Lipids and hypertension: Implications of new guidelines for cholesterol management in the treatment of hypertension

Lipids and Hypertension Implicationsof New Guidelinesfor Cholesterol Management in the Treatment of Hypertension

RICHARD H. GRIMM, Jr., M.D., Ph.D. DONALD 6. HUNNINGHAKE, M.D. Minneapolis,

The approach to management of cardiovascular risk factors has been greatly enhanced by the recent publication of results from several large intervention studies. This increased knowledge has led to rapid changes in perspective and to some controversies regarding cardiovascular risk management. The major cardiovascular disease risk factors are high blood pressure, elevated serum cholesterol, and cigarette smoking. in the past, physicians have paid little attention to the latter two factors, focusing primarily on severe hypertension. initially, the pharmacologic treatment of hypertension consisted mostly of thiazide diuretics, since they were the only agents generally available that were well-tolerated by most patients. Over the past decade, however, new data from large-scale intervention studies and the development of many new classes of antihypertensive agents have considerably improved the approach to managing ail three primary risk factors. Recently published results of major clinical trials are likely to further alter physicians’ perspectives and influence their practice habits. This article proposes an approach to comprehengive risk management that simultaneously involves all the major risk factors, with emphasis on blood pressure and lipids. The rationale for this integrated approach is based on the following facts: (1) Hypertension trials have not convincingly demonstrated that lowering blood pressure alone reduces the risk for coronary heart disease; (2) Cholesterol lowering has been shown conclusively to reduce the risk of coronary heart disease; (3) Several classes of antihypertensive agents have now been found to significantly affect blood lipids, either adversely or beneficially; and (4) Past observational epidemiologic studies have shown a positive association between blood lipids (cholesterol and triglycerides) and blood pressure, implying that these two conditions commonly occur together. The background supporting these facts, as well as a practical approach to the treatment of hypertension that takes into consideration the management of blood lipids, is provided in this article.

Minnesota

LIPIDS AND CARDIOVASCULAR DISEASE RISK From the Division of Epidemiology, School of PubI/c Health, and the Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Dr. Richard H. Grimm, Jr., is an established investigator of the American Heart Association. Requests for reprints should be addressed to Dr. Richard H. Grimm, Jr., University of Minnesota, School of Public Health, Stadium Gate 27, 611 Beacon Street Southeast, Minneapolis, Minnesota 55455.

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There is general agreement that blood levels of total cholesterol and lowdensity lipoprotein cholesterol are positively correlated and that high-density lipoprotein cholesterol levels are inversely related to the risk of developing coronary heart disease. The triglyceride level is also positively associated with the risk of developing coronary heart disease in some studies, but there is less agreement on whether it is an independent risk factor or serves as a marker for the presence of other risk factors. There have

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been a number of studies that evaluated the effects on coronary heart disease risk of reducing cholesterol levels by either diet or drugs, and although the results generally suggested a beneficial effect, the evidence was largely interpreted as inconclusive. The results of more recent studies, however, analyzed either singly or in combination with other data, indicate that cholesterol lowering is associated with a reduced risk of coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial (1,2] attempted to determine whether reducing plasma cholesterol, particularly low-density lipoprotein cholesterol, would decrease the incidence of fatal and nonfatal myocardial infarction. A total of 3,800 men with plasma cholesterol levels greater than 285 mg/dl participated. All were maintained on a modest cholesterol-lowering diet and were then randomly assigned to receive either placebo or cholestyramine (a cholesterol-resin binding agent) and followed for seven to 10 years. The cholestyramine-treated group had average reductions in total cholesterol and low-density lipoprotein cholesterol for the entire study that were 9 and 13 percent greater, respectively, than those observed in the placebo group, and there was an associated 19 percent reduction in the incidence of fatal and nonfatal coronary heart disease (p ~0.05). Participants who took the full dose of cholestyramine and had a 25 percent reduction in total cholesterol (35 percent decrease in low-density lipoprotein cholesterol) had a 49 percent lower incidence of coronary heart disease. The findings of the Coronary Primary Prevention Trial provided a convenient rule of thumb: for every 1 percent reduction in total serum cholesterol, coronary heart disease risk was reduced by 2 percent. A wide variety of other studies or analyses of the data from multiple studies indicate that a reduction in cholesterol levels is associated with a decreased risk of coronary heart disease, either for primary prevention or for patients with clinical manifestations of coronary heart disease [l81. However, beneficial effects of a reduction in cholesterol levels on total mortality have not been conclusively demonstrated. Consensus Conference. In December 1984, the National Heart, Lung, and Blood Institute sponsored a consensus workshop entitled “Lowering Blood Cholesterol To Prevent Heart Disease” [7]. A diverse group of experts convened to consider the implications of the Lipid Research Clinics Coronary Primary Prevention Trial as well as all previous studies and to make recommendations for the management of cholesterol. Conclusions of this consensus group included the following: (1) Elevated blood cholesterol is a major cause of coronary heart disease; (2) It is now established that reducing elevated blood cholesterol (specifically low-density lipoprotein cholesterol) will decrease the risk of myocardial infarctions due to coronary heart disease; (3) A cholesterol-lowering diet is recommended for all adults and children over the age of two

