Prognostic evaluation of primary non-small cell lung carcinoma patients using biological fluid variables. A systematic review

There is growing experimental evidence to suggest the role of oxidatively modified low‐density lipoprotein (LDL) in the initiation and progression of atherosclerosis. The oxidation of lipoprotein moiety causes modification of positively charged lysine residues and results in negative net charge of lipoprotein particles. Objective: To measure the amount of circulating electronegatively charged LDL particles (LDL–) in plasma of patients with angiographically documented coronary artery disease (CAD). Methods: Thirty patients were assigned to the study group (CAD+) and 10 patients to the control group (Ctrl). LDL– was quantitated in homogeneous LDL fractions obtained by ultracentrifugation, using ion exchange high performance liquid chromatography. Plasma lipids were measured using enzymatic kits. Results: The CAD+ group had significantly higher levels of LDL– in the whole LDL fraction (7.66±1.92 vs. 5.14±0.84%, p=0.0003). Moreover the CAD+ group had significantly higher levels of total cholesterol (255.4±35.1 vs. 210.4±22.4?mg/dL), LDL cholesterol (154.5±26.9 vs. 122.4±21.1?mg/dL) and significantly lower levels of high‐density lipoprotein (HDL) cholesterol (40.4±9.4 vs. 51.0±11.5?mg/dL). LDL– remained significantly higher in the CAD+ group after adjustment for total cholesterol, LDL cholesterol and HDL cholesterol (6.3 vs. 5.14% at p=0.0095). There is a trend towards a positive correlation between LDL– levels and LDL cholesterol in the control group (Spearman R=0.55 at p=0.098). Conclusions: Electronegatively charged LDL appears to be an additional hallmark of coronary artery disease, independently of established lipid risk factors. The trend towards a positive correlation between LDL cholesterol concentration and the level of LDL– in the control group may reflect the susceptibility of LDL cholesterol to autoxidation, Moreover, this may indicate other oxidative mechanisms in coronary artery disease. Nonetheless, further studies assessing the prognostic value of electronegatively charged LDLs are necessary.     

Family history of early cardiovascular disease in children with moderate to severe hypercholesterolemia: relationship to lipoprotein (a) and low-density lipoprotein cholesterol levels

Lipoprotein (a) (Lp(a)) is an established cardiovascular risk factor in adults. We sought to evaluate whether raised Lp(a) levels were predictive of a family history of early cardiovascular disease (CVD) in children already at increased risk for premature atherosclerosis because of elevated low-density lipoprotein (LDL) cholesterol levels. Lp(a) and serum lipid levels were measured in 69 children and offspring with established moderate to severe hypercholesterolemia (serum cholesterol > 170 mg/dL) who were aged 10.7 +/- 4.3 years (range 1.5 to 21 years) and had been referred to a pediatric lipid center. The children represented families with a positive (n = 27) or negative (n = 42) history for premature CVD (<55 years of age in parent or grandparent). In all children, Lp(a) levels ranged from 1 to 140 mg/dL, with a median of 29 mg/dL. Mean total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol levels were 234 mg/dL, 166 mg/dL, and 45 mg/dL, respectively. There was no difference in median Lp(a) levels between the children with a positive family history and those with a negative family history (29.9 mg/dL vs 29.0 mg/dL, respectively). In contrast, children with a positive family history showed significantly higher LDL cholesterol levels (186 +/- 61 mg/dL vs 153 +/- 52 mg/dL, P = .02). Thus, in this group of hypercholesterolemic children, LDL cholesterol but not Lp(a) levels were associated with a family history of premature CVD. Further studies are needed to identify additional specific risk factors associated with the development of CVD in this population.     

Oat-derived beta-glucan significantly improves HDLC and diminishes LDLC and non-HDL cholesterol in overweight individuals with mild hypercholesterolemia

