Extended-release niacin vs gemfibrozil for the treatment of low levels of high-density lipoprotein cholesterol. Niaspan-Gemfibrozil Study Group

OBJECTIVE: To provide a direct comparison of agents that raise plasma levels of high-density lipoprotein cholesterol (HDL-C) to help devise strategies for coronary risk reduction. METHODS: In a multicenter, randomized, double-blind trial, we compared the effects of extended-release niacin (Niaspan), at doses increased sequentially from 1000 to 2000 mg at bedtime, with those of gemfibrozil, 600 mg given twice daily, in raising low levels of HDL-C. Enrollment criteria included an HDL-C level of 1.03 mmol/L or less (< or =40 mg/dL), a low-density lipoprotein cholesterol level of 4.14 mmol/L or less (< or =160 mg/dL) or less than 3.36 mmol/L (<130 mg/dL) with atherosclerotic disease, and a triglyceride level of 4.52 mmol/L or less (< or =400 mg/dL). RESULTS: Among 173 patients, 72 (82%) of the 88 assigned to Niaspan treatment and 68 (80%) of the 85 assigned to gemfibrozil treatment completed the study. Niaspan, at 1500 and 2000 mg, vs gemfibrozil raised the HDL-C level more (21% and 26%, respectively, vs 13%), raised the apolipoprotein A-I level more (9% and 11% vs 4%), reduced the total cholesterol-HDL-C ratio more (-17% and -22% vs -12%), reduced the lipoprotein(a) level (-7% and -20% vs no change), and had no adverse effect on the low-density lipoprotein cholesterol level (2% and 0% change vs a 9% increase). Significance levels for comparisons between medications ranged from P<.001 to P<.02. Gemfibrozil reduced the triglyceride level more than Niaspan (P<.001 to P = .06, -40% for gemfibrozil vs -16% to -29% for Niaspan, 1000 to 2000 mg). Effects on plasma fibrinogen levels were significantly favorable for Niaspan compared with gemfibrozil (P<.02), as gemfibrozil increased the fibrinogen level (from 5% to 9%) and Niaspan tended to decrease the fibrinogen level (from -1% to -6%). CONCLUSIONS: In patients with a low baseline HDL-C level, Niaspan at its higher doses provided up to 2-fold greater HDL-C increases, decreases in lipoprotein(a), improvements in lipoprotein cholesterol ratios, and lower fibrinogen levels compared with gemfibrozil. Gemfibrozil gave a greater triglyceride reduction but also increased the low-density lipoprotein cholesterol level, which did not occur with Niaspan.     

Prevalence of high plasma triglyceride combined with low HDL-C levels and its association with smoking, hypertension, obesity, diabetes, sedentariness and LDL-C levels in the Canadian population. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report the associations of plasma triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) with nonlipid coronary artery disease risk factors. In particular, the associations for persons with high triglyceride and low HDL-C levels were examined. DESIGN: A stratified random probability sample of 29,855 men and women aged 18 to 74 years from the Canadian Heart Health Surveys (1986 to 1992) in 10 provinces. Blood samples were obtained from 18,555 participants who had fasted for 8 h or more. Plasma lipids were determined at the J Alick Little Lipid Research Laboratory, Toronto, Ontario, with standardization of the Centers for Disease Control Lipid Standardization Program, Atlanta. OUTCOME MEASURES: Fasting plasma total cholesterol, triglyceride, LDL-C and HDL-C levels. MAIN RESULTS: The prevalence of men with triglyceride levels above 1.7 mmol/L and HDL-C levels below 0.9 mmol/L was 10%, compared with 3% for men with triglyceride levels below 1.7 mmol/L and HDL-C levels below 0.9 mmol/L. The prevalence of women with triglyceride levels above 1.7 mmol/L and HDL-C levels below 0.9 mmol/L was 3% compared with a prevalence of less than 1% for women with triglyceride levels below 1.7 mmol/L and HDL-C levels below 0.9 mmol/L. Even when plasma LDL-C was low at less than 3.4 mmol/L, there was an age trend for increasing prevalences of the combination of triglyceride levels 2.3 mmol/L or greater and HDL-C levels less than 0.9 mmol/L in both sexes. The prevalence of a triglyceride levels 2.3 mmol/L or greater combined with an HDL-C level below 0.9 mmol/L was increased in groups who were cigarette smokers, diabetic, hypertensive, obese or sedentary, or who had higher LDL-C levels in both sexes, and the increase was even greater in the presence of two or more of these other risk factors. CONCLUSIONS: Among men or women with low HDL-C and high triglyceride levels, smoking, diabetes, sedentariness, hypertension and obesity were much more prevalent than among those at low risk with high HDL-C and low triglyceride levels.     

