Total Lp Research Articles

Endothelial dysfunction and inflammatory process in transfusion-dependent patients with beta-thalassemia major

Background Beta-thalassemia major is associated with increased cardiovascular risk, although the underlying mechanisms remain unclear. We examined endothelial function and serum levels of inflammatory mediators in transfusion-dependent patients with beta-thalassemia major. Methods The study population consisted of 67 patients with homozygous beta-thalassemia major, (aged 24.6±0.7 years) and 71 healthy age and sex matched controls. Forearm blood flow was measured with gauge-strain plethysmography. Forearm vasodilatory response to reactive hyperemia (RH%) or to nitrate (NTG%) was expressed as the percentage change of forearm blood flow from baseline to the maximum flow during reactive hyperemia or sublingual nitroglycerin, respectively. Serum levels of interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1) and soluble intercellular adhesion molecule (sICAM-1) were determined with ELISA. Results Patients had significantly lower levels of total cholesterol (125±4.5 vs. 207±7 mg/ml, p<0.01), ApoA1 (120±3 vs. 129±5 mg/ml, p<0.05), ApoB (60.5±2 vs. 95±4 mg/ml, p<0.01), ApoE (3±2 vs. 4±0.2 mg/ml, p<0.01) and Lp(a) (7.9±1.3 vs. 14.5±3.2 mg/ml, p<0.01) than controls. IL-6 levels were significantly higher in patients (3.03±0.31 pg/ml) than controls (1.15±0.15 pg/ml, p<0.01). Similarly, sVCAM-1 and sICAM-1 levels were significantly higher in patients (513±31 and 368±25.5 ng/ml, respectively) than controls (333±13.8 and 272±14.05 ng/ml, respectively, p<0.01 for both). Maximum hyperemic forearm blood flow and RH% were lower in patients (7.1±0.3 ml/100 ml tissue/min and 49±2.8%, respectively) than controls (8.26±0.32 ml/100 ml tissue/min and 86.3±5.57%, respectively, p<0.01 for both). Conclusions Beta-thalassemia major is associated with impaired endothelial function and increased levels of IL-6, sVCAM-1 and sICAM-1, suggesting a potential role of inflammation and endothelial dysfunction in the complications of the disease.

Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study

Objective: Isoflavone supplementation in high doses is associated with plasma lipid, glucose and insulin levels. Little is known about the effects of intake within the range of western diets on these endpoints. Design: We conducted a population-based cross-sectional study in 301 women aged 60–75 years. Methods: Dietary isoflavone and lignan intake was assessed with a food frequency questionnaire covering habitual diet during the year preceding enrolment. The outcome measures were total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), fasting glucose and insulin levels. Data were analysed using linear regression and logistic regression models. In the analyses we adjusted for a wide range of potential confounders. Results: High intake of isoflavones was associated with lower Lp(a) levels (tertile three versus tertile one: odds ratio 0.36, 95% CI 0.16; 0.80). No relation was found between blood levels and the other plasma lipids, glucose or insulin was found. Conclusion: The results of this study suggest that an effect of dietary phytoestrogen intake at low levels on plasma lipid levels is of limited magnitude. It is premature to advise postmenopausal women with low phytoestrogen intake to change their diet towards a phytoestrogen rich diet with the sole aim to prevent cardiovascular disease.

Lipids and clotting factors during low dose transdermal estradiol/norethisterone use

Objective: To demonstrate the effects of 2-year transdermal continuous combined low-dose estradiol (0.025 mg/day) and norethisterone acetate (0.125 mg/day) on lipid/lipoprotein profile and coagulation/fibrinolysis. Methods: A double-blind, randomized, multicenter, parallel, 1-year trial enrolled 266 healthy women at least 2 years post menopause. Patients received either 0.025 mg estradiol and 0.125 mg norethisterone acetate daily or placebo transdermally. One hundred and thirty five women completed a second year open follow-up (96 had used Estragest TTS, 39 placebo during the first year), where all women had the estradiol/norethisterone patch. Lipid/lipoprotein profile and coagulation/fibrinolysis parameters were studied at 0, 24, 48, 72 and 96 weeks. Results: In women on estradiol/norethisterone total cholesterol, Lp(a) and VLDL cholesterol decreased significantly more than in the placebo group after 24 weeks and LDL cholesterol after 48 weeks. Women on estradiol/norethisterone had no change in HDL, triglycerides or Lp(a), an increased HDL/total cholestrol ratio and decreased LDL, VLDL and total cholesterol at 48 weeks compared to placebo. Women with active treatment also showed a significant reduction compared with the placebo group of Factor VII and antithrombin III at 24 and 48 weeks and a reduction of fibrinogen at 24 weeks. These changes persisted over the second year. Conclusions: A continuous combined low-dose transdermal patch daily delivering 0.025 mg estradiol and 0.125 mg norethisterone acetate provided beneficial effects on lipid/lipoprotein profile and coagulation/fibrinolysis. The changes were similar to those previously described after higher dose oral and transdermal estrogen/progestogen regimens.

