Periodontal health improves systemic inflammatory and haemostatic status in subjects with coronary heart disease.

OBJECTIVES: A relationship between poor oral health and coronary heart disease (CHD) and systemic inflammatory and haemostatic factors has been recently documented in an Italian population. The present study was performed to assess whether intensive dental care may produce a periodontal improvement along with a change in systemic inflammatory and haemostatic factors. MATERIAL AND METHODS: The study population consisted of 18 males aged 40-65 years with proven CHD and elevated values of systemic inflammatory and haemostatic factors. A detailed description of their oral status was given by using two different dental indices (clinical periodontal sum score and clinical and radiographic sum score). Blood samples were taken for measurement of the following systemic markers of inflammation [(C-reactive protein (CRP), leucocytes, fibrinogen)] and haemostatic factors [(von Willebrand factor, fibrin D-dimer and oxidized-low density lipoprotein (Ox-LDL)]. All parameters were determined in each subject at baseline, after 4 months as a control and 3 months after an intensive protocol of scaling and root planing. anova for repeated measures was used for the statistical analysis. RESULTS: No statistical difference was found between values at baseline and at the 4-month-control. All oral indexes showed a significant decrease (p< .01) 3 months after periodontal treatment. All systemic inflammatory indexes decreased but only the decrease in CRP reached statistical significance (p< .05). A significant decrease (p< .01) was also found as regards Ox-LDL among haemostatic factors. CONCLUSIONS: Preliminary results from the present study suggest an association between poor oral status and CHD, and provide evidence that the improvement of periodontal status may influence the systemic inflammatory and haemostatic situation.

[Late-appearing cholestatic icterus after a month of treatment with ticlopidine]. / Ittero colestatico a comparsa ritardata dopo trattamento per un mese con ticlopidina.

A 65-year-old man was submitted to coronary angioplasty and stent implantation for stable angina. The treatment included a 30-day therapy with ticlopidine (in addition to aspirin, metoprolol, ramipril, amlodipine and nitrates). One month after ticlopidine withdrawal a progressive cholestatic jaundice took place. Viral, immunogenic as well as nutritional causes were ruled out. The abdominal echography disclosed a normal biliary tree and the liver biopsy showed a centrolobular cholestasis pattern. Drug-induced cholestatic reaction was diagnosed and attributed to ticlopidine. There was a progressive improvement in clinical and laboratory findings 4 months after steroid treatment. The clinical picture was normalized after 6 months. When considering the option ticlopidine, even for a short time after coronary angioplasty, the possibility of drug-induced hepatotoxicity should be kept in mind. Consequently, markers of liver toxicity should be monitored carefully.

Long-term arterial patency after coronary reperfusion.

Coronary reocclusion is a frequent event after reperfusion and may be responsible for the deterioration of left ventricular function. It may occur early as well as in the chronic phase after hospital discharge. Current, evidence based, strategies to prevent reocclusion include antiplatelet and anticoagulant agents as well as the use of intracoronary stenting in those patients who are treated by PTCA. The combination of aspirin and ticlopidine adds on the results of stenting. Further treatments are currently investigated and may significantly improve the long-term coronary patency.

Prognostic value of the admission electrocardiogram in acute coronary syndromes.

CONTEXT: The presence of ischemic changes on electrocardiogram (ECG) correlates with poorer outcomes in patients with acute chest pain. OBJECTIVE: To determine the prognostic value of various ECG presentations of acute myocardial ischemia. DESIGN: Retrospective analysis of the presenting ECGs of patients enrolled in Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb). SETTING: Three hundred seventy-three hospitals in 13 countries in North America, Europe, Australia, and New Zealand. PATIENTS: A total of 12142 patients who reported symptoms of cardiac ischemia at rest within 12 hours of admission and had signs of myocardial ischemia confirmed by ECG. On presenting ECG, 22% of patients had T-wave inversion, 28% had ST-segment elevation, 35% had ST-segment depression, and 15% had a combination of ST-segment elevation and depression. MAIN OUTCOME MEASURE: Ability of presenting ECG to predict death or myocardial reinfarction during the first 30 days of follow-up. RESULTS: The 30-day incidence of death or myocardial reinfarction was 5.5% in patients with T-wave inversion, 9.4% in those with ST-segment elevation, 10.5% in those with ST-segment depression, and 12.4% in those with ST-segment elevation and depression (P<.001). After adjusting for factors associated with an increased risk of 30-day death or reinfarction, compared with those who had T-wave inversion only, the odds of 30-day death or reinfarction were 1.68 (95% confidence interval [CI], 1.36-2.08) in those with ST-segment elevation, 1.62 (95% CI, 1.32-1.98) for those with ST-segment depression, and 2.27 (95% CI, 1.80-2.86) for those with combined elevation and depression. An elevated creatine kinase level at admission correlated with a higher risk of death (odds ratio [OR], 2.36; 95% CI, 1.92-2.91) and death or reinfarction (OR, 1.56; 95% CI, 1.32-1.85). The ECG category and creatine kinase level at admission remained highly predictive of death and myocardial infarction after multivariate adjustment for the significant baseline predictors of events. CONCLUSIONS: The ECG at presentation allows immediate risk stratification across the spectrum of acute coronary syndromes. An elevated creatine kinase level at admission is associated with worse outcomes.

