Effect of fish oil concentrate on lipoprotein composition in NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated with elevated very-low-density lipoprotein (VLDL) triglyceride concentrations and abnormalities of low-density lipoprotein (LDL) composition. Because fish oil supplementation may favorably affect lipid and lipoprotein concentrations in nondiabetic subjects, we determined the effect of fish oil concentrate on plasma lipids and lipoprotein composition in patients with NIDDM. Dietary-supplementation 1-mo periods of 4.0 and 7.5 g of omega-3 fatty acids in fish oil were compared with a placebo of 12 g safflower oil by use of a single-blind crossover design. Medications, including antidiabetic therapy, were continued through the study. Compared with safflower oil treatment, fish oil supplementation resulted in a significant reduction of total plasma triglycerides of 24% at the 4-g dose and a larger reduction of 39% at the 7.5-g dose. These decreases were due to similar reductions in VLDL triglycerides. LDL cholesterol levels were mildly elevated, but a larger 20% increase in LDL apolipoprotein B (apoB) concentration was observed. During supplementation with the fish oil concentrate, the LDL cholesterol-to-apoB ratio was significantly reduced when compared with pretreatment values, but not when compared with safflower oil treatment. High-density lipoprotein (HDL) cholesterol and plasma apoA1 levels were not significantly changed during fish oil treatment. At the 7.5-g dose, fasting glucose and glycohemoglobin levels increased by 20 and 12%, respectively, but were unchanged at the lower level of supplementation. Thus, in NIDDM patients, dietary supplementation with omega-3 fatty acids induces a reduction in total plasma and VLDL triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary artery disease risk factors from a genetic and developmental perspective.

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.

A history of hypercholesterolemia influences cholesterol measurements.

Elevated plasma cholesterol levels identified during cholesterol screening are often lower when repeated because of the regression to the mean effect. We evaluated the effect of the presence or absence of a history of hypercholesterolemia on the regression to the mean phenomenon. Of 564 volunteers undergoing cholesterol screening, 53 subjects between the ages of 20 and 65 years found to have total plasma cholesterol levels above the 90th percentile for age and sex returned for a second determination. No dietary or behavioral changes occurred during the study. Individuals with a history of hypercholesterolemia showed no change in plasma cholesterol level between the first and second visits; however, a net 13.1% reduction in mean plasma cholesterol level was observed in the group without this history, with 59% of subjects dropping below the 90th percentile level. These findings demonstrate that the regression to the mean effect is confined to those individuals who do not report a history of hyperlipidemia. Subjects with this history are more likely to have their initial cholesterol elevation confirmed when the test is repeated.

Distribution of lipid phenotypes in community-living men with coronary heart disease. High prevalence of isolated low levels of high-density lipoprotein cholesterol.

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.

Combination drug therapy for hypercholesterolemia. The trade-off between cost and simplicity.

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.

Preventing restenosis with fish oils following coronary angioplasty. A meta-analysis.

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.

Polyunsaturated and saturated fat, cholesterol, and fatty acid supplementation.

Almost all of risk factors for arteriosclerosis and coronary heart disease identified in population studies are overrepresented in diabetes. Of these risk factors, plasma lipids and lipoproteins are the target for altered dietary habits, particularly regarding fat. Such an alteration must be qualified with an understanding of the relationship between diabetes mellitus and lipoprotein metabolism and evidence of a favorable outcome of a fat-modified diet on this relationship. In seeking a revision of the current dietary fat recommendations of the American Diabetes Association, we have addressed five major questions. Is the serum lipid or lipoprotein concentration in diabetes different from that of the nondiabetic population? Are the familial or genetic forms of hyperlipidemia coinherited and/or overrepresented in diabetic subjects? What is the mechanism of the lipid/lipoprotein disorder in diabetes, and to what extent could it be related to the diabetic metabolic milieu? What is the effect of antidiabetic treatment on plasma lipids and lipoprotein metabolism? What evidence is there that a modified-fat diet could exert favorable benefits over and above what could be achieved by optimal antidiabetic therapy? This article outlines the revised dietary fat recommendations of the American Diabetes Association Nutrition Task Force and their rationale.

