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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been demonstrated that high cholesterol levels are correlated with development of atherosclerosis, while high levels of high density lipoprotein (HDL) are associated with reduced cardiovascular mortality. Some endocrine disorders accelerate atherosclerosis in association with hypercholesterolemia, hypertension, low level of HDL and hypertriglyceridemia. In patients with acromegaly, hypertriglyceridemia is sometimes accompanied with and aggravated by the presence of impaired glucose tolerance. In patients with hypothyroidism, coronary atherosclerosis may develop in association with hypertension, hypercholesterolemia and moderate elevation of triglyceride which is often accumulation of intermediate lipoprotein. Cushing syndrome may accelerate atherosclerosis by the fact that corticosteroid may induce or exacerbate several known coronary risk factors including hypertension, hypercholesterolemia and impaired glucose tolerance. Estrogen has beneficial effects on the cardiovascular system for postmenopausal women by affecting lipid metabolism, decrease of LDL and increase of HDL.
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PMID:[Atherosclerosis and endocrine disorders]. 841 91

At Brigham and Women's Hospital in Boston, Massachusetts, data on 5 women aged 22-24 years using low-dose oral contraceptives (OCs) containing .035 mg ethinyl estradiol were compared with data on 6 women aged 23-27 years not using OCs so researchers could study the metabolism of individual very low density lipoprotein (VLDL) subfractions of low density lipoprotein (LDL) in users of low-dose OCs and nonusers. Specifically, they wanted to determine the mechanisms by which OC use increases plasma VLDL and triglyceride levels. They infused a nonradioactive amino acid tracer (D3-leucine) intravenously into the 11 women to endogenously label the primary protein component of VLDL and of LDL, apoB, allowing them to measure VLDL and LDL synthesis and catabolism. OC users had large triglyceride-rich VLDL subfraction plasma levels 3 times higher than those of nonusers (20.2 nmol/l vs. 6.7 nmol/l; p , .05). OC use increased large, triglyceride-rich VLDL subfraction production rates 5-fold (16.7 nmol/kg/d vs. 3.4 nmol/kg/d; p .005). OC users had 2.2 times higher small VLDL subfraction levels (36.7 nmol/l vs. 16.7 nmol/l; p .05) and 3.4 times higher small VLDL subfraction production rates (22.5 nmol/kg/d vs. 6.7 nmol/kg/d; p .01) than nonusers. The fractional catabolic rates of large and small VLDL were essentially the same for OC users and nonusers (19.4 pool/d vs. 18.2 pool/d and 15.1 pool/d vs. 17 pool/d). Thus, low-dose OC use increases VLDL levels via a rise in the production rate of large VLDL and not by impeding VLDL catabolism. Learning that low-dose OCs do not curb VLDL catabolism, the researchers proposed that the OC-induced hypertriglyceridemia is less likely to be atherogenic than impaired lipolysis induced hypertriglyceridemia. This hypothesis may provide the answer as to why longterm OC use does not apparently foster atherosclerosis.
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PMID:Effects of low dose oral contraceptives on very low density and low density lipoprotein metabolism. 848 79

The changes in lipid metabolism which occur with the use of oral contraceptives (OCs) have prompted concern about the potential for OCs to increase the risk of premature atherosclerosis. Findings are reported from the study of the effects on lipid metabolism of six modern low-dose OCs. 466 women aged 18-38 years recruited from 21 study centers throughout Europe participated. Subjects were randomly assigned to the following OC formulations: norgestimate 250 mcg and 35 mcg ethinyl estradiol (EE), 180/215/250 mcg of norgestimate and 35 mcg EE, 150 mcg desogestrel and 20 mcg EE, 150 mcg desogestrel and 30 mcg EE, 75 mcg gestodene and 30 mcg EE, and 50/70/100 mcg gestodene and 30/40/30 mcg EE. There were three parallel studies with six parallel patient groups. Fasting blood samples were drawn for the analysis of cholesterol, lipoproteins, and triglycerides between days 24 and 28 and on days 18-22 of cycles 6 and 12. 282 women completed all 12 cycles and were included in the final evaluation. Triglyceride and total cholesterol concentrations increased in all study groups, but to lesser levels with the formulations containing gestodene. All OCs, except the monophasic gestodene preparation, slightly but significantly increased high-density lipoprotein (HDL) cholesterol. The HDL(2) cholesterol subfraction slightly, but significantly, decreased among women using the monophasic gestodene preparation. The low-density lipoprotein (LDL) cholesterol concentration increased slightly with the monophasic and triphasic norgestimate preparations and with desogestrel combined with 20 mcg EE. The only significant change, a slight decrease, in the LDL/HDL ratio occurred with the use of the triphasic norgestimate preparation. While all of the OCs tested altered lipid levels, after 12 cycles there were no statistically significant differences in lipid effects among OC preparations. These findings suggest that, although modern combined OCs containing norgestimate, desogestrel, or gestodene all have some impact upon lipid levels, they probably do not contribute to atherogenesis in healthy women.
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PMID:Metabolic profile of six oral contraceptives containing norgestimate, gestodene, and desogestrel. 857 57