Intravascular Stenting in a Female Patient with Spontaneous Coronary Dissection and Von WillebrandÕs Disease.

We report a case of spontaneous coronary dissection occurring in a 46-year-old women affected by von WillebrandÕs disease presenting with anterior myocardial infarction. The patient was treated with thrombolytic therapy and stent implantation. We believe that in patients with single vessel spontaneous coronary dissection and unstable clinical condition, coronary stenting may provide an alternative treatment in place of coronary surgery.

[Multiple spontaneous coronary dissection. Case report and review of the literature]. / Dissezione coronarica spontanea multipla. Descrizione di un caso e revisione della letteratura.

We refer a case of a 57-year-old woman with an acute myocardial infarction of the anterior wall, treated with rt-PA, aspirin and heparin. In the following days, in spite of the therapy, occurred a second acute myocardial infarction of the inferior wall complicated with ventricular fibrillation. Coronary angiography showed multiple coronary dissection involving the left anterior descending and the circumflex coronary arteries. The characteristic feature of this case consists of the multiple coronary dissection responsible for myocardial infarctions, an event seldom reported in the literature.

Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin in unstable angina. Studio Epoorine Sottocutanea nell'Angina Instobile (SESAIR) Refrattorie Group.

Intravenous heparin has been used in the control of myocardial ischaemia in patients with unstable angina. We set out to assess the efficacy of subcutaneous heparin in reducing myocardial ischaemia in patients with unstable angina. 343 of 399 patients with unstable angina were monitored for 24 h and 108 were refractory to conventional antianginal treatment and were entered into a randomised multicentre trial. 37 patients were assigned to heparin infusion (partial thromboplastin time 1.5-2 times baseline), 35 to subcutaneous heparin (adjusted dose with partial thromboplastin time 1.5-2 times baseline), and 36 to aspirin (325 mg daily). All had additional conventional antianginal therapy. After the run-in patients were monitored for 3 days. The primary endpoint was reduced myocardial ischaemia assessed by the number of anginal attacks, silent ischaemic episodes, and duration of ischaemia per day. At 1 week and 1 month we accounted for anginal attacks and other clinical events (myocardial infarction, revascularisation procedures, and death). Aspirin did not significantly affect the incidence of myocardial ischaemia. On the first 3 days, infused and subcutaneous heparin significantly decreased the frequency of angina (on average by 91% and 86%, respectively), episodes of silent ischaemia (by 56% and 46%), and the overall duration of ischaemia (66% and 61%) versus run-in day and aspirin (p < 0.001 for all variables). The favourable effects of heparin therapy remained evident during follow-up. Only minor bleeding complications occurred. Subcutaneous heparin is effective in the control of myocardial ischaemia in patients with unstable angina.

[Chronic ischemic cardiopathy: antiplatelet agents and anticoagulants, new protocols for prevention and treatment]. / Cardiopatia ischemica cronica: antiaggreganti ed anticoagulanti, nuovi regimi di profilassi e terapia.

