Risk factors and prevention of acute coronary syndrome

Acute coronary syndromes (ACS) such as unstable angina, myocardial infarction, or sudden ischemic death evolve from coronary thrombosis consequence of atherosclerotic plaque disruption. Plaque stabilization is an important therapeutic strategy in the prevention of ACS. Coronary risk factors include age, male sex, cigarette smoking, hypertension, dislipidemia, diabetes mellitus, insulin resistance and/or hyper insulinemia, obesity, sedentary lifestyle, stress, and the morning surge of sympathetic activity. New risk factors are emerging such as high homocystein, inflammation, and some kinds of infection. Control of blood pressure and cholesterol clearly reduce the risk of coronary events and mortality although the effects of antihypertensive therapy have been less than expected. The benefits of smoking cessation, moderate alcohol consumption, low-dose aspirin prophylaxis, estrogen-replacement therapy in postmenoposal women have also been shown.     

Danaparoid in the prevention of thromboembolic complications

OBJECTIVE: To review the therapies used to prevent postoperative thromboembolic complications with a focus on the role of danaparoid, a new low-molecular-weight glycosaminoglycan. DATA SOURCES: A MEDLINE search was performed to identify pertinent English-language literature including studies, abstracts, and review articles. Key search terms included danaparoid, heparinoid, lomoparin, heparin, prophylaxis, thrombosis, embolism, thromboembolism, and thromboembolic and postoperative complications. The manufacturer of danaparoid was contracted for additional information related to this compound. STUDY SELECTION AND DATA EXTRACTION: All identified articles were reviewed for possible inclusion in this review. Comparisons primarily focused on data obtained from prospective, randomized, controlled, blind clinical trials. Another important consideration was the use of venography to determine the presence of deep venous thrombosis. DATA SYNTHESIS: Various therapies are available for the prevention of postoperative thromboembolic complications. Effective pharmacologic treatments currently available include adjusted-dose heparin, warfarin, aspirin, dextran, and low-molecular-weight heparins (LMWHs). Until recently, warfarin was considered the drug of choice for thromboprophylaxis in high-risk patients, including patients undergoing orthopedic surgical procedures. Because of their comparable efficacy and greater ease of use, LMWHs are gaining favor over warfarin in this patient population. In well-designed clinical trials involving patients undergoing elective total hip replacement or fractured hip surgery, danaparoid has demonstrated greater efficacy than other active treatments, including warfarin, dextran, aspirin, and heparin plus dihydroergotamine. While studies comparing danaparoid with LMWHs have not yet been published, danaparoid may be more useful in patients with heparin-associated thrombocytopenia. CONCLUSIONS: Danaparoid is an antithrombotic agent with characteristics that distinguish it from heparin and LMWHs. Based on the efficacy and safety data reviewed, danaparoid should be considered one of the drugs of choice for the prevention of thromboembolic complications in patients undergoing orthopedic hip procedures and the drug of choice for the management of any patient with heparin-induced thrombocytopenia who requires anticoagulant therapy.     

Risk factors and prevention of vascular complications in polycythemia vera

Two experiments investigated long-term verbal memory performance in groups of 20-year-old heavy (HSDs) and light social drinkers (LSDs), in the presence and absence of a pharmacological challenge (lorazepam 2 mg). In Experiment 1 (n = 13), a verbal learning task was presented visually and it was found that lorazepam significantly impaired delayed verbal recall performance in both groups. Experiment 2 (n = 14) assessed the effect of presenting the verbal learning task in the auditory compared to the visual modality. Both groups' performance on the delayed trials of the visually presented task was reduced in the lorazepam treatment. However, in the auditory presented task, lorazepam reduced 30-min delayed recall performance in the HSDs but not in the LSDs. The differential effect of lorazepam on HSDs compared to LSDs on delayed recall performance when material is presented in the auditory modality may suggest that frequent heavy social drinking results in changes in CNS functioning.     

Common risk and protective factors in successful prevention programs

A review of 1,200 outcome studies in six areas of research identified common risk and protective factors emerging from successful and often multilevel prevention programs, some of which had prevented multiple problems. The inter-relatedness of the factors is explored, as is their association with multiple outcomes. Implications for further research and for the design of future intervention programs are discussed.     

