Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Decisions to resect small aortic aneurysms or employ non-operative treatment for aorto-iliac occlusive disease must depend on current rather than historical surgical results. To assess current morbidity and mortality, we reviewed 200 consecutive aortic resections in two groups of patients treated from 1981 to 1989: those undergoing elective aortofemoral bypass for occlusive disease (AFB, no. 100) or resection of infrarenal abdominal aortic aneurysms (AAA, no. 100). Indications for AFB included claudication (54%), rest pain (32%), and gangrene (13%). AAA size ranged from 3 to 14 cm (mean 6.5 +/- 2.4 cm); 45% presented with abdominal or back pain. Patients undergoing AFB were younger (AFB 61.5 +/- 10 years vs AAA 68.7 +/- 8.9 years) with a higher incidence of some atherosclerotic risk factors, diabetes mellitus 30% vs 10%, tobacco use 77% vs 49%, hyperlipidemia 21% vs 7%; p less than 0.001). Coronary artery disease (CAD) was more prevalent in AAA patients (49% vs 34%; p less than 0.001). Postoperative mortality was not different in occlusive or aneurysmal disease (3% AFB vs 2% AAA), nor was the occurrence of serious complications such as myocardial infarction (2% vs 1%) or pulmonary embolism (2% vs 3%). Improvements in patient selection, perioperative care and surgical technique have lowered the mortality of elective aortic surgery. Given the current standard of care, an aggressive approach to AAA even in high risk patients is appropriate. The low morbidity of AFB for occlusive disease mandates a critical appraisal of less effective nonoperative therapies.
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PMID:Current results of elective aortic reconstruction for aneurysmal and occlusive disease. 221 95

To determine the prevalence, time course and factors responsible for hyperlipidemia after heart transplantation, 83 consecutive 1-year survivors were studied. By 1 year, 83% of patients had serum total cholesterol levels greater than 5.2 mmol/liter (200 mg/dl) and 28% of the patients had serum total cholesterol higher than the age- and sex-matched ninety-fifth percentile. At the end of 1-year follow-up, serum total cholesterol correlated with the recipient age (p less than 0.0001), the preoperative cholesterol level (p less than 0.001), the actual dose of maintenance prednisone at 1 year (p less than 0.02) and the cumulative 1-year steroid dose (p less than 0.03). Similarly, the serum triglyceride level at 1 year correlated with the pretransplant level of serum triglycerides (p less than 0.0001), recipient age (p less than 0.03) and cumulative 1-year steroid dose (p less than 0.03). Patients with a pretransplant diagnosis of coronary artery disease had a significantly higher level of serum total cholesterol and triglyceride levels at 1 year (p less than 0.02 and p less than 0.03, respectively). Heart transplant recipients with body mass index greater than or equal to 25 kg/m2 also presented with significantly elevated serum total cholesterol and triglyceride levels at 1 year compared with nonobese patients (p less than 0.01 and p less than 0.002, respectively). Hyperlipidemia occurs frequently and is detected within the first month after heart transplantation. Optimal management of this problem requires further study.
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PMID:Serial evaluation of lipid profiles and risk factors for development of hyperlipidemia after cardiac transplantation. 187 95

Familial hypercholesterolemia is an inherited disease in humans that is associated with coronary artery disease and is caused by a deficiency of the receptor that mediates the internalization of low density lipoprotein (LDL). We have used an animal model for familial hypercholesterolemia, the Watanabe heritable hyperlipidemic (WHHL) rabbit, to design a therapeutic approach for this disease, which attempts to correct the hepatic defect in LDL receptor expression. Hepatocytes were harvested from WHHL rabbits, plated in primary cultures, and exposed to recombinant retroviruses capable of efficiently transferring a functional human LDL receptor gene. Genetically modified cells were harvested and infused into the portal vein of WHHL recipients, who were analyzed for metabolic consequences of human LDL receptor expression. Each animal exhibited a statistically significant decrease in total serum cholesterol 2-6 days after transplantation, with an eventual return to pretreatment levels. Proviral DNA sequences and virus-directed transcripts were detected in liver tissue 24 hr after transplantation. In situ hybridization demonstrated provirus expression in a small population of hepatocytes distributed in periportal sections of the liver. This study illustrates the potential of somatic gene therapy in ameliorating hyperlipidemia associated with familial hypercholesterolemia.
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PMID:Temporary amelioration of hyperlipidemia in low density lipoprotein receptor-deficient rabbits transplanted with genetically modified hepatocytes. 223 51

