Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to examine the effects on lipoprotein risk markers for CHD of oestradiol given alone and in combination with the androgenic progestogen, norethisterone. Eighty postmenopausal women were randomly allocated to receive oestradiol (2 mg/day) alone or with continuous norethisterone (1 mg/day). Serum lipoprotein levels, including lipoprotein(a), were monitored during 12 months on treatment in all the women, and in a sub-set of 32 patients cholesterol was measured in the two major density subfractions of LDL. Oestradiol caused a transient rise in triglycerides, a small decrease in LDL cholesterol (significant only at 3 and 6 months, P < 0.05) and a consistent significant increase in HDL cholesterol (16%, P < 0.01). There was a downward trend in lipoprotein(a) levels which did not achieve statistical significance. The combined preparation caused significant, sustained decreases in triglycerides (31%, P < 0.01), total cholesterol (15%, P < 0.001), VLDL (42%, P < 0.01), LDL (9%, P < 0.05) and HDL (11%, P < 0.001). Lipoprotein(a) was also reduced (39%, P < 0.05). In the sub-set of patients in which LDL subfractions were measured, the reduction in LDL induced by oestradiol monotherapy was significant only at the 3-month visit (6%, P < 0.05). This was due to a decrease in the 'light' (1.025 < d < 1.044 g/ml) subfraction (10%, P < 0.05) and resulted in an apparent shift in subfraction distribution towards the 'heavy' (1.044 < d < 1.060 g/ml) subfraction, although there was no absolute increase in the latter. None of these changes was statistically significant at 12 months. Oestradiol/norethisterone caused sustained decreases in both 'light' (15%, P < 0.05) and 'heavy' (29%, P < 0.05) subfractions, with no significant change in the relative amounts. The changes in 'light' and 'heavy' LDL in this group were highly correlated with changes in triglyceride levels (r = -0.57, P < 0.05 and r = 0.82, P < 0.01 respectively). Therefore, at the end of 1 year's treatment with unopposed oestradiol the only statistically significant change was an increase in HDL cholesterol. Addition of norethisterone to the preparation reversed this potentially beneficial change, but favourably influenced triglycerides, VLDL, LDL subfraction profile and lipoprotein(a), which may counteract the adverse effect on HDL.
Atherosclerosis 1996 Sep 27
PMID:Effects of postmenopausal hormone replacement therapy on lipoproteins including lipoprotein(a) and LDL subfractions. 887 36

Seasonal variation in the plasma lipids and lipoproteins is reported in the literature. Whether this variation is the result of changes in diet or other factors has not been adequately addressed. We investigated the effects of a controlled diet on the seasonal variation in the levels of plasma lipids and apolipoproteins and also on the excretion of urine metabolites of TXA2 and PGI2 in healthy males. Two well-controlled diet studies were conducted to evaluate effects of dietary fatty acids on plasma lipids (Studies 1 and 2; n = 33) and eicosanoid excretion (Study 2 only; n = 15). Participants consumed whole-food test diets in a randomized, four-period crossover design during each 26-day experimental period. A non-intervention control group also participated in each study (Study 1, n = 12; Study 2, n = 11). Blood was collected monthly and analyzed for plasma lipids and apolipoproteins A-1 (Apo A-1) and B100 (Apo B). Twenty-four hour urine samples were collected monthly only in Study 2 and analyzed for TXB2 and 6-keto-PGF1 alpha by RIA. Seasonal fluctuations were observed in all subjects in plasma Apo A-1 (zenith = July, with 95% CI June-July; P < 0.05) and Apo B (zenith = October, 95% CI September-November, P < 0.05). Although there was no significant variation in plasma cholesterol levels, the increase in Apo B is consistent with an increase in LDL particle number during the fall/winter. Additionally, excretion of both eicosanoid metabolites and the ratio of 6-keto-PGF1 alpha/TXB2 was markedly elevated in July (95% CI June-July, P < 0.001). Three seasonal fluctuations were observed both in participants who consumed a highly-controlled experimental diet and in the non-intervention controls. Thus, these results suggest a diet-independent seasonal variation in parameters thought to be involved in coronary heart disease risk status. An understanding of these variations is important not oly for clinical evaluation and metabolic study design issues, but more importantly, to clarify their clinical significance with the seasonal incidence of CHD events.
Atherosclerosis 1996 Sep 27
PMID:Seasonal variation in parameters related to coronary heart disease risk in young men. 887 40

