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BACKGROUND: Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol. METHODS: We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes. RESULTS: The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels did not differ significantly between the groups. A primary event occurred in 275 of the 1267 patients assigned to placebo (21.7 percent) and in 219 of the 1264 patients assigned to gemfibrozil (17.3 percent). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22 percent (95 percent confidence interval, 7 to 35 percent; P=0.006). We observed a 24 percent reduction in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (P< 0.001). There were no significant differences in the rates of coronary revascularization, hospitalization for unstable angina, death from any cause, and cancer. CONCLUSIONS: Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.

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OBJECTIVE: To evaluate long-term continuation rates for cholesterol-lowering therapy (niacin, sequestrants, statins) in a multidisciplinary lipid clinic and to evaluate the effectiveness of 2 different dosing strategies designed to improve long-term continuation of therapy. STUDY DESIGN: An observational study was done at the Milwaukee Department of Veterans Affairs Medical Center Lipid Clinic, where healthcare personnel were trained to improve patient tolerance to cholesterol-lowering medications. Primary outcomes were recorded prospectively. PATIENTS AND METHODS: Patients were 970 consecutive veterans who began therapy with niacin, sequestrants, or statins between March 1988 and December 1995. In 1992, two different dosing strategies were initiated to reduce the discontinuation rates for niacin and sequestrants: (1) the niacin titration schedule was lengthened from 3 to 6 weeks and (2) the initial sequestrant dose was reduced from four to two scoops daily. RESULTS: Discontinuation rates for niacin and sequestrants were both very high. For niacin, 48% and 71% of all patients who began therapy discontinued the drug by 1 and 4 years, respectively. For sequestrants, drug discontinuation rates were 59% and 83% at 1 and 4 years, respectively. On the other hand, statin discontinuation rates at 1 and 4 years were only 10% and 28%, respectively. Neither the longer niacin titration schedule nor the lower sequestrant initiation dose reduced these high discontinuation rates. CONCLUSIONS: Despite initiation of niacin and sequestrant therapy in the setting of a multidisciplinary lipid clinic, drug discontinuation rates were high and were similar to rates observed in primary-care settings. Neither the specialized resources available in a lipid clinic nor protocols designed to improve tolerance to therapy reduced the high drug discontinuation rate. Unless more tolerable niacin and sequestrant formulations become available, reliance on statins as the preferred cholesterol-lowering agents will continue because they have fewer side effects and lower discontinuation rates.

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To assess the importance of postprandial lipemia and delayed chylomicron clearance as early atherogenic risk factors, 60 male offspring of parents with early coronary artery disease (CAD) and 41 controls were administered a fat-rich meal containing vitamin A. There were no significant differences between CAD-positive (CAD+) offspring and CAD-negative controls for areas under the postprandial curves for triglyceride and plasma, chylomicron, and chylomicron remnant retinyl palmitate. Older CAD+ offspring, aged 31-45 yr, had significantly increased very low density lipoprotein (VLDL) cholesterol, VLDL triglyceride, VLDL apoprotein B, and areas under postprandial curves for triglyceride and plasma, chylomicron, and chylomicron remnant retinyl palmitate than younger CAD+ offspring, aged 15-30 yr. Correcting for waist/hip ratio eliminated significant differences between the two groups for VLDL and areas under the triglyceride and chylomicron remnant curves, but this was not the case for the insulin sensitivity index. We conclude that neither increased postprandial lipemia nor abnormalities of chylomicron clearance are important early atherogenic risk factors in this population. An increase in age is associated with increased VLDL and postprandial lipemia and decreased chylomicron remnant clearance. This is due mainly to an increase in the waist/hip ratio and not to a change in insulin sensitivity.

