Management of Hypercholesterolemia in the Hypertensive Patient

CLINICAL MANAGEMENT

Management of hypercholesterolemia in the hypertensive patient

MICHAEL D. CRESSMAN, DO

• Measurement of serum total cholesterol (TC) and high-density lipoprotein-cholesterol (HDL-C) is recommended in the comprehensive evaluation of hypertensive patients. The prevalence of hypercholesterolemia is higher in hypertensive compared to normotensive individuals and the cardiovascular risk associated with high blood pressure is increased when hypercholesterolemia is present. Diuretics and/or beta blockers may increase TC, triglyceride (TG), and very low-density lipoprotein-cholesterol (VLDL-C) levels and/or reduce HDL-C levels, but it is not certain if these changes in blood lipids and lipoproteins decrease the benefits of the blood pressure reduction that they produce. Blood pressure and blood cholesterol levels may be reduced through dietary modification and low-fat diets blunt the changes in lipids and lipoproteins induced by diuretics or beta blockers. Despite these changes, many hypertensive patients require lipid-lowering drugs to reduce low-density lipotrotein-cholesterol (LDL-C) levels to an acceptable range. Lipid lowering drugs may produce bothersome side effects and/or increase the cost of medical therapy considerably. However, several lipid lowering drugs have been shown to reduce primary CHD incidence in middle-aged men with hypercholesterolemia. • INDEX TERM: HYPERCHOLESTEROLEMIA • CLEVE CLIN ] MED 1989; 56:351-358

sion has increased over the past few decades, the cardiovascular mortality rate in the U.S. has declined.4 The reason for this effect is difficult to determine and is prob- YPERCHOLESTEROLEMIA IS COMMON IN ably multifactorial. Clinical trials in hypertensive Hhypertensive patients and its presence in- patients have generally shown a decreased incidence of creases the risk of cardiovascular complica- pressure-related complications, such as stroke, but no tions.1 Reduction of blood cholesterol levels decrease in the incidence of coronary heart disease decreases the incidence of CHD in middle-aged men (CHD) during diuretic-based antihypertensive ther- with hypercholesterolemia.2"3 For these reasons, evalua- apy.5-7 Although it is not certain why antihypertensive tion of the hypertensive patient should include measure- drug treatment has not been shown to reduce CHD in- ment of blood lipid and lipoprotein levels. cidence, adverse effects of antihypertensive agents on FroAms aggressivthe Departmente detectios of nHear antd antreatmend Hypertensiot of hypertenn and Ne-- blood lipids may be involved. phrology, The Cleveland Clinic Foundation. Submitted March This report presents recommendations for the detec- 1989; accepted March 1989. tion and treatment of lipoprotein abnormalities in hy- Address reprint requests to Department of Heart and Hyperten- sion, The Cleveland Clinic Foundation, One Clinic Center, 9500 pertensive patients. These guidelines are consistent with Euclid Avenue, Cleveland, Ohio 44195. recent recommendations from the Joint National Com-

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TABLE 1 TABLE 2 CLASSIFICATION OF BLOOD PRESSURE (mmHg) IN ADULTS4 CLASSIFICATION OF TOTAL BLOOD CHOLESTEROL (mg/dL) IN ADULTS5 Systolic (when DBP <90 mmHg) <140 normal blood pressure <200 desirable blood cholesterol 140-159 borderline isolated systolic hypertension 200-239 borderline-high blood cholesterol >160 isolated systolic hypertension >240 high blood cholesterol Diastolic <85 normal blood pressure The classification of total cholesterol in adults 20 years of age or older does 85-89 high normal blood pressure not depend on age or sex. 90-104 mild hypertension 105-114 moderate hypertension >115 severe hypertension sive men were rare exceptions. The norm was high blood pressure combined with an elevated serum cholesterol level and, in a sizable proportion of the co- TABLE 3 hort, cigarette use as well." CLASSIFICATION OF LDL-C LEVELS (mg/dL) IN ADULTS5

