Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipoprotein(a) [Lp(a)] level is a newly established vascular risk factor which has been suggested to play a role in dementia. However, the majority of Lp(a) cell-to-cell interactions are mediated by its specific apolipoprotein(a) [apo(a)] moiety. This suggests that the size polymorphism of apo(a) may be of importance in conveying the Lp(a)-related risk. Specifically, we postulated that variation in apo(a) isoform size may lead to increased risk of vascular dementia (VaD), Alzheimer's disease (AD), stroke, or all three of them. Under a case-control design we compared Lp(a) plasma levels and the distribution of apo(a) phenotypes in groups of subjects consisting of 50 VaD patients, 162 sporadic AD patients, 95 non-demented stroke patients (NDS), and 105 normal controls. The prevalence of small-sized apo(a) isoforms in the VaD group was significantly higher than that in the stroke and normal control groups, with an odds ratio of 5.29 (95% CI 2.24-12.49, p = 0.0001) for the development of VaD for individuals with at least one apo(a) isoform of low molecular weight (LMW). Furthermore, the possession of at least one small-sized apo(a) isoform significantly increased the risk of AD to 1.92 (95% CI 1.02-3.61, p = 0.0434). Our results demonstrate that possession of at least one LMW apo(a) isoform is significantly associated with dementia and specifically offer new evidence of a strong association between the lipoprotein system and post-stroke dementia.
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PMID:Relation of apolipoprotein(a) size to alzheimer's disease and vascular dementia. 1521 Oct 75

The aim of the work was to recognize whether often observed high levels of apolipoprotein (a) [Lp(a)] in patients shortly after an ischemic stroke are a result of the acute phase reaction. In 13 patients Lp(a) was determined within the first 24 hours after the stroke onset, after the next 7 days and after three months i.e. when it could be considered that Lp(a) level was the same as before onset of the disease. In 17 patients only two determinations were performed. Another acute phase indicator: C-reactive protein (CRP), as well as serum lipids were also determined. CRP level was increased in the first determination and increased further after 7 days. After three months it returned to low values. High density lipoprotein (HDL) cholesterol which demonstrates a negative acute phase response changed in the opposite way. No similar fluctuations of Lp(a) level were observed. It can be concluded that during the investigated period Lp(a) had no properties of the acute phase reactant.
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PMID:[Changes in lipoprotein (a) [Lp(a)] level after an ischemic stroke]. 1535 32

LPA, the gene coding for apolipoprotein(a) [apo(a)], is the major determinant of lipoprotein(a) [Lp(a)] plasma levels, which are associated with risk for coronary heart disease (CHD) and stroke. It is not completely understood how variation in LPA relates to Lp(a) concentrations. One type of variation related to Lp(a) levels is the number of Kringle (K) IV-2 (g.61C>T; GenBank L14005.1) repeats in LPA, but sequence variation may also contribute. Human apo(a) contains from two to >40 nearly identical K IV-2 repeats of genomic size 5.5 kb, which makes it difficult to detect mutations. To elucidate the genetic variation of the apo(a) K IV-2 domain, we isolated a single "nonexpressing" apo(a) allele with 26 K IV-2 repeats, followed by PCR, cloning and sequencing of 96 clones, resulting in an average coverage of each K IV-2 repeat of approximately four-fold. The previously described K IV types 2A and 2B (K IV-2A and K IV-2B) were detected in 74% of the clones. In addition, a new type designated 2C (K IV-2C) was present. A nonsense mutation in the first exon of K IV-2 (g.61C>T) predicted to result in a truncated protein (p.R21X) was found in nine clones on a K IV-2A background. The presence of this mutation was confirmed by analysis of genomic DNA and was shown to represent the rare allele (frequency 0.02) of a SNP. Immunoblot analysis of apo(a) from plasma confirmed the presence of a truncated apo(a) isoform in the index individual and family members. Our data show that SNPs affecting Lp(a) plasma concentrations also exist in the apo(a) K IV-2 domain.
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PMID:A common nonsense mutation in the repetitive Kringle IV-2 domain of human apolipoprotein(a) results in a truncated protein and low plasma Lp(a). 1552 44

