Remnant-like Particle Cholesterol Levels Research Articles

Effects of Bezafibrate on HDL2/HDL3 Ratio in Postmenopausal Hypertriglyceridemic Women

The short-term effects of bezafibrate on high-density lipoprotein cholesterol quality and triglyceride-rich lipoprotein metabolism in 186 postmenopausal hypertriglyceridemic women were investigated. Patients were randomized to an untreated group and to bezafibrate (400 mg/d) for 6 months. Fasting lipid concentrations, high-density lipoprotein 2, and high-density lipoprotein 3 levels were measured at baseline and after 3 and 6 months. At 3 months, bezafibrate had significantly decreased mean serum triglycerides and remnant-like particle cholesterol levels (105.7 +/- 43.4 mg/dL and 5.33 +/- 2.1 mg/dL, P < .001, respectively) from baseline values (232.5 +/- 63.9 mg/dL and 9.69 +/- 3.8 mg/dL, respectively). It also maintained lower total cholesterol, low-density lipoprotein cholesterol, triglycerides, and remnant-like particle cholesterol concentrations to 6 months. After 3 months, it significantly increased mean serum high-density lipoprotein cholesterol (55.1 +/- 14.7 vs 64.8 +/- 12.1 mg/dL; P < .0001) and maintained higher high-density lipoprotein cholesterol at 6 months. The high-density lipoprotein 2-high-density lipoprotein 3 ratio was decreased after 3 months of therapy with bezafibrate (2.13 +/- 0.68) from the baseline (2.42 +/- 0.71) (P < .01).

Relation between charge-based apolipoprotein B-containing lipoprotein subfractions and remnant-like particle cholesterol levels

Objective Both mildly modified LDL subfraction that carries a more-negative electric charge and remnant-like particles (RLP) are closely related to triglyceride (TG) levels. We examined the relation between the RLP-cholesterol (C) level and charge-based apolipoprotein (apo) B-containing lipoprotein subfractions as determined by capillary isotachophoresis (cITP) in patients with hypercholesterolemia. Methods and results cITP apo B lipoprotein subfractions were identified by analyzing plasma depleted of the related lipoproteins. While fast-migrating triglyceride-rich lipoprotein (fTRL) subfraction contained both chylomicrons and VLDL fraction, slow TRL (sTRL) only contained VLDL. cITP fLDL also contained VLDL fraction, i.e., β-VLDL. Levels of cITP fTRL and sTRL were significantly correlated with serum levels of TG, RLP-C, apo C-II, and C-III. Levels of cITP sTRL were also correlated with apo E. Levels of cITP fLDL were positively correlated with not only LDL-C levels but also levels of TG, RLP-C, apo C-II, C-III, and E. Conclusion cITP fast LDL correlated with RLP-C levels and modified the relation between RLP-C and TG levels.

Triglycerides and remnant particles as risk factors for coronary artery disease

Coronary artery disease (CAD) is the largest cause of morbidity and mortality in the world. A relationship between CAD and elevated levels of low-density lipoprotein cholesterol has been established. However, risk assessment limited to low-density lipoprotein fails to identify a significant portion of patients at risk for CAD. Remnant lipoproteins, derived from very low-density lipoprotein and chylomicrons, have been considered atherogenic. Recently, a simple and reliable immunoaffinity separation method for the isolation of remnant-like particles (RLP) has been developed. It has been shown that RLP cholesterol levels are significantly correlated with CAD, and thus cellular mechanisms have been determined by which RLP cholesterol causes progression of atherosclerosis. Measurement of RLP cholesterol is useful for the assessment of risk and the evaluation of therapy in patients at risk for CAD.

