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)

Researchers have found that oral contraceptives (OCs) change carbohydrate and lipoprotein metabolism and these changes are like those linked with increased risk of cardiovascular (CV) disease, especially myocardial infarction and stroke. Since CV disease is the major cause of death in US women, it is important that OCs not induce changes in carbohydrate and lipoprotein metabolism. A new progestin, norgestimate, has an advantage over other progestins in that it tends not to induce male traits. This is beneficial because androgenicity is related to atherosclerosis which increases the risk of myocardial infarction. Further studies show that the new combined OC (250 mcg norgestimate/35 mcg ethinyl estradiol) does not influence serum glucose tolerance levels. It also does not affect the physiologic regulating system of prostacyclin, the inhibitor of platelet aggregation, by high density lipoprotein (HDL). In addition, it increases prostacyclin metabolites and HDL which may indeed decrease the risk of occlusive thrombotic vascular diseases. Moreover a study in Germany demonstrates that it causes no changes in fibrinopeptide A,m the anticoagulation factors antithrombin III and protein C, or coagulation promoting factors fibrinogen, factor VII, and the components of VIII. In women, it is absorbed well and metabolized extensively before the body eliminates it. Moreover this new combined OC has an overall Pearl index of 0.25. Studies to data indicate that norgestimate/ethinyl estradiol may be more advantageous than other OC formulations. Yet only long term epidemiologic studies can determine if it can indeed decrease the risk of CV diseases linked with older OCs.
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PMID:Norgestimate: a clinical overview of a new progestin. 160 87

Previous results, presented in abstract form, indicate that replacement of thromboplastin with a mixture of phospholipid and truncated soluble tissue factor apoprotein results in a coagulation assay that can directly measure plasma factor VIIa levels without interference from zymogen factor VII (Atherosclerosis Thromb 11:1544a, 1991 [abstr]). We have exploited the specificity and sensitivity of such a factor VIIa specific coagulation assay to directly assess the in vivo relationship of factor VIII and factor IX on the production of factor VIIa levels under nonthrombotic and nonstimulatory conditions. Normal individuals (n = 20) were found to possess an average circulating factor VIIa level corresponding to 4.34 +/- 1.57 ng/mL, or approximately 1% of their total factor VII antigen. Severe factor VIII deficient patients (n = 13) possessed a slightly lower but statistically significant (P less than .01) decrease in their basal factor VIIa levels (2.69 +/- 1.52 ng/mL), corresponding to approximately 60% of that observed in normal individuals. On the other hand, severe factor IX deficient patients (n = 7) were found to possess even lower levels of factor VIIa corresponding to 0.33 +/- 0.15 ng/mL, or less than 10% of that observed in normal individuals. Measurement of total factor VII antigen levels shows that the variation in basal factor VIIa levels stems from differences in the degree of factor VII activation as opposed to differences in factor VII antigen levels. Our present data are consistent with the hypothesis that factor IXa is the principal in vivo activator of factor VII under basal conditions.
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PMID:Measurement of basal levels of factor VIIa in hemophilia A and B patients. 146 30

It has been shown previously that individuals possessing the Gln353 allele of factor VII have significantly lower factor VIIc levels. In this population based study of Europeans, Afro-Caribbeans and Gujarati Indians, the Gln353 allele was associated with lower factor VIIc in all groups, carriers having factor VIIc levels 20-25% below the group mean. Although the Afro-Caribbeans had the lowest factor VIIc levels, the frequency of the Gln353 allele was not different from the European sample. However, in the Gujaratis, the frequency of the Gln353 allele was significantly higher than in the Europeans (0.25 compared to 0.09, P less than 0.001). Factor VIIc is known to be positively correlated with plasma triglyceride levels, although the Gujaratis, having the highest mean triglyceride levels, did not have the highest mean factor VIIc levels. On examination of the relationship between triglycerides and factor VIIc in the Gujaratis there was a correlation (r = 0.23, P = 0.13) in individuals homozygous for the factor VII Arg353 allele, but no correlation (r = 0.001, P = 0.5) among Gln353 carriers. This striking difference suggests that the effect of triglycerides on factor VIIc is genotype specific and thus provides an example of gene-environment interaction. The high frequency of the Gln353 allele, with its associated lack of relationship between triglyceride and factor VIIc levels, may explain the lower than expected factor VIIc levels in the Gujaratis.
Atherosclerosis 1992 May
PMID:Genetic and environmental determinants of factor VII coagulant activity in ethnic groups at differing risk of coronary heart disease. 163 58