<130 desirable DETECTION OF LIPID ABNORMALITIES 130-159 borderline high-risk >160 high risk Measurement of TC as well as high-density lipoprotein cholesterol (HDL-C) is recommended in the Measurement of LDL-C requires a fasting blood sample for determination of 8 TC, TG, and HDL-C levels. Treatment decisions are based on LDL-C levels. initial evaluation of all hypertensive patients. A fasting blood sample is not needed, and analysis of the TC:HDL mittee (JNC) on Detection, Evaluation, and Treatment ratio is a more reliable predictor of CHD risk than TC of High Blood Pressure and the Expert Panel on Detec- alone.13,14 If the TC level is 200 mg/dL or greater or the tion, Evaluation, and Treatment of High Blood HDL-C level is lower than 35 mg/dL, a fasting blood Cholesterol in Adults.8,9 sample should be obtained to estimate low-density (LDL-C).8 When fasting triglyceride (TG) levels are less DEFINITIONS AND PREVALENCE than 400 mg/dL, LDL-C levels may be calculated using the formula15: The cardiovascular risk associated with increased di- LDL-C = TC - (TG/5 + HDL-C) astolic blood pressure (DBP) and TC is continuous and graded. Therefore, definitions of hypertension and hy- The National Cholesterol Education Program treat- percholesterolemia are arbitrary. Martin et al10 reported ment guidelines are based on LDL-C levels,9 which are that the age-adjusted six-year death rate per 1,000 men classified in Table 3. screened for the Multiple Risk Factor Intervention Trial (MRFIT) increased as either DBP or TC rose. The risk DEVELOPMENT OF HYPERCHOLESTEROLEMIA was accentuated when DBP was greater than 94 mmHg or TC was above 253 mg/dL; these levels were observed Genetic and environmental factors influence the in about 15% of the men screened. development of high blood pressure or abnormal blood Blood pressure and cholesterol levels are classified in lipid and lipoprotein levels. Hubert et al16 noted a strong Tables 1 and 2.8,9 Based on these classifications, the prev- association between weight gain and increased blood alence of hypertension and hypercholesterolemia in- pressure and cholesterol levels among the young adult creases with age, from about 15% in the third decade to offspring of the Framingham Heart Study Cohort. Body approximately 40% in the fifth decade of life. 11,12 Stam- mass index had a negative correlation with HDL-C ler et al1 noted that 20% of all men screened in the levels in adults in the second National Health and MRFIT had TC levels of 245 mg/dL or greater; among Nutrition Examination Survey. men who were hypertensive without baseline evidence Changes in body weight also may influence blood of myocardial infarction, the prevalence of TC levels in lipid and lipoprotein levels in patients receiving diuret- this range increased to 27%. The relative risk of CHD ics.17 All men in the Special Intervention group of the increased more than threefold in hypertensive men MRFIT were offered a diet low in saturated fat and whose baseline TC was 245 mg/dL or greater compared cholesterol, and hypertensive patients received diuretic to those whose TC was less than 182 mg/dL. Con- therapy as well.18 Among participants who lost 10 or sequently, noted Stamler, "relatively low-risk hyperten- more pounds in the Special Intervention group of

