Showing papers by "Terho Lehtimäki published in 1999"
TL;DR: The data suggest that oxidized LDL plays a role in the pathogenesis of atherosclerosis and suggest a protective function for HDL against LDL oxidation and elevated levels of antibodies against oxidization LDL were associated with CAD.
Abstract: —Oxidation of low density lipoproteins (LDL) obviously plays an important role in the pathogenesis of atherosclerosis. The purpose of the study was to determine whether antibodies against oxidized LDL are associated with coronary artery disease (CAD). We determined the serum levels of antibodies against copper-oxidized LDL by enzyme-linked immunosorbent assay in 58 patients with angiographically verified CAD and 34 controls without CAD. The mean antibody level, expressed in optical density units, was significantly higher in patients than in controls (0.150±0.088 versus 0.094±0.054, respectively; P =0.00089). In logistic regression analysis, high antibody level against oxidized LDL was associated significantly with CAD ( P =0.0114), independent of age ( P =0.00137), gender ( P =0.0021), body mass index ( P =0.5947), triglyceride concentration ( P =0.9813), and total cholesterol–high density lipoprotein (HDL) cholesterol ( P =0.0080) group. Similar analysis in nondiabetic subjects (n=79) and in men only (n=75) showed analogous results, with only minor changes in P values. The antibody level against oxidized LDL differed significantly between nonsmokers and smokers in CAD patients ( P P =NS). In addition, the antibody level against oxidized LDL differed significantly between nonsmokers and smokers in subjects with low HDL cholesterol (≤0.9 mmol/L) but not in subjects with high HDL cholesterol (>0.9 mmol/L). In conclusion, elevated levels of antibodies against oxidized LDL were associated with CAD. The data suggest that oxidized LDL plays a role in the pathogenesis of atherosclerosis and suggest a protective function for HDL against LDL oxidation.
206 citations
TL;DR: In men, the apoE epsilon4 allele is a significant genetic risk factor for coronary atherosclerosis in early middle age, and this suggests that at older age, other known risk factors of CHD play a more important role in the atherosclerotic process than apolipoprotein E polymorphisms.
Abstract: Background—Apolipoprotein E (apoE) polymorphism is one of the genetic determinants of serum cholesterol values. The apoE e4 allele has been associated with advanced coronary heart disease (CHD) diagnosed by angiography, but the role of the apoE genotype in atherosclerosis has not been confirmed at vessel-wall level, nor is any age-dependent effect of the apoE genotype on the development of CHD known. Methods and Results—The right and left anterior descending coronary arteries (RCA and LAD) and the aorta from 700 male autopsy cases (Helsinki Sudden Death Study) in 1981-1982 and 1991-1992 (average age 53 years, range 33 to 70 years) were stained for fat, and all areas covered with fatty streaks, fibrotic plaques, and complicated lesions were measured. In the RCA and LAD, the apoE genotype was significantly associated with the area of total atherosclerotic lesions in men <53 years old but not with that in older men (P=0.0085 and P=0.041, respectively, for age-by-genotype interaction). Men <53 years old with ...
167 citations
TL;DR: Apolipoprotein E (Apo E) genotyping on its own is neither sufficiently sensitive nor specific enough for use as a predictive diagnostic test for Alzheimer disease (AD) but is still of diagnostic value in the classification of type III hyperlipidemia.
Abstract: Apolipoprotein E (Apo E) genotyping on its own is neither sufficiently sensitive nor specific enough for use as a predictive diagnostic test for Alzheimer disease (AD) (1). Nevertheless, it is still of diagnostic value in the classification of type III hyperlipidemia (2). Furthermore, there exists a great research need and interest for Apo E genotyping in conjunction with other data relating to genetic polymorphisms. Several independent studies have now established that the inheritance of one or more Apo e4 alleles increases an individual’s risk of developing atherosclerosis and AD (3)(4). Conversely, the inheritance of one or more e2 alleles confers protection against AD (5) and is associated with lower lipid concentrations (6). Thus, a rapid and simple genotyping test is needed for any laboratory that takes part in clinical research related to Apo E.
Apo E is a polymorphic protein consisting of a single polypeptide chain, 299 amino acids long. In plasma, it exists mainly in a nonglycosylated form. The three major isoforms of the protein are Apo E2, Apo E3, and Apo E4. These differ from each other by cysteine-arginine interchanges at amino acid residues 112 and 158. The biosynthesis of each protein isoform is under the control of three independent codominant alleles, e2, e3, and e4, located at a single Apo E gene locus on chromosome 19q13. Depending on the inheritance of any two alleles, six common Apo E genotypes are possible, three homozygotes (e2e2, e3e3, and e4e4) and three heterozygotes (e2e3, e3e4, and e2e4) (7).
