Reference values of plasma apolipoproteins A-I and B, and association with nonlipid risk factors in the populations of two Canadian provinces: Quebec and Saskatchewan. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To determine the population distribution of apolipoproteins A-I and B, and the relationship of apolipoprotein B to lipid risk factors for coronary artery disease. DESIGN: A stratified random sample of men and women aged 18 to 74 years selected from the provinces of Saskatchewan and Quebec in 1989 and 1990. OUTCOME MEASURES: Plasma concentrations of apolipoproteins A-I and B, triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol and nonhigh density lipoprotein cholesterol for subjects who provided a fasting blood sample. MAIN RESULTS: Apolipoprotein B mean values increased with age from 0.80 g/L at age 18 to 24 years to a maximum of 1.16 g/L in the 45 to 54 year age group for men. For women, the values increased more gradually from 0.81 g/L for ages 18 to 24 to 1.19 g/L at ages 65 to 74 years. The distribution of apolipoprotein A-I was unrelated to age. Means for men varied from 1.35 g/L to 1.42 g/L and for women from 1.50 g/L to 1.61 g/L. Apolipoprotein B was strongly correlated with nonhigh density lipoprotein cholesterol (r2=0.89), and this was used to define apolipoprotein B concentrations less than 1.04 g/L as indicating low risk for coronary artery disease, from 1.04 g/L to less than 1.22 g/L as moderate risk, from 1.22 g/L to less than 1.40 g/L as high risk, and 1.40 g/L or greater as very high risk. The prevalence of high risk plasma apolipoprotein B levels was higher in men and women with triglycerides greater than 2.3 mmol/L. Apolipoprotein A-I was strongly correlated with high density lipoprotein cholesterol (r2=0.67), and this was use to identify apolipoprotein A-I concentrations of less than 1.20 g/L as a risk factor and 1.65 g/L or greater as an antirisk factor for coronary artery disease. The prevalence of apolipoprotein A-I of less than 1. 20 g/L was 19% in men and 6% in women, whereas the prevalence of apolipoprotein AI 1.65 g/L or greater was 9% in men and 28% in women. CONCLUSION: Reference values for plasma apolipoproteins A-I and B in a Canadian population random sample are given. Plasma apolipoprotein B and apolipoprotein A-I provide information that is complementary to that provided by low density lipoprotein and high density lipoprotein cholesterol levels.     

High prevalence of hypertriglyceridaemia and apolipoprotein abnormalities in coronary artery disease.

Serum lipids and apolipoproteins A-I and B were measured in 174 men aged less than 60 with angiographically confirmed coronary artery disease and in 572 healthy control men. Two thirds of the patients had raised age-corrected values of fasting serum cholesterol and/or triglyceride and/or a low high density lipoprotein (HDL) cholesterol compared with the controls. Eighteen (30%) of the 61 normolipidaemic patients had a concentration of serum apolipoprotein A-I below the 5th percentile of 233 controls. In normolipidaemic patients on beta blockers the relative prevalence of serum low density lipoprotein (LDL)-apolipoprotein B values above the 95th percentile of 339 controls was significantly increased. Discriminant function analysis showed that a raised concentration of serum triglyceride was the best discriminant between patients and controls, with raised LDL-apolipoprotein B and reduced apolipoprotein A-I coming second only to triglyceride in analyses where each was separately compared with all the lipid variables. These associations were highly significant and were independent of other influences, including beta blockade. These findings re-emphasise the importance of hypertriglyceridaemia as a risk factor and confirm that apolipoprotein abnormalities occur frequently in coronary disease, even in normolipidaemic patients.     

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.     

High prevalence of hypertriglyceridaemia and apolipoprotein abnormalities in coronary artery disease

Serum lipids and apolipoproteins A-I and B were measured in 174 men aged less than 60 with angiographically confirmed coronary artery disease and in 572 healthy control men. Two thirds of the patients had raised age-corrected values of fasting serum cholesterol and/or triglyceride and/or a low high density lipoprotein (HDL) cholesterol compared with the controls. Eighteen (30%) of the 61 normolipidaemic patients had a concentration of serum apolipoprotein A-I below the 5th percentile of 233 controls. In normolipidaemic patients on beta blockers the relative prevalence of serum low density lipoprotein (LDL)-apolipoprotein B values above the 95th percentile of 339 controls was significantly increased. Discriminant function analysis showed that a raised concentration of serum triglyceride was the best discriminant between patients and controls, with raised LDL-apolipoprotein B and reduced apolipoprotein A-I coming second only to triglyceride in analyses where each was separately compared with all the lipid variables. These associations were highly significant and were independent of other influences, including beta blockade. These findings re-emphasise the importance of hypertriglyceridaemia as a risk factor and confirm that apolipoprotein abnormalities occur frequently in coronary disease, even in normolipidaemic patients.     