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MRFIT, the reduction in TC was 62% less in those re- drugs are any more effective in reducing cardiovascular ceiving compared to those not receiving diuretics.13 mortality than diuretics or beta blockers. Hypertension and blood lipid abnormalities aggregate in certain families.19 Williams et al20 recently proposed Thiazide diuretics that a syndrome characterized by mixed lipid abnormali- Grimm et al24 compared the effects of chlorthalidone ties is present in about 12% of patients with essential hy- and hydrochlorothiazide on blood lipids in a ran- pertension. They observed concordant abnormalities in domized, placebo-controlled, double-blind study of 24 fasting serum lipid or lipoprotein levels in two or more weeks' duration. Men with mild diastolic hypertension siblings of nearly half the individuals with essential hy- received a placebo, 100 mg chlorthalidone, or 100 mg pertension diagnosed before age 60. These investigators hydrochlorothiazide after a four-week period of observa- suggested that dyslipidemia and essential hypertension tion without medication. In this study, chlorthalidone or represented manifestations of a common familial syn- hydrochlorothiazide increased plasma TC and TG levels drome. The presence of a variety of lipid and lipoprotein by approximately 15 mg/dL and 25 mg/dL, respectively. abnormalities (increased TG and LDL-C and low HDL- Chlorthalidone increased LDL-C as well; HDL-C levels C) in these families raises the possibility of familial com- did not change. There were no significant changes in bined hyperlipidemia syndrome. This syndrome is TC, TG, HDL-C, or LDL-C in individuals receiving a characterized by the presence of multiple lipoprotein placebo. A cholesterol-lowering diet appeared to pre- phenotypic abnormalities (Type IIA, IIB, IV) that may vent the diuretic-associated increase in TC but not in change over time in affected patients and their first- TG levels. However, it could be argued that diuretic ad- degree relatives.21 ministration blunted the expected reduction in TC and Approximately 20% of patients with premature CHD LDL-C levels associated with the low cholesterol diet. are thought to have familial combined hyperlipidemia The long-term effects of diuretics on blood lipid and syndrome.22 In addition to increased TC, fasting TG, or lipoprotein levels have been evaluated in several large LDL-C levels, there may be low HDL-C concentrations multicenter clinical Srials. In the Medical Research or abnormal composition of LDL particles.21 These LDL Council (MRC) trial, no change in serum cholesterol particles may be small and dense and contain a high level was observed in men who received diuretics during ratio of LDL apoprotein B (apoB) to LDL-C. Their in- a three-year observation period.25 Since men receiving creased atherogenic potential may contribute to a placebo had a reduction in TC levels during this time, it higher incidence of premature atherosclerosis in the af- is possible that the diuretic had an adverse effect on fected individuals. blood cholesterol levels. Similar trends were apparent in The presence of normal LDL-C levels does not rule women. out the possibility of abnormalities in LDL composition. Lasser et al18 reported the effects of diuretics on lipid Sniderman et al23 identified a subset of patients with an- levels in men receiving a diet low in saturated fat and giographic evidence of coronary artery disease whose cholesterol in the Special Intervention Group of the LDL-C levels were normal, but whose LDL-apoB levels MRFIT. In this study, 1,917 participants received diuret- were similar to those observed in phenotype II hyper- ics for six years and 2,537 received no diuretics (Table 4). lipoproteinemia. They referred to this syndrome as "hy- The mean reduction in TC levels was 4.3 mg/dL greater perapobetaliproteinemia." This diagnostic possibility in participants who did not receive diuretics. The pri- should be considered in the evaluation of hypertensive mary reason for the difference was that participants re- patients who have a strong family history of premature ceiving diuretics had a 2.8 mg/dL increase in very low- CHD. density lipoprotein cholesterol (VLDL-C) level while participants receiving no diuretics had a 2.8 mg/dL

EFFECTS OF ANTIHYPERTENSIVE AGENTS ON BLOOD LIPIDS decrease in VLDL-C levels. Reduction in LDL-C levels did not differ in the two groups, which suggests that Lipoprotein changes have been observed with thi- major changes in LDL-C levels do not occur in patients azide diuretic and beta blocker therapy, but there is no receiving low-fat diets during long-term diuretic ther- consensus about the influence of these changes on car- apy. HDL-C levels increased 0.1 mg/dL in participants diovascular risk. Newer drugs such as calcium channel not receiving diuretics and fell 0.8 mg/dL in those re- blockers or angiotensin converting enzyme inhibitors do ceiving diuretics—a statistically significant difference not appear to alter lipoprotein metabolism. However, (P<.01). A summary of the effects of diuretics on the there is no data that clearly documents whether newer lipid and lipoprotein levels after six years in this group is

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TABLE 4 CHANGES IN PLASMA LIPIDS AND LIPOPROTEINS IN SPECIAL INTERVENTION MEN RECEIVING OR NOT RECEIVING DIURETICS SIX-YEAR MRFIT DATA13

A TC (mg/dL) A TG (mg/dL) A HDL-C (mg/dL) A LDL-C (mg/dL)

Diuretics (1,917) - 8.9 20.8 -0.8 -10.8 No diuretics (2,537) -13.2* -13.6* O.lt -10.4

