Circulating electronegatively charged low-density lipoprotein in patients with angiographically documented coronary artery disease

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.     

Lipid profile in patients with microvascular angina

Lipid, lipoprotein and apolipoprotein levels, as well as the susceptibility of low-density lipoprotein (LDL) to oxidation, were studied in patients with microvascular angina in comparison with patients with coronary artery disease (CAD) and normal subjects. Total cholesterol, LDL-cholesterol and apolipoprotein B levels in microvascular angina patients (235±46 mg dL^?1, 135±33 mg dL^?1 and 146±32 mg dL^?1 respectively) were significantly higher than in control subjects (204±40 mg dL^?1, 116±35 mg dL^?1 and 129±29 mg dL^?1 respectively, P<0.01). These parameters were also significantly higher in CAD patients than in control subjects. By contrast, high-density lipoprotein (HDL)-cholesterol levels in microvascular angina patients were no different from those in control subjects, although both were significantly higher than in the CAD patients (48±16 mg dL^?1 and 45±12 mg dL^?1 compared with 40±10 mg dL^?1, P<0.01 and P<0.05 respectively). Similar results were obtained for the apolipoprotein AI levels. Furthermore, the atherogenic risk ratio, LDL-cholesterol/HDL-cholesterol, in microvascular angina patients was significantly lower than in the CAD patients (3.4±1.2 vs. 4.1±1.5 respectively, P<0.01). Median (range) serum lipoprotein (a) [Lp(a)] levels in microvascular angina patients and CAD patients [13 mg dL^? (0.8–92) and 16 mg dL^? (0.8–96) respectively] were significantly higher than in control subjects [7 mg–dL^? (0.8–44)], P<0.01 and P<0.005 respectively. Sigmoidal curves and electrophoretic mobility of the Cu²⁺-oxidized LDL in both microvascular angina and CAD patients were not significantly different from those of control subjects. Finally, no significant differences were found between groups in total triglyceride levels or in very low-density lipoprotein (VLDL), LDL and HDL triglyceride levels. Our results show that the microvascular angina patients exhibit lipid abnormalities similar to those observed in CAD patients, with the important exception of the HDL-cholesterol and apolipoprotein AI levels, which are significantly higher in microvascular angina patients. We suggest that the abnormal cholesterol and Lp(a) levels may be involved in the pathophysiology of microvascular angina by affecting endothelial function and endothelium-mediated vasodilator responses, whereas the higher HDL levels may be a factor contributing to the absence of angiographically documented CAD in microvascular angina patients.     

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.     

Insulin resistance phenotypes and coronary artery disease in a native Pakistani cohort

Objective: To determine the relationship between insulin resistance (IR) and atheroma burden in Pakistanis. Methods: A prospective case–control study of 400 patients selected for the presence/absence of angiographic disease. Coronary atheroma burden was quantified and IR and cardiovascular risk factors were measured. Results: The patients were divided into two groups by QuickI score. Waist circumference (90 ± 10 vs. 90 ± 9 cm; p = 0.7) was similar but the groups differed in body mass index (26.5 ± 3.7 vs. 24.2 ± 3.5 kg/m²; p < 0.001) and waist:hip ratio (0.94 ± 0.09 vs. 0.90 ± 0.06; p < 0.001). Lipid parameters showed similar high‐density lipoprotein cholesterol (HDL‐C) (0.77 ± 0.23 vs. 0.82 ± 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08–3.98) vs. 1.12 (0.37–3.61) mmol/l; p = 0.01], but no difference in low‐density lipoprotein cholesterol (LDL‐C) (2.75 ± 1.00 vs. 2.90 ± 0.94 mmol/l; p = 0.14). In insulin‐resistant patients C‐reactive protein (CRP) [6.8 (0.3–175.1) vs. 3.9 (0.2–57.9) mg/l: p < 0.001], sialic acid (82 ± 14 vs. 77 ± 15 mg/l; p < 0.001) aspartate transaminase [24 (7–171) vs. 21 (7–83) IU/l; p < 0.001] and gamma‐glutamyl transferase [27 (8–482) vs. 21 (7–168) IU/l; p = 0.005] levels were increased. In insulin‐resistant patients (n = 187), coronary artery disease (CAD) burden correlated (r = 0.55) with age (β = 1.62; p < 0.001), HDL‐C (β = ?53.2; p < 0.001), lipoprotein (a) (β = 11.4; p = 0.007), smoking (β = 7.98; p = 0.004), CRP (β = 6.06; p = 0.03) and QuickI index (β = ?146; p = 0.04). In contrast in insulin‐sensitive patients (n = 178) CAD burden (r = 0.46) correlated with LDL‐C (β = 10.0; p = 0.02), CRP (β = 7.13; p = 0.03), HDL‐C (β = ?38.1; p = 0.03), and weakly with age (β = 0.73; p = 0.07) and smoking (β = 5.52; p = 0.09). Conclusions: Indian Asians show a dichotomous insulin‐resistance phenotype. Atheroma is associated with low HDL‐C and inflammation associated in all but LDL‐C is a factor in the insulin sensitive in contrast to age and extent of IR in the insulin resistant.     