Effect of mild aerobic exercise on serum lipids and apolipoproteins in patients with coronary artery disease

The effects of mild aerobic exercise on serum lipids, apolipoproteins and lecithin-cholesterol acyltransferase (LCAT) activity were examined in 11 male patients with coronary artery disease and 4 healthy male controls. The mild aerobic exercise program involved exercise intensity at 50% of maximal oxygen uptake, as determined from the blood lactate threshold, for 60 min periods 3 times per week for 10 weeks. Following mild aerobic exercise, serum levels of high density lipoprotein cholesterol (HDL-C) were increased significantly from 50 +/- 7 mg/dl to 59 +/- 11 mg/dl (p less than 0.05) with a simultaneous increase in apolipoprotein A-I (apo A-I) in normal controls. The LCAT activity was significantly increased from 65 +/- 22 nmol/ml/hr to 99 +/- 30 nmol/ml/hr in normal controls (p less than 0.05). Furthermore, maximal oxygen uptake (VO2max) was significantly increased in normal controls. In contrast, no significant changes were found in HDL-C, apo A-I, apo B, VO2max and body weight in patients with coronary artery disease. There was significant correlation between the initial HDL-C level and the change in HDL-C level following the exercise program in the combined group of normal controls and patients with coronary artery disease.     

Associations of abdominal adiposity, fasting insulin, sex hormone binding globulin, and estrone with lipids and lipoproteins in post-menopausal women

The associations of abdominal adiposity, fasting serum levels of insulin, and sex hormones with blood lipids, lipoproteins, and apolipoproteins A-I and B were studied cross-sectionally in 75 healthy, postmenopausal white women. In univariate analyses, abdominal adiposity (increased waist-to-hip girth ratio) and fasting insulin concentrations were negatively and significantly associated (P less than 0.05) with plasma high density lipoprotein cholesterol (r = -0.47 and -0.38, respectively) and apolipoprotein A-I (r = -0.37 and -0.36), and positively associated with log triglycerides (r = 0.54 and 0.33) and apolipoprotein B (r = 0.43 and 0.22). Sex hormone binding globulin was positively and significantly associated with high density lipoprotein cholesterol (r = 0.32) and negatively associated with log triglyceride (r = -0.45) and apolipoprotein B (r = -0.36). Estrone was positively and significantly associated with high density lipoprotein cholesterol (r = 0.27), apolipoprotein A-I (r = 0.23) and negatively associated with low density lipoprotein cholesterol (r = -0.24) and apolipoprotein B (r = -0.25). Total estradiol, free estradiol, free testosterone, and total testosterone were more weakly associated with the lipid measures. In multivariate analyses, abdominal adiposity remained significantly associated with high density lipoprotein cholesterol, log triglycerides, apolipoproteins A-I and B after adjustment for sex hormone binding globulin, estrone, and insulin concentrations. Insulin remained associated only with apolipoprotein A-I after adjustment for abdominal adiposity, estrone, and sex hormone binding globulin. Sex hormone binding globulin remained marginally associated with log triglyceride (P = 0.07) after adjustment for the remaining three factors. Estrone remained significantly associated with high density lipoprotein cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary artery disease is associated with the ratio of apolipoprotein A-I/B and serum concentration of apolipoprotein B, but not with paraoxonase enzyme activity in Iranian subjects

