Median Lp Research Articles

Apolipoprotein (A) Isoform Distribution and Plasma Lipoprotein (a) Levels In Nigerian Subjects With and Without Coronary Heart Disease

Plasma lipoprotein (a) Concentrations and apo(a) isoforms were determined in 101 healthy Nigerian subjects (M=63), F=38; age range 17-68 years), and coronary heart disease (CHD) patients (M=19, F=17, age range 30-79 years). Median Lp(a) level was 24.4 mg/di in the CHD patients and 22.1 mg/di in the controls. The iso forms S1, S”, S and S4 were observed in both populations of CHD and controls. In the CHD group, a low molecular weight isoform (F) was also detected in a single heterozygous subject. No significant difference was observed between the distribution of the apo(a) isoforms in the controls and CHD subjects. Thus, Lp(a) levels or apo(a) isoform type may not be valuable predictors of CHD in the Nigerian population. Key Words: Lp(a), apo(a) isoforms, CHD, Africans [Jnl Medicine & Medical Sciences Vol.1(1) 1999: 1-5]

Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion.

To determine whether heritable thrombophilia and hypofibrinolysis were risk factors for retinal vein occlusion. Measures of thrombophilia (increased likelihood of thrombus formation) included anticardiolipin antibodies (IgG and IgM), the lupus anticoagulant (including dilute Russell viper venom clotting time), antigenic proteins C and S, and homocysteine. Polymerase chain reaction assays were performed for 3 thrombophilic gene mutations (factor V Leiden, methylenetetra-hydrofolate reductase, and prothrombin gene). Measures of hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein Lp(a), plasminogen activator inhibitor activity, and polymerase chain reaction analysis of the hypofibrinolytic 4G/5G polymorphism of the PAI1 gene. These coagulation measures were performed in 17 patients with retinal vein occlusions with comparison with serologic coagulation measures and polymerase chain reaction assays in 40 and 234 healthy normal volunteers as controls, respectively. Of 14 patients with retinal vein occlusion with measures of dilute Russell viper venom clotting time, a thrombophilic antiphospholipid antibody, 6 (43%) had abnormal results (> 38.8 seconds) compared with 1 (3%) of 30 controls (P = .002). Of 17 patients with vein occlusion, 3 (18%) were heterozygous for the thrombophilic factor V Leiden G1691A mutation compared with 7 (3%) of 233 controls (P = .02). Of 17 patients with vein occlusion, 2 (12%) had normal alleles (5G/5G) for the plasminogen activator inhibitor gene promoter; the other 15 (88%) were heterozygous or homozygous for the 4G polymorphism, which is associated with hypofibrinolysis. Of 234 controls, 85 (36.3%) had the 5G/5G allele; 149 (63.7%) were heterozygous or homozygous for the 4G polymorphism (P = .03). Patients with vein occlusion were more likely to have high levels of the major determinant of hypofibrinolysis, plasminogen activator inhibitor activity. These levels were high (> 22 U/L) in 6 (38%) of 16 patients with vein occlusion compared with 1 (2%) of 40 controls (chi 2 = 12.8; P = .001). Patients with vein occlusion were more likely (8/16 [50%]) to have high levels of hypofibrinolytic Lp(a) (> 35 mg/dL) than controls (5/40 [13%]; chi 2 = 9; P = .003). The median Lp(a) level in patients with vein occlusion who had the 4G/4G genotype was 62 mg/dL compared with 5.3 mg/dL in controls with the 4G/4G genotype (P = .05). Thrombophilia and hypofibrinolysis are possible causes of retinal vein occlusion.

Lipoprotein(a) levels and apolipoprotein(a) isoforms related to life style risk factors.