Low-density lipoprotein apheresis using the liposorber dextran sulfate cellulose system for patients with hypercholesterolemia refractory to medical therapy

A subset of patients with familial hypercholesterolemia (FH) have an inadequate lipid-lowering response to diet and drug treatment and should be considered for low-density lipoprotein (LDL)-apheresis therapy. This procedure selectively removes apolipoprotein B-containing particles [LDL, very-low-density lipoprotein, lipoprotein(a)] from plasma independent of diet and drug therapy. Methods for performing LDL-apheresis include dextran sulfate cellulose adsorption, immunoadsorption, and heparin-induced extracorporeal precipitation. The Liposorber Study Group evaluated LDL removal using the Liposorber® LA-15 LDL-apheresis System in 64 patients with FH who had not responded adequately to diet and maximal drug therapy. Mean acute reductions in LDL cholesterol (LDL-C) were 76% in heterozygous FH (HtFH) patients and 81% in homozygous FH (HoFH) patients. Time-averaged levels of LDL-C were lowered 41% in HtFH and 53% in HoFH patients. Hypotension was the most frequent side effect, occurring in 3% of procedures. The Liposorber® LA-15 System has been approved by the Food and Drug Administration and is recommended for 1) patients with functional homozygous FH (LDL-C level >500 mg/dL; 2) patients with coronary artery disease (CAD) and LDL-C levels ≥200 mg/dL; 3) patients without CAD, but an LDL-C level ≥300 mg/dL. © 1996 Wiley-Liss, Inc.     

