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1.
Bairaktari ET Tselepis AD Millionis HJ Elisaf MS 《European journal of endocrinology / European Federation of Endocrine Societies》1999,140(5):474-476
It has been reported that euthyroid normolipidemic males and postmenopausal females exhibit significantly higher serum lipoprotein (a) (Lp(a)) levels compared with age- and sex-matched normolipidemic controls. However, it is well known that there is an inverse correlation between Lp(a) concentration and apolipoprotein (a) (apo(a)) isoform size. Thus, it is imperative to exclude differences in apo(a) isoform frequencies between subjects with or without thyroid autoimmunity in order to verify if there is an association between thyroid autoimmunity and increased Lp(a) concentration. To exclude such an effect of different apo(a) isoform frequencies, we determined apo(a) phenotypes in 22 patients (9 males and 13 postmenopausal females) with thyroid autoimmunity and in 64 (29 males and 35 females) age- and sex-matched individuals without thyroid autoimmunity (control group). There were no significant differences in the values of lipid parameters between the two groups, including Lp(a). We did not detect any significant differences in the apo(a) phenotype frequencies between the two groups. Additionally, in neither of the subgroups formed according to the presence of low molecular vs high molecular weight apo(a) isoforms were there any significant differences in median serum Lp(a) levels between patients with and without thyroid autoimmunity. Thus, our results contradict the previously reported association between thyroid autoimmunity and Lp(a) concentrations. 相似文献
2.
Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine. 总被引:7,自引:0,他引:7
Haralampos J Milionis Zoe Efstathiadou Alexandros D Tselepis Eleni T Bairaktari Loukas D Tsironis Agathocles Tsatsoulis Moses S Elisaf 《Thyroid》2003,13(4):365-369
The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms. 相似文献
3.
Paultre F Pearson TA Weil HF Tuck CH Myerson M Rubin J Francis CK Marx HF Philbin EF Reed RG Berglund L 《Arteriosclerosis, thrombosis, and vascular biology》2000,20(12):2619-2624
Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (>/=50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; P:=0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P:=0.043). Elevated Lp(a) levels (>/=30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P:<0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a). 相似文献
4.
A high serum lipoprotein(a) [Lp(a)] level, which is genetically determined by apolipoprotein(a) [apo(a)] size polymorphism, is an independent risk factor for coronary atherosclerosis. However, the associations among Lp(a) levels, apo(a) phenotypes, and myocardial infarction (MI) have not been studied. Patients with MI (cases, n = 101, M/F: 86/15, age: 62+/-10y) and control subjects (n = 92, M/F: 53/39, age: 58+/-14y) were classified into quintile groups (Groups I to V) according to Lp(a) levels. Apo(a) isoform phenotyping was performed by a sensitive, high-resolution technique using sodium dodecyl sulfate-agarose/gradient polyacrylamide gel electrophoresis (3-6%), which identified 26 different apo(a) phenotypes, including a null type. Groups with higher Lp(a) levels (Groups II, III, and V) had higher percentages of MI patients than that with the lowest Lp(a) levels (Group I) (54%, 56%, or 75% vs. 32%, p<0.05). Groups with different Lp(a) levels had different frequency distributions of apo(a) isoprotein phenotypes: Groups II, III, IV, and V, which had increasing Lp(a) levels, had increasingly higher percentages of smaller isoforms (A1-A4, A5-A9) and decreasingly lower percentages of large isoforms (A10-A20, A21-A25) compared to Group I. An apparent inverse relationship existed between Lp(a) and the apo(a) phenotype. Subjects with the highest Lp(a) levels (Group V) had significantly (p<0.05) higher serum levels of total cholesterol, apo B, and Lp(a). Patients with MI and the controls had different distributions of apo(a) phenotypes: i.e., more small isoforms and more large size isoforms, respectively (A1-A4/A5-A9/A10-A20/A21-A25: 35.7%/27.7%/20.8%/15.8% and 22.8%/23.9%/29.4%/23.9%, respectively). Lp(a) (parameter estimate +/- standard error: 0.70+/-0.20, Wald chi2 = 12.4, p = 0.0004), apo(a) phenotype (-0.43+/-0.15, Wald chi2 = 8.17, p = 0.004), High-density lipoprotein-cholesterol, apo A-I, and apo B were significantly associated with MI after adjusting for age, gender, and conventional risk factors, as assessed by a univariate logistic regression analysis. The association between Lp(a) and MI was independent of the apo(a) phenotype, but the association between the apo(a) phenotype and MI was not independent of Lp(a), as assessed by a multivariate logistic regression analysis. This association was not influenced by other MI- or Lp(a)-related lipid variables. These results suggest that apo(a) phenotype contributes to, but does not completely explain, the increased Lp(a) levels in MI. A stepwise logistic regression analysis with and without Lp(a) in the model identified Lp(a) and the apo(a) phenotype as significant predictors for MI, respectively. 相似文献
5.