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years; (4) Treatment is recommended for persons whose blood cholesterol levels are within the upper 25 percent of the population distribution. HYPERTENSION DISEASE RISK

AND CARDIOVASCULAR

Guidelines for the management of hypertension have been revised over the years based upon studies that demonstrate benefits from treatment. Suggested guidelines have progressed from the management of severe hypertension only, to the current recommendation that even mild hypertension should be treated. When treating hypertension, it is important to consider the results of several major studies reported in recent years. The Hypertension Detection and Follow-Up Program [S-lo], which studied 10,940 men and women with diastolic hypertension, showed convincingly that treatment of diastolic hypertension, including mild hypertension, was beneficial in preventing mortality from all causes. In addition, stroke mortality was substantially reduced in persons receiving stepped-care versus referred care [ll]. The Australian Trial (121 of mild hypertension supported the findings of the previous study and showed a reduction in cardiovascular events in patients with diastolic blood pressure greater than or equal to 95 mm Hg and less than 110 mm Hg who were treated actively compared with patients who received placebo. The Multiple Risk Factor Intervention Trial [13,14] reported results that were generally consistent with the Australian and Hypertension Detection and Follow-Up Program studies, in that there were fewer coronary heart disease deaths among hypertensive patients with normal baseline electrocardiograms who received special intervention as compared with those who received community care (usual care). The Multiple Risk Factor Intervention Trial, however, did contradict most other blood pressure studies in that one subgroup, hypertensive patients with baseline electrocardiographic abnormalities, appeared to do worse with intensive stepped-care therapy than with usual care [15]. The Medical Research Council Working Party has recently published results of the Medical Research Clinics Trial on treatment of mild hypertension [16]. The aim of that study was to determine whether drug treatment of mild hypertension (diastolic blood pressure from 90 to 109 mm Hg) reduced the rate of stroke or of death due to hypertension and coronary events in men and women between the ages of 35 and 64. Patients (n = 17,354) were randomly allocated to three groups-a placebo group, a diuretic (bendrofluazide) group, or a beta-blocker (propranolol) group-and followed for at least five years. Although active treatment significantly reduced the stroke rate, coronary event rates in the treatment groups were not significantly different from the rates in the placebo group. Subgroup analysis suggested there were potentially important differences according to type of treatment:

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TABLE I

THERAPY-GRIMM

and HUNNINGHAKE

Physicians’ Attitudes on Risk Factors* Percent+

Riskfactor Cigarette smoking High blood pressure Obesity/overweight Sedentary life-style Stress Serum cholesterol “Type A” behavior pattern

91 86 58 44 43 40 32

‘Data from a physicians’ survey conducted by the Minnesota Heart Health Program, based on 373 physician respondents (60 percent) from four upper-Midwest communities. +Percent responding that a reduction in the risk factor would have a substantial effect on reducing the incidence of cardiovascular disease.

