Original Article
Relation of Serum Lipoprotein(a) Concentration and Apolipoprotein(a) Phenotype to Coronary Heart Disease in Patients with Familial Hypercholesterolemia
N Engl J Med 1990; 322:1494-1499May 24, 1990
- Abstract
- Abstract
Familial hypercholesterolemia carries a marked increase in the risk of coronary heart disease (CHD), but there is considerable variation between individuals in susceptibility to CHD. To investigate the possible role of lipoprotein(a) as a risk factor for CHD, we studied the association between serum lipoprotein(a) levels, genetic types of apolipoprotein(a) (which influence lipoprotein(a) levels), and CHD in 115 patients with heterozygous familial hypercholesterolemia.
The median lipoprotein(a) level in the 54 patients with CHD was 57 mg per deciliter, which is significantly higher than the corresponding value of 18 mg per deciliter in the 61 patients without CHD. According to discriminant-function analysis, the lipoprotein(a) level was the best discriminator between the two groups (as compared with all other lipid and lipoprotein levels, age, sex, and smoking status).
Phenotyping for apolipoprotein(a) was performed in 109 patients. The frequencies of the apolipoprotein(a) phenotypes and alleles differed significantly between the patients with and those without CHD. The allele LpS2, which is associated with high lipoprotein(a) levels, was found more frequently among the patients with CHD (0.33 vs. 0.12). In contrast, the LpS4 allele, which is associated with low lipoprotein(a) levels, was more frequent among those without CHD (0.27 vs. 0.15).
We conclude that an elevated level of lipoprotein(a) is a strong risk factor for CHD in patients with familial hypercholesterolemia, and the increase in risk is independent of age, sex, smoking status, and serum levels of total cholesterol, triglyceride, or high-density lipoprotein cholesterol. The higher level of lipoprotein(a) observed in the patients with CHD is the result of genetic influence. (N Engl J Med 1990; 322:1494–9.)
Media in This Article
Figure 1
Frequency Distribution of Serum Lipoprotein(a) Concentrations among Patients with Familial Hypercholesterolemia Who Did and Did Not Have CHD.Table 1
Clinical Characteristics of Patients with Familial Hypercholesterolemia, According to the Presence or Absence of CHD.Article Activity
- Article
LIPOPROTEIN(a) was described over 25 years ago by Berg as a genetic trait found in human plasma.1 Subsequent workers characterized its physicochemical properties and distribution in plasma, as well as the association of high levels of lipoprotein(a) with coronary heart disease (CHD), reviewed by Morrisett et al.2 Angiographic studies suggest that the level of lipoprotein(a) in plasma is a risk factor for disease of both native coronary vessels and saphenous-vein bypass grafts, and that the risk associated with an elevated level is of the same order of magnitude as that associated with low-density lipoprotein (LDL) cholesterol.3 , 4 Evidence that lipoprotein(a) and LDL are similarly atherogenic has been obtained by the localization of both proteins in atheromatous arteries5 and vein grafts.6 , 7
The structure, metabolism, and epidemiology of lipoprotein(a) have been reviewed in detail recently.8 It is now known that apolipoprotein(a) — a glycoprotein that is present in lipoprotein(a) and is covalently linked to apolipoprotein B-100, the principal apolipoprotein of LDL — has close structural homology with plasminogen,9 both gene loci being closely linked on the long arm of chromosome 6.10 This finding has led to the suggestion that lipoprotein(a) may have thrombogenic as well as atherogenic properties11 — a concept that has received support from two recent studies.12 , 13 As we have shown, apolipoprotein(a) is genetically polymorphic, and lipoprotein(a) levels in plasma are largely determined by several alleles at the apolipoprotein(a) structural gene locus.14 15 16
Although lipoprotein(a) is closely related to LDL structurally, the level of lipoprotein(a) in plasma is thought to be regulated independently.2 As shown recently, however, apolipoprotein(a) alleles with a large effect on levels of lipoprotein(a) also have a significant effect on levels of total cholesterol,17 and it has been suggested that the association between lipoprotein(a) and CHD depends on the concomitant elevation of LDL cholesterol.18 Both markedly elevated LDL levels and a predisposition to CHD are features of familial hypercholesterolemia, a monogenically inherited disorder characterized by defective catabolism of LDL.19 Variability in the phenotypic expression of familial hypercholesterolemia, especially the age at onset and the severity of CHD, is only partly explained by the multiplicity of mutations of the LDL-receptor gene that underlie this disorder.20 Other genetic influences, such as the apolipoprotein E phenotype, also appear to play a part.21 To examine the possible role of lipoprotein(a) in this respect, we studied the serum lipoprotein(a) concentrations and the apolipoprotein(a) phenotypes of a group of patients heterozygous for familial hypercholesterolemia and compared the patients who had CHD with those who did not.
Methods
Patients
A total of 115 patients with heterozygous familial hypercholesterolemia (61 men and 54 women, all of whom were white and more than 20 years old) were selected from among patients attending lipid clinics at Charing Cross Hospital and Hammersmith Hospital in London. Most of these patients had been attending the clinics for several years, having been referred to them by their physicians because of hypercholesterolemia, but none had previously undergone measurement of lipoprotein(a). During this study, blood samples for this measurement were obtained from all patients with familial hypercholesterolemia who attended either clinic during the 12-month period beginning in October 1986. The diagnosis of familial hypercholesterolemia was made according to standard criteria —i.e., a serum total cholesterol level of more than 7.5 mmol per liter, together with the presence of tendinous xanthomas in the patient or a first-degree relative. The patients were grouped according to whether they had symptomatic CHD (n = 54) or not (n = 61), as indicated by a history of angina together with either a positive exercise test or an abnormal coronary angiogram (stenosis of >70 percent in a major vessel) or by a history of a myocardial infarction, or coronary-artery bypass grafting. The diagnosis of myocardial infarction was based on electrocardiographic criteria and cardiac-enzyme changes. Among the patients with CHD the frequency of an abnormal angiogram, myocardial infarction, and Coronary Artery bypass grafting was 75 percent, 60 percent, and 33 percent, respectively. The average age at the onset of CHD was 39 years.
Serum lipids were measured at the time of initial diagnosis, before drug therapy to lower lipid levels was begun. However, lipoprotein(a) was measured subsequently, when many patients were receiving the anion-exchange resin cholestyramine (54 percent), the 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitor lovastatin (25 percent), or both (13 percent); neither drug has been found to influence lipoprotein(a) levels.22 , 23 These drugs were taken alone or in combination by 95 percent of the patients with CHD and by 89 percent of those without CHD. None were taking drugs or undergoing procedures that might have affected lipoprotein(a) levels — e.g., niacin, neomycin, or extracorporeal removal of cholesterol.
Venous-blood samples were obtained from all patients, who visited the clinic in the morning after fasting for 12 to 14 hours. The serum was extracted and stored at 4°C for analysis of total cholesterol, triglyceride, and high-density lipoprotein (HDL) cholesterol. The cholesterol and triglyceride were analyzed enzymatically on a Technicon RA-1000 (Technicon methods SM4–0139A85 and SM4–0173J85), as was the HDL cholesterol after precipitation of the serum with heparin—manganese.24 The concentration of LDL cholesterol was calculated with the formula of Friedewald et al.25 Serum for the assay of lipoprotein(a) was frozen and stored at — 70°C. The lipoprotein(a) concentration was measured by end-point immunonephelometry in London, as described below, or by electroimmunodiffusion in Innsbruck, as described previously.17 The two methods gave virtually identical results in 80 split-sample assays (r = 0.97, over a range of concentrations of 4 to 110 mg per deciliter).
Lipoprotein(a) Assay
Sheep antiserum to apolipoprotein(a), a reference standard (containing 50 mg of lipoprotein(a) per deciliter), normal human control serum (containing 40 mg of lipoprotein(a) per deciliter), and concentrated polyethylene glycol buffer were purchased from Immuno Ltd. (Sevenoaks, England). Sodium chloride solution (0.15 M) containing sodium azide (1 g per liter), and polyethylene glycol buffer diluted 1:10 with deionized water were filtered before use (Acrodisc, 0.45 nm, Gelman Sciences, Ann Arbor, Mich.).
The antiserum was diluted 1:30 with dilute polyethylene glycol buffer, allowed to stand for 30 minutes at room temperature, and then filtered as described above. The reference standard was diluted 1:8 with sodium chloride solution. Serial dilution produced preparations with dilutions of 1:16, 1:32, and 1:64 of the original reference standard. A further standard was produced by dilution (1:10) of the original reference standard.