OBJECTIVE: To investigate the effect of bread formulated with 6 g of beta-glucan (oat soluble fiber) on serum lipids in overweight normotensive subjects with mild to moderate hypercholesterolemia. DESIGN: Thirty-eight male subjects [mean age 59.8 +/- 0.6 yr, mean body mass index (BMI) 28.3 +/- 0.6 kg/m(2)] who were eligible for the study ate an isocaloric diet for a 1-week period. They were then divided into 2 groups: group A (n = 19), who were maintained on American Heart Association (AHA) Step II diet, including whole wheat bread, and group B (n = 19), who were maintained on AHA Step II diet containing high levels of monounsaturated fatty acids plus bread containing 6 g of beta-glucan (Nutrim-OB) for 8 weeks. Plasma lipids and glucose were measured at baseline and after weeks 8 in all subjects. All subjects were advised to walk for 60 minutes every day. RESULTS: There was a significant increase (upward arrow 27.8%) in plasma high density lipoprotein (HDL) cholesterol in the beta-glucan group (group A) from 39.4 +/- 2.0 to 49.5 +/- 2.1 mg/dL (P < 0.001), but there was no change in group B. There was a significant reduction in total cholesterol in the 2 groups to approximately the same extent: group A, from 232.8 +/- 2.7 mg/dL to 202.7 +/- 6.7 mg/dL; P < 0.001; and group B, from 231.8 +/- 4.3 mg/dL to 194.2 +/- 4.3 mg dL; P < 0.001. Plasma low density lipoprotein (LDL) cholesterol also decreased significantly in the two groups: group A, from 160.3 +/- 2.8 mg/dL to 133.2 +/- 5.4 mg/dL; P < 0.001; group B, from 167.9 +/- 4.3 mg/dL to 120.9 +/- 4.3 mg/dL; P < 0.001; however, the beta-glucan fortified diet was significantly more effective (downward arrow 27.3% vs. downward arrow 16.8%; P < 0.04). There was a small and insignificant reduction in plasma very LDL (VLDL) cholesterol and triglycerides in the two groups. Similarly, non-HDL cholesterol levels were also decreased, with beta-glucan diet producing significantly higher effect (downward arrow 24.5% vs. downward arrow 16.1%; P < 0.04). The beta-glucan diet also produced higher reduction in total cholesterol/HDL cholesterol ratio (downward arrow 33.3% vs. downward arrow 8.4%; P < 0.003) and LDL cholesterol/HDL cholesterol ratio (downward arrow 42.1% vs. downward arrow 13.3%; P < 0.001) than the diet without beta-glucan. The beta-glucan diet also decreased fasting plasma glucose (P < 0.4), whereas the other diet had no effect. Interestingly, both diets reduced body weight and BMI significantly, with beta-glucan diet having a greater effect. CONCLUSIONS: Six grams of beta-glucan from oats added to the AHA Step II diet and moderate physical activity improved lipid profile and caused a decrease in weight and, thus, reduced the risk of cardiovascular events in overweight male individuals with mild to moderate hypercholesterolemia. The diet with added beta-glucan was well accepted and tolerated.     

Antibody titer against malondialdehyde-modified LDL compares with HDL cholesterol concentration in identifying angiographically verified coronary artery disease. Comparison of tests by ROC analysis.

Antibody titer against malondialdehyde (MDA)-modified low-density lipoprotein (LDL) has been found to be associated with atherosclerosis, but it has not been established whether it would detect subjects with coronary artery disease (CAD). In the present study, receiver-operating characteristic (ROC) analysis was used to compare the diagnostic accuracy of the antibody titer against MDA-modified LDL and high-density lipoprotein (HDL) and LDL cholesterol levels in discrimination between subjects with (n = 51) and without (n = 35) angiographically verified 3-vessel CAD. As a result, the antibody titer against MDA-modified LDL was lower in subjects with CAD compared with subjects without CAD (p < 0.0001). The area under the ROC plot was 0.822 (95% CI, 0.727 to 0.918) for the antibody titer and 0.769 (95% CI, 0.661 to 0.876) for the HDL cholesterol concentration. Both the antibody titer and the plasma HDL cholesterol level were more accurate markers of CAD than the LDL cholesterol level. As a conclusion, our results indicate that the antibody titer against MDA-modified LDL discriminates between subjects with widespread CAD and those without CAD similarly as the HDL cholesterol concentration. Moreover, the antibody titer against MDA-modified LDL is inversely correlated with the risk of severe CAD.     

Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind,placebo-controlled study

OBJECTIVE: The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension. RESEARCH DESIGN AND METHODS: We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 +/- 0.8 mmol/l; HDL cholesterol, 1.1 +/- 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment. RESULTS: At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 +/- 0.30 to 20.13 +/- 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 +/- 0.0024 to 1.0371 +/- 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol. CONCLUSIONS: The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.     

Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients

OBJECTIVE: Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured. RESULTS: The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18-58.68], P = 0.034) and nephropathy (21.98 [1.24-388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients. CONCLUSIONS: Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.     

Detection of electronegative low density lipoprotein (LDL-) in plasma and atherosclerotic lesions by monoclonal antibody-based immunoassays

OBJECTIVES: To produce a monoclonal antibody (MAb) against electronegative LDL (LDL-) for detecting this modified lipoprotein in blood plasma and tissues. DESIGN AND METHODS: LDL- was isolated from human blood plasma and used as an antigen for immunization of Balb/c mice. Lymphocytes of immunized mice were fused with myeloma cells (SP2/0) to obtain the hybridomas. LDL- was detected in blood plasma and atherosclerotic lesions of humans and rabbits by MAb-based ELISA and immunohistochemistry, respectively. RESULTS: LDL- concentrations were higher (P < 0.05) in the blood plasma of hypercholesterolemic subjects (HC, 248 +/- 77 mg/dL of total cholesterol) than in normolipidemic subjects (NL, 173 +/- 82 mg/dL of total cholesterol) and rabbits (HC, 250 +/- 15 mg/dL of cholesterol versus NL, 81 +/- 12 mg/dL of cholesterol). Moreover, LDL- was detected in the atherosclerotic lesions of humans and rabbits. CONCLUSION: These MAb-based immunoassays are adequate to detect LDL- in biological samples and represent an important tool for investigating the role of LDL- in atherosclerosis.     

The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease

OBJECTIVES: The aim of the present study was to determine and correlate tissue factor pathway inhibitor (TFPI), lipoprotein (a) (Lp(a)), oxidized low-density lipoprotein (LDL) antibody (oLAB), and thiobarbituric acid reactive substances (TBARS; as a marker of lipid peroxidation) levels in patients with coronary artery disease (CAD) and in a control group. DESIGN AND METHODS: Peripheral blood samples from patients with coronary heart disease were provided by the Department of Cardiology. Serum oLAB, Lp(a), plasma total TFPI, and plasma-free TFPI levels were determined by ELISA. Serum TBARS levels were determined by a spectrophotometric method using thiobarbituric acid. RESULTS: The CAD and the control group were matched for age and sex. Serum Lp(a), oLAB, and plasma total TFPI levels in patients with coronary heart disease were found to be significantly higher than in the control group (P < 0.001). But there was no difference in plasma-free TFPI levels between patients with CAD and the control group (P > 0.05). In patients with single (P < 0.05), double, and triple vessel (P < 0.01) disease, the mean serum Lp(a) levels were significantly higher than in the control group. On the other hand, in patients with single vessel disease (P < 0.05), double vessel disease (P < 0.05), and triple vessel disease (P < 0.001), plasma total TFPI levels were found to be significantly higher than in the control group. We also found a significant positive correlation (r = 0.28, P < 0.05) between serum Lp(a) and plasma total TFPI levels in CAD. In the patient group, TBARS, total cholesterol, triglyceride (TRG), and LDL cholesterol levels were found to be significantly higher than those in the control group. In addition, high-density lipoprotein (HDL) cholesterol levels were found to be significantly lower than the control group. CONCLUSIONS: These results suggest that elevated plasma levels of total TFPI, Lp(a), and oLAB may be useful diagnostic and monitoring markers in patients with CAD.     

Achieving National Cholesterol Education Program goals for low-density lipoprotein cholesterol in cardiac patients: importance of diet, exercise, weight control, and drug therapy.