*P <.001 or t P <-01 for diuretic v no diuretic groups. provided in Table 4- blockers, or both are increased TC, increased TG, and reduced HDL-C levels. Propranolol may exacerbate the Beta blockers tendency of diuretics to increase TG and reduce HDL-C Beta blockers were recommended as first-step antihy- in hypertensive patients receiving a low-fat diet.18 In the pertensive agents by the JNC 1984 and 1988.8,26 There MRFIT, mean HDL-C was reduced 3.2 mg/dL in the are a number of reports and studies regarding changes in group receiving diuretics plus propranolol; the reduction lipoprotein metabolism during beta blocker monother- was significantly (P<.01) greater than that observed in apy and during therapy with diuretics plus beta blocker, the diuretic-only group. Mean TG level increased 52.2 which have been summarized by Hegeland.27 mg/dL with the diuretic plus propranolol combination; The effect of beta blockers on blood lipids depends on there was no difference in the diet-associated LDL-C re- the type of beta blocker used. Beta blockers with intrin- duction in participants receiving no drugs, diuretics sic sympathomimetic activity, such as acebutolol and alone, or diuretics plus propranolol. pindolol, have no effect on blood lipids,27,28 nor does the combined beta blocker/alpha, receptor, labetalol appear NONPHARMACOLOGIC THERAPY IN HYPERTENSIVE PATIENTS to affect blood lipid levels.29 WITH HYPERCHOLESTEROLEMIA Tanaka et al30 evaluated the effects of propranolol on lipoprotein composition in 10 patients with normal pre- An initial trial of nonpharmacologic treatment, in- treatment blood lipid levels. After an eight-week pro- cluding weight control and alcohol and sodium restric- pranolol treatment period, plasma TC and TG levels tion, is recommended for patients with mild to moderate were unchanged. During the treatment period, post-he- hypertension.8,26,33 Alcohol intake should be restricted to parin lipolytic activity was reduced and TG content of less than 2 oz of ethanol per day and sodium to less than VLDL increased while TG content of LDL was 2 g per day. These measures, combined with reduced in- decreased. Thus, propranolol administration altered take of total fat, saturated fat, and cholesterol, are par- lipoprotein composition without changing blood lipid ticularly important when hypercholesterolemia is pre- concentration. sent. The recent emphasis on "heart-healthy" diets may A Veterans Administration multicenter study help motivate patients to make recommended dietary assessed the effects of one year of propranolol therapy on changes. Even so, many patients find it difficult to make blood TC and TG levels in more than 100 patients.31 changes and may benefit from appropriate counseling or Although propranolol monotherapy produced no signif- referral to facilities where more detailed information can icant change in TC levels, TG levels increased by 42 be provided. mg/dL (P<.01). Significant changes in TC or TG levels Weight reduction may decrease both blood pressure were not observed in participants who received hy- and blood cholesterol levels. Reduced intake of fatty drochlorothiazide for one year. HDL-C levels were not foods and increased consumption of low-fat foods, such measured in this study. However, Ames32 reported that as fresh fruits and vegetables, are particularly useful. The increased TG levels and decreased HDL-C levels were caloric density of carbohydrates is only approximately generally present in studies with sufficient sample sizes one-half as high as the caloric density of fat; many and propranolol treatment periods of at least four weeks. patients who reduce their fat intake also reduce their caloric intake and lose weight. Since a considerable per- Effects of combination therapy centage of the total fat intake is ingested as meat, it is The major blood lipid and lipoprotein abnormalities prudent to advise reduced intake of all meats and partic- that develop during treatment with diuretics, beta ularly of red meat.

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TABLE 5 TABLE 6 MAJOR CONTRIBUTORS OF TOTAL FAT, SATURATED FAT AND NUTRITIONAL GUIDELINES FOR MANAGEMENT OF HYPER- CHOLESTEROL IN THE U.S. DIET: NHANES II DATA (1976-1980)" TENSIVE PATIENTS WITH HYPERCHOLESTEROLEMIA