The samples and normal human control serum were diluted 1:8 and 1:16 with sodium chloride solution. Duplicate volumes (50 μl) of diluted samples and control and reference standards were transferred to disposable culture tubes (10 by 75 mm, Corning Glass Works, Corning, N.Y.) with a pipette. Dilute antiserum (800 μl) was added to one of each pair of tubes and mixed into it; dilute polyethylene glycol buffer (800 μl) was added to the other tube, which was to serve as a blank. A buffer blank was produced by adding 800 μl of polyethylene glycol buffer to 50 μl of sodium chloride solution, and an antiserum blank by adding 800 μl of diluted antiserum to 50 μl of sodium chloride. The tubes were stoppered and left standing for three to four hours at room temperature. The contents of the tubes were thoroughly mixed, and the turbidity was measured by nephelometry (Hyland Laser Nephelometer PDQ, American Instrument Co., Silver Spring, Md.) against buffer blank and antiserum blank. Each sample was compared with its own sample blank, and the results were read off a standard linear calibration curve. Samples too concentrated or too turbid to be read at 1:8 dilution were measured at 1:16 or an appropriate dilution so that the reading would fall within the calibration curve.
To assess the possibly confounding effect of hypertriglyceridemia, 14 samples of serum with a mean triglyceride value of 2.6 mmol per liter (range, 0.98 to 5.24) were assayed for lipoprotein(a) before and after ultracentrifugation at 1.006Xg. The mean level of lipoprotein(a) in plasma was 21.1 mg per deciliter, and that of the lipoprotein(a) fraction with a density of more than 1.006 was 23.9 mg per deciliter (r = 0.92). These results suggest that moderate increases in triglyceride-rich lipoproteins, such as those occurring in a minority of patients with familial hypercholesterolemia, do not interfere with the immunonephelometric assay of lipoprotein(a). However, two serum samples with triglyceride levels of 28 and 29 mmol per liter (not from patients with familial hypercholesterolemia) could not be assayed for lipoprotein(a), suggesting that severe hypertriglyceridemia does interfere with this assay.
Of the 115 patients, 109 subsequently underwent phenotyping for apolipoprotein(a) at Innsbruck (55 without CHD and 54 with CHD). Phenotyping was performed with the use of immunoblotting as described elsewhere,17 but with a monoclonal antibody26 to apolipoprotein(a), IA2.
Data Analysis
Before statistical analysis was carried out, the lipid and lipoprotein values were standardized in relation to the age of 40, on the basis of regression of each variable against age, as described previously.20 The equality of lipoprotein(a) levels among the strata thus produced was tested with the Mann—Whitney rank-sum test for nonparametric data.27 The principal analyses of the data were multiple-discriminant function analyses, performed with the SPSS program (Northwestern University, Chicago). Before these analyses were performed, the distribution of each variable was tested for its goodness of fit to a normal distribution. The distributions of both triglyceride and lipoprotein(a) values were significantly skewed, and a logarithmic transformation was therefore applied to produce approximately normal distribution. The groups were then compared with the use of stepwise discriminant analysis; the criterion for inclusion was a P value of less than 0.05, as determined with the F test.
The frequencies of the apolipoprotein(a) alleles were estimated according to a model with five apolipoprotein(a)-band—producing alleles (S1, S2, S3, S4, and B) and one operational null allele. We assumed codominance among the band-producing alleles and their dominance over the operational null allele. As we have discussed before,15 , 16 the existence of a true null allele has yet to be established. Pearson's chi-square statistic and a likelihood-ratio test were used to assess the independence of the apolipoprotein(a) phenotype and allele frequencies in the patients with CHD and those without CHD. Unless otherwise noted, a finding was considered to be statistically significant when the probability of these data under the null hypothesis was less than 0.05 according to a two-tailed test.
Results
Some of the clinical features of patients with familial hypercholesterolemia are shown in Table 1Table 1
Clinical Characteristics of Patients with Familial Hypercholesterolemia, According to the Presence or Absence of CHD.. There were significantly more men and smokers among the patients with CHD, who were also significantly older than those without CHD, but there was no significant difference between the two groups in the frequency of hypertension. None of the patients had diabetes mellitus. As shown in Table 2Table 2
Fasting Serum Lipid and Lipoprotein Levels, According to Study Group.*, the average serum concentrations of total, LDL, and HDL cholesterol did not markedly differ according to whether CHD was present or absent, but the average serum triglyceride concentration was significantly higher in the group with CHD.Lipoprotein(a) Levels
The frequency distribution of serum lipoprotein(a) concentrations in the groups with and without CHD is shown in Figure 1Figure 1
Frequency Distribution of Serum Lipoprotein(a) Concentrations among Patients with Familial Hypercholesterolemia Who Did and Did Not Have CHD.. The distribution was skewed, especially among the patients without CHD, but concentrations above 40 mg per deciliter were much more common among those with CHD. Median lipoprotein(a) levels were significantly higher among patients with CHD (57 mg per deciliter) than among those without CHD (18 mg per deciliter; P<0.0001), as shown in Table 2. No significant correlations were observed between lipoprotein(a) levels and age (r = 0.047), nor did median values of lipoprotein(a) differ between men and women (30 vs. 33 mg per deciliter).Univariate comparison revealed five variables in which the group with CHD differed significantly from the group without CHD: age, sex, smoking status, log triglyceride, and log lipoprotein(a). No significant differences were observed between the two groups in serum total cholesterol, HDL cholesterol, or LDL cholesterol. Stepwise multiple-discriminant analysis of only the variables for which differences were significant was carried out post hoc to investigate the independence of these risk factors in predicting CHD among patients with familial hypercholesterolemia (Table 3Table 3
Multiple-Discriminant Analysis of Risk Factors for CHD in Both Study Groups Combined (N = 115).). Log lipoprotein(a) was included at the first step (step 0) since it was the best discriminator between the two groups. At the second step (step 1), log triglyceride was added since it was the best of the remaining discriminants, but age, sex, smoking status, and any of the other lipid variables could not be included when the inclusion criterion (P<0.05) was applied (step 2, Table 3). Both lipoprotein(a) and triglyceride therefore appeared to be independent risk factors for CHD in patients with familial hypercholesterolemia, and lipoprotein(a) was the better discriminator.Apolipoprotein(a) Phenotypes
In view of the known association between the serum lipoprotein(a) concentration and the apolipoprotein(a) phenotype, frozen samples of serum from 55 of the 61 patients without CHD and all of the 54 with CHD were typed for their apolipoprotein(a) isoforms.
The median value of lipoprotein(a) was again found to be much higher in the patients with CHD than in those without CHD (57 vs. 22 mg per deciliter). The results of apolipoprotein(a) phenotyping of the 109 patients are shown in Table 4Table 4
Frequency of Apolipoprotein(a) Phenotypes and Lipoprotein(a) Concentrations, According to Study Group.*, and the estimated frequencies of apolipoprotein(a) alleles in Table 5Table 5
Estimated Frequencies of Apolipoprotein Alleles, According to Study Group.*. A comparison of the apolipoprotein(a) phenotypes and estimated allele frequencies demonstrated significant differences between the groups with and without CHD (P<0.05). The LpS1 and LpS2 alleles were found more frequently among the patients with CHD, whereas the LpS4 allele was more frequent among the patients without CHD. Since the LpS1 and LpS2 alleles are associated with higher lipoprotein(a) levels than the LpS4 allele in the general population14 , 17 and in the patients studied here (Table 4), this suggests that part of the difference between the two groups in lipoprotein(a) levels was determined by the apolipoprotein(a) gene locus. That this was not the sole determinant is shown by the much higher median value for lipoprotein(a) among patients with CHD and the S2 phenotype than among those without CHD. We have previously estimated that just over 40 percent of the variance in lipoprotein(a) levels is attributable to differences in apolipoprotein(a) phenotype.17 Entering the variable of the apolipoprotein(a) phenotype into a logistic prediction equation27 after the lipoprotein(a) concentration had been entered did not further contribute to the risk of CHD.Discussion
The principal finding of this study was that serum lipoprotein(a) concentrations were significantly higher in patients heterozygous for familial hypercholesterolemia who had CHD than in those without CHD. In a previous comparison of lipoprotein(a) levels and apolipoprotein(a) phenotypes in 102 patients with familial hypercholesterolemia and 279 controls (Tyrolean blood donors, representing a healthy white population), we found higher lipoprotein(a) values in the patients, especially when we compared patients and controls with the same apolipoprotein(a) phenotype.28 However, in the present study, apolipoprotein(a) phenotyping showed that the higher lipoprotein(a) concentration of the patients with CHD was at least partly due to their having a high prevalence of the alleles that predispose people to increased levels of lipoprotein(a), notably the LpS1 and LpS2 alleles, which were present in 55 percent of all patients in our study, as compared with only 14 percent of a normal population.26 Conversely, the lower lipoprotein(a) concentrations of the patients without CHD reflected a high prevalence of alleles associated with low concentrations of lipoprotein(a), especially LpS4. The relation of the apolipoprotein(a) phenotype to the concentration of lipoprotein(a) in plasma has been described previously14 and indicates the importance of the apolipoprotein(a) gene locus in this respect; the molecular mechanisms responsible for the association between the apolipoprotein(a) phenotype and the lipoprotein(a) level have recently been elucidated.29 , 30
We also examined the distribution of other variables that might account for the differences in serum lipoprotein(a) levels between the patients with and without CHD. More of those with CHD were older, were men, or smoked. However, we found no evidence that age, sex, or smoking status significantly influenced lipoprotein(a) levels in this study. The lack of association between age and the lipoprotein(a) concentration has been noted previously.31 We excluded patients taking drugs known to influence lipoprotein(a) levels, such as neomycin and niacin.32 , 33 Mean LDL cholesterol values in the two groups of patients were very similar, which makes it highly unlikely that there was any major bias in the nature of the underlying defects of the LDL receptors, which if present might have influenced lipoprotein(a) levels differentially. The patients with CHD had significantly higher serum triglyceride levels than those without CHD, but our analysis showed that lipoprotein(a) was a better discriminator between the two groups than age, sex, smoking status, or triglyceride concentration. We therefore conclude that the occurrence of CHD among patients heterozygous for familial hypercholesterolemia is influenced by lipoprotein(a) levels, and that this effect is independent of the other risk factors.
