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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several epidemiological studies have established that elevated serum lipoprotein (a) [Lp(a)] levels are independent risk factors for coronary heart disease, stroke, and restenosis of coronary lesions in white and Asian populations. Serum Lp(a) levels vary over a 1000-fold range among individuals and are under strict genetic control. Serum Lp(a) levels are significantly higher in populations with African ancestry than in populations of European ancestry. The APOA gene exhibits hypervariable length polymorphism resulting from a variable number of expressed kringle 4 repeats. An inverse relationship exists between the size of kringle 4 repeats and serum Lp(a) levels. However, most studies have been conducted in whites, and the data are scanty in African populations. To explore this relationship among Africans, we determined serum Lp(a) levels and APOA Kringle 4 size polymorphisms in 781 unrelated Africans (490 men, 291 women) from Benin City, Nigeria. Mean and median serum Lp(a) values were 25.6 +/- 0.6 mg/dl and 20.9 mg/dl, respectively. Although there was no difference in mean Lp(a) values between men and women, median Lp(a) values were higher in women than in men (p = 0.02). Using SDS-agarose gel electrophoresis, we detected 38 APOA isoforms, the highest number recorded to data. There were 10 consecutive medium-size alleles whose frequencies ranged between 4.2% and 10.9%, and together they accounted for 72.8% of the alleles observed in this population. Spearman's correlation coefficients showed an inverse relationship between the size of the APOA isoform and Lp(a) levels using either single-banded (r = 0.46; p < 0.0001) or double-banded (r = 0.42; p < 0.0001) phenotypes. Using random effects analysis of variance on the entire sample, the APOA size polymorphism explained about 15% of the phenotypic variation in Lp(a) levels. These data suggest that despite significant correlation between the APOA kringle 4 size polymorphism and Lp(a) levels, other sequence variations either in the APOA gene or closely linked genes may account for relatively higher Lp(a) levels found in Africans.
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PMID:Apolipoprotein A kringle 4 polymorphism and serum lipoprotein (a) concentrations in African blacks. 959 40

Hypertension is more common among African Americans than Americans of European descent. However, the genetic etiology has not been defined. Similarly, lipoprotein (Lp) (a), an independent risk factor for cardiovascular disease, is higher among African Americans. To explore the relationship between Lp (a) and hypertension, we measured the blood pressure of transgenic mice expressing apolipoprotein(a), the unique protein moiety of lipoprotein(a). As controls, we also determined blood pressure for apoE deficient mice, low density lipoprotein-receptor (LDL-R) deficient mice, and wild type C57Bl/6 mice. Apo(a) expression was not associated with hypertension. Surprisingly, LDL-R deficient mice exhibited male-associated hypertension. This observation could explain the higher incidence of atherosclerosis in male LDL-R deficient mice and human familial hypercholesterolemia (FH) patients. LDL-R deficient mice were more sensitive to photochemically induced cerebral stroke. However, this hypersensitivity was only modestly associated with sexual dimorphism. The presented data suggest that LDL-R deficiency results in hitherto unrecognized changes in the vascular tone.
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PMID:Male-associated hypertension in LDL-R deficient mice. 964 16

Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0 +/- 12.1 years; 32% women) presenting with AIS (evaluated within 9.7 +/- 12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225 +/- 57.6, 154 +/- 56.0, 40 +/- 10.4, 181 +/- 93.7, 52 +/- 28.6, 130 +/- 24.6, and 141 +/- 46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.
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PMID:Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study. 971 47