Lipoprotein(a) [Lp(a)] has been considered to be a predictor of premature coronary heart disease and other cardiovascular diseases. Lp(a) levels are largely genetically determined, but the detailed mechanism of Lp(a) elevation is uncertain. We examined the association between Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes as well as that of Lp(a) level and other various conditions. The subjects were 280 healthy Japanese (102 males and 178 females) aged 39 to 70 years who were living in a rural community in 1992. We obtained apo(a) phenotypes determined by SDS-PAGE as well as Lp(a) levels and other cardiovascular risk factors. We combined apo(a) phenotypes form 4 groups according to molecular weights (from high apo(a) molecular weight to low: I, II, III and IV). Lp(a) levels were associated with apo(a) phenotype-groups, that is, they were inversely associated with apo(a) molecular weight. Small apo(a) phenotypes were less frequent than large ones. The median Lp(a) level was higher in smoking (29.2 mg/dL) than in non-smoking subjects (18.5 mg/dL) in phenotype-group III. Adjusted means of total cholesterol and fibrinogen levels in apo(a) phenotype-group IV were the highest of all phenotype-groups. Age, apo(a) phenotype, smoking status, total cholesterol and fibrinogen were positively correlated with Lp(a) levels by multiple regression analysis. Lp(a) levels were found to be mainly associated with apo(a) phenotype, but varied broadly within the same apo(a) phenotype at various conditions, such as smoking status and high total cholesterol.

Serum lipoprotein (a) concentrations among Arab children: a hospital-based study in Kuwait.

Elevated lipoprotein (a) [Lp(a)] is an independent risk factor for premature atherosclerosis and coronary heart disease, both of which are prevalent among Kuwaitis. Our objective was to measure serum lipids, including Lp(a), in Arab children and compare them with values reported for other ethnic groups. To that end, serum concentrations of Lp(a), total cholesterol [T-CHOL], high density lipoprotein [HDL], low density lipoprotein [LDL], and triglyceride [TG] were assessed in 103 Arab children. The mean and median Lp(a) were 140.4 mg/l and 95 mg/l, respectively. The Lp(a) frequency distribution was skewed to the right with the highest frequencies appearing at low levels. Serum Lp(a) correlated positively with T-CHOL and LDL but did not correlate with age, HDL and TG. Only nine children (8.7%) had serum Lp(a) levels associated with increased cardiovascular risk, namely > or = 300 mg/l.

Regional serum cholesterol differences in Belgium: do genetically determined cardiovascular risk factors contribute?

Differences in serum lipid distribution and mortality from ischaemic heart disease have repeatedly been reported between Belgian northerners and southerners. We investigated whether serum lipoprotein(a) (Lp(a)) and apolipoprotein (apo) E polymorphism were involved. Fasting serum lipids, apo A-I and B, and Lp(a) levels were examined in randomly selected, 20-39 year old Belgian males and females from the north (Flanders) and the south (Wallonia) of Belgium (N = 900). Apo E phenotype distribution was investigated in random subsamples from either region (N = 249). Mean serum cholesterol, low density lipoprotein cholesterol (LDL-c), apo B and triglyceride levels were higher in Walloons compared to Flemings within each gender, the difference being significant in 30-39 year old males. Average high density lipoprotein cholesterol and apo A-I levels were significantly lower in 30-39 year old male southerners, compared to their northern counterparts. Median Lp(a) was 67 mg/l in northerners and 75 mg/l in southerners (NS). The apo E phenotype distribution was similar in both regions (chi2 = 7.213; d.f. = 5; P = 0.2053), whereas the average effects of the apo E alleles differed between the regions. In southerners the epsilon4 effect upon adjusted apo B and LDL-c levels was approximately+12% and the epsilon2 effect was approximately-15%; in northerners the epsilon4 and epsilon2 effects were approximately+5% and approximately-25%, respectively. The apo E polymorphism did not affect serum Lp(a) levels. Regional cholesterol differences between Flemings and Walloons cannot be explained by differences in serum Lp(a) or apo E phenotype distribution. The less favourable epsilon2 and epsilon4 effects in southerners compared to northerners reflect modulation of the apo E gene by particular environments.