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The relationship between low-density lipoprotein (LDL) peak particle diameter and insulin sensitivity, very-low-density lipoprotein (VLDL) + intermediate-density lipoprotein (LDL) triglyceride, cholesterol, and apoprotein B, postprandial lipemia, and LDL + high-density lipoprotein (HDL) triglyceride was assessed. The subjects were 101 healthy males aged 15 to 45 years. Sixty-one subjects (60.4%) were offspring of a parent with coronary artery disease before age 60, and 40 subjects (39.6%) had no parental history of coronary artery disease. LDL peak particle diameter was measured following polyacrylamide gradient gel electrophoresis. An insulin sensitivity index (Si) was determined from a frequently sampled intravenous glucose tolerance test using a minimal modeling method. A fat tolerance test was performed with a test meal containing 70 g/m2 fat, with triglyceride concentrations measured hourly for 12 hours. LDL peak particle diameter was significantly correlated with body mass index (BMI) (r = -.282, P < .01), waist to hip ratio (r = -.291, P < .01), fasting triglyceride (logarithmically [log] transformed) (r = -.566, P < .001), area under the postprandial triglyceride curve (log transformed) (r = -.562, P < .001), VLDL + IDL triglyceride (log transformed) (r = -.462, P < .001), VLDL + IDL cholesterol (log transformed) (r = -.477, P < .001), VLDL + IDL apoprotein B (log transformed) (r = -.321, P < .001), LDL + HDL triglyceride (log transformed) (r = .583, P < .001), and HDL cholesterol (r = .347, P < .001), but there was no significant correlation with Si. Using stepwise regression analysis, LDL + HDL triglyceride showed the strongest relationship to LDL peak particle diameter, accounting for 34% of the variation in size. Si was not an independent predictor of LDL particle size. In conclusion, insulin sensitivity appears to have little influence on LDL particle size. The importance of LDL + HDL triglyceride should be considered a preliminary finding warranting verification in this and other populations.

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The aim of this study was to assess the importance of low-density lipoprotein (LDL) particle size as a marker of atherogenic risk in male offspring of a parent with early coronary artery disease (CAD) before the age of 60 years. CAD-positive (CAD+) offspring were recruited into two groups based on age, 15 to 30 years (n = 20) and 31 to 45 years (n = 41), and matched to CAD-negative (CAD-) offspring by age and body mass index (BMI) (n = 20 and 21 per group). LDL peak particle diameter was assessed by polyacrylamide gradient gel electrophoresis. There was no significant difference in LDL peak particle diameter between CAD+ and CAD- offspring (26.2 +/- 0.1 v 26.2 +/- 0.1 nm, mean +/- SE). There was also no difference between CAD+ offspring and CAD- offspring when comparisons were made within their own age group (26.5 +/- 0.1 nm in younger CAD+ offspring v 26.2 +/- 0.1 nm in younger CAD- offspring, and 26.0 +/- 0.1 nm in older CAD+ offspring v 26.1 +/- 0.2 nm in older CAD- offspring). Peak particle diameter was significantly greater in younger CAD+ offspring than in older CAD+ offspring (26.5 +/- 0.1 v 26.0 +/- 0.1 nm, P < .05). We conclude that small LDL particle size is not a discriminating marker for early atherogenic risk, and that measurement of LDL particle size has limited value in the assessment of coronary risk, at least in the age ranges we studied.

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PURPOSE: To develop an optimal treatment strategy that reduces low-density lipoprotein (LDL) cholesterol levels and improves adherence to therapy by reviewing clinical trials that define the dose-response characteristics for 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), bile acid sequestrants, and niacin. DATA SOURCES: Data were obtained from a MEDLINE search of the English-language literature published from 1975 through November 1995 and from an extensive bibliography review. STUDY SELECTION: Controlled, clinical trials were reviewed if they evaluated 1) the effectiveness and toxicity of one LDL cholesterol-lowering agent (statins, bile acid sequestrants, or niacin, at two or more doses) or 2) monotherapy with two LDL cholesterol-lowering agents at defined doses used alone and in combination. Studies that had fewer than 10 patients in a treatment group or that selected patients on the basis of previous response to therapy were not included. DATA EXTRACTION: Trials were reviewed for overall methodology, inclusion and exclusion criteria, sources of bias, and outcomes. DATA SYNTHESIS: Dose-response relations for bile acid sequestrants and statins are nonlinear, and most of their LDL cholesterol-lowering effects can be obtained with lower doses. The few dose-response studies of niacin that have been done suggest that most of niacin's high-density lipoprotein cholesterol-increasing effect can also be achieved with relatively low doses, but higher doses are needed to substantially reduce LDL cholesterol levels. If bile acid sequestrants or niacin are added to statin therapy, the effect of combined therapy on LDL cholesterol levels is additive. CONCLUSION: The nonlinear dose-response relation of statins, bile acid sequestrants, and niacin and their additive LDL cholesterol-lowering effect when used together suggest a strategy for treating hypercholesterolemia that may optimize effectiveness while minimizing adverse effects and cost.