Long-term predictors of subsequent cardiovascular events with coronary artery disease and 'desirable' levels of plasma total cholesterol.

BACKGROUND. Patients with coronary artery disease (CAD) are at considerable risk for subsequent cardiovascular events. Although hyperlipidemia accentuates the risk, predictors of subsequent events with CAD and desirable total cholesterol (TC) (less than 5.2 mmol/l) have not been assessed. METHODS AND RESULTS. A survival analysis was performed in a subset of 740 consecutive patients who underwent diagnostic coronary arteriography between 1977 and 1978. Eight-three men and 24 women with angiographically documented CAD and desirable TC were followed for subsequent cardiovascular events, including myocardial infarction and cardiovascular death. Over a 13-year period, 75% of CAD subjects with reduced high density lipoprotein cholesterol (HDL-C) (less than 0.9 mmol/l) developed a subsequent cardiovascular event compared with 45% of those with HDL-C greater than or equal to 0.9 mmol/l (p = 0.002). A Kaplan-Meier analysis revealed significantly greater survival from cardiovascular end points in patients with baseline levels of HDL-C greater than or equal to 0.9 mmol/l (p = 0.005). After 11 variables were tested, an age-adjusted Cox proportional-hazards model identified two pairs of independent predictors of subsequent cardiovascular events: they were a left ventricular ejection fraction (LVEF) less than 35% (relative risk [RR], 6.5; 95% confidence interval [CI], 2.8, 15.3; p less than 0.001) and reduced HDL-C (RR, 2.0; 95% CI, 1.2, 3.3; p = 0.01) in the first model and LVEF less than 35% (RR, 6.5; 95% CI, 2.7, 15.6; p less than 0.001) and TC:HDL ratio greater than or equal to 5.5 (RR, 1.9; 95% CI, 1.1, 3.1; p = 0.02) in the second model. CONCLUSIONS. Low HDL-C (or high TC:HDL-C) is strongly predictive of subsequent cardiovascular events in subjects with CAD, despite desirable TC. As such, identification of this potentially modifiable risk factor should be actively pursued in this high-risk subgroup.     

High density lipoprotein cholesterol and triglycerides as markers of angiographically assessed coronary artery disease.

Serum triglycerides, high density lipoprotein (HDL) cholesterol, and total cholesterol were measured in 698 patients examined by angiography. The ratio of HDL cholesterol to total cholesterol was significantly lower in patients with single, double, and triple vessel disease than in patients without disease. The serum concentration of triglyceride was significantly higher in patients with single, double, and triple vessel disease than in those without coronary artery disease. Similar proportion of patients with coronary artery disease and without had serum cholesterol concentrations of greater than or equal to 6.5 mmol/l, but total cholesterol was significantly higher in patients with single, double, and triple vessel disease than in those without. HDL cholesterol (less than 1.0 mmol/l), triglycerides (greater than 2.0 mmol/l), and the ratio of HDL cholesterol to total cholesterol (less than 0.20) were significantly better than total cholesterol as indicators of coronary risk.     

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.     

Comparison of gemfibrozil and lovastatin in patients with high low-density lipoprotein and low high-density lipoprotein cholesterol levels.

