Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Partial ileal bypass (PIB) surgery is a method in the treatment of heterozygous familial hypercholesterolemia (FH). Since the first report in 1964 about 150 cases of FH who underwent the surgical procedure have been described. This number is very low when compared to other types of cholesterol-lowering treatment. On average, PIB decreases the level of plasma total cholesterol by 35% in FH patients, and the surgical procedure can be considered the most effective, single cholesterol-lowering method. PIB-induced reduction of plasma cholesterol is permanent. Further decrease of plasma cholesterol may be obtained in combination with an inhibitor of cholesterol biosynthesis. PIB specifically lowers plasma LDL cholesterol; the concentration of HDL cholesterol is not systematically influenced. The mechanism underlying the hypocholesterolemic action of PIB is discussed. Until now there is no evidence that PIB reduces atherosclerotic coronary death in FH patients. After PIB more patients experience improvement of angina pectoris rather than deterioration (15 versus 2 out of 41), but the number of patients is too small to allow solid conclusions. In 50% of FH patients PIB may cause regression of xanthomata. Out of 209 hyperlipidemic patients described, 14 patients had postoperative complications, which caused death in 3 patients. Diarrhea is the most common side-effect of PIB; out of 99 operated patients serious diarrhea troubled 38 patients, whereas 40 patients had minor complaints during the first year postoperatively. Diarrhea may persist as long as 10 years after PIB. There is no evidence that PIB enhances gallstone formation and severely impairs liver function, but PIB may increase the incidence of renal stones. It is suggested that PIB can be considered in the treatment of FH. However, in each individual case the disadvantages and possible advantages should be carefully weighed out, and this consideration should form the basis to decide whether or not surgery is indicated.
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PMID:Partial ileal bypass surgery in the treatment of heterozygous familial hypercholesterolemia: a review. 351 66

Patients with homozygous familial hypercholesterolemia (FH), reveal a marked heterogeneity in plasma cholesterol levels, response to diet as well as drug treatment, and clinical course. Low-density lipoprotein (LDL) receptor activities were assessed by the rate of 14C-oleate cholesteryl ester biosynthesis in fibroblasts from 13 FH homozygotes in tissue culture. The receptor activity of the individual patients was highly correlated with initial pretreatment plasma cholesterol and LDL cholesterol levels (P less than .001, r = -0.89). In addition, the LDL receptor activity was positively correlated with the age of onset of angina based on the Cox model (P less than .035, likelihood ratio = 6.71). An association was also noted between LDL receptor activity and cholesterol reduction with drugs. These data provide direct evidence for the correlation between the heterogeneity of the LDL receptor and the expression of the clinical manifestations of homozygous FH. The determination of pretreatment plasma cholesterol level and LDL receptor activity in patients with homozygous FH provide useful parameters on which to base predictions of the clinical progression of cardiovascular disease. These parameters may also influence the selection of a program for diet and drug therapy. Patients with markedly elevated plasma cholesterol levels and very low LDL receptor activity should be considered to be candidates for multiple drug therapy, and portacaval shunt, and/or periodic plasma exchanges.
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PMID:The association of LDL receptor activity, LDL cholesterol level, and clinical course in homozygous familial hypercholesterolemia. 385 94

Partial ileal bypass is effective in reducing circulating cholesterol levels. In our study the 10 year effects of the procedure on serum lipids and lipoproteins were studied in 27 patients with heterozygous familial hypercholesterolemia. The ileal bypass patients were compared with conservatively treated case controls matched for age, sex, serum cholesterol level, relative body weight, blood pressure, and smoking habits and also for the existence of diabetes and coronary heart disease. Serum triglycerides were initially slightly higher in the patients undergoing ileal bypass. During the 10 year follow-up eight surgically treated and seven control patients suffered fatal or nonfatal myocardial infarctions. Of these all but one male subject who underwent surgery had had manifest coronary heart disease at entry. Male sex, smoking, triglyceride levels, and angina were significant predictors of new coronary events. The fall in serum cholesterol in patients who underwent ileal bypass and had fatal myocardial infarctions was smaller than in the corresponding subjects without events. The serum lipid levels of the survivors at the end of the 10 year follow-up showed that ileal bypass, as compared with the conservative treatment, had led to a larger decrease in total serum cholesterol (-33% vs -11% in the control patients; p less than .001); lower total serum cholesterol (360 vs 468 mg/dl; p less than .001), low-density lipoprotein (LDL) cholesterol (236 vs 324 mg/dl, p less than .001), and LDL apoprotein B levels (186 vs 231 mg/dl; p less than .001); and higher serum high-density lipoprotein (HDL) (46 vs 38 mg/dl; p less than .05) and HDL2 cholesterol levels (25 vs 16 mg/dl; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of ileal bypass on lipoproteins in patients with familial hypercholesterolemia. 673 83

