Apolipoprotein concentrations during treatment and recurrent coronary artery disease events

The effect of untreated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) as cardiovascular risk factors in both primary and secondary prevention has been extensively investigated. The predictive value of on-treatment lipid and apolipoprotein levels on subsequent cardiovascular events is as yet uncertain. Eight hundred forty-eight patients (675 men and 173 women) with angiographically proven coronary artery disease (CAD) who received effective statin therapy (>/=30% decrease of baseline TC) were studied. We analyzed the predictive value of on-treatment levels of TC, LDL-C, triglycerides (TG), apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) on subsequent myocardial infarction (MI) and all cause mortality. On-treatment LDL-C levels were 2.55+/-0.55 mmol/L and 2.58+/-0.62 mmol/L for men and women respectively. Age-adjusted Cox regression analysis showed that only on-treatment apoA-I was predictive for future CAD events in both men and women, whereas on-treatment HDL-C was exclusively predictive in women. On-treatment apoB levels were predictive for recurrent CAD events in the total population but not after separate analysis for men and women. On-treatment levels of TC, LDL-C, and TG did not predict subsequent events. Multivariate analysis showed that on-treatment apoA-I and apoB were the only significant predictors for future cardiovascular events. On-treatment levels of TC, LDL-C, and TG were no longer associated with increased risk of recurrent cardiovascular events in CAD patients treated to target levels, which justifies the current guidelines. However, on-treatment levels of apoB and in particular apoA-I (and HDL-C in women) were significantly predictive for MI and all-cause mortality and may therefore be more suitable for cardiovascular risk assessment in this population.     

Effects of age and cigarette smoking on serum concentrations of lipids and apolipoproteins in a male military population

The effects of age and cigarette smoking on lipids and apolipoproteins were studied in men, 20-65 years old, randomly selected from a military population in the Madrid area, Spain. Subjects were classified as non-smokers, medium smokers (10-20 cigarettes/day) and heavy smokers (more than 20 cigarettes/day). Smoking prevalence was 58%. Serum apolipoprotein A-I and HDL-cholesterol (HDL-C) were not age-dependent, while total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C) and the TC/HDL-C ratio increased with age. None of the variables studied was age-dependent over 30 years. The effects of smoking on TC, TG, LDL-C, HDL-C, TC/HDL-C ratio, apolipoprotein A-I, apolipoprotein B, and apo A-I/apo B ratio in the 20-29-year-old group appeared to be prominent in heavy smokers (P values less than 0.001, less than 0.05, less than 0.01, less than 0.05, less than 0.001, less than 0.05, less than 0.01 and less than 0.05, respectively) but not in medium smokers, in which only TG increased significantly (P less than 0.001). Few differences were noted between non-smokers and smokers over 30 although the TC/HDL-C ratio did increase in heavy smokers (P less than 0.05).     

Influence of triglyceride concentration on the relationship between lipoprotein cholesterol and apolipoprotein B and A-I levels

A sample of 2,103 men aged 47 to 76 years from the Québec Cardiovascular Study cohort was examined to quantify the influence of plasma triglyceride (TG) levels on the relationship between plasma lipoprotein cholesterol and either apolipoprotein A-I (apo A-I) or apo B concentrations. Regression analyses between high-density lipoprotein cholesterol (HDL-C) and apo A-I through TG tertiles showed highly significant correlations (.62 < or = r < or = .75, P < .0001) in all TG tertiles between these 2 variables. The associations for plasma apo B versus low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels were also studied on the basis of TG concentrations, and correlation coefficients between either LDL-C or non-HDL-C and apo B were essentially similar among TG tertiles (.78 < or = r < or = .85 and .83 < or = r < or = .86 for LDL-C and non-HDL-C, respectively, P < .0001). Regression analyses also showed that lower HDL-C levels were found for any given apo A-I concentration among men in the 2 upper TG tertiles, whereas lower LDL-C concentrations were observed at any given apo B level among subjects in the upper TG tertile. We further investigated whether there were synergistic alterations in the HDL-C/apo A-I and LDL-C/apo B ratios as a function of increasing plasma TG. A significant association was noted between these 2 ratios (r = .37; P < .0001). Mean HDL-C/apo A-I and LDL-C/apo B ratios were then calculated across quintiles of plasma TG concentrations. Increased TG concentrations were first associated with a reduced HDL-C/apo A-I ratio, followed by a decreased LDL-C/apo B ratio. These results suggest that a relatively modest increase in TG may rapidly alter the relative cholesterol content of HDL particles. Finally, the cholesterol content of the non-HDL fraction appears to be influenced less by TG levels than HDL-C and LDL-C fractions. Thus, the plasma apo B-containing lipoprotein cholesterol level may provide a better index of number of atherogenic particles than the LDL-C concentration, particularly in the presence of hypertriglyceridemia (HTG).     