BACKGROUND--The efficacy of gemfibrozil and lovastatin in the treatment of patients who have an elevated low-density lipoprotein cholesterol (LDL-C) level and a low high-density lipoprotein cholesterol (HDL-C) level was compared. METHODS--After at least 6 weeks of a cholestgerol-lowering diet, 17 patients who had a mean baseline LDL-C level above 4.14 mmol/L (160 mg/dL) and an HDL-C level below 1.03 mmol/L (40 mg/dL) received gemfibrozil 600 mg twice daily and lovastatin 20 mg twice daily each for 6 weeks according to a randomized, crossover, double-blind research design. RESULTS--Lovastatin and gemfibrozil reduced LDL-C levels 34% and 9% and raised HDL-C levels 15% and 18%, respectively. CONCLUSIONS--Lovastatin is more effective in lowering LDL-C levels and is as effective as gemfibrozil in increasing HDL-C levels in these patients.     

High density lipoprotein cholesterol and triglycerides as markers of angiographically assessed coronary artery disease

Serum triglycerides, high density lipoprotein (HDL) cholesterol, and total cholesterol were measured in 698 patients examined by angiography. The ratio of HDL cholesterol to total cholesterol was significantly lower in patients with single, double, and triple vessel disease than in patients without disease. The serum concentration of triglyceride was significantly higher in patients with single, double, and triple vessel disease than in those without coronary artery disease. Similar proportion of patients with coronary artery disease and without had serum cholesterol concentrations of greater than or equal to 6.5 mmol/l, but total cholesterol was significantly higher in patients with single, double, and triple vessel disease than in those without. HDL cholesterol (less than 1.0 mmol/l), triglycerides (greater than 2.0 mmol/l), and the ratio of HDL cholesterol to total cholesterol (less than 0.20) were significantly better than total cholesterol as indicators of coronary risk.     

Cost-effectiveness of gemfibrozil for coronary heart disease patients with low levels of high-density lipoprotein cholesterol: the Department of Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial.

BACKGROUND: Although numerous clinical trials and economic analyses have established the efficacy and cost-effectiveness of lowering cholesterol for the prevention of coronary heart disease, there are few data on the role of raising high-density lipoprotein cholesterol (HDL-C) levels and lowering triglyceride levels. The US Department of Veterans Affairs (VA) Cooperative Studies Program HDL-C Intervention Trial (VA-HIT) was a multicenter, randomized trial of gemfibrozil, an agent that raised HDL-C levels and lowered triglyceride levels, yet had no effect on low-density lipoprotein cholesterol (LDL-C) levels. The study showed that gemfibrozil therapy significantly reduced major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in patients with coronary heart disease, low HDL-C levels, and low LDL-C levels. OBJECTIVE: To report the results of a cost-effectiveness study based on the results of the VA-HIT. METHODS: The cost per year of life gained with gemfibrozil therapy was calculated. Hazard functions were estimated, and the resulting probabilities were used in a Markov model simulation to estimate the effect of gemfibrozil on life expectancy and costs over a simulated lifetime. Sensitivity analyses were used to account for uncertainty. RESULTS: Using the prices of gemfibrozil that were negotiated by the VA, gemfibrozil was cost saving. Using drug prices found outside the VA, a quality-adjusted life-year saved by gemfibrozil therapy cost between $6300 and $17 100. CONCLUSIONS: Gemfibrozil reduces major cardiovascular events in male coronary heart disease patients with low levels of HDL-C and low levels of LDL-C and would result in cost saving at annual drug costs of $100 or less in 1998 dollars. Even at the higher drug prices represented by the average wholesale price in the United States, the cost of a life-year saved is well below the threshold that would be deemed cost-effective. To our knowledge, this is the first economic analysis based on clinical trial data to assess the cost-effectiveness of raising HDL-C levels and lowering triglyceride levels in a setting in which LDL-C levels were not lowered.     

Lipoprotein lipids in older people. Results from the Cardiovascular Health Study. The CHS Collaborative Research Group.

