Low-density lipoprotein and apolipoprotein B: Clinical use in patients with coronary heart disease

Managing low-density lipoprotein (LDL) is an integral part of clinical practice. What remains controversial is whether we are using the best measure of LDL quantity for this purpose. Historically, the cholesterol content of LDL particles (LDLC) has been used to express LDL quantity. However, because of variability in the cholesterol carried in LDL particles, frequent disagreement occurs between LDLC and particle measures of LDL quantity, including apolipoprotein B-100 (apo B) or nuclear magnetic resonance (NMR) LDL particle number (LDL-P). Studies consistently demonstrate apo B and LDL-P are superior predictors of coronary heart disease (CHD) risk and superior indicators of low CHD risk on lipid-lowering therapy. Recent recommendations advocate that, in addition to LDLC and non-high-density lipoprotein cholesterol, apo B (or NMR LDL-P) be used as a target of therapy. This article reviews the rationale supporting these recommendations and provides a model for integrating LDL particle measures in clinical practice.     

Low-density lipoprotein cholesterol to apolipoprotein B ratio is independently associated with metabolic syndrome in Korean men

The low-density lipoprotein cholesterol to apolipoprotein B (LDL-C/apo B) ratio is associated with cardiovascular risk factors and the prevalence of metabolic syndrome. The aim of this study was to assess the relationship between LDL-C/apo B ratio and metabolic syndrome in Korean men. This study included 499 men (mean age, 49.1 years) without metabolic syndrome at baseline who were followed for an average of 2.9 years. Subjects were divided into 4 groups according to baseline LDL-C/apo B ratio quartiles: greater than 1.243 in group I, 1.164 to 1.243 in group II, 1.070 to 1.163 in group III, and less than 1.070 in group IV. The incidence of metabolic syndrome at follow-up was compared according to LDL-C/apo B ratio group. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. The overall incidence of metabolic syndrome was 9.6%: 1.6% in the highest quartile (group I), 9.7% in group II, 11.2% in group III, and 16.0% in the lowest quartile (group IV) (P = .001). In multivariable regression analysis model adjusting for age, lifestyle status, homeostasis model assessment of insulin resistance, LDL-C, and high-sensitivity C-reactive protein, groups II, III, and IV had significantly increased odds ratio for the incidence of metabolic syndrome compared with the highest LDL-C/apo B quartile (group I). The LDL-C/apo B ratio is independently associated with metabolic syndrome in Korean men, indicating that this ratio may provide additional information when assessing cardiometabolic risks and predicting future development of metabolic syndrome.     

Small dense low-density lipoprotein cholesterol is a useful marker of metabolic syndrome in patients with coronary artery disease

AIM: An evaluation of the relation between small dense low-density lipoprotein cholesterol (sd-LDL-C) levels measured by the heparin-magnesium precipitation method and metabolic syndrome (MetS). METHODS: We have prospectively measured sd-LDL-C levels by the heparin-magnesium precipitation method in 112 Japanese patients (male/female=80/32) with coronary artery disease (CAD) who received percutaneous coronary intervention (PCI). Patients were diagnosed with MetS according to modified Japanese criteria. RESULTS: A total of 36 patients (32%) met the criteria for MetS. Sd-LDL-C levels were significantly higher in the MetS group than non-MetS group (20.7 +/- 1.5 mg/dL vs. 17.1 +/- 1.0 mg/dL, p=0.042), especially among patients without lipid-lowering therapy (26.4 +/- 2.6 mg/dL vs. 17.5 +/- 1.5 mg/dL, p= 0.0034). Sd-LDL-C levels gradually increased with the number of components used to define MetS (0; 14.5 +/- 1.8 mg/dL, 1; 16.5 +/- 1.8 mg/dL, 2; 16.7 +/- 1.3 mg/dL, 3; 19.3 +/- 1.7 mg/dL, 4; 23.1 +/- 2.1 mg/dL, 5; 40.0 mg/dL, p=0.0071). High-sensitivity C-reactive protein (hs-CRP) levels were significantly higher in the patients with MetS (1.09 +/- 0.17 mg/L vs. 0.67 +/- 0.09 mg/L, p=0.0204). CONCLUSION: The sd-LDL-C level measured by the heparin-magnesium precipitation method is a useful marker of MetS in Japanese patients with CAD.     