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To assess whether fish oil-induced alterations in low-density-lipoprotein (LDL) composition have distinct and important effects on LDL metabolism, we evaluated LDL kinetic behavior in cynomolgus macaques fed an atherogenic diet supplemented with either fish oil (1.6 g n-3 fatty acids; n = 10) or olive oil (n = 9) for > or = 6 mo. LDL from monkeys supplemented with fish oil or olive oil was isolated, labeled with either 125I or 131I, and simultaneously reinjected so that each monkey received its own (autologous injection) and donor (homologous injection) LDL. For LDL injected autologously (monkeys that received their own LDL), the LDL fractional clearance rate (FCR) was reduced in fish oil-supplemented monkeys compared with the olive oil-supplemented controls (0.42 +/- 0.03 compared with 0.56 +/- 0.05 pools/d, P = 0.04). The cholesteryl ester content of fish oil LDL increased compared with olive oil LDL (43 +/- 2% and 36 +/- 3%, respectively, P = 0.03), and the LDL cholesteryl ester content was strongly correlated with autologous LDL clearance (r = -0.76, P = 0.0001). Compared with olive oil LDL, fish oil LDL had a reduced dissociation constant (KD) for binding to the LDL receptor in vitro (KD for fish oil LDL compared with olive oil LDL: 13.9 +/- 1.8 and 7.4 +/- 1.0 mg LDL protein/L, P = 0.03). When both fish oil LDL and olive oil LDL were simultaneously injected into fish oil-supplemented monkeys, the FCR of fish oil LDL was decreased compared with olive oil LDL (0.42 +/- 0.03 and 0.52 +/- 0.04 pools/d, P = 0.006). These data suggest that dietary supplementation with fish oil decreases LDL clearance, and that this effect is mediated, at least in part, by altering LDL structure and reducing the affinity of LDL for its receptor.

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Calculated low-density lipoprotein cholesterol (LDL-C) concentrations determined from the Friedewald equation have a large intraindividual CV, in part because the calculation incorporates the variability of cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglyceride measurements. We studied whether a new assay that measures LDL-C directly will reduce this variability and reduce the need for averaging serial specimens. Four blood samples were obtained 1 week apart from 35 mildly hypercholesterolemic subjects and analyzed for total cholesterol, triglycerides, and HDL-C. LDL-C was calculated by the Friedewald equation, and was also measured directly with a commercially available direct LDL-C assay. The intraindividual CV for the direct and calculated LDL-C assays were similar [CV of direct LDL-C assay (mean +/- SE): 6.8 +/- 0.5% vs calculated LDL-C: 7.3 +/- 0.6%; difference 0.44%, 95% confidence interval: -0.7-1.5%]. For both assays, at least two blood tests were required from each subject to reduce total variability of LDL-C to less than or equal to 5%. We conclude that the direct LDL-C assay did not reduce the variability in LDL-C compared with the conventional LDL-C calculation. However, it may have a specific role in lipid disorder evaluation and (or) monitoring when triglycerides are increased or the LDL-C value alone is needed.