The thromboembolic risk of the pill

In this review, the clinical reality, the statistical risk, and the frequency of thromboembolism in pill users are evaluated, 6 cases described, and premonitory signs, treatment, and etiology are discussed. Clinically these thromboembolisms appear in unlikely subjects and unusual bodily locations such as the mesenteric veins, without warning. The risks are 8-11 times higher for pulmonary thrombosis, 3-6 times higher for myocardial infarction, based on previously used higher dosed pills. The frequency is about .5-1/1000, or 500-1000/year in France. Some of the cases described used pills with less than .05 mg estrogen, some were heavy smokers, 1 woman died, 1 had a lower extremity amputation, and 1 woman had demonstrated IgG lamda antibodies against ethinyl estradiol. Premonitory signs are rare, and unsually ignored. The immediate action is to stop the pill and start anticoagulants. The cause of these disorders is not known in detail, but is presumed to be estrogens, therefore, low-dose pills, i.e., those with .05 or .03 mg ethinyl estradiol, should be used if possible. Other risk factors are surgery, age, immobilization, history of vein disorders, smoking, hyperlipidemia, hypertension, especially since the pill potentiates hypertension, hyperlipidemia, and hypercoagulation. Some mechanisms proposed are hyperlipidemia, disturbed blood coagulation factors, decreased fibrinolysis, alterations in the blood vessel endothelium and immunity against the estrogen in the pill.     

Fractures of the upper tibia and thromboembolic risk

Phenylhydroxylamine added to human red cells under aerobic conditions and in the presence of glucose was partly reduced to aniline. About half the hydroxylamine was recovered as amine after a 2-hr incubation. The aniline, after acetylation, was identified as acetanilide by melting point, Rf-value in TCL as well as UV, IR, and NMR spectroscopy. The fate of the remaining phenylhydroxylamine was followed by use of 14C-labeled phenylhydroxylamine. About 30% of the total radioactivity was bound to hemoglobin or other proteins and about 20% was found in highly polar low-molecular substances which were insoluble in organic solvents. The elucidation of the sites at which phenylhydroxylamine was bound to hemoglobin was complicated by the lability of the bonds. When purified human hemoglobin had reacted with radioactive phenylhydroxylamine, large proportions of the radioactivity bound to hemoglobin were removed by treatment with acid or with PMB for separation of alpha- and beta-chains. The radioactive compound liberated from hemoglobin by acid was found to be aniline. After reaction with phenylhydroxylamine the number of SH groups titrable with PMB was found to be diminished. Pretreatment of hemoglobin with N-ethylmaleimide or PMB decreased the amount of phenylhydroxylamine bound to hemoglobin but did not fully prevent the reaction. Tryptic digestion of hemoglobin after reaction with radioactive phenylhydroxylamine yielded tryptic peptides with lower specific activity than that of hemoglobin. Chymotryptic digestion of the tryptic core yielded a core with specific activity much higher than that of hemoglobin. Fingerprinting of the tryptic or chymotryptic hydrolyzates showed the presence of peptides with high and other ones with low or no radioactivity and of radioactive compounds which did not react with ninhydrin. In the covalent binding of phenylhydroxylamine to globin the SH group beta93 plays an important role, but other yet unknown sites are also reactive.     

Risk of thromboembolic events in patients with atrial flutter

Based on multiple studies, clear, guided anticoagulation therapy is recommended for patients with atrial fibrillation. The value of anticoagulation therapy in patients with atrial flutter, however, is less well established. Little is known about the incidence of thromboembolism in patients with atrial flutter. We evaluated the risk of thromboembolism in 191 consecutive unselected patients referred for treatment of atrial flutter. A history of embolic events was noted in 11 patients. Acute embolism (<48 hours) occurred in 4 patients (3 after direct current cardioversion, 1 after catheter ablation). During follow-up of 26+/-18 months, 9 patients experienced thromboembolic events. During the follow-up, the overall embolic event rate (including acute embolism and thromboembolic events during follow-up) was 7 % in this patient population. Risk indicators for an embolic event in an univariate analysis were organic heart disease (p = 0.037), depressed left ventricular function (p = 0.02), history of systemic hypertension (p = 0.004), and diabetes mellitus (p = 0.0038). Using multivariate analysis, a history of hypertension was the only independent predictor for elevated embolic risk in this patient population (odds ratio = 6.5; 95% confidence intervals 1.5 to 45). Thus, the thromboembolic risk is higher than previously recognized for patients with atrial flutter. Anticoagulation therapy may decrease this risk.     