To determine the association of serum apolipoprotein (apo) A-I and B concentrations, and paraoxonase (PON) high-density lipoprotein (HDL) associated enzyme activity with angiographically determined coronary artery disease (CAD) in Iranian diabetic and non-diabetic CAD patients and non-diabetic control subjects, 251 subjects aged 30-70 years, who underwent their first coronary angiography were matched and randomly assigned into three groups: CAD(+)DM(+), CAD(+)DM(-), and CAD(-)DM(-) (control). Stenosis of > or =50% in one or more coronary arteries was classified as CAD(+). CAD(-) was defined as a maximum stenosis of 10% in any coronary artery. Fasting serum concentrations of cholesterol (TC), triglycerides (TGs), LDL-C, HDL-C, apo A-I/B and PON activity were determined. Apolipoprotein concentrations were measured in a fasting serum sample by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate. Information concerning non-lipid risk factors were collected by questionnaires. No significant difference was observed in HDL-C, LDL-C, apo A-I, and PON/arylesterase activity between the study groups. The values of TC (213+/-38 vs 196+/-45, P<0.05), TGs (209+/-187 vs 151+/-113, P<0.01), apo B (99+/-22 vs 96+/-24, P<0.0001), TC/HDL-C (4.8+/-1.5 vs 4.0+/-1.3, P<0.001) and LDL-C/HDL-C (2.9+/-1.1 vs 2.4+/-1.1, P<0.05) were higher and apo A-I/B (1.7+/-0.4 vs 2.0+/-0.6, P<0.01) was lower in CAD(+)DM(+) patients than in control subjects. In CAD(+)DM(-) group, only the level of apo B (96+/-24 vs 85+/-18, P<0.01), and the ratio of apo A-I/B (1.8+/-0.4 vs 2.0+/-0.6, P<0.01), were significantly higher than those of control group. On multiple logistic regression analysis, the best markers for discrimination between CAD(+) groups and CAD(-) control subjects were the ratio of apo A-I/B in diabetic and apo B in non-diabetic patients. The results suggest that in Iranian diabetic and non-diabetic patients with CAD the concentration of apolipoproteins are better markers than traditional lipid parameters in discriminating between CAD(+) and CAD(-) subjects. Lack of significant difference in PON activity between CAD patients and CAD(-) controls supports the concept of interethnic variability in PON polymorphism and unimodal distribution of its activity in non-Europid populations observed in other studies.     

Association between plasma lipids, and apolipoproteins and coronary artery disease: a cross-sectional study in a low-risk Korean population

BACKGROUND: Due to the lower level of the traditional lipid profiles in Koreans than in the series of patients from the western countries, the need to investigate other lipid parameters to help identify the individuals at high risk of CAD has been emphasized. AIM AND METHODS: To investigate whether apolipoprotein B (apo B), apolipoprotein A-I (apo A-I) and their ratio give additional information to the traditional lipid risk factors for discriminating the individuals at high-risk for coronary artery disease (CAD), 544 subjects, who met the lipid criteria of total cholesterol (TC) <230 mg/dl, low-density lipoprotein cholesterol (LDL-C) <120 mg/dl and high-density lipoprotein cholesterol (HDL-C) >40 mg/dl were recruited. Patients were considered to be CAD(+) if they had > or =50% stenosis in at least one coronary artery. RESULTS: In men, TC and apo B/apo A-I ratio were significantly different between groups with and without CAD after adjusting for age and diabetes (P = 0.037 and 0.035), and in women, triglyceride (TG), HDL-C and apo B/apo A-I ratio were significantly different after adjusting for age, diabetes and smoking status (P = 0.006, 0.007 and 0.030, respectively). In the lowest quartile of TC, TG and LDL-C, and the highest quartile of HDL-C, only apo B/apo A-I ratio was associated with CAD in both men and women. The only variable showing a significant difference between patients with and without CAD was apo B/apo A-I ratio. In models assessing whether apolipoproteins give additional information to traditional lipid risk factors, HDL-C, LDL-C, apo B/apo A-I ratio and in women but not in men, TG and apo B were all independent markers for the presence of CAD. Among the nontraditional lipid factors, only apo B/apo A-I ratio showed its additional value for identifying the presence of CAD. CONCLUSION: Apo B/apo A-I ratio is the only variable that differentiates the patients with CAD from those without and, furthermore, gives additional information to that supplied by traditional lipid risk factors in a low-risk Korean population.     