TABLE ii

Diastolic Blood Pr&%Wo

Seturn

Cholesterol (ma/W

(mmHII) 100 100 *Adapted

Coronary Heart Disease Risk (Fatal or Nonfatal Myocardiai Infarction) in Two Male Hypertensive Nonsmokers According to Serum Cholesterol Level*

180 240 from

Five-Year Risk (percent) 3.5 5.8

20-Year

Risk (percent) 18 30

[49], with permission.

diuretic therapy, for example, appeared to be more effective in reducing the incidence of stroke than was betablocker treatment [16]. Although many answers have been provided by these studies, additional questions have been raised concerning specific approaches to the management of hypertension. One question concerns the value of using’diuretics as an initial step in all patients with hypertension. Diuretics, the most frequently used drugs, have been found, in many studies, to reduce mortality from ail causes and the incidence of stroke. it is possible, however, that certain subgroups of hypertensive patients (such as those with resting electrocardiographic abnormalities, as defined in the Multiple Risk Factor intervention Trial) with coronary heart disease end points do not benefit from or do poorly with diuretic therapy. Other questions relate to whether the selection of antihypertensive therapy should consider the mechanism by which blood pressure is reduced and/or the side effect profile of a drug. These factors could influence the ability of a drug to prevent mortality and morbidity, independent of its effects on decreasing blood pressure. Still other questions involve recognizing potential interactions between risk factors and the possibility that treatment regimens designed to address these interac-

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tions may be more effective than the traditional, standardized stepped-care approach recently recommended by the Joint National Committee [17]. Total Cardiovascular Risk Profile. Today, more attention is being focused on coordinating efforts to reduce multiple risk factors. It is now recognized that factors other than hypertension play a major role in increasing cardiovascular risk and that efforts designed to reduce multiple risk factors may maximize the overall benefit of treatment. The adverse effects of smoking are well established. It is also known that levels of lipids and lipoproteins prospectively predict the risk of coronary heart disease, and that modification of these factors in a favorable direction can reduce this risk. Although it has not been proven that drug-induced adverse effects on lipids and lipoproteins (such as those produced by antihypertensive agents) do increase the risk of coronary heart disease, it is reasonable to suspect that an increased risk could result. Although pharmacologic treatment of hypertension is now routine in the primary care specialties, recognition of elevated cholesterol levels as a risk factor and systematic approaches to reducing these levels are not common. in conjunction with the Minnesota Heart Health Program, a survey of physicians was conducted in four upperMidwest communities to assess attitudes and practice habits concerning cardiovascular risk factors [18]. Table I shows how physicians in that survey ranked risk factors according to their perception of the factor’s importance. Hypertension and cigarette smoking were rated the most important. Serum cholesterol was ranked much lower. Additional results indicated that these physicians possessed greater knowledge about treating hypertension than they did about methods of lowering blood cholesterol. They also rated themselves poor in terms of their effectiveness in treating elevated cholesterol levels. Standard current medical practice is to intervene only in cases of extreme elevations in risk factors, with the possible exception of hypertension. However, of the approximately one million patients who have myocardial infarctions each year, the majority have mild to moderate elevations in multiple risk factors. Table ii illustrates this point. In this example, although both patients have diastolic blood pressures of 100 mm Hg, their serum cholesterol levels differ-l 80 mg/dl versus 240 mg/dl. Because of the difference in cholesterol, the 20-year risk of coronary heart disease is almost twice as great in the patient with the higher cholesterol level. Awareness of the overall increased risk associated with elevations in multiple risk factors is especially important for hypertensive patients. Several classes of antihypertensive agents have been found to significantly alter blood cholesterol and lipoprotein levels. Table iii summarizes the lipid effects seen with the three classes of agents that have been extensively studied: thiazide diuretics, beta blockers, and alpha blockers. Several studies have now documented that thiazide

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TABLE III

THERAPY-GRIMM

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Effects of Antihypertensive Drugs on Lipids Total Cholesterol (percent)

Thiazide diuretics Beta blockers Alpha blockers

TABLE IV

ON INITIAL ANTIHYPERTENSIVE

High-Density LipoproteinChoiestemi (percent)

Low-Density LipopmteinChoiestemi (percent)

t 5-a

t 5-8 -

J
L3

Triglycerides (percent) f 15-25 t 30 -

Estimated Coronary Heart Disease Risk in %-Year-Old Male Hypertensive Nonsmoker by Type of Treatment* Riskot Myocardiai infarction (percent) Treatment

No treatment Cholesterol-lowering diet alone Thiazide diuretic with no dietary controls Thiazide diuretic plus a cholesterollowering diet Prazosin plus a cholesterollowering diet

DiastolicBloodPmssum (mmHg)