The authors studied whether haemostatic abnormalities connected with the development of cerebral circulatory disturbances can be demonstrated in young stroke patients in whom Doppler and angiographic examination failed to reveal deviations indicative of stroke. They determined the in vivo activation of the coagulation system (TAT, F 1 + 2), the degree of secondary fibrinolysis (D-dimer), the plasma levels of the markers of fibrinolysis, with special regard to inhibitors: plasminogen activator inhibitor (PAI-1), alpha 2 antiplasmin (alpha 2 AP), alpha 2 macroglobulin (alpha 2 M), the frequency of pathologic serum lipoprotein (a)-Lp(a)-values and the association of PAI-1 and Lp(a) with the fibrinolytic system. They conclude that in the acute phase of the disease, the TAT and F 1 + 2 values were significantly elevated compared to the control, without change in the D-dimer value. The results suggest that in the tested period increased thrombin generation dominated and it significantly surpassed plasmin activity since the D-dimer values of that period did not indicate substantial increase in secondary fibrinolysis. The results of the study were separately analyzed in acute, chronic TIA and stroke groups. In the TIA and acute group the F 1 + 2 values, while in stroke the TAT values were more elevated. The in vitro fibrinolytic capacity of the patients significantly decreased compared to controls, showing significant correlation with the Lp(a) level, but not with the PAI value. Examination of the marker molecules renders possible to assess the degree of hypercoaguability and of endogenous lysis. Their knowledge is held important for judging the progression of the disease and the therapeutic consequences.
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PMID:[Hemostatic abnormalities in ischemic stroke]. 981 Jan 64

Increased plasma lipoprotein (a) (Lp(a)) levels are strongly associated with premature cardiovascular disease and stroke. Recently we, as well as other groups, found that apolipoprotein (a) (apo(a)) fragments appear in the urine of healthy individuals, and that renal transplant patients with impaired renal function excrete fewer apo(a) fragments into their urine compared with controls. As the excretion mode of apo(a) is presently unknown, we determined plasma Lp(a) levels and urinary apo(a) excretion in relation to kidney function in 58 proteinuric patients and 58 healthy controls. For the first time, urinary apo(a) excretion was related to apo(a) isoforms. Plasma Lp(a) values were higher in the proteinuric patients compared with the controls, independent of their renal function. The patients with low-molecular-weight apo(a) isoforms had higher Lp(a) plasma levels, whereas the patients with high-molecular-weight apo(a) isoforms had lower Lp(a) plasma levels. Urinary apo(a) showed a very similar pattern to that of plasma Lp(a), being significantly higher in patients with low-molecular-weight isoforms as compared with patients with high-molecular-weight isoforms. Urinary apo(a) excretion was significantly decreased in the patient group when compared with healthy controls. There was a close correlation (P < 0.001) between the plasma Lp(a) and urinary apo(a) excretion in both the patient group and the control group. Urinary apo(a) excretion did not correlate with protein excretion, creatinine clearance or plasma creatinine levels. We conclude that urinary apo(a) excretion correlates with plasma Lp(a) and Lp(a) isoforms, and that proteinuric patients excrete significantly less apo(a) into their urine than healthy controls, a factor that might contribute to increased plasma Lp(a) levels in these patients.
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PMID:Urinary apolipoprotein (a) excretion in patients with proteinuria. 981 37

High serum lipoprotein(a) (Lp(a)) concentration which is largely determined by genetic factors, mainly the apolipoprotein(a) (apo(a)) polymorphism, is associated with ischemic cerebrovascular disease. The aim of this study was to investigate whether apo(a) size was associated with acute ischemic stroke in young adults for which causal factors often remain undetermined. Lipid parameters, Lp(a) concentration and apo(a) isoform size distribution were determined in 90 young patients (37.4+/-8.7 years) with acute cerebral ischemia, and compared to those of control subjects with similar age and sex ratio. Apo(a) size was expressed as its apparent number of kringle 4 (Kr 4) repeats. Serum Lp(a) concentrations were significantly higher in patients than in controls (median values: 0.18 vs. 0.07 g/l, P=0.009) and were as expected inversely related to the number of kringle 4 repeats in both controls (r2=-0.61, P < 0.001) and patients (r2=-0.56, P < 0.001). However there was no difference in the apo(a) isoform size distributions between the two groups (median isoform size: 27 vs. 27 Kr 4, P=0.25). Lp(a) levels were increased as well in patients with size apo(a) isoform < or = 22 Kr 4 as in those with isoforms > 25 Kr 4. Multivariate analysis showed that apo(a) phenotype did not appear as a risk factor for cerebrovascular infarction. Thus, our results indicate that serum Lp(a) was significantly increased in young people with ischemic stroke but fail to reveal a role of small-sized apo(a) isoforms in the occurrence of this event. They suggest that other factors, genetic or environmental in nature, than the apo(a) size contribute to increase the serum Lp(a) concentrations in these young patients.
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PMID:Apolipoprotein(a) size polymorphism in young adults with ischemic stroke. 992 May 27