BACKGROUND. Cardiovascular disease is the leading cause of death and disability in older people. There is little information about the distributions of risk factors in older populations. This article describes the distribution and correlates of lipoprotein lipids in people greater than or equal to 65 years old. METHODS AND RESULTS. Lipoprotein lipid concentrations were measured in 2,106 men (M) and 2,732 women (F) who were participants in the Cardiovascular Health Study, a population-based epidemiological study. Distributions of lipids by age and sex and bivariate and multivariate relations among lipids and other variables were determined in cross-sectional analyses. Mean concentrations of lipids were cholesterol: M, 5.20 +/- 0.93 mmol/l (201 +/- 36 mg/dl) and F, 5.81 +/- 0.98 mmol/l (225 +/- 38 mg/dl); triglyceride (TG): M, 1.58 +/- 0.85 mmol/l (140 +/- 75 mg/dl) and F, 1.57 +/- 0.78 mmol/l (139 +/- 69 mg/dl); high density lipoprotein cholesterol (HDL-C): M, 1.23 +/- 0.33 mmol/l (48 +/- 16 mg/dl), and F, 1.53 +/- 0.41 mmol/l (59 +/- 16 mg/dl); low density lipoprotein cholesterol (LDL-C): M, 3.27 +/- 0.85 mmol/l (127 +/- 33 mg/dl) and F, 3.57 +/- 0.93 mmol/l (138 +/- 36 mg/dl). The total cholesterol to HDL-C ratios were M, 4.49 +/- 1.29 and F, 4.05 +/- 1.22. TG, total cholesterol, and LDL-C concentrations were lower with increasing age, the last more evident in men than in women. TG concentration was positively associated with obesity (in women), central fat patterning, glucose intolerance, use of beta-blockers (in men), and use of estrogens (in women) and negatively associated with age, renal function, alcohol use, and socioeconomic status. In general, HDL-C had opposite relations with these variables, except that estrogen use was associated with higher HDL-C concentrations. LDL-C concentration was associated with far fewer variables than the other lipids but was negatively associated with age in men and women and positively correlated with obesity and central fat patterning and negatively correlated with renal function and estrogen use in women. There were no differences in total cholesterol and LDL-C concentrations among participants with and without prevalent coronary heart disease and stroke, but TG concentration was higher and HDL-C lower in men with both coronary heart disease and stroke and in women with coronary heart disease. CONCLUSIONS. Cholesterol and cholesterol/HDL-C ratio were lower and HDL-C higher than previously reported values in older people, suggesting that lipid risk profiles may be improving in older Americans. TG and HDL-C concentrations, and to a lesser extent LDL-C, were associated with potentially important modifiable factors such as obesity, glucose intolerance, renal function, and medication use.     

Effects of treatment of hypertriglyceridaemia with gemfibrozil on serum lipoproteins and the transfer of cholesteryl ester from high density lipoproteins to low density lipoproteins.

Lipoprotein composition and cholesterol esterification, before and after treatment with gemfibrozil, have been examined in the fasting and postprandial state in nine patients with primary hypertriglyceridaemia who participated in a double-blind, placebo controlled study. After 8 weeks of treatment fasting serum triglycerides were reduced significantly from 6.05 mmol/l (range 2.48-10.99 mmol/l) to 1.76 mmol/l (range 1.16-11.90 mmol/l) (P less than 0.001). This was mainly due to a decrease in the triglyceride content of the Sf 12-20, 60-400 and Sf greater than 400 lipoprotein fractions (P less than 0.05). The Sf 0-12 fraction showed an increase in cholesteryl ester, free cholesterol, phospholipids and protein. Consistent with these findings there was a net increase in the mass concentration of the Sf 0-12 fraction (P less than 0.05) and a decrease in that of small very low density lipoproteins (Sf 20-60) (P less than 0.05). In the 8 patients in whom it was measured there was a 40% reduction in the rate at which cholesteryl esters derived from radiolabelled-free cholesterol appeared in very low density lipoprotein (VLDL) and low density lipoprotein (LDL) measured in an in vitro system (P less than 0.02), but serum lecithin:cholesterol acyl transferase (LCAT) activity was unchanged. At the end of each treatment phase (placebo or gemfibrozil) patients were given a mixed meal containing 100 g of fat. Treatment with gemfibrozil resulted in a reduction in serum triglyceride concentrations at all time points for at least 5 h after the meal (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.

