Interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in non-ST-elevation acute coronary syndromes.

OBJECTIVES: The goal of this study was to determine the interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in patients admitted with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: An increased incidence of the P1(A2) polymorphism in smokers presenting with ST-elevation acute myocardial infarction (AMI) has recently been reported. We, therefore, postulated that, as a consequence of this interaction, fewer smokers with the P1(A2) polymorphism would present with non-ST-elevation ACS. METHODS: We performed a prospective cohort analysis of 220 white Caucasoid patients admitted with non-ST-elevation ACS fulfilling Braunwald class IIIb criteria for unstable angina who were stratified by smoking status. RESULTS: There were twice as many nonsmokers as smokers. Nonsmokers compared with smokers were older (mean [SD]; 63.9 [11.2] vs. 57.6 [10.3]; p < 0.0001), more likely to have had a previous admission with unstable angina (24.3% vs. 13.2%; p = 0.051) and AMI (45.8% vs. 30.3%; p < 0.026), more likely to have undergone revascularization (24.3% vs. 1.8%; p = 0.028) and were more likely to be on aspirin on admission (60.4% vs. 44.7%; p = 0.026). The proportion of nonsmokers positive for the P1(A2) polymorphism was equivalent to that expected for this population but was significantly reduced in smokers (28.7% vs. 10%; Pearson chi-square = 9.09, p = 0.0026). In a logistic regression model, the odds ratio (OR) for being positive for the P1(A2) polymorphism was significantly reduced by smoking (OR [interquartile range]: 0.26 [0.11 to 0.62]; p = 0.0026). CONCLUSIONS: There is a significant reduction in the P1(A2) polymorphism in smokers admitted with non-ST-elevation ACS compared with nonsmokers, which suggests an interaction between smoking and this polymorphism.

Genetic susceptibility to macrovascular complications of type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus have a threefold increased risk of developing macrovascular disease such that 75% of such patients will die of cardiovascular complications. This increased risk is, however, not completely explained by traditional risk factors such as smoking, hypercholesterolaemia, hypertension and glycaemic control. Moreover, the fact that not all patients with type 2 diabetes develop these complications, together with evidence of family clustering (a heritability of 50%), suggests that a proportion of the susceptibility to ischaemic heart disease in type 2 diabetes may be genetic. Unravelling the polygenic susceptibility factors for the complications of a disease that itself has multifactorial inheritance has proved difficult and has focused largely on the candidate gene approach. A review of some of the studies testing candidate genes specifically in patients with both type 2 diabetes and ischaemic heart disease is presented. These studies focus largely on four main areas: lipoprotein metabolism, glycation and oxidation pathways, haemostatic cascade, and other candidate genes.

Socioeconomic differentials in recurrent ischaemia and mortality after acute myocardial infarction.

OBJECTIVE: To examine the influence of socioeconomic deprivation on case fatality following acute myocardial infarction. DESIGN: Prospective cohort observational study. SETTING: General hospital. PATIENTS: 1417 white and south Asian patients admitted with acute myocardial infarction between January 1988 and December 1996, and classified by the Carstairs socioeconomic deprivation score of the enumeration district of residence. MAIN OUTCOME MEASURES: 30 day and one year survival. RESULTS: There was little variation across deprivation groups in age, sex, or smoking status, though a higher proportion of patients from more deprived enumeration districts were diabetic and of south Asian origin, and a higher proportion of them developed Q wave infarction and left ventricular failure. There was no appreciable variation in clinical treatment with deprivation. Patients from more deprived enumeration districts had a higher risk of recurrent ischaemic events (death, recurrent myocardial infarction, or unstable angina) over the first 30 days: event free survival (95% confidence interval (CI)) of the most deprived quartile was 0.79 (95% CI 0.74 to 0.83) compared with 0.85 (95% CI 0.80 to 0.88) in the least deprived quartile. The unadjusted hazard ratio corresponding to an increase from the 5th to 95th centile of the deprivation distribution was 1.54 (95% CI 1.02 to 2.32), and 1.59 (95% CI 1.03 to 2.44) after adjustment for age, sex, racial group, diabetes, acute treatment with thrombolysis and aspirin, and left ventricular failure. Survival from 30 days to one year, however, did not show a socioeconomic gradient (hazard ratio adjusted for the same variables was 1.07 (95% CI 0.68 to 1.70)). CONCLUSIONS: In patients hospitalised with acute myocardial infarction, there is a strong association between early recurrent ischaemic events and socioeconomic deprivation that is not accounted for by clinical presentation or treatment. This association appears to be attenuated over time.

Screening for carotid artery disease before cardiac surgery: is current clinical practice evidence based?