The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease

Objectives: The aim of the present study was to determine and correlate tissue factor pathway inhibitor (TFPI), lipoprotein (a) (Lp(a)), oxidized low-density lipoprotein (LDL) antibody (oLAB), and thiobarbituric acid reactive substances (TBARS; as a marker of lipid peroxidation) levels in patients with coronary artery disease (CAD) and in a control group. Design and methods: Peripheral blood samples from patients with coronary heart disease were provided by the Department of Cardiology. Serum oLAB, Lp(a), plasma total TFPI, and plasma-free TFPI levels were determined by ELISA. Serum TBARS levels were determined by a spectrophotometric method using thiobarbituric acid. Results: The CAD and the control group were matched for age and sex. Serum Lp(a), oLAB, and plasma total TFPI levels in patients with coronary heart disease were found to be significantly higher than in the control group ( P < 0.001). But there was no difference in plasma-free TFPI levels between patients with CAD and the control group ( P > 0.05). In patients with single ( P < 0.05), double, and triple vessel ( P < 0.01) disease, the mean serum Lp(a) levels were significantly higher than in the control group. On the other hand, in patients with single vessel disease ( P < 0.05), double vessel disease ( P < 0.05), and triple vessel disease ( P < 0.001), plasma total TFPI levels were found to be significantly higher than in the control group. We also found a significant positive correlation ( r = 0.28, P < 0.05) between serum Lp(a) and plasma total TFPI levels in CAD. In the patient group, TBARS, total cholesterol, triglyceride (TRG), and LDL cholesterol levels were found to be significantly higher than those in the control group. In addition, high-density lipoprotein (HDL) cholesterol levels were found to be significantly lower than the control group. Conclusions: These results suggest that elevated plasma levels of total TFPI, Lp(a), and oLAB may be useful diagnostic and monitoring markers in patients with CAD.

Cardiovascular risk factors in women with and without rheumatoid arthritis

The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA). The objective of this study was to examine the distribution of known CVD risk factors and biomarkers of CVD in women with and without RA. This study included two components: an examination of clinical CVD risk factors among women participating in the Nurses' Health Study, a prospective longitudinal cohort, and an analysis of CVD biomarkers among a subgroup of women from this cohort who provided a blood specimen in 1989 (biospecimen cohort). Data regarding clinical risk factors for CVD were collected in 1990 by mailed questionnaire. The diagnosis of RA was confirmed through a structured medical record abstraction. We compared clinical risk factors for CVD and biomarkers of CVD between women with and without RA, adjusting for age, body mass index (BMI), smoking status, and menopause status. Women with RA (n = 287) were significantly more likely than women without RA (n = 87,019) to report no alcohol use (48.2% versus 39.4%) and past cigarette smoking (47.8% versus 38.0%). No significant differences between these groups were observed for current smoker status, BMI, regular aspirin use, diabetes, hypertension, physical activity, and family history of early myocardial infarction. In the biospecimen cohort (69 RA cases and 491 controls), the levels of several inflammatory biomarkers linked to CVD were significantly elevated in women with RA, including CRP, fibrinogen, sICAM-1, sTNFRI, sTNFRII, and osteoprotegerin. Levels of total cholesterol, low-density lipoprotein, triglycerides, apolipoprotein B, and Lp(a) were similar between groups. Levels of homocysteine were similar, but vitamin B(12) was significantly higher among women with RA than among the controls. In women participating in the Nurses' Health Study, most traditional CVD risk factors were similar between those who had RA and those who did not. However, as expected, biomarkers of inflammation associated with CVD were generally elevated in women with RA.