Total fat Saturated fat Cholesterol Nutritional factor Goal

hamburgers, cheese- hamburgers, cheese- eggs Total calories body weight within 15% of desirable weight burgers, meat loaf burgers, meat loaf Alcohol less than 2 oz ethanol per day hot dogs, ham, lunch while milk, whole beefsteaks, roasts Sodium less than 2 g per day meats milk beverages Total fat less than 30% of total calories whole milk, whole milk cheese, excluding hamburgers, cheese- Saturated fat less than 10% of total calories beverages cottage cheese burgers, meat loaf Cholesterol less than 300 mg per day doughnuts, cookies, beef steaks, roasts whole milk, whole milk cake beverages beef steaks, roasts hot dogs, ham, lunch hot dogs, ham, lunch meats meats white bread, rolls, doughnuts, cookies, pork, including chops, Possibly, stearic acid (a major saturated fatty acid in crackers cake roast beef fat) is converted rapidly to oleic acid by chain elon- eggs eggs doughnuts, cookies, gation and desaturation; this may explain why dietary cake cheeses, excluding pork, including chops, cheeses, excluding stearic acid does not raise blood cholesterol to a great cottage cheese roast cottage cheese extent. margarine butter liver Grundy36 reported that a diet rich in monounsatu- mayonnaise, salad white bread, rolls, chicken or turkey, dressing crackers including fried rated fatty acids (the type in olive oil) was as effective as a very low-fat, high-carbohydrate diet in reducing blood cholesterol levels. In certain patients, a very high carbo- In their review of data obtained during the second hydrate, low-fat diet causes increased blood TC levels National Health and Nutrition Examination Survey and reduced HDL-C levels—changes not observed with (NHANES II), Block et al34 assessed the nutritional diets high in monounsaturated fatty acids. Certain contribution of specific foods in a population of 11,658 patients respond to very low-cholesterol diets with a adults. The 10 most important contributors of total fat, marked reduction in HDL-C levels; whether this reduc- saturated fat, and cholesterol are summarized in Table 5. tion is detrimental is unknown, but it may be prevented Beef products are the major contributors of both satu- with a diet high in monounsaturated fats. rated fat and cholesterol, but whole milk products, Finally, there is considerable interest in the car- baked goods, and cheeses also make a substantial con- diovascular effects of the polyunsaturated fats contained tribution. At the time of the survey, 35% of dietary in fish oils (omega-3 PUFAs).37 Diets that are high in cholesterol was ingested as eggs. A single egg yolk con- omega-3 PUFAs appear to decrease platelet aggregation tains approximately 250 mg cholesterol, which is close and reduce blood TG levels. The low cardiovascular to the maximum recommended daily intake.9 mortality in Eskimos may be related to the effects of Restriction of total fat, saturated fat, and cholesterol omega-3 PUFAs on platelet function or lipoprotein me- intake is recommended for the treatment of high-risk tabolism.38 In large amounts, dietary supplements of fish LDL-C levels.9 The patient should be advised that oil concentrates, packaged in capsules, will produce several dietary saturated fats, in addition to dietary changes in platelet function or lipoprotein metabolism. cholesterol, increase blood cholesterol levels. Further- Because the doses needed for effect are likely to be high more, certain vegetable oils, such as palm, palm kernel, in calories and cholesterol, the use of fish oil supple- or coconut, contain saturated fat but may be labeled "no ments is not generally recommended.39 Fish, on the cholesterol." other hand, is advocated by many as a dietary substitute The cholesterol-raising potential of different satu- for red meat. rated fatty acids is variable. For example, Bonanome and Nutritional therapy for hypertensive patients with Grundy35 reported that plasma TC associated with a hypercholesterolemia can be complex, since advice high stearic acid diet was 14% lower than that as- about sodium and fiber intake also should be provided. sociated with a high palmitic acid diet. (Palmitic acid is The assistance of a registered dietitian who is trained to the major fatty acid in palm oil.) A diet high in oleic counsel these patients can be invaluable. For nutritional acid (a monounsaturated fatty acid) produced a plasma therapy to be successful, scientific information must be TC 10% lower than that associated with a high palmitic translated into understandable dietary advice. A sum- acid diet. mary of nutritional guidelines for managing hyperten-