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OBJECTIVE: Treatment of elevated cholesterol levels reduces morbidity and mortality from coronary heart disease in high-risk patients, but can be costly. The purpose of this study was to determine whether physician extenders emphasizing diet modification and, when necessary, effective and inexpensive drug algorithms can provide more cost-effective therapy than conventional care. DESIGN: Randomized controlled trial. SETTING: A Department of Veterans Affairs Medical Center. PATIENTS: Two hundred forty-seven veterans with type IIa hypercholesterolemia. INTERVENTIONS: Patients assigned to either a cholesterol treatment program (CTP) or usual health care provided by general internists (UHC). CTP included intensive dietary therapy administered by a registered dietitian utilizing individual and group counseling and drug therapy initiated by physician extenders for those failing to achieve goal low-density lipoprotein (LDL) levels with diet alone. A drug selection algorithm for CTP subjects utilized niacin as initial therapy followed by bile acid sequestrants and lovastatin. Subjects were followed prospectively for 2 years. MEASUREMENTS: Primary outcome measurements were effectiveness of therapy defined as reductions in LDL cholesterol (LDL-C), and whether goal LDL-C levels were achieved; costs of therapy; and cost-effectiveness defined as the cost per unit reduction in the LDL-C. MAIN RESULTS: Total program costs were higher for CTP patients than for UHC patients ($659 +/- $43 vs $477 +/- $42 per patient, p < .001). However, at 24 months the patients in CTP were more likely to achieve LDL goal levels (65% vs 44%, p < .005), and also achieved greater reductions in LDL-C 27% +/- 2% vs 14% +/- 2% at 24 months, p < .001). Program costs per unit (mmol/L) reduction in the LDL-C, a measure of cost-effectiveness, was significantly lower for CTP ($758 +/- $58 vs $1,058 +/- $70, p = .002). CONCLUSIONS: Although more expensive than usual care, the greater effectiveness of physician extenders implementing cholesterol treatment algorithms resulted in more cost-effective therapy.

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PURPOSE: To determine the extent that goal lipid levels derived from the National Cholesterol Education Program (NCEP) are achievable in clinical practice, and to identify factors associated with the achievement of these goals. PATIENTS AND METHODS: We conducted a retrospective cohort study consisting of a consecutive sample of 244 patients with either coronary artery disease or peripheral vascular disease treated for hypercholesterolemia at a large Veterans Affairs medical center. Primary outcomes, recorded prospectively, were lipid levels and lipoprotein cholesterol response, and tolerance and compliance to drug therapy. Goal lipid levels were defined as low-density lipoprotein cholesterol (LDL-C) < or = 130 mg/dL and triglyceride (TG) < or = 200 mg/dL. RESULTS: Lipid-lowering drug therapy reduced LDL-C from 25% to 42% below baseline in patients with hypercholesterolemia varying from mild (130 to 160 mg/dL) to severe ( > 220 mg/dL), respectively. Approximately 75% of patients with LDL-C < or = 160 mg/dL ultimately achieved their lipid goal with drug therapy; however, less than half of patients with baseline LDL-C > 160 mg/dL achieved target lipid values. Multivariate analysis indicated that lower baseline LDL-C and triglycerides, use of combinations of drug therapy rather than monotherapy, and patient adherence to treatment predicted the achievement of goal lipid levels. CONCLUSIONS: Successful implementation of NCEP guidelines, frequently requires combination drug therapies, and is limited by poor patient tolerance and acceptance of niacin and the sequestrants.

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The genetic nature of obesity, hypertension, non-insulin-dependent diabetes, and low-density lipoprotein levels was reviewed. Obesity, hypertension, and diabetes are evolving conditions that are associated with early changes in lipid and carbohydrate metabolism. An appreciation of the genetic nature of these conditions should be useful in devising screening strategies for family members who are at risk for coronary artery disease because of their family history.