Association between fast-migrating low-density lipoprotein subfraction as characterized by capillary isotachophoresis and intima-media thickness of carotid artery

Background A mildly modified LDL subfraction that is characterized by an increased negative charge exists in plasma. This electronegative LDL separated by ion-exchange chromatography has been shown to be inflammatory and its proportion is increased in patients with hyperlipidemia and diabetes mellitus. The present study examined the association between the level of fast (f)-migrating LDL subfraction characterized by capillary isotachophoresis (cITP) and carotid-artery intima-media thickness (CA-IMT). Methods and results This study included 469 subjects who underwent a physical examination. CA-IMT was determined by high-resolution B-model ultrasonoraphy. Levels of charge-based LDL subfractions were measured by cITP on a Beckman P/ACE MDQ system. An increased serum LDL-C level and cITP fLDL level were associated with increased CA-IMT after adjusting for age. The extent of the associations between cITP fLDL and CA-IMT and between LDL-C and CA-IMT were similar as assessed by a receiver-operating characteristic curve analysis. LDL-C, triglyceride, and remnant-like particle cholesterol levels were independently correlated with cITP fLDL, and the LDL-C level had the strongest correlation with cITP fLDL. The association between the cITP fLDL level and CA-IMT was significant in the high LDL-C stratum but not in the low stratum, indicating that it is modified by the LDL-C level. The high-LDL-C-high-fLDL group had the highest relative risk for a high CA-IMT among the groups with each combination of LDL-C and cITP fLDL level. Conclusion The cITP fLDL level was associated with CA-IMT and its combination with the LDL-C level is a stronger indicator for a high CA-IMT.

High Plasma Level of Remnant-Like Particle Cholesterol in the Metabolic Syndrome

The metabolic syndrome is associated with a high incidence of cardiovascular disease even when the abnormalities present in the syndrome are mild. The underlying mechanism of the metabolic syndrome has not been elucidated. We investigated whether a strong atherogenic lipoprotein, remnant-like particle (RLP) lipoprotein cholesterol, is elevated in the metabolic syndrome. We performed a health examination among the residents of a rural community in Japan. Complete datasets, including fasting RLP cholesterol levels, were obtained in 1,261 subjects (509 men and 752 women) without diabetes and who were not taking lipid-lowering drugs. The subjects' medical history, use of alcohol, and smoking habits were ascertained by a questionnaire. All of the components of the metabolic syndrome were significantly related to RLP cholesterol by univariate analysis. Total cholesterol and smoking habits were also positively associated with RLP cholesterol. The subjects with the metabolic syndrome showed only mild abnormalities of each component. When RLP cholesterol levels were stratified by the number of the components of the metabolic syndrome, there was a strong association between RLP cholesterol levels and the number of components (P < 0.001 and F = 72.7). RLP cholesterol levels are elevated in the metabolic syndrome, and this elevation may underlie the high incidence of cardiovascular disease in the metabolic syndrome.

Are Remnant-Like Particles Independent Predictors of Coronary Heart Disease Incidence?

Remnant-like particles have been proposed as a new risk factor for coronary heart disease (CHD). This is the first long-term prospective investigation of the relationship between remnant-like particles and a cardiovascular disease outcome in healthy men. A cohort of 1156 Japanese-American men aged 60 to 82 from the Honolulu Heart Program was followed for 17 years. During that period 164 incident cases of CHD were identified. In multivariate Cox regression analyses, baseline remnant-like particle cholesterol (RLP-C) and triglyceride (RLP-TG) levels were significantly related to CHD incidence independently of nonlipid cardiovascular risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. Total triglyceride levels were an independent predictor of CHD incidence. However, in models including RLP and triglyceride level simultaneously, neither variable was significant when adjusted for the other. This finding can be attributed to the strong correlation between RLP-C and RLP-TG levels and total triglycerides. When individuals with normal triglyceride levels (n=894) were separated from those with elevated triglycerides (n=260), the association between RLPs and CHD relative risk was only significant for the group with elevated triglyceride levels. RLP levels predicted CHD incidence independently of nonlipid risk factors and of total cholesterol or high-density and low-density lipoprotein cholesterol levels. However, RLP levels did not provide additional information about CHD incidence over and above total triglyceride levels. Therefore, this study does not support the need for testing of remnants in men if measures of fasting triglycerides are available.