Familial hypercholesterolemia (FH) is a disorder of LDL receptor abnormalities, and the resultant high-LDL-cholesterolemia produces atherosclerosis. More than 150 different mutations in the LDL receptor gene have been reported in the world. Seven variants of the LDL receptor gene have been identified in our laboratory. These seven mutants in 85 patients from 31 families accounted for only 15.5% of the FH cases. LDL receptor gene abnormalities are highly heterogenous in Japan, and the variation of the LDL receptor mutant may determine the severity of hypercholesterolemia and coronary heart disease in FH. A serum HDL above 60 mg/dl is a negative risk factor for coronary atherosclerosis. We found that familial hyperalphalipoproteinemia can be produced by CETP deficiency due to a CETP gene. Two common mutants of the CETP gene produce a CETP deficiency and resultant antiatherogenic lipoprotein pattern (i.e. hyper-HDL-cholesterolemia and hypo-LDL-cholesterolemia), and the frequency of the mutant allele is more than 1 in 10 subjects in Japan. Finally, we found unique patients with double heterozygotes of FH and CETP deficiency. We found 16 double heterozygotes of the LDL receptor gene and CETP gene. Four of the 16 patients showed myocardial infarction and 4 showed angina pectoris. These findings suggest that the atherogenicity of hyper-LDL-cholesterolemia in FH is more powerful than antiatherogenicity of hyper-HDL-cholesterolemia in CETP deficiency.
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PMID:[Molecular genetics of cholesterol transport and cholesterol reverse transport disorders (familial hypercholesterolemia and CETP deficiency), and coronary heart disease]. 773 14

Familial hypercholesterolemia is an autosomal dominant disorder caused by a mutation of the gene for the low-density lipoprotein receptor and is characterized by rapidly progressing coronary atherosclerosis. We assessed the long-term results of coronary artery bypass grafting performed during the past 13 years in 62 patients with heterozygous familial hypercholesterolemia, whose mean plasma total and low-density lipoprotein cholesterol level was 327 mg/dl, respectively. The patients had severe coronary atherosclerosis, with coronary stenosis index of 19.7, and the prevalence of extracoronary atherosclerotic lesions was 27%. Sixty-one patients underwent successful coronary artery bypass operation, with an average of 2.5 grafts, and the coronary stenosis index decreased to 7.1. After operation, all patients consumed a cholesterol-lowering diet and received drug therapy with pravastatin, probucol, or cholestyramine. Seven patients who were resistant to drug therapy were treated with plasma low-density lipoprotein apheresis. The cholesterol-lowering therapy reduced plasma total cholesterol level by 37%, low-density lipoprotein cholesterol level by 42%, and low-density lipoprotein/high-density lipoprotein cholesterol ratio by 37% (p < 0.001). During the follow-up period (mean, 52 months; range, 10 to 157 months), there was no cardiac death, but three patients died of malignant disease. The actuarial survival rate was 95% at 5 years and 89% at 12 years after operation. The actuarial freedom from recurrent angina was 90% at 5 years and 53% at 11 years after operation. Four patients underwent reoperation, an average of 8 years postoperatively, because of vein graft atherosclerosis. In spite of severe coronary atherosclerosis, these patients with familial hypercholesterolemia showed good long-term outcome after coronary artery bypass operation. The present findings suggest that aggressive use of arterial grafts, intensive cholesterol-lowering drug therapy, and low-density lipoprotein apheresis may be useful in patients with familial hypercholesterolemia.
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PMID:Coronary artery bypass grafting in familial hypercholesterolemia. 785 88