Vascular risk factors and lipoprotein(a) levels in the differential diagnosis of dementias

Summary Several vascular risk factors, including lipoprotein(a) (Lp(a)) levels, and its apo(a) isoforms were evaluated in 104 consecutively hospitalized demented patients, with the aim of comparing their prevalence in dementias of different etiology. The sample included 67 vascular dementias (VD), 29 senile dementias of Alzheimer's type (SDAT), and 8 hemorrhagic dementias (HD). The NINDS-AIREN and NINCDS/ADRDA criteria were used for the diagnosis. Hypertension, and signs of left ventricular hypertrophy (LVH) were more frequent in VD and HD, than in SDAT, and were positively associated with cortical-subcortical infarction; signs of LVH were also associated with leukoaraiosis. Demented patients had lower total cholesterol (TC) and high density lipoprotein-C (HDL-C) levels than controls. No differences in serum lipids emerged between the 3 demented groups. Median Lp(a) was higher in VD, as compared to SDAT and controls, and in patients with lacunar infarctions. Lp(a) higher than 30 mg/dl was more frequent in VD than in SDAT and controls. Apo(a) S1 isoforms were significantly more frequent in VD than in SDAT + HD; isoforms heavier than S4 were more frequent in HD than in VD and SDAT. The Hachinski ischemic score (HIS) was positively correlated with Lp(a) levels (Spearman Rho = 0.23, p

High level of lipoprotein(a) is a strong predictor for progression of coronary artery disease.

Elevated levels of serum lipoprotein(a) [Lp(a)] are reported to be associated with risk of atherosclerosis and thrombosis. Little is known about the influence of Lp(a) on the progression of coronary artery disease. We evaluated the association of serum Lp(a) and the long-term changes of angiographic severity in patients who underwent repeated coronary angiography at intervals of more than 2 years. We evaluated 70 patients, and divided them into 3 groups by angiographic findings. Median Lp(a) concentration was significantly higher in the progression group (N=36) than in the no-change group (N=23) or the regression group (N=11) (32.4 vs 22, 19.3 mg/dl, p<0.05). Furthermore, the progression group had more patients whose Lp(a) levels were greater than 30 mg/dl (p=0.006), while in the regression group all patients were under 30 mg/dl. Stepwise logistic regression analysis for progression of lesions showed that Lp(a) > or =30 mg/dl remained significant, giving an estimated odds ratio (OR) of 2.46 (p= 0.005). In the subgroup analysis, OR in patients with mild lesions was reduced to 2.05 (p<0.05) while in patients with severe lesions OR was increased to 3.39 (p=0.003). The serum Lp(a) level has a close correlation with angiographic progression, and may be an important predictor for progression.

Relationship between lipoprotein (a) and both stroke and carotid atheroma.

In vitro studies provide mechanisms by which elevated lipoprotein (a) [Lp(a)] concentrations may promote both thrombosis and atherogenesis. Case-control studies have reported raised Lp(a) concentrations in patients with stroke, but prospective studies have failed to confirm the association. A potential confounding factor is that Lp(a) may rise acutely after stroke. We determined Lp(a) concentrations in 164 patients studied at least 21 days after stroke or transient ischaemic attack, and in 91 controls. In the patient group we correlated Lp(a) concentrations with both the degree of carotid stenosis estimated on duplex ultrasonography, and with stroke subtype (large vessel disease, lacunar infarction, and cardioembolic and unknown pathogenesis). There was no difference between Lp(a) concentration in cases and controls [median (quartiles) 0.10 (0.04, 0.39) versus 0.12 (0.04, 0.30) g/L, P = 0.34]. There was no difference in the proportion of cases compared with controls with a markedly elevated Lp(a) of > 0.4 g/L (21.3 versus 16.5%, P = 0.34). There was non-significant trend towards higher median Lp(a) concentrations in women [median (quartiles) 0.16 (0.04, 0.32) g/L versus 0.12 (0.04, 0.28) g/L, P = 0.3]. In view of this trend we analysed the differences between cases and controls for each sex separately. Lp(a) concentrations in men were median (quartiles) 0.08 (0.04, 0.26) g/L in the 101 cases and 0.12 (0.04, 0.28) g/L in the 43 controls (P = 0.6). Lp(a) concentrations in women were median (quartiles) 0.25 (0.04, 0.44) g/L in the 63 cases, and 0.16 (0.04, 0.32) g/L in the 48 controls (P = 0.16). Within the patient group there was no difference between Lp(a) concentrations in the different stroke subgroups. There was no relationship between Lp(a) concentrations and mean percentage carotid stenosis (rs = 0.14, P = 0.07). Our results suggest that in an unselected population of men studied more than 3 weeks post event there is no relationship between lipoprotein(a) concentrations and either stroke/transient ischaemic attack, or carotid atheroma. The relationship in women requires further study.