Changes in remnant-like particle cholesterol level during treatment of hypertension with amlodipine and cilnidipine

This study was designed to determine the effect of antihypertensive agents (calcium channel blockers) on the levels of remnant-like particle (RLP) cholesterol; a major risk factor for coronary heart disease, during treatment of hypertension. Thirty six hypertensive patients of both sexes were selected into this study. Twenty-five of them were treated with amlodipine while eleven patients were treated with cilnidipine all for 3 months. At the beginning and after 3 months of treatment, serum RLP-cholesterol levels were measured in the two treatment groups. RLP-cholesterol level was significantly reduced after clinidipine treatment while the reduction in RLP-cholesterol level after amlodipine treatment was not statistically significant. Our findings show that calcium channel blockers may lower the risk of myocardial infarction, coronary atherosclerosis and/or coronary thrombus formation through reduction in RLP-cholesterol levels during antihypertensive pharmacotherapy. Key Words: RLP-cholesterol, amlodipine, cilnidipine, hypertension treatment. Journal of Biomedical Investigation Vol.2(2) 2004: 72-75

Serum sphingomyelin levels are related to the clearance of postprandial remnant-like particles

It is known that sphingomyelin (SM) content is higher in apolipoprotein B-containing particles (BLps) than in high density lipoproteins and that BLp levels, including chylomicrons and their remnant particles, are positively related to atherosclerosis. To evaluate the relationship between serum SM and postprandial remnant particle levels, we determined SM, triglyceride (TG), and cholesterol levels in serum and in remnant-like particles (RLPs) before and 3, 5, 7, and 10 h after a high-fat meal in 31 healthy subjects. We found that serum SM, like serum TG, was increased to its maximum 3 h after fat loading and then gradually decreased to basal levels after 10 h. More important, we determined that SM and TG levels in RLPs were parallel. Serum SM was positively correlated with serum TG (P <0.001), RLP SM (P <0.001), RLP TG (P <0.001), and RLP cholesterol (P <0.001) levels. It is our conclusion that serum SM is a marker for the clearance of RLPs.

Remnant-like lipoproteins, hormone therapy, and angiographic and clinical outcomes: The Women's Angiographic Vitamin & Estrogen trial

Background Little is known about the impact of post-menopausal hormone therapy on remnant-like particle (RLP) concentrations and about the relationship between RLP concentration and angiographic progression of coronary artery disease and clinical events in women. Methods RLP cholesterol and triglyceride levels were measured at baseline and 3 months after randomization in 397 post-menopausal women enrolled in The Women's Angiographic Vitamin & Estrogen (WAVE) trial. Correlates of baseline RLP levels and changes in levels with post-menopausal hormone therapy were determined with multiple linear regression. Coronary angiography was performed at baseline and after a mean of 2.9 years. Changes in minimal and average luminal diameter were modeled with multivariate linear regression, clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death) with multiple logistic regression. Results The mean subject age was 65 years, 66% of subjects were white, 18% of subjects smoked, most subjects were overweight or obese, and 35% of subjects had diabetes mellitus. RLP cholesterol (0.277 ± 0.254 mmol/L) and triglyceride (0.386 ± 0.552 mmol/L) levels corresponded approximately to the 90th percentile in women in the Framingham study. RLP levels did not change significantly with hormone therapy. RLP levels at baseline, changes in RLP levels, and on treatment RLP levels did not relate to angiographic changes or clinical outcomes (non-fatal myocardial infarction, stroke, or cardiovascular death). Conclusions RLP levels were high among post-menopausal women enrolled in the WAVE study, were not affected by hormone therapy, and did not relate to angiographic progression of coronary artery disease or clinical outcomes.