Dyslipoproteinemia in patients with active rheumatoid arthritis: effects of disease activity, sex, and menopausal status on lipid profiles

OBJECTIVE: To investigate the lipid profiles in patients with active rheumatoid arthritis (RA) and to assess the relationship of inflammatory disease activity markers, sex, and menopausal status with lipid profiles. METHODS: Three groups of patients with active RA (n = 184) were studied: men (n = 61, mean age 50.8 +/- 4.81 yrs), premenopausal women (n = 58, mean age 39.2 +/- 2.44 yrs), and postmenopausal women (n = 65, mean age 60.4 +/- 2.14 yrs), and healthy controls (n = 161): men (n = 65, mean age 50.9 +/- 3.42 yrs), premenopausal women (n = 47, mean age 40.3 +/- 1.66 yrs), and postmenopausal women (n = 49, mean age 61.3 +/- 3.16 yrs). We measured fasting plasma levels of total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), lipoprotein (a) [LP(a)], apolipoprotein A1 (apo A1), apolipoprotein B (apo B), and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). RESULTS: Male RA patients had significantly higher apo B/apo A1 and LP(a) and lower HDL-C than male controls. Female RA patients had significantly higher TC, LDL-C, and LP(a) than female controls. Premenopausal RA patients had significantly higher LDL-C, TC/HDL-C, LDL-C/HDL-C, and apo B/apo A1 and lower TG and HDL-C than premenopausal controls. Postmenopausal RA women had significantly higher TG and LP(a) and lower TC than postmenopausal controls. Female RA patients had higher HDL-C, apo A1, and TC/HDL-C and lower apo B/apo A1 than male RA patients. Postmenopausal RA patients had significantly higher TC, TG, TC/HDL-C, apo B, LP(a), and LDL-C/HDL-C than premenopausal RA patients. CRP correlated positively with TC/HDL-C, LDL-C/HDL-C, and apo B/apo A1 and negatively with HDL-C in male RA patients. In female RA patients CRP had positive correlation with TC/HDL-C and LDL-C/HDL-C and negative correlation with HDL-C. CONCLUSION: These findings suggest that patients with active RA have altered lipid profiles and that disease activity, sex, and menopausal status affect lipid profiles, and these would be expected to change the pattern of atherosclerotic events in RA.     

Subclinical hypothyroidism and lipid abnormalities in older women attending a vascular disease prevention clinic: effect of thyroid replacement therapy

The authors evaluated the frequency and type of lipid disorders associated with subclinical hypothyroidism (SH) in older women referred to their university vascular disease prevention clinic. They also assessed the results of thyroid replacement therapy. Fasting serum lipid profiles and thyroid function tests were measured in 333 apparently healthy women (mean age: 71.8 +/- 7 years). These women were divided into 3 groups: group I: 60-69 years old (n = 132); group II: 70-79 years old (n = 153); group III: 80-89 years old (n = 48). SH was defined as a serum thyrotropin concentration higher than 3.20 mlU/mL with a normal free thyroxine concentration. The prevalence of SH was 7.5%. Thyrotropin was higher than 3.20 mU/mL in 25 women; 7 (5.3%), 14 (9.2%), and 4 (8.3%) in groups I, II, and III, respectively. Low-density lipoprotein cholesterol (LDL-C) concentrations were higher in the women with SH (p = 0.037). The mean values of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/HDL-C ratio, lipoprotein (a) (Lp[a]), apolipoprotein A-I (apo AI) apolipoprotein B100 (apo B) and apo B/apo A ratio were higher and triglycerides (TG) were lower, compared with those with normal levels of thyrotropin. However, none of these differences reached significance. Restoration of euthyroid status (thyroxine: 50-100 microg/day) in 17 SH women significantly improved TC (p = 0.017), LDL-C (p = 0.014), TC/HDL-C (p = 0.05), LDL-C/HDL-C (p = 0.03), apo B (p = 0.013), and Lp(a) (p = 0.0005) values. SH is relatively common in older women attending a vascular disease prevention clinic. Thyroid hormone replacement therapy significantly improved serum lipids. In particular, the reduction in LDL-C and Lp(a) concentrations may be of clinical benefit.     