Assessment of atrial conduction time in patients with coronary artery ectasia

Background: Coronary artery ectasia (CAE) is associated with increased sympathetic activity, plasma levels of inflammatory markers, and oxidative stress. These factors can also cause arrhythmias such as atrial fibrillation. Atrial conduction abnormalities in patients with CAE have not been investigated in terms of atrial electromechanical delay obtained by tissue Doppler echocardiography. Methods: Ninety patients with pure CAE (n = 30), nonobstructive coronary artery disease (NO‐CAD) (n = 30), and angiographically normal coronary arteries “controls” (n = 30) were compared in terms of electrocardiographic P‐wave measurements, echocardiographic atrial electromechanical coupling (AEC) parameters, and interatrial conduction delay. Results: The mean left atrium diameter in the CAE group was similar to the NO‐CAD group but significantly greater than the control group (3.62 ± 0.28 vs 3.46 ± 0.32 vs 3.41 ± 0.31 cm, P = 0.021). P maximum and P‐wave dispersion were significantly increased in the CAE group compared to the NO‐CAD group and the control group (108.6 ± 6.6 vs 97.9 ± 6.6 vs 93.5 ± 6.2, P = 0.0001; 34.4 ± 7.6 vs 23.2 ± 7.8 vs 19.4 ± 7.7 ms, P < 0.0001). Mitral AEC, septal AEC, and tricuspid AEC were significantly higher in the CAE group than the NO‐CAD group and the control group (68 ± 4.5 vs 57 ± 4.5 vs 53 ± 4.6 ms, P < 0.0001; 50.7 ± 7 vs 42.7 ± 7 vs 41.7 ± 7.2 ms, P = 0.0001; 47 ± 6.7 vs 39.1 ± 6.7 vs 38.1 ± 6.6 ms, P < 0.0001). Interatrial conduction delay was significantly increased in the CAE group compared to the NO‐CAD group and the control group (21 ± 5.5 vs 17.8 ± 5.6 vs 15 ± 5.6 ms, P < 0.0001).The correlation analysis demonstrated that the interatrial conduction delay and P‐wave dispersion (Pd) were positively correlated with number of ectatic segments (ESN) (r = 0.41, P = 0.024 vs r = 0.49, P = 0.006). Stepwise multiple linear regression analysis revealed that the ESN was the only independent determinants of interatrial conduction delay (P = 0.024). Conclusion: Pd and interatrial conduction delay are prolonged in patients with CAE compared to NO‐CAD patients and the healthy controls. (PACE 2011; 34:1468–1474)     

High-density lipoprotein cholesterol, C-reactive protein, and prevalence and severity of coronary artery disease in 5641 consecutive patients undergoing coronary angiography

Background Although high‐density lipoprotein cholesterol (HDL‐C) and C‐reactive protein (CRP) are well‐established predictors for future cardiovascular events, little information is available regarding their correlation with the prevalence and severity of angiographically evaluated coronary artery disease (CAD). Material and methods Five thousand six hundred forty‐one consecutive patients undergoing coronary angiography for the evaluation of CAD were analysed. Cardiovascular risk factors were assessed by routine blood chemistry and questionnaire. CAD severity was graded by visual estimation of lumen diameter stenosis with significant stenoses defined as lumen diameter reduction of ≥ 70%. Coronary angiograms were graded as one‐, two‐ or three‐vessel disease, as nonsignificant CAD (lumen irregularities < 70%) or non‐CAD. Results HDL‐C (60·3 ± 18·5 vs. 51·9 ± 15·3 mg dL^?1; P < 0·001) was higher and CRP was lower (0·65 ± 1·68 vs. 1·02 ± 2·38 mg dL^?1; P < 0·001) in non‐CAD (n = 1517) compared to overall CAD patients (n = 4124). CAD patients were older (65·2 ± 10·5 years vs. 59·9 ± 11·4 years), more often diabetics (19·2% vs. 10·6%) and hypertensives (79·2% vs. 66·0%) and included more smokers (18·8% vs. 16·5%) (all P < 0·005). Low‐density lipoprotein cholesterol (124·5 ± 38·3 vs. 126·0 ± 36·3 mg dL^?1; P = NS) was similar in overall CAD and non‐CAD patients with more statin users (43·4% vs. 27·9%; P < 0·001) among CAD patients. Comparing non‐CAD with different CAD severities using analysis of variance, results did not change substantially. In a multivariate analysis, HDL‐C and CRP remained independently associated with the prevalence of CAD. In addition, HDL‐C is also a potent predictor for the severity of CAD. Conclusions In this large consecutive patient cohort, HDL‐C and CRP are independently associated with the prevalence of CAD. In this analysis, HDL‐C is an even stronger predictor for CAD than some other major classical risk factors.     

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.     