Cholesterol (Wdl)

5 Years

20 Years

Percent Reducliont

100

220

4.0

21.0

-

100

202

3.2

18.0

14

90

238

3.2

17.0

19

90

220

2.6

15.0

29

90

189

2.0

11.5

45

*Adapted from [49], with permission. +The percent reduction is compared with no treatment. Assumptions are made of a 10 mm Hg decrease in diastolic blood pressure with thiazide diuretic and alpha-blocker treatment and an 8 percent reduction in serum cholesterol with the cholesterol-lowering diet. Also assumed is a 6 percent decrease in cholesterol with prazosin treatment, which is additive to the reduction with the cholesterol-lowering diet.

diuretics increase total serum cholesterol by 5 to 8 percent and also cause significant increases in low-density lipoprotein cholesterol and total triglycerides [l g-221. Both cardioselective and noncardioselective beta-blocking agents have been shown to substantially increase serum triglycerides by up to 30 percent and also significantly reduce high-density lipoprotein cholesterol by up to 10 percent [23-271. In several studies, the alpha-blocking agent prazosin has been found to decrease total serum cholesterol by 5 to 8 percent [28-311. Some studies have also suggested that prazosin may increase high-density lipoprotein cholesterol and, therefore, favorably influence the ratio of total cholesterol to high-density lipoprotein cholesterol. The pathophysiologic significance of these lipid effects is not known. Although past hypertension trials using thiazide diuretics have clearly demonstrated the benefit of treatment relative to the consequent complications of untreated hypertension (e.g., stroke, congestive heart failure), they have generally failed to show a clear benefit for atherosclerotic end points (acute myocardial infarction, coronary heart disease death). It is conceivable that the

February

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adverse effects on lipids observed with specific antihypertensive agents may even negate the expected beneficial effect of a reduction of blood pressure on coronary heart disease end points. This possibility has been underscored by the results of the Coronary Primary Prevention Trial discussed previously, i.e., a 1 percent change in serum cholesterol results in a 2 percent change in coronary heart disease risk. Table IV shows the theoretic impact on risk of myocardial infarction in a 50-year-old man treated with various combinations of antihypertensive drugs and diet. The fiveyear estimated risk of infarction ranges from 4 percent with no treatment to 2 percent with prazosin combined with a cholesterol-lowering diet. The corresponding 20year estimated risks range from 21 .Oto 11.5 percent. Potentially, there are major differences in coronary heart disease risk according to the type of treatment. The importance of multiple measurements and averaging these measures to more accurately assess risk will be emphasized later. It is also helpful in the initial assessment and subsequent evaluation of a coronary heart disease risk man-

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TABLE V 4~ (van) 20-29

and HUNNINGHAKE

Blood Cholesterol Levels (mg/dl) Requiring Trestment* Moderate Risk >200 >220 >240

30-39 240

THERAPY-GRIMM

High Risk >220 >240 >260

Goals 01 Therapy ~180 <200 <200

Note: Ratios of total cholesterol to high-density lipoprotein cholesterol that are between 3.5 and 4.5 are defined as moderate risk; ratios of more than 4.5 are defined as high risk. *Adapted from r], with permission.

agement program to try to determine the total coronary heart disease risk or “risk score.” This estimate includes changes in all major risk factors and provides a perspective for focusing on each major source of risk, such as cigarette smoking. Several techniques are available for overall risk assessment that are based on data from trials such as the Framingham Heart Study and the U.S. Railway Study. Two methods that we recommend for overall risk assessment are the American Heart Association Coronary Risk Handbook and the “CHD Risk Slide Rule” [32,33]. Desired Lipid and Lipoprotein Levels. The Consensus Conference defined moderate- and high-risk cholesterol levels requiring treatment as those levels representing the upper 25th and 10th percentiles, respectively [34], based upon the Lipid Research Clinics Prevalence Study. The suggested values that require more intensive treatment and the desired goals for treatment as defined in the consensus report are given in Table V. The recommendations are that persons in their 20s should be treated if their cholesterol values exceed 200 mg/dl. The suggested levels that require intensive treatment increase until age 40; at that time, cholesterol levels of 240 mg/dl or more should be treated. The suggested treatment goals are cholesterol values less than 180 mg/dl for persons under 30 years and less than 200 mg/dl for those over the age of 30. It should also be noted that more aggressive lowering of cholesterol is recommended in the presence of associated risk factors, such as a family history of premature coronary heart disease, low highdensity lipoprotein levels, or the presence of clinically manifest coronary heart disease. We would suggest an additional definition of moderate and high risk based on the ratio of total cholesterol to high-density lipoprotein. These ratio recommendations are derived from the Framingham data [35]. High-density lipoprotein is a powerful independent predictor of coronary heart disease and its measurement can be made in most clinical laboratories, although the technique involved is frequently not as well standardized as is that for measuring total cholesterol. The optimal high-density lipoprotein cholesterol level as defined in the Framingham study [35], is approximately 28