Lipoprotein Compositional Changes With Combination Hormone Therapy (Conjugated Estrogen And Medroxyprogesterone) in African American Women

To determine whether combination hormone therapy (HT) significantly alters lipoprotein composition in healthy African American women. Postmenopausal African American women, 45 to 65 years old, were randomly assigned to receive daily HT (conjugated equine estrogen, 0.625 mg, and medroxyprogesterone, 2.5 mg) or placebo (treated, 44; placebo, 16) for 12 weeks. Lipoproteins were separated by gradient ultracentrifugation into very-low-density, intermediate-density, and low-density lipoproteins (VLDL, IDL, and LDL) and 3 high-density lipoprotein (HDL) subfractions (light, medium, and dense--L, M, and D). Apolipoprotein (apo) A-I, A-II, C-III, C-II, and C-I were measured by high-performance liquid chromatography. Apo B, phospholipids, triglycerides, cholesterol, and free cholesterol were measured by standard assays. Total plasma cholesterol, triglycerides, LDL apo B, and total apo B did not change during HT. A small, transient reduction occurred in LDL cholesterol, and a persistent reduction was noted in VLDL apo B, apo C-II, and apo C-III. Total HDL phospholipids, cholesterol, apo A-I, and apo A-II increased, whereas the LDL/HDL ratio and the apo B/apo A-I ratio decreased. Cholesterol ester increased in both HDL-L and HDL-M, but only a transient increase occurred in HDL-L phospholipids. Apo A-I increased in HDL-L, HDL-M, and HDL-D; however, a similar increase occurred in HDL-D apo A-I in the control subjects. Moreover, an increase occurred in apo A-II in HDL-M. A reduction in the apo A-II:A-I ratio in HDL-L but not in HDL-M indicated an increase in HDL-L LpA-I particles. The increase in HDL particles in HDL-M was entirely due to an increase in LpA-I:A-II particles. Apo C-III increased in both HDL-L and HDL-M. The absence of changes in the HDL lipid ratios indicated an unaltered lipid composition of these particles. No changes were found in IDL compositional measurements. In 12 treated patients and 4 control subjects, Lp(a) was detected by ultracentrifugation; no changes were noted in Lp(a) composition or quantity with HT. Total Lp(a) measured by enzyme immunosorbent assay showed a trend toward an increase in treated patients after 12 weeks of HT. African American women had a beneficial response to HT by increasing the number of LpA-I particles in HDL-L and LpA-I:A-II particles in HDL-M as well as cholesterol esters in both. There was a small reduction in VLDL apo B (and thus particle number) but only a transient reduction in LDL cholesterol. A shift of apo C-III from VLDL to HDL was noted. No detrimental changes occurred in any lipoprotein subfraction (specifically, no increase in triglycerides).

Influence of the Type of Membrane and Heparin on Serum Lipid Parameters during a Dialysis Session: A Pilot Study

Background/Aim: The type of heparin and membrane used might influence the lipids in patients on hemodialysis (HD). However, there are limited and debatable data concerning the lipid changes during an HD session. The aim of our study was to examine the changes in serum lipid parameters during the HD session in relation to the heparin and dialysis membrane used. Methods: Ten patients on HD 3 times/week participated in the study. The study was performed in three phases (A, B, C), each of 1 week’s duration. The types of membranes used were Hemophan (phase A), ethylene vinyl alcohol (phase B) and polyacrylonitrile (phase C), respectively, in a random order. During the midweek session of each phase we used classic heparin, while during the session at the end of the week low molecular weight heparin was administered. Serum total cholesterol, triglycerides, HDL cholesterol, Lp(a), albumin and total proteins were measured before and 5 min after the HD and hourly during the HD session. Results: In all phases, we found a progressive increase in all lipid parameters during the HD session, except Lp(a). This increase, however, was possibly due to hemoconcentration. Conclusions: This pilot study showed that (1) the type of heparin and membrane used does not seem to affect the serum lipid profile during a single HD procedure, and (2) the changes observed in serum lipid parameters are mainly due to hemoconcentration.