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 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.     

Randomized dose-response study of rosuvastatin in Japanese patients with hypercholesterolemia

Rosuvastatin is a novel statin that has been shown to produce large dose-dependent reductions in low-density lipoprotein cholesterol (LDL-C) in Western hypercholesterolemic patients. Rosuvastatin dose response was assessed in a randomized, double-blind phase II trial in which 112 Japanese patients with fasting LDL-C > 160 and < 220 mg/dl and triglycerides < 300 mg/dl received placebo or rosuvastatin 1, 2.5, 5, 10, 20, or 40 mg once daily for 6 weeks. LDL-C change from baseline showed a linear dose response (p < 0.0001 for slope of regression line) over the rosuvastatin dose range, with each doubling of dose producing an additional 5.12% reduction. Mean reductions (least-squares mean percentage change from baseline from ANOVA) in LDL-C were 35.8% to 66.0% and significantly different from placebo at all doses (p < 0.0001). Linear dose response was also observed for total cholesterol (TC) and apolipoprotein (apo) B, but not for triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or apo A-I or A-II. Mean changes at 6 weeks were - 25.5 to - 45.1% for TC, - 16.0 to - 26.2% for TG, + 7.5 to + 12.8% for HDL-C, - 31.9 to - 57.8% for apo B, + 5.5 to + 10.0% for apo A-I, and + 0.4 to + 8.1% for apo A-II. Rosuvastatin was well tolerated. Although there was some suggestion of increased frequency of treatment-related adverse events at higher doses, there were no clear dose relationships in safety parameters. Only one patient withdrew from the study because of a treatment-related adverse event. No patients had clinically significant elevations in liver transaminases or creatine kinase. Rosuvastatin produces good dose-related reductions in LDL-C and beneficial changes in other lipid fractions in Japanese hypercholesterolemic patients and is well tolerated.     

Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy

Hepatic lipase (HL) is a lipolytic enzyme that catalyzes hydrolysis of triglycerides and phospholipids in all major classes of lipoproteins. Recently, a -514C/T polymorphism in the promoter region of the HL gene was found to be associated with variations in hepatic lipase activity and serum high density lipoprotein cholesterol (HDL-C) levels. Postmenopausal hormone replacement therapy (HRT) has known favorable effects on serum lipid and lipoprotein levels. In this study, we examined the relation between the -514C/T polymorphism and serum lipid and lipoprotein levels in postmenopausal women prior to and after 3 months of HRT. Significant associations between the -514 C/T polymorphism and HDL-C, low density lipoprotein cholesterol (LDL-C) and apolipoprotein A-I (apo A-I) levels were observed before and/or after 3 months of HRT. With HRT, serum total cholesterol (TC), LDL-C and apolipoprotein B (apo B) levels were reduced significantly (P=0.0001), and HDL-C and apo A-I levels were increased significantly (P=0.0001). However, the degrees of change in lipid and lipoprotein levels due to HRT did not differ significantly between the HL genotypes.     

Total cholesterol/HDL cholesterol ratio vs LDL cholesterol/HDL cholesterol ratio as indices of ischemic heart disease risk in men: the Quebec Cardiovascular Study.