Oral contraceptives (OC) have been shown to enhance the risk of atherosclerosis. In the present study we sought to determine which component of the OC (containing 0.067 mg estrogen and 0.667 mg of progestin) counts for alteration in lipids profile. Female rats were administered with 0.067 mg of 17 beta-estradiol and 0.667 mg of norethindron acetate/kg body weight. Estrogen treatment exhibited higher levels of lipids in the serum and tissues. LDL-cholesterol increased by three folds but HDL-cholesterol decreased significantly, while progestin group showed decreased levels of lipids and LDL cholesterol. Elevated hepatic cholesterogenesis was observed as indicated by increased activity of HMG-CoA reductase and elevated incorporation of labelled acetate into liver cholesterol in estrogen group. On the other hand, progestin treatment did not alter the activity of HMG-CoA reductase and the rate of incorporation of labelled acetate into hepatic cholesterol. Hepatic degradation of cholesterol to bile acids however, decreased with estrogen treatment. No considerable changes were observed in hepatic bile acid levels in progestin group. Release of lipoprotein into circulation increased but their clearance from the circulation decreased as revealed by the activity of lipoprotein lipase (LPL) of extrahepatic tissues in estrogen group. With progestin treatment, activity of LPL increased significantly in adipose tissue. Activity of hepatic malic enzyme and glucose 6-phosphate dehydrogenase enhanced considerably in estrogen group, while activities of these enzymes were depressed with progestin administration. Thus results indicate that estrogen component of oral pills counts for major changes in lipid and lipoprotein metabolism favouring the development of atherosclerosis.
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PMID:Influence of components of oral contraceptive on lipid metabolism. 864 14

Widespread application of proven primary and secondary preventive strategies for coronary heart disease would result in substantial savings of life and health care dollars. Proven strategies (excluding lipid therapy) include quitting smoking, treating hypertension, physical activity, aspirin therapy, and appropriate use of anticoagulants, beta blockers, and angiotensin-converting enzyme inhibitors in survivors of myocardial infarction. Estrogen replacement therapy is currently under clinical investigation. Avoidance of obesity and tight control of diabetes are prudent interventions as yet unproved by clinical trials. Unfortunately, preventive strategies are frequently underutilized. The greatest challenge for preventive cardiology is to put into practice what we already know to prevent the development and progression of atherosclerosis.
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PMID:Nonlipid primary and secondary prevention strategies for coronary heart disease. 872 3

A protective effect of estrogen is the most obvious reason for the substantial and consistent favored status of women vs. men with regard to coronary heart disease (CHD). This paper briefly reviews the history of studies of the estrogen-heart disease hypothesis, the reason why clinical trials of postmenopausal estrogen are necessary (despite the strength, consistency, and plausibility of the 'protection' seen in observational studies), and the status of the 'Postmenopausal Estrogen/Progestin Interventions' (PEPI) trial results and ongoing trials. The potential for nonhormonal primary prevention is emphasized.
Atherosclerosis 1995 Dec
PMID:Postmenopausal estrogen and heart disease. 882 60

The Atherosclerosis Risk in Communities Study investigators examined nearly 4000 postmenopausal women from 1987 through 1989 and 3 years later to determine changes in plasma lipids occurring with the starting or stopping of hormone replacement therapy. Women who started estrogen plus progestin therapy (n = 74) had decreases of 9.8 mg/dl in low-density lipoprotein (LDL) cholesterol and 5.8 mg/dl in apolipoprotein B and increases of 1.2 mg/dl in high-density lipoprotein (HDL) cholesterol (HDL change not significant), 13.5 mg/dl in apolipoprotein A-I, and 14.0 mg/dl in triglycerides. Women who started estrogen alone (n = 149) had similar changes, except for a much larger increase in HDL cholesterol (5.8 mg/dl), principally in HDL-2. Women who stopped hormone therapy (n = 138) had lipid changes opposite to those who started therapy, but smaller in magnitude. These results confirm those of the Postmenopausal Estrogen/Progestin Interventions Trial in a community-based longitudinal cohort: women initiating estrogen plus progestin therapy have decreases in LDL cholesterol, but the increase in HDL cholesterol is less than that for starting estrogen alone. In addition, the current study extends findings to apolipoproteins and HDL subfractions.
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PMID:Changes in plasma lipids and lipoproteins associated with starting or stopping postmenopausal hormone replacement therapy. Atherosclerosis Risk in Communities Study. 889 66

