Accuracy of the triglyceride to high-density lipoprotein cholesterol ratio for prediction of the low-density lipoprotein phenotype B

This study examined the accuracy of a triglyceride/high-density lipoprotein (HDL) cholesterol ratio of 3.8 for the prediction of low-density lipoprotein (LDL) phenotype B. The ratio of 3.8 was based on Adult Treatment Panel recommendations for normal fasting triglycerides (<150 mg/dl) and HDL cholesterol (>40 mg/dl). Fasting blood samples were obtained from 658 patients. LDL phenotype analysis was performed by nuclear magnetic resonance spectroscopy. A triglyceride/HDL cholesterol ratio of 3.8 divided the distribution of LDL phenotypes with 79% (95% confidence interval [CI] 74 to 83) of phenotype B greater than and 81% (95% CI 77 to 85) of phenotype A less than the ratio of 3.8. The ratio was reliable for identifying LDL phenotype B in men and women.     

Prevalence of low high-density lipoprotein cholesterol in patients with documented coronary heart disease or risk equivalent and controlled low-density lipoprotein cholesterol

Current guidelines identify low-density lipoprotein (LDL) cholesterol as the primary target for cardiovascular prevention but also recognize low high-density lipoprotein (HDL) cholesterol as an important secondary target. This study was conducted to determine the prevalence of low HDL cholesterol in a contemporary ambulatory high-risk population across various LDL cholesterol levels, including patients taking statins. Screening of 44,052 electronic medical records from a primary care practice identified 1,512 high-risk patients with documented coronary heart disease (CHD) or CHD risk equivalents. Low HDL cholesterol (< or =40 mg/dl in men, < or =50 mg/dl in women) was present in 66% of the 1,512 patients. Low HDL cholesterol was prevalent across all LDL cholesterol levels but most prevalent in patients with LDL cholesterol < or =70 mg/dl (79% vs 66% in those with LDL cholesterol 71 to 100 mg/dl and 64% in patients with LDL cholesterol >100 mg/dl, p <0.01). Low HDL cholesterol was equally and highly prevalent in patients taking statins (67%) and those not taking statins (64%) (p = NS). HDL cholesterol and LDL cholesterol levels correlated poorly (R(2) = 0.01), and this was unaffected by gender or statin treatment. In conclusion, in high-risk patients with CHD or CHD risk equivalents, low HDL cholesterol levels remain prevalent despite statin treatment and the achievement of aggressive LDL cholesterol goals.     

Role of small dense low-density lipoprotein in coronary artery disease patients with normal plasma cholesterol levels

OBJECTIVES: The relationship between plasma low-density lipoprotein (LDL) cholesterol and the risk of coronary artery disease (CAD) is known, but the other characteristics of LDL, particularly particle size and density, are unclear. The relationship between small dense LDL phenotype and non-diabetic, normocholesterolemic CAD was investigated in 70 patients with angiographically documented CAD, and 38 age-matched control subjects. METHODS: Peak LDL particle diameter was determined by using 2-16% polyacrylamide gradient gel electrophoresis. Small dense LDL phenotype was defined as particle diameter equal to or less than 255 A. RESULTS: LDL particle diameters in patients with CAD were significantly smaller than those in controls (252.4 +/- 6.9 vs 259.3 +/- 8.8 A, mean +/- SD, p < 0.0001). Prevalence of small dense LDL was markedly higher in patients with CAD (72%) than in subjects without CAD (24%). CAD patients had significantly lower high-density lipoprotein (HDL)-cholesterol and apolipoprotein A-I levels (39.3 +/- 8.8 vs 49.8 +/- 12.0, 108.1 +/- 20.6 vs 122.9 +/- 20.1 mg/dl), and higher lipoprotein (a) and apolipoprotein B levels (28.8 +/- 30.4 vs 16.8 +/- 18.8, 96.5 +/- 21.8 vs 80.2 +/- 14.9 mg/dl) than non-CAD subjects, whereas total cholesterol, LDL-cholesterol, triglyceride, remnant-like particle cholesterol and insulin levels were not increased in CAD patients compared with non-CAD subjects. Stepwise regression analysis revealed that LDL particle size was the most powerful independent determinant of CAD (F value = 20.04, p < 0.0001). Logistic regression analysis revealed that small dense LDL phenotype [relative risk (RR) of 7.0, 95% confidence interval (95% CI) 2.4-20.1], low HDL-cholesterol (RR of 5.6, 95% CI 2.1-15.2), and increased apolipoprotein B (RR of 5.8, 95% CI 1.8-18.5) were independently associated with incidence of CAD. CONCLUSIONS: High prevalence of small dense LDL is a leading cause of CAD with even normal cholesterol levels.     