A STUDY OF LIPID PROFILE BEFORE AND AFTER CORONARY ARTERY BYPASS GRAFTING

SUMMARY This study was undertaken to establish the variability in the levels of total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol before and after coronary artery bypass graft (CABG) surgery, in order to determine postoperatively when an accurate assessment can be made of the lipid status. During a prospective study over 4 months, fasting venous samples were taken pre- and postoperatively on day 5, and in the 4th, 8th and 12th weeks. Ninety-six patients admitted to the cardiothoracic and cardiac wards for CABG were recruited to the study. The mean preoperative levels were: TC 5.94 (± 0.1 mmol/l), LDL cholesterol 4.02 (± 0.09mmol/l) and HDL cholesterol 1.00 (± 0.03mmol/l). These were significantly different (p<0.01) from the levels on the 5th postoperative day when the mean level of TC was 4.14 (± 0.084mmol/l), LDL cholesterol was 2.45 (± 0.07mmol/l) and HDL cholesterol was 0.74 (±0.03mmol/l). By the 4th postoperative week, mean TC (5.73±0.13mmol/l), LDL cholesterol (3.79 ±0.14mmol/l) and HDL cholesterol (1.03 ± 0.04mmol/l) did not vary significantly from the mean preoperative values. There was no significant difference in the mean TG levels pre- and postoperatively. The mean TC, LDL cholesterol and HDL cholesterol rise to preoperative levels by the 4th week after CABG. Thus, an accurate assessment of patients' lipid status can be made from this period. An earlier postoperative assessment may be falsely reassuring.     

Aorta and coronary angiographic follow-up of children with severe hypercholesterolemia treated with low-density lipoprotein apheresis

BACKGROUND: In this single‐center, nonrandomized, prospective study, 11 children with severe genetic hypercholesterolemia, without previous cardiovascular disease events, were treated with low‐density lipoprotein apheresis (LDLa). STUDY DESIGN AND METHODS: LDLa was given every 1 or 2 weeks for 2 to 17 years. Clinical cardiovascular events and coronary revascularization, as well as aortic and coronary angiographic findings and ejection fractions, were serially evaluated for 2 to 17 years. RESULTS: Total cholesterol (TC) and LDL cholesterol levels at baseline were 826.1 ± 183.3 and 767.8 ± 181.9 mg/dL, respectively. After LDLa, these levels decreased to 122.6 ± 24.4 and 79.1 ± 20.7 mg/dL, respectively (both differences, p ≤ 0.001). There were no cardiac deaths, and 6 children were free from any coronary lesions. Nonfatal myocardial infarction was not observed, and coronary revascularization was not required in any patient. Regression of coronary stenosis in children with existing angiographically established lesions after treatment with LDLa was prospectively demonstrated. The statistical analysis applicable to a scoring model (overall atherogenic index [OAI]) highlighted a significant relation between values of 0 to 4 years relevant to the score (p ≤ 0.018) and a weaker significant statistic for the value of OAI between 0 and 2 years (p ≤ 0.03). The OAI score at baseline was significantly related to the basal values of TC (p = 0.015), LDL cholesterol (p = 0.015), and triglycerides (p = 0.01), but not of high‐density lipoprotein cholesterol (p = 0.075) as demonstrated by the logistic regression analysis (Cox and Snell pseudo‐R² of 0.67). CONCLUSION: LDLa interrupted the development of new aortic and coronary lesions in the native arteries and prevented cardiac events and the need for coronary revascularization in children without previous cardiovascular disease events.     

Effect of nateglinide on the size of LDL particles in patients with type 2 diabetes

The objective of the present study was to evaluate the efficacy of nateglinide in controlling blood glucose levels and regulating lipid metabolism in patients with type 2 diabetes by focusing attention particularly on low-density lipoprotein (LDL) particle size. The subjects were 23 patients with type 2 diabetes who were given nateglinide, 90 to 270 mg/d. Laboratory studies were conducted at treatment initiation and 3 mo later. Despite a decline that occurred in the level of fasting plasma glucose before and after administration of nateglinide, no significant difference was recognized. Hemoglobin A1c decreased significantly from 6.37±0.75% to 5.91±0.64% (P<.001). A significant decline was also seen in the fasting level of immunoreactive insulin, from 9.82±5.69 μU/mL to 8.59±4.05 μU/mL (P<.05), and in the homeostasis model assessment for insulin resistance, from 3.0±1.83 to 2.55±1.26 (P<.05). Regarding lipids, triglycerides significantly decreased from 140.7±61.8 mg/dL to 117.3±34.7 mg/dL (P<.05). The significant reduction in migration index value, which was used as an index to LDL particle size, from 0.374±0.034 to 0.357±0.035 (P<.05), confirmed that LDL particle size had increased. The results of the present study show that nateglinide is effective in controlling blood glucose and improving insulin resistance, hypertriglyceridemia, and LDL particle size in patients with mild type 2 diabetes. These effects suggest that nateglinide may effectively control coronary artery disease in this population.     