The mechanism of the association between lipoprotein(a) and CHD remains to be defined, but it could operate on either an atherogenic or a thrombogenic basis or both.11 An analysis of coronary-artery bypass grafts has shown that the ratio of apolipoprotein(a) in tissue to apolipoprotein(a) in plasma is twice as high as the ratio of apolipoprotein B,6 presumably reflecting greater binding34 or slower clearance of apolipoprotein(a) by the vessel wall. The thrombogenic potential of apolipoprotein (a) remains hypothetical, but its close homology with plasminogen could theoretically result in competitive inhibition of the fibrinolytic properties of plasminogen. In vitro evidence that supports this proposition has been presented by Miles et al.,12 who showed that lipoprotein(a) prevents binding of plasminogen to its binding sites on endothelial cells, and by Hajjar et al.,13 who showed that the prevention of binding leads to a reduction in tissue plasminogen activator—induced generation of plasmin from plasminogen.
These findings have implications for the management and prognosis of familial hypercholesterolemia. The current practice is to treat patients heterozygous for the disorder by administering the highly effective LDL-lowering combination of an anion-exchange resin and a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor.35 , 36 However, neither class of drug lowers lipoprotein(a) levels, 22,23 although each up-regulates LDL receptors very efficiently37; it may be that lipoprotein(a) is cleared to a lesser extent by way of the LDL-receptor pathway than has previously been suggested.38 The proposal that the association between high levels of lipoprotein(a) and CHD is dependent on accompanying increases in LDL cholesterol levels18 raises the question of whether concomitant reduction of both LDL and lipoprotein(a) levels is necessary to prevent CHD in patients with familial hypercholesterolemia or whether reduction of LDL levels alone will suffice. It has been shown that neomycin and niacin together can reduce lipoprotein(a) levels by almost 50 percent32 and that extracorporeal removal by apheresis can achieve even greater reductions.39 However, each of these treatments has its drawbacks, and it is therefore imperative to ascertain whether reducing the levels of both lipoprotein(a) and LDL is more advantageous in clinical practice than reducing the levels of LDL alone in patients with increased levels of both lipoproteins.
Supported in part by grants from Merck Sharp & Dohme to Dr. Seed, from the Fonds für Förderung der Wissenschaftlichen Forschung im Österreich (P4610) to Dr. Utermann, and from the National Institutes of Health (HL-40613) to Dr. Boerwinkle.
We are indebted to Valerie Luck and Ulrike Keller for technical assistance and to Dr. K. MacRae, Reader in Medical Statistics (London University) for advice on statistical analysis of risk factors.
Source Information
From the Departments of Medicine and Chemical Pathology, Charing Cross and Westminster Medical School, London (M.S, D.R.); the Medical Research Council Lipoprotein Team, Hammersmith Hospital, London (S.McC., G.R.T.); the Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston (E.B.); and the Institute of Medical Biology and Genetics, University of Innsbruck, Innsbruck, Austria (F.H., G.U.). Address reprint requests to Dr. Seed at the Department of Medicine, Charing Cross and Westminster Medical School, Fulham Palace Rd., London W6 8RS, United Kingdom.
- References
References
1
Berg
CrossRef | Medline2
Morrisett JD, Guyton JR, Gaubatz JW, Gotto AM Jr. Lipoprotein (a): structure, metabolism and epidemiology. In: Gotto AM Jr, ed. Plasma lipoproteins. Amsterdam: Elsevier Science, 1987:129–52.
3
Dahlen
CrossRef | Web of Science | Medline4
Hoff
CrossRef | Web of Science | Medline5
Walton
CrossRef | Web of Science | Medline6
Cushing
CrossRef | Medline7
Rath 8
Utermann
CrossRef | Web of Science | Medline9
McLean
CrossRef | Web of Science | Medline10
Lindahl
CrossRef | Web of Science | Medline11
Brown
CrossRef | Web of Science | Medline12
Miles
CrossRef | Web of Science | Medline13
Hajjar
CrossRef | Web of Science | Medline14
Utermann
CrossRef | Web of Science | Medline15
Utermann
CrossRef | Web of Science | Medline16
Utermann
CrossRef | Web of Science | Medline17
Boerwinkle
CrossRef | Web of Science | Medline18
Armstrong
CrossRef | Web of Science | Medline19
Goldstein JL, Brown MS. Familial hypercholesterolemia. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The metabolic basis of inherited disease. 5th ed. New York: McGraw-Hill, 1983:672–712.
20
Thompson 21
Eto
CrossRef | Web of Science | Medline22
Vessby
CrossRef | Web of Science | Medline23
Thiery
CrossRef | Medline24
Warnick
Web of Science | Medline25
Friedewald
Web of Science | Medline26
Kraft
CrossRef | Medline27
Conover WJ. Practical nonparametric statistics. New York: John Wiley, 1980.
28
Utermann
CrossRef | Web of Science | Medline29
Gavish
CrossRef | Web of Science | Medline30
Lindahl 31
Guyton
CrossRef | Medline32
Gurakar
CrossRef | Web of Science | Medline33
Carlson
CrossRef | Web of Science | Medline34
Bihari-Varga
CrossRef | Medline35
Mabuchi
Full Text | Web of Science | Medline36
Illingworth
Web of Science | Medline37
Bilheimer
CrossRef | Web of Science | Medline38
Krempler
CrossRef | Web of Science | Medline39
Armstrong
CrossRef | Web of Science | Medline
- Citing Articles (158)
Citing Articles
1
Julio A. Carbayo Herencia. (2011) Nuevos marcadores de riesgo cardiovascular. ¿Pueden influir en la clasificación del riesgo cardiovascular?. Clínica e Investigación en Arteriosclerosis
CrossRef2
Anders Hovland, Santica Marcovina, Randolf Hardersen, Terje Enebakk, Tom Eirik Mollnes, Knut Tore Lappegård. (2011) Three different LDL apheresis columns efficiently and equally reduce lipoprotein(a) concentrations in patients with familial hypercholesterolemia and small apolipoprotein(a) particles. Transfusion and Apheresis Science
CrossRef3
Florian Kronenberg, Gerd Utermann. (2011) Lipoprotein(a): Reloaded. Current Cardiovascular Risk Reports
CrossRef4
Adam Taleb, Joseph L Witztum, Sotirios Tsimikas. (2011) Oxidized phospholipids on apoB-100-containing lipoproteins: a biomarker predicting cardiovascular disease and cardiovascular events. Biomarkers in Medicine 5:5, 673-694
CrossRef5
Marybeth U Allian-Sauer, James M Falko. (2011) Role of apheresis in the management of familial hypercholesterolemia and elevated Lp(a) levels. Clinical Lipidology 6:5, 523-538
CrossRef6
Ornella Guardamagna, Francesca Abello, Giovanni Anfossi, Matteo Pirro. (2011) Lipoprotein(a) and Family History of Cardiovascular Disease in Children with Familial Dyslipidemias. The Journal of Pediatrics 159:2, 314-319
CrossRef7
Marit S. Nenseter, Henriette Walaas Lindvig, Thor Ueland, Gisle Langslet, Leiv Ose, Kirsten B. Holven, Kjetil Retterstøl. (2011) Lipoprotein(a) levels in coronary heart disease-susceptible and -resistant patients with familial hypercholesterolemia. Atherosclerosis 216:2, 426-432
CrossRef8
G. Utermann. (2011) Lipoproteinstoffwechsel und koronare Herzkrankheit. medizinische genetik 23:1, 7-14
CrossRef9