Low-density lipoprotein apolipoprotein B100 turnover in hypopituitary patients with GH deficiency: a stable isotope study

BACKGROUND: Epidemiological studies suggest that hypopituitary patients have an increased risk for cardiovascular mortality. The dyslipidaemia associated with this condition is often characterised by an increase in total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol (LDL-C) and may contribute to these findings. The underlying mechanisms are not fully elucidated. MATERIALS AND METHODS: LDL apolipoprotein B (apoB) production rate and metabolic clearance rate were measured in seven patients with hypopituitarism (including GH deficiency) under stable conventional replacement therapy (three males and four females; age 40-16.1 years; body mass index 29.0-6.1 kg/m(2) (means +/- s.d.)) and seven age-, gender- and body mass index-matched control subjects with an infusion of 1-(13)C-leucine. Fasting lipid profile and lipid composition of LDL were also measured. RESULTS: Fasting TC, triglycerides (TG), high-density lipoprotein-C, LDL-C and free fatty acid concentrations were not different between hypopituitary patients and control subjects. LDL-TG (P < 0.006) and LDL-TG/LDL apoB ratio (P < 0.02) were significantly increased in hypopituitary patients. LDL apoB pool size was not statistically different between patients and control subjects. In the hypopituitary patients, LDL apoB metabolic clearance rate (P < 0.05) and LDL apoB production rate (P < 0.02) were lower than in the control subjects. CONCLUSIONS: The present results suggest that LDL apoB turnover and LDL composition is altered in hypopituitary patients. Whether these findings explain the increased risk for cardiovascular disease in hypopituitary patients remains to be established.     

Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease: a cohort study

BACKGROUND The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease(CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B(apoB), non-high-density lipoprotein cholesterol(non-HDL-C), low-density lipoprotein cholesterol(LDL-C), apoB/apolipoprotein A-1(apoA-1) and non-HDL-C/HDL-C for myocardial infarction(MI) in CAD patients treated with statins in the setting of secon...     

稳定型冠心病患者血清低密度脂蛋白胆固醇和载脂蛋白B浓度与SYNTAX评分的关系

目的探讨稳定型冠状动脉粥样硬化性心脏病(stable coronary artery disease,SCAD)患者血清低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)和载脂蛋白B浓度与SYNTAX评分的关系。方法回顾性选择2016年1月至2017年12月在宝鸡市中心医院接受冠状动脉造影检查确诊的SCAD患者150例作为研究对象,根据SYNTAX评分结果将患者分为0~22分组(低分组,n=80)、23~32分组(中分组,n=40)和33分以上组(高分组,n=30)。SYNTAX评分与不同临床特征间的相关性采用Spearman相关性分析和多元线性回归分析。结果3组患者血小板分布宽度(platelet distribution width,PDW)、红细胞分布宽度(red cell distribution width,RDW)、纤维蛋白原、总胆固醇、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)、LDL-C、脂蛋白a、载脂蛋白A1、载脂蛋白B、SYNTAX评分比较,差异有统计学意义(P<0.05)。Spearman相关性分析结果显示,SYNTAX评分与HDL-C、载脂蛋白A1呈负相关(P<0.05),与纤维蛋白原、总胆固醇、LDL-C、PDW、RDW、脂蛋白a、载脂蛋白B呈正相关(P<0.05)。多元线性回归分析结果显示,HDL-C、LDL-C、纤维蛋白原、载脂蛋白B均是影响冠状动脉病变的危险因素(P<0.05)。结论随着血清LDL-C、载脂蛋白B浓度的升高,SCAD患者SYNTAX评分升高,冠状动脉病变严重程度加重。血清LDL-C、载脂蛋白B浓度可作为判断SCAD患者冠状动脉病变严重程度的参考指标。     

Lipoprotein cholesterol, apolipoprotein A-I and B and lipoprotein (a) abnormalities in men with premature coronary artery disease.