Relation between lipoprotein (a) and in vitro oxidation of apolipoprotein B-containing lipoproteins

OBJECTIVES: To assess the relationship between lipoprotein (a) [Lp (a)] and lipoprotein oxidation in patients with coronary artery disease (CAD). DESIGN AND METHODS: Oxidation of apolipoprotein (apo)B-containing lipoproteins, vitamin E, carotenoids, lipid-lipoprotein levels were determined in 171 CAD and 70 non-CAD subjects. RESULTS: In CAD patients with Lp (a) concentrations >/= 30 mg/dL; total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA), and apo B levels were significantly higher and lag-time and age were significantly lower than those of CAD patients with Lp (a) concentrations < 30 mg/dL. In non-CAD subjects with Lp (a) concentrations >/= 30 mg/dL; TC, LDL-C, and vitamin E levels were significantly higher and lag-time was significantly lower than those of non-CAD subjects with Lp (a) concentrations < 30 mg/dL. In CAD patients, Lp (a) correlated negatively with lag-time and positively with MDA levels. Lp (a) correlated negatively with lag-time and vitamin E levels in non-CAD subjects. CONCLUSIONS: We have shown that plasma apo B-containing lipoproteins of both CAD and non-CAD subjects with Lp (a) levels >/= 30 mg/dL are more susceptible to in vitro oxidative modification than those of subjects with Lp (a) levels < 30 mg/dL. The relationship between Lp (a) and enhanced susceptibility of apo B-containing lipoproteins to oxidation, appears to support routine investigation of Lp (a).     

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.     

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.     