Emil M. deGoma, Matthew T. Wheeler, Santica M. Marcovina, Euan A. Ashley. (2010) Extremely elevated lipoprotein(a), combined hyperlipidemia, and premature atherosclerosis in a Chinese family. Journal of Clinical Lipidology 4:6, 543-547
CrossRef10
G. Lupattelli, A. R. Roscini, D. Siepi, E. Mannarino. (2010) CASE REPORT: Hyperlipoproteinaemia(a): which is the optimal therapy? A case report. Journal of Clinical Pharmacy and Therapeutics 35:5, 613-615
CrossRef11
Jianghua Feng, Huili Liu, Limin Zhang, Kishore Bhakoo, Lehui Lu. (2010) An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids. Nanotechnology 21:39, 395101
CrossRef12
Pia R. Kamstrup. (2010) Lipoprotein(a) and ischemic heart disease—A causal association? A review. Atherosclerosis 211:1, 15-23
CrossRef13
Albert Dirisamer, Harald Widhalm, Elsie Aldover-Macasaet, Sylvia Molzer, Kurt Widhalm. (2008) Elevated Lp(a) with a small apo(a) isoform in children: risk factor for the development of premature coronary artery disease. Acta Paediatrica 97:12, 1653-1657
CrossRef14
Mehdi Rasouli, Asadollah Mohseni Kiasari. (2008) Interactions of lipoprotein(a) with diabetes mellitus, apolipoprotein B and cholesterol enhance the prognostic values for coronary artery disease. Clinical Chemistry and Laboratory Medicine 46:5, 667-673
CrossRef15
Shuji Kitajima, Yingji Jin, Tomonari Koike, Ying Yu, Enqi Liu, Masashi Shiomi, Santica M. Marcovina, Masatoshi Morimoto, Teruo Watanabe, Jianglin Fan. (2007) Lp(a) enhances coronary atherosclerosis in transgenic Watanabe heritable hyperlipidemic rabbits. Atherosclerosis 193:2, 269-276
CrossRef16
Idoia Narvaez, Jose Domingo Sagastagoitia, Marta Vacas, Yolanda Saez, Manolo Lafita, Santos Monica, Jesus Pablo Saez de Lafuente, Enrique Molinero, Jose Antonio Iriarte. (2007) Prevalence and biologic profile of aspirin resistance in patients with angiographically proven coronary artery disease. Thrombosis Research 120:5, 671-677
CrossRef17
J. S. Rana, A. C. Jansen, A. H. Zwinderman, E. S. van Aalst-Cohen, J. W. Jukema, M. D. Trip, J. J. P. Kastelein. (2006) Lipoprotein (a) and risk of cardiovascular disease in patients with metabolic syndrome in a population of familial hypercholesterolaemia. Journal of Internal Medicine 260:2, 183-185
CrossRef18
C. H. Saely, L. Koch, F. Schmid, T. Marte, S. Aczel, P. Langer, G. Hoefle, H. Drexel. (2006) Lipoprotein(a), type 2 diabetes and vascular risk in coronary patients. European Journal of Clinical Investigation 36:2, 91-97
CrossRef19
Kürşad Ünlühızarcı, Sabahattin Muhtaroğlu, Şevki Kabak, Fahri Bayram, Fahrettin Keleştimur. (2006) Serum lipoprotein (a) levels in patients with diabetic foot lesions. Diabetes Research and Clinical Practice 71:2, 119-123
CrossRef20
Richard W.C. Pang, Sidney Tam, Edward D. Janus, Simon T.S. Siu, Oliver C.K. Ma, T.H. Lam, Karen S.L. Lam. (2006) Plasma lipid, lipoprotein and apolipoprotein levels in a random population sample of 2875 Hong Kong Chinese adults and their implications (NCEP ATP-III, 2001 guidelines) on cardiovascular risk assessment. Atherosclerosis 184:2, 438-445
CrossRef21
William Discepolo, Ted Wun, Lars Berglund. (2006) Lipoprotein(a) and Thrombocytes: Potential Mechanisms Underlying Cardiovascular Risk. Pathophysiology of Haemostasis and Thrombosis 35:3-4, 314-321
CrossRef22
Robert C. Block, Thomas A. Pearson. (2005) Lipoprotein(a): Implications for clinical practice. Current Atherosclerosis Reports 7:5, 327-329
CrossRef23
Rolf Bambauer. (2005) Is Lipoprotein (a)-Apheresis Useful?. Therapeutic Apheresis and Dialysis 9:2, 142-147
CrossRef24
Livia Pisciotta, Claudio Cortese, Agostino Gnasso, Laura Liberatoscioli, Anna Pastore, Liliana Mannucci, Concetta Irace, Giorgio Federici, Stefano Bertolini. (2005) Serum homocysteine, methylenetetrahydrofolate reductase gene polymorphism and cardiovascular disease in heterozygous familial hypercholesterolemia. Atherosclerosis 179:2, 333-338
CrossRef25
Enzo Emanuele, Emmanouil Peros, Piercarlo Minoretti, Angela D'Angelo, Lorenza Montagna, Colomba Falcone, Diego Geroldi. (2004) Significance of apolipoprotein(a) phenotypes in acute coronary syndromes: relation with clinical presentation. Clinica Chimica Acta 350:1-2, 159-165
CrossRef26
A. C. M. Jansen, E. S. Aalst-Cohen, M. W. Tanck, M. D. Trip, P. J. Lansberg, A. H. Liem, H. W. O. Roeters van Lennep, E. J. G. Sijbrands, J. J. P. Kastelein. (2004) The contribution of classical risk factors to cardiovascular disease in familial hypercholesterolaemia: data in 2400 patients. Journal of Internal Medicine 256:6, 482-490
CrossRef27
M. Kusama, K. Miyauchi, H. Aoyama, M. Sano, M. Kimura, S. Mitsuyama, K. Komaki, H. Doihara. (2004) Effects of toremifene (TOR) and tamoxifen (TAM) on serum lipids. Breast Cancer Research and Treatment 88:1, 1-8
CrossRef28
(2004) The Influences of Meles meles Oil on Health Status, Diabetic Index and Serum Lipid Profile in Non - Insulin Dependent Diabetes Mellitus Patients. Journal of the Korean Society of Food Science and Nutrition 33:7, 1139-1146
CrossRef29
Fernando Civeira. (2004) Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis 173:1, 55-68
CrossRef30
Carsten Otto, Peter Kern, Rolf Bambauer, Stefan Kallert, Peter Schwandt, Klaus G. Parhofer. (2003) Efficacy and Safety of a New Whole-blood Low-density Lipoprotein Apheresis System (Liposorber D) in Severe Hypercholesterolemia. Artificial Organs 27:12, 1116-1122
CrossRef31
Gérald Luc, Jean-Marie Bard, Dominique Arveiler, Jean Ferrieres, Alun Evans, Philippe Amouyel, Jean-Charles Fruchart, Pierre Ducimetiere. (2002) Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study. Atherosclerosis 163:2, 377-384
CrossRef32
Tatsuya Suzuki, Kenzo Oba, Yoshimasa Igari, Noriaki Matsumura, Yuki Inuzuka, Yoshiaki Kigawa, Yoshiki Matsuura, Yumiko Ajiro, Kyoji Okazaki, Hiroshi Nakano. (2002) Relation of Apolipoprotein (a) Phenotypes to Diabetic Retinopathy in Elderly Type 2 Diabetes. Journal of Nippon Medical School 69:1, 31-38
CrossRef33
Tomonaga Ichikawa, Hiroyuki Unoki, Huijun Sun, Hiroaki Shimoyamada, Santica Marcovina, Hisataka Shikama, Teruo Watanabe, Jianglin Fan. (2002) Lipoprotein(a) Promotes Smooth Muscle Cell Proliferation and Dedifferentiation in Atherosclerotic Lesions of Human Apo(a) Transgenic Rabbits. The American Journal of Pathology 160:1, 227-236
CrossRef34
L Van Gaal. (2001) Low-density lipoprotein receptor gene mutation analysis and clinical correlation in Belgian hypercholesterolaemics. Molecular and Cellular Probes 15:6, 329-336
CrossRef35
Andrei C Sposito, Antonio P Mansur, Raul C Maranhão, Tania R.L Martinez, Jose M Aldrighi, Jose A.F Ramires. (2001) Triglyceride and lipoprotein (a) are markers of coronary artery disease severity among postmenopausal women. Maturitas 39:3, 203-208
CrossRef36
Arnold Eckardstein, Gerd Assmann. (2001) Clinical implications of elevated lipoprotein(a). Current Atherosclerosis Reports 3:4, 267-270
CrossRef37
C. Gazzaruso, A. Garzaniti, C. Falcone, D. Geroldi, G. Finardi, P. Fratino. (2001) Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non-diabetic subjects. Diabetic Medicine 18:7, 589-594
CrossRef38
Leonardo Pantoni, Cristina Sarti, Giovanni Pracucci, Antonio Di Carlo, Paola Vanni, Domenico Inzitari, For The Italian Longitudinal Study. (2001) Lipoprotein(a) Serum Levels and Vascular Diseases in an Older Caucasian Population Cohort. Journal of the American Geriatrics Society 49:2, 117-125