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sive patients with hypercholesterolemia is provided in helps prevent flushing, these preparations cause a higher Table 6.8,9,33 incidence of hepatitis than regular release nicotinic acid.41 LIPID-LOWERING DRUG THERAPY The low cost of nicotinic acid, its documented prevention of secondary CHD, and its favorable effects on Drug therapy is indicated for treatment of hyper- lipid and lipoprotein levels support is use in the initial cholesterolemia in middle-aged men with LDL-C levels treatment of lipid and lipoprotein abnormalities. Hyper- above 190 mg/dL after a 3- to 6-month trial of dietary tensive patients who are taking diuretics or beta block- therapy.9 Treatment is particularly important for men ers or both are particularly likely to benefit from treat- with hypertension. Nicotinic acid or the bile acid ment with nicotinic acid because of the tendency of sequestrants (cholestyramine, colestipol) are the agents nicotinic acid to reduce TG levels and reduce HDL-C recommended for initial treatment in the National levels. Cholesterol Education Program (NCEP) guidelines. Selection of one or the other depends on factors such as Bile acid sequestrants cost, side effects, and lipoprotein phenotype. Although Cholestyramine and colestipol selectively lower other drugs are available for treatment of hyper- LDL-C levels by increasing the clearance of LDL. The cholesterolemia, the scope of this paper is limited to dis- agents bind bile acid in the gut, which leads to increased cussion of the classes recommended as first-line agents conversion of hepatic cholesterol to bile acids. Stimula- in the NCEP guidelines. tion of LDL receptor synthesis leads to enhanced clear- Cost is a major issue for patients who receive chronic ance of LDL from the blood. drug therapy, and nicotinic acid is unquestionably the The bile acid binding resins produce bothersome least expensive lipid-altering drug available. Cholesty- gastrointestinal side effects (bloating, abdominal pain, ramine has been shown to reduce primary CHD inci- and constipation), but because they are not absorbed, dence in middle-aged men with TC levels above 265 serious side effects are infrequent.2 Constipation can be mg/dL.2 Subsequent to the release of the first NCEP a major problem for older adults, particularly if they are guidelines, the Helsinki Heart Study showed gemfibrozil taking other drugs that cause constipation. The to be effective in primary prevention of fatal and non- gastrointestinal side effects can be minimized by mixing fatal myocardial infarction in middle-aged men with hy- the resin with a pulpy noncarbonated beverage, increas- percholesterolemia3; it will likely be considered a first- ing fluid and dietary fiber intake, and increasing the dose line drug in the future. slowly. The bile acid sequestrants should be administered with meals or before bedtime. Nicotinic acid Because bile acid sequestrants may increase trigly- Nicotinic acid has been used for more than three de- ceride levels, they should be avoided in patients with cades to treat patients with lipoprotein abnormalities. It TG levels above 500 mg/dL. It is uncertain whether di- reduces TC, TG, and LDL-C levels,40 and increases uretics or beta blockers increase the hypertriglyceri- HDL-C levels. Although cutaneous and gastrointestinal demic tendency of the resins. Bile acid binding resins side effects may occur, nicotinic acid is a good first may reduce the absorption of either of several drugs; choice drug for most hypercholesterolemic patients. Ex- therefore, other drugs should be administered at least ceptions include patients with poorly controlled dia- one hour before or several hours after the ingestion of betes, peptic ulcer disease, chronic liver disease, and re- the resins. Cholestyramine is available in 4-g packets current gouty arthritis. and bulk containers; colestipol is available in 5-g pack- Cutaneous flushing is common with nicotinic acid, ets and bulk containers. The bulk containers are less ex- particularly early in the course of therapy. To reduce the pensive than the individual packets. The dosage of effect, the patient can increase the dose slowly, take the cholestyramine ranges from 4 to 24 g/d, and that of drug with meals, or precede the dose with aspirin or a colestipol from 5 to 30 g/d. nonsteroidal anti-inflammatory drug. A slow release preparation also is helpful in this regard; several are CONCLUSION available without prescription and are relatively inex- pensive; i.e., a 2,000 mg/dL dosage regimen costs about Because of the prevalence of hypercholesterolemia $6 a month. The regular release formulations are even among hypertensive patients, clinicians who treat hy- less expensive. Although slow-release nicotinic acid pertensive patients are well advised to develop a system-

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atic approach to the evaluation and treatment of lipid crease LDL-C levels. Whether these drug-induced abnormalities. changes in lipoprotein metabolism blunt the beneficial The evaluation of hypertensive patients should in- effects of blood pressure reduction is uncertain; a large clude measurement of TC and HDL-C levels to predict clinical trial and years of observation are needed to re- CHD risk. The prevalence of hypercholesterolemia is solve this question and, in the current economic cli- higher in hypertensive patients than in normal individu- mate, the cost of such a study may be prohibitive. als, and CHD risk increases in these patients as blood Nicotinic acid is widely accepted as a first choice cholesterol rises. Weight gain increases the risk of hyper- agent for treatment of high LDL-C levels; its low cost tension and hypercholesterolemia while weight loss may and ability to reduce TC, TG, LDL-C, and VLDL-C lower blood pressure, TC, TG, and LDL-C levels. A trial levels while increasing HDL-C levels are major advan- of nutritional therapy with a diet low in sodium, satu- tages. The bile acid sequestrants effectively reduce LDL- rated fat, and cholesterol is indicated for patients with C levels, have no serious side effects, and decrease CHD mild to moderate hypertension and hypercholesterol- incidence in middle-aged men with hypercholes- emia. Diuretics and beta blockers may elevate TG levels terolemia. and reduce HDL-C levels, but they do not appear to in-

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