Low density lipoprotein particle diameter in young,nonobese, normolipidemic Japanese men

Background: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. Methods and results: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18–20 years (mean±S.D. body mass index: 21.9±3.7 kg/m², total cholesterol: 180±29 mg/dl, triglyceride: 62±34 mg/dl, HDL cholesterol: 58±12 mg/dl). Men with small LDL (PPD <25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD <26.9 nm) had higher serum levels of LDL cholesterol (120±31 vs 104±24 mg/dl), triglyceride (72±39 vs 49±16 mg/dl) and apolipoprotein (apo) B (84±21 vs 68±14 mg/dl), and lower HDL cholesterol (54±10 vs 60±12 mg/dl). They also had greater body mass index (23.2±4.6 vs 20.9 3.1 kg/m²) and percent body fat (21.5±7.7 vs 17.5±4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002) and was negatively correlated with apoB (R=0.34, P<0.001), triglyceride (R=0.32, P<0.001), percent body fat (R=0.26, P<0.001), body mass index (R=0.24, P<0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. Conclusion: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.     

Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.     

Heterogeneity of low-density lipoprotein particle number in patients with type 2 diabetes mellitus and low-density lipoprotein cholesterol <100 mg/dl

Patients with type 2 diabetes mellitus have an increased risk of cardiovascular events even when treated to low-density lipoprotein (LDL) cholesterol goals. The purpose of this study was to determine how many diabetic patients with low LDL cholesterol have correspondingly low numbers of LDL particles (LDL-P) and the extent to which those achieving target levels of LDL cholesterol and non-high-density lipoprotein (HDL) cholesterol might still harbor residual risk associated with increased LDL-P. Split-sample measurements of LDL cholesterol, non-HDL cholesterol, and nuclear magnetic resonance measured LDL-P were performed on plasma samples from 2,355 patients with type 2 diabetes seen in clinical practice and who had LDL cholesterol levels <100 mg/dl. Substantial heterogeneity of LDL-P was noted among patients with low or very low levels of LDL cholesterol. Of 1,484 patients with low LDL cholesterol (70 to 99 mg/dl), only 385 (25.9%) had low levels of LDL-P (<20th percentile of an ethnically diverse contemporary reference population), whereas 468 (31.6%) had LDL-P values >50th percentile (>1,300 nmol/L). Among the 871 patients with very low LDL cholesterol, i.e., <70 mg/dl, 349 (40.1%) had LDL-P levels >1,000 nmol/L (>20th percentile) and 91 (10.4%) had LDL-P levels >50th percentile. For patients with high triglyceride values (200 to 400 mg/dl), there was less discordance between LDL-P and non-HDL cholesterol than between LDL-P and LDL cholesterol. However, for those with triglyceride levels <200 mg/dl, LDL-P distributions were similarly wide for patients having achieved low or very low targets of LDL cholesterol or non-HDL cholesterol. In conclusion, these data demonstrate that patients with type 2 diabetes mellitus and LDL cholesterol levels <100 mg/dl are extremely heterogeneous with regard to LDL-P and, by inference, LDL-based cardiovascular risk.     