CrossRef39
C. A. Dane-Stewart, G. F. Watts, J. C. L. Mamo, S. B. Dimmitt, P. H. R. Barrett, T. G. Redgrave. (2001) Elevated apolipoprotein B-48 and remnant-like particle-cholesterol in heterozygous familial hypercholesterolaemia. European Journal of Clinical Investigation 31:2, 113-117
CrossRef40
Arnold von Eckardstein, Helmut Schulte, Paul Cullen, Gerd Assmann. (2001) Lipoprotein(a) further increases the risk of coronary events in men with high global cardiovascular risk. Journal of the American College of Cardiology 37:2, 434-439
CrossRef41
Rhobert W Evans, Ofer Shpilberg, B.Jessica Shaten, Shabnam Ali, M.Ilyas Kamboh, Lewis H Kuller. (2001) Prospective association of lipoprotein(a) concentrations and apo(a) size with coronary heart disease among men in the Multiple Risk Factor Intervention Trial. Journal of Clinical Epidemiology 54:1, 51-57
CrossRef42
M. Nauck, H. Wieland. (2001) Die Differentialdiagnostik von Fettstoffwechselstörungen unter besonderer Berücksichtigung methodischer Aspekte. Differential Diagnostics of Disorders in Lipid Metabolism with Special Consideration of Methodical Aspects. LaboratoriumsMedizin 25:1-2, 16-22
CrossRef43
Zuowei Xiong, Mark L Wahlqvist, Beryl Biegler, Nicholas DH Balazs, Paul Van Buynder, Naiyana Wattanapenpaiboon. (2000) Plasma lipoprotein (a) concentrations and apolipoprotein (a) phenotypes in an Aboriginal population from Western Australia. Asia Pacific Journal of Clinical Nutrition 9:3, 235-240
CrossRef44
Robert J. Wityk, Steven J. Kittner, Jennifer L. Jenner, J.Richard Hebel, Anne Epstein, Marcella A. Wozniak, Paul D. Stolley, Barney J. Stern, Michael A. Sloan, Thomas R. Price, Robert J. McCarter, Richard F. Macko, Constance J. Johnson, Christopher J. Earley, David W. Buchholz, Ernst J. Schaefer. (2000) Lipoprotein (a) and the risk of ischemic stroke in young women. Atherosclerosis 150:2, 389-396
CrossRef45
Kwame O Akosah, Elizabeth Gower, Linda Groon, Brenda L Rooney, Ana Schaper. (2000) Mild hypercholesterolemia and premature heart disease: do the national criteria underestimate disease risk?. Journal of the American College of Cardiology 35:5, 1178-1184
CrossRef46
Serena Tonstad. (2000) Role of Lipid-Lowering Pharmacotherapy in Children. Pediatric Drugs 2:1, 11-22
CrossRef47
Chris Spencer, David Crook, David Ross, Alison Cooper, Malcolm Whitehead, John Stevenson. (1999) A randomised comparison of the effects of oral versus transdermal 17beta-oestradiol, each combined with sequential oral norethisterone acetate, on serum lipoprotein levels. BJOG: An International Journal of Obstetrics and Gynaecology 106:9, 948-953
CrossRef48
Anne Wehinger, Adnan Kastrati, Shpend Elezi, Hannsjörg Baum, Siegmund Braun, Franz-Josef Neumann, Albert Schömig. (1999) Lipoprotein(a) and coronary thrombosis and restenosis after stent placement. Journal of the American College of Cardiology 33:4, 1005-1012
CrossRef49
Ana Cenarro, Elena Casao, Fernando Civeira, Henrik K. Jensen, Ole Færgeman, Miguel Pocovı́. (1999) PlA1/A2 polymorphism of platelet glycoprotein IIIa and risk of acute coronary syndromes in heterozygous familial hypercholesterolemia. Atherosclerosis 143:1, 99-104
CrossRef50
Alan H.B Wu, John H Contois, Thomas G Cole. (1999) Reflex testing I: Algorithm for lipid and lipoprotein measurement in coronary heart disease risk assessment. Clinica Chimica Acta 280:1-2, 181-193
CrossRef51
Lars F. Andersen, Jørgen Gram, Sven O. Skouby, Jørgen Jespersen. (1999) Effects of hormone replacement therapy on hemostatic cardiovascular risk factors. American Journal of Obstetrics and Gynecology 180:2, 283-289
CrossRef52
(1999) Mortality in treated heterozygous familial hypercholesterolaemia: implications for clinical management. Atherosclerosis 142:1, 105-112
CrossRef53
K Sankaranarayanan, R Chakraborty, E.A Boerwinkle. (1999) Ionizing radiation and genetic risks. Mutation Research/Reviews in Mutation Research 436:1, 21-57
CrossRef54
Carmine Gazzaruso, Adriana Garzaniti, Paola Buscaglia, Graziella Bonetti, Colomba Falcone, Pietro Fratino, Giorgio Finardi, Diego Geroldi. (1999) Association between apolipoprotein(a) phenotypes and coronary heart disease at a young age. Journal of the American College of Cardiology 33:1, 157-163
CrossRef55
Tonstad, Joakimsen, Stensland-Bugge, Ose, Bonaa, Leren. (1998) Carotid intima-media thickness and plaque in patients with familial hypercholesterolaemia mutations and control subjects. European Journal of Clinical Investigation 28:12, 971-979
CrossRef56
Paul N. Hopkins, Steven C. Hunt, Pamela J. Schreiner, John H. Eckfeldt, Ingrid B. Borecki, Curtis R. Ellison, Roger R. Williams, Kimberly D. Siegmund. (1998) Lipoprotein(a) interactions with lipid and non-lipid risk factors in patients with early onset coronary artery disease. Atherosclerosis 141:2, 333-345
CrossRef57
Jorge Joven, José M Simó, Elisabet Vilella, Jordi Camps, Luis Masana, Gabriel de Febrer, Mercè Camprubı́, Cristobal Richart, Alfredo Bardaji, Elena Casao, Miguel Pocovi, Fernando Civeira. (1998) Lipoprotein(a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction. Atherosclerosis 140:1, 155-159
CrossRef58
S. Banyai, J. Streicher, W. Strobl, H. Gabriel, M. Gottsauner-Wolf, M. Rohac, F. Weidinger, W.H. Hörl, K. Derfler. (1998) Therapeutic efficiency of lipoprotein(a) reduction by low-density lipoprotein immunoapheresis. Metabolism 47:9, 1058-1064
CrossRef59
Jean Davignon, Jacques Genest. (1998) GENETICS OF LIPOPROTEIN DISORDERS. Endocrinology & Metabolism Clinics of North America 27:3, 521-550
CrossRef60
Jai-Wun Park, Mechthild Merz, Peter Braun. (1998) Effect of HELP-LDL-apheresis on outcomes in patients with advanced coronary atherosclerosis and severe hypercholesterolemia. Atherosclerosis 139:2, 401-409
CrossRef61
Roselyne Garnotel, Frédérique Monier, Fabrice Lefèvre, Philippe Gillery. (1998) Long-Term Variability of Serum Lipoprotein(a) Concentrations in Healthy Fertile Women. Clinical Chemistry and Laboratory Medicine 36:5, 317-321
CrossRef62
Raúl A Schwartzman, Ian D Cox, Jan Poloniecki, Robert Crook, Carol A Seymour, Juan Carlos Kaski. (1998) Elevated Plasma Lipoprotein(a) Is Associated With Coronary Artery Disease in Patients With Chronic Stable Angina Pectoris. Journal of the American College of Cardiology 31:6, 1260-1266
CrossRef63
M. Penotti, L. Sironi, L. Miglierina, M. Farina, L. Barletta, L. Gabrielli, M. Vignali. (1998) The effect of tamoxifen and transdermal 17β-estradiol on cerebral arterial vessels: A randomized controlled study. American Journal of Obstetrics and Gynecology 178:4, 801-805
CrossRef64
Bernard Cantin, France Gagnon, Sital Moorjani, Jean-Pierre Després, Benoit Lamarche, Paul-Joseph Lupien, Gilles R Dagenais. (1998) Is Lipoprotein(a) an Independent Risk Factor for Ischemic Heart Disease in Men? The Quebec Cardiovascular Study. Journal of the American College of Cardiology 31:3, 519-525
CrossRef65
Heidrun Ullrich, Karl J. Lackner, Gerd Schmitz. (1998) Lipoprotein(a) Apheresis in Severe Coronary Heart Disease: an Immunoadsorption Method. Artificial Organs 22:2, 135-139
CrossRef66
Daiva Rastenyt