The levels of lipids, lipoproteins and apolipoproteins in healthy people in the central region of the Black Sea

Lipids, lipoproteins and apolipoproteins are among the risk factors for the most serious health problem of the age--coronary artery disease (CAD). They vary from country to country, from area to area within a country, depending on genetic, environmental, dietary and many other factors. Our aim was to determine the levels of lipids, lipoproteins and apolipoproteins in healthy people in the central Black Sea region of Turkey. Subjects included 1348 volunteers (682 women, 666 men) referred to the Medical Faculty hospital from the study area. The population consisted of healthy people or those whose disease was not affecting the metabolism of lipids. Cholesterol, triglyceride and HDL-cholesterol levels in the obtained serum samples were measured spectrophotometrically, while apolipoprotein A-I, apolipoprotein B, apolipoprotein E and lipoprotein(a) levels were measured nephelometrically. The levels of lipid parameters were as follows: total cholesterol for men was 4.22 +/- 1.00 mmol/l (mean arithmetic +/- SD), triglyceride 1.20 mmol/l (0.30-4.44) [geometric mean (range)], HDL-cholesterol 0.88 +/- 0.22 mmol/l, LDL-cholesterol 2.69 +/- 0.85 mmol/l, apolipoprotein A-I 1.26 +/- 0.22 mmol/l apolipoprotein B 1.12 +/- 0.32 mmol/l, apolipoprotein E 0.037 +/- 0.012 mmol/l and lipoprotein(a) 0.25 g/l (0.03-2.75); total cholesterol for women was 4.53 +/- 1.00 mmol/l, triglyceride 1.05 mmol/l (0.28-4.50), HDL-cholesterol 1.08 +/- 0.26 mmol/l, LDL-cholesterol 2.87 +/- 0.88 mmol/l, apolipoprotein A-I 1.45 +/- 0.25 mmol/l, apolipoprotein B 1.11 +/- 0.31 mmol/l, apolipoprotein E 0.039 +/- 0.011 mmol/l and lipoprotein(a) 0.22 g/l (0.03 2.16). In conclusion, our study in four different regions in Turkey reflected that the people living in the central Black Sea region are less vulnerable to the risk of CAD, although at a relatively higher risk compared to some other countries.     

Influence of probucol administration on lipoprotein cholesterol and apolipoproteins in normolipemic males

In order to interpret the known lipoprotein changes in probucol-treated patients, serum concentrations of apolipoproteins (A-I, A-II, B, C-II, C-III, E) were measured before, during and after probucol administration (2 X 500 mg p.d.), in 16 healthy males (30.3 +/- 5.6 years old). Cholesterol concentrations were determined in LDL and VLDL fractions as well as in HDL subfractions which were isolated by preparative ultracentrifugation. In addition, apolipoprotein A-I and A-II concentrations were measured in the HDL subfractions. Compared with the baseline values, significant apolipoprotein changes were found in the serum apolipoprotein A-I (151 +/- 18 to 115 +/- 31 mg/dl; P less than 0.001) and C-II levels during administration. The HDL subfraction analysis showed that the decrease of HDL-cholesterol and apolipoprotein A-I (59.9 +/- 23.5 to 34.4 +/- 16.4 mg/dl, P less than 0.001, and 65.7 +/- 49.0 to 37.5 +/- 23.5 mg/dl, P less than 0.05, respectively) was predominantly related to the HDL2b subfraction (d = 1.063-1.100 g/ml).     

Clinical significance of measurements of serum apolipoprotein A-I, A-II and B in hypertriglyceridemic male patients with and without coronary artery disease

To examine the relationship of hypertriglyceridemia to coronary artery disease (CAD), we measured serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and apolipoproteins (apo) A-I, A-II and B in 82 male patients with angiographically defined CAD and 140 age-matched healthy controls. The CAD patients had significantly lower apo A-I and A-II and HDL-C levels, but had higher apo B and triglyceride levels than the controls. After adjustments of apolipoproteins for serum triglyceride, CAD patients had significantly higher apo B and lower apo A-I and A-II levels than the controls. Discriminant analysis showed that apo B was the best discriminator and that apo A-I was next. In the normotriglyceridemic subgroup HDL-C also had a sufficient power for discrimination between CAD patients and the controls, but in the hypertriglyceridemic subgroup HDL-C had no discriminative power. Both apo A-I and B had significant discriminative power between CAD patients and the controls, independently of the serum triglyceride level. These results indicate that measurements of serum apo A-I and apo B are useful for the study of coronary risk factor in hypertriglyceridemic subjects. Finally, it is necessary to sub-classify dyslipoproteinemia by serum apolipoprotein levels for predicting the future occurrence of CAD in the general population.     