BACKGROUND: Total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratios are used to predict ischemic heart disease risk. There is, however, no consensus on which of these 2 indices is superior. The objective of the present study was to present evidence that the LDL-C/HDL-C ratio may underestimate ischemic heart disease risk in overweight hyperinsulinemic patients with high triglyceride (TG)-low HDL-C dyslipidemia. METHODS: A total of 2103 middle-aged men in whom measurements of the metabolic profile were performed in the fasting state were recruited from 7 suburbs of the Quebec metropolitan area. RESULTS: The relationship of LDL-C/HDL-C to TC/HDL-C ratios was examined among men in the Quebec Cardiovascular Study classified into tertiles of fasting TG levels. For any given LDL-C/HDL-C ratio, the TC/HDL-C ratio was higher among men in the top TG tertile (>168 mg/dL [>1.9 mmol/L]) than in men in the first and second TG tertiles. Adjustment of the TC/HDL-C ratio for LDL-C/HDL-C by covariance analysis generated significant differences in average TC/HDL-C ratios among TG tertiles (P<.001). Greater differences in features of the insulin resistance syndrome (insulinemia, apolipoprotein B, and LDL size) were noted across tertiles of the TC/HDL-C ratio than tertiles of the LDL-C/HDL-C ratio. CONCLUSION: Variation in the TC/HDL-C ratio may be associated with more substantial alterations in metabolic indices predictive of ischemic heart disease risk and related to the insulin resistance syndrome than variation in the LDL-C/HDL-C ratio.     

Effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia

The effects of fenofibrate on lipids, lipoproteins, and apolipoproteins in 33 subjects with primary hypercholesterolemia were assessed in a 6-month parallel group study, placebo (n = 15) versus fenofibrate 300 mg/day (n = 18), followed by an open label 6-month treatment period. After stabilization on an isocaloric low fat (less than 35% total calories) diet with less than 250 mg cholesterol/day and a P/S ratio of 1, and maintenance of LDL-cholesterol (LDL-C) levels greater than or equal to 175 mg/dl, subjects received placebo for 6 weeks and were then randomized into placebo or fenofibrate groups for 6 months, followed by open label treatment for 6 months. During the 6-month double-blind period, compared to the placebo group, the treatment group had significant reductions in total cholesterol, LDL-C, total apo B, and triglyceride, and increments in HDL-cholesterol, apolipoprotein A-I and apolipoprotein A-II (P less than 0.01 for all comparisons). Compared to placebo baseline, therapy with fenofibrate resulted in a reduction of LDL-C, apo B, and the LDL-C/HDL-C ratio of 15%, 13%, and 18% respectively; HDL-C, apo A-I, and apo A-II increased respectively 12%, 13% and 30% (P less than 0.01 for all comparisons). Mean adherence during the double blind phase of the trial was 95% in the drug group and 96% in the placebo group. An additional 6 months of open label fenofibrate therapy maintained the reduced total and LDL-C as well as the elevated HDL-C, apo A-I and apo A-II in the drug-drug group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The triglyceride:high-density lipoprotein-cholesterol ratio and steno-occlusive disease in the intracranial arteries

The extent of carotid artery atherosclerosis correlates with increased plasma concentrations of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) and with a decreased plasma concentration of high-density lipoprotein-cholesterol (HDL-C). However, emerging data suggest that a triglyceride (TG):HDL-C ratio may be a better predictor of vascular risk than the traditional lipid measures such as TC and LDL-C. The purpose of this study was to evaluate the association between TC, LDL-C, TG, HDL-C, and the TG:HDL-C ratio with steno-occlusive disease in the intracranial cerebral arteries. We analyzed the records of 361 stroke-free subjects who underwent brain magnetic resonance angiography as part of their voluntary health checks. The presence of a steno-occlusive lesion in the basilar artery (BA) and in the horizontal portion of the middle cerebral artery (MCA) was assessed using brain 3D time of flight magnetic resonance angiography. All patients had fasting lipid panels drawn. We categorized serum lipid indices into quartiles and logistic regression analyses were performed. No serum lipid index was associated with the prevalence of MCA disease; TC, LDL-C, and HDL-C concentrations were not correlated with the prevalence of BA disease. A TG concentration in the third quartile compared with the lowest quartile was associated with increased prevalence of BA disease. The TG:HDL-C ratios in the upper three quartiles compared with the lowest quartile were associated with increased prevalence of BA disease. In conclusion, the TG:HDL-C ratio is more highly associated with the intracranial steno-occlusive disease than any standard lipid measure.     