The purpose of this study was to test whether the insulin sensitivity, lipid metabolism and the susceptibility of the heart to ischemia/reperfusion injury are modulated by the chronic estrogen status. Rats were ovariectomized (OVX), not ovariectomized (sham) or ovariectomized and treated with subcutaneous 17 -estradiol (30 mug/kg/day, OVX+E2) (n=14-17 per group). Within 3 months after operation, body weight, the serum levels of estrogen, glucose, insulin, total cholesterol (T-chol), HDL-chol, LDL-cholesterol (LDL-chol), triglycerides (TG) and lipoprotein a (Lp(a)) were monitored. Three months after operation, hearts of partial rats (n=6-8 per group) were isolated and allowed an initial 20-min stabilization period, and then cardiac function was recorded and creatine kinase (CK) release in the coronary effluent was measured after 4 h of hypothermic ischemia in isolated rat hearts. The experimental results showed that from 2 weeks after ovariectomy to the end of the study, body weights of OVX were significantly higher compared with the other two groups (p<0.05). On weeks 5 and 9, insulin level of OVX was significantly higher than that of the other two groups (p<0.05), whereas it was not different among the three groups on weeks 12 and 13 (p>0.05). Blood glucose on week 13 was significantly higher in OVX (p<0.05). Consequently, Insulin Sensitivity Index (ISI) of OVX was lower than that of the other two groups on weeks 5 and 9 (p<0.05), but not on weeks 12 and 13. Serum values for T-chol, HDL-chol and LDL-chol were not significantly different among the three groups within the observing period. On week 13, TG level in ovariectomized group was significantly lower than in the sham- and E2-treated groups (p<0.05). Compared with sham, Lp(a) level was slight increased in OVX rats (p<0.05), while it was further increased in E2-treated rats (p<0.05). Cardiac function (left ventricular pressure (LVP) and +/-dp/dtmax) of hearts removed from OVX rats was depressed, and CK release was markedly increased (p<0.05). However, treatment with E2 significantly improved cardiac function, as shown by increasing left ventricular pressure,+dp/dtmax and -dp/dtmax, and decreased CK release. In conclusion, chronic E2 treatment has some beneficial effects on cardiovascular disease (CVD), which come from the results of improvement of insulin sensitivity and post-ischemia cardiac function. However, the mechanism did not include changes in lipids and lipoproteins. The change in Lp(a) level shows that estrogen does not confer cardiovascular protection and may increase the risk of stroke.
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PMID:Influence of ovariectomy and 17beta-estradiol treatment on insulin sensitivity, lipid metabolism and post-ischemic cardiac function. 1556 37

Carotid stenosis and atrial fibrillation are the strongest risk factors for ischemic stroke. Ongoing prevention efforts include the identification of novel factors that increase the risk for carotid atherosclerosis. The aim of this study was to determine the thrombophilic risk profile of patients with severe carotid stenosis by evaluating a number of genetic and metabolic risk factors [factor (F)II G20210A, factor V Leiden, MTHFR C677T polymorphisms, anticardiolipin antibodies (aCL), lipoprotein(a) (Lp(a)), and homocysteine (Hcy)]. The study population consisted of 615 patients [(410 M/205 F; median age 73 (26-94) years] with severe (> 70%) carotid stenosis, and 615 apparently healthy subjects [(410 M/205 F; age 73 (31-92) years]. On multivariate analysis, independent risk factors were elevated Hcy [odds ratio (OR) 7.6, 95% confidence interval (CI) 4.8, 11.8] and Lp(a) levels (OR 2.9, 95% CI 2.1, 3.9), the presence of aCL (OR 5.7, 95% CI 3.1, 10.4) and heterozygosity for FII G20210A polymorphism (OR 2.8, 95% CI 1.3, 5.9). In the subgroup of women, independent risk factors for severe carotid atherosclerosis were: high levels of Hcy and Lp(a) and the presence of aCL, whereas hyperhomocysteinemia, elevated Lp(a) levels, aCL, FII G20210A and MTHFR 677TT polymorphisms remained independent risk factors in the subgroup of men. The results of the present study demonstrate that the prevalence of the thrombophilic risk factors is increased in patients with severe carotid atherosclerosis.
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PMID:Thrombophilic risk factors in patients with severe carotid atherosclerosis. 1574 40