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OBJECTIVE: Noxious adverse effects frequently limit patient acceptance of niacin and bile acid sequestrants (BAS), first-line agents in the management of hypercholesterolemia. The purpose of this study was to determine whether telephone contacts from a healthcare professional could improve drug adherence and tolerance in patients prescribed these medications. PATIENTS AND METHODS: This was a randomized, single-blind trial of telephone contacts vs. no intervention in patients with hyperlipidemia who were prescribed either niacin or BAS in a large, Veterans Affairs, lipid clinic. Patients randomized to telephone contact (n = 81) received weekly calls from a trained healthcare professional during the first month of drug therapy. Counseling regarding adverse effects, and prescriptions to overcome minor adverse effects, were provided as needed to patients during the telephone contact. RESULTS: Significant differences were not observed between groups in the drug discontinuance rate, adherence assessed by two independent methods, or in the final dosage of medication ingested. CONCLUSIONS: Telephone contacts do not improve either adherence or tolerance to niacin or BAS. Alternative approaches to enhance acceptance of these medications requires further evaluation.

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BACKGROUND: The National Cholesterol Education Program recommends achievement of a defined target level of low-density lipoprotein cholesterol (LDL-C) for the treatment of hypercholesterolemia. They endorse the use of niacin and/or sequestrants as the first line of therapy to achieve such target LDL-C level. This recommendation has not been compared with the use of lovastatin as initial therapy if multidrug regimens are required to achieve goal LDL-C. METHODS: Prospectively collected data on tolerance and effectiveness for niacin, sequestrants, and lovastatin were obtained from a lipid clinic at a large midwestern Veterans Affairs medical center. We used a decision tree to compare the complexity and cost of three sequential drug algorithms used for the following initial LDL-C levels: 4.14, 4.91, 5.69, and 6.47 mmol/L (160, 190, 220, and 250 mg/dL). Algorithm 1 was niacin followed by a sequestrant and then lovastatin; algorithm 2, a sequestrant followed by niacin and then lovastatin; and algorithm 3, lovastatin followed by niacin and a sequestrant. Drug and laboratory costs were obtained from the pharmacy and pathology services at the same institution. Sensitivity analyses were performed on the tolerance and effectiveness of each drug as well as drug and laboratory cost estimates. RESULTS: The probability of achieving target LDL-C level (3.36 mmol/L [130 mg/dL]) decreased as initial LDL-C level increased. As a rule, algorithm 3 required fewer drugs in combination to achieve the target level for all initial LDL-C levels modeled. In addition, the use of lovastatin was high across all algorithms at all initial LDL-C levels modeled. Algorithm 1 was less expensive than algorithm 2 or 3 at a low initial LDL-C level (4.14 mmol/L [160 mg/dL]), with an average cost of $375 vs $454 vs $585, respectively. At all other initial LDL-C levels (4.91, 5.69, and 6.47 mmol/L [190, 220, and 250 mg/dL]), algorithm 2 was slightly less expensive than algorithm 1. Algorithm 3 became relatively less expensive as initial LDL-C level increased: 56% more expensive than algorithm 1 at an initial LDL-C level of 4.14 mmol/L (160 mg/dL) as compared with 7% more expensive than algorithm 1 at an initial LDL-C level of 6.47 mmol/L (250 mg/dL). CONCLUSIONS: Fulfillment of the target LDL-C approach recommended by the National Cholesterol Education Program often requires the use of multiple drugs. When lovastatin is used initially, the regimen becomes simpler, albeit more expensive. At initial LDL-C levels of 4.91 mmol/L (190 mg/dL) or higher, this difference in cost becomes progressively smaller (7% at 6.47 mmol/L [250 mg/dL]), making algorithm 3 the better alternative; at low initial LDL-C levels (4.14 mmol/L [160 mg/dL]), a niacin-first regimen is reasonably simple and substantially less expensive. At moderate and severe initial LDL-C levels (4.91 and 5.69 mmol/L [190 and 220 mg/dL]), the lovastatin-first regimen may be advantageous.