BACKGROUND: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)-low HDL-C dyslipidemia. METHODS: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. RESULTS: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDL-C/HDL-C ratio. CONCLUSION: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio.     

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.     

Plasma lipids and lipoprotein reference values, and the prevalence of dyslipoproteinemia in Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To report reference values for plasma lipids and lipoproteins in Canadian adults and the prevalence in the population of various levels of risk for coronary artery disease from dyslipoproteinemia. DESIGN, SETTING AND PARTICIPANTS: Population- based provincial heart health cross-sectional surveys in 10 provinces between 1986 and 1992 invited 29,855 men and women aged 18 to 74 years to participate. During a clinic visit after a home interview a blood sample was obtained following a fast of 8 h or more from 18,555 people. Plasma lipid levels were determined at the J Alick Little Lipid Research Laboratory, Toronto, with standardization of the Centers for Disease Control Lipid Standardization Program, Atlanta. OUTCOME MEASURES: Fasting plasma total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-HDL-C levels. MAIN RESULTS: Mean plasma total cholesterol, LDL-C, non-HDL-C and triglyceride levels increased with age in men to a peak at around age 54 years, while in women the increases were more gradual at a lower level until age 54 years, after which they increased appreciably eventually exceeding values for men. A high percentage of adults were at increased risk for coronary artery disease: 44% had elevated total cholesterol levels above 5.2 mmol/L; 14% had LDL-C levels above 4.1 mmol/L; 8% had HDL-C values below 0.9 mmol/L; and 14% had triglyceride levels above 2.3 mmol/L. Eleven per cent of adults had both total cholesterol level above 6.2 mmol/L and LDL-C level above 4.1 mmol/L. CONCLUSION: The high prevalence of Canadian adults at risk because of elevated plasma lipid levels strongly indicates the need for comprehensive public health programs to reduce plasma lipid levels in the population and the need to encourage physicians to treat those at high risk.     

Serum cholesterol, high-density lipoprotein cholesterol and five-year survival in elderly people

In the year 1982 serum cholesterol and high-density lipoprotein (HDL) cholesterol were measured in 535 people aged 85 years participating in a health survey screening. All subjects were living at home. During the 5-year follow-up, 186 (34.8%) of the subjects died. There was a J-shaped relation between serum cholesterol and mortality. Mortality was lowest at serum cholesterol 5.0-5.9 mmol/l for men and 7.0-7.9 mmol/l for women. The greatest mortality was observed in men with cholesterol greater than or equal to 6.0 mmol/l and in women with cholesterol greater than or equal to 8.0 mmol/l. There was a significant negative association of serum HDL cholesterol with mortality. Mortality was highest (53.3%) in men with serum HDL cholesterol less than 0.80 mmol/l. Mortality was low (16.5%) in women with serum HDL cholesterol greater than 1.8 mmol/l.     

Predictive value of remnant-like particle cholesterol as an indicator of coronary artery stenosis in patients with normal serum triglyceride levels

OBJECTIVE: We designed the present study to evaluate the association of various lipid and fibrinolytic components with coronary artery stenosis with respect to the triglyceride (TG) level. METHODS: Levels of TG, remnant-like particle cholesterol (RLP-C), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein-(a), uric acid, blood glucose, tissue plasminogen activator (t-PA), t-PA inhibitor type 1, antithrombin III, and protein C were measured in 208 patients who underwent diagnostic coronary angiograms. PATIENTS: Of these 208 patients, 59 were hypertriglyceridemic (150 mg/dl or higher) and 149 were normotriglyceridemic. RESULTS: Both LDL-C and HDL-C showed significant differences between patients with and those without coronary artery stenosis in both hypertriglyceridemic and normotriglyceridemic patient subgroups. However, RLP-C showed a significant difference in the normotriglyceridemic patient subgroup (p=0.012) but not in the hypertriglyceridemic patient subgroup (p=0.736). CONCLUSION: Our current retrospective study disclosed that RLP-C levels are closely associated with coronary artery stenosis in patients with normal TG levels.     

