Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma lipoprotein(a) (Lp(a)) concentrations are associated with an increased risk of coronary artery disease in adults with familial hypercholesterolemia (FH). We hypothesized that Lp(a) concentrations in children with FH were higher among those with myocardial ischemia on stress thallium scans and among those with a family history of premature coronary artery disease. Twenty-nine asymptomatic heterozygotes with FH (range 9 to 23 years) and 7 homozygotes (range 4 to 13 years) were evaluated with clinical assessment, lipoprotein measurement and stress thallium scans. Compared with subjects with normal stress thallium scans, mean Lp(a) was significantly higher in homozygotes with stress thallium abnormalities (79 +/- 18 vs 15 +/- 5.5 mg/dl, p = 0.03), and tended to be higher in heterozygotes with stress thallium abnormalities (39 +/- 12 vs 20 +/- 4.2 mg/dl, p = 0.10). Lp(a) tended to be higher in heterozygotes with a family history of premature coronary artery disease (30 +/- 6.4 vs 14 +/- 4.1 mg/dl, p = 0.12). It is concluded that Lp(a) is higher in hypercholesterolemic children who have abnormal stress thallium scans. Lp(a) may be useful in assessing coronary artery disease risk in children with FH.
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PMID:Elevated plasma lipoprotein(a) associated with abnormal stress thallium scans in children with familial hypercholesterolemia. 835 82

Hyperlipidemia is first detected by an increase in the plasma concentrations of cholesterol and/or triglycerides, and implies an abnormality of plasma lipoprotein metabolism. Disorders of lipoprotein metabolism are often classified specifically according to the lipoprotein affected. The WHO classification of lipoprotein phenotypes is a useful means of showing which lipoproteins are present in excess in individual hyperlipidemic patients. Hyperlipoproteinemia can be secondary to other well-known diseases that affect plasma lipoprotein metabolism, for example, diabetes mellitus, hypothyroidism or nephrotic syndrome. When such diseases are excluded, the hyperlipoproteinemia is defined as primary hyperlipoproteinemia. Many primary hyperlipoproteinemias have a genetic basis and the underlying molecular defect has been clarified in some genetic disorders. Hyperlipoproteinemia is considered to be one of the major risk factors for atherosclerosis and the development of atherosclerosis depends on the type of hyperlipoproteinemia. In this sense, familial hypercholesterolemia is a clinically important primary hyperlipoproteinemia because of its high risk of ischemic heart disease and its high prevalence in a normal population (1/500). It is necessary to make an exact diagnosis of specific genetic disorder, if possible, to provide prognostic and therapeutic information.
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PMID:[Primary hyperlipoproteinemia]. 841 90

We have determined the prevalence of familial hypercholesterolaemia (FH) in a rural Afrikaner community by means of direct DNA screening for three founder-related Afrikaner low density lipoprotein (LDL) receptor gene mutations. A random sample of 1612 persons, aged 15-64 years, was selected as a subsample of 4583 subjects from an Afrikaner community living in the south-western Cape, South Africa. Participants who had a total serum cholesterol (TC) in the high TC category as defined in the consensus recommendations by the Southern African Heart Foundation, were screened for three founder-related LDL receptor gene mutations, causing FH in 90% of Afrikaners. Of the subsample, 201 participants (12.5%) had TC levels above the 80th percentile. In this group the combined prevalence of the three common Afrikaner LDL receptor gene defects (D206E, FH Afrikaner-1; V408M, FH Afrikaner-2; D154N, FH Afrikaner-3) was calculated as 1: 83. When taking into account the reported background prevalence of other FH gene defects of 1:500 in this community, their overall prevalence of FH was estimated to be 1:72. The significant differences found between the FH patients and other high risk patients with raised cholesterol levels were higher TC and LDL cholesterol levels and lower high density lipoprotein cholesterol levels in FH patients. The treatment status of the molecularly identified FH patients and other hypercholesterolaemic persons suggests that this condition is inadequately diagnosed and poorly managed in this study population. An extrapolation to the entire South African population suggests that there are about 112000 FH patients in the country who are under-diagnosed as a group and therefore not receiving the care that would help to reduce the burden of FH-associated ischaemic heart disease in South Africa.
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PMID:Estimation of the prevalence of familial hypercholesterolaemia in a rural Afrikaner community by direct screening for three Afrikaner founder low density lipoprotein receptor gene mutations. 879 26

A plethora of different mutations in the gene for the low density receptor (LDLR) are responsible for the autosomal dominant inherited disorder familial hypercholesterolemia (FH). However, only a few splice site mutations have been identified in this gene. We here report a defect presumably affecting the splicing of precursor mRNA, resulting from a novel mutation, a G to A transition at the terminal nucleotide of intron 12, of the LDLR gene detected in three unrelated families with heterozygous FH. This mutation markedly reduced the steady-state transcript level of the mutant LDLR allele as compared to the corresponding normal LDLR allele in heterozygous FH patients as measured by a fluorescence based, allele-specific quantitation technique. In the FH families, the acceptor splice site mutation cosegregates with hypercholesterolemia, and it is associated with onset of ischemic heart disease in the fifth and sixth decade of life.
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PMID:A G-1-to-A acceptor splice site LDLR mutant allele leads to reduced relative transcript levels in patients with heterozygous familial hypercholesterolemia. 882 81