OBJECTIVES: To evaluate the relationships between alcohol intake and serum lipoprotein(a) [Lp(a)], a powerful predictor of organ damage, in patients with essential hypertension with a wide range of alcohol intake, and to investigate whether the association between alcohol intake and serum Lp(a) concentrations occurs over the entire spectrum of apo(a) phenotypes. DESIGN: Cross-sectional study of a case series. SETTING: University medical centre. PATIENTS: Four hundred and two patients with untreated essential hypertension recruited at a hypertension clinic. MAIN OUTCOME MEASURES: Serum Lp(a) concentrations, apo(a) isoforms, alcohol consumption, smoking habits and cardiovascular status. RESULTS: No difference in Lp(a) concentrations was observed between teetotalers and occasional drinkers. Light drinkers (1-20 g/day ethanol), moderate drinkers (21-50 g/day), and heavy drinkers (> 50 g/day) had, respectively, 21, 26 and 57% lower median Lp(a) concentrations than teetotalers and occasional drinkers. Similar findings were obtained when male and female patients were analysed separately. Log Lp(a) concentrations were inversely and independently correlated with alcohol consumption in both men and women with hypertension. The frequency distributions of apo(a) isoforms and liver function parameters were comparable across the different alcohol intake groups. Patients with evidence of cardiovascular damage had greater concentrations of serum Lp(a) and higher frequency of low-molecular weight apo(a) isoforms as compared with patients without such evidence. CONCLUSIONS: Serum Lp(a) is inversely and dose-dependently related with alcohol intake in patients with hypertension, and this relationship is independent of the size distribution of apo(a) isoforms. Reduction of Lp(a) concentrations by regular consumption of alcohol might favourably affect the atherosclerotic risk profile of patients with hypertension and thereby decrease cardiovascular morbidity. 相似文献
6.
C. Gazzaruso A. Garzaniti P. Buscaglia G. D'Annunzio A. Porta G. Vandelli R. Lorini G. Finardi P. Fratino D. Geroldi 《Acta diabetologica》1998,35(1):13-18
To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] polymorphism in relation to
the presence of microvascular and neurological complications in type 1 diabetes mellitus, 118 young diabetic patients and
127 age-matched controls were recruited. Lp(a) levels were higher in patients than in controls, but the apo(a) isoforms distribution
did not differ between the two groups [higher prevalence of isoforms of high relative molecular mass (RMM) in both groups].
Microalbuminuric patients had Lp(a) levels significantly greater than normoalbuminuric patients, and normoalbuminuric patients
showed higher Lp(a) levels than controls. Patients with retinopathy or neuropathy showed similar Lp(a) levels to those without
retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were observed between subgroups with and without
complications (higher prevalence of isoforms of high RMM in every subgroup). However, among patients with retinopathy, those
with proliferative retinopathy had higher Lp(a) levels and a different apo(a) isoforms distribution (higher prevalence of
isoforms of low RMM) than those with non-proliferative and background retinopathy (higher prevalence of isoforms of high RMM).