Postprandial Increase in Plasma Concentrations of Remnant-Like Particles: An Independent Risk Factor for Restenosis after Percutaneous Coronary Intervention

Postprandial increase in remnant lipoprotein concentrations has been suggested as an important atherogenic factor. However, the influence of these remnants on the development of restenosis after percutaneous coronary intervention (PCI) remains to be examined. The present study was designed to address this point. In 60 consecutive patients with successful PCI, the influences of possible risk factors on the development of restenosis, including remnant-like particles (RLP) cholesterol (RLP-C) and triglyceride (RLP-TG), were examined. While mean concentrations of RLP-C and RLP-TG were normal in fasting state, postprandial change in RLP-C concentrations was a significant and independent risk factor for restenosis after PCI. The calculated cut-off index (COI) for the change was +64%. When the patients were divided into 2 groups according to this COI, minimal lumen diameter (MLD) and reference coronary diameter were comparable before and immediately after PCI between the high- (COI < 64%) and the low- (COI < 64%) responders. However, follow-up coronary angiography 3 to 6 months after PCI demonstrated that MLD, late loss, and loss index were all worse in the high responders compared with the low responders. These results indicate that post-prandial increase in RLP-C concentrations is an independent risk factor for restenosis after successful PCI, even in patients with normal fasting RLP-C levels.

Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type ii diabetes mellitus

ObjectivesThis study prospectively examined whether the levels of high remnant-like lipoprotein particles (RLP) cholesterol have a significant risk and influence prognosis in patients with coronary artery disease (CAD) and type II diabetes mellitus (DM). BackgroundSeveral studies have shown that triglyceride-rich lipoproteins contribute to atherosclerotic complications in type II DM. However, it remains to be established which triglyceride-rich lipoproteins contribute to this risk. MethodsLevels of RLP cholesterol in fasting serum were measured by an immunoseparation method in 240 type II DM patients with (n = 120) or without (n = 120) CAD. The patients with CAD were followed up for a period of ≤24 months until the occurrence of one of the following clinical coronary events: re-admission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, or cardiac death. ResultsPatients with CAD had higher RLP levels than patients without CAD. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>4.7 mg cholesterol/dl, representing the 75th percentile of the distribution of RLP cholesterol levels in control subjects) were a significant risk factor for the presence of CAD, independent of traditional risk factors. Kaplan-Meier analysis demonstrated that higher RLP cholesterol levels in patients with CAD resulted in a significantly higher probability for the development of coronary events. Multivariate Cox hazards analysis showed that high RLP cholesterol levels in patients with CAD were a significant predictor of future coronary events, independent of other risk factors. ConclusionsIncreased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in patients with CAD and type II DM.

Elevated Remnant-Like Particle Cholesterol Concentration

Patients at increased risk of coronary artery disease (CAD) frequently exhibit an atherogenic lipoprotein phenotype characterized by elevated plasma levels of both triglyceride-rich lipoproteins (TRL) and small, dense LDL and low concentrations of HDL cholesterol. Recently, in a large observational study, the calculated non-HDL plasma cholesterol concentration (the sum of the cholesterol contents of LDL, intermediate-density lipoprotein [IDL], and very-low-density lipoprotein [VLDL]) was a stronger predictor of cardiovascular events than plasma cholesterol alone.1–3 Improvement in the predictability of CAD on inclusion of VLDL and IDL cholesterol emphasizes the proatherogenic nature of TRL and their remnant particles. The atherogenic lipoprotein phenotype has been defined by Austin et al4 as the presence of a predominance of small, dense LDL particles, elevated plasma triglyceride (TG) levels, and low plasma HDL cholesterol levels in the lipoprotein profile, which is associated with an approximately 3-fold increased risk of atherosclerotic disease.5–8 It is now commonly accepted that small, dense LDL particles are the products of the intravascular remodeling of TG-rich VLDL particles after interaction primarily with lipoprotein lipase, hepatic lipase, and cholesterol ester transfer protein9,10 (Figure). The atherogenic lipoprotein phenotype is strongly linked to obesity, insulin resistance, familial combined hyperlipidemia (FCHL), hypertension, and abnormalities in postprandial lipid metabolism.7,11,12 Epidemiological data from the Framingham study have already revealed that plasma TG concentration is an important independent risk indicator of CAD in women13; additional evidence supporting this observation was obtained by Yarnell et al14 in a 10-year follow-up study and confirmed by others.15,16 In the PROCAM (Prospective Cardiovascular Munster) study,17 this relationship was dependent on plasma HDL cholesterol concentration. Criqui et al,18 however, could not demonstrate an independent relationship between plasma TG and cardiovascular mortality in a North American population participating in the Lipid Research Clinics Follow-up. …