Long-term results of coronary artery bypass grafting (CABG) in consecutive 32 patients with familial hypercholesterolemia, 6 homozygotes and 26 heterozygotes between 1976 and 1990, were analyzed. Seventeen patients in the early series underwent CABG with vein grafts alone. Subsequently, 15 patients underwent CABG with internal mammary artery grafting to the left anterior descending artery and received intensive lipid-lowering treatments early after CABG. All homozygotes and 1 heterozygote received intermittent low-density lipoprotein apheresis after CABG. There was only one late noncardiac death (3%), and the actuarial rates of freedom from cardiac events (myocardial infarction, cardiac death, and angina pectoris) were 60% at 5 and 10 years for homozygotes, and 87% and 73% for heterozygotes. The cardiac event-free curve for the heterozygous familial hypercholesterolemia group was comparable with that for the random age-matched subset of patients without familial hypercholesterolemia who underwent CABG during the same period. Two of 3 homozygotes and 4 of 14 heterozygotes in the early series had one or more cardiac events, whereas no patients in the late period had cardiac events. The patency rate of internal mammary artery grafts to the left anterior descending artery from 1 to 3 years after CABG was significantly higher than that of vein grafts to the left anterior descending artery (92 versus 45%; p < 0.05). Abdominal aortic aneurysm developed postoperatively in 2 homozygotes and 2 heterozygotes without sufficient cholesterol reduction. In conclusion, internal mammary artery grafting in combination with postoperative intensive lipid-lowering treatments, including low-density lipoprotein apheresis, may provide acceptably good long-term results of coronary revascularization in patients with FH.
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PMID:Long-term appraisal of coronary bypass operations in familial hypercholesterolemia. 837 22

Two deletions of the low density lipoprotein (LDL) receptor gene account for about 90% of the mutations that cause familial hypercholesterolemia (FH) in eastern Finland. The FH-Helsinki mutation deletes exons 16, 17 and a portion of exon 18, while the FH-North Karelia allele is characterized by a deletion of seven nucleotides from exon 6 of the LDL receptor gene. We developed a DNA assay based on the use of polymerase chain reaction (PCR) which simultaneously detects both of these mutations. We have screened 90 young (< 45 years) eastern Finns with symptomatic coronary heart disease (CHD) for the presence of these FH genes. One or the other of the mutations was present in 4 out of 55 survivors of acute myocardial infarction (AMI) and 4 out of 35 patients with angina pectoris (AP), but in none of 50 healthy controls of similar age. These data show a relatively high prevalence of confirmed FH in young CHD patients (AMI and MI combined: 8/90, or 9%), and also demonstrate the feasibility of PCR techniques in diagnosis of FH among populations with enrichment of specific types of LDL receptor gene mutations.
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PMID:Prevalence of familial hypercholesterolemia among young north Karelian patients with coronary heart disease: a study based on diagnosis by polymerase chain reaction. 842 61

Hyperlipoproteinemia is frequently observed in patients after renal transplantation and contributes to cardiovascular morbidity and mortality. In addition, it was recently shown that hypercholesterolemia accelerates the progression of renal disease. In a renal transplant recipient (RTR) with severe coronary heart disease, familial hypercholesterolemia and decreased renal function, immunospecific LDL-apheresis was instituted since dietary restrictions failed to sufficiently improve hyperlipoproteinemia and medication had to be avoided due to drug interactions. Over a period of 36 months 145 LDL-apheresis treatments were performed at weekly intervals. The desorption of 5600 ml plasma volume allowed a mean reduction of total cholesterol by 56.6% (from 256 mg/dl to 110 mg/dl), of LDL-cholesterol by 63.0% (from 163 mg/dl to 58 mg/dl), of Lp(a) by 68.3% (from 34 mg/dl to 11 mg/dl) and of triglycerides by 49.6% (from 332 mg/dl to 163 mg/dl). Although temporarily decreasing during each apheresis session by 9.0%, HDL-cholesterol values increased during the first 9 months of treatment and remained within the normal range (> 45 mg/dl) thereafter. Cyclosporine A blood trough values were decreased by 32% during LDL-apheresis. Symptoms of angina pectoris rapidly improved and disappeared after 8 months of apheresis treatment. Initial coronary angiography exhibited serious three-vessel-disease, without the possibility of bypass grafting. Coronary angiography repeated after two years of therapy showed a regression of the disease. Serum creatinine levels declined during treatment (from 2.7 mg/dl to 1.8 mg/dl) and proteinuria did not increase further. This is the first report to show that long-term LDL-immunoadsorption is a safe and highly effective treatment of severe hyperlipidemia and coronary heart disease in a RTR, resulting in regression of vascular pathology. Moreover, amelioration of hyperlipidemia may have improved transplant function. Multicenter studies are necessary to confirm our results.
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PMID:Regression of coronary atherosclerosis and amelioration of renal function during LDL-immunoadsorption therapy in a renal transplant recipient. 878 84