Comparison of gemfibrozil and clofibrate on serum lipids in familial combined hyperlipidemia. A randomized placebo-controlled, double-blind, crossover clinical trial

A randomized double blind, placebo-controlled crossover design was used to determine the efficacy of gemfibrozil and clofibrate in the treatment of familial combined hyperlipidemia and to determine which one of these agents would be more effective. Sixteen patients, 12 men and 4 women, mean age 49.5 years (40-68 yrs), had the entry criteria of increased cholesterol and/or triglyceride with an increase in triglyceride and/or cholesterol in one or more first degree relatives and/or family history of premature cardiovascular disease. Patients received 6 weeks of placebo followed by clofibrate 1000 mg bid or gemfibrozil 600 mg bid for 12 weeks, placebo for 6 weeks and the other drug for 12 weeks. Plasma total cholesterol, triglycerides, HDL-C, LDL-C, apo B and apo A-I were measured every 6 weeks during the study. Gemfibrozil was associated with a significant (P less than 0.05) decrease in plasma triglyceride concentration compared to placebo but it was not significantly different compared to clofibrate. For ease of comparison, the mean value for serum triglycerides during gemfibrozil treatment (average of the 6 and 12 week measurements) was calculated and was 232 +/- 198 mg/dl (mean +/- 1 SD) compared to the average of the placebo treatment values of 381 +/- 410 mg/dl and the average value during the clofibrate treatment period of 217 +/- 178 mg/dl. HDL-C was significantly (P less than 0.05) increased with both drugs and to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia

The effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia were assessed in a 6-month parallel group study, placebo (n = 15) versus fenofibrate 300 mg/day (n = 18), followed by an open label 6-month treatment period. After stabilization on an isocaloric low fat (less than 35% total calories) diet with less than 250 mg cholesterol/day and a P/S ratio of 1, and maintenance of LDL-cholesterol (LDL-C) levels greater than or equal to 175 mg/dl, subjects received placebo for 6 weeks and were then randomized into placebo or fenofibrate groups for 6 months, followed by open label treatment for 6 months. During the 6-month double-blind period, compared to the placebo group, the treatment group had significant reductions in total cholesterol, LDL-C, total apo B, and triglyceride, and increments in HDL-cholesterol, apolipoprotein A-I and apolipoprotein A-II (P less than 0.01 for all comparisons). Compared to placebo baseline, therapy with fenofibrate resulted in a reduction of LDL-C, apo B, and the LDL-C/HDL-C ratio of 15%, 13%, and 18% respectively; HDL-C, apo A-I, and apo A-II increased respectively 12%, 13% and 30% (P less than 0.01 for all comparisons). Mean adherence during the double blind phase of the trial was 95% in the drug group and 96% in the placebo group. An additional 6 months of open label fenofibrate therapy maintained the reduced total and LDL-C as well as the elevated HDL-C, apo A-I and apo A-II in the drug-drug group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors associated with plasma lipids and lipoproteins in type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIM: To assess the determinants and prevalence of hyperlipidaemia in Type 1 diabetic patients in the EURODIAB IDDM Complications Study. METHODS: Standardized questionnaire data were obtained and anthropometric and biochemical measurements performed on 3159 Type 1 diabetic patients, randomly selected from 31 diabetes clinics. Plasma lipid levels were determined centrally, using enzymatic methods RESULTS: Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), and HDL subfractions were higher in women than in men, while plasma triglycerides were higher in men (P < 0.001). Total cholesterol, low-density lipoprotein cholesterol (LDL-C) and HDL-C and HDL-C subfractions were, as expected, significantly associated with age and HbA1c in both sexes. Age and HbA1c adjusted values of triglyceride, total cholesterol, LDL-C, HDL-C and HDL3-C in men and triglyceride and HDL2-C in women showed significant associations with central obesity, measured as the waist to hip ratio (WHR). Current smokers had lipid profiles characteristic of insulin resistance in comparison to nonsmokers. Significant positive associations were observed between hypertension and plasma triglycerides, total cholesterol and LDL-C in men and women. In men, degree of physical activity was negatively associated with triglyceride and positively related to HDL-C and HDL3-C. The prevalence of LDL-hypercholesterolaemia (LDL-C > 3.35 mmol/L) was 45% in men and in women, while plasma triglyceride levels > 1.7 mmol/L were observed in 12% of men and 8% of women. CONCLUSION: The results of this study indicate that lipid levels in Type 1 diabetic patients are strongly influenced by smoking habit and central obesity in a way that is characteristic of the insulin resistance syndrome.     