OBJECTIVE: To determine how frequently the National Cholesterol Education Program (NCEP) goal of a low-density lipoprotein (LDL) cholesterol level of 100 mg/dL or less is achieved in clinical practice in patients with coronary artery disease and what fraction of patients can achieve this goal without drug therapy. DESIGN: We examined the results of lipid management in 152 consecutive patients who had completed cardiac rehabilitation after an acute coronary event. Patients were randomized to follow-up by specially trained nurses or by preventive cardiologists, and they were not receiving lipid-lowering drugs at the start of the study. MATERIAL AND METHODS: Patients were given aggressive diet and exercise recommendations and lipid-lowering drugs in accordance with NCEP guidelines. Follow-up was continued for a mean of 526 days after the first lipid assessment subsequent to the coronary event. Multiple logistic regression analysis was used to identify independent predictors of a final LDL cholesterol level of 100 mg/dL or less. RESULTS: Of the study group, 39% achieved the NCEP goal LDL cholesterol level of 100 mg/dL or less. Characteristics of the patients with LDL cholesterol levels of 100 mg/dL or less in comparison with those with LDL cholesterol levels of more than 100 mg/dL included a greater frequency of drug therapy (65% versus 38%), more rigorous dietary compliance, longer follow-up (586 +/- 317 days versus 493 +/- 264 days), more favorable weight change (-0.3 +/- 4.9 kg versus +1.7 +/- 5.0 kg), and more extensive weekly exercise (183 +/- 118 minutes versus 127 +/- 107 minutes). CONCLUSION: The registered nurses managed the lipids of these patients as effectively as did the preventive cardiologists. Appropriate drug therapy was the most important factor in achieving an LDL cholesterol level of 100 mg/dL or less, but 35% of patients attaining this NCEP goal were not receiving drug therapy. Exercise, dietary compliance, and weight loss were also important factors.     

Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.     

Lipoproteins and apolipoproteins in young nonobese Arab women with NIDDM treated with insulin

The effects of insulin on the lipid values of nonobese non-insulin-dependent diabetic (NIDDM) Arab women requiring insulin was investigated to find whether these patients have the same coronary artery risk factor related to lipid levels. In this study, 55 NIDDM women on insulin therapy (mean age 28 +/- 8.1 yr and duration of disease 5 +/- 1.2 yr) and 70 control subjects (matched for sex, age, and body mass index) were studied for their plasma levels of lipids, lipoproteins, and apolipoproteins. Concentrations of total cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride (TG), LDL TG, high-density lipoprotein triglyceride (HDL TG), phospholipid, glucose, glycosylated hemoglobin (HbAtc), apolipoprotein B (apoB), LDL-apoB, and apoB/apoAl were significantly elevated in diabetic women compared with control subjects. There was no significant change in the levels of apoAll in plasma and lipoprotein fractions. Concentrations of HDL cholesterol (chol), HDL2-chol, HDL3-chol, plasma apoAl, HDL2-apoAl, HDL3-apoAl, and HDL-apoAl were significantly lower in diabetic women than in control subjects. There was no significant correlation between glucose or HbAtc and most of the lipids, lipoprotein lipids, and apolipoproteins measured. Despite normal body weight and insulin therapy, abnormalities in lipids, lipoprotein lipids, and apoB persisted in NIDDM patients compared with control subjects. Our data may favor an enhanced affinity toward atherosclerosis in these patients.     

绝经后女性冠状动脉钙化患者的相关危险因素分析

目的探讨影响绝经后女性患者发生冠状动脉钙化的相关危险因素。 方法选取2020年1月至2020年12月行冠状动脉CT血管造影术的121例绝经后女性患者。根据冠状动脉钙化评分（CACS）将所有患者分成钙化组（CACS>10分,57例）及非钙化组（CACS ≤ 10分,64例）。对两组患者的一般资料进行比较,并检测所有患者的雌二醇、促黄体生成素（LH）、卵泡刺激素（FSH）、载脂蛋白A1（APOA1）、载脂蛋白A2（APOA2）、脂蛋白A、胆固醇、高密度脂蛋白（HDL）及低密度脂蛋白（LDL）水平。同时,采用Logistic多因素回归分析影响绝经后女性冠状动脉钙化的危险因素。 结果与非钙化组比较,钙化组患者的年龄[（54 ± 9）岁vs.（60 ± 11）岁,t = 3.031,P = 0.003]、胆固醇[（5.2 ± 0.5）mmol/L vs.（5.6 ± 0.9）mmol/L,t = 3.410,P = 0.001]及LDL[（2.5 ± 0.6）mmol/L vs.（3.0 ± 0.7）mmol/L,t = 3.790,P< 0.001]水平显著升高,雌二醇[（26 ± 19）ng/L vs.（17 ± 11）ng/L,t = 3.052,P = 0.003]及脂蛋白A[（232 ± 36）mg/L vs.（144 ± 21）mg/L,t = 2.047,P = 0.043]水平均显著降低。Logistic回归分析表明,年龄[比值比（OR）= 1.046,95%置信区间（CI）（1.001,1.094）,P = 0.047]及胆固醇[OR = 2.040,95%CI（1.034,4.025）,P = 0.040]为绝经后女性冠状动脉钙化的危险因素,雌二醇则为绝经后女性冠状动脉钙化的保护因素[OR = 0.993,95%CI（0.984,0.998）,P = 0.049]。 结论年龄及胆固醇水平为绝经后女性冠状动脉钙化的危险因素,雌二醇则为绝经后女性冠状动脉钙化的保护因素。     