Our data suggest that young type 1 diabetic patients without microalbuminuria have Lp(a) levels higher than healthy subjects
of the same age. Lp(a) levels are further increased in microalbuminuric patients. High Lp(a) levels and apo(a) isoforms of
low RMM seem to be associated with the presence of proliferative retinopathy, but have no relation to neuropathy.
Received: 23 June 1997 / Accepted in revised form: 27 November 1997 相似文献
7.
Fontana P Mooser V Bovet P Shamlaye C Burnand B Lenain V Marcovina SM Riesen W Darioli R 《Arteriosclerosis, thrombosis, and vascular biology》1999,19(4):1075-1082
Serum or plasma levels of Lp(a) vary widely between individuals and are higher in Africans and their descendants compared with white persons. In whites, high serum levels of Lp(a) are associated with the premature development of atherosclerosis. In both ethnic groups, serum Lp(a) levels are highly genetically determined and only a few environmental or physiological factors, like testosterone or estrogen, have been shown to lower serum Lp(a) levels. In whites, alcohol consumption is associated with lower serum Lp(a) levels. However, the mechanism underlying this association and whether it holds true for blacks is not known. To address these questions, we analyzed serum Lp(a) levels in 333 middle-aged males of African descent from the Seychelles Islands (Indian Ocean). In addition, we analyzed the size of the apo(a) isoforms and the serum levels of albumin and sex hormones in a subset of 279 subjects. Serum Lp(a) levels were similar in teetotalers (median, 32.5 mg/dL; n=42) and occasional drinkers (median, 34.1 mg/dL; n=112). In contrast, individuals consuming 10 to 80 g of ethanol/d (n=83) and heavy drinkers (>80 g of ethanol/d, n=96) had a 9% and 32% lower median Lp(a) level than teetotalers, respectively (P=0.01). The size distribution of the apo(a) isoforms and the mean serum levels of albumin, estradiol, and luteinizing hormone were similar in teetotalers and occasional drinkers compared with moderate and heavy drinkers. These latter 2 groups had lower serum levels of testosterone and sex hormone-binding globulin. These data indicate that alcohol intake is associated in a dose-dependent manner with lower serum Lp(a) levels in males of African descent and that this association is not related to the size of the apo(a) isoforms, to the synthetic function of the liver, or to sex hormone biochemical status. 相似文献
8.
Lipoprotein(a) and atherosclerosis 总被引:30,自引:0,他引:30
Lipoprotein(a) [Lp(a)], a lipoprotein variant, was relegated for almost 25 years to the study of a few specialists. During the past 3 to 4 years, however, there has been a tremendous upsurge of interest in Lp(a), primarily because of multidisciplinary efforts in structural and molecular biology. Findings emerging from these efforts include the following: Lp(a) represents a cholesteryl-ester, low-density-lipoprotein (LDL)-like particle with apolipoprotein (apo) B-100 linked to apo(a); apo(a) is a glycoprotein coded by a single gene locus on the long arm of chromosome 6, which has several alleles, accounting for its remarkable size polymorphism (300 to 800 kD); apo(a) size polymorphism relates to plasma levels and density distribution of Lp(a); apo(a) is strikingly similar to plasminogen; and in vitro, Lp(a), in appropriate levels, competes for some physiologic functions of plasminogen in the coagulation and fibrinolytic cascade and may thus be thrombogenic. The LDL-like properties of Lp(a) may also confer atherogenic potential, but the mechanisms underlying this atherogenicity remain to be defined. In epidemiologic studies, high plasma Lp(a) levels have been associated with an increased incidence of atherosclerotic cardiovascular disease, especially in patients less than 60 years of age. Moreover, Lp(a) has been found as an intact particle in the arterial intima, particularly in association with atherosclerotic plaque. This finding suggests that Lp(a) can transverse the endothelium, possibly by a non-receptor-mediated process, and, at the intimal level, acquire thrombogenic and atherogenic potentials. Current information justifies the need to determine plasma Lp(a) levels in patients with a history of atherosclerotic cardiovascular disease. Unfortunately, the available techniques need to be standardized. Apolipoprotein(a) exists in isoforms of different sizes, and the importance of determining apo(a) phenotypes in clinical practice remains to be established. 相似文献
9.