, Jaakko Tuomilehto, Cinzia Sarti. (1998) Genetics of stroke—a review. Journal of the Neurological Sciences 153:2, 132-145
CrossRef67
Christa Cobbaert, J.Wouter Jukema, Aeilko H. Zwinderman, Adrie J.A.M. Withagen, Jan Lindemans, Albert V.G. Bruschke. (1997) Modulation of Lipoprotein(a) Atherogenicity by High Density Lipoprotein Cholesterol Levels in Middle-Aged Men With Symptomatic Coronary Artery Disease and Normal to Moderately Elevated Serum Cholesterol. Journal of the American College of Cardiology 30:6, 1491-1499
CrossRef68
E. Bigot, B. Robert, J.M. Bard, F. Mainard. (1997) Lipoprotein (a) phenotype distribution in a population of bypass patients and its influence on lipoprotein (a) concentration. Clinica Chimica Acta 265:1, 99-111
CrossRef69
A Blann. (1997) von Willebrand factor and soluble E-selectin in the prediction of cardiovascular disease progression in hyperlipidaemia. Atherosclerosis 132:2, 151-156
CrossRef70
Andrew D. Blann, Alison Davis, J. Paul Miller, Charles N. McCollum. (1997) Von Willebrand factor and soluble E-selectin in hyperlipidaemia: Relationship to lipids and vascular disease. American Journal of Hematology 55:1, 15-23
CrossRef71
Y. Kitano, G.R. Thompson. (1997) The Familial Hypercholesterolemia Regression Study: A Randomized Comparison of Therapeutic Reduction of Both Low-Density Lipoprotein and Lipoprotein(a) Versus Low-Density Lipoprotein Alone. Therapeutic Apheresis and Dialysis 1:2, 187-190
CrossRef72
Carmine Gazzaruso, Paola Buscaglia, Adriana Garzaniti, Colomba Falcone, Stefania Mariotti, Sandra Savino, Graziella Bonetti, Giorgio Finardi, Diego Geroldi. (1997) Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary heart disease in patients with essential hypertension. Journal of Hypertension 15:3, 227-235
CrossRef73
T. B. Clarkson, J. M. Cline, J. K. Williams, M. S. Anthony. (1997) Gonadal hormone substitutes: Effects on the cardiovascular system. Osteoporosis International 7:S1, 43-51
CrossRef74
Charles N. Rotimi, Richard S. Cooper, Santica M. Marcovina, Daniel McGee, Eme Owoaje, Modupe Ladipo. (1997) Serum distribution of lipoprotein(a) in African Americans and Nigerians: Potential evidence for a genotype-environmental effect. Genetic Epidemiology 14:2, 157-168
CrossRef75
David J Galton. (1997) Genetic determinants of atherosclerosis-related dyslipidemias and their clinical implications. Clinica Chimica Acta 257:2, 181-197
CrossRef76
Serena Tonstad, Elisabeth Sundt, Leiv Ose, Tor-Arne Hagve, Jean-Charles Fruchart, Jean M. Bard, Staffan Edén. (1996) The effect of growth hormone on low-density lipoprotein cholesterol and lipoprotein(a) levels in familial hypercholesterolemia. Metabolism 45:11, 1415-1421
CrossRef77
Thomas Maca, Ramazanali Ahmadi, Kurt Derfler, Walter-Hermann Hörl, Renate Koppensteiner, Erich Minar, Barbara Schneider, Andreas Stümpflen, Herbert Ehringer. (1996) Elevated Lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females?. Atherosclerosis 127:1, 27-34
CrossRef78
P. S. LOW, C. K. HENG, N SAHA, J. S. H. TAY. (1996) Racial Variation of Cord Plasma Lipoprotein(a) Levels in Relation to Coronary Risk Level: A Study in Three Ethnic Groups in Singapore. Pediatric Research 40:5, 718-722
CrossRef79
John H. Contois, Carol J. Lammi-Keefe, Silke Vogel, Judith R. McNamara, Peter W.F. Wilson, Tatyana Massov, Ernst J. Schaefer. (1996) Plasma lipoprotein(a) distribution in the Framingham Offspring Study as determined with a commercially available immunoturbidimetric assay. Clinica Chimica Acta 253:1-2, 21-35
CrossRef80
N. VON AHSEN, M. HELMHOLD, T. EISENHAUER, V. W. ARMSTRONG, M. OELLERICH. (1996) Decrease in lipoprotein(a) after renal transplantation is related to the glucocorticoid dose. European Journal of Clinical Investigation 26:8, 668-675
CrossRef81
Yukihiro Matsuda, Paul S. Malchesky, Yukihiko Nose. (1996) Low-Density Lipoprotein Removal Methods by Membranes and Future Perspectives. Artificial Organs 20:4, 346-354
CrossRef82
JP Pfammatter, FP Stocker, O Oetliker, U Wiesmann, B Meier. (1996) Familial hypercholesterolaemia with severe cardiac involvement in a boy: successful management and mid-term follow-up. Acta Paediatrica 85:2, 254-257
CrossRef83
A.J. Ward, M. O'Kane, D.P. Nicholls, I.S. Young, N.C. Nevin, C.A. Graham. (1996) A novel single base deletion in the LDLR gene (211delG): Effect on serum lipid profiles and the influence of other genetic polymorphisms in the ACE, APOE and APOB genes. Atherosclerosis 120:1-2, 83-91
CrossRef84
Yechiel Friedlander, Eran Leitersdorf. (1996) Influence of apolipoprotein E genotypes on plasma lipid and lipoprotein concentrations: Results from a segregation analysis in pedigrees with molecularly defined familial hypercholesterolemia. Genetic Epidemiology 13:2, 159-177
CrossRef85
Florian Kronenberg, Gerd Utermann, Hans Dieplinger. (1996) Lipoprotein(a) in renal disease. American Journal of Kidney Diseases 27:1, 1-25
CrossRef86
Theo J.C van Berkel, Kees Fluiter, Agnes G van Velzen, Carla J.M Vogelezang, Gijsbertus J Ziere. (1995) LDL receptor-independent and -dependent uptake of lipoproteins. Atherosclerosis 118, S43-S50
CrossRef87
A. A. KROON, N. AJUBI, W. N. J. C. ASTEN, A. F. H. STALENHOEF. (1995) The prevalence of peripheral vascular disease in familial hypercholesterolaemia. Journal of Internal Medicine 238:5, 451-459
CrossRef88
W. BARTENS, D. J. RADER, G. TALLEY, H. B. BREWER JR. (1995) Lipoprotein (a) in patients with hyperlipidaemia. European Journal of Clinical Investigation 25:9, 647-653
CrossRef89
Clinton D. Brown, Neal Azrolan, Lorraine Thomas, Kathleen G. Roberts, Andrew Bostom, Zhong H. Zhao, E.A. Friedman. (1995) Reduction of lipoprotein(a) following treatment with lovastatin in patients with unremitting nephrotic syndrome. American Journal of Kidney Diseases 26:1, 170-177
CrossRef90
Fritz Hoppichler, Christoph Sandholzer, Roy Moncayo, Gerd Utermann, Hans Georg Kraft. (1995) Thyroid hormone (fT4) reduces lipoprotein(a) plasma levels. Atherosclerosis 115:1, 65-71
CrossRef91
Stevhn Haffner, Trevor Orchard, Evan Stein, Donald Schmidt, Patrice Labelle. (1995) Effect of simvastatin on Lp(a) concentrations. Clinical Cardiology 18:5, 261-267
CrossRef92
T. KUUSI, H. YKI-JÄRVINEN, R. KAUPPINEN-MAKELIN, M. JAUHIAINEN, C. EHNHOLM, M. KAUPPILAy, P. SEPPÄLÄ, J. VIIKARI, E. KUJANSUU, S. RAJALA, J. LAHTI, L. NISKANEN, T. MARJANEN, S. SALO, L. RYYSY, T. TULOKAS, M.-R. TASKINEN. (1995) Effect of insulin treatment on serum lipoprotein(a) in non-insulin-dependent diabetes. European Journal of Clinical Investigation 25:3, 194-200
CrossRef93
S Gilligan. (1995) The effect of reduction of lipoprotein (a) on cellular cholesterol synthesis in non-diabetic and Type 2 diabetic subjects. Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism 1254:2, 187-192
CrossRef94
C. M. Barbagallo, M. R. Averna, T. Dimarco, L. Spano, V. Scafidi, G. Marino, A. Rao Camemi, A. Notarbartolo. (1995) Effectiveness of cascade filtration plasmapheresis in two patients affected by familial hypercholesterolemia. Journal of Clinical Apheresis 10:2, 96-100
CrossRef95
Yechiel Friedlander, Eran Leitersdorf. (1995) Segregation analysis of plasma lipoprotein(a) levels in pedigrees with molecularly defined familial hypercholesterolemia. Genetic Epidemiology 12:2, 129-143
CrossRef96