Lipoprotein lipase and hepatic lipase: their relationship with HDL subspecies Lp(A-I) and Lp(A-I,A-II)

HDL subspecies Lp(A-I) and Lp(A-I,A-II) have different anti-atherogenic potentials. To determine the role of lipoprotein lipase (LPL) and hepatic lipase (HL) in regulating these particles, we measured these enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and studied their relationship with Lp(A-I) and Lp(A-I,A-II). LPL was positively correlated with the apolipoprotein A-I (apoA-I), cholesterol, and phospholipid mass in total Lp(A-I), and with the apoA-I in large Lp(A-I) (r >or= 0.58, P >or= 0.001). HL was negatively correlated with all the above Lp(A-I) parameters plus Lp(A-I) triglyceride (r >or= -0.53, P <or= 0.003). No correlation was detected between LPL and Lp(A-I,A-II). However, HL was inversely correlated with total Lp(A-I,A-II) phospholipid, and with large Lp(A-I,A-II) (r >or= 0.50, P <or= 0.006). Similar studies were performed with phospholipid transfer protein (PLTP). Only total Lp(A-I) triglyceride in women (not men) (r = 0.71, P = 0.009) was significantly correlated with PLTP activity. These observations indicate that LPL and HL play major roles in determining the level and composition of plasma Lp(A-I), particularly large Lp(A-I), but not with Lp(A-I,A-II) level. Furthermore, select correlations of LPL and/or HL with the apoA-I, cholesterol, and triglyceride of Lp(A-I) but not Lp(A-I,A-II) imply that the apoA-I and lipid of Lp(A-I) and Lp(A-I,A-II) are not fully equilibrated.

Prevalence of dyslipidemic risk factors in hemodialysis and CAPD patients

Dyslipidemic factors obviously contribute to the high cardiovascular risk in dialysis patients but are often an underestimated problem. Therefore, we determined the prevalence of dyslipidemic factors in a large group of unselected hemodialysis (N = 564) and CAPD (N = 168) patients. We used the recently published recommendations of the Medical Experts Group concerning cardiovascular risk factors for the categorization of dyslipidemic factors. These were total cholesterol>200 mg/dL, low-density lipoprotein (LDL) cholesterol>100 mg/dL, high-density lipoprotein (HDL) cholesterol <40 mg/dL, triglycerides>180 mg/dL, and Lp(a)>30 mg/dL. CAPD patients had, in sum, a markedly worse lipid profile when compared with HD patients. They had higher frequencies of elevated total cholesterol (67% vs. 34%), triglycerides (47% vs. 28%), and Lp(a) concentrations (37% vs. 30%) when compared with HD patients. In both patient groups, about two thirds of the patients had LDL cholesterol above 100 mg/dL and HDL cholesterol below 40 mg/dL. When we analyzed the total frequency of dyslipidemic factors, we observed that the CAPD group included a markedly higher number of patients with three or four concurrent dyslipidemic factors than HD patients (P < 0.001). Furthermore, we analyzed apolipoprotein A-IV (apoA-IV), which was recently shown to be associated with cardiovascular disease, and which was about twice as high in both patient groups when compared with controls (P < 0.001). Dyslipidemic risk factors are highly prevalent in dialysis patients, and the concomitant occurrence of several risk factors in a given patient is more often observed in CAPD than HD patients.

Serum lipoprotein (a) and lipid profile in young South Indian patients with myocardial infarction

Coronary artery disease is now a major health problem in India. In past few decades the battle to reduce the incidence of coronary artery disease has led the researchers to look for various clinical markers, which would help early diagnosis of the diseases. The present study was undertaken to assess the level of lipoprotein (a) [Lp(a)] and few other lipids in selected myocardial infarction (MI) patients below 45 years without having any traditional risk factors but with positive family history. Fasting blood samples were taken from 65 patients and their total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglycerides and serum Lp(a) were determined. The control group consisted of 50 age matched healthy individuals. The mean Lp(a) level was 58.6±3.20 mg/dl in patients and 19.70±0.18 mg/dl in controls. Thus Lp(a) levels were found significantly higher in patients with MI (p<0.05 for patients versus control) as compared to the controls. There was no significant difference in the levels of total cholesterol (TC), LDL, VLDL HDL, TGL as compared to controls but there was an increase in TC/HDL cholesterol ratio. The results of this study suggest that high level of Lp(a) and TC/HDL ratio has a distinctive association with MI, independent of other common coronary risk factors. Hence, Lp(a) level in serum emerges to be a promising marker for diagnosis of coronary artery diseases.