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BACKGROUND: No medical therapy has been shown to reduce the rate of restenosis following percutaneous transluminal coronary angioplasty. We examined the existing evidence for the use of omega-3 fatty acids in this capacity with the tool of meta-analysis. METHODS: A computerized search and a bibliographic review of published articles were performed. Abstracts were identified through journals, Index Medicus, and an unpublished listing of recent requests for fish oil for experimental use. All English-language randomized clinical trials with available reports were included in the analysis. The quality, design differences, and outcomes were evaluated for each study. RESULTS: For four studies that used angiography to define coronary restenosis, the absolute difference in restenosis rates between treatment and control groups was 13.9% (95% confidence interval [CI], 3.2% to 24.5%). Furthermore, regression analysis revealed a positive linear relationship between the dose of omega-3 fatty acids used and the absolute difference in restenosis rates (r = .99, P < .03). When three studies that used stress testing as a means of determining restenosis rates were added to the four studies that used angiography, the risk difference was 5.1% (95% CI, -3.8% to 13.9%). CONCLUSIONS: Restenosis after coronary angioplasty is reduced by supplemental fish oils, and the extent of the observed benefit may be dependent on the dose of omega-3 fatty acids used.

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Decreasing the large test variability associated with measurements of blood cholesterol, triglyceride, and high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol is likely to improve the classification of coronary heart disease (CHD) risk and allow improved monitoring of lipid-lowering treatments. However, improving test precision will benefit the clinician only if (a) the analytical test variability is high relative to the biological test variability and (b) detecting subtle responses to diet or drug therapy is clinically important. Improving HDL- and LDL-cholesterol test precision can be expected to increase the clinical usefulness of these measurements because values for HDL- and LDL-cholesterol correlate closely with CHD risk; are associated with small, yet clinically important, changes in response to diet and (or) drug therapy; and have substantial analytical test variability relative to biological variability. On the other hand, measurements of both blood cholesterol and triglyceride have high biological relative to analytical variability, and do not correlate as closely with CHD risk. Therefore, further improvements in precision for these measurements are less likely to be useful to the clinician.

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This analysis of a large, population based, cross-sectional survey demonstrates that the association of smoking with decreased serum ascorbic acid (AA) levels is independent of the reduced AA intake found in smokers. Smokers have a threefold higher incidence of low serum AA levels (< or = 11 mumol/L) which could place them at increased risk for the clinical manifestations of AA deficiency. Smokers not taking vitamin supplements who consumed less than 15 servings weekly of fruits and vegetables were especially prone to have serum AA levels less than 11 mumol/L. An AA intake of > or = 200 mg was necessary to provide smokers with equivalent protection from hypovitaminosis AA as had nonsmokers whose AA intake exceeded the recommended dietary allowance (RDA [60 mg]). This level of dietary AA intake is considerably higher than the newly increased RDA for smokers of 100 mg. Although the simplest and most direct method to increase the low serum vitamin C levels found in many smokers would be to stop smoking, markedly increasing dietary AA consumption is appropriate when this is unsuccessful. However, if dietary modification fails to sufficiently increase AA intake, then vitamin supplementation may be necessary to significantly reduce the high prevalence of hypovitaminosis AA present in smokers.

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Veterans are frequently older, have more chronic illnesses, and take more medications than subjects volunteering for clinical trials. Because these factors may impair the effectiveness of lipid-lowering drug therapy, the effectiveness of drug therapy in veterans may differ from that measured in randomized controlled trials. In 297 patients with type IIa hyperlipidemia attending a large Veterans Administration Medical Center lipid clinic, adverse effects, compliance, lipid and lipoprotein responses to drug therapy were prospectively monitored. Bile acid sequestrants (4 packets/day) were associated with a high rate of adverse effects, and had the highest drug discontinuance rate (37%) and poorest compliance (73 +/- 3% of the doses prescribed reported ingested) of all agents. Patients aged > 60 years tolerated therapy with bile acid sequestrants less well than did younger veterans (p < 0.01). Niacin (1.5 g/day) also had a high drug discontinuance rate (27%). Lovastatin (20 mg/day) had the lowest drug discontinuance rate (2%) and the highest compliance (90 +/- 2%). Lovastatin also reduced low-density lipoprotein (LDL) cholesterol the most (-21.6 +/- 2.0%), whereas niacin produced the largest increase in high-density lipoprotein (HDL) cholesterol (+/- 14.3 +/- 2.2%); both niacin and lovastatin produced similar reductions in the LDL/HDL ratio. However, psyllium (10.4 g/day) reduced LDL cholesterol by only 2%, and had no effect on the LDL/HDL ratio. Psyllium produced larger LDL cholesterol reductions in patients aged < 60 years than in older patients (p < 0.01). Niacin and lovastatin are effective drugs for hypercholesterolemia management in the Veterans Administration Medical Center setting.(ABSTRACT TRUNCATED AT 250 WORDS)