Effects of exercise intervention on patients with stroke with prior coronary artery disease: aerobic capacity, functional ability, and lipid profile: a pilot study.

OBJECTIVE: To assess the effects of exercise intervention on aerobic capacity, functional ability and lipid profile in patients after stroke with prior coronary artery disease. PATIENTS: Fifteen patients after stroke with prior coronary artery disease. METHODS: Patients were enrolled in a moderate-intensity exercise intervention using a graded treadmill for 12 weeks. Before and after the intervention, their aerobic capacity and functional ability were assessed by the exercise testing and Barthel index, respectively. The total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), triglyceride, and TC/HDL were also evaluated using an enzyme auto-analyser. RESULTS: After training, the patients'absolute peak oxygen consumption (VO2) was increased (p < 0.01); their functional ability was significantly improved (p < 0.01); and their TC, LDL, triglyceride, and TC/HDL levels were significantly reduced (p < 0.01). However, HDL level did not change significantly. In addition, Pearson analysis demonstrated a strong correlation between the increase in peak VO2 and the decrease in TC/HDL (r = -0.72, p < 0.01). CONCLUSION: These results suggest that exercise intervention is beneficial for aerobic capacity, functional ability, and some parts of the lipid profile in patients after stroke with prior coronary artery disease.     

Plasma lipoprotein changes after treatment with pravastatin and gemfibrozil in patients with familial hypercholesterolemia

The ability of pravastatin, a new hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, to lower plasma lipid levels and modify lipoprotein patterns was compared with that of gemfibrozil in 18 patients with familial hypercholesterolemia who participated in a 16-week, double-blind, parallel trial. Pravastatin proved better than gemfibrozil in lowering total and low-density lipoprotein (LDL) cholesterolemia: -23.6% and -28.2% versus -18.1% and -21.4%, respectively. A significant positive correlation was found between the starting level of serum cholesterol (both total and LDL) and the gemfibrozil-induced reduction (r = 0.72 and 0.69), whereas the hypocholesterolemic effect of pravastatin was apparently independent from pretreatment levels (r = 0.32 and 0.10). Apolipoprotein B concentrations were lowered by 25.4% (pravastatin) and 22.0% (gemfibrozil). Pravastatin and gemfibrozil reduced triglyceride levels by 13.9% and 49.4%, respectively. Both drugs increased the level of high density lipoprotein (HDL) cholesterol, but this change was significant only with gemfibrozil (p less than 0.05). The HDL subfraction structure and distribution were not modified by pravastatin treatment. Gemfibrozil, in contrast, increased HDL3 cholesterol level by 9% because of an enrichment of HDL3 particles in both free cholesterol and cholesteryl esters and lowered the flotation rate of HDL3 (p less than 0.05). LDL particles became smaller after gemfibrozil treatment (diameter: 25.4 +/- 0.3 nm vs 26.1 +/- 0.4 nm, p less than 0.01) and were not modified by pravastatin. This comparison shows a more pronounced efficacy of the HMG CoA reductase inhibitor on total and LDL cholesterol levels, also indicating that pravastatin acts by a single major mechanism, reducing the number of circulating LDL particles. Gemfibrozil may exert additional activities, possibly consequent to the stimulation of very low density lipoprotein catabolism.     

Early onset of subclinical atherosclerosis in women with gestational diabetes mellitus.