Of the major risk factors for atherosclerosis, high factor VII and fibrinogen levels, genetic predisposition, gender and age cannot be influenced. Reduction of high blood pressure reduces the cerebral but not the coronary vascular risk and correction of dyslipidaemia correlates with cardiovascular risk. Other major risk factors (tobacco consumption, obesity, sedentary lifestyle and diabetes) can also be modified. Aspirin in doses of approximately 300 mg/day may be recommended for the primary prevention of myocardial infarction (MI), but only in those patients with a moderate to high risk of cardiovascular disease. Aspirin reduces the risk of fatal and nonfatal MI by about 50% and also decreases the overall mortality rate among patients with unstable angina. A lower dose of aspirin (150 mg/day) also reduces mortality by 23% in the acute phase of MI. In doses of 300 mg/day, aspirin is useful in the secondary prevention of MI and reduces the overall mortality rate by 15%. Various antiplatelet agents, including aspirin (alone or combined with dipyridamole) and ticlopidine, have proved useful in the prevention of thrombosis in aorto-coronary grafts, provided treatment begins at the latest 6 hours after surgery. The usefulness of antiplatelet drugs has been well established in the prevention of immediate reocclusion following coronary angioplasty, but not in the prevention of late reocclusion. Aspirin and ticlopidine are also beneficial in extracorporeal circulation techniques. In patients with a synthetic cardiac valve prosthesis, antivitamin K-anticoagulants are still indispensable lifelong, but their antithrombotic effect can be reinforced by dipyridamole or aspirin. Diuretics probably provide the best primary protection against cerebrovascular accidents, although medium doses of aspirin may be considered in elderly people at high risk of such accidents. Aspirin (alone or combined with dipyridamole) and ticlopidine may be recommended for the secondary prevention of cerebral ischaemic accidents. Aspirin (with or without dipyridamole) and ticlopidine reinforce the treatment of obliterative arterial disease in the lower limbs.
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PMID:Risk factors, interventions and therapeutic agents in the prevention of atherosclerosis-related ischaemic diseases. 172 14

Recent prospective investigations have reported that higher plasma fibrinogen concentrations and higher factor VII coagulant activity are associated with greater risk of cardiovascular disease. To discover what characteristics may influence fibrinogen and factor VII, we analyzed data from the Atherosclerosis Risk in Communities Study obtained from over 12,000 men and women, aged 45-64 years, from four communities in December 1986 to June 1989. Fibrinogen was higher in blacks than whites and in women than men; in general, it increased with age, smoking, body size, diabetes, fasting serum insulin, LDL cholesterol, lipoprotein(a), leukocyte count, and menopause, and it decreased with ethanol intake, physical activity, HDL cholesterol, and female hormone use. Factor VII was higher in women than men and, in women, increased with age; in both sexes, it increased with body size, triglycerides, LDL cholesterol, and HDL cholesterol, and it decreased with ethanol intake. These findings indicate that elevations in fibrinogen and factor VII may be modifiable through appropriate lifestyle changes.
Atherosclerosis 1991 Dec
PMID:Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors. 178 4

Nine adults took two 7-day diets of standardised energy and total fat content, but with a dietary polyunsaturated/saturated fat ratio of less than 0.3 and greater than 3.0 respectively, while adhering to their daily routine. Blood was drawn on 6 occasions between 09.00 and 22.45 h on the final day of each dietary period for factor VII activity (VIIc), factor VII antigen (VIIag) and lipoprotein lipid concentrations. Diurnal variation was described for each variable in terms of its deviation from the individual's daily mean value at each time point across the day. Plasma triglyceride remained low until after the midday meal, whereafter a marked rise was sustained into the later evening. Plasma VIIc declined until early afternoon, but showed a marked rise in the late afternoon. Plasma VIIag showed no significant diurnal variation. Changes in plasma triglyceride concentration during the day were related positively to changes in VIIc about 160 min later, but not to VIIc at other time points. This effect of postprandial triglyceridaemia on VIIc persisted after allowance for the effect of VIIag on VIIc. Dietary fat composition did not influence VIIc or VIIag. The results suggested an acute but evanescent effect of triglyceride-rich lipoproteins on the reactivity of factor VII, irrespective of their lipid core composition.
Atherosclerosis 1991 Feb
PMID:Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition. 187 11