Efficacy of cholesterol levels and ratios in predicting future coronary heart disease in a Chinese population

In this study, we assessed the efficacy of various lipid and lipoprotein measurements at baseline for predicting the risk for coronary heart disease (CHD) and determined the associated risk of CHD in subgroups stratified by different lipid and lipoprotein screening strategies to evaluate the adequacy of current total and low-density lipoprotein (LDL) cholesterol-based approaches in lipid management. We analyzed data from the Chin-Shan Community Cardiovascular Cohort study, a Chinese population-based prospective cohort study that began in 1990. During an 8-year follow-up period, 213 of 3,159 participants (6.7%) without CHD (aged > or =35 years) developed CHD. The total cholesterol/high-density lipoprotein (HDL) cholesterol ratio was the most powerful lipoprotein predictor of future CHD (hazard ratio 1.21 for a 1.0 increment in ratio; p <0.001). Subjects with "high-risk" LDL cholesterol levels (>160 mg/dl) and low total cholesterol/HDL cholesterol ratios (< or =5) had an incidence of CHD similar to those with low levels of both LDL cholesterol (< or =130 mg/dl) and total cholesterol/HDL cholesterol ratios (4.9% vs 4.6%). In contrast, subjects with "low-risk" LDL cholesterol levels (< or =130 mg/dl) and high total cholesterol/HDL cholesterol ratios (>5) had a 2.5-fold higher incidence of CHD than those with similar LDL cholesterol levels but low total cholesterol/HDL cholesterol ratios (p <0.001). Compared with using an LDL cholesterol level of 130 mg/dl as the cut-off point, using a total cholesterol/HDL cholesterol ratio of 5 was associated with superior specificity (73% vs 59%, p <0.001) and accuracy (72% vs 58%, p <0.001), and similar sensitivity (50% vs 53%). Our data indicate that current guidelines for lipid management may misclassify subjects with high levels of HDL and LDL cholesterol as well as those with low levels of HDL and LDL cholesterol. Using the ratio of total to HDL cholesterol as the initial screening tool can obviate this discrepancy.     

Garlic powder, effect on plasma lipids, postprandial lipemia, low-density lipoprotein particle size, high-density lipoprotein subclass distribution and lipoprotein(a)

OBJECTIVES: To test the hypothesis that a garlic supplement alters plasma lipoproteins, postprandial lipemia, low-density lipoprotein (LDL) size and high-density lipoprotein (HDL) subclass distribution differently in 50 moderately hypercholesterolemic subjects classified as LDL subclass pattern A or B. BACKGROUND: Garlic has been variably reported to reduce or not affect plasma cholesterol values. Low-density lipoprotein pattern B is a common inherited disorder of lipoprotein metabolism that has been shown to have a significantly greater response to several lipid lowering treatments including low fat diet when compared with LDL pattern A individuals. METHODS: A double blind, randomized, placebo controlled trial in an outpatient lipid research clinic was performed and included fifty moderately hypercholesterolemic subjects (mean LDL cholesterol = 166 +/- 22 mg/dl) classified as LDL subclass pattern A (predominantly large LDL, n = 22) or B (predominantly small LDL, n = 28). Following a two-month stabilization period, subjects were randomly assigned to a placebo or 300 mg three times a day of a standardized garlic tablet for three months. RESULTS: For all subjects, LDL pattern A and B subjects combined, garlic treatment for three months resulted in no significant change in total cholesterol, LDL cholesterol, HDL cholesterol, HDL subclass distribution, postprandial triglycerides, apolipoprotein B, lipoprotein (a) (Lp[a]), LDL peak particle diameter or LDL subclass distribution. There was no significant difference in response for the same parameters among subjects classified as LDL pattern A or B with the exception of significantly greater (p = 0.01) reduction in mean peak particle diameter in pattern A subjects treated with either garlic or placebo. There was no significant change in LDL subclass distribution. CONCLUSIONS: This investigation confirms that garlic therapy has no effect on major plasma lipoproteins and further, that it has no impact on HDL subclasses, Lp(a), apolipoprotein B, postprandial triglycerides or LDL subclass distribution. Garlic may have a greater effect on LDL particle diameter in LDL pattern A compared with pattern B subjects. This difference was not reflected in other plasma lipid measurements.     

Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease

To determine if non-high-density lipoprotein (HDL) cholesterol is a more useful predictor of coronary heart disease (CHD) risk than low-density lipoprotein (LDL) cholesterol and if very-low-density lipoprotein (VLDL) cholesterol is an independent predictor of CHD risk, data from the Framingham Heart Study (2,693 men, 3,101 women) were used for this analysis. All subjects were aged > or =30 years and free of CHD at baseline, and incident CHD was the end point (618 men, 372 women). Cox proportional-hazards models were used to assess the risk for CHD (relative risks and 95% confidence intervals) on the basis of the joint distribution of LDL cholesterol and non-HDL cholesterol (in milligrams per deciliter), as well as LDL cholesterol, non-HDL cholesterol, and VLDL cholesterol as continuous variables. After multivariate adjustment, within non-HDL cholesterol level, no association was found between LDL cholesterol and the risk for CHD, whereas within LDL cholesterol levels, a strong positive and graded association between non-HDL cholesterol and risk for CHD was observed. When the analysis was repeated within triglyceride levels (<200 vs > or =200 mg/dl), the risk pattern did not change significantly. Also, VLDL cholesterol was found to be a significant predictor of CHD risk after adjusting for LDL cholesterol at triglyceride levels of > or =200 or <200 mg/dl. In conclusion, these results suggest that non-HDL cholesterol level is a stronger predictor of CHD risk than LDL cholesterol; that is, VLDL cholesterol may play a critical role in the development of CHD.     

Evaluation of Low-Density Lipoprotein Particle Number Distribution in Patients With Type 2 Diabetes Mellitus With Low-Density Lipoprotein Cholesterol <50 mg/dl and Non-High-Density Lipoprotein Cholesterol <80 mg/dl

Many patients with type 2 diabetes mellitus (T2DM) have relatively normal levels of low-density lipoprotein (LDL) cholesterol yet have increased risk for cardiovascular events. Distribution of lipoprotein subclasses in patients with T2DM who have achieved very low levels of LDL cholesterol (<50 mg/dl) or non-high-density lipoprotein (HDL) cholesterol (<80 mg/dl) have not been extensively examined. The aim of this study was to assess variations in lipoprotein particle concentration in patients with diabetes with "very low" LDL cholesterol and non-HDL cholesterol levels to elucidate the drivers of residual cardiovascular risk. Data were selected from a single large clinical laboratory database. Cases were patients with T2DM diagnosis codes (International Classification of Diseases, Ninth Revision, codes 250 to 250.93). Lipoprotein particle concentrations were analyzed using nuclear magnetic resonance spectroscopy. The Friedewald equation was used to calculate LDL cholesterol. Among the 1,970 patients with T2DM, the mean age was 61 years, and approximately 51% were men. At LDL cholesterol concentrations <50 mg/dl (triglyceride <150 mg/dl and HDL cholesterol >40 mg/dl), 16% had LDL particle concentrations <500 nmol/L, 70% had concentrations of 500 to 1,000 nmol/L, and 14% had concentrations >1,001 nmol/L. At non-HDL cholesterol levels <80 mg/dl, 8% had LDL particle concentrations <500 nmol/L, 67% had concentrations of 500 to 1,000 nmol/L, and 25% had concentrations >1,001 nmol/L. In conclusion, despite attainment of LDL cholesterol <50 mg/dl or non-HDL cholesterol <80 mg/dl, patients with diabetes exhibited significant variation in LDL particle levels, with most having LDL particle concentrations >500 nmol/L, suggesting the persistence of potential residual coronary heart disease risk.     