Normal postprandial lipemia and chylomicron clearance in offspring of parents with early coronary artery disease.

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.

Ascorbic acid requirements for smokers: analysis of a population survey.

The recommended dietary allowance (RDA) of ascorbic acid for smokers was recently increased from 60 to 100 mg. To determine whether this new RDA for smokers is sufficient to reduce the risk of low serum ascorbic acid (AA) concentrations (LoC) to the same concentration as nonsmokers, we analyzed the dietary intakes and serum concentrations of AA in 11,582 adult respondents in the National Health and Nutrition Examination Survey (1976-1980). Serum AA concentrations and the risk of LoC (serum ascorbic acid levels less than 23 mumol/L) for smokers consuming different amounts of AA were compared with those for nonsmokers whose AA intake exceeded the RDA (60 mg). Serum AA concentrations were reduced, and risk of LoC increased, in smokers maintaining AA intakes greater than 60, 100, and 150 mg. Only smokers consuming greater than 200 mg AA/d had serum ascorbate concentrations and risk of LoC equivalent to nonsmokers meeting the RDA.

Dietary fish oil decreases low-density-lipoprotein clearance in nonhuman primates.

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.

Drug therapy for hypercholesterolemia in patients with cardiovascular disease: factors limiting achievement of lipid goals.

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.

Evaluation of the effectiveness of lipid-lowering therapy (bile acid sequestrants, niacin, psyllium and lovastatin) for treating hypercholesterolemia in veterans.

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)

Effectiveness of low-dose colestipol therapy in patients with moderate hypercholesterolemia.

Recommended doses of bile-acid binding resins have an established hypocholesterolemic effect, but data on responses to low doses, especially in women and subjects with moderate hypercholesterolemia, are sparse. A double-blind, placebo-controlled, randomized trial of 3 low doses of colestipol hydrochloride was conducted in women and men with moderate hypercholesterolemia. Men and women with plasma low-density lipoprotein (LDL) cholesterol concentrations greater than 4 mmol/liter (155 mg/dl) and triglyceride concentrations less than 2.82 mmol/liter (250 mg/dl) were recruited for the study. Eligible patients (54 women and 98 men) were placed on the American Heart Association step I diet 6 weeks before randomization. Participants were subsequently assigned to 1 of 4 drug treatment groups (placebo, and 5, 10 and 15 g/day of colestipol in 2 divided doses) for an additional 12 weeks. Of the 152 patients randomized, 141 completed all aspects of the study. For the treatment groups--placebo, and 5, 10 and 15 g of colestipol--LDL cholesterol reductions (mmol/liter) were observed respectively (n = 141): 0.10 +/- 0.49 (2.7%), 0.65 +/- 0.41 (16.3%), 0.98 +/- 0.36 (22.8%) and 1.17 +/- 0.47 (27.2%) (p less than 0.001). Similar changes were observed in total cholesterol and apolipoprotein B concentrations. The apolipoprotein B/LDL cholesterol ratio increased significantly with increasing colestipol dosage. Modest but insignificant changes in plasma triglyceride levels occurred, and high-density lipoprotein cholesterol levels remained unchanged. A dose of 5 g/day of colestipol achieved 51% of the LDL cholesterol reduction noted with 15 g/day. Low-dose colestipol therapy is effective in the treatment of patients with moderate hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Rationale and design of the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (HIT) for secondary prevention of coronary artery disease in men with low high-density lipoprotein cholesterol and desirable low-density lipoprotein cholesterol.

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.

Estimating ascorbic acid requirements for cigarette smokers.

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.

Lack of effect of salt on the glucose and insulin response to mashed potatoes, white rice, and lima beans.

The effect of 4.25 g of table salt on the insulin and glucose response to three forms of carbohydrate with varying glycemic indices was studied. There was no statistical difference in the peak response or area under the glucose or insulin curves for any of these foods in the presence of salt. It is concluded that salt has no effect on the absorption of starches.

Insulin resistance is not a major determinant of low-density lipoprotein particle size.

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.

Low-density lipoprotein particle size is not a discriminating marker for atherogenic risk in male offspring of parents with early coronary artery disease.

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.

Discontinuation rates of cholesterol-lowering medications: implications for primary care.

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.