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percent of total cholesterol or a ratio of total cholesterol to high-density lipoprotein cholesterol of 3.5. Ratios of total cholesterol high-density lipoprotein cholesterol defined as moderate risk would then be between 3.5 and 4.5, and high-risk ratios would be greater than 4.5, or a highdensity lipoprotein that is less than 22 percent of the total cholesterol level. Antihypertensive Drug Selection. The specific antihypertensive agent selected for initial and subsequent therapy is important in managing patients who have elevated blood pressure, since many hypertensive patients also have lipid abnormalities, and many antihypertensive agents have been shown to affect blood lipids. Thiazide and beta-blocking agents are of special concern because of their adverse effects on lipids. In those hypertensive patients with moderate- and high-risk cholesterol levels, and also those with elevated triglyceride levels, thiazide diuretics and beta blockers should be used cautiously, if at all. In such patients, intervention for lowering lipid levels and maintaining ideal body weight should be vigorous. Lipid measurements should be repeated at least six to eight weeks after antihypertensive drugs are started and also after adding new agents to the regimen. Alpha blockers should be seriously considered as the initial antihypertensive medication in these patients, or as additional antihypertensive agents if needed, to control blood pressure, because of the body of data showing favorable lipid alterations. Beta-blocking agents should also be avoided or used cautiously in patients with high triglyceride and/or low high-density lipoprotein levels. This latter group frequently includes patients with diabetes. In those patients whose cholesterol levels are below the 75th percentile or whose triglyceride levels are normal and who are being treated with thiazides and beta blockers, lipids should be monitored closely to check for sudden and important changes. Lipid Management Diet: Diet is the initial form of therapy for all lipid disorders. Currently, it is suggested that all adult patients with lipid disorders adhere to a cholesterollowering diet. Patients with other risk factors such as hypertension should have more aggressive treatment for their cholesterol levels. They may need more stringent dietary controls that include weight management, sodium reduction, and avoidance of excessive alcohol intake. If a problem with blood lipids develops in a patient after antihypertensive therapy, that patient should also be treated more aggressively with diet. The current recommendation is that all patients with hyperlipidemia be treated with the same diet, the American Heart Association Diet, which follows a phased approach with progressively more rigid dietary restraints (Table VI) [38]. Phase I of this diet recommends that 30 percent of total calories be derived from fat, with the fats to be evenly divided into 10 percent monounsaturated, 10 percent saturated, and 10 percent polyunsaturated fat.