Lipoprotein(a) in homozygous familial hypercholesterolemia 总被引:2,自引:0,他引:2
Kraft HG Lingenhel A Raal FJ Hohenegger M Utermann G 《Arteriosclerosis, thrombosis, and vascular biology》2000,20(2):522-528
Lipoprotein(a) [Lp(a)] is a quantitative genetic trait that in the general population is largely controlled by 1 major locus-the locus for the apolipoprotein(a) [apo(a)] gene. Sibpair studies in families including familial defective apolipoprotein B or familial hypercholesterolemia (FH) heterozygotes have demonstrated that, in addition, mutations in apolipoprotein B and in the LDL receptor (LDL-R) gene may affect Lp(a) plasma concentrations, but this issue is controversial. Here, we have further investigated the influence of mutations in the LDL-R gene on Lp(a) levels by inclusion of FH homozygotes. Sixty-nine members of 22 families with FH were analyzed for mutations in the LDL-R as well as for apo(a) genotypes, apo(a) isoforms, and Lp(a) plasma levels. Twenty-six individuals were found to be homozygous for FH, and 43 were heterozygous for FH. As in our previous analysis, FH heterozygotes had significantly higher Lp(a) than did non-FH individuals from the same population. FH homozygotes with 2 nonfunctional LDL-R alleles had almost 2-fold higher Lp(a) levels than did FH heterozygotes. This increase was not explained by differences in apo(a) allele frequencies. Phenotyping of apo(a) and quantitative analysis of isoforms in family members allowed the assignment of Lp(a) levels to both isoforms in apo(a) heterozygous individuals. Thus, Lp(a) levels associated with apo(a) alleles that were identical by descent could be compared. In the resulting 40 allele pairs, significantly higher Lp(a) levels were detected in association with apo(a) alleles from individuals with 2 defective LDL-R alleles compared with those with only 1 defective allele. This difference of Lp(a) levels between allele pairs was present across the whole size range of apo(a) alleles. Hence, mutations in the LDL-R demonstrate a clear gene-dosage effect on Lp(a) plasma concentrations. 相似文献
10.
《Atherosclerosis》1999,142(1):233-239
High serum lipoprotein(a) (Lp(a)) concentration which is largely determined by genetic factors, mainly the apolipoprotein(a) (apo(a)) polymorphism, is associated with ischemic cerebrovascular disease. The aim of this study was to investigate whether apo(a) size was associated with acute ischemic stroke in young adults for which causal factors often remain undetermined. Lipid parameters, Lp(a) concentration and apo(a) isoform size distribution were determined in 90 young patients (37.4±8.7 years) with acute cerebral ischemia, and compared to those of control subjects with similar age and sex ratio. Apo(a) size was expressed as its apparent number of kringle 4 (Kr 4) repeats. Serum Lp(a) concentrations were significantly higher in patients than in controls (median values: 0.18 vs. 0.07 g/l, P=0.009) and were as expected inversely related to the number of kringle 4 repeats in both controls (r2=−0.61, P<0.001) and patients (r2=−0.56, P<0.001). However there was no difference in the apo(a) isoform size distributions between the two groups (median isoform size: 27 vs. 27 Kr 4, P=0.25). Lp(a) levels were increased as well in patients with size apo(a) isoform≤22 Kr 4 as in those with isoforms>25 Kr 4. Multivariate analysis showed that apo(a) phenotype did not appear as a risk factor for cerebrovascular infarction. Thus, our results indicate that serum Lp(a) was significantly increased in young people with ischemic stroke but fail to reveal a role of small-sized apo(a) isoforms in the occurrence of this event. They suggest that other factors, genetic or environmental in nature, than the apo(a) size contribute to increase the serum Lp(a) concentrations in these young patients. 相似文献
11.