Efficacy of prevention of thromboembolic complications with LMW-heparin in experiment

The authors used an antithrombotic agent (Nadroparin Calcium) with anti-Xa effect in their experiments to prevent thromboembolic complications in the model of endoprosthetic replacement of the hip joint in mongrel dogs. 10 experimental animals (Group I.) were given doses of 100 A Xa ICU/kg/bwt of Nadroparin Calcium subcutaneously 4 hours prior to the operation and also once a day until the 3rd postoperative day; between the 4th and 10th postoperative days doses of 150 A Xa ICU/kg/bwt Nadroparin Calcium were given. The 10 control animals (Group II.) did not receive anticoagulant treatment. In both groups platelet count, activated partial thromboplastin times (APTT), prothrombin and fibrinogen levels as well as activated factor X inhibition (F Xa) were measured prior to surgery and also until the 14th postoperative day. No changes in APTT and prothrombin levels were detected during the experiment, however platelet count and fibrinogen levels as well as the extent of F Xa inhibition showed significant and different changes in groups I. and II. The Group I. which had received thromboembolic prophylaxis did not develop deep venous thrombosis or pulmonary embolism, but the control group did. Based on their investigations, the authors concluded that they had been able to achieve F Xa inhibition by giving the above mentioned doses of Nadroparin Calcium which was enough to prevent thromboembolic complications in their model experiment of implanting hip endoprosthesis.     

Modifiable stroke risk factors in volunteers willing to participate in a prevention program

The current trends in stroke incidence require continued efforts to improve primary prevention. Compared to large-scale public health approaches, more limited programs targeting volunteers may offer some advantages. We invited all 12,824 members of a health insurance company program who lived within 50 km form one of two study sites to participate in a vascular screening program and aimed at reducing modifiable risk factors. 1,837 persons registered and participated (14.3%, mean age 53 +/- 12 years, 50% men). Using the Framingham stroke risk profile for persons aged 55 years or above (n = 961, 52.3%), 97 stroke events can be predicted for this age group within 10 years. The majority of these 97 events will occur in those with men resting blood pressure values +/- 140mm Hg (systolic) or +/- 90 mm Hg (diastolic; 420 persons, mean age 64 +/- 7 years, 60 expected events), or with a particularly high age- and sex-adjusted risk (288 persons, mean age 68 +/- 7 years, 60 expected events). Our pilot study provides an estimate of the prevalence of modifiable vascular risk factor among volunteer participants of a prevention program. Possible benefits of this approach will be investigated in a second step using a randomized intervention.     

Perception of the risk of venous thromboembolic disease in primary care

OBJECTIVES: To determine the prevalence in out-patients of risk factors leading to venous thromboembolic disease (VTE); and to analyse what perception primary care centre (PCC) doctors have of this risk and what attitude they adopt to therapy. DESIGN: 1) An observational, crossover study, with patients included at random. 2) A study with a teaching intervention, which was neither controlled nor randomised. PATIENTS: PCC patients over 25 seen either on demand, with appointments or at home. INTERVENTION: A clinical history was composed, using a closed questionnaire. A risk category and therapeutic attitude were then assigned. A guide on prevention and treatment of VTD was presented and discussed in clinical sessions. RESULTS: 11 PCC doctors polled 272 patients. 45 of these had moderate to high risk of VTD; and 4 had one of the criteria of the European Accord on VTD prevention for commencing prophylactic treatment. In two of these four, it was thought necessary to start prophylaxis. CONCLUSIONS: The prevalence of patients with moderate to high risk of VTD is 17% in patients over 25 who seek medical attention at PCCs. Doctors detected 50% of moderate to high risk patients. If the criteria used for in-patients were followed, prophylaxis should have been started in 1.5% of patients.     

Risk factors for venous thrombosis: prevalence, risk, and interaction

Annually, 1 in 1,000 individuals is affected by venous thrombosis. Risk factors that are known to increase the risk of thrombosis may be either genetic or acquired, or have a combined origin. Many of these risk factors are very frequent, among which several have been recently identified, such as resistance to activated protein C by factor V Leiden, hyperhomocysteinemia, high levels of factors VIII, as well as the classical acquired risk factors, such as surgery and malignancies. When the prevalence of risk factors is high, it becomes likely that in some individuals two or more risk factors will be present simultaneously. The question "What happens to the risk in these circumstances?" is one involving interaction, also known as effect modification or synergy. In this article we review the prevalence and risk estimates for the various genetic and acquired risk factors for venous thrombosis, discuss the concept of interaction, and give an overview of the evidence for interaction of these risk factors.     

