitamins that could retard atherosclerosis.1617 On balance, this type of diet therapy is likely to be beneficial and should be recommended. The CHD patients with "desirable" total cholesterol levels in the report of Miller et a14 have total cholesterol levels that range from about 130 to 200 mg/dl and LDL levels that range from below 100 mg/dl to about 150 mg/dl. How strong is the scientific basis for a strategy that aims to lower these already low levels? Observational epidemiological studies demonstrate that the relation between serum cholesterol and coronary disease cannot be described accurately by a straight line. Rather, rates of CHD increase slightly as serum cholesterol levels increase from the mid 100s to the low 200s.5618-20 From the mid-200s upward, risk of CHD increases sharply, and the threshold of 240 mg/dl for "undesirable" classification corresponds to the beginning of this high-risk range. These curves are similar in populations who do or do not have CHD when the period of observation begins.56"18-20 Therefore, as serum cholesterol decreases within the "desirable" or "borderline" ranges, the decreases in rates of CHD become progressively smaller. Accordingly, in the study of Miller et al,4 the event rate did not change over the range of LDL,
Editorial Comment Desirable Serum Total Cholesterol With Low HDL Cholesterol Levels An Undesirable Situation in Coronary Heart Disease Frank M. Sacks, MD
As awareness of the important effects of serum low density lipoprotein (LDL) and high density lipoprotein (HDL) levels on cardiovascular diseases becomes widespread, concerned physicians are asking for guidance on therapy for the patient with cardiovascular disease who has normal or even belowaverage levels of total cholesterol. It has recently become known that patients classified as having "desirable" total cholesterol levels (240 mg/dl), the accompanying report of Miller et a14 found that over 13 years, 61% experienced a cardiovascular event despite a remarkably favorable mean serum cholesterol level of
See p 1165 175 mg/dl and LDL of 115 mg/dl. In this study,4 two measurements emerged all-important for predicting future events -the serum HDL cholesterol concentration and the left ventricular ejection fraction. These findings, although potentially relevant to many patients in a clinical practice, must be considered tentative and in need of confirmation in a larger population. The small sample size limits generalizability and diminishes the ability of the multiple regression analysis to determine the separate contribution of the intercorrelated risk factors. Nonetheless, these findings are consistent with previous work in patients with a wider range of cholesterol levels.56 Therefore, this study underscores the need to measure the HDL concentration and left ventricular ejection fraction on every patient with CHD. The typical CHD patient in the study of Miller et al,4 in addition to having a low HDL level, is a smoker and has a sedentary lifestyle. Where should therapy be focused? It is axiomatic that every effort should be made to help the patient stop smoking as the intervention of paramount importance. The patient also should be enrolled in a weight-loss program, particularly if The opinions expressed in this editorial comment are not necessarily those of the editors or of the American Heart Association. From the Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, and the Department of Nutrition, Harvard School of Public Health, Boston. Address for correspondence: Dr. Frank M. Sacks, Harvard School of Public Health, Department of Nutrition, 665 Huntington Avenue, Boston, MA 02115.
overweight has produced a paunch, and in a supervised, low-intensity exercise program unless this is contraindicated for cardiological reasons. Although these measures each increase HDL, this effect is small and all too easily lost within the noise of random biological and laboratory variability. However, the physician should keep in mind that the influences of smoking, central adiposity, and inactivity on CHD are likely to be only partly mediated through HDL levels.7'8 Thus, whatever happens to the HDL level, the patient who has made favorable changes in these risk factors should be considered at overall lower risk. Alcoholic beverages, whatever their source and color, and oral estrogen replacement for postmenopausal women each raise HDL9,10 and are associated with decreased risk of CHD.1'12 However, for all too obvious reasons, alcohol, as an intervention, defies general prescription. A reasonable position for physicians is to give reassurance to patients who choose moderate intake that is appropriate to their lifestyle rather than encouragement to teetotalers to begin drinking. Estrogen replacement therapy is associated with reduced risk of fatal coronary events in women with preexisting CHD.12 Although direct information from clinical trials is lacking and the practical use of estrogens is complex, many women, particularly those at high risk of coronary events, would be advised to take estrogen. It is also essential to know whether left ventricular dysfunction exists. It is well established that the left ventricular ejection fraction is a risk factor after myocardial infarction for the development of heart failure and coronary death even in the patient who does not have symptoms of heart failure.13 Knowledge of the ejection fraction after myocardial infarction has gained new importance with the recent demonstration that patients who have ejection fractions of less than 40% and who do not have symptoms of heart failure had improved survival and reduction in major cardiovascular events with long-term therapy with the angiotensin converting enzyme inhibitor captopril.14 Diet therapy is prescribed reflexively, but clinicians rarely consider what type of dietary change will affect HDL. Diet therapy that lowers LDL has an established basis to prevent CHD. But because conventional low fat diets also lower HDL, therapy will be frustrating and of uncertain value when a low HDL is the only lipoprotein abnormality. However, as we noted recently,15 diets that replace saturated animal fats with natural, unhydrogenated, mono-, or polyunsaturated vegetable oils do not
Downloaded from http://circ.ahajournals.org/ at Imperial College London Library on April 21, 2015
1342
Circulation Vol 86, No 4 October 1992
materially lower HDL. Thus, if diet therapy is prescribed, (and it is not proven that it can benefit coronary atherosclerosis in this type of patient as opposed to the patient with higher levels of LDL), then it should have a moderate content of vegetable oil. Also, diets that are rich in vegetable products including unprocessed vegetable oils have antioxidant vitamins that could retard atherosclerosis.1617 On balance, this type of diet therapy is likely to be beneficial and should be recommended. The CHD patients with "desirable" total cholesterol levels in the report of Miller et a14 have total cholesterol levels that range from about 130 to 200 mg/dl and LDL levels that range from below 100 mg/dl to about 150 mg/dl. How strong is the scientific basis for a strategy that aims to lower these already low levels? Observational epidemiological studies demonstrate that the relation between serum cholesterol and coronary disease cannot be described accurately by a straight line. Rather, rates of CHD increase slightly as serum cholesterol levels increase from the mid 100s to the low 200s.5618-20 From the mid-200s upward, risk of CHD increases sharply, and the threshold of 240 mg/dl for "undesirable" classification corresponds to the beginning of this high-risk range. These curves are similar in populations who do or do not have CHD when the period of observation begins.56"18-20 Therefore, as serum cholesterol decreases within the "desirable" or "borderline" ranges, the decreases in rates of CHD become progressively smaller. Accordingly, in the study of Miller et al,4 the event rate did not change over the range of LDL,