Comparison of high-density and low-density lipoprotein cholesterol subclasses and sizes in Asian Indian women with Caucasian women from the Framingham Offspring Study

BACKGROUND: Asian Indian women have a higher rate of coronary artery disease (CAD) than do other ethnic groups, despite similar conventional risk factors and lipid profiles. Smaller high-density lipoprotein cholesterol (HDL-C) particle size is associated with reduced cardiac protection or even an increased risk of CAD. Exceptional longevity correlates better with larger HDL-C particle sizes. HYPOTHESIS: Higher rates of CAD among Asian Indian women may partly be explained by the differenes in the prevalence of atherogenic HDL-C and low-density lipoprotein cholesterol (LDL-C) sizes and their subclass concentrations among Asian Indian women compared with Caucasian women. METHODS: We measured HDL-C concentrations and sizes by nuclear magnetic resonance spectroscopy in 119 relatively healthy Asian Indian women and compared them with those of 1752 Caucasian women from the Framingham Offspring Study (FOS). RESULTS: Asian Indian women were significantly younger (47.9 +/- 11.2 vs. 51.0 +/- 10.1 years, p = 0.0001), leaner (body mass index 24.0 +/- 4.7 vs. 26.0 +/- 5.6, p = < 0.0002), less likely to be postmenopausal (32 vs. 54%, p = < 0.0001), or smoke (< 1 vs. 20%, p = < 0.0001); nevertheless, prevalence of CAD was higher in Asian Indian women (4.2 vs. 1%, p = 0.0006). Asian Indian women had similar HDL-C (53 +/- 13 vs. 53 +/- 13 mg/dl, p = 0.99), smaller HDL-C particle size (8.9 +/- 0.35 vs. 9.4 +/- 0.44 nm, p = < 0.0001), higher total cholesterol (209 +/- 40 vs. 199 +/- 42 mg/dl, p = 0.01), and similar triglyceride (120 +/- 77 vs. 108 +/- 110 mg/d, p = 0.24) levels. Low-density lipoprotein cholesterol, particle concentrations and sizes, as well as prevalence of pattern B were similar. CONCLUSIONS: Compared with the FOS, Asian Indian women have significantly smaller overall HDL particle size and similar levels of HDL-C, which may reflect impaired, reverse cholesterol transport. Total cholesterol was higher, whereas triglyceride and LDL-C levels were similar. This may partly explain the higher CAD rates in Asian Indian women. Further large scale, prospective, long-term studies are warranted.     

The triglyceride/high-density lipoprotein cholesterol ratio, the small dense low-density lipoprotein phenotype, and ischemic heart disease risk

This study investigated the relevance of using the plasma triglyceride to high-density lipoprotein cholesterol ratio (Log TG/HDL-C) for the prediction of the small dense lowdensity lipoprotein (LDL) phenotype and the risk of ischemic heart disease (IHD). Analyses were based on data from the Quebec Cardiovascular Study in a cohort of 2072 men free of IHD at baseline, among whom 262 had a first IHD event (coronary death, non fatal myocardial infarction and unstable angina) during a 13-year follow-up period. LDL particle size phenotype was characterized using 2-16% polyacrylamide gradient gel electrophoresis (PAGGE) of whole plasma. There were significant associations between the Log TG/HDL-C ratio and features of LDL size phenotype such as the proportion of LDL with a diameter <255A (r = 0.43, p < 0.001) and LDL peak particle size (r = -20.55, p < 0.001). However, the Log TG/HDL-C ratio brought no additional value (p a yen 0.1) in predicting the small dense LDL phenotype (area under the receiver operating curve (AUROC = 71.9%) compared to TG alone (AUROC = 71.2%) or to a combination of Log TG and HDL-C (AUROC = 72.4%) after multivariate adjustment for non lipid risk factors. Finally, elevations in the Log TG/HDL-C ratio did not improve the discrimination of incident IHD cases from non IHD cases compared to the use of plasma TG levels alone (p = 0.5) or a combination of the individual TG and HDL-C values (p = 0.5). The Log TG/HDL-C ratio does not improve our ability to identify individuals with the small dense LDL phenotype compared to plasma TG levels alone. The Log TG/HDLC is also not superior to plasma TG levels alone in predicting IHD risk in men of the QuA(c)bec Cardiovascular Study.     