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Although a large body of epidemiologic evidence suggests that low levels of high-density lipoprotein (HDL) cholesterol are strongly associated with an increased risk of coronary artery disease (CAD), no large-scale clinical trials focusing on this association have been reported. This report describes the rationale and design of the Department of Veterans Affairs HDL Intervention Trial (HIT), a multicenter, randomized, controlled clinical trial designed to determine whether lipid therapy reduces the combined incidence of CAD death and nonfatal myocardial infarction in men with established CAD who have low levels of HDL cholesterol with "desirable" levels of low-density lipoprotein (LDL) cholesterol. Twenty-five hundred men with CAD and HDL cholesterol < or = 40 mg/dl, LDL cholesterol < or = 140 mg/dl, and triglycerides < or = 300 mg/dl are being recruited at 20 Department of Veterans Affairs medical centers, randomized to either gemfibrozil or placebo, and followed in a double-blind manner for an average of 6 years. In this population, gemfibrozil is expected to increase HDL cholesterol by 10 to 15%, have a negligible effect on LDL cholesterol, and lower triglycerides by 30 to 40%. Because an estimated 20 to 30% of patients with CAD have a low HDL cholesterol as their primary lipid abnormality, the results of this trial are expected to have far-reaching clinical implications.

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BACKGROUND: Risk factor modification, including treatment of dyslipidemias, has been recommended for the prevention of future coronary events in patients with coronary heart disease (CHD). Since the prevalence of various dyslipidemias among outpatients with CHD has not been well documented, the purpose of this study was to determine the frequency of specific lipid phenotypes among ambulatory men with CHD. METHODS: Lipid profiles were obtained in 255 men (mean age, 65.5 +/- 9.1 years) with CHD in three Veterans Affairs medical centers. Desirable levels of lipids were defined according to National Cholesterol Education Program guidelines as follows: low-density lipoprotein cholesterol (LDL-C) levels less than 3.36 mmol/L (130 mg/dL); high-density lipoprotein cholesterol (HDL-C) levels equal to or greater than 0.90 mmol/L (35 mg/dL); and triglyceride levels less than 2.83 mmol/L. RESULTS: Seventy-six percent of the group had one or more abnormalities on lipid profile: 51% had high LDL-C levels with or without abnormalities of HDL-C and/or triglyceride levels; 22% had low HDL-C levels with desirable levels of LDL-C; and 3% had hypertriglyceridemia without any cholesterol abnormalities. Normal lipid profiles were significantly more prevalent in subjects over the age of 65 years than in younger patients (40% vs 14%). CONCLUSIONS: These data suggest that (1) a high proportion of men with CHD have dyslipidemia, including 50% with LDL-C level elevations. For these men, the potential benefits of therapeutic intervention have been documented in clinical trials, although the cost-efficiency of wide-scale treatment has not been determined; (2) isolated hypertriglyceridemia is rare in this population; and (3) low HDL-C levels in association with desirable LDL-C levels are present in more than one fifth of male patients with CHD. Clinical trials focusing on this large group are urgently needed to determine whether efforts to raise HDL-C levels result in reduced cardiac morbidity and/or mortality.

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