The relationship among postmenopausal estrogen use, coronary stenosis, and survival was examined retrospectively in 2268 women undergoing coronary angiography. The patients were selected for study if their age was 55 years or older at the time of angiography or if they had previously undergone bilateral oophorectomy. Postmenopausal estrogen use in 1178 patients with coronary artery disease (greater than 70% stenosis) and 644 patients with mild to moderate coronary artery disease (5% to 69% stenosis) was compared with 446 control subjects (0% stenosis) using life-table analysis. Over 10 years of follow-up, there was no significant difference in survival among patients initially free of coronary lesions on arteriography who had either never used (377) or ever used (69) estrogens. Among patients with mild to moderate coronary stenosis, 10-year survival of those who had never used estrogens was 85.0% and it was 95.6% among 99 "ever users." Survival was 60.0% among those with more than 70% coronary stenosis who had never used estrogen and it was 97.0% among 70 ever users. The "never users" group were older (65 vs 59 years), had a lower proportion of cigarette smokers (40% vs 57.1%), a higher proportion of subjects with diabetes (21.7% vs 12.9%) and hyperlipidemia (58% vs 44%), and approximately equal numbers of hypertensives (56.0% vs 54.3%). Cox's proportional hazards model was used to estimate survival as a function of multiple covariables. Estrogen use was found to have a significant, independent effect on survival in women. We conclude that estrogen replacement after menopause prolongs survival when coronary artery disease is present, but it has less effect in the absence of coronary artery disease.
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PMID:Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women. 224 72

CAD results from atherosclerosis, a chronic disease process that has its origin in childhood. Children and adolescents can be at higher risk for CAD by virtue of being from families with premature CAD or familial dyslipoproteinemias. The plasma lipid and lipoprotein levels result from a number of complex metabolic processes that are under the control of genetic and environmental (e.g., diet) influences. The normal ranges of plasma lipids and lipoproteins in children are known, and children and adolescents with dyslipoproteinemia are ordinarily defined as those having levels of plasma total, LDL, or triglyceride above the 95th percentile or with a low HDL cholesterol below the 5th percentile. Children of a parent with documented dyslipoproteinemia or with family history of premature CAD may be screened in the fasting state any time after 2 years of age. Following the exclusion of secondary causes of dyslipoproteinemia, the diagnosis of primary dyslipoproteinemia can be made. Lipoprotein patterns are not diagnostic for a given genotype. Efforts to determine further the biochemical defects responsible for a given phenotype have led to the investigation of gene coding for the apolipoproteins, the key enzymes in the lipoproteins pathways (LPL, HDL, and LCAT) and the receptors that process lipoproteins, such as the LDL receptor and the chylomicron remnant receptor. From a practical standpoint, the diagnosis of the kind of dyslipoproteinemia in a child will depend upon the nature and severity of the dyslipoproteinemia, both in the child (or adolescent) and in parents and siblings. Marked increases in plasma total and LDL cholesterol in the child and in at least one of the parents often reflect the presence of familial hypercholesterolemia, an inherited dominant condition due to a defect in the LDL receptor gene. The triglyceride levels are often normal. If the child has a different dyslipoproteinemia pattern from siblings and parents, then the diagnosis of familial combined hyperlipidemia or hyperapobetalipoproteinemia should be considered. Most children with mild or borderline elevations in total and LDL cholesterol will have polygenic hypercholesterolemia. Triglyceride problems in children and adolescents are relatively uncommon, particularly the more severe hypertriglyceridemia such as that found in lipoprotein lipase and apoC-II deficiency, dysbetalipoproteinemia, and type V hyperlipoproteinemia. High levels of Lp(a) lipoprotein, in isolation or in combination with other dyslipoproteinemia, accelerate risk for CAD. Low levels of HDL cholesterol in the absence of other abnormalities suggest the diagnosis of hypoalphalipoproteinemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis and management of familial dyslipoproteinemia in children and adolescents. 225 50

The overall risk of oral contraceptive (OC) use is minimal when women over 35 years of age, smokers, and those with multiple risk factors (thromboembolic disorders, cerebrovascular or coronary artery disease, liver tumors, breast cancer, estrogen-dependent neoplasms, undiagnosed abnormal genital bleeding, and congenital hyperlipidemia) are excluded. OC use increases the risk of hypertension by 1-5%, depending on age, parity, and duration of use, but even this small risk is decreased when multiphasic OCs are prescribed. Deep venous thrombosis in the leg is 4 times more prevalent in OC users than nonusers and the risk of superficial thrombosis is doubled. Again, fewer thromboembolic complications occur when the estrogen dosage is low. The risk of myocardial infarction is not believed to increase with OC use as long as other risk factors--smoking, obesity, hypertension, age over 35 years, hypercholesterolemia--are not present. Studies involving the original high-dose OCs revealed a 3-fold increase in the risk of thrombotic stroke and a 2-fold increase in the risk of hemorrhagic stroke, but low-dose OCs appear to have no effect on the potential for stroke. The impact of OC use on breast cancer cannot yet be determined given the very long latency period of this cancer. In terms of benign breast disease, OC users have been shown to be at substantially reduced risk of lesions, fibroadenomas, and fibrocystic changes. OCs also protect women from endometrial and ovarian cancer, although the pill seems to accelerate the progression of cervical dysplasia. Other beneficial effects of OC use include reductions in the incidence of pelvic inflammatory disease, endometriosis, ectopic pregnancy, and ovarian cysts.
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PMID:Oral contraceptive pills. Part II: Potential complications and health benefits. 228 19