Lipoprotein(a) [Lp(a)] levels are increased in dialysis patients, suggesting that they may play a role in the elevated atherosclerotic cardiovascular disease (ASCVD) risk in this population. Few prospective studies of Lp(a) level, apolipoprotein(a) [apo(a)] size, and ASCVD have been performed in the dialysis population. An inception cohort of 833 incident dialysis patients were followed prospectively. Baseline Lp(a) was measured by apo(a) size-independent ELISA and apo(a) size by Western blot after SDS-agarose gel electrophoresis. A combined prospective nonfatal and fatal ASCVD end point included myocardial infarction, coronary revascularization, cerebrovascular accident, carotid endarterectomy, peripheral revascularization, gangrene, or limb amputation. Survival analyses were performed with adjustment for baseline demographics, comorbid conditions, ASCVD risk factors, albumin, lipids, and C-reactive protein. Median follow-up was 27.4 mo, with 297 ASCVD events, 130 non-ASCVD deaths, and seven losses to follow-up over 1649 person-years. In multivariate Cox regression models, both high Lp(a) concentration (>/=53 nmol/L) and low molecular weight (LMW) apo(a) isoforms (</=22 Kringle-IV repeats) predicted ASCVD events (relative hazard [RH] = 1.38, P = 0.02; RH = 1.58, P < 0.0005, respectively). In models that included both Lp(a) concentration and apo(a) size, only apo(a) size remained associated with ASCVD. Among those with both LMW apo(a) and Lp(a) level >123 nmol/L, the relative hazard (RH) of ASCVD was 1.73 (P < 0.0005), compared with high molecular weight apo(a) and Lp(a) level <123 nmol/L. No interactions by age, race, gender, diabetes, or ASCVD were present. Both LMW apo(a) size and high Lp(a) level predict ASCVD risk in dialysis patients, but the association of ASCVD with LMW isoforms is stronger than the association with high Lp(a) concentration.
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PMID:High lipoprotein(a) levels and small apolipoprotein(a) size prospectively predict cardiovascular events in dialysis patients. 1587 82

Using analyses of the large cohort (n=5732) from the prospective study of pravastatin in the elderly at risk (PROSPER), we tested the hypothesis that Lp(a) concentration is an independent predictor of major vascular events and cognitive impairment in the elderly. Baseline Lp(a) levels were measured on fresh samples from 5732 subjects aged 70-82, who were followed for 3.2 years on average. Lp(a) levels were not significantly different across the age range in PROSPER, but were significantly higher in women (geometric mean 14.8 versus 12.4 mg/dl, P<0.0001). Those with a history of vascular disease had significantly higher Lp(a) levels, which remained after adjustment (P<0.0001). There was no statistically significant association between baseline Lp(a) and the risk of the primary endpoint (CHD death, non-fatal MI and fatal or non-fatal stroke) (hazard ratio 1.05, 95% CI 1.00-1.11, P=0.077), but after adjustment for baseline risk factors this did achieve statistical significance (1.06, 1.005-1.12, P=0.032). Finally, there was no statistically or clinically significant association between any adjusted baseline or dynamic cognition variables and Lp(a), and nor was there any significant association between Lp(a) and indices of disability throughout the study. This is the first study of the association between Lp(a) and a range of cardiovascular endpoints including cognitive and disability indices in the elderly. The main finding is that Lp(a) level, while influenced by a number of baseline characteristics, is not a significant predictor of cognitive function or levels of disability, but is a predictor of combined cardiovascular events over an average 3.2 year follow-up.
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PMID:Plasma lipoprotein(a) [Lp(a)] concentrations and cardiovascular events in the elderly: evidence from the prospective study of pravastatin in the elderly at risk (PROSPER). 1591 Aug 66

In a population-based case-control study, we investigated the association of acute ischaemic stroke with lipoprotein(a) (Lp(a)) levels and apolipoprotein (Apo) (a) isoform size in subjects aged older than 70 years. A total of 163 patients with a first-ever-in-a-lifetime acute ischaemic/nonembolic stroke and 166 controls were included. Compared to controls, stroke patients exhibited higher Lp(a) concentrations (median value, 12.2 mg/dl versus 6.4 mg/dl, p < 0.001) and a higher frequency of small Apo(a) isoforms (44.2% versus 29.5%, p < 0.01). Multivariate logistic regression analysis showed a significant association of acute ischaemic stroke with Lp(a) levels [adjusted odds ratio (OR), 1.37, 95% CI (1.12-1.67); p = 0.002], and small Apo(a) isoform size [OR, 1.74 (1.10-3.03); p = 0.04]. Compared to subjects with Lp(a) levels in the lowest quintile, those within the highest quintile had a 3.2-times adjusted risk to suffer an acute ischaemic/nonembolic stroke (1.60-6.62, 95% CI; p < 0.001). Furthermore, analysis of interaction between lipid variables revealed that in the presence of elevated Lp(a) levels the inverse relationship between HDL-cholesterol levels and ischaemic stroke was negated [OR, 1.01 (1.00-1.03); p = 0.015]. Our study suggests that determination of Lp(a) levels and Apo(a) isoform size may be important in identifying elderly individuals at risk of ischaemic stroke independently of other risk factors and concurrent metabolic derangements.
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PMID:Serum lipoprotein(a) levels and apolipoprotein(a) isoform size and risk for first-ever acute ischaemic nonembolic stroke in elderly individuals. 1619 51

