LpA-I Levels Research Articles

A complex phenotype in a child with familial HDL deficiency due to a novel frameshift mutation in APOA1 gene (apoA-IGuastalla)

We describe a kindred with high-density lipoprotein (HDL) deficiency due to APOA1 gene mutation in which comorbidities affected the phenotypic expression of the disorder. An overweight boy with hypertriglyceridemia (HTG) and HDL deficiency (HDL cholesterol 0.39mmol/L, apoA-I 40mg/dL) was investigated. We sequenced the candidate genes for HTG (LPL, APOC2, APOA5, GPIHBP1, LMF1) and HDL deficiency (LCAT, ABCA1 and APOA1), analyzed HDL subpopulations, measured cholesterol efflux capacity (CEC) of sera and constructed a model of the mutant apoA-I. No mutations in HTG-related genes, ABCA1 and LCAT were found. APOA1 sequence showed that the proband, his mother and maternal grandfather were heterozygous of a novel frameshift mutation (c.546_547delGC), which generated a truncated protein (p.[L159Afs*20]) containing 177 amino acids with an abnormal C-terminal tail of 19 amino acids. Trace amounts of this protein were detectable in plasma. Mutation carriers had reduced levels of LpA-I, preβ-HDL and large HDL and no detectable HDL-2 in their plasma; their sera had a reduced CEC specifically the ABCA1-mediated CEC. Metabolic syndrome in the proband explains the extremely low HDL cholesterol level (0.31mmol/L), which was half of that found in the other carriers. The proband's mother and grandfather, both presenting low plasma low-density lipoprotein cholesterol, were carriers of the β-thalassemic trait, a condition known to be associated with a reduced low-density lipoprotein cholesterol and a reduced prevalence of cardiovascular disease. This trait might have delayed the development of atherosclerosis related to HDL deficiency. In these heterozygotes for apoA-I truncation, the metabolic syndrome has deleterious effect on HDL system, whereas β-thalassemia trait may delay the onset of cardiovascular disease.

Acquired lecithin:cholesterol acyltransferase deficiency as a major factor in lowering plasma HDL levels in chronic kidney disease.

It has been suggested that a low plasma high-density lipoprotein cholesterol (HDL-C) level contributes to the high cardiovascular disease risk of patients with chronic kidney disease (CKD), especially those undergoing haemodialysis (HD). The present study was conducted to gain further understanding of the mechanism(s) responsible for the low HDL-C levels in patients with CKD and to separate the impact of HD from that of the underlying CKD. Plasma lipids and lipoproteins, HDL subclasses and various cholesterol esterification parameters were measured in a total of 248 patients with CKD, 198 of whom were undergoing HD treatment and 40 healthy subjects. Chronic kidney disease was found to be associated with highly significant reductions in plasma HDL-C, unesterified cholesterol, apolipoprotein (apo)A-I, apoA-II and LpA-I:A-II levels in both CKD cohorts (with and without HD treatment). The cholesterol esterification process was markedly impaired, as indicated by reductions in plasma lecithin:cholesterol acyltransferase (LCAT) concentration and activity and cholesterol esterification rate, and by an increase in the plasma preβ-HDL content. HD treatment was associated with a further lowering of HDL levels and impaired plasma cholesterol esterification. The plasma HDL-C level was highly significantly correlated with LCAT concentration (R=0.438, P<0.001), LCAT activity (R=0.243, P<0.001) and cholesterol esterification rate (R=0.149, P=0.031). Highly significant correlations were also found between plasma LCAT concentration and levels of apoA-I (R=0.432, P<0.001), apoA-II (R=0.275, P<0.001), LpA-I (R= 0.326, P<0.001) and LpA-I:A-II (R=0.346, P< 0.001). Acquired LCAT deficiency is a major cause of low plasma HDL levels in patients with CKD, thus LCAT is an attractive target for therapeutic intervention to reverse dyslipidaemia, and possibly lower the cardiovascular disease risk in these patients.