Because coronary atherosclerosis after heart transplantation has been a limiting problem in long-term survival of adults, we reviewed the coronary angiograms, and autopsy data when available, from 21 of 30 children who underwent orthotopic heart transplantation and survived the perioperative period. Six patients had coronary atherosclerosis, and five of these patients died 6 months to 3 years after heart transplantation. The late deaths were sudden and unexpected. Coronary angiography demonstrated several types of lesions, including concentric narrowing, tubular segmental lesions, and abrupt obliteration of major coronary vessels. Risk factors assessed included hypertension, hyperlipidemia, cytomegalovirus infection, type of immunosuppressive regimen, number of rejection episodes, and major histocompatibility antigen mismatches. Only the frequency and duration of rejection episodes seemed to be more prevalent in the patients in whom coronary atherosclerosis developed. Despite the benefits of heart transplantation in treating children with end-stage heart disease, coronary atherosclerosis may limit long-term survival. We suggest that these children should undergo serial coronary angiography to identify those at risk for subsequent events related to coronary artery disease.
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PMID:Coronary arteriosclerosis in pediatric heart transplant survivors: limitation of long-term survival. 229 87

Elevated blood cholesterol levels, a major risk for coronary artery disease in adults, has been associated with atherosclerotic disease in children. More than 10% of North American children have blood cholesterol levels higher than the desirable levels for adults. Current guidelines recommend screening only in children who have a family history of hyperlipidemia or myocardial infarction at an early age; however, this method fails to identify most children with hypercholesterolemia. Office-based cholesterol screening is an effective means to identify children and family members for dietary assessment and counseling. Should these measures be insufficient to lower the child's cholesterol level, referral for pharmacologic treatment is indicated.
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PMID:Cholesterol screening in children during office visits. 229 54

The objectives of this study were (1) to determine the incidence of dominantly inherited hyperlipoproteinemia in children referred to our medical center because of hyperlipidemia associated with a family history of premature coronary artery disease and (2) to assess the degree of expression in childhood of the most common inherited hyperlipoproteinemia, familial combined hyperlipidemia. Among 129 families referred to us by area pediatricians, we identified a dominantly inherited hyperlipoproteinemia in 97 of them. Twenty had familial hypercholesterolemia, 65 familial combined hyperlipidemia, 11 hyperapobetalipoproteinemia, and one familial hypertriglyceridemia. As expected, almost half (9/20) of the siblings of probands with familial hypercholesterolemia were affected. Although we expected incomplete gene penetrance in the siblings of the probands with familial combined hyperlipidemia, we found 43 affected and 40 unaffected among the 83 siblings of the 65 probands. Our findings suggest that hyperlipidemia in children, caused by familial combined hyperlipidemia, occurs more than three times as frequently as familial hypercholesterolemia and that in families identified by a child proband, the penetrance is complete. Pediatricians should identify this primary hyperlipidemia in childhood and attempt to prevent the associated risk of premature coronary artery disease by prescribing appropriate diet and life-style modifications.
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PMID:Prevalence and expression of familial combined hyperlipidemia in childhood. 231 96

The relationship between apolipoprotein E (Apo E) phenotypes and progression of coronary atherosclerosis was investigated in 125 patients with coronary artery disease (CAD) proven angiographically (101 males, 24 females). To elucidate the pure effect of Apo E phenotypes on lipoproteins and coronary atherosclerosis, patients with familial hypercholesterolemia were excluded from the subjects. As a control group, 129 normal healthy volunteers (84 males, 45 females) were studied. In the CAD group, VLDL and LDL levels increased and HDL level decreased regardless of Apo E phenotypes in both sexes. The incidence of E4 was higher and that of E2 was slightly lower in the CAD group than in the control group. Two patients with E5/3 who had high LDL-cholesterol levels were found in the male CAD group. LDL-cholesterol level in E3/2 was lower than in E4/3 and E3/3 in the male CAD group. VLDL-cholesterol/triglyceride and VLDL cholesterol/phospholipid ratios in E3/2 were significantly higher than in E4/3 and E3/3 in the male CAD group, but the difference was not so marked as found in typical type III hyperlipidemia. When the male patients with effort angina were examined, coronary score (index of the severity of CAD) was the lowest in E3/2. In addition, the mean age at the onset of CAD was significantly higher in E3/2 than in E4/3. In conclusion, E2 acts protectively against coronary atherosclerosis, while E4 promotes it through the modulation of LDL-cholesterol level.
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PMID:Apolipoprotein E phenotypes in patients with coronary artery disease. 235 52


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