Stroke represents a major health burden in our country. Ischaemic stroke has got several risk factors associated with increased chance of atherosclerosis. A small hospital-based study was done to look into the risk factors associated with ischaemic stroke. Forty patients with CT-confirmed cerebral infarction were taken for the study and detailed history and clinical findings were obtained. Investigations like complete haemogram, fasting blood glucose, urea, creatinine, lipid profile, serum Lp(a), homocysteine, fibrinogen, ECG, chest x-ray, echocardiography, MRI/MRA where indicated, were done to identify the risk factors as well. Results indicated that hypertension was the most prevalent (87.5%) risk factor followed by ischaemic heart disease (35%) and diabetes. Dyslipidaemia was also found in a significant number of cases, mostly elevated LDL, low HDL and elevated Lp(a). Fibrinogen and homocysteine were of less significance.
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PMID:Risk factor analysis in ischaemic stroke: a hospital-based study. 1657 Jul 59

Dyslipidemia is a potent cardiovascular (CV) risk factor in the general population. Elevated low-density lipoprotein cholesterol (LDL-C) and/or low high-density lipoprotein (HDL-C) are well-established CV risk factors, but more precise determinants of risk include increased apoprotein B (ApoB), lipoprotein(a) [Lp(a)], intermediate and very low-density lipoprotein (IDL-C, VLDL-C; "remnant particles"), and small dense LDL particles. Lipoprotein metabolism is altered in association with declining glomerular filtration rate such that patients with non dialysis-dependent chronic kidney disease (CKD) have lower levels of HDL-C, higher triglyceride, ApoB, remnant IDL-C, remnant VLDL-C, and Lp(a), and a greater proportion of oxidized LDL-C. Similar abnormalities are prevalent in hemodialysis (HD) patients, who often manifest proatherogenic changes in LDL-C in the absence of increased levels. Patients treated with peritoneal dialysis (PD) have a similar but more severe dyslipidemia compared to HD patients due to stimulation of hepatic lipoprotein synthesis by glucose absorption from dialysate, increased insulin levels, and selective protein loss in the dialysate analogous to the nephrotic syndrome. In the dialysis-dependent CKD population, total cholesterol is directly associated with increased mortality after controlling for the presence of malnutrition-inflammation. Treatment with statins reduces CV mortality in the general population by approximately one third, irrespective of baseline LDL-C or prior CV events. Statins have similar, if not greater, efficacy in altering the lipid profile in patients with dialysis-dependent CKD (HD and PD) compared to those with normal renal function, and are well tolerated in CKD patients at moderate doses (<or=20 mg/day atorvastatin or simvastatin). Statins reduce C-reactive protein as well as lipid moieties such as ApoB, remnants IDL and VLDL-C, and oxidized and small dense LDL-C fraction. Large observational studies demonstrate that statin treatment is independently associated with a 30%-50% mortality reduction in patients with dialysis-dependent CKD (similar between HD- and PD-treated patients). One recent randomized controlled trial evaluated the ability of statin treatment to reduce mortality in type II diabetics treated with HD ("4D"); the primary end point of death from cardiac cause, myocardial infarction, and stroke was not significantly reduced. However, results of this trial may not apply to other end-stage renal disease populations. Two ongoing randomized controlled trials (SHARP and AURORA) are underway evaluating the effect of statins on CV events and death in patients with CKD (including patients treated with HD and PD). Recruitment to future trials should be given a high priority by nephrologists and, until more data are available, consideration should be given to following published guidelines for the treatment of dyslipidemia in CKD. Additional consideration could be given to treating all dialysis patients felt to be at risk of CV disease (irrespective of cholesterol level), given the safety and potential efficacy of statins. This is especially relevant in patients treated with PD, given their more atherogenic lipid profile and the lack of randomized controlled trials in this population.
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PMID:Statins for treatment of dyslipidemia in chronic kidney disease. 1729 64


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