Toxic-shock syndrome: epidemiologic features, recurrence, risk factors, and prevention

Surveillance for toxic-shock syndrome (TSS) in Wisconsin detected 38 cases with onsets from September 1975 through June 1980. Thirty-seven of the cases occurred after January 1, 1979; 37 of the patients were women, 35 cases occurred during menses; 38 patients were white; and one patient died. Cervical or vaginal cultures were obtained before antibiotic therapy in 23 patients, and 17 cultures were positive for Staphylococcus aureus. Ten patients had at least one recurrent episode during subsequent menstrual periods. The recurrence rate was lower in patients who had been treated with beta-lactamase-resistant antibiotics. Thirty-five patients were matched for age and menstruation to 105 controls: 34 of 35 cases (versus 80 of 105 controls) used tampons during every menstrual period (P < 0.01); nine of 35 cases (versus 64 of 105 controls) practiced contraception (P < 0.001). In Wisconsin the minimum incidence of TSS as defined by clinical criteria is 6.2 cases per 100,000 menstruating women per year. The rate of TSS among menstruating women younger than 30 years was 2.4 to 3.3 times the rate among those who were 30 or older.     

Primary prevention of cardiovascular disease risk factors: review and implications for population-based practice

This review analyzed the results of population-based intervention studies targeting primary prevention of cardiovascular disease risk factors among children and adolescents in the United States. In general, the findings indicate that cardiovascular disease risk factors may be amenable to interventions in school-based programs. Although the interventions have small effects on risk factor outcomes, they should be interpreted within the context of population-based approaches that ultimately may have a greater impact on disease prevention than much larger effects among the small proportion of individuals at the highest levels of risk.     

Mechanism and prevention of port-site tumor recurrence after laparoscopy in a murine model

Functional activation of somatosensory cortex was studied in alpha-chloralose anesthetized rats by functional magnetic resonance imaging (fMRI), using both perfusion-weighted and T2*-weighted (blood oxygenation level dependent, BOLD) imaging. The sensitivity of functional activation was altered by ventilating animals for 3 minutes with 6% CO2. Before hypercapnic conditioning, electrical stimulation of the left forepaw at a frequency of 3 Hz led to an increase of signal intensity (relative to the unstimulated baseline condition) in the right somatosensory cortex by 6+/-2% (means+/-SD) in T2*-weighted images and by 45%+/-48% in perfusion-weighted images. After hypercapnic conditioning the signal intensity increase in perfusion-weighted images doubled to 91%+/-62% (P=0.034), whereas that of T2*-weighted images only marginally increased to 7+/-4% (not significant). This different behavior in both imaging modalities is interpreted as evidence for an increased flow response in combination with a higher oxygen extraction. Thus, the fMRI data reflect hypercapnia-induced resetting of the functional-metabolic coupling of the tissue during activation.     

Use of a thromboembolic risk score to improve thromboprophylaxis in surgical patients

OBJECTIVE: The correlations between steady-state plasma concentrations of mianserin and its active metabolite desmethylmianserin and those of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were examined in 19 depressed patients. METHODS: Ten patients received first mianserin (30 mg per day) and second trazodone (150 mg per day), while 9 patients received these treatments in the opposite sequence, with at least 2-week intervals between the two phases. Blood was sampled at steady state, 1-3 weeks after initiation of each treatment. Plasma concentrations of mianserin, the separate enantiomers S(+)- and R(-)-mianserin, desmethylmianserin, trazodone and m-CPP were measured by means of high-performance liquid chromatography. RESULTS: There was a significant correlation between steady-state plasma concentrations of trazodone and total mianserin (r = 0.59) or S(+)-mianserin (r = 0.57), but not R(-)-mianserin (r = 0.33). CONCLUSION: The present study thus suggests that the metabolic capacity of mianserin, especially the more active S(+)-enantiomer, and that of trazodone correlate to each other. This finding supports the previous suggestions that cytochrome P4502D6 is involved in the metabolism of mianserin and trazodone.