Selective evaluation of high density lipoprotein from mouse small intestine by an in situ perfusion technique

The small intestine (SI) is the second-greatest source of HDL in mice. However, the selective evaluation of SI-derived HDL (SI-HDL) has been difficult because even the origin of HDL obtained in vivo from the intestinal lymph duct of anesthetized rodents is doubtful. To shed light on this question, we have developed a novel in situ perfusion technique using surgically isolated mouse SI, with which the possible filtration of plasma HDL into the SI lymph duct can be prevented. With the developed method, we studied the characteristics of and mechanism for the production and regulation of SI-HDL. Nascent HDL particles were detected in SI lymph perfusates in WT mice, but not in ABCA1 KO mice. SI-HDL had a high protein content and was smaller than plasma HDL. SI-HDL was rich in TG and apo AIV compared with HDL in liver perfusates. SI-HDL was increased by high-fat diets and reduced in apo E KO mice. In conclusion, with our in situ perfusion model that enables the selective evaluation of SI-HDL, we demonstrated that ABCA1 plays an important role in intestinal HDL production, and SI-HDL is small, dense, rich in apo AIV, and regulated by nutritional and genetic factors.

Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

BackgroundIn a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C).To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups.Methodology/PrincipalOutcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12–25.17, p = 0.036). Furthermore, high LpA-I:A-II levels interacted with high apoE levels in establishing subgroup risk.Conclusions/SignificanceWe conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP.

Apolipoprotein-defined lipoprotein abnormalities in rheumatoid arthritis patients and their potential impact on cardiovascular disease

Objectives: The aim of this study was to explore apolipoprotein-defined lipoproteins for abnormalities when comparing non-rheumatological controls to rheumatoid arthritis (RA) patients.Methods: Apolipoprotein and lipoprotein profiles were measured on 94 RA patients and 79 controls by immunoturbidimetric procedures, electroimmunoassays, and immunoprecipitation. Differences between means were tested with a two-sided Student t test with Satterthwaite adjustment. p-values were adjusted for multiple comparisons using the Bonferroni procedure.Results: RA patients had significantly higher levels of total cholesterol (TC), triglycerides (TG), and very low density lipoprotein cholesterol (VLDL-C) than controls, but no significant differences in the levels of high density lipoprotein cholesterol (HDL-C) and LDL-C. RA patients had significantly lower levels of apolipoprotein (apo)A-I and lipoprotein (Lp)A-I:A-II, but no difference in levels of LpA-I than normal controls. There was a significant difference in the levels of LpB:C but not in LpB:C:E between RA patients and controls. The main abnormality among apoB lipoproteins was the significantly increased concentration of the LpA-II:B:C:D:E subclass in RA patients in comparison with controls. The high levels of LpA-II:B:C:D:E are also reflected in significantly increased levels of apoC-III, and apoC-III bound to apoB lipoproteins.Conclusion: The LpA-II:B:C:D:E subclass has potential as a new marker for cardiovascular disease (CVD) in RA patients.

Effect of the amyloidogenic L75P apolipoprotein A-I variant on HDL subpopulations

Background Hereditary amyloidosis due to mutations of apolipoprotein A-I (apoA-I) is a rare disease characterized by the deposition of amyloid fibrils constituted by the N-terminal fragment of apoA-I in several organs. L75P is a variant of apoA-I associated with systemic amyloidosis predominantly involving the liver, kidneys, and testis, identified in a large number of unrelated subjects. Objective of the present paper was to evaluate the impact of the L75P apoA-I variant on HDL subpopulations and cholesterol esterification in carriers. Methods and results Plasma samples were collected from 30 carriers of the amyloidogenic L75P apoA-I (Carriers) and from 15 non affected relatives (Controls). Carriers displayed significantly reduced plasma levels of HDL-cholesterol, apoA-I, and apoA-II compared to Controls. Plasma levels of LpA-I, but not LpA-I:A-II, were significantly reduced in Carriers. HDL subclass distribution was not affected by the presence of the variant. The unesterified to total cholesterol ratio was higher, and cholesterol esterification rate and LCAT activity were lower in Carriers than in Controls. Conclusions The L75P apoA-I variant is associated with hypoalphalipoproteinemia, a selective reduction of LpA-I particles, and a partial defect in cholesterol esterification.