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Dietary cholesterol is limited to no more than 250 to 300 mg per day. If desired effects are not obtained under this regimen, then further limitations of dietary cholesterol and total fat are made. All patients should be encouraged to maintain their ideal weight. Weight reduction and alcohol restrictions are especially important in hypertensive patients with hypertriglyceridemia. Weight reduction and maintenance, cessation of cigarette smoking, and regular physical activity should also be advised because of the potentially beneficial effects on high-density lipoprotein levels. Drugs: If diet does not adequately control lipid and lipoprotein levels, drug therapy may occasionally be indicated in a limited number of patients [37]. The drugs generally used to reduce lipid levels include the following: Cholestyramine and colestipol are bile acid sequestering agents that primarily lower total cholesterol and low-density lipoprotein cholesterol; both agents can significantly decrease the absorption of many drugs, including the thiazide diuretics and beta blockers 138,391. Nicotinic acid lowers total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and it increases high-density lipoprotein [40]. Gemfibrozil primarily lowers triglycerides and produces moderate increases in high-density lipoprotein [41]. Clofibrate, primarily effective in lowering triglycerides [42,43], is not recommended routinely because of questions of long-term adverse effects [44]. Lipid Measurements and interpretation. In many laboratories, total blood cholesterol, triglycerides, and lipoprotein fractions are not measured with precision. The difficulty in measuring plasma lipids and lipoproteins had led to the development of a standardization system that is coordinated by the Centers for Disease Control [45]. It is important for physicians who treat patients with hypertension and lipid elevations to be aware of the quality of the lipid measurements done by the laboratory they utilize. The most desirable standardization and quality control procedures are those of the Centers for Disease Control. Laboratories not standardized to that system commonly produce unreliable measurements. It is not unusual for a cholesterol level measured in a noncertified laboratory to deviate by 20 to 30 mg/dl or more from a laboratory standardized to the Centers for Disease Control system. In addition to laboratory variations in the measurement of cholesterol and lipoprotein fractions, there are large seasonal and intra-individual variations due to biologic and temporal factors. The individual standard deviation in blood cholesterol done under ideal free-living conditions in laboratories standardized to the Centers for Disease Control system is approximately 20 to 25 mg/dl. A typical response to a cholesterol-lowering diet or to thiazide diuretics in a patient with an initial blood cholesterol of 230 mg/dl would be a decrease or an increase in blood cholesterol of 8 to 10 percent or 2 18 to 23 mg/dl. Therefore, in an individual patient, the use of only one measure as a

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ON INITIAL ANTIHYPERTENSIVE

TABLE Vi

THERAPY-GRIMM

and HUNNINGHAKE

American Heart Association Dietary Goals (phases I, ii, and iii)

Phase

I

II

Ill

Fat (percent of calories) Carbohydrate (percent of calories) Protein (percent of calories) Cholesterol (mg) Ratio of polyunsaturated to saturated fat

35 55

25 60

20 65

15

15

15

“Adapted

<300 1

200-250 1

loo-150 l-2

from (361, with permission.

TABLE VII

Interpretation of Berum Cholesterol Changes in an individual When One Cholesterol Measurement is Used for Foiiow-Up’

Absolute Chaws (mg percent) O-20 21-30 31-40 >40

Pmbablllty Difference Dueto Chance’ (percent) 100-32 32-16 16-6 <6

*Adapted from [50], with permission. +Based on an intra-individual variability

lnterpmtatlon Probably unchanged Possibly changed Probably changed Almost certainly changed (standard

deviation)of

15 mg/dl.

baseline and then one measure to assess the cholesterol response at follow-up may not detect an 8 to 10 percent real change in cholesterol. Table Vii provides a guide for assessing cholesterol changes in patients if only one measurement is used for follow-up. This is a conservative estimate based on an intra-individual variability in cholesterol of 15 mg/dl. Variability tends to increase with the initial level of cholesterol, making this assessment problem greater in patients with moderate- to high-risk cholesterol levels. It is recommended that at least two initial measurements be taken prior to initiating diet and/or drug therapy and that an average of these measures be used as the baseline. In addition to biologic sources of variability, there are also procedural ones. It is important to standardize the blood collection procedure when measuring blood lipids. Blood specimens should be collected on an outpatient basis at a time when the patient is feeling well (i.e., has no acute illness). The patient’s posture (supine, sitting) should also be standardized. It is not necessary for persons to fast when measuring total cholesterol, but it is important that they fast for at least 12 hours and avoid alcohol for the previous 24 to 48 hours if triglycerides and high-density lipoprotein cholesterol are measured [48481.

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TABLE

VIII

COMMENTS

Summary of Risk Factor Management

In summary, research over the past decade has greatly expanded our knowledge and sophistication concerning the recognition and treatment of risk factors for coronary heart disease. Physicians are now convinced of the role of cigarette smoking and hypertension in the development of coronary heart disease and have actively intervened against these risk factors. However, attitudes, knowledge, and practice habits concerning blood cholesterol and intervention efforts aimed at reducing cholesterol levels have lagged behind. New guidelines are encouraging physicians to become more active in managing cholesterol levels. Risk factor management is especially important in hypertensive patients. Many antihypertensive agents commonly in use are now known to significantly affect blood cholesterol and lipoproteins. Although the stepped-care pharmacologic approach to treating hypertension is still recommended for many hypertensive patients, it may be ill-advised to use diuretics as initial therapy, especially for those hypertensive patients in whom cholesterol levels are of concern. In such patients, comprehensive risk management suggests that alpha blockers may be the treatment of choice as the initial antihypertensive agents. Table VIII summarizes the approach we recommend for risk management. Comprehensive risk management involves initial systematic measurement of all coronary heart disease risk factors and regular followup and reassessment of risk status (i.e., smoking, weight reduction, dietary counseling, and careful consideration of antihypertensive drugs).