Currently, several different Apo E genotyping techniques have been described; these include minisequencing (8), single-strand conformation polymorphism (9), allele-specific oligonucleotide probes (10), oligonucleotide ligation assays (11), restriction isotyping with Hha I or Afl III/ Hae II (12)(13), and the amplification refractory mutation system (ARMS) (14). The ARMS …
121 citations
TL;DR: CSF t Tau levels are stable over extended periods of time in a group of mild-to-moderately demented AD subjects and that CSF tau levels do not predict the severity or rate of progression of AD, at least not during the middle stages of the illness.
112 citations
Journal Article•
TL;DR: Cystatin C measurement is a more sensitive and specific test for GFR in patients with type 2 diabetes than plasma creatinine or its clearance, when GFR is normal or only slightly reduced.
Abstract: Aim: To evaluate plasma cystatin C as a marker of the glomerular filtration rate in patients with type 2 diabetes and their age and sex-matched controls. Materials and methods: Forty-seven patients with one decade of type 2 diabetes and 51 non-diabetic control subjects were studied. Plasma cystatin C was measured by particle-enhanced turbidimetric immunoassay in a new application for the Hitachi 704 analyzer. For comparison, plasma creatinine and creatinine clearance were measured. The plasma clearance of 5 1 Cr-EDTA by the single injection method was utilized as reference. Results: In patients with type 2 diabetes the correlation coefficient between plasma cystatin C and the plasma clearance of 51 Cr-EDTA was 0.774 (Spearman's coefficient) and that between plasma creatinine and the plasma clearance of 51 Cr-EDTA was 0.556 (p = 0.001 for the difference). The correlation between creatinine clearance and the plasma clearance of 51 Cr-EDTA was 0.411. In receiver operating characteristic (ROC) curve analysis the diagnostic accuracy of plasma cystatin C was significantly better than that of plasma creatinine (p = 0.047) or creatinine clearance (p = 0.001). The best diagnostic efficiency (98%) for cystatin C was obtained when the cut-off limit was set at 1.32 mg/l. In the control group the correlation coefficients were: between cystatin C and the plasma clearance of 51 Cr-EDTA 0.627, between creatinine and the plasma clearance of 51 Cr-EDTA 0.466 and between creatinine clearance and the plasma clearance of 51 Cr-EDTA 0.416. The area under the ROC plot curve of cystatin C was also greatest in the control group, but the diagnostic accuracy of cystatin C was marginally better than that of either plasma creatinine (p = 0.05) or creatinine clearance (p = 0.08). Among the control subjects various non-renal causes may have interfered with cystatin C concentrations reducing the correlations. Conclusions: Cystatin C measurement is a more sensitive and specific test for GFR in patients with type 2 diabetes than plasma creatinine or its clearance, when GFR is normal or only slightly reduced. If an elevated cystatin C concentration is found, non-renal factors have to be excluded. The turbidimetric application described here can easily be applied for most clinical chemistry analyzers and is therefore useful in daily clinical practice.
95 citations
TL;DR: A prospective study of the role of the Met54Leu polymorphism on the risk of acute myocardial infarction in healthy men from eastern Finland, carried out among participants in the Kuopio ischaemic heart disease risk factor study.
Abstract: Increased lipid peroxidation is associated with accelerated progression of atherosclerosis.1 Paraoxonase (paraoxonase/arylesterase) is an antioxidative enzyme in high density lipoproteins, which protect against coronary disease2 3 It eliminates organophosphorus pesticides but also the products of lipid peroxidation2 4 The mutation at position 54 of the paraoxonase gene in which methionine is substituted by leucine (Met54Leu) has an effect on paraoxonase, increasing its activity; people who have the methionine allele show decreased paraoxonase activity.4 Only a few studies have looked at the association of the Met54Leu polymorphism with coronary disease,2 5 and the findings are inconclusive. Thus we carried out a prospective study of the role of this polymorphism on the risk of acute myocardial infarction in healthy men from eastern Finland.