The Effect of Alcohol Withdrawal on Serum Concentrations of Lp(a), Apolipoproteins A-1 and B, and Lipids

Moderate alcohol consumption is associated with a decreased risk of coronary artery disease. The mechanism of the putative protective effect of alcohol intake, however, remains elusive. Recent studies suggest that a ratio of apolipoprotein A-I/apolipoprotein B and Lp(a) are better indicators of the risk of atherosclerosis than total cholesterol and high density lipoprotein cholesterol. To assess the effect of alcohol on these analytes, we determined the concentration of Lp(a), apolipoprotein A-I, apolipoprotein B, total cholesterol, and high-density lipoprotein cholesterol, and calculated low-density lipoprotein cholesterol in serum of 12 patients meeting DSM-III-R criteria for alcohol dependence at the time of admission for treatment of alcohol withdrawal (before). The analyses were repeated after 4 weeks of supervised abstinence on a locked research unit (after). With abstinence, there was a significant increase in the concentration of Lp(a), the atherogenic index and the ratio of low-density to high-density lipoprotein cholesterol but a significant decrease in total cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-I, and the apolipoprotein A-I/B ratio. Apolipoprotein B and low-density lipoprotein cholesterol showed no significant changes before and after alcohol abstinence. Thus, decreased Lp(a) and increased high-density lipoprotein cholesterol and apolipoprotein A-I may be factors mediating the putative protective effect of alcohol in coronary artery disease.     

Association of lipids, lipoproteins, apolipoproteins and paraoxonase enzyme activity with premature coronary artery disease

BACKGROUND AND DESIGN: The association of serum apolipoprotein (apo) A-I and apo B concentrations and paraoxonase (PON) enzyme activity with angiographically determined coronary artery disease (CAD) was investigated in Iranian non-diabetic patients with premature CAD and control participants in a sex- and age-matched case-control study. METHODS: The study population consisted of 59 non-diabetic patients with premature CAD and 55 CAD control participants. Premature CAD was defined as the presence of angiographically proven coronary stenosis (> or =50% involvement) in men and women younger than 55 and 65 years, respectively. Apolipoprotein concentrations were measured by immunoturbidometric assay and paraoxonase/arylesterase activities by spectrophotometric assay of p-nitrophenol/phenol production following addition of paraoxon/phenylacetate to serum. RESULTS: In CAD patients, increased concentrations of total cholesterol (215 +/- 43 compared with 193 +/- 43, P < 0.001), low-density lipoprotein cholesterol (137 +/- 46 compared with 116 +/- 39, P < 0.05) and apo B (102 +/- 24 compared with 84 +/- 17, P < 0.001) and a decreased ratio of apo A-I/apo B (1.7 +/- 0.4 compared with 2.0 +/- 0.6, P < 0.001) were observed compared to the control group. Other study variables were not significantly different between the two groups. On multiple logistic regression analysis, the only marker for discrimination between the CAD+ group and the CAD- control group was apo B level. CONCLUSIONS: In Iranian non-diabetic patients with premature CAD, the concentration of apo B is a better marker than traditional lipids in discriminating between CAD+ and CAD- patients. The lack of significant difference in PON activity between CAD patients and control participants supports the concept of interethnic variability in PON activity and gene polymorphism observed in other studies.     

Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age

PURPOSE: Because the effects of androgen replacement on lipoprotein levels are uncertain, we sought to determine the effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in elderly men. SUBJECTS AND METHODS: One hundred and eight healthy men more than 65 years of age who had serum testosterone concentrations >1 SD below the mean for young men were randomly assigned to receive either testosterone (54 men; 6 mg/day) or placebo (54 men) transdermally in a double-blind fashion for 36 months. Serum concentrations of lipids and apolipoproteins were measured, and cardiovascular events recorded. RESULTS: Serum total cholesterol concentrations decreased in both the testosterone-treated men and placebo-treated men, but the 3-year mean (+/- SD) decreases in the two groups (testosterone treated, -17 +/- 29 mg/dL; placebo treated, -12 +/- 38 mg/dL) were not significantly different from each other (P = 0.4). Similarly, serum low-density lipoprotein (LDL) cholesterol levels decreased in both treatment groups, but the decreases in the two groups (testosterone treated, -16 +/- 24 mg/dL; placebo treated, -16 +/- 33 mg/dL) were similar (P = 1.0). Levels of high-density lipoprotein (HDL) cholesterol, triglycerides, and apolipoproteins A-I and B did not change. Lipoprotein(a) levels increased in both groups by similar amounts (testosterone treated, 3 +/- 9 mg/dL; placebo treated, 4 +/- 6 mg/dL; P = 1.0). The number of cardiovascular events was small and did not differ significantly between the testosterone-treated men (9 events) and the placebo-treated men (5 events) during the 3-year study (relative risk = 1.8; 95% confidence interval: 0.7 to 5.0). CONCLUSIONS: As compared with placebo, transdermal testosterone treatment of healthy elderly men for 3 years did not affect any of the lipid or apolipoprotein parameters that we measured. The effect of testosterone treatment on cardiovascular events was unclear, because the number of events was small.     