K. Hirata Dr. K. Saku S. Jimi S. Kikuchi H. Hamaguchi K. Arakawa 《Diabetologia》1995,38(12):1434-1442
Summary We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA1c7.1±1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3–6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8±33.3 vs 22.3±19.5 mg/dl, p<0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p<0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p<0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data, together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.Abbreviations Lp(a)
Lipoprotein(a)
- apo(a)
apolipoprotein(a)
- NIDDM
non-insulin-dependent diabetes mellitus
- TC
total cholesterol
- LDL
low density lipoprotein
- TG
triglycerides
- HDL-C
high density lipoprotein-cholesterol
- LDL-C
low density lipoprotein-cholesterol
- PBS
phosphate buffered saline
The first two authors contributed equally to this work 相似文献
12.
Koruk M Savaş MC Yilmaz O Tayşi S Karakok M Gündoğdu C Yilmaz A 《Journal of clinical gastroenterology》2003,37(2):177-182
GOALS/BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a form of liver disease that is histologically indistinguishable from alcoholic hepatitis but occurs in persons who do not consume alcohol in excess. The objectives of this study are to measure serum levels of lipids, lipoproteins and apolipoproteins (apo AI, apo B), lipoprotein (a) [Lp (a)] in patients with nonalcoholic steatohepatitis (NASH), and to investigate the relationship with liver histology. STUDY: The scope of this study is composed of 36 patients (27 males, 9 females) with NASH, diagnosed by biochemical liver function tests, sonographic examination of liver and liver biopsy and 32 healthy adults as a control group (22 males, 10 females). Serum lipids, lipoproteins and apo AI, apo B, and Lp (a) measurements were taken in the study group and controls, and a correlation with histopathologic findings was searched for. RESULTS: Serum mean levels (+/- SD as mg/dl) of total cholesterol (201.05 +/- 34.48), triglyceride (225.94 +/- 156.50), and LDL-cholesterol (111.77 +/- 19.85) in patients with NASH were significantly higher than those of the control group (170.68 +/- 31.06; 138.81 +/- 49.96; 100.68 +/- 17.98; respectively) and serum HDL-cholesterol level (41.22 +/- 2.47) was less than that of the control group (45.06 +/- 8.32) (P = 0.017). The serum mean level of apo AI (151.54 +/- 30.90) in the study group was lower than that of the controls (160.62 +/- 22.11), but the difference was not significant (P = 0.17). However, the serum apo AI level in patients with liver fibrosis (140.62 +/- 35.62) was significantly lower than that of patients without liver fibrosis (164.57 +/- 25.47) (P = 0.01). The serum mean level of apo B (89.80 +/- 20.62) in the patients was significantly higher than the control group (73.25 +/- 25.39) (P = 0.004), but not correlate with liver histopathology. The serum Lp (a) levels in both the patients (13.09 +/- 9.61) and the controls (12.01 +/- 7.50) were not different (P = 0.61). Hypertriglyceridemia (above 220 mg/dL) had a positive correlation with steatosis of the liver (r = 0.333, P = 0.04) and a negative correlation with liver fibrosis (r = -0.438, P = 0.008). There was a significant negative correlation between apo AI and steatosis (r = -0.360, P = 0.03), inflammation (r = -0.364, P = 0.03) and fibrosis of liver (r = -0.418, P = 0.01). A positive correlation of serum LDL-cholesterol (r = 0.507, P = 0.002) and Lp(a) (r = 0.394, P = 0.01) concentrations with liver fibrosis was also noted. CONCLUSIONS: Abnormalities of lipid metabolism such as the increase of serum triglyceride, cholesterol and LDL-cholesterol level and decrease of HDL-cholesterol may be the contributing factors in the development of NASH. The decrease in apo AI and the increase in LDL and Lp (a) in patients were correlated with liver fibrosis. Apo AI may be a serum marker for liver fibrosis in patients with NASH. 相似文献
13.