The atherosclerotic process is negatively affected by all the components of the haemostatic system (vascular, platelets, blood coagulation, fibrinolysis). The diseased coronary tree is a high shear rate flow system which, in turn, implies a high number of platelet collisions at sites of vascular injury. This a distinctive feature of coronary thrombosis and illustrates the relevance of blood rheology in thrombosis development. It is appalling how the clinical benefit derived from a conceptually simple intervention such as the partial inhibition of platelet function or blood coagulation is actually discernible by a crude tool such as a clinical trial. Almost all the subgroups take advantage from the treatment and coronary as well as non-coronary events are prevented. Although strong arguments exist for the chronic use of oral anticoagulants in patients with previous myocardial infarction, antiplatelet regimens are more attractive because they do not require any particular skill and are unlikely to determine haemorrhagic complications. New strategies in the chronic antithrombotic treatment of patients with coronary atherosclerosis may involve the pharmacologic manipulation of GpIIb/IIIa (or other platelet integrins) as well as the direct blockade of thrombin. However it is the combination of different antithrombotic agents that appears most promising presently. The combined use of antiplatelet and anticoagulant drugs has already been shown to be effective in acute coronary syndromes and in patients with prosthetic heart valves. It is hoped that the same pattern will be confirmed also in the chronic phase of coronary artery disease by ongoing clinical trials.

Pharmacodynamic characteristics of low-molecular-weight dermatan sulphate after subcutaneous administration in acute myocardial infarction.

Sixteen patients (5 female and 11 male, mean age 59.1 years) who had had an acute myocardial infarction within the previous 7 days, were enrolled in an open pharmacodynamic study. Patients were randomly allocated to two treatment groups and given a single subcutaneous dose of 100 or 200 mg of a new low-molecular-weight dermatan sulphate. The drug pharmacodynamic profile was determined 1, 2, 4, 6, 8, 12 and 24 h after administration. The following coagulation and fibrinolysis tests were performed: activated partial thromboplastin time, thrombin time, activated factor X inhibition, Heptest (global clotting time), heparin cofactor II affinity, functional and antigenic plasminogen activator inhibitor and fibrin plate assay. Both Heptest and heparin cofactor II affinity were significantly increased (P < 0.001) in a dose-dependent manner. The XaI was enhanced, though to a lesser extent. None of the other coagulation or fibrinolysis tests showed significant changes at either dose. Systemic and local tolerance were always very good.

Benefit of adding low molecular weight heparin to the conventional treatment of stable angina pectoris. A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Patients with chronic coronary artery disease exhibit a dysfunctioning endothelium, which may be responsible for exercise-induced platelet activation and expression of a procoagulant moiety. In this study, we evaluated the therapeutic efficacy of a low molecular weight heparin (Parnaparin) in patients with stable angina pectoris. METHODS AND RESULTS: According to a double-blind, randomized, placebo-controlled trial, 29 patients with stable exercise-induced angina pectoris and angiographically proven coronary artery disease received a single daily subcutaneous injection of Parnaparin or placebo on top of aspirin and conventional antianginal medication over 3 months. Patients randomized to Parnaparin showed a significant decrease in the fibrinogen level (P = .035) and an improvement in both the time to 1-mm ST segment depression (P = .008) and the peak ST segment depression (P = .015). The Canadian Cardiovascular Society class for angina pectoris was also improved by Parnaparin (P = .016). Parnaparin did not affect ADP and collagen-induced platelet aggregation, whereas thrombin-induced aggregation was reduced (P = .0001). The bleeding time was slightly prolonged, but this was not associated with any significant bleeding. CONCLUSIONS: Patients with stable angina pectoris may be treated with Parnaparin in addition to aspirin and conventional antianginal medication. Side effects are negligible, and compliance is excellent.

Performance of fineneedle aspiration cytology of the breast. Clinical experience in Ravenna (Italy).

AIMS AND BACKGROUND: Fineneedle aspiration cytology (FNAC) is a routine test in the evaluation of breast lesions. We assessed the diagnostic accuracy of mammography (MG), physical examination (PE), ultrasonography (US) and FNAC in 1064 histologically confirmed breast lesions (638 malignant, 426 benign) observed consecutively at the Cancer Prevention Center of Ravenna (Italy). METHODS: The performance of each test and the additional contribution of FNAC were determined. RESULTS: FNAC was done in 69.6% of cancers and 39.7% of benign lesions (P = 0.00000), the frequency of aspiration being significantly associated with severity at MG, PE, and US. For FNAC, the true positive rate was 95.1% and the true negative rate 67.4%. Only one breast cancer case was detected by FNAC alone (additional true positive rate 0.2%). The positive predictive value of FNAC in the absence of other abnormalities was 5%. The negative predictive value of a benign report at MG, PE, US and FNAC was 100%. CONCLUSIONS: All breast lesions should be evaluated by all available techniques, especially FNAC, and open biopsy should be avoided for those reported as benign at all tests.