Sib-pair analysis detects elevated Lp(a) levels and large variation of Lp(a) concentration in subjects with familial defective ApoB.

Whether or not Lp(a) plasma levels are affected by the apoB R3500Q mutation, which causes Familial Defective apoB (FDB), is still a matter of debate. We have analyzed 300 family members of 13 unrelated Dutch index patients for the apoB mutation and the apolipoprotein(a) [apo(a)] genotype. Total cholesterol, LDL-cholesterol, and lipoprotein(a) [Lp(a)] concentrations were determined in 85 FDB heterozygotes and 106 non-FDB relatives. Mean LDL levels were significantly elevated in FDB subjects compared to non-FDB relatives (P < 0.001). Median Lp(a) levels were not different between FDB subjects and their non-FDB relatives. In contrast, sib-pair analysis demonstrated a significant effect of the FDB status on Lp(a) levels. In sib pairs identical by descent for apo(a) alleles but discordant for the FDB mutation (n = 11) each sib with FDB had a higher Lp(a) level than the corresponding non-FDB sib. Further, all possible sib pairs (n = 105) were grouped into three categories according to the absence/presence of the apoB R3500Q mutation in one or both subjects of a sib pair. The variability of differences in Lp(a) levels within the sib pairs increased with the number (0, 1, and 2) of FDB subjects present in the sib pair. This suggests that the FDB status increases Lp(a) level and variability, and that apoB may be a variability gene for Lp(a) levels in plasma.

A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants.

Lipoprotein(a) [Lp(a)] is formed by the assembly of LDL particles and a carbohydrate-rich protein, apolipoprotein(a) [apo(a)], which has a high degree of structural homology with plasminogen. While the majority of retrospective studies have found an association between Lp(a) level and cardiovascular disease (CVD), the few prospective studies to date have reported contradictory results. We conducted a nested case-control study using the participants in the Stanford Five-City Project, a long-term CVD prevention trial. Participants with an incident possible or definite myocardial infarction or coronary death were matched to a single control subject for age, sex, ethnicity, residence in a treatment or control city, and time of survey. This process yielded 134 case-control pairs, 90 male and 44 female, for whom plasma was available for analysis of Lp(a). Lp(a) values in nanomoles per liter were determined by an enzyme-linked immunoassay that measures Lp(a) independently of apo(a) size polymorphism. Apo(a) size isoforms were determined by SDS-agarose gel electrophoresis. Median Lp(a) level in male cases was almost double that in control subjects (41.8 versus 21.2 nmol/L; P < .01); in female cases, median Lp(a) was 34% higher than in control subjects (32.5 versus 21.2 nmol/L), but this difference was not statistically significant. Among the male cases, there was an increased frequency of small apo(a) isoforms, while no significant difference was found in apo(a) size between female cases and control subjects. The association between Lp(a) level and case-control status in men was independent of total, HDL, and non-HDL cholesterol levels, as well as apo(a) size isoform, cigarette smoking, blood pressure, and obesity. In men, the most efficient threshold value of Lp(a) concentration for separating cases and control subjects was 35 nmol/L; the odds ratio for being a case above this level compared with below was 2.84 (95% confidence interval: 1.53-5.27, P < .001). This study provides strong evidence that Lp(a) level is a prospective, independent risk factor for developing coronary artery disease in men and indicates that the size of apo(a) may also play a role. The lack of a significant association in women deserves further evaluation in larger studies.