The prevalence of abnormalities of lipoprotein cholesterol and apolipoproteins A-I and B and lipoprotein (a) [Lp(a)] was determined in 321 men (mean age 50 +/- 7 years) with angiographically documented coronary artery disease and compared with that in 901 control subjects from the Framingham Offspring Study (mean age 49 +/- 6 years) who were clinically free of coronary artery disease. After correction for sampling in hospital, beta-adrenergic medication use and effects of diet, patients had significantly higher cholesterol levels (224 +/- 53 vs. 214 +/- 36 mg/dl), triglycerides (189 +/- 95 vs. 141 +/- 104 mg/dl), low density lipoprotein (LDL) cholesterol (156 +/- 51 vs. 138 +/- 33 mg/dl), apolipoprotein B (131 +/- 37 vs. 108 +/- 33 mg/dl) and Lp(a) levels (19.9 +/- 19 vs. 14.9 +/- 17.5 mg/dl). They also had significantly lower high density lipoprotein (HDL) cholesterol (36 +/- 11 vs. 45 +/- 12 mg/dl) and apolipoprotein A-I levels (114 +/- 26 vs. 136 +/- 32 mg/dl) (all p less than 0.005). On the basis of Lipid Research Clinic 90th percentile values for triglycerides and LDL cholesterol and 10th percentile values for HDL cholesterol, the most frequent dyslipidemias were low HDL cholesterol alone (19.3% vs. 4.4%), elevated LDL cholesterol (12.1% vs. 9%), hypertriglyceridemia with low HDL cholesterol (9.7% vs. 4.2%), hypertriglyceridemia and elevated LDL cholesterol with low HDL cholesterol (3.4% vs. 0.2%) and Lp(a) excess (15.8% vs. 10%) in patients versus control subjects, respectively (p less than 0.05). Stepwise discriminant analysis indicates that smoking, hypertension, decreased apolipoprotein A-I, increased apolipoprotein B, increased Lp(a) and diabetes are all significant (p less than 0.05) factors in descending order of importance in distinguishing patients with coronary artery disease from normal control subjects. Not applying a correction for beta-adrenergic blocking agents, sampling bias and diet effects leads to a serious underestimation of the prevalence of LDL abnormalities and an overestimation of HDL abnormalities in patients with coronary artery disease. However, 35% of patients had a total cholesterol level less than 200 mg/dl after correction; of those patients, 73% had an HDL cholesterol level less than 35 mg/dl.     

Risk factors for coronary artery disease in patients with elevated high-density lipoprotein cholesterol

High high-density lipoprotein (HDL) levels protect against coronary artery disease (CAD) development. We hypothesized that patients with CAD and high HDL levels would have higher prevalence of other CAD risk factors compared with patients with CAD and normal HDL. We identified 41,982 patients from a single center with normal levels (40 to 60 mg/dl in men, 50 to 70 mg/dl in women) or high HDL levels (> or =70 mg/dl in men, > or =80 mg/dl in women) when last measured between January 2000 and April 2004. From this overall population, we characterized a cohort of 1,610 patients with CAD, including 98 patients with high HDL levels. We measured prevalence of traditional CAD risk factors by comparing these 98 patients with patients with CAD and normal HDL levels (n = 1,512). We performed manual chart review in patients (n = 196) matched 1:1 by age, gender, and HDL level to obtain further detail with regard to differences in family history and lifestyle factors. In patients with CAD, those with high HDL levels (98 of 1,610, 6.1%) were of similar age (71.1 vs 69.6 years, p = 0.23), had similar prevalence of hypertension (78.6% vs 88.7%, p = 0.30), lower levels of low-density lipoprotein (85.3 vs 90.9 mg/dl, p = 0.04) and triglycerides (87.1 vs 141.2 mg/dl, p <0.01), and a lower prevalence of diabetes (28.6% vs 38.4%, p = 0.05) compared with patients with normal HDL levels. In logistic regression models, patients with high HDL levels and CAD were less likely to have diabetes (adjusted odds ratio 0.60, 95% confidence interval 0.38 to 0.95, p = 0.03) or obesity (adjusted odds ratio 0.50, 95% confidence interval 0.25 to 0.99, p = 0.046) than patients with normal HDL levels and CAD. In conclusion, patients with high HDL and CAD had a similar or lower prevalence of traditional CAD risk factors compared with patients with normal HDL levels and CAD.     

Lipid lowering in patients with coronary artery disease: low density lipoprotein cholesterol and beyond

Now that the importance of LDL-C and its reduction are well established in the prevention of atherosclerotic vascular complications, we are moving to a new era in which physicians must pay more attention to factors beyond LDL-C lowering. More emphasis should be put on TRL and remnant lipoproteins as well as other contributors to the cardiovascular risk burden, such as thrombotic risk factors and impaired fibrinolysis. This should be carried out within the standard framework of a global approach to risk factor management in CAD patients.     