Paula K. Locker, Gail L. Jungbluth, Steven F. Francom, George S. Hughes. (1995) Lifibrol: A novel lipid-lowering drug for the therapy of hypercholesterolemia*. Clinical Pharmacology & Therapeutics 57:1, 73-88
CrossRef97
M. Flesch, A. Sachinidis, Y. D. Ko, K. Kraft, H. Vetter. (1994) Plasma lipids and lipoproteins and essential hypertension. The Clinical Investigator 72:12, 944-950
CrossRef98
Peter T.KUO. (1994) Dyslipidemia and coronary artery disease. Clinical Cardiology 17:10, 519-527
CrossRef99
Pamela J. Schreiner, L.E. Chambless, Spencer A. Brown, Robert L. Watson, James Toole, Gerardo Heiss. (1994) Lipoprotein(a) as a correlate of stroke and transient ischemic attack prevalence in a biracial cohort: The ARIC study. Annals of Epidemiology 4:5, 351-359
CrossRef100
R.E. Gilbert, M.E. Cooper, P.G. McNally, R.C. O'Brien, J. Taft, G. Jerums. (1994) Microalbuminuria: Prognostic and Therapeutic Implications in Diabetes Mellitus. Diabetic Medicine 11:7, 636-645
CrossRef101
Sandra Harris-Hooker, Gary L. Sanford. (1994) Lipids, lipoproteins and coronary heart disease in minority populations. Atherosclerosis 108, S83-S104
CrossRef102
Ernst J. Schaefer, Jacques J. Genest, Jose M. Ordovas, Deeb N. Salem, Peter W.F. Wilson. (1994) Familial lipoprotein disorders and premature coronary artery disease. Atherosclerosis 108, S41-S54
CrossRef103
Gösta H. Dahlén. (1994) Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis 108:2, 111-126
CrossRef104
Werner Bartens, Daniel J. Rader, Glenda Talley, H.Bryan Brewer. (1994) Decreased plasma levels of lipoprotein(a) in patients with hypertriglyceridemia. Atherosclerosis 108:2, 149-157
CrossRef105
Israel Karmansky, Nachman Gruener. (1994) Structure and Possible biological roles of Lp(a). Clinical Biochemistry 27:3, 151-162
CrossRef106
G. FEUSSNER, V. FEUSSNER, R. ZIEGLER. (1994) Apolipoprotein (a) phenotypes and lipoprotein (a) concentrations in patients with type III hyperlipoproteinaemia. Journal of Internal Medicine 235:5, 425-430
CrossRef107
Michael M. Ritter, Hans C. Geiss, Werner O. Richter, Peter Schwandt. (1994) Lipoprotein(a) concentrations and phenotypes in controls and patients with hypercholesterolemia or hypertriglyceridemia. Metabolism 43:5, 572-578
CrossRef108
B. Robert, M. Grandhomme, F. Mainard, Y. Madec. (1994) Effect of storage of sera and apolipoprotein(a) phenotypes on detection of lipoprotein(a) by a new agarose gel. Clinica Chimica Acta 225:2, 195-201
CrossRef109
Wayne Huey-Herng Sheu, Chih-Hsueh Hsu, Yan-Shiun Chen, Chii-Yuang Jeng, Martin Mao-Tsu Fuh. (1994) Prospective evaluation of insulin resistance and lipid metabolism in women receiving oral contraceptives. Clinical Endocrinology 40:2, 249-255
CrossRef110
Jin Q. Kim, Jung H. Song. (1994) High allele frequency of apolipoprotein(a) phenotype LpS4 is associated with low serum Lp(a) concentrations in Koreans. Clinical Biochemistry 27:1, 57-62
CrossRef111
Sohvi Hörkkö, Kaisa Huttunen, Taina Korhonen, Y Antero Kesäniemi. (1994) Decreased clearance of low-density lipoprotein in patients with chronic renal failure. Kidney International 45:2, 561-570
CrossRef112
H. Lind, P. Nilsson, N. Holthuis, L. Lindholm. (1994) Non-obese men with high lipoprotein(a) values– a cardiovascular risk group different from those with the metabolic syndrome?. Scandinavian Journal of Clinical & Laboratory Investigation 54:2, 177-183
CrossRef113
Victor William Armstrong, Peter Schuff-Werner, Thomas Eisenhauer, Marion Helmhold, Margit Stix, Dietrich Seidel. (1994) Heparin extracorporeal LDL precipitation (HELP): an effective apheresis procedure for lowering Lp(a) levels. Chemistry and Physics of Lipids 67-68, 315-321
CrossRef114
Gert M. Kostner, Harald Grillhofer. (1994) The interaction of Lp(a) with normal and LDL-receptor-deficient human skin fibroblasts. Chemistry and Physics of Lipids 67-68, 153-159
CrossRef115
Steven M. Haffner, Myrto Frangos, Joseph Williamson, Julio Santiago, Rodolfo Valdez, Gilbert Aldrete, Leena Mykkänen, Katherine K. Gruber, David L. Rainwater. (1994) Lp(a) concentrations and phenotypes in children with insulin-dependent diabetes mellitus. Chemistry and Physics of Lipids 67-68, 223-231
CrossRef116
Carmen R. Rodriguez, Leo J. Seman, Jose M. Ordovas, Jennifer Jenner, M.S.Jacques Genest, Peter W.F. Wilson, Ernst J. Schaefer. (1994) Lipoprotein(a) and coronary heart disease. Chemistry and Physics of Lipids 67-68, 389-398
CrossRef117
Giancarlo Ghiselli, Antonio Gaddi. (1994) The relation of LDL receptor activity to lipoprotein(a) plasma concentration in patients without coronary artery disease. Chemistry and Physics of Lipids 67-68, 305-311
CrossRef118
Kari Kervinen, Markku J. Savolainen, Juhani Salokannel, Antti Hynninen, Jukka Heikkinen, Christian Ehnholm, M. Juhani Koistinen, Y. Antero Kesäniemi. (1994) Apolipoprotein E and B polymorphisms - longevity factors assessed in nonagenarians. Atherosclerosis 105:1, 89-95
CrossRef119
Thomas B. Ledue, Louis M. Neveux, Glenn E. Palomaki, Robert F. Ritchie, Wendy Y. Craig. (1993) The relationship between serum levels of lipoprotein(a) and proteins associated with the acute phase response. Clinica Chimica Acta 223:1-2, 73-82
CrossRef120
M. A. LASUNCIÓN, J. L. TERUEL, J. J. ALVAREZ, P. CARRERO, J. ORTUÑO, D. GÓMEZ-CORONADO. (1993) Changes in Iipoprotein(a), LDL-cholesterol and apolipoprotein B in homozygous familial hypercholesterolaemic patients treated with dextran sulfate LDL-apheresis. European Journal of Clinical Investigation 23:12, 819-826
CrossRef121
Takaki Hiraga, Minoru Okubo, Tetsuro Kobayashi, Kohji Nakanishi, Tadao Sugimoto, Toshio Murase. (1993) Serum lipoprotein(a) levels differ in different phenotypes of primary hyperlipoproteinemia. Metabolism 42:10, 1327-1330
CrossRef122
Akira Abe, Akio Noma, Hiroshige Itakura. (1993) Lipoprotein(a) phenotyping using a computerized micro scale and phenotype frequencies in a healthy Japanese population. Clinica Chimica Acta 219:1-2, 149-157
CrossRef123
Juan J. Álvarez, Miguel A. Lasunción, Jose M. Olmos, Emilio Herrera. (1993) Interindividual variation in the partition of lipoprotein(a) into lipoprotein subfractions. Clinical Biochemistry 26:5, 399-408
CrossRef124
Hiroshi Nakata, Kazutoshi Horita, Masaaki Eto. (1993) Alteration of lipoprotein(a) concentration with glycemic control in non-insulin-dependent diabetic subjects without diabetic complications. Metabolism 42:10, 1323-1326
CrossRef125
B. J. HEESEN, B. H. R. WOLFFENBUTTEL, P. B. LEURS, J. P. J. E. SELS, P. P. C. A. MENHEERE, S. E. C. JÄCKLE-BECKERS, A. C. NIEUWENHUIJZEN KRUSEMAN. (1993) Lipoprotein(a) levels in relation to diabetic complications in patients with non-insuIin-dependent diabetes. European Journal of Clinical Investigation 23:9, 580-584
CrossRef126
Federico Tatò, Christiane Keller, Herbert Schuster, Florentin Spengel, Günther Wolfram, Nepomuk Zöllner. (1993) Relation of lipoprotein(a) to coronary heart disease and duplexsonographic findings of the carotid arteries in heterozygous familial hypercholesterolemia. Atherosclerosis 101:1, 69-77
CrossRef127
Manuel Castro Cabezas, Tjerk W.A. de Bruin, Margreet Van Linde-Sibenius Trip, Luciënne A.W. Kock, Hans Jansen, D.Willem Erkelens. (1993) Lipoprotein(a) plasma concentrations associated with lipolytic activities in eight kindreds with familial combined hyperlipidemia and normolipidemic subjects. Metabolism 42:6, 756-761