Atherosclerosis, the precursor of coronary heart disease may originate in childhood. The atherogenic potential of food is related to its cholesterol and saturated-fat content. The study population consisted of children from CHD-parents under the age 12 years with plasma total cholesterol > 170 mg/dl, LDL-Ch > 90 mg/dl and ApoB > 70 mg/dl. All the patients were advised a 6 month diet following National Program of Cholesterol Prevention recommendation. Plasma, TCh, LDL-Ch, ApoB, TG, Ch-esters saturated/unsaturated ratio and platelet factor 4 concentration decreased, LCAT activity and Ch-esters unsaturated increased during study period. We observed interesting correlation between: PF4 and ApoB, PF4 and LDL-Ch and PF4 and HDL-ECh 18:3. Our data show, that proper diet can modify risk factors of CHD in children with family history of CHD.
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PMID:[Effect of dietetic recommendations on the level of some lipid and hemostatic parameters in offspring of parents with risk factors for coronary heart disease]. 908 47

Is Lp(a) culpable in atherosclerosis? This is a question for scientists. Lp(a) fulfills two of Koch's four criteria for causation for CHD. However, the actual mechanism by which Lp(a) promotes atherosclerosis remains unproven. Should we investigate Lp(a) as part of assessment of CHD risk? There are some reasons that favour measuring plasma Lp(a) in selected patients. First, a high Lp(a) can exist without physical or historical evidence. Second, the measurement of Lp(a) might affect diagnosis, treatment and/or prognosis. However, presently there is no standard assay for Lp(a) and there is no evidence for benefit of treatment elevated Lp(a). Furthermore, there is no current evidence that knowledge of a patient's Lp(a) status would affect management of other aspects of a patient's CHD risk. Lp(a) can be considered to be a non-modifiable potential CHD risk factor, as are family history and gender. If Lp(a) is to be measured, it must be done so using a validated, reliable and commonly used assay. Measuring Lp(a) could be reserved for subjects in whom there is equivocation over how aggressively to treat the traditional CHD risk factors, such as elevated plasma LDL cholesterol. If Lp(a) were found to be high in such a subject, the modifiable CHD risk factors should be addressed more aggressively. However, the medical community awaits the results of prospective studies addressing this particular issue.
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PMID:Is it time to measure Lp(a) as part of coronary heart disease risk assessment? 925 23

Familial hypercholesterolemia (FH) is characterized by an increased level of LDL cholesterol, tendon xanthomas and an elevated risk of premature coronary artery disease (CAD). FH is caused by different mutations in the low density lipoprotein receptor (LDLR) gene or by a G to A mutation in exon 26 of the apolipoprotein B gene causing familial defective apolipoprotein B-100 (FDB). To compare the phenotypic expression of either defect, we studied 83 patients (76 heterozygous and 7 homozygous persons) with LDLR defects and 33 heterozygous FDB patients from Germany. We took into account other risk factors for CAD. In contrast to earlier studies, our patients where prospectively ascertained from the lipid clinic and tested for the G-A mutation. The average total cholesterol level in plasma was 413.7 mg/dl in LDLR patients and 321.8 mg/dl in FDB patients. Patients with LDLR defects had a significantly higher risk of myocardial infarction, coronary artery bypass graft, positive coronary angiography, atherosclerotic plaques in the carotid arteries and CAD (p<0.01) than patients with FDB. CAD was present in 33% and plaques in the carotid arteries in 82% of the patients with LDLR defects. No patient with FDB had severe CAD, while only 52% had plaques in the carotid arteries (p<0.05). Thus in our study, hypercholesterolemia and premature atherosclerosis were more common in LDLR patients than in FDB patients. We believe that the striking difference in CHD incidence is not sufficiently explained by the higher LDL levels in LDLR patients. A possible explanation may be that in LDLR patients, the metabolism of low density lipoproteins, intermediate density lipoproteins and very low density lipoproteins is disrupted, whereas in FDB patients there is only disruption in apo B-containing LDL.
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PMID:Familial hypercholesterolemia and familial defective apolipoprotein B-100: comparison of the phenotypic expression In 116 cases. 936 Sep 38