The human plasma lipoprotein Lp(a) has gained considerable clinical interest as a genetically determined risk factor for atherosclerotic vascular diseases. Numerous (including prospective) studies have described a correlation between elevated Lp(a) plasma levels and coronary heart disease, stroke and peripheral atherosclerosis. Lp(a) consists of a large LDL-like particle to which the specific glycoprotein apo(a) is covalently linked. The apo(a) gene is located on chromosome 6 and belongs to a gene family including the highly homologous plasminogen. Lp(a) plasma concentrations are controlled to a large extent by the extremely polymorphic apo(a) gene. More than 30 alleles at this locus determine a size polymorphism. The size of the apo(a) isoform is inversely correlated with Lp(a) plasma concentrations, which are non-normally distributed in most populations. To a minor extent, apo(a) gene-independent effects also influence Lp(a) concentrations. These include diet, hormonal status and diseases like renal disease and familial hypercholesterolemia. The standardisation of Lp(a) quantification is still an unresolved problem due to the enormous particle heterogeneity of Lp(a) and homologies of other members of the gene family. Stability problems of Lp(a) as well as statistical pitfalls in studies with small group sizes have created conflicting results. The apo(a)/Lp(a) secretion from hepatocytes is regulated at various levels including postranslationally by apo(a) isoform-dependent prolonged retention in the endoplasmic reticulum. This mechanism can partly explain the inverse correlation between apo(a) size and plasma concentrations. According to numerous investigations, Lp(a) is assembled extracellularly from separately secreted apo(a) and LDL. The sites and mechanisms of Lp(a) removal from plasma are only poorly understood. The human kidney seems to represent a major catabolic organ for Lp(a) uptake. The underlying mechanism is rather unclear; several candidate receptors from the LDL-receptor gene family do not or poorly bind Lp(a) in vitro. Lp(a) plasma levels are elevated over controls in patients with renal diseases like nephrotic syndrome and end-stage renal disease. Following renal transplantation, Lp(a) concentrations decrease to values observed in controls matched for apo(a) type. Controversial data on Lp(a) in diabetes mellitus mainly result from insufficient sample sizes in numerous studies. Large studies and those including apo(a) phenotype analysis have come to the conclusion that Lp(a) levels are not or only moderately elevated in insulin-dependent patients. In non-insulin-dependent diabetics Lp(a) is not elevated. Several rare disorders, such as LCAT and LPL deficiency, as well as liver diseases and abetalipoproteinemia are associated with low plasma levels or lack of Lp(a).
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PMID:Genetics and metabolism of lipoprotein(a) and their clinical implications (Part 1). 1006 65

High plasma concentrations of lipoprotein(a) [Lp(a)], a covalent low-density lipoprotein-apolipoprotein(a) [apo(a)] complex, are associated with coronary heart disease and stroke. Heritability of Lp(a) levels is high and the major locus determining Lp(a) concentrations is the apo(a) gene. We here demonstrate that a G-->A substitution at the +1 donor splice site of the apo(a) kringle (K) IV type 8 intron occurs with a high frequency ( approximately 6%) in Caucasians but not in Africans and is associated with congenital deficiency of Lp(a) in plasma. This mutation alone accounts for a quarter of all 'null' apo(a) alleles in Caucasians. RT-PCR analysis based on apo(a) illegitimate transcription in lympho- blastoid cells demonstrated that the donor splice site mutation results in an alternative splicing of the K IV type 8 intron and encodes a truncated form of apo(a). Expression of the alternatively spliced cDNA analogue in HepG2 cells showed that the truncated apo(a) form is secreted but is unable to form the covalent Lp(a) complex. Immunoprecipitated plasma apo(a) from homozygotes for the mutation was almost completely fragmented. Taken together, our data indicate that a failure in complex formation followed by fast degradation in plasma of the truncated free apo(a) is one mechanism which underlies the null Lp(a) type associated with the donor splice site mutation.
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PMID:Molecular basis of congenital lp(a) deficiency: a frequent apo(a) 'null' mutation in caucasians. 1048 79