High-density lipoprotein cholesterol is reduced in patients with sarcoidosis

PURPOSE: Sarcoidosis is a disease in which the proliferation of monocyte-macrophage-derived cells is observed. In other diseases characterized by expansion of the monocyte-macrophage system, such as Gaucher's disease and myeloid metaplasia, abnormalities of lipoprotein metabolism have been demonstrated. To determine whether similar abnormalities in lipoprotein cholesterol concentrations could be identified in patients with sarcoidosis, we studied total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol as well as triglyceride levels in 52 patients with biopsy-proven sarcoidosis. PATIENTS AND METHODS: Patients had no other medical disorders and were not being treated with corticosteroids or antimalarial agents. Blood samples were collected by venipuncture after an overnight fast. Plasma total cholesterol and triglyceride levels were measured using enzymatic techniques. Lipoprotein cholesterol was quantified by lipoprotein fractionation. HDL cholesterol was measured as cholesterol remaining in the supernatant after precipitation of LDL and very-low-density lipoprotein from whole plasma by the heparin-maganese chloride method. Computation was used to determine the level of LDL cholesterol. RESULTS: We found significantly reduced levels of total cholesterol (183.9 +/- 27.6 versus 194.3 +/- 16.5 mg/dl, mean +/- SD, p = 0.021) and HDL cholesterol (41.2 +/- 13.0 versus 51.9 +/- 6.1 mg/dl, p = 0.0001) in sarcoid patients versus an age-, sex-, and race-matched reference group. Differences were not observed in triglyceride or LDL cholesterol levels (p greater than 0.05). CONCLUSION: These findings are similar to those observed in the myeloproliferative diseases, Gaucher's disease, and rheumatoid arthritis and suggest a functional role for monocytes-macrophages in the regulation of serum lipoprotein cholesterol levels.     

Predictors of low-density lipoprotein particle size in a high-risk African-American population

A predominance of small, dense, low-density lipoprotein particles (pattern B) has been associated with increased cardiovascular risk independent of absolute cholesterol levels in primarily white populations. Because of the putative association of pattern B with increased risk, some investigators have proposed that routine measurement of low-density lipoprotein particle size may be beneficial for cardiovascular risk assessment. Because no studies have specifically examined this possibility in African-Americans, it remains unclear whether measurement of low-density lipoprotein particle size adds information beyond that of traditional lipid risk factors. We compared standard lipid profile measurements with extended measurements concurrently in an apparently healthy, high-risk population of African-American siblings of patients who had premature cardiovascular disease. We determined the extent to which patients who had pattern B would be identifiable from the usual lipid profile. A high triglyceride level alone was a strong independent correlate of pattern B. In subjects whose triglyceride level was >/=150 mg/dl, 67% had pattern B, whereas only 17% of subjects whose triglyceride level was <150 mg/dl had pattern B. The area under the receiver-operating characteristic curve was 0.77. Our data suggest that the standard lipid profile, primarily fasting triglyceride measurement, appears to be a useful surrogate for direct measurement of particle size in a high-risk African-American population.     

LDL-cholesterol/apolipoprotein B ratio is a good predictor of LDL phenotype B in type 2 diabetes