To asses the relationship between fibrinogen, factor VII coagulant (VIIc) activity and extent of coronary artery disease, we studied 43 white males shown to have greater than 50% stenosis of at least one major coronary artery. Thirty six had a definite history of myocardial infarction at least 3 months earlier and were classified as having 1, 2 or 3 vessel disease while 7 had 2 or 3 vessel disease, but no prior infarction. Groups were similar with regard to age, body mass index and blood pressure. In those with documented prior infarction, there was a significant relationship between the extent of atheroma and coagulation variables factor VIIc and fibrinogen. However, given a similar degree of atheroma, patients with prior infarction had significantly higher levels of factor VIIc activity compared with patients without such a history. These results corroborate those from prospective studies confirming a significant role for the coagulation system in the clinical manifestation of coronary artery disease.
Atherosclerosis 1990 Dec
PMID:Fibrinogen, factor VII clotting activity and coronary artery disease severity. 210 80

The influence of coffee and caffeine consumption on hemostatic factors was studied in 2 randomized trials. Both studies were conducted in young, healthy adults. In the first study, 107 participants were randomly allocated to one or 3 intervention groups, drinking filtered coffee, boiled coffee or no coffee at all, respectively, for a period of 9 weeks. In the second study, 69 subjects received either 4-6 tablets containing 75 mg caffeine or the same amount of placebo tablets, while using decaffeinated coffee. In this double-blind study caffeine intake from any other source was not allowed. Blood samples for hemostatic factors were obtained at baseline and after 9 weeks of intervention. The findings indicate no effect of coffee consumption on fibrinogen, clotting factor VII activity, factor VIII antigen, protein C and protein S and also no effect of caffeine consumption on fibrinogen and factor VII activity.
Atherosclerosis 1990 Aug
PMID:Coffee, caffeine and hemostasis: results from two randomized studies. 214 67

In a strictly controlled cross-over study (twice 2 weeks) of 11 healthy adults, the effects of a low-fat diet (32% of total energy from fat) with a low or a high ratio of polyunsaturated to saturated fatty acids (0.28 and 0.89, respectively) were observed. Factor VII activity and antigen levels, serum cholesterol, HDL-cholesterol and triglycerides were measured. Factor VII activity was determined in clotting assays using human and bovine thromboplastin (interacting primarily with activated factor VII, F VIIa), allowing differentiation between F VIIc and F VIIa. A significant decrease of F VII levels (median 11.0-14.5%, P less than 0.05) and triglycerides (median 0.22-0.27 mmol/l, P less than 0.05) was observed on both diets, while only the highly unsaturated diet reduced serum cholesterol levels (median 0.65 mmol/l, P less than 0.001). There were no significant correlations between changes in blood lipids and F VIIc. Low fat diets may reduce the risk for ischemic heart disease without lowering of cholesterol levels by eliminating states of hypercoagulability such as elevated factor VII coagulant activity.
Atherosclerosis 1990 Jan
PMID:Effects of total fat content and fatty acid composition in diet on factor VII coagulant activity and blood lipids. 231 Apr 28

In order to carry out a multicenter study aimed at understanding the association of hemostatic factors with atherosclerotic vascular disorders for the Atherosclerosis Risk In Communities (ARIC) Study, we compared a blood collection and processing system developed in our laboratory with the state-of-the-art-procedures. The salient features of our system included the use of a new phlebotomy set for venipuncture, the use of Millipore filters for removing platelet residues in the plasma and the use of a mixture of anticoagulants and antiplatelet agents for inhibiting the in vitro activation of platelets, coagulation and fibrinolytic system. The results derived from systematic evaluations indicate that this newly developed system yields the lowest values of plasma beta TG, PF 4 and FPA when compared with the reported values. The technique also gave reliable values of representative hemostatic measurements such as fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin-III, protein C, tissue-type plasminogen activator, and serum thromboxane B2. Further experiments revealed that the samples withstood temporary storage at -70 degrees C and overnight "shipping" manipulations without significant changes in the hemostatic values. We conclude that the described blood collection and processing system may be a valuable asset for conducting multicenter cooperative clinical trials and epidemiologic studies involving blood collection by multiple field centers or clinics.
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PMID:ARIC hemostasis study--I. Development of a blood collection and processing system suitable for multicenter hemostatic studies. 252 84


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