冠心病患者血清Lp-PLA2与HCY检测及其与冠状动脉病变程度的相关性分析

目的 探讨血清脂蛋白相关磷脂酶A2(Lp-PLA2)和同型半胱氨酸(HCY)水平检测与冠心病(CHP)患者冠状动脉病变程度的关系。方法 选取2017年1月～2018年5月延安大学附属医院经冠状动脉造影确诊的冠心病患者266例为实验组,其中男性161例,平均年龄57.3±8.5岁,女性105例,平均年龄61.1±11.6岁,选取同期该院冠状动脉造影阴性的体检者180例为对照组,其中男性97例,平均年龄54.6±10.5岁,女性83例,平均年龄47.5±6.3岁,记录两组性别、年龄、糖尿病史、卒中病史、心肌梗死病史、吸烟史和饮酒史,使用贝克曼AU2700全自动生化分析仪测定两组HCY,Lp-PLA2,空腹血糖(FBG)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和脂蛋白(a)[Lp(a)]水平,分析两组各项指标的差异。秩和检验比较Gensini积分组 [低积分组(Gensini积分<14分,n=128),中积分组(Gensini积分14～28分,n=83),高积分组(Gensini积分>28分,n=55)共3组] Lp(a),HCY水平之间的差异,秩和检验比较冠状动脉不同支数病变组 [1支病变组(n=87)、2支病变组(n=91)、3支及3支以上病变组(n=88)共3组] Lp(a),HCY水平之间的差异。采用Pearson法分析Gensini积分与Lp-PLA2,HCY水平之间的相关性及Lp-PLA2与HCY水平之间的相关性。结果 实验组与对照组吸烟史、饮酒史及HCY,Lp-PLA2,Lp(a)水平为:59.77% vs 38.9%,86.84% vs 76.67%,53.7±21.8 μmol/L vs 6.5±4.1 μmol/L,366.1±114.3 μg/L vs 115.4±48.4 μg/L,569±283 mg/L vs 107±75.8 mg/L,差异均有统计学意义(t或χ²=7.78～18.75,均P<0.05)。Gensini低积分组、中积分组、高积分组HCY和Lp-PLA2水平为:39.6±20.2 μmol/L,50.7±26.4 μmol /L,68.5±31.8 μmol/L和245.4±88.3 μg/L,326.1±104.3 μg/L,459.4±113.5 μg/L,差异均有统计学意义(Z=5.81,15.25,均P<0.05)。冠状动脉1支病变组、2支病变组、3支及3支以上病变组HCY和Lp-PLA2水平为:48.6±27.2 μmol/L,47.8±23 μmol /L,74.1±38.6 μmol/L和201.4±73.5 μg/L,344.1±134.2 μg/L,530.6±255.3 μg/L,差异均有统计学意义(Z=5.63,17.91,均P<0.05),随Gensini积分的增加和冠状动脉病变支数的增多,HCY和Lp-PLA2水平升高,差异有统计学意义(t=5.43～16.57,均P<0.05),相关性分析显示Gensini积分与Lp-PLA2,HCY水平呈正相关(r=0.454,0.991,均P<0.05)。Lp-PLA2与HCY水平呈正相关(r=0.336,P<0.05)。结论 冠心病患者Lp-PLA2,HCY水平与冠状动脉病变程度呈正相关。     

Effect of resistance training on risk of coronary artery disease in women with multiple sclerosis

The effects of a lower‐extremity progressive resistance‐training program (PRT) on risk factors for coronary artery disease (CAD) were determined in patients with multiple sclerosis (MS). Twelve ambulatory women with MS (47.3±4.7 years; Expanded Disability Status Score (EDSS), 4.00±1.37) completed twice weekly lower‐body PRT for 8 weeks. Knee extensor and ankle flexor strength improved significantly (p<0.05) after training, and self‐reported fatigue decreased (p<0.05). Serum triglyceride concentrations decreased (p<0.05) but body‐weight and fatness, blood pressure, and serum glucose, total cholesterol and high‐density lipoprotein cholesterol were unchanged. However, the number of CAD risk factors that reached the clinical threshold for each subject declined after PRT, suggesting that resistance training can promote CAD risk reduction in ambulatory female MS subjects.     

Efficacy and tolerability of a nutraceutical combination of red yeast rice,guggulipid, and chromium picolinate evaluated in a randomized,placebo-controlled,double-blind study

Hypercholesterolemia is the major risk factor in the development of coronary heart disease. Coronary heart disease is a leading cause of morbidity and mortality in many countries worldwide. An increasing attention is now paid to nutraceuticals development for prevention and cure of dyslipidemia, especially for patients who do not wish to use chemical statins. The cholesterol lowering effect and the tolerability of NutraforChol®, a nutraceutical product containing red yeast rice extract, guggulipid extract and chromium picolinate, was evaluated on subjects who had total cholesterol level 200−239 mg/dL and LDL cholesterol level 100-159 mg/dL. In this study, a randomized, placebo-controlled, double-blind study which consisted of 4 weeks run-in period and 8 weeks treatment period was performed. Based on the study results, NutraforChol® effectively decreased total cholesterol (−15.9 %) and LDL level (-19.9 %) after two weeks consumption. The total cholesterol and LDL reduction were maintained during 8 weeks study period. At study termination (week 8), there was a significant difference between total cholesterol level of NutraforChol® treated group (173.5 ± 21.7 mg/dL) and placebo-treated group (204.5 ± 22.8 mg/dL) (p < 0.05). In addition, there was a significant difference between LDL level at week 8 in NutraforChol® group (115.5 ± 22.2 mg/dL) and placebo-treated group (145.1 ± 23.7 mg/dL) (p < 0.05). The tolerability of NutraforChol® was also evaluated. There were no significant changes (p > 0.05) on renal and liver function parameters between baseline and study termination. Thus, NutraforChol® may be considered as a complementary or alternative safe nutraceuticals for the treatment of mild dyslipidemic subjects.     