Early Elevation of Lipoprotein(a) Levels in Chronic Renal Insufficiency

Serum lipoprotein(a) [Lp(a)] concentrations in chronic renal failure patients were investigated in relation to the degree of renal insufficiency, treatment by maintenance hemodialysis, and correction of uremia by renal transplantation with or without cyclosporin immunosuppression. Fast serum levels of Lp(a) (mg/100 mL) were determined in 34 chronic renal failure patients not in need of maintenance dialysis (16 with serum creatinine 2.0–4.0 mg/100 mL; 18 with serum creatinine higher than 4.0 mg/100 mL), 40 patients treated by hemodialysis, 55 successful renal transplant recipients (28 under cyclosporin treatment and 27 receiving no cyclosporin), and 34 healthy controls. Age and sex distributions were similar among groups. Pregnant women; non-White individuals; subjects with obesity, diabetes, nephrotic syndrome, and hepatic and thyroid diseases; and those treated with oral contraceptives or lipid-lowering drugs were excluded from the study. Compared to controls, median Lp(a) was increased in nondialyzed renal failure patients (11 vs. 47.5 p < 0.001) and this was the only lipid abnormality observed in the group. There was no significant difference in Lp(a) levels between nondialized renal failure patients with serum creatinine 2.0–4.0 and >4.0 mg/100 mL (47 vs. 49, NS). Moreover, Pearson correlation coeficient (r = 0.01, NS) showed that Lp(a) values were not related to serum creatinine in nondialyzed patients. In hemodialysis subjects Lp(a) concentrations (median = 29) were intermediate between those observed in nondialyzed patients and controls but the differences were not significant. Lp(a) levels in renal transplant patients treated with cyclosporin (median = 6) and not receiving cyclosporin (median = 13) were similar and did not differ from controls. Serum Lp(a) increases and attains maximum levels with mild/moderate reduction in renal function, and does not seem to change through late renal failure stages or in relation to the introduction of maintenance hemodialysis treatment. Correction of uremia by successful renal transplant caused normalization of Lp(a) levels regardless of the use of cyclosporin. Increased Lp(a) levels may be the earliest and more consistent lipid alteration seen in predialysis renal failure.

Lipoprotein (a) Concentrations in Patients with Various Dyslipidaemias

Although the genetic background is the most important determinant of lipoprotein (a) (Lp(a)) concentration other factors, such as coexistent dyslipidaemia, could modify its levels. We undertook the present study to examine the serum Lp(a) concentration in various dyslipidaemias and to reveal any correlation of serum Lp(a) concentration with the other lipid parameters in a large group of dyslipidaemic Greek patients. A total of 242 patients followed as outpatients in our lipid clinic were studied. The patients were stratified into four main groups. Patients with cholesterol levels greater than 5.17 mmol/ L but normal triglycerides were regarded as hypercholesterolaemic (n = 85), patients with triglycerides greater than 2.25 mmol/L but normal cholesterol levels as hypertriglyceridaemic (n = 51), patients with both increased cholesterol and triglyceride levels as having mixed hyperlipidaemia (n = 62), and finally patients with decreased (<0.90 mmol/L) high-density lipoprotein (HDL) cholesterol but normal cholesterol and triglyceride levels as having primary hypoalphalipoproteinaemia (n = 44). Hypercholesterolaemic patients exhibited the highest serum Lp(a) levels, while hypertriglyceri-daemic patients exhibited the lowest. Patients with mixed hyperlipidaemia had intermediate serum Lp(a) concentration, which was significantly higher than that of hypertriglyceridaemic patients but significantly lower than that of hypercholesterolaemic patients. Interestingly, patients with low serum HDL-cholesterol levels presented with low serum Lp(a) concentration similar to that of hypertriglyceridaemic patients. In hypercholesterolaemic patients no correlation was found between serum total and low-density lipoprotein (LDL) cholesterol nor apolipoprotein B (apoB) levels and Lp(a) concentration. On the contrary, in hypertriglyceridaemic patients an inverse correlation was observed between serum triglycerides and Lp(a) concentration. After dividing the hypertriglyceridaemic patients into one group with elevated (>1.3 g/L) serum apoB levels (n = 32) and another group with normal apoB levels (n = 19), we found that the median serum Lp(a) concentration was three times higher in hyperapoB patients compared to patients with normal apoB levels. We conclude that serum Lp(a) levels are different in various types of primary hyperlipidaemia and are modulated according to the type of lipid elevation.