LDL phenotype B is a component of diabetic dyslipidaemia, but its diagnosis is cumbersome. Our aim was to find easily available markers of phenotype B in a group of type 2 diabetic subjects. We studied 123 type 2 diabetic patients (67.5% male, aged 59.3±10.1 years, mean HbA1c 7.4%). Clinical features and fasting total cholesterol, triglyceride, HDL cholesterol, LDL cholesterol (LDLc, using Friedewald's equation and an alternative formula), apolipoprotein B (apoB), lipoprotein (a) and LDL particle size (on gradient polyacrylamide gel electrophoresis) were assessed. Patients with phenotypes A (predominant LDL size ≥25.5 nm) and B (<25.5 nm) were compared, and regression analysis was performed to find the best markers of LDL particle. Cut-off points were obtained and evaluated as predictors of phenotype B (kappa index). Patients with phenotype B (36%) showed higher total cholesterol, triglyceride and apolipoprotein B, and lower HDL cholesterol and LDLc/apoB ratio. Triglyceride was the best predictor of LDL particle size (r=−0.632, p<0.01), but an LDLc/apoB ratio below 1.297 mmol/g detected phenotype B best (sensitivity 65.9%, specificity 92.4%, kappa=0.611). Although triglyceride concentration is the best predictor of LDL size in type 2 diabetes, LDLcholesterol/apolipoproteinB ratio is the best tool to detect phenotype B. Received: 23 August 2001 / Accepted in revised form: 12 July 2002 Correspondence to A. Pérez     

Serum HDL cholesterol values are associated with apoB-containing lipoprotein metabolism and triglyceride-body fat interrelation in young Japanese men

Serum levels of total cholesterol, high density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein (apo) AI, ApoB, ApoE and body fat were measured in 226 fasting male Japanese college students aged 18 to 20 years. They were normolipidemic (total cholesterol: 169±31 mg/dl, triglyceride: 56±25 mg/dl) and their HDL cholesterol concentrations were high (61±13 mg/dl). An HDL cholesterol value <35 mg/dl was observed in only one student (0.4%). In contrast, 112 men (49.6%) had an HDL cholesterol level ≥60 mg/dl. Even in this normolipidemic group, as compared with students in a top HDL cholesterol tertile (HDL cholesterol; 75±9 mg/dl), students in a lower HDL cholesterol tertile (HDL cholesterol; 48±5 mg/dl) had significantly increased serum levels of LDL cholesterol (103±30 vs. 91±26 mg/dl), triglyceride (68±30 vs. 45±16 mg/dl) and apoB (83±20 vs 73±17 mg/dl). In addition, they had greater body mass index (23.2±3.6 vs. 20.6±2.5 kg/m²) and greater percent body fat (20.2±6.2 vs. 16.2±4.2%) determined using a bioelectrical impedance analyzer. HDL cholesterol levels were much more strongly related to triglyceride (r=−0.37) than was apoAI (r=−0.13). In stepwise multiple regression analysis in 184 nonsmokers, apoE, apoB and fat mass explained 21% of apoAI variability. Triglyceride in addition to these three parameters explained 41% of HDL cholesterol variability. These results suggest that serum levels of HDL cholesterol are associated with metabolism of apoB-containing lipoproteins as well as triglyceride-body fat interrelationship.     

Comparisons of apolipoprotein B levels estimated by immunoassay, nuclear magnetic resonance, vertical auto profile, and non-high-density lipoprotein cholesterol in subjects with hypertriglyceridemia (SAFARI Trial)

Low-density lipoprotein (LDL) cholesterol and triglyceride-rich lipoproteins constitute non-high-density lipoprotein (non-HDL) cholesterol. These are atherogenic lipoproteins and non-HDL cholesterol is a secondary target of treatment beyond LDL cholesterol in patients with hypertriglyceridemia. Some investigators favor total apolipoprotein B over non-HDL cholesterol as the secondary target of treatment. This is based on publications suggesting that total apolipoprotein B is more predictive of cardiovascular events than non-HDL cholesterol. Several methods are available for estimating total apolipoprotein B. This study compared total apolipoprotein estimated by immunonephelometric assay (INA), vertical auto profile (VAP), nuclear magnetic resonance (NMR), and non-HDL cholesterol levels in patients with hypertriglyceridemia from the previously reported Simvastatin plus Fenofibrate for Combined Hyperlipidemia (SAFARI) trial. Total apolipoprotein B levels were found to be highest by INA, intermediate by NMR and non-HDL cholesterol, and lowest by VAP. Concordance for non-HDL cholesterol levels among the INA, VAP, and NMR methods was better than that for total apolipoprotein B levels; the correlation between non-HDL cholesterol and apolipoprotein B by INA was strongest (0.929). In patients with a low triglyceride/HDL cholesterol ratio (<3.5), total apolipoprotein B determined by INA was higher than that estimated from non-HDL cholesterol levels, whereas in patients with a high triglyceride/HDL C ratio (≥3.5), apolipoprotein B predicted using non-HDL cholesterol was in better agreement with INA-determined apolipoprotein B levels. Similar trends were observed with VAP using equations specific for LDL particle size. In conclusion, more work is needed to improve agreement of apolipoprotein B measurements among methods employed clinically. Non-HDL cholesterol is also useful to predict total apolipoprotein B and some improvement may be attained by taking into account the ratio of triglyceride/HDL cholesterol as a measurement of LDL particle size.     