Palm oil-enriched diets reduced plasma Lp(a) in volunteers with abnormally high concentrations: involvement of decreased triglyceride-rich APO(a)

Although plasma Lp(a) concentration is thought to be genectically determined, several studies have shown that certain dietary oils such as palm and fish oils can reduce its concentration in plasma. The present study, therefore, was conducted to identify possible mechanism whereby these dietary fat modifications lowered plasma Lp(a) concentration. Eleven healthy subjects with plasma Lp(a) concentrations >30 mg/dl received a palm oil diet (65% total fat intake) for 4 weeks. Blood samples were taken 12 hours pre-prandially and 4 hours post-prandially, for baseline assays prior to consumption of experimental diets, and at 2 week intervals thereafter. Individuals were therefore deemed to be their own controls. Pre- and post-prandial total Lp(a) decreased by 10% ( P < 0.001) and 7% respectively at the end of the study compared to baseline values. Plasma samples were separated into triglyceride-rich particle-(TRP)-apo(a) and cholesterol ester (CE) Lp(a) fractions by ultra-centrifugation. Individual contributions to the significant decrease in pre-prandial total Lp(a) concentrations were determined. Post-prandial TRP-apo(a) concentrations at week 4 were decreased compared to baseline (week 0). 10 subjects showed decreases of 0.25 mg/dl to 3.5 mg/dl. At week 0, post-prandial CE-Lp(a) concentrations were higher than pre-prandial levels. In contrast, at week 4 the post-prandial CE-Lp(a) levels were lower compared to respective pre-prandial levels. Increased pre-prandial concentrations of 0.6 to 12.5 mg/dl in 7 of the subjects and decreases in post-prandial concentrations of 0.1 to 27 mg/dl in 8 of the subjects at week 4 compared to week 0 were similar to changes observed in plasma TRP-apo(a) concentrations. This suggested that both fractions (TRP-apo(a) and CE-Lp(a)), contributed to the observed changes in total Lp(a) concentrations. Reductions in post-prandial total Lp(a) concentrations were most likely due to changes in post-prandial TRP-apo(a). Reciprocal changes in apo(a) between the TRP- and CE-Lp(a) fractions, particularly during the post-prandial phase, were also determined. No consistent relationships between the apo(a) content in the two fractions were observed but the mean ratio of TRP-apo(a) to CE-Lp(a) fraction was 1:50 in the pre-prandial states and ∼1:25 in the post-prandial states suggesting an increased preference of post-prandial apo(a) for TRP. The significance of these changes to total plasma Lp(a) concentration and to vascular disease risk is unclear at present.

Relation of lipid and lipoprotein(a) to ischaemic stroke

The relationship of lipids and Lp(a) to ischemic stroke hasn't been established yet. Our aim was to determine lipid profile and vascular risk factors in stroke patients and compare them with control subjects. Seventy-nine consecutive patients with ischemic stroke were analyzed by total cholesterol, HDL-C, LDL-C, triglyceride, Lp(a) and doppler ultrasonography and vascular risk factors were recorded. Thirty control subjects of same ages were compared with the patient group. Lp(a) and lipids were correlated with stroke subtype and carotid atherosclerosis. There was no statistical significance between patients and control subjects related to total cholesterol, triglyceride, HDL-C, LDL-C and Lp(a) (P>0.05). Atherotrombotic and lacunar strokes didn't show any difference correlated with lipids and Lp(a). Hypertension and diabetes mellitus were important risk factors with (OR=4.50, 95% CI=1.25–16.22) and (OR=4.43, 95% CI=1.79–10.93) respectively. These results were statistically significant (P<0.05). Total cholesterol (308.67±85.82) and Lp(a) (32.10±17.30) values showed statistical significance (P<0.05) in patients with marked stenosis when compared with patients of normal doppler ultrasonography. Hypertension and diabetes mellitus were found as independent risk factors for ischemic stroke. Lipids and Lp(a) were not independent for atherotrombotic and lacunar stroke. Lp(a) concentration and carotid atherosclerosis in ultrasonography were associated significantly.