新疆牧区哈萨克族与蒙古族低密度脂蛋白胆固醇水平调查与影响因素分析

目的 调查新疆牧区哈萨克族、蒙古族低密度脂蛋白胆同醇(LDL-C)水平,观察其差异,分析其影响因素.方法 采用整群随机抽样的方法选取新疆和丰县牧区年龄≥30岁的牧民632人为调查对象,其中哈萨克族325人,蒙古族307人;抽取空腹12 h静脉m 3ml,采用日立7600全自动生化分析仪测定血浆总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)的浓度,并根据公式计算出LDL-C的浓度,对资料进行汇总,并采用t检验、方差分析或协方差分析的方法观察两民族间血浆LDL-C水平的差异,并进一步采用多元逐步同归分析的统计方法研究其影响因素.结果 哈萨克族、蒙占族的LDL-C平均水平分别为(3.68±1.16)mmol/L和(3.29±1.23)mmol/L,两民族间LDL-C平均水平存在明显的差异(P<0.001);哈萨克族人群中LDL-C水平主要与平均动脉压相关,而蒙占族主要与体质指数密切相关.结论 血浆LDL-C水平受多种因素的影响,存在明显的民族差异,即便是主要劳动方式和生活习惯十分相似的民族问LDL-C水平的主要影响凶素也各不相同.     

Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia.

AIMS: This randomized, double-blind, placebo-controlled, parallel-group study evaluated the safety and efficacy of ezetimibe 10 mg/day in patients with primary hypercholesterolemia. METHODS AND RESULTS: Following dietary stabilization, a 2-12-week washout period, and a 4-week, single-blind, placebo lead-in period, 827 patients with baseline low-density lipoprotein cholesterol (LDL-C) > or =3.36 mmol/l (130 mg/dl) to < or =6.47 mmol/l (250 mg/dl) and triglycerides < or =3.95 mmol/l (350 mg/dl) were randomized 3:1 to receive ezetimibe 10 mg or placebo orally once daily in the morning for 12 weeks. The primary efficacy endpoint was percentage reduction in direct plasma LDL-C. Ezetimibe reduced direct LDL-C by a mean of 17.7% from baseline to endpoint, compared with an increase of 0.8% with placebo (P<0.01). Response to ezetimibe was generally consistent across all subgroups analyzed. Ezetimibe also significantly improved levels of plasma total cholesterol, apolipoprotein B, high-density lipoprotein(2)-cholesterol and lipoprotein(a), and elicited a trend toward lower triglyceride levels. Ezetimibe did not alter the serum concentrations of lipid-soluble vitamins or significantly affect baseline or stimulated cortisol production. Ezetimibe was well tolerated, with a safety profile similar to that of placebo. CONCLUSIONS: Ezetimibe, which significantly reduces LDL-C and favorably affects other lipid variables, may provide a well tolerated and effective new option for lipid management in the future.