Effect of alcohol intake on human apolipoprotein A-I-containing lipoprotein subfractions

High-density lipoprotein comprises two main types of lipoprotein particles: (1) those that contain apolipoproteins A-I and A-II, designated LpA-I:A-II, and (2) those that contain apolipoprotein A-I but not apolipoprotein A-II, designated LpA-I. Both have been extensively studied and are believed to represent distinct metabolic entities that may confer differing protection against coronary artery disease risk. We have previously suggested that LpA-I might represent the antiatherogenic effect, which has been ascribed mainly to its effect on high-density lipoprotein cholesterol; we set out to investigate, in 344 men, the relation between LpA-I:A-II and LpA-I levels and alcohol consumption. As the alcohol intake rose, LpA-I:A-II levels increased, while LpA-I levels fell. On the assumption that LpA-I is the antiatherogenic fraction of high-density lipoprotein, the putative protective action of alcohol consumption against coronary artery disease should be reconsidered.     

Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy

To assess whether subclinical hypothyroidism is associated with changes in lipoprotein fractions, 13 patients maintained in a stable state of subclinical hypothyroidism for at least 3 months were studied prior to and 2 and 4 months following restoration of a euthyroid state with incremental levothyroxine sodium therapy. Thyrotropin levels ( +/- SEM) had decreased from 16.6 +/- 3.2 mU/L to 3.1 +/- 0.7 mU/L and 3.2 +/- 0.7 mU/L at 2 months and 4 months. At 2 months, levothyroxine treatment led to a decrease in levels of total cholesterol from 5.5 +/- 0.3 mmol/L (213 +/- 12 mg/dL) to 4.8 +/- 0.3 mmol/L (186 +/- 12 mg/dL), in low-density lipoprotein cholesterol (LDL-C) from 3.7 +/- 0.3 mmol/L (143 +/- 12 mg/dL) to 2.9 +/- 0.3 mmol/L (112 +/- 12 mg/dL), and in apolipoprotein B from 91 +/- 8 mg/dL to 74 +/- 7 mg/dL. At 4 months, levels of LDL-C and apolipoprotein B remained significantly lower than pretreatment values (2.9 +/- 0.2 mmol/L [112 +/- 8 mg/dL] and 75 +/- 6 mg/dL, respectively). While high-density lipoprotein cholesterol (HDL-C), HDL3-C, and apolipoprotein A-I were not significantly affected by levothyroxine therapy, there was a slight trend of increase in HDL2-C during levothyroxine substitution. There was also a tendency for a decrease in triglyceride levels from 1.3 +/- 0.2 mmol/L (115 +/- 18 mg/dL) to 0.9 +/- 0.1 mmol/L (80 +/- 9 mg/dL) at 4 months of levothyroxine therapy. Levels of HDL-C tended to decrease from 4.8 +/- 0.4 mmol/L (186 +/- 15 mg/dL) to 4.5 +/- 0.5 mmol/L (174 +/- 19 mg/dL) at 2 months and to 3.9 +/- 0.4 mmol/L (151 +/- 15 mg/dL) at 4 months. The LDL-C/HDL-C ratio also decreased from 3.3 +/- 0.3 mmol/L (128 +/- 12 mg/dL) to 2.9 +/- 0.5 mmol/L (112 +/- 19 mg/dL) and 2.5 +/- 0.3 mmol/L (97 +/- 12 mg/dL) at 2 months and 4 months, respectively. These results suggest that long-term levothyroxine therapy in patients with subclinical hypothyroidism is associated with a decrease in LDL-C and apolipoprotein B levels that are reflected in a trend of decreases in cholesterol/HDL-C and LDL-C/HDL-C ratios known to have a relationship with coronary artery disease.     

Apolipoprotein A-I and apolipoprotein B containing lipoprotein particles in coronary patients treated with extracorporal low density lipoprotein precipitation (HELP).