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.     

Association between lipoprotein(a) levels, apo(a) isoforms and family history of premature CAD in young Asian Indians

ObjectivesThe purpose of this study was to explore the association between lipoprotein (a) [Lp(a)] levels, apo(a) isoforms and family history of premature coronary artery disease (CAD) in young Asian Indians.Design and methods220 patients (age < 40 years) with angiographic evidence of CAD and 160 age matched healthy controls were enrolled for the study. Thirty one percent of the patients and 17% of the controls had positive family history (PFH) of premature CAD. Plasma Lp(a) levels were determined by ELISA and apo(a) isoform size was determined using high-resolution immunoblotting method.ResultsMedian plasma Lp(a) levels were 2.5 times higher in patients as compared to controls (30 mg/dL vs 12.7 mg/dL; p < 0.05). The patient group having a heterozygous apo(a) isoform pattern showed higher Lp(a) levels as compared to the homozygous group (44.0 ± 38.7 vs 28.0 ± 26.4 mg/dL; p < 0.001). Further low molecular weight apo(a) isoforms (LMW; < 22 KIV repeats) were prevalent among CAD patients with PFH as compared to negative family history (62% vs 14%, p < 0.05) and this group had the highest Lp(a) levels. Stepwise regression analysis showed that Lp(a) levels and not the apo(a) isoform size, entered the model as significant independent predictors of CAD in young Asian Indians.ConclusionsThis study suggests that elevated Lp(a) levels confer genetic predisposition to CAD in young Asian Indians. Thus determination of Lp(a) levels along with other risk factors should be used to assess overall risk for CAD in this ethnic group.     

Evolocumab and lipoprotein apheresis combination therapy may have synergic effects to reduce low‐density lipoprotein cholesterol levels in heterozygous familial hypercholesterolemia: A case report

A 49 years old woman (weight 68 kg, BMI 27.3 kg/m²) with heterozygous familial hypercholesterolemia (HeFH) and multiple statin intolerance with muscle aches and creatine kinase elevation, presented at the Outpatient Lipid Clinic of Verona University Hospital in May 2015. Hypercholesterolemia was firstly diagnosed during adolescence, followed in adulthood by a diagnosis of Cogan's syndrome, a rheumatologic disorder characterized by corneal and inner ear inflammation. No xanthomas, corneal arcus, or vascular bruits were detectable at physical examination. Screening for macrovascular complications did not reveal relevant damages. Ongoing medical therapy included salicylic acid, methylprednisolone, methotrexate, and protonic‐pump inhibitor. In the absence of specific lipid‐lowering therapy, plasma lipid levels at first visit were: total‐cholesterol = 522 mg/dL, LDL‐cholesterol = 434 mg/dL, HDL‐cholesterol = 84 mg/dL, triglycerides = 120 mg/dL, Lp(a) = 13 mg/dL. On December 2015, evolocumab 140 mg sc every 2 weeks was initiated. After a 24‐week treatment, the LDL‐cholesterol levels decreased by an average of 21.2% to 342 ± 22 mg/dL (mean ± SD). On May 2016, LDL‐apheresis (H.E.L.P.system) was started as add‐on therapy. Compared to the average levels obtained during the evolocumab monotherapy period, the LDL‐cholesterol was reduced by 49.4%, thus reaching an inter‐apheresis level (mean ± SD) of 173 ± 37 mg/dL. This report suggests that a combination therapy with evolocumab and lipoprotein‐apheresis may have synergic effects on circulating lipid levels. Its relevance as a highly effective treatment option for hyperlipidemia in HeFH patients warrants further investigation in larger datasets.