Estrogen provides beneficial effects on hyperlipidemia in climacteric and elderly women. In this study of 68 women (37 to 67 years old), hepatic triglyceride lipase (HTGL), lipoprotein lipase (LpL) serum lipids and apolipoproteins were analyzed to investigate the effects of estrogen replacement therapy (ERT). After menopause, LpL, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apolipoprotein B increased. But ERT suppressed total cholesterol, LDL-cholesterol, apolipoprotein B, and especially apolipoprotein E in menopausal women. The mechanism was thought that ERT significantly suppressed HTGL, but LpL was not affected. Estrogen also increases hepatic LDL receptors and accelerates transfer of serum LDL-C (and TC). It was said that HTGL accelerates conversion of intermediate-density lipoprotein (IDL) to LDL. The suppression of HTGL by the ERT may decrease conversion of IDL to LDL and lower LDL-C (and TC). These estrogen's beneficial effects on lipids, may prevent the atherosclerosis. In addition, apolipoprotein E increases senile plaques in senile dementia-Alzheimer's type. The decrease in apolipoprotein E with ERT may be related to cognitive functions of elderly women.
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PMID:Effect of estrogen replacement therapy on hepatic triglyceride lipase, lipoprotein lipase and lipids including apolipoprotein E in climacteric and elderly women. 907 16

Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women and inhibits progression of coronary artery atherosclerosis in monkeys. Tamoxifen is a nonsteroidal compound with mixed estrogen agonist and antagonist properties. Its antagonist activity is useful in chemotherapy of breast cancer and may have protective effects on plasma lipid concentrations, but its effects on atherogenesis have not been defined. The goal of this study was to examine the effect of tamoxifen on plasma lipids, arterial and hepatic LDL metabolism, and progression of coronary artery atherosclerosis in surgically postmenopausal female monkeys. Thirty-five monkeys were fed an atherogenic diet containing 1.3 mg.kg-1.d-1 tamoxifen (equivalent to the usual dose of 20 mg/d given to women). Thirty-one monkeys were fed the same atherogenic diet with no tamoxifen. Ten monkeys from each treatment group were fed the test diets for 12 weeks to examine the short-term effects of tamoxifen on arterial LDL metabolism. The rest of the monkeys were fed the test diets for 3 years to study the long-term effects of tamoxifen on development of atherosclerosis. In the short term, tamoxifen inhibited the rate of arterial accumulation of LDL degradation products overall (P = .03) and decreased hepatic cholesterol content (P = .003). In the long term, tamoxifen increased plasma concentrations of triglycerides (0.60 +/- 0.67 versus 0.23 +/- 0.02 mmol/L, P = .001) and reduced average LDL molecular weight (5.3 +/- 0.2 versus 4.8 +/- 0.1 g/mumol, P = 0.004) but had no effects on plasma total, LDL, or HDL cholesterol concentrations. Coronary artery atherosclerosis (intimal area, mean +/- SEM) was 0.25 +/- 0.06 mm2 in control monkeys and 0.12 +/- 0.03 mm2 in tamoxifen-treated monkeys (P = .057). We conclude that tamoxifen has antiatherogenic effects that may be modulated in part through direct effects on arterial LDL metabolism.
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PMID:Tamoxifen inhibits arterial accumulation of LDL degradation products and progression of coronary artery atherosclerosis in monkeys. 908 97

In previous studies conducted in rats and in women, we have shown that oral contraceptive (OC) administration induced a platelet hyperaggregation simultaneously with an increased platelet lipid biosynthesis which might be related to lipid peroxidation. In the present study, we specifically studied the arachidonic acid and the fibrinolytic pathways in relation to the fatty acid composition in female rats treated for 6 weeks with OC (ethinyl estradiol plus lynestrenol). We found that platelets of treated animals were not only hyper-responsive to thrombin and ADP, but also to sodium arachidonate. In addition, the results of the thrombin-induced release of labeled arachidonic acid pre-incorporated into platelet membrane phospholipids showed an increased biosynthesis of lipoxygenase and cyclooxygenase metabolites after OC treatment. These data indicated a stimulated platelet arachidonate metabolism in OC animals compared to controls which was further confirmed by the increased thrombin-induced production of thromboxane B2 (TXB2) as measured with a radioimmunoassay. The platelet thrombin-stimulated TXB2 biosynthesis was inhibited in vitro in the presence of 500 mu M aspirin and 1 mM vitamin E; the erythrocytes from OC animals compared with controls presented an enhanced in vitro susceptibility to free radical-induced hemolysis. These data indicated that a free radical mediated-process might occur. This hypothesis is confirmed by an increase of plasma lipid peroxidation parameters (conjugated dienes, lipid peroxides, thiobarbituric acid reactive substances). After OC-treatment, a decrease in plasma and platelet long chain polyunsaturated fatty acids, particularly (n-3), is in keeping with this idea. Furthermore, the results of the peritoneal macrophage-dependent fibrinolytic activity indicated that OC induced a drastic decrease in urokinase plasminogen activator activity which might further contribute to the platelet hyperactivity. Altogether these data suggest that besides the reported increase in clotting factors, platelet hyperactivity, possibly through a stimulated free radical-induced arachidonic acid metabolism, might be involved in the known high thrombogenic risk observed in OC users.
Atherosclerosis 1996 Apr 05
PMID:Enhanced platelet thromboxane synthesis and reduced macrophage-dependent fibrinolytic activity related to oxidative stress in oral contraceptive-treated female rats. 912 95


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