Evidence for chemical and biological heterogeneity of human plasma lipoprotein density classes has been steadily accumulating over the last 15 years. Furthermore, several recent reports have indicated potential clinical significance of certain lipoprotein subspecies as either atherogenic or antiatherogenic. It is generally accepted that lipid lowering treatments can retard or even reverse development of atherosclerotic lesions. However, very little is known about effects of various lipid lowering treatments on specific lipoprotein particles. The purpose of this study was to explore the effects of heparin induced extracorporal low density lipoprotein precipitation (HELP) on various subspecies of plasma lipoprotein particles defined primarily by their apolipoprotein composition. Using particle specific enzyme immunoassays, the immediate changes in lipoprotein particle profiles were analyzed after a single HELP treatment in 12 patients with angiographically documented coronary artery disease. In a separate group of 6 patients, particles were repeatedly measured over a period of 96 h following a HELP treatment. Single HELP treatment caused an immediate and highly significant decrease (67%) in the concentration of simple lipoprotein particles containing apolipoprotein B (apo B) as a sole apolipoprotein (LP-B). Various subspecies of complex particles containing apo B and other apolipoproteins (Lp-B-complex) were also decreased although to a lesser degree (44-53%). HELP treatment caused an insignificant, 3% decrease of lipoprotein particles containing apo A-I but no apo A-II (Lp-A-I) and a 6% decrease in the concentration of particles containing both apo A-I and apo A-II (Lp-A-I:A-II). During the 96-h period following HELP treatment various apo B containing particles recovered at different rates in different patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

The effect of age, sex, alcohol consumption and cigarette smoking on serum concentrations of lipids and apolipoproteins in Zimbabwean blacks

Serum concentrations of total cholesterol, HDL cholesterol, triglycerides and apolipoproteins A-I and B were studied in black subjects with no known risk factor for coronary heart disease and in subjects with a single risk factor. The concentrations of lipids and apolipoproteins were sex-dependent. HDL cholesterol and apolipoprotein A-I were age-dependent in females (P less than 0.05 and P less than 0.01, respectively). There was a dose-related association between alcohol consumption and serum concentrations of triglycerides, HDL cholesterol, apolipoproteins A-I and B in males (P less than 0.001 and P less than 0.002, respectively in the heavy drinkers). The effects of cigarette smoking on the concentrations of serum lipids and apolipoproteins appear to be prominent in the heavy smoking subjects (P less than 0.001 and P less than 0.001, respectively). This work suggests that HDL cholesterol and apolipoprotein A-I may discriminate black subjects at risk of developing atherosclerosis.     

Polymorphisms in the apolipoprotein B-100 gene: association with plasma lipid concentration and coronary artery disease

BACKGROUND: The aim of this study was to investigate the association of apolipoprotein B gene polymorphisms with coronary artery disease and lipid levels in Indians. METHODS AND RESULTS: One hundred patients of angiographically proven atherosclerotic coronary artery disease and one hundred age- and sex-matched control subjects (treadmill negative) were included in the study. Serum lipids including cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, and apolipoprotein B were analyzed. Genomic DNA was extracted and the apolipoprotein B 3' hypervariable region amplified by polymerase chain reaction. Regions carrying Xba1, EcoR1, and Msp1 restriction sites present in the apolipoprotein B gene were amplified and digested separately by the respective enzymes. Restriction fragment length polymorphism analysis showed that EcoR1 with the R+/R+ genotype was significantly more common in patients with coronary artery disease. Overall, the genotypes EcoR1+/+, Msp1+/+, Xba1+/+ and Eco R1+/+ Msp1+/-, Xba1-/- were significantly more common in patients as compared to controls (p<0.05). When gene polymorphisms were compared with lipid abnormalities, the genotypes EcoR1+/+, Xba1-/-, and Msp1+/+ were more frequent in patients with elevated apolipoprotein B and very low-density lipoprotein levels. On the other hand, these genotypes were less common in patients with increased total cholesterol and low-density lipoprotein levels. When we studied the individual alleles of the variable number of tandem repeats region, we observed that allele 34 was significantly increased in patients with coronary artery disease as compared to controls. Allele 36 was present with a frequency of 1% in controls while it was totally absent in patients. CONCLUSIONS: This study identifies the apolipoprotein B gene polymorphism associated with coronary artery disease. An association between apolipoprotein B gene polymorphisms and elevated apolipoprotein B and very low-density lipoprotein levels was observed. However, there was no positive association with other elevated lipid levels in North Indians from Uttar Pradesh.     

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.