LpA-I, LpA-I:A-II HDL and CHD-risk: The Framingham Offspring Study and the Veterans Affairs HDL Intervention Trial

Objective We tested the hypothesis that concentrations of LpA-I and/or LpA-I:A-II HDL subclasses are significantly associated with CHD prevalence and recurrent cardiovascular events. Methods LpA-I levels were determined by differential electroimmunoassay in male participants with ( n = 169) and without CHD ( n = 850) from the Framingham Offspring Study (FOS) and in male participants with CHD from the placebo arm of the Veterans Affairs HDL Intervention Trial (VA-HIT) ( n = 741). Data were analyzed cross-sectionally (FOS) and prospectively (VA-HIT) and were adjusted for established lipid and non-lipid CHD risk factors. Results We observed slightly but significantly higher LpA-I levels in CHD cases compared to all or to HDL-C-matched controls and slightly but significantly higher LpA-I:A-II levels in CHD cases compared to HDL-C-matched controls it the FOS. Neither LpA-I nor LpA-I:A-II levels were significantly different between groups with and without recurrent cardiovascular events in the VA-HIT. No significant differences were observed in LpA-I and LpA-I:A-II levels in low HDL-C (≤40mg/dl) subjects with CHD (VA-HIT, n = 711) and without CHD (FOS, n = 373). Plasma LpA-I concentration had a positive correlation with the large LpA-I HDL particle (α-1) but no correlation with the small LpA-I HDL particle (preβ-1). LpA-I:A-II concentration had a positive correlation with the large (α-2) and an inverse correlation with the small (α-3) LpA-I:A-II HDL particles. Conclusion Our data do not support the hypothesis that CHD prevalence (FOS) or recurrence of cardiovascular events (VA-HIT) are associated with significant reductions in the concentrations of LpA-I and/or LpA-I:A-II HDL subclasses.

Apolipoprotein AI– and AI:AII—containing lipoproteins in white men and women of the HERITAGE Family study: associations with metabolic risk profile variables

It is now well established that an increased high-density lipoprotein (HDL) cholesterol level, especially in the HDL 2 subfraction, is associated with a reduced risk of coronary heart disease (CHD). However, little is known about the associations between the apolipoprotein (apo) composition of HDL and CHD metabolic risk factors. In the present study, we examined the gender differences in plasma concentration of HDL containing apo AI only (LpAI) versus both apoAI and apoAII (LpAI/AII), and also compared their associations with body composition, adipose tissue (AT) distribution, and metabolic risk profile variables. For that purpose, we measured fasting plasma lipoprotein-lipid levels including LpAI and LpAI/AII concentrations in a sample of 215 men and 174 women, all Caucasians, of the HERITAGE Family Study. All subjects underwent anthropometric, body fatness (underwater weighing) and abdominal AT accumulation (computed tomography) measurements. We found that, women had higher LpAI and lower LpAI/AII concentrations compared with men. Whereas in women, LpAI levels were correlated to body fat mass and waist circumference, no association between body composition, fat distribution, and LpAI concentrations was noted in men. Increased LpAI concentrations were associated with higher HDL 2 cholesterol levels in both men and women. Overall, elevated LpAI and LpAI/AII concentrations showed contrasting associations with metabolic risk profile variables as high LpAI, but not LpAI/AII concentrations were associated with a more favorable metabolic risk profile. We also found that high HDL cholesterol appeared to be more closely related to a better metabolic risk profile than high LpAI in both genders. Our results suggest that LpAI and HDL cholesterol levels are good correlates of the metabolic profile, but that HDL cholesterol concentrations could still represent a better index in CHD risk assessment.