Differences in Lp[a] concentrations and apo[a] polymorphs between black and white Americans

Lp[a] concentrations in nmol/L and apo[a] size isoforms, expressed in terms of the relative number of apo[a] kringle 4 (K4) repeats, were determined in 3959 whites and blacks from four U.S. communities. Plasma Lp[a] analyses were performed by an ELISA method insensitive to apo[a] size heterogeneity and apo[a] size isoforms were determined by high resolution agarose gel electrophoresis. Allele frequencies were estimated by maximum likelihood methods in order to account for the presence of null alleles and coalescence of hands on gels. The apo[a] allele frequencies and phenotype distributions differed significantly between blacks and whites (P < 0.0001). Blacks had a higher relative frequency of the intermediate alleles K4(22) through K4(28) whereas whites had a higher relative frequency of the small alleles K4(17) through K4(24) and large alleles K4(29) through K4(33). The estimated frequency of the null allele was low in both blacks (1.0%) and whites (6.7%). The Lp[a] distribution was less skewed and Lp[a] concentrations were higher in blacks than whites (mean 94 nmol/L and 48 nmol/L, median 74 nmol/L and 20 nmol/L for blacks and whites, respectively). The relationship between apo[a] size and Lp[a] concentration also differed significantly between these two racial groups. For the large polymorphs (> 31 K4 repeats) both blacks and whites exhibited uniformly low Lp[a] values. For the intermediate isoforms K4(20) through K4(30), a considerable range of Lp[a] values was evident in blacks; the median Lp[a] for each isoform increased nearly linearly as the apo[a] size decreased. In contrast in whites there was little change in median Lp[a] concentrations for isoforms K4(20) through K4(30). For the small apo[a] size (< 20 K4) both blacks and whites exhibited high median Lp[a] levels and a wide variation of Lp[a] levels. The major difference in Lp[a] levels between the two racial groups occurred in the intermediate size isoform range of K4(20) through K4(25). In conclusion, whites and blacks differ significantly in Lp[a] concentrations, allele and phenotype frequencies, and in the relationship between apo[a] size isoform and Lp[a] concentration.

Low lipoprotein (a) levels during acute viral hepatitis

High serum concentrations of lipoprotein (a) [Lp(a)] are considered a risk factor for premature atherosclerosis. Besides apolipoprotein B-100, Lp(a) consists of apolipoprotein (a) [apo(a)], which shows a remarkable size polymorphism. The serum concentration of Lp(a) is considerably influenced by this apo(a) phenotype. Because Lp(a) is synthesized in the liver, we wondered whether and to what extent Lp(a) levels might be affected by acute liver disease. We compared Lp(a) serum concentrations in 74 patients (54% male, 46% female; mean age, 46 years) with acute viral hepatitis (32, 28, and 14 with hepatitis A, B, and C, respectively) with those in 404 healthy controls (57% men, 43% women; mean age, 47 years). In addition, the intraindividual course of Lp(a) concentration during and after acute hepatitis was followed in a subgroup of 23 patients (15, 6, and 2 with hepatitis A, B, and C, respectively). During acute hepatitis, median Lp(a) concentrations in the patient group were significantly diminished compared with controls (7 vs. 17 mg/dL;P < .0001, Mann-Whitney test). Any bias by an unequal isoform distribution was excluded because there was no significant difference in the isoform distribution between patients and controls (P > .10, chi2 test). Furthermore, the decrease in Lp(a) concentration during acute hepatitis was independent of the molecular weight of the apo(a) isoform. Longitudinally observed patients showed a marked increase in Lp(a) concentration during convalescence (7 to 32 mg/dL;P < .0001, Wilcoxon test). Our results show that acute hepatitis is associated with decreased Lp(a) serum levels. Further studies are needed to evaluate whether Lp(a) serum concentration might be clinically useful as a parameter of liver function. (Hepatology 1996 Dec;24(6):1334-7)

Effects of gemfibrozil or simvastatin on apolipoprotein-B-containing lipoproteins, apolipoprotein-CIII and lipoprotein(a) in familial combined hyperlipidaemia