CrossRef128
Junji Koizumi, Ichiro Koizumi, Yoshihide Uno, Akihiro Inazu, Kouvi Kajinami, Tatsuo Haraki, Kunimasa Yagi, Nobuo Kamon, Susumu Miyamoto, Tadayoshi Takegoshi, Hiroshi Mabuchi, Ryoyu Takeda, Nobutaka Tani, Satoshi Takada. (1993) Reduction of lipoprotein(a) by LDL-apheresis using a dextran sulfate cellulose column in patients with familial hypercholesterolemia. Atherosclerosis 100:1, 65-74
CrossRef129
I. C. KLAUSEN, L. U. GERDES, H. MEINERTZ, F. A. HANSEN, O. FAERGEMAN. (1993) Apolipoprotein(a) polymorphism predicts the increase of Lp(a) by pravastatin in patients with familial hypercholesterolaemia treated with bile acid sequestration. European Journal of Clinical Investigation 23:4, 240-245
CrossRef130
Winfried März, Rüdiger Siekmeier, Elke Groβ, Werner Groβ. (1993) Determination of lipoprotein(a): enzyme immunoassay and immunoradiometric assay compared. Clinica Chimica Acta 214:2, 153-163
CrossRef131
L. BERGLUND, O. WIKLUND, G. EGGERTSEN, S.-O. OLOFSSON, M. ERIKSSON, T. LINDÉN, G. BONDJERS, B. ANGELIN. (1993) Apolipoprotein E phenotypes in familial hypercholesterolaemia: importance for expression of disease and response to therapy. Journal of Internal Medicine 233:2, 173-178
CrossRef132
W. März, R. Siekmeier, W. Groβ, G. M. Kostner. (1993) Determination of Lipoprotein(a): Evaluation of Three Methods. Clinical Chemistry and Laboratory Medicine 31:5, 295-302
CrossRef133
J. Tashiro, T. Nishide, M. Shinomiya, K. Shirai, Y. Saito, S. Yoshida, M. Yamashita, H. Ohshima, H. Murayama. (1993) The ‘midband’ lipoprotein is a coronary risk factor in Japanese patients with familial hypercholesterolaemia. Scandinavian Journal of Clinical & Laboratory Investigation 53:4, 335-338
CrossRef134
J.D. Kark, C. Sandholzer, Y. Friedlander, G. Utermann. (1993) Plasma Lp(a), apolipoprotein(a) isoforms and acute myocardial infarction in men and women: a case-control study in the Jerusalem population. Atherosclerosis 98:2, 139-151
CrossRef135
Peter H. Winocour, Paul N. Durrington, Deepak Bhatnagar, Anthony D. Mbewu, Monica Ishola, Michael Mackness, Sharon Arrol. (1992) A cross-sectional evaluation of cardiovascular risk factors in coronary heart disease associated with Type 1 (insulin-dependent) diabetes mellitus. Diabetes Research and Clinical Practice 18:3, 173-184
CrossRef136
Marek Naruszewicz, Elizabeth Selinger, Robert Dufour, Jean Davignon. (1992) Probucol protects lipoprotein(a) against oxidative modification. Metabolism 41:11, 1225-1228
CrossRef137
L. Slunga, O. Johnson, G. H. Dahlén. (1992) Changes in Lp(a) lipoprotein levels during the treatment of hypercholesterolaemia with simvastatin. European Journal of Clinical Pharmacology 43:4, 369-373
CrossRef138
J. TYRRELL, T. COOKE, M. REILLY, M. COLGAN, D. MOORE, D. G. SHANIK, C. BERGIN, J. FEELY. (1992) Lipoprotein [Lp(a)] and peripheral vascular disease. Journal of Internal Medicine 232:4, 349-352
CrossRef139
Charng-Ming Huang, Ronald J. Elin, Mark Ruddel, John Schmitz, Markku Linnoila. (1992) The Effect of Alcohol Withdrawal on Serum Concentrations of Lp(a), Apolipoproteins A-1 and B, and Lipids. Alcoholism: Clinical and Experimental Research 16:5, 895-898
CrossRef140
A. Abe, A. Noma, Y.J. Lee, H. Yamaguchi. (1992) Studies on apolipoprotein(a) phenotypes. Part 2. Phenotype frequencies and Lp(a) concentrations in different phenotypes in patients with angiographically defined coronary artery diseases. Atherosclerosis 96:1, 9-15
CrossRef141
Giancarlo Ghiselli, Antonio Gaddi, Giuseppe Barozzi, Alessandro Ciarrocchi, Giancarlo Descovich. (1992) Plasma lipoprotein(a) concentration in familial hypercholesterolemic patients without coronary artery disease. Metabolism 41:8, 833-838
CrossRef142
G. FULCHER. (1992) Lipoprotein(a): a new independent risk factor for atherosclerosis. Australian and New Zealand Journal of Medicine 22:4, 326-328
CrossRef143
Angelo M. Scanu. (1992) Lipoprotein(a) link between structure and pathology. Annals of Epidemiology 2:4, 407-412
CrossRef144
A. M. SCANU. (1992) Genetic basis and pathophysiological implications of high plasma Lp(a) levels. Journal of Internal Medicine 231:6, 679-683
CrossRef145
A. K. SOUTAR. (1992) Familial hypercholesterolaemia and LDL receptor mutations. Journal of Internal Medicine 231:6, 633-641
CrossRef146
A. B. Irish, L. A. Simons, E. Savdie, J. M. Hayes, J. Simons. (1992) Lipoprotein(a) levels in chronic renal disease states, dialysis and transplantation. Australian and New Zealand Journal of Medicine 22:3, 243-248
CrossRef147
S.M. WILKINSON, A. ATKINSON, R.H. NEARY, A.G. SMITH. (1992) Normolipaemic plane xanthomas: an association with increased vascular permeability and serum lipoprotein(a) concentration. Clinical and Experimental Dermatology 17:3, 211-213
CrossRef148
Steven M. Haffner, Scot E. Moss, Barbara E.K. Klein, Ronald Klein. (1992) Lack of association between lipoprotein (a) concentrations and coronary heart disease mortality in diabetes: The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Metabolism 41:2, 194-197
CrossRef149
Steven M. Haffner, Katherine R. Tuttle, David L. Rainwater. (1992) Lack of change of lipoprotein (a) concentration with improved glycemic control in subjects with type II diabetes. Metabolism 41:2, 116-120
CrossRef150
Nader Rifai, Gerardo Heiss, Karl Doetsch. (1992) Lipoprotein(a) at birth, in blacks and whites. Atherosclerosis 92:2-3, 123-129
CrossRef151
Epstein, Franklin H., , Fuster, Valentin, Badimon, Lina, Badimon, Juan J., Chesebro, James H., . (1992) The Pathogenesis of Coronary Artery Disease and the Acute Coronary Syndromes. New England Journal of Medicine 326:5, 310-318
Full Text152
Kimmo Kontula, Ulla-Maija Koivisto, Pekka Koivisto, Hannu Turtola. (1992) Molecular Genetics of Familial Hypercholesterolaemia: Common and Rare Mutations of the Low Density Lipoprotein Receptor Gene. Annals of Medicine 24:5, 363-367
CrossRef153
A. A. KROON, P. N. M. DEMACKER, A. F. H. STALENHOEF. (1991) N-acetylcysteine and serum concentrations of lipoprotein(a). Journal of Internal Medicine 230:6, 519-526
CrossRef154
John A. Farmer, Christie M. Ballantyne, O.Howard Frazier, Branislav Radovancevic, Charlotte Payton-Ross, Wolfgang Patsch, Joel D. Morrisett, Antonio M. Gotto, James B. Young. (1991) Lipoprotein(a) and apolipoprotein changes after cardiac transplantation. Journal of the American College of Cardiology 18:4, 926-930
CrossRef155
L.J. Garcia Frade, J.J. Alvarez, I. Rayo, M.C. Torrado, M.A. Lasunción, A. Garcia Avello, A. Hernandez, E. Marin. (1991) Fibrinolytic parameters and lipoprotein (a) levels in plasma of patients with coronary artery disease. Thrombosis Research 63:4, 407-418
CrossRef156
(1991) Lipoprotein (a). The Lancet 337:8738, 397-398
CrossRef157
Kari Kervinen, Markku J Savolainen, Y Antero Kesäniemi. (1991) A rapid increase in lipoprotein (a) levels after ethanol withdrawal in alcoholic men. Life Sciences 48:22, 2183-2188
CrossRef158
(1990) Lipoprotein(a) and Coronary Heart Disease in Patients with Familial Hypercholesterolemia. New England Journal of Medicine 323:25, 1773-1774
Full Text
- Letters