Effects of estrogen and medroxyprogesterone acetate on subpopulations of triglyceride-rich lipoproteins and high-density lipoproteins

Hormonal replacement therapy (HRT) in postmenopausal women has been shown to increase both triglyceride (TG) and high-density lipoprotein (HDL) cholesterol levels. To better understand the effects of conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA), the 2 most commonly prescribed hormones in HRT, on the different subpopulations of TG-rich and HDL lipoproteins, we conducted a placebo-controlled, double-blind, randomized, crossover study consisting of 3 different phases in 14 postmenopausal women. The 3 phases, each 8-week long, included: (1) placebo, (2) CEE 0.625 mg/d, and (3) CEE 0.625 mg/d and MPA 2.5 mg/d. Slight and statistically nonsignificant elevations in TG levels were observed during the CEE treatment. While very-low-density lipoprotein (VLDL) cholesterol levels were not significantly affected by CEE and CEE + MPA, both HRT treatments lowered remnant lipoprotein (RLP) cholesterol (−14% and −37%, respectively). Compared with placebo, CEE caused a significant increase in HDL, HDL 2, apolipoprotein (apo) A-I, LpAI, α1, and preα1 levels (12%, 27%, 17%, 26%, 60%, and 102%, respectively). The combination therapy blunted the CEE effect on all HDL parameters, resulting in HDL, HDL 2, and LpAI levels being no longer significantly different from placebo. Apo A-I levels and α1, and preα1 levels were still significantly higher than placebo (+11%, +50%, and +112%, respectively). These results indicate that HRT has beneficial effects on RLP levels and that, while the estrogen component of HRT has a beneficial effect on the HDL subpopulations mostly associated with coronary heart disease (CHD) protection, MPA partially inhibits this effect.

Niacin and cholesterol: role in cardiovascular disease (review)

Niacin has been widely used as a pharmacologic agent to regulate abnormalities in plasma lipid and lipoprotein metabolism and in the treatment of atherosclerotic cardiovascular disease. Although the use of niacin in the treatment of dyslipidemia has been reported as early as 1955, only recent studies have yielded an understanding about the cellular and molecular mechanism of action of niacin on lipid and lipoprotein metabolism. In brief, the beneficial effect of niacin to reduce triglycerides and apolipoprotein-B containing lipoproteins (e.g., VLDL and LDL) are mainly through: a) decreasing fatty acid mobilization from adipose tissue triglyceride stores, and b) inhibiting hepatocyte diacylglycerol acyltransferase and triglyceride synthesis leading to increased intracellular apo B degradation and subsequent decreased secretion of VLDL and LDL particles. The mechanism of action of niacin to raise HDL is by decreasing the fractional catabolic rate of HDL-apo AI without affecting the synthetic rates. Additionally, niacin selectively increases the plasma levels of Lp-AI (HDL subfraction without apo AII), a cardioprotective subfraction of HDL in patients with low HDL. Using human hepatocytes (Hep G2 cells) as an in vitro model system, recent studies indicate that niacin selectively inhibits the uptake/removal of HDL-apo AI (but not HDL-cholesterol ester) by hepatocytes, thereby increasing the capacity of retained HDL-apo AI to augment cholesterol efflux through reverse cholesterol transport pathway. The studies discussed in this review provide evidence to extend the role of niacin as a lipid-lowering drug beyond its role as a vitamin.

Relationships between alcoholic beverages and cardiovascular risk factor levels in middle-aged men, the PRIME study

The relationships between alcoholic beverages and cardiovascular risk factors were assessed in 6730 men living in France or Northern Ireland. In France, all alcoholic beverages were significantly correlated with body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), high density lipoprotein (HDL) parameters, PAI-1 and Factor VII, whereas only wine was negatively related with fibrinogen levels. After adjusting for center, age, BMI, educational level, smoking and marital status, wine had a lesser effect on blood pressure, triglyceride, apo B and LpE:B levels than beer. Wine was associated with lower fibrinogen levels and beer with higher PAI-1 activity levels independent of the amount of alcohol consumed. In Northern Ireland, wine was negatively correlated with BMI, triglycerides, LpE:B and fibrinogen, whereas beer was positively correlated with SBP and DBP, triglycerides, HDL, apoprotein A-I and fibrinogen. Multivariate analysis showed wine to be positively associated with HDL parameters, and negatively with fibrinogen levels. Wine was also associated with higher LpA-I levels and lower fibrinogen levels independent of the amount of alcohol consumed. We conclude that alcohol consumption is related to lipid, lipoprotein and haemostatic variables, but the magnitude of the relationships depends on the type of alcoholic beverage. Also, some effects might be related to non-alcoholic components.