L Brazier L Tiret G Luc D Arveiler J B Ruidavets A Evans J Chapman F Cambien J Thillet 《Atherosclerosis》1999,144(2):323-333
Lp(a) concentrations are largely determined by apo(a) isoform size, but several studies have shown that apo(a) isoforms could not entirely explain the increase of Lp(a) levels observed in patients with coronary heart disease (CHD). Since up to 90% of the variance in Lp(a) levels has been suggested to be attributable to the apo(a) locus, the hypothesis that polymorphisms of the apo(a) gene other than size could contribute to the increase of Lp(a) levels in CHD patients must be considered. This hypothesis was tested in the ECTIM Study comparing 594 patients with myocardial infarction and 682 control subjects in Northern Ireland and France. In addition to apo(a) phenotyping, five previously described polymorphisms of the apo(a) gene were genotyped: a (TTTTA)n repeat at position -1400 from the ATG, a G/A at -914, a C/T at -49, a G/A at -21 and a Met/Thr affecting amino acid 4168. As reported earlier [Parra HJ, Evans AE, Cambou JP, Amouyel P, Bingham A, McMaster D, Schaffer P, Douste-Blazy P, Luc G, Richard JL, Ducimetiere P, Fruchart JC, Cambien F. A case-control study of lipoprotein particles in two populations at contrasting risk for coronary heart disease. The ECTIM study. Arterioscler Thromb 1992; 12:701-707], mean Lp(a) levels were higher in cases than in controls (20.7 vs 14.6 mg/dl in Belfast, 17.2 vs 8.9 mg/dl in France, P < 0.001 for case-control and population differences). In the present study, mean apo(a) isoform size differed significantly between cases and controls (25.7 vs 26.6 kr in Belfast, 25.9 vs 27.4 kr in France, P < 0.001 for case-control and P = 0.13 for population difference). After adjustment for apo(a) isoforms, Lp(a) levels remained significantly higher in cases than in controls (difference, 4.6 mg/dl; P < 0.001). Genotype and allele frequencies did not differ significantly between cases and controls for any of the five polymorphisms studied. The five polymorphisms were in strong linkage disequilibrium and had a combined heterozygosity of 0.83. In multivariate regression analysis adjusted for apo(a) isoforms, only the (TTTTA)n polymorphism was significantly associated with Lp(a) levels; it explained 4.5% of Lp(a) variability in cases and 3.1% in controls. The Lp(a) case/control difference was not reduced after taking into account the (TTTTA)n effect. We conclude that the increase of Lp(a) levels observed in MI cases, and which was not directly attributable to apo(a) size variation, was not related to the five polymorphisms of the apo(a) gene considered. 相似文献
14.
Carantoni M Zuliani G Bader G Palmieri E Volpato S Passaro A Imbastaro T Mezzetti A Fellin R 《Nutrition, metabolism, and cardiovascular diseases : NMCD》1999,9(5):228-233
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. 相似文献
15.
BACKGROUND: Patients with type 2 diabetes mellitus have a greater than normal risk of developing atherosclerotic vascular diseases. Higher than normal plasma concentrations of lipoprotein (a) [Lp(a)] have been associated with premature atherosclerosis in several studies. OBJECTIVE: To determine the concentrations of lipids, lipoproteins, and Lp(a) in 107 type 2 diabetic patients, and the distribution of apolipoprotein (a) [apo(a)] phenotypes for this group, and to compare the results found with results for healthy subjects. RESULTS: Plasma concentrations of cholesterol, triglycerides, and apolipoprotein B in the diabetics were significantly higher than those in control subjects. Diabetic patients had slightly lower Lp(a) concentrations than did nondiabetic subjects, but these differences were not statistically significant. Distributions of Lp(a) concentrations both in type 2 diabetic patients and in control subjects were markedly skewed, the highest prevalences being of low values. CONCLUSION: Distributions of apo(a) phenotypes for patients with type 2 diabetes mellitus and controls were remarkably alike. Smaller isoforms were similarly prevalent for the two populations, as were the null, single-band and double-band apo(a) phenotypes. 相似文献
16.