Background: Familial combined hyperlipidaemia (FCH), characterized by elevated very-low-density lipoprotein (VLDL) and/or low-density lipoprotein (LDL), is associated with an increased prevalence of premature cardiovascular disease. Therefore, lipid-lowering is frequently indicated. Methods: We evaluated in a parallel, double-blind randomized fashion the effect of gemfibrozil (1200 mg/day) (n = 40) or simvastatin (20 mg/day) (n = 41) on lipids, apolipoprotein-B (apo-B)-containing lipoproteins, apo-CIII and lipoprotein(a) [Lp(a)], in 81 well-defined FCH patients. Results: While both drugs lowered plasma cholesterol and triglyceride levels, gemfibrozil lowered plasma triglycerides more effectively by reduction of triglycerides in VLDL and LDL, whereas simvastatin was more effective in its reduction of total plasma cholesterol by exclusively decreasing LDL cholesterol. High-density lipoprotein (HDL) increased to an equal extent on both therapies. Total serum apo-B levels were reduced with both drugs; however, gemfibrozil decreased apo-B only in VLDL + IDL, whereas simvastatin decreased apo-B in both VLDL + IDL and LDL. In keeping with a more effective reduction of VLDL particles, a more pronounced reduction of apo-CIII also was observed after gemfibrozil, which correlated with the reduction in plasma triglycerides. Baseline concentrations of Lp(a) showed a wide range in both treatment groups. Median Lp(a) levels increased after simvastatin, but were not affected by gemfibrozil. Conclusion: Both therapies exhibited their specific effects, although none of the drugs alone completely normalized the lipid profiles of these patients with FCH. Therefore, the choice of treatment should be based on the most elevated lipoprotein fraction, and in some cases a combination of the two drugs may be indicated.

Decrease in lipoprotein(a) after renal transplantation is related to the glucocorticoid dose.

Serum lipoprotein(a) [Lp(a)] concentrations and apolipoprotein(a) phenotypes were determined in 46 patients with end-stage renal disease both before as well as 1 week and 1, 3 and 6 months after renal transplantation. Immunosuppressive therapy consisted of cyclosporin A, prednisone and azathioprine. Before transplantation median Lp(a) levels did not differ between the patients and a healthy control group. A highly significant decrease (P < 0.001) in Lp(a) levels was observed in both male and female patients 1 week after transplantation. This marked reduction in Lp(a) occurred at a time when patients were receiving the highest doses of corticosteroids. As steroid doses were gradually tapered, Lp(a) concentrations subsequently increased, although at 6 months levels were still significantly reduced (P < 0.01) in women. No significant correlation was observed between Lp(a) and whole-blood cyclosporin levels, nor was there any correlation with the azathioprine dose. The reduction in Lp(a) concentrations was seen for all apo(a) phenotypes observed in the study.

Serum lipoprotein(a) [Lp(a)] in alcoholic men: Effect of withdrawal

This study examines the effect of alcohol withdrawal on lipoprotein(a) [Lp(a)] in 24 male, middle-aged chronic alcohol abusers admitted for withdrawal therapy. Serum concentration of Lp(a) was determined before and during the first 3 weeks of abstinence. The changes in three sialylated proteins [Lp(a), α1-antitrypsin (α1-AT), and haptoglobin (Hp)] and in desialylated transferrin (CDT) were also determined in 14 patients. After the 3 weeks of withdrawal therapy, the mean and median Lp(a) concentrations increased ( p = 0.0001). The changes in Lp(a) levels were not related to the changes in dietary intake nor to the decrease in total HDL, HDL 3, HDL 2 cholesterol, Apo A-I, and Apo B. In the subgroup of 14 chronic alcohol abusers, Lp(a) levels increased parallel with Hp and α1-AT, whereas CDT decreased. It is concluded that the impact of alcohol on sialylated proteins may be one of the mechanisms responsible for the increase in plasma Lp(a) after alcohol withdrawal.

Correlation of toddlers' serum lipoprotein(a) concentration with parental values and grandparents' coronary heart disease: the STRIP baby study.