THE EFFECT OF ENDURANCE EXERCISE TRAINING ON PLASMA LPAI AND LPAI

The effect of six months of endurance exercise training on plasma concentrations of LpAI (HDL containing apo A-I but not apo A-II), LpAI:AII (HDL containing apo A-I and apo A-II), and the molar ratio of apo A-II to apo A-I within LpAI:AII particles was determind in 39 sedentary subjects (17 males, 22 females, average age = 57) with abnormal cholesterol levels. Following the exercise training, there were significant changes in VO2max (+4.2 ± 0.4 ml/kg/min; p < 0.001) (mean ± S.E.), body weight (−1.0 ± 0.3kg; p = 0.004), % body fat (−1.0 ± 0.2%; p < 0.001), and intra-abdominal fat mass (−16.2 ± 3.4 cm2; p < 0.001). LpAI levels also increased (+5.9 ± 1.2 mg/dl; p < 0.001), but there was no change in either total apoA-I, LpAI:AII, or the molar ratio of apo A-II to apo A-I within LpAI:AII particles following the exercise training. The change in LpAI concentration was positively correlated to changes in total HDL-C (r = 0.495, p = 0.001), the sum of HDL4-Cnmr + HDL5-Cnmr (r = .417, p = 0.008), and average HDL particle size (r = 0.415, p = 0.009), but not to changes in VO2max or body composition indices. Training-induced changes in the size of the LpAI and LpAI:AII particles also were measured in 8 subjects. Both “medium” (7.8 ± 9.8 nm) and “large” (9.8 ± 12.2 nm) LpAI particles were detected in 7 of the 8 subjects tested, and there was a significant increase in the peak size of the “medium” LpAI particles of 0.1 nm (p = 0.048) following exercise training. For LpAI:AII, only “medium” sized particles were detected, and there was no change in the average size of these particles follwing exercise training. Furthermore, there was no evidence of “small” (< 7.8 nm) LpAI or LpAI:AII particles in any of the subjects tested. In conclusion, these data indicate that endurance exercise training increases the average size and plasma levels of LpAI, but not LpAI:AII, particles, and these changes represent possible enhancements of reverse cholesterol transport following exercise training.

Coronary artery disease in patients at low risk — apolipoprotein AI as an independent risk factor

Many risk factors for coronary artery disease (CAD) have been established by large epidemiological studies. However, some patients without the major risk factors still develop disease. Preliminary analysis of individuals referred for angiography, who had no major risk factors associated with CAD, indicated that apolipoprotein-AI (apoAI) was significantly lower in patients with positive angiograms. The hypothesis that apoAI was an independent risk factor for CAD in low risk populations was put forth. One thousand and seventy-five consecutive patients underwent angiography, lipid analysis, and completed a risk factor questionnaire. Individuals with total cholesterol<5.2 mmol/l, high density lipoprotein (HDL)-cholesterol>0.9 mmol/l, systolic blood pressure<140 mmHg and diastolic blood pressure<90 mmHg, no diabetes, and no family history of premature CAD in first degree relatives were selected. Fifty-four patients met these selection criteria, 29 having positive evidence of CAD and 25 with no evidence of disease. Multivariate analysis revealed that, after adjusting for age and gender, serum apoAI level was the only variable predictive of CAD. This effect was independent of HDL cholesterol level and fractional esterification rate of HDL (FER HDL). These results point to an important role for apoAI in the atherogenic process, particularly in populations with no major CAD risk factors. Decreased levels of apoAI or LpAI may initiate atherosclerosis in a highly selected group of low risk patients.