Serum apolipoprotein AI, B levels in patients with coronary diseases

The levels of total cholesterol, triglyceride, LDL-C, HDL-C, apolipoprotein A1 and apolipoprotein B in the serum were measured in a selected series of 100 CAD patients (77 men and 23 women) who underwent coronary angiography and 141 non-CAD controls. Mean values of those variables differed significantly between the CAD and non-CAD groups matched in age, body weight, hypertension and smoking. There are significant difference in apolipoproteins A1, B and the ratio of apolipoprotein B to A1 between angina and myocardial infarction groups. Using stratified and multivariate stepwise regression analysis, it was shown that the apo A1, apoB/apoA1 are more sensitive and specific than the ordinary indices (e.g. total cholesterol, triglycerides, LDL-C and HDL-C) in estimating the degree of coronary artery stenosis and the differentiation of CAD from other diseases.     

Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL

One strategy for treating coronary artery disease (CAD) patients with low HDL cholesterol (HDL-C) is to maximally increase the HDL-C to LDL-C ratio by combining lifestyle changes with niacin (N) plus a statin. Because HDL can prevent LDL oxidation, the low-HDL state also may benefit clinically from supplemental antioxidants. Lipoprotein changes over 12 months were studied in 153 CAD subjects with low HDL-C randomized to take simvastatin and niacin (S-N), antioxidants (vitamins E and C, beta-carotene, and selenium), S-N plus antioxidants (S-N+A), or placebo. Mean baseline plasma cholesterol, triglyceride, LDL-C, and HDL-C levels of the 153 subjects were 196, 207, 127, and 32 mg/dL, respectively. Without S-N, lipid changes were minor. The S-N and S-N+A groups had comparably significant reductions (P相似文献   

Low density lipoprotein cholesterol, lipoprotein(a), and apo(a) isoforms in the elderly: relationship to fasting insulin. Associazione Medica Sabin

BACKGROUND AND AIM: Insulin resistance/hyperinsulinemia are often associated with aging and could play an important role in the development of glucose intolerance and dyslipidemia in the elderly. We investigated the relationship between plasma fasting insulin with total cholesterol (TC) and low density lipoprotein LDL cholesterol (LDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)] levels apolipoprotein (a) [apo (a)] isoforms in 100 free-living "healthy" octo-nonagenarians. METHODS AND RESULTS: Fasting insulin was positively correlated with TG, whereas a negative relation was found with TC and LDL-C (r = -0.29 and r = -0.28 respectively; p < 0.01), LDL-C/apo B, HDL-C and apo A-I levels. Fasting insulin was also inversely correlated with Lp(a) levels (r = -0.22; p < 0.03), whereas the latter were significantly related with TC and LDL-C (r = 0.30 and r = 0.31; p < 0.005), TG (r = 0.21; p < 0.05) and apo B (r = 0.26; p < 0.02). There was a negative relation between Lp(a) levels and apo(a) isoforms: the greater the apo(a) molecular weight, the lower the Lp(a) level (p < 0.0001). Fasting insulin increased with apo(a) size, though the difference in insulin levels among apo(a) isoforms was not significant (p = 0.4). Multiple regression analysis showed that fasting insulin was the best predictor of LDL-C (R2 = 0.14; p = 0.002) irrespective of age, gender, BMI, waist circumference and TG, while apo(a) isoform size, BMI and waist circumference were related with Lp(a) irrespective of TC and LDL-C, TG and apo B (R2 = 0.35 to 0.37; p < 0.0001). CONCLUSIONS: These results suggest that fasting insulin levels significantly influence LDL-C metabolism in old age. Lp(a) levels seem to be very strongly related to genetic background, although an indirect relation with insulin through adiposity and/or other associated lipid abnormalities cannot be ruled out.     

Effects of switching statins on lipid and apolipoprotein ratios in the MERCURY I study