Association of the apolipoprotein B/apolipoprotein A-I ratio and low-density lipoprotein cholesterol with insulin resistance in a Chinese population with abdominal obesity

The aim of this study is to assess the relationships among the apolipoprotein B/apolipoprotein A-I ratio (apoB/apoA-I ratio), low-density lipoprotein cholesterol (LDL-C) and insulin resistance (IR) in a Chinese population with abdominal obesity. This is a population-based, cross-sectional study of 3,945 men and 2,141 women with abdominal obesity. Individuals were referred to a primary health service and recruited for analysis. IR was measured using a homeostasis model assessment of insulin resistance (HOMA2-IR) with a HOMA2 calculator. Metabolic syndrome (MetS) was diagnosed using International Diabetes Federation (IDF) criteria. Comparing the apoB/apoA-I ratio and lipid indices using the HOMA2-IR showed that the ratio, LDL-C, total cholesterol level (TC) and triglyceride level (TG) were higher; and the high-density lipoprotein cholesterol level (HDL-C) was lower in the fourth than in the first quartile in both sexes (p????0.001). After adjustment for age, HOMA2-IR was positively correlated with the apoB/apoA-I ratio, LDL-C, TC and TG; and negatively correlated with HDL-C in men (all p?<?0.0001). HOMA2-IR was also positively correlated with the apoB/apoA-I ratio, LDL-C, TC and TG; and negatively correlated with HDL-C in women (all p?<?0.01). After adjustment for age and LDL-C, HOMA2-IR was found to be correlated with the apoB/apoA-I ratio in both men and women (r?=?0.066 and 0.116, p?<?0.0001). After adjustment for age and the apoB/apoA-I ratio, HOMA2-IR was correlated with LDL-C in men and women (r?=?0.063 and 0.044, p?<?0.0001 and p?=?0.0431, respectively). Gender, age, LDL-C, BMI, HOMA2-IR and apoB/apoA-I were the covariates independently associated with presence of the MetS (Odds ratio, OR: 2.183, 1.034, 1.013, 1.157, 1.726 and 1.570, respectively; all p?<?0.05). In conclusion, the study showed that the apoB/apoA-I ratio and LDL-C were positively correlated with IR. Excluding reciprocal interactions, the apoB/apoA-I ratio and LDL-C were still significantly correlated with IR, but the apoB/apoA-I ratio showed a greater correlation with IR than LDL-C in women with abdominal obesity, compared with men with abdominal obesity. Both LDL-C and apoB/apoA-I were independent risk factors of MetS, and the apoB/apoA-I ratio was stronger in this regard than LDL-C for this obese population.     

载脂蛋白A-I／载脂蛋白B值对急性冠脉综合征患者的临床预测价值

目的探讨不同血脂成分及载脂蛋白A-I（apolipoproteinA-I,apoA-I）／载脂蛋白B（apolipoprotein B,apoB）值对急性冠状动脉（冠脉）综合征的临床预测价值。方法收集586例胸痛患者行冠脉造影术的资料,其中急性冠脉综合征组426例,另外160例造影阴性者为对照组。测定并比较两组三酰甘油（TG）,总胆固醇（TC）,高密度脂蛋白胆固醇（HDL-C）,低密度脂蛋白胆固醇（LDL-C）,apoA-I／apoB值及冠脉Gensini积分。结果急性冠脉综合征组apoA-I／apoB值明显高于对照组,差异有统计学意义（P〈0．05）。apoA-I／apoB值与冠脉病变支数负相关（r=0．152．P=0．031）。结论apoA-I／apoB值是急性冠脉综合征强有力的预测因子,且优于其他血脂指标。     

The myocardial oxygen supply/demand ratio in patients with and without coronary artery disease

This study was performed to assess the relationship between coronary sinus blood flow (by thermodilution) and myocardial oxygen demand (heart rate-systolic arterial pressure double product) during atrial pacing in patients with and without coronary artery disease. In 11 individuals with coronary artery disease, pacing was performed to ischemia, as reflected by electrocardiographic changes or lactate production; 8 patients without coronary artery disease served as controls. Coronary sinus blood flow (in ml/min) was similar for the two groups at rest. However, the increase in coronary blood flow from rest to peak pacing was less (P = 0.025) in those with coronary artery disease (50 ± 26 ml/min) than in controls (79 ± 26 ml/min). The ratio of coronary sinus blood flow to double product was the same at rest in both groups (11.1 ± 2.2 × 10^?3 controls, 11.6 ± 2.7 × 10^?3 coronary artery disease; NS). At peak pacing, it was unchanged in the controls (10.4 ± 2.0 × 10^?3) but fell in those with coronary artery disease (9.0 ± 2.5 × 10^?3; P = 0.002). The aortic-coronary sinus oxygen content difference was similar at rest in both groups and did not change in response to pacing in either group. Thus, in response to augmented myocardial oxygen demand, patients without coronary artery disease have an appropriate increase in coronary blood flow and myocardial oxygen supply, while in those with coronary artery disease who develop ischemia the increment in myocardial blood flow (and oxygen supply) is inappropriately low.     