Gender differences in the effect of type 2 diabetes on serum lipids, pre-heparin plasma lipoprotein lipase mass and other metabolic parameters in Japanese population

Design: Cross-sectional study of fasting serum lipid and lipoprotein levels, pre-heparin lipoprotein lipase (LPL) mass, several other metabolic parameters, and intra-abdominal fat areas in 26 Japanese poorly controlled type 2 diabetic men and 23 women when matched for age, body mass index (BMI), and HbA 1c between genders. Subjects: Study subjects were Japanese type 2 diabetic patients who were admitted to our hospital between Jun 2001 and Aug 2002 because of their poorly controlled diabetes. A total of 49 subjects [40–79 years of age, average age 61.5±8.7; mean BMI 23.2±3.7 kg/m 2] with fasting plasma glucose (PG) and HbA 1c levels being 251±76.5 mg/dl and 10.8±2.2%, respectively, were involved in this study. Methods: Pre-heparin LPL mass was determined by enzyme linked immunosorbent assay. Remnant like particle cholesterol (RLP-C) level was measured using an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-I and anti-apo B monoclonal antibodies. Serum leptin level was determined by radioimmunoassay. Intra-abdominal fat area was determined by computerized tomography analysis at the umbilical level. Results: The men group showed a higher serum triglycerides (TG) and RLP-C levels, and lower high density lipoprotein–cholesterol levels and pre-heparin plasma LPL mass than did women. Serum leptin level was higher in women than in men counterparts. The intra-abdominal subcutaneous fat areas were significantly larger in women than in men counterparts, whereas the visceral fat areas did not differ. Conclusion: In Japanese population, poorly controlled type 2 diabetic men had more unfavorable lipid profile than did women counterparts, which may be associated with decreased lipolysis of plasma TG-rich lipoproteins by LPL.

4P-0995 Glutathione S-transferase P1 polymorphism affected plasma malondialdehyde-modified LDL levels in patients with coronary artery disease

Oxidized low-density lipoprotein (OxLDL) and remnant lipoprotein play a crucial role in the development of atherosclerosis. Recently, a novel method for measuring remnant cholesterol levels (remnant lipoproteins cholesterol homogenous assay: RemL-C) has been established. However, the correlation between OxLDL and remnant lipoprotein, including RemL-C, has not been fully investigated.We enrolled 25 consecutive patients with documented coronary artery disease (CAD) and 20 controls. Remnant-like particle cholesterol (RLP-C) and RemL-C were used to determine the levels of remnant lipoprotein cholesterol. Serum levels of malondialdehyde-modified LDL (MDA-LDL) and OxLDL using a monoclonal antibody DLH3 (OxPC) were used to measure the concentration of circulating OxLDL.The CAD group had high levels of fasting glucose and glycosylated hemoglobin (HbA1c), and low levels of high-density lipoprotein cholesterol compared with the control group. Serum levels of total cholesterol or LDL cholesterol were not significantly different between the two groups. The levels of RemL-C (p = 0.035), MDA-LDL (p = 0.018), and MDA-LDL/LDL-C (p = 0.036) in the CAD group were significantly higher than those in the control group. The levels of RLP-C tended to be higher in the CAD group than those in the control group (p = 0.096). Positive correlations were demonstrated between remnant lipoprotein cholesterol and OxLDL (RLP-C and MDA-LDL/LDL-C, r = 0.45, p = 0.0024, RLP-C and OxPC, r = 0.51, p = 0.0005, RemL-C and MDA-LDL/LDL-C, r = 0.42, p = 0.0044, RemL-C and OxPC, r = 0.43, p = 0.0043). Similar trends were observed in non-diabetic subjects and in subjects without metabolic syndrome. Positive correlations were also observed between RLP-C and RemL-C (r = 0.94, p < 0.0001) and between MDA-LDL/LDL-C and OxPC (r = 0.40, p = 0.0074).These results suggest that the association between high levels of remnant lipoprotein cholesterol and high OxLDL levels might be linked to atherogenesis in patients with CAD.