Comparison of levels of large and small high-density lipoprotein cholesterol in Asian Indian men compared with Caucasian men in the Framingham Offspring Study

Asian Indians have a higher incidence of coronary artery disease (CAD) than do other ethnic groups, despite similar standard risk factors and lipid profiles. The large subclass of high-density lipoprotein (HDL) cholesterol is predominantly associated with protection against coronary artery disease. We compared various lipoprotein concentrations and sizes in 211 healthy Asian Indian men with those in 1,684 Caucasian men from the Framingham Offspring Study as measured by nuclear magnetic resonance spectroscopy. Concentrations of HDL cholesterol were similar in the 2 groups, but concentrations of large HDL cholesterol were lower and concentrations of small HDL cholesterol were significantly higher in Asian Indian than in Caucasian men. HDL particle size was smaller in Asian Indians. Levels of low-density lipoprotein cholesterol, low-density lipoprotein particle size, and prevalence of pattern B were similar in the 2 groups.     

Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dyslipidemic women.

The effects of oral estrogen replacement (ethinyl estradiol 0.02 mg/d) on plasma triglyceride, total cholesterol, very-low-density lipoprotein (VLDL) cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) A-I and B levels and LDL particle size were assessed in 20 postmenopausal women with a previous hysterectomy and various forms of dyslipidemia (LDL cholesterol > or = 4.14 mmol/L [160 mg/dL] and/or HDL cholesterol < or = 1.03 mmol/L [40 mg/dL]). All subjects were studied while on a standard cholesterol-lowering diet, and were sampled in the fasting state before beginning estrogen therapy and after a mean of 13 weeks of estrogen therapy. Lipids were measured by standardized enzymatic techniques, apos were measured by enzyme-linked immunoassays, and LDL particle size was measured by gradient gel electrophoresis. Mean values for plasma lipid parameters (mmol/L) at baseline and during estrogen replacement were as follows: triglyceride, 2.11 and 2.75 (30% increase); total cholesterol, 7.45 and 6.52 (13% decrease); VLDL cholesterol, 1.09 and 1.22 (12% increase); LDL cholesterol, 5.09 and 3.70 (27% decrease); and HDL cholesterol, 1.27 and 1.58 (24% increase). Mean values for apo A-I were 163 and 254 mg/dL (56% increase), and for apo B they were 170 and 148 mg/dL (13% decrease). The LDL particle score was 4.09 and 4.52 (11% smaller). Changes in all parameters were statistically significant (P = .05) except for VLDL cholesterol. These data indicate that estrogen replacement is effective in decreasing LDL cholesterol and apo B concentrations and increasing HDL cholesterol and apo A-I concentrations in dyslipidemic postmenopausal women, but it should not be used in patients with baseline fasting triglyceride levels higher than 2.82 mmol/L (250 mg/dL) unless it is accompanied by a progestin. Our data indicate that this form of estrogen replacement could lower the risk of coronary artery disease (CAD) by more than 50% in these women, based on favorable alterations in plasma lipoproteins.