Emanuele E Peros E Minoretti P D'Angelo A Piccinni MN Montagna L Geroldi D 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2004,14(4):193-199
BACKGROUND AND AIM: In addition to high serum cholesterol levels, various cardiovascular risk factors may be involved in the development of coronary heart disease (CHD) in hypercholesterolemic subjects. As the levels of lipoprotein(a) [Lp(a)], an important and independent cardiovascular risk factor, are high in polygenic hypercholesterolemia (PH), we investigated plasma Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of CHD events in PH patients. METHODS AND RESULTS: Lp(a) levels and apo(a) isoforms were determined in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94 normocholesterolemic controls without CHD. Lp(a) levels were similar in the hypercholesterolemic subjects with (n=100) or without CHD (n=91): 21.4 (range 6.6-59.23) vs 18.5 (range 5.25-57.25) mg/dL (p=NS). Low molecular weight apo(a) isoforms were more prevalent (55%) in the PH patients with CHD, whereas high molecular weight apo(a) isoforms were more prevalent (62.6%) in those without CHD: this difference was significant (p<0.05). A stepwise multiple-discriminant analysis made in order to determine the independence of common cardiovascular risk factors, Lp(a) levels and low molecular weight apo(a) isoforms in predicting CHD among hypercholesterolemic subjects showed that the presence of a positive family history of CHD, smoking, age, and the presence of at least one apo(a) isoform of low molecular weight were independently associated with CHD. CONCLUSIONS: Despite high Lp(a) levels, our findings do not support the hypothesis that Lp(a) plays an independent role in determining clinical CHD in PH subjects. However, the presence of at least one low molecular weight apo(a) isoform is an independent genetic predictor of CHD in hypercholesterolemic subjects. Together with other cardiovascular risk factors, apo(a) phenotypes should be assessed to evaluate the overall CHD risk status of all subjects with high serum cholesterol levels. 相似文献
17.
目的: 研究阿托伐他汀药物对大鼠动脉粥样硬化斑块内血管生成的影响及可能机制,观察粥样斑块内血管生成与斑块稳定性的关系。方法: 将36只大鼠随机分为正常组,高脂组和阿托伐他汀组。14周后处死大鼠,取血测定血脂及C反应蛋白,观察主动脉病理学变化;测量斑块面积及内膜中膜面积比(I/M);微血管密度(MVD)测定,免疫组化观察并分析斑块内Ⅷ因子的表达。结果: ①高脂组和阿托伐他汀组血清脂质水平高于正常组(P<0.05),而二者之间无明显差异性;②高脂组和阿托伐他汀组I/M较正常组明显增多(P<0.05),而阿托伐他汀组I/M较高脂组明显减少(P<0.05);③阿托伐他汀和高脂组斑块内MVD及Ⅷ因子阳性率均明显均高于正常组,而阿托伐他汀组MVD及Ⅷ因子阳性率均低于高脂组(P<0.05);结论: 新生血管多发生在不稳定斑块内,斑块内血管生成是增加斑块不稳定性的又一因素,阿托伐他汀可以减少斑块内血管生成,达到稳定斑块的作用。 相似文献
18.
单克隆多克隆抗体酶联免疫吸附法测定血清脂蛋白(a)的比较 总被引:2,自引:0,他引:2
应用淋巴细胞杂交瘤技术,建立了抗人血清脂蛋白(a)杂交瘤细胞株,对制备的单克隆抗体进行了特异性鉴定和抗原位点测定。建立了多克隆双抗体夹心酶联免疫吸附法、载蛋白(a)、载脂蛋白B双位点酶联免疫吸附法、单克隆单株、混合株双抗体夹心酶联免疫吸附法对脂蛋白(a)进行了检测,并对结果进行了分析。认为样本、参考品间载脂蛋白(a)的多态型不同可引起结果间的差异。 相似文献
19.