Four-year study of large-particle vertical distribution (0–1000m) in the NW Mediterranean in relation to hydrology, phytoplankton, and vertical flux

Abstract Data on large particles (LP; >0.15 mm), phytoplankton communities, vertical fluxes, and hydrology were collected between January 1992 and June 1996 in the NW Mediterranean Sea, during DYFAMED, an interdisciplinary program part of JGOFS France. LP concentrations at the study sites were typical for values found in other open-ocean studies. LP temporal evolution showed an annual cycle. Concentrations were the highest in winter/spring (20–120 l−1, 5–280 mg m−3) and lowest in summer and autumn (0–20 l−1, 0.8–60 mg m−3). We estimated that LP accounted on average, for 2–30% of the total particulate (>0.7 μm) dry weight (DW). LP temporal evolution between 0–200 m was correlated with total Chl a and fucoxanthin (diatoms), and inversely correlated to zeaxanthin (cyanobacteria and prochlorophytes). Although diatoms were clearly associated to LP, prymnesiophytes were associated to the two highest accumulation of particles >1 mm. The DW fraction of particle >0.5 mm to total LP increased from 10% in regenerated systems dominated by picoplankton to 50% during spring blooms. LP concentrations in the upper 200 m were correlated to mass flux recorded in sediment trap at 200 and 1000 m. We defined three main periods for LP downward export related to physical stratification. (1) The major LP export occurred in winter and may be affected by deep vertical mixing; (2) in spring, at the onset of the thermal stratification LP downward export decreased, although pulses of phytoplanktonic production may have enhanced LP sedimentation over short time scales; (3) during the summer stratification, the deep water was generally depleted in LP.

Effects of androgen manipulation on postprandial triglyceridaemia, low-density lipoprotein particle size and lipoprotein(a) in men

Although androgenic hormones decrease HDLC concentration, no direct evidence has linked them to atherosclerosis. The present study was undertaken to extend our ability to assess risk associated with androgen induced lipoprotein(Lp) changes by simultaneously gathering information about postprandial triglyceridaemia (PPT), LDL particle size, HDL and Lp(a) in men either taking exogenous androgens or with suppressed endogenous androgen concentrations. The experimental groups comprised nine male bodybuilders who self-administered anabolic-androgenic steroids (AAS) for a mean period of 6.5 weeks, and 10 healthy men whose testosterone concentration had been reversibly suppressed for 5 weeks using the GnRH agonist triptorelin (Decapeptyl®; d-Trp-6-LHRH). A separate group receiving no hormonal treatment provided analytical control ( n=7). Lipoprotein size was assessed by gradient gel electrophoresis categorisation (GGE), lipoprotein concentrations by immuno and enzymatic assays and PPT by a standardised oral fat tolerance test (65g /m 2). Testosterone concentration was significantly reduced on triptorelin from 7.32±1.92 to 1.15±0.57 ng/ml ( P=0.002). High dose AAS use was confirmed by urinalysis. With AAS use, mean HDLC and Lp(a) concentrations and PPT decreased from 0.9±0.3 to 0.7±0.3 mmol/l ( P=0.004), 125±128 to 69±73 U/l ( P=0.008) and 11.6±10.0 mmol/l h to 7.5±5.4 mmol/l h ( P=0.027) respectively. Mean total cholesterol and LDLC were unchanged. LDL size was unchanged in six AAS users, decreased in one but remaining in the normal size range, and increased in two from small LDL to the normal range. Size changes in the latter two subjects were associated with 42 and 58% reductions in PPT respectively. In the triptorelin group, mean total cholesterol, HDLC and Lp(a) were increased from 4.8±0.8 mmol/l to 5.2±1.0 mmol/l ( P=0.039), 1.1±0.2 to 1.4±0.3 mmol/l ( P=0.002) and 278±149 to 377±222 U/l ( P=0.004) respectively. Mean LDLC concentration and PPT were unchanged. LDL particle size increased in four, decreased in two, and was unchanged in four subjects. LDL size decreased in two and showed no change in the other five control subjects. Other lipid measures were unchanged in the control group. Thus, apart from lowering HDLC concentrations, no other potentially atherogenic effects of endogenous androgens or AAS were observed. A suppression of Lp(a) as well as a reduced PPT and increased LDL size in predisposed individuals may be antiatherogenic effects of AAS.