Data from literature indicate that immune processes play an important role in atherogenesis. Modified lipoproteins might be immunogenic and generate autoantibodies in plasma. To determine whether the level of such circulating autoantibodies correlates with the extent of atherosclerosis expressed as cholesterol values in plasma (C), very low density (VLDL-C), low density (LDL-C), and high density lipoproteins (HDL-C), we compared the level of plasma autoantibodies of a group of coronary heart disease patients (CHD-P) with that of normal, age-matched donors, with no history of cardiac disease (N). All CHD-P (even normocholesterolemic) were characterized by an LDL-C/HDL-C ratio > 4, while all N (even hypercholesterolemic) had this ratio < 4. A double level of circulating autoantibodies against VLDL and LDL in CHD-P as compared to N group was detected. The anti-LDL antibodies level correlated well with LDL-C level and was negatively correlated with the age of patients. For tissue localization of native and modified LDL (as well as other possibly modified proteins) we used immunohistochemical techniques, employing antihuman LDL, antihydroxynonenal-lysine (HNE-Lys), and antiadvanced glycation end-products (AGE) proteins. Antibodies were applied on consecutive cryosections of the aortic arch, valves and coronary arteries of CHD-P. The immunodetected antigens were colocalized in focal deposits, in the cap and shoulders of the atheroma. Native LDL and modified proteins (AGE, HNE-Lys) were detected either diffuse-extracellularly or associated with macrophage-derived foam cells and smooth muscle cells of the intima. These data indicate the following: a) the existence of an elevated level of circulating autoantibodies against VLDL and LDL, which correlates negatively with the age of CHD patients; b) the presence of LDL (possibly glycated or oxidized) in detectable amounts in the intima of atherosclerosis-affected arteries; c) the modified lipoproteins are immunoactive components in the atherosclerotic process.
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PMID:Immunodetection of modified lipoproteins in plasma and arterial walls of patients with coronary heart disease. 956 50

Diabetes mellitus type 2 (DM type 2) is a common disease that is associated with high mortality and morbidity due to macrovascular and microvascular complications. CHD mortality and morbidity is 2--3 times higher in diabetic than in non-diabetic patients/. There are many potentially atherogenic factors in diabetes these may underlie this problems. Except major risk factors (high serum cholesterol concentration, hypertension, cigarette smoking), insulin resistance is common in DM type 2 patients. The dyslipidemic component of insulin resistance is "atherogenic lipoprotein phenotype", its components include small LDL particles (pattern B) with higher atherogenic risk. Several recent studies have demonstrated the preponderance of small, dense LDL in patients with DM type 2 and IR. The question of whether small, dense LDL can be explained by triglyceride levels alone or whether it is directly related to DM type 2 and insulin resistance is still the subject of debate. If serum triglycerides exceed 1,3 mmol/l, small, dense LDL increases. The practical implication is that serum triglyceride levels should be maintained as low as possible to prevent the deleterious effects of triglycerides on LDL subclass distribution and size. There are several potential mechanisms to explain the increased atherogenicity of dense LDL (small dense LDL is more susceptible to lipid peroxidation and oxidation leading to its increased uptake by macrophages and subsequent removal by scavenger pathway, also has a lower binding affinity to LDL receptors). Theoretical grounds postulate that the treating of diabetic dyslipoproteinemias would reduce atherosclerosis disease. However, to date, there have been no intervention studies specifically designed to test this postulate in the diabetic population Such studies the Diabetes Atherosclerosis Intervention Study (DAIS), Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), Collaborative Atorvastatin in Diabetes Study and lipid in Diabetes Study are currently in progress (Tab. 4, Fig. 2, Ref. 81.).
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PMID:[In Process Citation] 966 34