Our prospective nested case-control study was carried out among participants in the Kuopio ischaemic heart disease risk factor study We examined 2682 (83%) of 3235 invited men aged 42, 48, 54 or 60 during 1984-9. Blood samples were collected and risk factors assessed at baseline. A DNA sample was available for this study for 1137 men who were free of coronary disease. We registered and verified all myocardial infarctions—definite or possible—between the baseline examinations and the end of 1995.3 The mean follow up time was 8.5 years, and in patients who had had multiple infarctions we considered only the first.
The cases were all 55 men (among the 1137) who had had an infarction by 1995. The controls were drawn from the remaining members of the same cohort. Two controls for each case (110 men) were matched …
73 citations
TL;DR: The associations betweenbrain atrophy and neurological disability expressed by EDSS suggests that the effect of MS therapies should be evaluated by measurement of brain atrophy.
64 citations
TL;DR: The results suggest that lipid peroxidation may have an effect on DNA oxidation in type 2 diabetes patients and non-diabetic control subjects.
Abstract: The paraoxonase enzyme (PON) gene polymorphism causes a change of methionine (M-allele) to leucine (L-allele). PON may reduce low density lipoprotein oxidation and prevent atherosclerosis. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive index of oxidative DNA damage. We have studied the association between the PON genotypes and the urinary excretion of 8-OHdG. The study population consisted of 93 Finnish type 2 diabetes patients and 106 non-diabetic control subjects. The 24-h excretion of 8-OHdG was significantly higher in diabetic patients than in control subjects (P < 0.001). In control subjects, the ratio of the 8-OHdG/glomerular filtration rate increased in order of genotype from MM to ML to LL (P < 0.0412). These results suggest that lipid peroxidation may have an effect on DNA oxidation.
31 citations
TL;DR: At present the measurement OxLDL-Abs still remains a method for basic research and is not applicable for screening of at-risk patients with OSA.
Abstract: Autoantibodies against oxidised low-density lipoprotein (OxLDL-Abs) have been proposed to be an indicator of endothelial dysfunction and a novel tool for finding individuals with a high cardiovascular risk. In a cross-sectional study, OxLDL-Abs were measured in 297 patients with obstructive sleep apnoea (OSA) and 54 controls using an enzyme-linked immunosorbent assay. The autoantibodies were increased in patients with OSA when compared to controls (age, body mass index (BMI) and gender adjusted, p = 0.001). However, within the OSA patients, OxLDL-Abs were not related to smoking, hypertension or BMI, and there was a weak negative correlation (r = -0.16, P = 0.007) between age and levels of OxLDL-Abs. In conclusion, at present the measurement OxLDL-Abs still remains a method for basic research and is not applicable for screening of at-risk patients with OSA.
29 citations
TL;DR: The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role incarotid atherosclerosis.
Abstract: The insertion/deletion (I/D) polymorphism of the human angiotensin-converting enzyme (ACE) gene is a major determinant of circulating ACE levels. The D allele has been suggested to be a potent risk factor for coronary artery disease; however, the effect of the ACE gene on carotid atherosclerosis remains controversial. We therefore studied the relationship between the ACE gene I/D polymorphism and carotid artery intima-media thickness (IMT). A random sample of 300 men aged 50–59 years living in southern Finland were selected, and 233 agreed to participate (74%). Data were collected in 219 subjects. Quantitative B-mode ultrasonography was used to measure the maximum near and far wall IMT of right and left common, bifurcation, and internal carotid artery. The mean maximum IMT (overall mean) was calculated as the mean of 12 maximum IMTs at 12 standard sites. Patients with an IMT higher than 1.7 mm in at least one of 12 standard sites were assumed to have carotid atherosclerosis. The I/D polymorphism was determined by polymerase chain reaction. Overestimation of the frequency of the DD genotype was eliminated by insertion-specific primer and the inclusion of 5% dimethylsulfoxide. No significant differences were found in carotid wall thickness between the three genotypes; the overall mean IMT were 1.18±0.30, 1.22±0.24, and 1.08±0.40 mm in genotypes of II, ID, and DD, respectively. Similarly, the ACE genotypes and allele frequencies did not differ significantly between the subjects with and those without carotid atherosclerosis. There was no association in the subgroups among only nonsmoking subjects or subjects without chronic medication. The present data indicate that the I/D polymorphism of the ACE gene is not related to carotid IMT and is unlikely to play a major role in carotid atherosclerosis.
23 citations
TL;DR: In normal aging in the amygdala, extracellular Aβ appears later than neurofibrillary changes, indicating that Aβ deposits are degradable and removable and that even in severely atrophic amygdala, there are mechanisms of amyloid resolution.