Evaluation of Lp[a] and other independent risk factors for CHD in Asian Indians and their USA counterparts

Conventional risk factors for coronary heart disease (CHD) do not completely account for the observed increase in premature CHD in people from the Indian subcontinent or for Asian Indians who have immigrated to the USA. The objective of this study was to determine the effect of immigration to the USA on plasma levels of lipoprotein [a] (Lp[a]) and other independent risk factors for CHD in Asian Indians. Three subject groups were studied: group 1, 57 subjects living in India and diagnosed with CHD (CHD patients); group 2, 46 subjects living in India and showing no symptoms of CHD (control subjects); group 3, 206 Asian Indians living in the USA. Fasting blood samples were drawn to determine plasma levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein [LDL cholesterol (LDL-Chol)], high density lipoprotein [HDL cholesterol (HDL-Chol)], apolipoprotein B-100 (apoB-100), and Lp[a]. Apolipoprotein [a] (apo[a]) size polymorphism was determined by immunoblotting. Plasma TG, apoB-100, and Lp[a] concentrations were higher in CHD patients than in control and USA groups. CHD patients had higher levels of TC and LDL-Chol and lower HDL-Chol than control subjects. However, the USA population had higher levels of TC, LDL-Chol, and apoB-100 and lower HDL-Chol than control subjects. Plasma Lp[a] levels were inversely correlated with the relative molecular weight of the more abundant of each subject's two apo[a] isoforms (MAI), and CHD patients showed higher frequencies of lower relative molecular weights among MAI. Our observed changes in lipid profiles suggest that immigrating to the USA may place Asian Indians at increased risk for CHD. This study suggests that elevated plasma Lp[a] confers genetic predisposition to CHD in Asian Indians, and nutritional and environmental factors further increase the risk of CHD. This is the first report implicating MAI size as a predictor for development of premature CHD in Asian Indians. Including plasma Lp[a] concentration and apo[a] phenotype in screening procedures may permit early detection and preventive treatment of CHD in this population.

β 2-glycoprotein I deficiency: : prevalence, genetic background and effects on plasma lipoprotein metabolism and hemostasis

β 2-glycoprotein I (β 2-GPI=apolipoprotein H) is an important autoantigen in patients with the antiphospholipid syndrome. It also plays a role in lipoprotein metabolism, such as anti-atherogenic property, triglyceride removal, and enhancement of lipoprotein lipase. Serum β 2-GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with complete β 2-GPI deficiency were identified. In one family, all affected had increased serum LDL-cholesterol levels or smaller particle sizes of LDL, while the other had no apparent abnormality in lipid metabolism. Individuals investigated had no history of thrombosis or overt abnormalities in hemostatic tests. A thymine corresponding to position 379 of the β 2-GPI cDNA was deleted in every β 2-GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6.3% in Japanese and none in Caucasians. Heterozygotes had significantly lower concentrations of serum β 2-GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration of β 2-GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.

Resistance of pelvic arteries and plasma lipids in postmenopausal women: Comparative study of tibolone and continuous combined estradiol and norethindrone acetate replacement therapy

Objective: We sought to compare vascular resistance and plasma lipids in postmenopausal women assigned to tibolone (a synthetic estrogen replacement steroid) therapy or continuous combined hormone replacement therapy. Study Design: Pulsatility and resistance indexes in pelvic arteries (color Doppler transvaginal ultrasonography) and lipids were monitored in this double-blind 1-year trial of 100 women randomized to either 2.5 mg tibolone or 2 mg 17β-estradiol plus 1 mg norethindrone acetate daily. Results: Both indexes of the arcuate arteries (uterine arteries) were significantly reduced beyond 3 and 6 months (12 months) from baseline, respectively, by the combined regimen compared with tibolone alone. Tibolone increased the resistance index of arcuate arteries but did not affect uterine arteries. There was no effect of either regimen on the internal iliac arteries. The medians of the percentage changes from baseline of high-density lipoprotein cholesterol (triglycerides) were significant between groups after 1 year, as follows: –17% (–16%) in the tibolone group and –4% (+15%) in the combined group, respectively. Both regimens similarly reduced total and low-density lipoprotein cholesterol and lipoprotein Lp(a). Conclusion: Hormone replacement therapy may induce different or opposite changes of both vascular resistance and lipids. It is unknown whether these findings may modify cardiovascular risk. (Am J Obstet Gynecol 2000;183:575-82.)

Cardiovascular risk markers in hypothalamic amenorrhoea.