Calcium antagonists are well accepted in the prevention of ischaemia in patients with chronic stable angina, unstable angina, variant angina, and silent ischaemia, and in the treatment of hypertension. Although all of these compounds increase myocardial oxygen supply by reducing coronary tone and decrease myocardial oxygen demand by reducing systolic pressure and myocardial contractility, the magnitude of these effects may differ from one agent to another. Some calcium antagonists, such as verapamil and diltiazem, reduce heart rate and attenuate heart rate increases in response to stress, while in contrast, dihydropyridine calcium antagonists such as nifedipine may cause reflex increases in heart rate. These differences may be of importance in light of epidemiologic evidence that lower heart rates are associated with a reduced long-term risk of cardiovascular mortality, and experimental data showing that a lower heart rate may protect against the development of atherosclerosis. Calcium antagonists also inhibit platelet aggregation and thrombus formation which may contribute to their anti-ischaemic effects. Clinical trial data suggest that calcium antagonists may stay the progression of atherosclerosis. Mechanisms underlying an anti-atherosclerotic effect may include attenuation of endothelial dysfunction, prevention of LDL, peroxidation, stimulation of LDL receptor activity, inhibition of superoxide radical generation, and inhibition of vascular smooth muscle cell growth. Heart-rate-controlling calcium antagonists, such as verapamil and diltiazem, may reduce reinfarction rates following acute myocardial infarction and thus may have a role in post-infarction patients who do not show evidence of heart failure. Their use in heart failure patients receiving an angiotension-converting enzyme inhibitor (ACE-I) is under investigation in several large trials. Because calcium antagonists have a mechanism of action different from ACE-I, the pairing of a heart-rate-controlling calcium antagonist with an ACE-I might be expected to offer additive cardioprotective and vascular protective effects.
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PMID:The role of calcium antagonists in ischaemic heart disease. 884 1

Fifty-seven patients with familial hypercholesterolemia (FH) with mean age of 48 years (range 30 to 69), participated in a follow-up examination 5.5 years after the completion of a 1-year trial with lovastatin, cholestyramine, probucol, or omega-3 fatty acids. The goals were to record quality of life, compliance to treatment, adverse effects, and clinical outcome. The quality of life was similar to that in a Norwegian reference population. The factors causing most distress to patients were keeping a diet low in saturated fats, taking medication, and fear of death. The medication was mostly prescribed in maximum dosages. At follow-up, the reduction in total cholesterol was 36% (p < 0.05), low-density lipoprotein (LDL) cholesterol 38% (p < 0.05), triglycerides 20% (p < 0.05) compared with being on diet therapy only. High-density lipoprotein (HDL) cholesterol increased 8% (p < 0.05). Intake of saturated and monounsaturated fat increased 1.5% and 1.7% (p < 0.05), respectively; polyunsaturated fat was unchanged. Three patients experienced myocardial infarction, of whom 2 died and 1 developed angina pectoris. Before the start of lovastatin treatment, 27 coronary events occurred per 1,000 patient-years in this group compared with 12 events per 1,000 patient-years thereafter. Of 28 patients reporting adverse events, 4 discontinued lovastatin and 3 discontinued cholestyramine. Several practical and psychological difficulties were associated with FH. Long-term intensive lipid-lowering therapy was possible in FH outpatients without loss of effect and with good compliance to therapy. Intensive therapy, today is, however, not sufficient for many FH patients to reach a therapeutic goal of LDL cholesterol < 4.0 mmol/L. More potent lipid-lowering agents are needed.
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PMID:Results of intensive long-term treatment of familial hypercholesterolemia. 897 Apr 8


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