OBJECTIVE: Common carotid artery intima-media thickness (CIMT) is a non-invasively assessed marker of subclinical atherosclerosis. Our aim in this study was to investigate CIMT in women with gestational diabetes mellitus (GDM). METHODS: Thirty women with GDM and 40 unaffected women (as a control group) were included in the study. Blood samples were drawn from each woman in the morning after they had fasted for at least 8 h, and levels of fasting glucose, insulin, homocysteine, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and very low-density lipoprotein (VLDL) cholesterol were measured, along with the CIMT in the two groups. RESULTS: The mean triglyceride (P = 0.016) and VLDL cholesterol (P = 0.011) levels in the GDM group were significantly higher than those in the unaffected women. There were no significant differences between the groups with respect to plasma levels of total cholesterol, HDL cholesterol, LDL cholesterol and insulin. The mean homocysteine (P = 0.027) and fasting glucose (P = 0.019) levels in women with GDM were significantly higher than those in the control group. Patients with GDM had significantly higher CIMT than did the unaffected women (0.582 +/- 0.066 mm vs. 0.543 +/- 0.049 mm, P = 0.006). CIMT correlated positively with maternal age (r = 0.316, P = 0.008), body mass index (BMI) at the time of a 50-g oral glucose load test (r = 0.414, P = 0.001) and homocysteine levels (r = 0.332, P = 0.008), and fasting glucose (r = 0.265, P = 0.031) and 1-h glucose value (r = 0.410, P = 0.001) at the time of the oral glucose tolerance test. There was a positive correlation between the presence of GDM and CIMT (r = 0.372, P = 0.001). However, stepwise multiple regression analysis showed that GDM/no GDM (95% CI +0.012 to +0.076, P = 0.008) and BMI at the time of the 50-g test (95% CI +0.001 to +0.009, P = 0.011) were independent parameters related to CIMT. CONCLUSION: Women with GDM have increased CIMT compared with unaffected women.     

Association of high-density lipoprotein levels and carotid atherosclerotic plaque characteristics by magnetic resonance imaging

A low level of high-density lipoprotein cholesterol (HDL-C) is a risk factor for atherosclerotic disease. Magnetic resonance imaging (MRI) can provide detailed information on carotid atherosclerotic plaque size and composition. The purpose of this study was to correlate HDL levels with carotid plaque burden and composition by MRI. Thirty-four patients with coronary artery disease (CAD) receiving simvastatin plus niacin or placebo for both drugs for three years were randomly selected to undergo MRI of carotid arteries. Atherosclerotic plaque wall volumes (WVs) and plaque components including lipid rich/necrotic core (LR/NC), calcium, fibrous tissue, and loose matrix were measured. Mean WV or atherosclerotic burden was significantly associated with total HDL-C levels (r = −0.39, P = 0.02), HDL₂ (r = −0.36, P = 0.03), HDL₃ (r = −0.34, P = 0.04), and LDL/HDL ratio (r = 0.42, P = 0.02). Plaque lipid composition or LR/NC was significantly associated with HDL₃ (r = −0.68, P = 0.02). Patients with low HDL levels (≤35 mg/dL) had increased WV (97 ± 23 vs. 81 ± 19 mm³, P = 0.05) compared with patients with HDL levels > 35 mg/dL. Among CAD patients, low HDL-C levels were significantly associated with increased carotid atherosclerotic plaque burden and lipid content by MRI.     

Lipoprotein lipase gene polymorphisms in Croatian patients with coronary artery disease.

Modifications in lipoprotein lipase levels lead to elevated triglycerides and reduced high density lipoprotein (HDL), both of which are risk factors for coronary artery disease (CAD). Hence, we examined the influence of the -93T/G, D9N, N291S, and S447X polymorphisms in the lipoprotein lipase (LPL) gene on CAD risk and lipid levels in Croatian patients with and without angiographically confirmed CAD. The N291S polymorphism was significantly associated with CAD (OR = 0.36; 95% CI = 0.13, 0.99; p = 0.048). This association was only moderately affected by adjusting for various lipids (OR = 0.36; 95% CI = 0.12, 1.08; p = 0.068). HDL2-cholesterol and apolipoprotein A-I levels were significantly higher in non-carriers of the -93T/G and D9N polymorphisms in the CAD group (p = 0.017 and 0.028, respectively). The N291S genetic variant did not show any significant difference between carriers and non-carriers in either group studied for any of the lipids. Lower triglyceride and higher HDL2-cholesterol levels in the control group were associated with carriers of the S447X mutation (p = 0.043 and 0.056, respectively). LPL gene polymorphisms might be involved in predisposition to CAD and determination of lipid profiles.     