Plasma apolipoprotein B levels predict platelet-dependent thrombosis in patients with coronary artery disease

Elevated plasma apolipoprotein B is a known risk factor for atherosclerotic coronary artery disease (CAD), however its relationship to arterial thrombosis is unexplored. We prospectively assessed apolipoprotein B and platelet-dependent thrombosis (PDT) in 42 CAD patients (37 men, 5 women, mean age 68 +/- 9 years), by exposing porcine aortic media to their flowing unanticoagulated venous blood for 5 min using an ex vivo perfusion (Badimon) chamber. PDT was significantly correlated with apolipoprotein B (r = 0.41, p = 0.009), intracellular magnesium levels (r = -0.46, p = 0.003) fasting blood glucose (r = 0.47, p = 0.002), and total cholesterol (r = 0.43, p = 0.006). PDT did not correlate with serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I or fibrinogen levels. These findings suggest that the positive relationship of elevated apolipoprotein B to CAD may be, in part, related to its prothrombotic effects.     

Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease

We aimed to examine postprandial dyslipidemia in normolipidemic patients with coronary artery disease (CAD) and the effects of treatment with an hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin). Subjects with angiographicaly established CAD were randomized to treatment for 12 weeks with 80 mg/d atorvastatin or placebo and the effects on markers of postprandial lipoproteins and low-density lipoprotein (LDL)-receptor binding determined. LDL-receptor binding was determined in mononuclear cells, as a surrogate for hepatic activity. Fasting levels of cholesterol (P <.001), LDL-cholesterol (P <.001), apolipoprotein (apo)B(48) (P =.019), remnant-like particle-cholesterol (RLP-C) (P =.032), and total postprandial apoB(48) area under the curve (AUC) (P =.013) significantly decreased with atorvastatin compared with placebo. Atorvastatin also significantly increased LDL-receptor binding activity (P <.001), and this was correlated with changes in fasting apoB(48) (r =.80, P =.01). We report that aberrations in chylomicron metabolism in normolipidemic CAD subjects are correctable with atorvastatin by a mechanism involving increased LDL-receptor activity. This effect may, in part, explain the cardiovascular benefit of statins used in clinical trials of CAD patients with normal lipid levels.     

Usefulness of apolipoprotein B/apolipoprotein A-I ratio to predict coronary artery disease independent of the metabolic syndrome in African Americans

Studies have demonstrated that the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio predicts cardiovascular risk better than any of the cholesterol indexes. A number of factors that define the metabolic syndrome (MS) differ across African-American and European-American ethnicities. We assessed the relation of the apoB/apoA-I ratio to MS and coronary artery disease (CAD) in 224 African Americans and 304 European Americans. The MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and CAD was assessed as ≥50% stenosis or a continuous cardiovascular score (0 to 75). The European Americans had a greater apoB/apoA-I ratio than the African Americans (1.15 vs 1.07, p = 0.008). The apoB/apoA-I ratio was associated with presence of the MS in both European Americans (odds ratio 5.9, 95% confidence interval 2.53 to 13.57, p <0.001) and African Americans (odds ratio 8.3, 95% confidence interval 3.52 to 19.25, p <0.001) and was greater in subjects with the MS than in those without the MS (1.21 vs 1.04, p <0.001, for European Americans and 1.20 vs 0.94, p <0.001, for African Americans). A stepwise increase was seen in the prevalence of the MS across the apoB/apoA-I ratio tertiles in both ethnic groups (chi-square = 13.1, p <0.001, for European Americans and chi-square = 19.6, p <0.001, for African Americans). On multiple regression analyses, the apoB/apoA-I ratio independently predicted CAD in African Americans (β = 0.242, p = 0.011). The cardiovascular score was significantly increased across the apoB/apoA-I ratio tertiles in the European-American subjects with the MS (p = 0.001). However, this association was seen in the African-American subjects without the MS (p = 0.023). In conclusion, the apoB/apoA-I ratio differed across ethnicities and was associated with presence of the MS in both groups. Among African Americans, an elevated apoB/apoA-I ratio independently predicted a greater risk of CAD.