The correlation between lipoprotein(a) (Lp(a)) concentrations in children aged 7-24 months and their family members was determined and the association between the Lp(a) values of the children and a family history of coronary heart disease (CHD) was assessed. The Lp(a) values of the children correlated strongly with midparent Lp(a) values as early as at 7 months of age (r = 0.54 to 0.59, p < 0.0001). This correlation was stronger than the correlation of serum total cholesterol and total cholesterol corrected for Lp(a)-cholesterol between children and parents. None of the parents had CHD. The median Lp(a) concentration of the parents with a family history of CHD was significantly higher than that of parents with no such history (111 vs 87 mg/1, p = 0.024). However, the children's Lp(a) levels were not associated with CHD in their grandparents. The genetic dependence of the Lp(a) concentration is already evident in infancy. The Lp(a) concentration in young parents, but not in their 24-month-old children, is associated with CHD in grandparents. This may be explained by a dilution of the genetic influence on Lp(a) over two generations.

Effects of prospective, randomized cholesterol-lowering dietary intervention and apolipoprotein E phenotype on serum lipoprotein(a) concentrations of infants aged 7-24 mo

A high serum lipoprotein(a) [Lp(a)] concentration is associated with increased risk of coronary artery disease. Few external factors are able to markedly modify serum Lp(a) concentrations. The aim of this study was to evaluate how serum Lp(a) concentrations of infants between 7 and 24 mo of age change in a cholesterol-lowering dietary intervention, and to assess the influence of apolipoprotein (apo) E phenotypes on serum Lp(a) concentrations. The intervention children (n=394) had serum cholesterol, non-high-density-lipoprotein cholesterol, and cholesterol corrected for Lp(a)-cholesterol values (P for all <0.001) lower than those of the control children (n=390), but median serum Lp(a) concentrations at the age of 24 mo were not different from those of control children. Serum Lp(a) values differed according to the apo E phenotype as the median Lp(a) values increased from E2/2 to E3/2, E4/2, E3/3, E4/3, and to E4/4 (P for the difference=0.023, Mann-Whitney U test). Our results suggest that apo E phenotype influences serum Lp(a) concentrations noticeably, but the effect of the cholesterol-lowering dietary intervention was not significant in subjects aged 24 mo.

Interrelationship of triglyceride-rich lipoproteins, serum lipoprotein (a) concentration and apolipoprotein(a) size.

At present, the biochemical mechanisms underlying lipoprotein(a) (Lp(a)) metabolism are not fully understood. We analysed sera from 202 patients with atherosclerotic disease and 109 healthy subjects as a control group to investigate the possible relationship between triglyceride-rich lipoproteins (TRL) and serum lipoprotein(a) levels. To assess the influence of apolipoprotein (apo) (a) isoforms on the Lp(a)-TRL association, the apo(a) phenotypes of 177 patients and 95 controls were included in the analysis. Patients with atherosclerotic disease showed triglyceride levels almost within the normal range. There was no significant correlation between serum Lp(a) levels and triglyceride concentrations, or between Lp(a) and TRL levels in either group. When a subset of subjects from each group with serum triglycerides above 1.7 mmol l-1 was considered, a significant negative correlation between lipid concentration of very low density lipoproteins (VLDL) and serum Lp(a) levels was found only in patients. Control subjects with triglyceride levels under or over 1.7 mmol l-1 showed similar median Lp(a) levels (0.06 gl-1), in contrast to atherosclerotic patients, in whom median Lp(a) concentration was higher in the subset with serum triglycerides under 1.7 mmol l-1 than in those with triglyceride concentration above this value (0.16 vs. 0.13 gl-1). When patients with triglyceride concentrations above 1.7 mmol l-1 were classified into quartiles according to VLDL lipid concentration, subjects with the highest quartiles showed the lowest Lp(a) median levels. Despite the dependence of the Lp(a) concentration on apo(a) size isoforms, we found no effect of apo(a) genetic polymorphism on triglyceride levels or on TRL concentrations. We conclude that the variation in TRL metabolism may constitute a source of variation in serum Lp(a) concentrations that is independent of the genetically determined apo(a) molecule size.