Comparison of efficacy of low molecular weight heparin (parnaparin) with that of unfractionated heparin in the presence of activated platelets in healthy subjects.

Arterial thrombosis is typically platelet-rich. In this study, it is shown that heparin levels resulting in the usual activated partial thromboplastin time therapeutic range provide only a small anticoagulant effect in the presence of activated platelets. Thrombin inhibition is also negligible when heparin is added to platelet-rich plasma. Aspirin improves the anticoagulant effect of heparin in these circumstances, but the degree of anticoagulation is still considerably lower than that observed in platelet-poor plasma. A low molecular weight heparin (parnaparin) is more active in the presence of activated platelets (such as may occur in acute coronary syndromes) regardless of whether aspirin is used concomitantly.

Effect of enoximone alone and in combination with metoprolol on myocardial function and energetics in severe congestive heart failure: improvement in hemodynamic and metabolic profile.

The hemodynamic and myocardial metabolic effects of enoximone (phosphodiesterase III inhibitor), alone or in combination with metoprolol (beta-adrenergic blocker), were studied in patients with congestive heart failure. Ten patients (New York Heart Association Class III-IV) underwent right heart and coronary sinus catheterization, and parameters were assessed at basal condition, at peak enoximone response (mean intravenous loading dose = 2.2 mg/kg), and after the combination with metoprolol (mean intravenous dose = 8.5 mg). Heart rate tended to increase during enoximone administration (from 102 +/- 16 to 107 +/- 16 min-1, ns) and was reduced during enoximone plus metoprolol (to 88 +/- 15 min-1, p < 0.05 vs. basal). Cardiac index was increased during enoximone (from 2.2 +/- 0.2 to 3.8 +/- 0.5 1/min/m2, p < 0.05) and decreased during enoximone plus metoprolol (to 2.8 +/- 0.5 1/min/m2, p < 0.05 vs. enoximone). Mean pulmonary wedge pressure fell during enoximone and remained reduced during enoximone plus metoprolol (from 27 +/- 9 to 9 +/- 3 and to 13 +/- 4 mmHg, respectively, both p < 0.05). Myocardial oxygen consumption did not change during enoximone (from 27 +/- 8 to 25 +/- 13 ml/min, ns) and was reduced during enoximone plus metoprolol (to 19 +/- 8 ml/min, p < 0.05 vs. basal). Myocardial lactate extraction tended to be lower during enoximone and during enoximone plus metoprolol conditions (from 38 +/- 17% to 26 +/- 20% and to 29 +/- 24%, respectively), but no statistical significance was found. Myocardial efficiency was increased during enoximone and during enoximone plus metoprolol (from 9 +/- 3% to 15 +/- 6% and to 14 +/- 6%, respectively, both p < 0.05). Thus in patients with congestive heart failure enoximone improves hemodynamics and, in most cases, it does not influence energetics. The addition of metoprolol to enoximone reduces heart rate, cardiac index, and myocardial oxygen consumption without any other major changes, producing a more physiologic hemodynamic and metabolic profile.

Evidence of a partial escape of renin-angiotensin-aldosterone blockade in patients with acute myocardial infarction treated with ACE inhibitors.

Angiotensin-converting enzyme (ACE) inhibitors have been designed to block the renin-angiotensin system and can represent an effective therapeutic approach in those settings where such a system is active, such as myocardial infarction. In a randomized placebo-controlled study, 10 patients with acute myocardial infarction allocated to treatment with increasing doses of zofenopril calcium and 10 patients allocated to placebo were studied in hospital, within 24 hours from symptoms, during 11 sampling periods to assess the time course of ACE inhibition and renin-angiotensin-aldosterone blockade. Zofenopril administration was followed by a dose-dependent inhibition of in vitro ACE activity (7.5 mg, 65%; 15 mg, 89%; 30 mg, 94.5%) and a progressive increase in plasma active renin. Conversely, plasma aldosterone decreased during the first 3 days of treatment and then returned toward baseline values, as did blood pressure, despite a persistent inhibition of ACE. The present data suggest the existence of an interesting dissociation between the time-course of ACE inhibition and that of blockade of the renin-angiotensin system in patients with acute myocardial infarction. This discrepancy could arise from the combination of an only partial in vivo ACE inhibition and the compensatory increase in plasma renin that occurs during treatment with ACE inhibitors. A better understanding of this relationship would seem to be useful in addressing the correct use of ACE inhibitors in patients with acute myocardial injury.