Avoid thiazide diuretics and beta blockers or use with caution in patients with moderateor high-risk cholesterol levels Intervene intensively in patients with moderateor high-risk cholesterol levels with: cholesterol-lowering diet weight loss and maintenance Repeat lipid measurements six to eight weeks after initiating antihypertensive drug therapy and after adding new drugs to regimen Consider adding alpha blockers if needed to further control blood pressure Avoid beta blockers or use with caution in patients with elevated triglyceride levels or low high-density lipoprotein cholesterol levels and high total cholesterol to high-density lipoprotein cholesterol ratios

l

l

l

l

l

Providing Feedback to Patients. Providing patients with the result of each cholesterol and lipid measurement is common and, intuitively, seems appropriate. The basic assumption is that an improvement in the lipid measurement will reinforce the dietary or drug-taking regimen, providing incentive for even greater changes to occur. In practice, however, this basic intuitive assumption is fraught with problems that stem from the intra-individual variability in serum cholesterol measures. There is a significant chance of providing false feedback if only one measurement is used in an individual. The primary means to avoid the dilemma of inappropriate feedback is to evaluate progress by performing multiple measures that are standardized and averaging the results. As mentioned earlier, it is also helpful before starting therapy to attempt to assess the total coronary heart disease risk or “risk score.”

ACKNOWLEDGMENT We would like to thank Lisa Morgan for her valuable assistance in preparing this article.

REFERENCES 1.

2.

3.

4.

5.

6.

82

Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial results: I. Reduction in incidence of coronary heart disease. JAMA 1984; 251: 351-364. The Lipid Research Clinics Program: The Lipid Research Clinits Coronary Primary Prevention Trial results: II. The relationship of reduction in incidence of coronary hear-l disease to cholesterol lowering. JAMA 1984; 251: 385-374. Mann JI, Man JW: Coronary heart disease prevention: trials of diets to control hyperlipidemia. In: Miller NE, Lewis 8, eds. Lipoproteins atherosclerosis in coronary heart disease. Amsterdam: Elsevier North Holland Biomedical Press, 1981; 197-210. Levy RI, Brensike JF, Epstein SE, et al: The influence of changes in lipid values induced by cholestyramine and diet on progression of coronary artery disease: results of the NHLBI Type II Coronary Intervention Study. Circulation 1984; 69: 325-337. Arntzenius AC, Kromhout D, Barth JD, et al: Diet, lipoproteins, and the progression of coronary atherosclerosis: the Leiden Intervention Trial. N Engl J Med 1985; 312: 805-811. Hjermann I, Velve Byre K, Holme I, Leren P: Effect of diet and

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smoking intervention on the incidence of coronary heart disease: report from the Oslo Study Group of a randomized trial in healthy men. Lancet 1981; II: 1303-1310. Consensus Conference: Lowering blood cholesterol to prevent heart disease. JAMA 1985; 253: 2080-2086. Hypertension Detection and Follow-Up Program Cooperative Group. Five-year findings of the Hypertension Detection and Follow-Up Program: I. Reduction in mortality of persons with high blood pressure, including mild hypertension. JAMA 1979; 242: 2562-2571. Hypertension Detection and Follow-Up Program Cooperative Group: Five-year findings of the Hypertension Detection and Follow-Up Program: II. Mortality by race, sex and age. JAMA 1979; 242: 2572-2577. Hypertension Detection and Follow-Up Program Cooperative Group: The effect of treatment on mortality in “mild” hypertension: results of the Hypertension Detection and Follow-Up Program. N Engl J Med 1982; 307: 976-980. Hypertension Detection and Follow-Up Program Cooperative Group: Five-year findings of the Hypertension Detection and Follow-Up Program: Ill. Reduction in stroke incidence among

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62