Serum lipids, lipoprotein(a) level, and apolipoprotein(a) isoforms as prognostic markers in patients with coronary heart disease 总被引:10,自引:0,他引:10
Lundstam U Herlitz J Karlsson T Lindén T Wiklund O 《Journal of internal medicine》2002,251(2):111-118
OBJECTIVE: Our objective was to study prognostic factors for death in patients with coronary heart disease (CHD), focusing on serum lipids and lipoproteins. DESIGN AND SUBJECTS: The study subjects were 964 patients with angina pectoris who underwent coronary angiography between 1985 and 1987. Follow-up, including survival and cause of death, was carried out in April 1998. RESULTS: A total of 363 patients died. Increasing age, diabetes and low levels of HDL cholesterol and of apolipoprotein (apo) AI were associated with increased risk of total mortality and cardiac mortality. In men, low levels of LDL cholesterol and of apoB were associated with increased risk of death, but not of cardiac death only; high levels of lipoprotein(a) [Lp(a)] were not associated with increased risk. In women, however, there was a trend towards increased risk with increasing Lp(a) levels (P = 0.054); the smallest isoform of apo(a) was associated with a twofold increase in risk. In women, but not in men, risk decreased with increasing molecular weight of the apo(a) isoforms. CONCLUSIONS: Amongst lipoprotein variables, low levels of HDL cholesterol and of apoAI and the presence of low-molecular weight isoforms of apo(a) are associated with increased risk of death in patients with CHD. Apo(a) isoforms and Lp(a) levels seem to be more important as risk factors amongst women. Low LDL cholesterol and apoB levels were associated with increased risk, but only in men. These findings demonstrate the importance of a gender-specific analysis of risk factors for CHD. 相似文献
20.
Gonbert S Saint-Jore B Giral P Doucet C Chapman J Thillet J 《Arteriosclerosis, thrombosis, and vascular biology》2001,21(8):1353-1358
Hypercholesterolemia is frequently associated with elevated Lp(a) levels, an independent risk factor for coronary, cerebrovascular, and peripheral vascular disease. A portion of apolipoprotein(a) [apo(a)] circulates as a series of fragments derived from the N-terminal region of apo(a). The relationship of elevated lipoprotein(a) [Lp(a)] levels to those of circulating apo(a) fragments in polygenic hypercholesterolemia is indeterminate. Therefore, plasma Lp(a) and plasma and urinary apo(a) fragment levels were measured by ELISA in 82 patients with polygenic type IIa hypercholesterolemia (low density lipoprotein cholesterol >/=4.13 mmol/L and triglycerides <2.24 mmol/L) and in 90 normolipidemic subjects. Lp(a) levels were significantly elevated in patients compared with control subjects (0.35+/-0.4 and 0.24+/-0.31 mg/mL, respectively; median 0.13 and 0.11 mg/mL, respectively; P=0.039), although apo(a) isoform distribution did not differ. Patients displayed significantly higher plasma and urinary apo(a) fragment levels than did control subjects (respective values were as follows: 4.97+/-5.51 and 2.15+/-2.57 [median 2.85 and 1.17] microg/mL in plasma, P<0.0001; 75+/-86 and 40+/-57 [median 38 and 17] ng/mg urinary creatinine in urine, P<0.0001). The ratio of plasma apo(a) fragments to Lp(a) levels was also significantly higher in patients than in control subjects (1.93+/-1.5% and 1.75+/-2.36%, respectively; P<0.0001). We conclude that increased plasma Lp(a) levels in polygenic hypercholesterolemia are associated with elevated circulating levels of apo(a) fragments but that this increase is not due to decreased renal clearance of apo(a) fragments. Furthermore, we identified a new pattern of apo(a) fragmentation characterized by the predominance of a fragment band whose size was related to that of the parent apo(a) isoform and that was superimposed on the series of fragments described previously by Mooser et al (J Clin Invest. 1996; 98:2414-2424). This new pattern was associated with small apo(a) isoforms and did not discriminate between hypercholesterolemic and normal subjects. However, this new apo(a) fragment pattern may constitute a novel marker for cardiovascular risk. 相似文献