Cholesterol Efflux Capacity In Vitro Predicts the Severity and Extent of Coronary Artery Disease in Patients with and without Type 2 Diabetes

Objective - To investigate the relation between severity and extent of coronary artery disease (CAD) and in vitro cholesterol efflux capacity. Design - This study consisted of 46 type 2 diabetic, and 42 nondiabetic men undergoing coronary angiography. Quantitative coronary angiography was used to estimate the severity, extent, and overall "atheroma burden" of CAD. The capacity of patient plasma to induce cholesterol efflux from cultured Fu5AH rat hepatoma cells was measured in vitro. Results - In the combined study population (n = 88), there was a significant inverse correlation between efflux and global atheroma burden (r = -0.23, p < 0.05). In the diabetic group, the global atheroma burden index was independently associated both with cholesterol efflux and with LpA-I levels. However, in the nondiabetic CAD group this association was lost when efflux and LpA-I levels were included in the same model. Conclusion - The present study demonstrated that efflux capacity was inversely associated with the severity and extent of CAD. In the diabetic group this association was independent of LpA-I levels, suggesting impaired antiatherogenic potential of these particles in type 2 diabetic patients.

Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase: high density lipoprotein characterization and gender-specific effects of apolipoprotein E genotype

Turks have strikingly low levels of high density lipoprotein cholesterol (HDL-C) (10-15 mg/dL lower than those of Americans or Western Europeans) associated with elevated hepatic lipase mass and activity. Here we report that Turks have low levels of high density lipoprotein subclass 2 (HDL(2)), apoA-I-containing lipoproteins (LpA-I), and pre-beta-1 HDL and increased levels of HDL(3) and LpA-I/A-II particles (potentially an atherogenic lipid profile). The frequency distributions of HDL-C and LpA-I levels were skewed toward bimodality in Turkish women but were unimodal in Turkish men. The apoE genotype affected HDL-C and LpA-I levels in women only. In women, but not men, the varepsilon2 allele was strikingly more prevalent in those with the highest levels of HDL-C and LpA-I than in those with the lowest levels. The higher prevalence of the epsilon2 allele in these subgroups of women was not explained by plasma triglyceride levels, total cholesterol levels, age, or body mass index. The modulating effects of apoE isoforms on lipolytic hydrolysis of HDL by hepatic lipase (apoE2 preventing efficient hydrolysis) or on lipoprotein receptor binding (apoE2 interacting poorly with the low density lipoprotein receptors) may account for differences in HDL-C levels in Turkish women (the epsilon2 allele being associated with higher HDL levels). In Turkish men, who have substantially higher levels of hepatic lipase activity than women, the modulating effect of apoE may be overwhelmed. The gender-specific impact of the apoE genotype on HDL-C and LpA-I levels in association with elevated levels of hepatic lipase provides new insights into the metabolism of HDL.

Smaller, denser LDL particles are not a risk factor for cardiovascular disease in healthy nonagenarian women of the Cremona Population Study

We evaluated LDL particle size and its relation with other established risk factors for cardiovascular disease in a group of healthy nonagenarian (≥90 years) women participating in the Cremona Population Study. A group of younger healthy postmenopausal women (45–75 years) was used as control group. Nonagenarian women had significantly lower body mass index, systolic and diastolic blood pressure, and fasting insulin concentrations. Plasma total, LDL and HDL cholesterol, apo AI and apo B concentrations, and LpAI and LpAI:AII particles were significantly lower in the nonagenarian group as well. LDL particle size (262.7±0.9 vs. 270.1±1.1 Å) was also lower in the nonagenarian group. The presence of the E4 isoform of apo E in the nonagenarian group resulted in significantly higher levels of plasma apo AI and LpAI:AII particles, and a trend toward larger LDL particles, and a lower diastolic blood pressure. In conclusion, smaller and denser LDL particles might not represent an important risk factor for cardiovascular disease in healthy nonagenarian women of the Cremona Population Study, characterised by a reduced number of LDL particles and other protective factors, like low systolic and diastolic blood pressure, body mass index, and plasma insulin levels.