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are the drugs of choice in heterozygous familial hypercholesterolemia (FH), which has a high risk of ischemic heart disease. An open-label study was conducted to test the efficacy and safety of atorvastatin, a new synthetic HMG-CoA reductase inhibitor in proven FH. After a 4-week placebo phase, 22 subjects were randomized to either 80 mg atorvastatin at night (n = 11) or 40 mg twice a day for 6 weeks. The two dosage groups were well matched and had no difference in lipoprotein responses. After 6 weeks, the LDL cholesterol concentration was reduced by 57%, from 8.16 +/- 1.15 to 3.53 +/- 0.99 mmol/L (P < .001). The total cholesterol concentration decreased from 9.90 +/- 1.32 to 5.43 mmol/L (P < .001). HDL cholesterol concentration increased from 1.19 +/- 0.31 to 1.49 +/- 0.43 mmol/L (P < .001). Triglyceride concentrations decreased from 1.34 +/- 0.66 to 0.88 +/- 0.36 mmol/L (P < .01). Three subjects had single, transient increases of serum transaminase of up to twice the upper limit of normal. Apolipoprotein B concentration decreased significantly by 42%. Changes in apolipoproteins AI and (a) were not statistically significant. Nondenaturing gradient gel electrophoresis revealed increases in the size of smaller LDL particles in four subjects. Plasma fibrinogen concentration increased by 44%. The drug was well tolerated. One subject withdrew for personal reasons. Atorvastatin is a powerful and safe lipid-modifying agent for LDL cholesterol; it also modifies HDL cholesterol and triglyceride concentrations, and may suffice as a single agent for many subjects with heterozygous FH.
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PMID:Atorvastatin: an effective lipid-modifying agent in familial hypercholesterolemia. 930 31

The initial step in atherosclerosis is the rapid targeting of monocytes to the sites of inflammation and endothelial injury. Serum levels of intercellular adhesion molecule-1 were found to be increased in ischaemic heart disease patients and polymorphisms in the E-selectin gene were associated with accelerated atherosclerosis in young (age < 40 years) patients, further suggesting a role of inflammation in atherosclerosis. Cholesterol loading in macrophages was found to induce interleukin-8 expression, suggesting an association between foam cell formation and beta 2-integrin-dependent adhesion of leukocytes. Enhanced endothelium-platelet interaction induced by hypercholesterolaemia is mediated by von Willebrand factor, whereas platelet adhesion to subendothelial matrix is mediated by fibulin-fibrinogen complexes. Activated platelets mediate the homing of leukocytes by interaction with the subendothelial matrix under shear stresses that do not allow neutrophil adhesion. They may also contribute to the oxidative modification of LDL, provide a source of lipids for foam cell generation and contribute to smooth muscle cell proliferation. Oxidized LDL induces tissue factor in macrophages that also provide sites for fibrin polymerization and decreases the anticoagulant activity of endothelium by interfering with thrombomodulin expression and inactivating tissue factor pathway inhibitor. Intravascular fibrinolysis induced by tissue-type plasminogen activator or urokinase may contribute to the initiation of atherosclerosis by inducing P-selectin and platelet activating factor as well as to plaque rupture, either directly or indirectly, by activating metalloproteinases. Plasminogen activator inhibitor-1 inhibits smooth muscle cell migration and, in the presence of vitronectin, promotes the clearance of thrombin by LDL receptor-related protein at sites of endothelial injury.
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PMID:Thrombosis and atherosclerosis. 933 57