BACKGROUND: Lipid ratios are clinically useful markers of coronary artery disease (CAD) risk. The effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin on lipid ratios were investigated in the Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY (MERCURY) I trial. METHODS: This trial was conducted in 3140 hypercholesterolemic patients with CAD, atherosclerosis, type 2 diabetes mellitus, or a 20% 10-year risk for CAD. Patients were randomized to rosuvastatin 10 mg, atorvastatin 10 or 20 mg, simvastatin 20 mg, or pravastatin 40 mg for 8 weeks; all patients except those receiving rosuvastatin 10 mg either were switched to rosuvastatin 10 or 20 mg or remained on initial treatment for 8 more weeks. RESULTS: At 8 weeks, reductions in total cholesterol (TC):high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol:HDL-C, non-HDL-C:HDL-C, and apolipoprotein (apo) B:apo A-I ratios with rosuvastatin 10 mg were significantly greater than those with atorvastatin 10 mg, atorvastatin 20 mg, simvastatin 20 mg, and pravastatin 40 mg (P<0.0001 for all). At week 16, switching to rosuvastatin 10 mg from atorvastatin 10 mg, simvastatin 20 mg, and pravastatin 40 mg and to rosuvastatin 20 mg from atorvastatin 20 mg produced significantly greater reductions in all lipid ratios (P< or =0.0001 for all). Switching to rosuvastatin 10 mg from atorvastatin 20 mg produced significantly greater reductions in TC:HDL-C (P<0.025) and apo B:apo A-I (P<0.01). CONCLUSIONS: Rosuvastatin 10 mg reduces lipid ratios more than equivalent and higher doses of other statins; switching to equal or lower doses of rosuvastatin produces significantly improved reductions in lipid ratios.     

Lipids, lipoproteins, apolipoproteins, and other risk factors in Chinese men and women with and without myocardial infarction

One hundred and fifty-four male and 69 female Chinese patients, aged between 40 and 60 years, who had suffered myocardial infarction (MI) were investigated and compared with 216 men and 219 women who had no history or ECG evidence of coronary heart disease. The male MI patients had significantly raised levels of triglycerides (160 mg/dl), cholesterol (194 mg/dl), VLDL-CH (31 mg/dl), apolipoprotein B (122 mg/dl) and apolipoprotein E (4.7 mg/dl) and a lower apolipoprotein A-I level (126 mg/dl) than the control group (triglycerides 131, cholesterol 179, VLDL-CH 26, apo B 102, apo E4.2, and apo A-I 138 mg/dl). The women with MI also had higher values for the atherogenic lipids than the control group (triglycerides 175 vs. 134 mg/dl, cholesterol 218 vs. 186 mg/dl, LDL-CH 128 vs. 104 mg/dl, VLDL-CH 32 vs. 26 mg/dl, apo B 121 vs. 103 mg/dl and apo E 5.4 vs. 4.3 mg/dl), as well as lowered apolipoprotein A-I (128 vs. 144 mg/dl). The Lp(a) levels (men and women considered together) were significantly higher for the MI patients (34.3 mg/dl vs. 26.2 mg/dl). Anti-atherogenic lipoproteins such as HDL-cholesterol, HDL2-CH, HDL3-CH, phospholipids and apolipoprotein A-II, C-II and C-III showed no difference between the groups.     

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.     

Taq1B CETP polymorphism, plasma CETP, lipoproteins, apolipoproteins and sex differences in a Jewish population sample characterized by low HDL-cholesterol

Mean high-density lipoprotein cholesterol (HDL-C) concentrations are low in the Jewish population of Israel. With this in mind we assessed the association of the Taq1B CETP polymorphism, plasma CETP mass and plasma lipid, lipoprotein and apolipoprotein concentrations in a sample of 884 Jerusalem residents aged 28-32. The allele frequency (0.435 +/- 0.017(S.E.)) is similar to that reported elsewhere. There was a strong (apparently codominant) association of the Taq1 B allele with plasma CETP in both sexes, and an inverse association with HDL-C and apo A-1, significant in women and undiminished upon adjustment for plasma CETP. There was evidence in this population for an admixture of two plasma CETP distributions, with 9% belonging to a distribution with the higher mean, pointing to a possible major gene effect. Mean plasma CETP was higher in women than men. Plasma CETP was inversely associated with HDL-C in men but not in women (P< 0.05 for the sex difference, multivariate analysis), inversely related to the HDL-C/apo A-1 ratio in men and positively related in women (P < 0.005 for the sex difference), and was positively associated with total cholesterol (TC) and low-density lipoprotein cholesterol in both sexes, and with the TC/HDL-C ratio and apo B in men alone. The sex differences may reflect dissimilarities in the regulatory function of CETP in lipid exchange. The absence of an unusual allele frequency of the Taq1B CETP polymorphism and its relatively modest association with HDL-C argue against an important role for this or strongly linked sites in determining the low population levels of HDL-C in Israel.     

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.