Measures of fibrinolytic and thrombotic function have been examined in 55 subjects with recently identified coronary heart disease, and age and sex matched control subjects. Measurements were particularly directed at factors and processes which could be affected by changes in endothelial function and included the euglobulin lysis time as well as plasma levels of von Willebrand factor (vWF). Plasma levels of protein S and protein C were also measured. Measurements were made before and after a period of 10-min veno-occlusion combined with rhythmic hand exercise. In addition anthropometric, haemodynamic and biochemical measurements (plasma lipids and apolipoproteins, glucose and insulin) were obtained and correlated with the haematological parameters. Protein S and vWF levels were significantly higher, both before and after veno-occlusive exercise, in subjects with CHD than in the asymptomatic controls. Euglobulin lysis times were not significantly different but only shortened on veno-occlusive exercise in those without CHD. Protein S levels were significantly correlated with systolic blood pressure, plasma total cholesterol, plasma triglyceride, plasma phospholipid, plasma fasting glucose and both apolipoprotein A1 and B levels. vWF levels were not significantly related to any of the other variables. Subjects whose pre-exercise euglobulin lysis times exceeded 6 h had significantly higher BMI, plasma total cholesterol, triglyceride, phospholipid, insulin, glucose and apoB concentrations and lower HDL cholesterol than those with lysis in less than 6 h. The findings from this study are consistent with a role for endothelial dysfunction in the production of atherosclerotic vascular disease and may indicate additional, non-haemodynamic, mechanisms for such an association. In addition, the relationship between elevated levels of protein S and CHD does not appear to depend on the demonstrated associations between protein S and a number of other cardiovascular risk factors.
Atherosclerosis 1998 Sep
PMID:Relationships between protein C, protein S, von Willebrand factor and euglobulin lysis time and cardiovascular risk factors in subjects with and without coronary heart disease. 973 15

After a thorough review of the available literature, it appears that hyperhomocysteinemia is an independent risk factor for CHD. Furthermore, folic acid has been shown to reduce homocysteine concentration. Nevertheless, CHD is a multifactorial process, and many risk factors play a role in its pathogenesis. Several unanswered questions remain regarding the role of folic acid supplementation in hyperhomocysteinemia (Table 3). The absolute homocysteine concentration at which cardiovascular risk increases is not certain, and the magnitude of homocysteine-lowering needed to prevent events is unknown. Consequently, the number needed to treat cannot be calculated for folic acid supplements. Based on these data, the populations in whom to evaluate a homocysteine concentration have yet to be described. Because the POEMs are not yet available, it is unknown whether supplemental folic acid to lower homocysteine concentration will reduce CHD morbidity and mortality. It will take several years before any randomized, controlled trials are done, and primary prevention trials will need to be of very long duration to show any change in outcomes. Widespread use of folic acid supplementation has been recommended, however, and the need for clinical outcomes might be precluded. Even in the absence of outcome data, the potential benefits of using folic acid appear to outweigh any risks. A diet high in folic acid should be encouraged in everyone (Table 4). The FDA-mandated folic acid fortification of enriched grain products is most likely insufficient to lower homocysteine concentrations meaningfully, and a daily multivitamin that contains 400 microg of folic acid should be considered for patients who have documented CHD (especially when other risk factors are absent or in patients with premature atherosclerosis) and men and women who have cardiovascular risk factors, in addition to women of childbearing potential. Folic acid supplementation in the form of a multivitamin once daily is safe and inexpensive and might prevent the development and progression of CHD.
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PMID:Homocysteine and cardiovascular disease. 979 69

Life style measures (weight reduction and control, reduction of total fat calories to < 30% of total calories, modification of fat intake to increased monounsaturated vegetable fat, increased intake of dietary fibers, increased physical activity, controlled stress relaxation) are the basis of longterm therapy of coronary heart disease. For transformation to daily life both patient and doctor need motivation, information, patience, and realistic aims. For realization the 10 rules of medical information should be followed. The patient must be informed that the "new lifestyle" is not punishing but means a new quality of life. With respect to the most important metabolic syndrome with hyperinsulinemia due to insulin resistance, weight reduction is the most important measure for preventing complications of atherosclerosis. The patient should use a diary for weight control and blood pressure self-measurement. Secondary prevention of CHD has been shown useful and effective; however, most patients need additionally drug therapy to avoid or retard progression of the coronary heart disease. The targets for cholesterol and blood pressure control are low; the responsibility of the patient remains high. Besides weight reduction, stopping smoking, lowering lipids, controlling hypertension, and aspirin are the most important.
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PMID:[Changes in life style as a causal therapeutic approach in coronary heart disease]. 982 71


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