To determine whether women with oestrogen deficiency due to hypothalamic amenorrhoea (HA) would demonstrate a lipid and lipoprotein pattern similar to that seen in menopause with higher total cholesterol (TC), LDL, triglyceride and Lp(a) and lower HDL levels than women with regular menstrual cycles. Cross-sectional. Fifty subjects: 21 women with HA and 30 eumenorrhoeic controls (NL) matched for age, BMI and fat-free mass. Lipid and lipoprotein levels. There was a significant difference in Lp(a) levels in the HA group between women with >19% fat intake and those <19% fat intake (352+/-231 vs. 116+/-62 mg/l, P = 0.006). Percent fat intake was the most significant determinant of Lp(a) levels in HA, accounting for 51% of the variation in Lp(a) levels. Mean HDL levels were higher in the women with HA compared with the controls (1.3+/- 0.3 vs. 1.1+/-0.2 mmol/l, P = 0.002). There was no significant difference between the groups in TC [4.4+/-0.9 (HA) vs. 4.1+/-0.8 mmol/l (NL), P>0.05], LDL [2.8+/-0.6 (HA) vs. 2.7+/-0.7 mmol/l (NL), P>0.05], triglycerides [1.8+/-0.5 (HA) vs. 1.7+/-0.5 mmol/l (NL), P>0.05] or Lp(a) [234+/-199 (HA) vs. 247+/-222 (NL) mg/l, P>0.05] levels. Reduced Lp(a) levels were associated with low dietary fat in women with HA. Moreover, in contrast to menopausal oestrogen deficiency, young women with HA and oestrogen deficiency have increased levels of HDL and no increases in TC, LDL and triglycerides. These data suggest that the negative effects of oestrogen deficiency on cardiovascular risk factors may be modified in women with hypothalamic amenorrhoea.

Serum Lp(a) Lipoprotein Levels in Patients with Atherosclerotic Occlusive Disease of the Lower Extremities

Objective to evaluate the association between Lp(a) lipoprotein levels, other serum lipids and the presence of lower limb atherosclerotic occlusive disease. Materials and methods angiographic findings in 36 patients were related to serum Lp(a). Total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol and Lp(a) levels were compared with those of 73 age- and sex-matched healthy controls. Results atheromatous lesions were localised in the femoropopliteal (≈60%) and aortoiliac (≈40%) segments. The number of stenosed arteries was ≥2 and the range of stenosis severity was between 40% and 100%. There was a significant increase in serum Lp(a) (p= 0.000001) and a decrease in serum HDL (p= 0.000009) levels in patients compared to controls. No difference was observed in total cholesterol, LDL-cholesterol or triglyceride. However, the ratio of total cholesterol/HDL-cholesterol was significantly higher (p= 0.005) in patients. Conclusion a dyslipidaemic serum profile, characterised by increased Lp(a) levels and decreased HDL-cholesterol levels, is associated with atherosclerotic occlusive disease of the lower extremities.

Lipoprotein(a) in the Nephrotic Syndrome

Abstract. Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are elevated in kidney disease, which suggests a role of this organ in the metabolism of Lp(a). Additional evidence for a role of the kidney in the clearance of Lp(a) is provided by the fact that circulating N-terminal fragments of apolipoprotein(a) (apo(a)) are processed and eliminated by the renal route. To further understand the mechanism underlying such renal excretion, the levels of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome (n = 15). In plasma, the absolute (24.7 ± 20.4 versus 2.16 ± 2.99 μg/ml, P &lt; 0.0001) as well as the relative amounts of apo(a) fragments (4.6 ± 3.4% versus 2.1 ± 3.3% of total Lp(a), P &lt; 0.0001) were significantly elevated in nephrotic patients compared with a control, normolipidemic population. In addition, urinary apo(a) excretion in patients with nephrotic syndrome was markedly elevated compared with that in control subjects (578 ± 622 versus 27.7 ± 44 ng/ml per mg creatinine, P &lt; 0.001). However, the fractional catabolic rates of apo(a) fragments were similar in both groups (0.68 ± 0.67% and 0.62 ± 0.47% in nephrotic and control subjects, respectively), suggesting that increased plasma concentrations of apo(a) fragments in nephrotic subjects are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine revealed that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a) fragments similar in size to those present in plasma, as well as C-terminal fragments of apo(a) were detected in urine from nephrotic patients but not in urine from controls. All of these apo(a) forms were in addition to smaller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultracentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney through the glomerulus, whereas smaller apo(a) fragments are secreted into the urine.