Hyperalphalipoproteinemia: Characterization of a cardioprotective profile associating increased high-density lipoprotein 2 levels and decreased hepatic lipase activity

The aim of the present study was to investigate the high-density lipoprotein (HDL) strucutral characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol) [HDL-C], 92 ± 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 ± 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL 2 HDL 3 ratio. HALP profile A was characterized in 28 patients by increased HDL 2 HDL 3 ratio, HDL 2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL 2 HDL 3 ratio within the normal range and by the increase of all HDL subclasses (HDL 2b,2a,3a,3b,3c). LPA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL 2 HDL 3 , HDL 2b, and LpA-I levels associated with decreased HL activity.

Beneficial effect on serum apo AI, apo B and Lp AI levels of Ramadan fasting

In order to investigate for the first time in Morocco the effect of fasting in Ramadan, the ninth lunar month of the muslim year, on lipoprotein metabolism, we determined the levels of serum apolipoproteins; apolipoprotein AI (apo AI), apo B, apo AIV and those of lipoprotein particles; apo AI-containing lipoprotein particles (Lp AI) and also apo AI and apo AII containing lipoprotein particles (Lp AI:AII) in a group of 32 healthy, volunteer adult males. Determination of all these parameters was carried out on each week of the month of Ramadan and the results are compared with the pre-fasting and the post-fasting values. Ramadan fasting reduces significantly serum apo B ( P<0.05), while serum apo AI is significantly increased ( P<0.05) compared with the pre-fasting period. The increase of apo AI occurred on day 29 of Ramadan by 11.8%. Serum apo AIV was unchanged during the fasting period indicating that food intake during Ramadan is not based on lipid diet. The observed diet pattern during Ramadan showed an increase of total energy intake based on carbohydrates (+1.4% of total energy), proteins (+0.4% of total energy) but not on fat (−0.7% of total energy), compared with a usual diet used in the rest of the year. The fat diet is high in monounsaturated ( P<0.05) and polyunsaturated fatty acid in contrast to saturated fatty acid which decreased ( P<0.05) during Ramadan. On the other hand, analysis of serum Lp AI and Lp AI:AII showed that the levels of Lp AI:AII were unchanged but those of Lp AI were significantly increased ( P<0.01) at the end of Ramadan. These findings show that feeding behaviour that occurs during Ramadan beneficially affects serum apolipoprotein metabolism and may contribute to prevention of cardiovascular diseases.

1.P.335 LpAI levels in Japan

1.P.335 LpAI levels in Japan

LpA-I levels do not reflect pre β1-HDL levels in human plasma

High-density lipoprotein (HDL) containing apo A-I but no apo A-II (LpA-I) can promote cholesterol efflux from cells, while HDL containing apo A-I and apo A-II can not. Pre β1-HDL, a minor fraction of LpA-I, is the initial acceptor of cellular cholesterol. To determine whether the pre β1-HDL:LpA-I ratio is constant in human plasma, we measured LpA-I levels by differential electroimmunoassay, and HDL subfraction levels by nondenaturing 2-dimensional gel electrophoresis in 26 subjects. We found that the pre β1-HDL:LpA-I ratio was higher in hypercholesterolemia (0.21±0.09; n=11, P<0.05), coronary artery disease (0.26±0.13; n=5, P=0.08) and hypertriglyceridemia (0.39±0.22; n=3, P=0.16) than in normolipidemia (0.11±0.03, n=5). LpA-I levels were significantly correlated with HDL2b ( r=0.771, P=0.000001), HDL2a ( r=0.438, P<0.01), and pre β2-HDL levels ( r=0.496, P<0.005) but not with pre β1-HDL or HDL3 levels. In conclusion, the pre β1-HDL:LpA-I ratio is not constant in human plasma. These findings strongly suggest that size distribution of LpA-I may change in various disorders .