Effects of hormone replacement therapy and hepatic lipase polymorphism on serum lipid profiles in postmenopausal Japanese women.

The purpose of this study was to evaluate the relationships among hepatic lipase (HL) polymorphism, serum lipids, lipoproteins, and remnant-like particle cholesterol (RLP-C) and to determine the effects of hormone replacement therapy (HRT). We assessed the HL polymorphism in 209 postmenopausal Japanese women. Levels of serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein (Apo) AI, Apo B, Apo E, Apo CII, Apo CIII, and RLP-C were measured before and after 3 months of HRT. The frequency of each genotype was 32% for -514 C/C, 41% for C/T, and 27% for T/T. Subjects with the C/T and T/T genotypes had higher levels of HDL cholesterol and Apo AI than those with the C/C genotype. Those with the T/T genotype had higher levels of RLP-C than those with the C/C or C/T genotype. Serum total cholesterol, LDL cholesterol, Apo B, Apo E, and Apo CII were decreased, and HDL cholesterol and Apo AI were increased significantly in all genotypes after 3 months of HRT. There were no differences in these changes with genotype. The HL polymorphism was associated with higher levels of HDL cholesterol, Apo AI, and RLP-C, and the HL gene variation may contribute to HL activity and affect serum lipoprotein metabolism. Effects of HRT on serum lipids, lipoproteins, and remnant lipoprotein metabolism were unaffected by the HL polymorphism.

HMG-CoA reductase inhibitor decreases small dense low-density lipoprotein and remnant-like particle cholesterol in patients with type-2 diabetes

Patients with type 2 diabetes are known to have abnormalities in their remnant metabolism and low density lipoprotein (LDL) subfraction pattern, with a preponderance of small dense LDL. The effects of pitavastatin, a newly synthesized 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, on lipoprotein profiles in patients with type 2 diabetes were determined. Thirty-three patients were treated with pitavastatin with a daily dose of 2 mg for 8 weeks. After treatment, triglyceride, total and LDL cholesterol were significantly reduced by 28.7 ± 36.7%, 25.2 ± 14.3% and 36.1 ± 14.3%, respectively. Remnant-like particle cholesterol (RLP-C), an independent risk factor for CAD which is known to be elevated in diabetic patients, was also significantly reduced (−30.9 ± 30.5%) by the treatment and this decrease correlated well with the decrease in triglyceride level. The proportion of small dense LDL, which is known for its atherogenisity, decreased from 29.9 ± 26.2% to 19.7 ± 22.7% and the mean LDL particle size significantly increased from 26.36 ± 1.13 nm to 27.10 ± 1.36 nm. Pitavastatin, which is known to improve triglyceride levels and cholesterol levels, also improves RLP-C level and LDL subfraction profiles, and this in turn may reduce the cardiovascular risk in patients with type 2 diabetes and dyslipidemia.

Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients

Background: We previously showed that the apolipoprotein (apo) Eϵ2 allele is associated with the progression of diabetic nephropathy. The aim of the present study is to further investigate the association between apo E genetic polymorphism, plasma lipid levels (particularly remnant lipoproteins), and diabetic nephropathy. Subjects and Methods: One hundred fifty-eight patients with type 2 diabetes who had a duration of diabetes longer than 10 years were divided into the three apo E groups: apo E2 (n = 22), E3/3 (n = 102), and E4 (n = 34). Plasma levels of lipids and remnant lipoproteins were measured. The effect of apo E2 triglyceride (TG)-rich lipoproteins, including remnant lipoproteins, on the accumulation of cholesteryl esters by human mesangial cells (HMCs) was estimated by measuring the stimulation of radioactive carbon-labeled oleate incorporation into cholesteryl esters. Results: The frequency of overt nephropathy was significantly greater in apo E2 patients with diabetes (59.1%) than apo E3/3 (34.3%) or apo E4 patients (8.8%), and the frequency of normoalbuminuria was significantly greater in apo E4 patients with diabetes (67.6%) than apo E3/3 (34.3%) or apo E2 patients (4.5%). Logistical regression analysis showed that odds ratios of apo E2 and apo E4 genotypes for the presence of overt nephropathy were 10.179 (P = 0.0349) and 0.129 (P = 0.0028), respectively. Plasma TG and remnant-like lipoprotein particle cholesterol levels were significantly greater in apo E2 patients and significantly lower in apo E4 patients than apo E3/3 patients. Apo E2 TG-rich lipoproteins stimulated the accumulation of cholesteryl esters by HMCs significantly more than apo E3/3 or apo E4 TG-rich lipoproteins. Conclusion: Apo E2 is a positive factor and apo E4 is a negative factor for diabetic nephropathy. Apo E2 TG-rich lipoproteins, including remnant lipoproteins, affected HMCs. Remnant lipoproteins may have an important role in the progression of diabetic nephropathy. © 2002 by the National Kidney Foundation, Inc.

Comparison of fasting and postprandial plasma lipoproteins in subjects with and without coronary heart disease

Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in 88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p <0.0001). Percent increases in the PP state were not significantly different in cases versus controls. Following the fat-rich meal, LDL and HDL cholesterol decreased by 5% and 4% in controls, and by 7% and 6% in patients, with no significant difference in percent changes between groups. Fasting values correlated very highly with PP values for all parameters (all p <0.0001). Our data indicate that although patients with CHD have higher fasting and PP levels of triglycerides, RLP cholesterol, and RLP triglycerides than controls, the response (percent increase) to a fat-rich meal is comparable in both groups. Thus, a feeding challenge is not essential for assessment of these lipoproteins. Moreover, it is not necessary to obtain a fasting sample to assess direct LDL and HDL cholesterol.

Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The α 1-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2%∼16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA 1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6 ± 0.6 nm to 25.9 ± 0.4 nm ( P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r = −0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.

Elevated apolipoprotein B-48 and remnant-like particle-cholesterol in heterozygous familial hypercholesterolaemia.

Apolipoprotein B-48 (apoB-48) is a marker of triglyceride-rich lipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are causally related to atherosclerosis. We have shown previously that fasting plasma apoB-48 may predict postprandial lipaemia. Remnant-like particle-cholesterol (RLP-C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accumulation of remnants of intestinal origin, as reflected by fasting plasma apoB-48 and RLP-C levels. The fasting plasma concentrations of apoB-48 and RLP-C were measured in 15 subjects with heterozygous FH and 15 age- and sex-matched, normolipidaemic subjects. ApoB-48 was determined using SDS-PAGE and a western blotting/enhanced chemi-luminescence technique. RLP-C was measured using an immuno-separation assay. Serum apolipoprotein B-100 (apoB-100) levels were measured using immunonephelometry; lipids were assayed enzymatically. Compared with controls, FH subjects had significantly elevated plasma concentrations of apoB-48 (29.3 median, 16.7-45.1 mg L-1 range vs. 12.8, 7.3-28.6; P < 0.001) and RLP-C (16.2, 1.5-114.3 mg dL-1 vs. 8.5, 5.0-13.5; P = 0.003), as well as serum total apoB-100 (1.9, 1.3-2.6 g L-1 vs. 1.0, 0.3-1.3; P < 0.001), LDL-cholesterol (8.1, 4.6-10.4 mmol L-1 vs. 3.5, 2.4-4.4; P < 0.001) and triglyceride (1.5, 0.6-5.6 mmol L-1 vs. 1.0, 0.4-1.8; P = 0.018). There was no significant difference in HDL cholesterol. The findings suggest that patients with heterozygous FH have elevated plasma concentrations of TRL remnants, including those of intestinal origin. This may be a consequence of decreased clearance of these particles by the LDL-receptor.