Acetylcholine (Ach)-induced vascular relaxation is mediated by nitric oxide released from the endothelium. Hence, impaired Ach-induced relaxation reflects endothelial dysfunction. The action of lipoprotein lipase on chylomicrons and very low density lipoproteins produces remnant lipoproteins (RLP) rich in triglycerides (TG), cholesterol (C) and apolipoprotein E (apo E). Apo E on RLP serves as a ligand for uptake of RLP by macrophages, endothelial cells and other cells expressing the LDL receptor or the remnant receptor; uptake of RLP by vascular wall cells can promote atherosclerosis. Serum C, TG, Lp(a), apo E, apo A-I, apo B, HDL-C and RLP-C were measured in 652 patients who underwent diagnostic coronary angiography. Of these, 48 (32 males and 16 females, age 59 +/- 10 years) were suspected of having ischaemic heart disease because they had chest pain, but without angiographic evidence of atherosclerotic coronary artery disease defined as a discrete stenosis or intimal irregularity, and without any other known underlying heart disease. These were selected for acetylcholine provocation test in the left coronary artery. Nineteen of 48 patients had high RLP-C ( > or = 5 mg/dl, mean 8.7 +/- 3.1 mg/dl), 29 had normal RLP-C ( < or = 5 mg/dl, mean 2.4 +/- 0.4 mg/dl, P < 0.0001). The percent change (-, constriction, or +, dilation) in coronary artery diameter after intracoronary injection of Ach was smaller in the high RLP-C group, compared with the normal RLP-C group thus, in the left anterior descending artery, -33 +/- 23 vs -8 +/- 25 in the proximal segment (P <0.01), -30 +/- 37 vs -3 +/- 29 in the mid segment (P < 0.01), -17 +/- 47 vs 16 +/- 43 in the distal segment (P < 0.001); in the left circumflex artery, -29 +/- 46 vs -9 +/- 28 in the proximal segment (P < 0.01), -29 +/- 43 vs -5 +/- 34 in the mid segment (P < 0.01), -26 +/- 43 vs 10 +/- 31 in the distal segment (P < 0.001). There were no significant differences in other lipid levels. These results suggest that there is an association between high serum RLP-C and coronary vascular endothelial cell dysfunction and that RLP-C may be taken as a marker of early stage coronary artery atherosclerosis not detectable by angiography.
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PMID:Impaired endothelium-dependent acetylcholine-induced coronary artery relaxation in patients with high serum remnant lipoprotein particles. 971 43

The review is devoted to hypercholesterolemia which is one of the leading risk factors for IHD. By its origin it can be primary and secondary. Three major mechanisms of primary hypercholesterolemia in humans are discussed. They are: low activity of LDL receptors, reduced affinity of LAL for receptors and overproduction of lipoproteins containing apo B. Depending on mechanism nonidentical molecular defects leading to cholesterol imbalance in cells or in circulating lipoproteins are occurred. The understanding of the nature and mechanisms of hypercholesterolemia development is of great clinical value, because having determined molecular defect and using drugs combinations the majority of patients are a success to have their lipids normal. Only in the case of homozygous familial hypercholesterolemia medicamentous treatment becomes secondary and the principal therapeutic methods are plasmapheresis or selective LDL apheresis. Gene therapy as a method of homozygous familial hypercholesterolemia correction is in forthcoming future.
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PMID:[Primary hypercholesterolemia: mechanisms of its development in man]. 984 97

Levels of plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) increase in patients with peripheral vascular or ischemic heart disease. These factors are related to the progression of atherosclerosis. Furthermore, these substances and thrombomodulin (TM) are indicators for assessing the degree of damage to the endothelium. To evaluate the effect of double filtration plasmapheresis (DFPP) on these molecules, the plasma levels of vWF, sICAM-1, sVCAM-1, and TM were measured in 4 familial hypercholesterolemia (FH) patients who underwent treatment with DFPP at 2 week intervals for more than 3 years. The levels of sVCAM-1 and sICAM-1 in hypercholesterolemia patients with ischemic heart disease as a control was 773 +/- 109 and 334 +/- 82 ng/ml. These values were higher than the normal value. In the FH patients who underwent DFPP treatment, the average sICAM-1 levels were 221 +/- 47 and 197 +/- 36 ng/ml before and after, respectively. The average sVCAM-1 levels were 601 +/- 87 and 486 +/- 60 ng/ml. There were no significant differences between the pre- and post-DFPP values. The activities of plasma vWF before and after DFPP treatment were 158 +/- 23 and 45 +/- 9%. The levels of plasma TM before and after treatment were 3.0 +/- 0.3 and 3.4 +/- 0.5 FU/ml. From these results, it is suggested that DFPP treatment does not damage the endothelium and may prevent the progression of atherosclerosis by removing the substances that induce the production of sICAM-1 and sVCAM-1 due to long-term treatment.
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PMID:Double filtration plasmapheresis maintains normal adhesion molecule levels. 1022 74

Obstructive atherosclerotic coronary artery disease is uncommon in women during childbearing age, and the occurrence of myocardial ischemia during pregnancy has therefore been anecdotal. Two young patients with premature coronary artery disease in association with familial hypercholestrolemia had unstable angina in the second trimester of pregnancy. Workup revealed coronary artery disease and aortic stenosis. One patient opted for abortion at the twentieth week of gestation, and the other decided to continue pregnancy and was delivered by cesarean at 28 weeks' gestation. Coronary artery bypass grafting was performed after pregnancy in both patients. In addition, one of the patients underwent aortic valve replacement, and other had replacement of the narrowed ascending aorta with uneventful recovery. Our report describes an uncommon presentation of unstable angina during pregnancy in 2 young women with premature coronary artery disease and aortic valvular and supravalvular stenosis as a result of familial hypercholesterolemia. The management of these conditions during pregnancy is influenced by the effects of available therapeutic modalities on both maternal and fetal outcome.
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PMID:Unstable angina during pregnancy in two patients with premature coronary atherosclerosis and aortic stenosis in association with familial hypercholesterolemia. 1081 51


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