To elucidate the clinical significance of lipoprotein(a) [Lp(a)] in the elderly, 48 patients with Lp(a) of 35 mg/dl or more [the high Lp(a) group] and 97 patients with Lp(a) less than 20 mg/dl [the low Lp(a) group] were enrolled to investigate their outcome for five years. At registration, they were all examined by brain computerized tomography (CT) for cerebrovascular diseases, B-mode ultrasonography (US) for carotid lesions, ECG for myocardial ischemia, and Doppler arteriography for the ankle pressure index (API). They were followed up completely to study survival rates, cause of death, and morbidity rates of vascular events, including occurrence of stroke, myocardial infarction, and aortic aneurysm as well as progression of the stage in arteriosclerosis obliterans. The mean age of the high Lp(a) group was 78.1, whereas that of the low Lp(a) group was 76.8. Baseline clinical findings revealed no difference in age or gender between the two groups, although a previous history of stroke, abnormal CT and US findings, and low API were more frequent in the high Lp(a) group than in the low Lp(a) group. In the high Lp(a) group [vs. the low Lp(a) group], 18 patients (vs. 21 patients) died within five years, which resulted in a cumulative mortality rate of 37.5% (vs. 21.6%) and an annual mortality rate of 9.4% (vs. 4.8%). Based on log-rank analysis, the survival rate of the high Lp(a) group was significantly lower than that of the low Lp(a) group. The most common causes of death were vascular events and pneumonia, more than half of them were aspiration pneumonia complicated with stroke. Ten patients in the high Lp(a) group had vascular events (vs. 8 patients). The morbidity rate of vascular events, most of which were cerebral infarction, was higher in the high Lp(a) group (annual morbidity rate 5.5%) than in the low Lp(a) group (1.8%). These findings suggested that serum Lp(a) concentration, genetically determined and remaining consistent throughout life, had influenced vascular wall damage over a long time with age, therefore, a high Lp(a) level might promote atherothrombosis. In the elderly, therefore, high Lp(a) level, resulting in symptomatic vascular lesions with organ dysfunction, is a distinct and independent poor prognostic risk factor.
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PMID:[Clinical significance of serum lipoprotein(a) concentration in the elderly with regard to vascular complications and long-term prognosis]. 1055 60

Ischemic stroke is a rare event in childhood. In approximately one third of cases no obvious underlying cause or disorder can be detected. We investigated the importance of genetic risk factors of venous thromboembolism in childhood or stroke in adulthood as risk factors for spontaneous ischemic stroke in children. One hundred forty-eight Caucasian infants and children (aged 0.5 to 16 years) with stroke and 296 age-matched controls from the same geographic areas as the patients were analyzed for increased lipoprotein (a) [Lp(a)] levels >30 mg/dL; for the presence of the factor V (FV) G1691A mutation, the prothrombin (PT) G20210A variant, and the TT677 genotype of methylenetetrahydrofolate reductase (MTHFR); and deficiencies of protein C, protein S, and antithrombin. The following frequencies (patients v controls), odds ratios (ORs), and confidence intervals (CIs) of single risk factors were found: Lp(a) >30 mg/dL (26.4% v 4.7%; OR/CI, 7.2/3.8 to 13.8; P <.0001), FV G1691A (20.2% v 4%; OR/CI, 6/2.97 to 12.1; P <.0001), protein C deficiency (6% v 0.67%; OR/CI, 9.5/2 to 44.6; P =.001), PT G20210A (6% v 1.3%; OR/CI, 4.7/1.4 to 15.6; P =.01), and the MTHFR TT677 genotype (23.6% v 10.4%; OR/CI, 2.4/1.53 to 4.5; P <.0001). A combination of the heterozygous FV G1691A mutation with increased Lp(a) (n = 11) or the MTHFR TT677 genotype (n = 5) was found in 10. 8% of cases, but only 0.3% of controls (OR/CI, 35.75/4.7 to 272; P <. 0001). Increased Lp (a) levels, the FV G1691A mutation, protein C deficiency, the prothrombin G20210A variant, and the MTHFR TT677 are important risk factors for spontaneous ischemic stroke in childhood.
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PMID:Lipoprotein (a) and genetic polymorphisms of clotting factor V, prothrombin, and methylenetetrahydrofolate reductase are risk factors of spontaneous ischemic stroke in childhood. 1057 79


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