64层螺旋CT冠状动脉成像联合血脂动态变化评价冠心病

目的分析血脂动态变化与冠状动脉粥样硬化性心脏病的关系。方法回顾性分析108例怀疑冠心病首次住院病人,所有病人均行64层螺旋CT冠脉成像（CTA）检查,同时行血脂检查。依据CTA结果分4组,对照组（冠脉无狭窄）;轻度（狭窄〈50％）;中度（50％≤狭窄〈75％）;重度（狭窄≥75％）。结果与对照组比较,血总胆固醇（TC）、血三酰甘油（TG）、高密度脂蛋白胆固醇（HDL—C）及低密度脂蛋白胆固醇（LDL—C）均存在明显差异（P〈0．05）。TC、LDL—C在异常组间无显著性差异（P〉0．05）,而TG、HDL—C存在显著性差异（P〈0．05）。结论TC、LDL—C作为冠状动脉粥样硬化发生的始动因素,TG、HDL—C影响冠脉狭窄程度,在粥样硬化演进中可能起主要作用。动态分析血脂变化对评价冠心病具有一定指导意义。     

Quantification of lipoprotein subclasses by proton nuclear magnetic resonance-based partial least-squares regression models

BACKGROUND: Cardiovascular disease risk can be estimated in part on the basis of the plasma lipoprotein profile. Analysis of lipoprotein subclasses improves the risk evaluation, but the traditional methods are very time-consuming. Novel, rapid, and productive methods are therefore needed. METHODS: We obtained plasma samples from 103 fasting people and determined the plasma lipoprotein subclass profiles by an established ultracentrifugation-based method. Proton nuclear magnetic resonance (NMR) spectra were obtained from replicate samples on a 600 MHz NMR spectrometer. From the ultracentrifugation-based reference data and the NMR spectra, we developed partial least-squares (PLS) regression models to predict cholesterol and triglyceride (TG) concentrations in plasma as well as in VLDL, intermediate-density lipoprotein (IDL), LDL, 3 LDL fractions, HDL, and 3 HDL subclasses. RESULTS: The correlation coefficients (r) between the plasma TG and cholesterol concentrations measured by the 2 methods were 0.98 and 0.91, respectively. For LDL- and HDL-cholesterol concentrations, r = 0.90 and 0.94, respectively. For cholesterol concentrations in the LDL-1, LDL-2, and LDL-3 fractions, r = 0.74, 0.78, and 0.69, respectively, and for HDL subclasses HDL(2b), HDL(2a), and HDL(3), cholesterol concentrations were predicted with r = 0.92, 0.94, and 0.75, respectively. TG concentrations in VLDL, IDL, LDL, and HDL were predicted with correlations of 0.98, 0.85, 0.77, and 0.74, respectively. The cholesterol and TG concentrations in the main lipoprotein fractions and in LDL fractions and HDL subclasses predicted by the PLS models were 94%-100% of the concentrations obtained by ultracentrifugation. CONCLUSION: NMR-based PLS regression models are appropriate for use in research in which analyses of the plasma lipoprotein profile, including LDL and HDL subclasses, are required in large numbers of samples.     

Resolving hyperlipidemia after liver transplantation in a patient with primary sclerosing cholangitis

A 64-year-old man with primary sclerosing cholangitis (PSC) and resultant liver failure presented to our hospital with severe dyslipidemia (total cholesterol, 525 mg/dL; low-density lipoprotein (LDL) cholesterol, 489 mg/dL; high-density lipoprotein (HDL) cholesterol, 13 mg/dL; triglycerides, 114 mg/d) and coronary artery disease. The abnormal lipid profile of patients with cholestatic liver disease, such as PSC, includes an abnormal atherogenic LDL called lipoproteinX. The patient's dyslipidemia persisted despite treatment with a statin. Lipids normalized only after liver transplantation (total cholesterol, 135 mg/dL; LDL cholesterol, 60 mg/dL; high-density lipoprotein cholesterol, 48 mg/dL; triglycerides, 130 mg/dL). To the best of our knowledge, the dramatic improvement in the lipid profile after liver transplantation represents the first such published report for PSC. The recognition of dyslipidemia and atherosclerosis in those with cholestatic liver disease and the normalization of lipid profile after liver transplantation warrant further study. We present a review of dyslipidemia in cholestatic liver disease, its relationship to atherosclerosis, and its treatment.