BACKGROUND: There is no clear consensus as to the correct screening procedure to identify patients undergoing cardiac surgery and who are at greatest risk of stroke because of the presence of significant carotid artery stenosis. Such screening is important because some patients benefit from combined carotid and cardiac surgery and, regardless of this, the information gained puts the cardiac surgeon in a position to provide an accurate assessment of surgical risk. Our objective was to examine current clinical practice of carotid artery investigation prior to urgent cardiac surgery and to review this illustrative practice in the context of the world literature. HYPOTHESIS: The study aimed to establish that current typical practice for screening cardiac surgical patients for carotid artery disease is illogical according to the evidence in the world literature. METHODS: The study consisted of a retrospective assessment of all patients undergoing urgent cardiac surgery and a Medline-derived literature review, and included all patients undergoing urgent cardiac surgery at a tertiary cardiothoracic center between January 1 and December 31, 1997. RESULTS: Of 529 patients undergoing urgent cardiac surgery, 44 (8%) were screened preoperatively by duplex Doppler ultrasonography for carotid disease. The indications for screening were asymptomatic carotid bruit in 24 patients, history of stroke or transient ischemic attack (TIA) in 12 patients, and neither stroke, TIA, or bruit in 7 patients. The tests were requested either by the attending cardiologists or by the cardiac surgeon to whom they were referred. One patient had already been diagnosed as having carotid artery disease in the past. Thirteen patients underwent additional carotid investigations. Eleven patients were demonstrated to have internal carotid artery stenosis > or = 60% and 3 patients underwent combined cardiac and carotid surgery. Review of the literature revealed the following groups to be at increased risk of future stroke unrelated to surgery, and of postoperative stroke: those with a history of stroke or TIA, those with carotid bruits, and, of importance, all patients with significant carotid stenosis. Recent data suggest that symptomatic patients and the elderly are at greatest risk. CONCLUSIONS: Only 8% of patients undergoing urgent cardiac surgery in a 1-year period were screened for carotid artery disease. We suggest that screening should definitely be performed in all patients with a history of stroke or TIA, all patients with a bruit, and all patients aged > 65 years. The literature suggests, however, that significant reductions in stroke rate could be achieved by screening the whole cardiac surgical population, although there is a paucity of data that are specifically pertinent to this patient subgroup. Further data are therefore required for the construction of a scientifically valid and medicolegally sound policy.

Transvenous pacing lead-induced thrombosis: a series of cases with a review of the literature.

Although transvenous pacing is a safe treatment modality for bradyarrhythmias, serious thrombotic and embolic complications are reported to occur in 0.6-3.5% of cases. We describe 5 cases of pacemaker-associated thrombosis, 3 with a superior vena cava syndrome (SVC), 1 with an axillary vein thrombosis and 1 with a thrombus attached to the pacing lead in the right atrium. All of the patients were initially treated with intravenous heparin which proved successful as the sole treatment in only the least severe case (axillary vein thrombosis). One of the patients with SVC obstruction was successfully treated with intravenous heparin followed by thrombolytic therapy. The remaining 3 cases (2 SVC syndromes and 1 right atrial thrombus) required surgical removal of thrombus and pacing leads. Both of the patients with evidence of infection were in the group for whom failure of medical therapy necessitated surgery.

Influence of previous aspirin treatment and smoking on the electrocardiographic manifestations of injury in acute myocardial infarction.

OBJECTIVE: To examine demographic and clinical characteristics of patients with acute myocardial infarction in order to identify factors affecting the electrocardiographic evolution of injury. METHODS: Prospective cohort study of 1399 consecutive patients with a first myocardial infarction. Baseline clinical data associated with ST elevation and Q wave development were identified and 12 month survival was estimated. RESULTS: Smoking had complex effects on the evolution of injury, increasing the odds of ST elevation (odds ratio (OR) 1.61; 95% confidence interval (CI) 1.08 to 2.36), but reducing the odds of Q wave development (OR 0.69, 95% CI 0.49 to 0.96). The effects of previous aspirin treatment were more consistent with reductions in the odds of ST elevation (OR 0.57, 95% CI 0.35 to 0.94) and Q wave development (OR 0.53, 95% CI 0.34 to 0. 84). ST elevation and Q wave development were both associated with an adverse prognosis, with estimated 12 month survival rates of 80. 6% (95% CI 78.2% to 83.1%) and 80.0% (95% CI 77.5% to 82.5%), respectively, compared with 86.5% (95% CI 81.2% to 91.9%) and 89.9% (95% CI 86.2% to 93.7%) for patients without these ECG changes. CONCLUSIONS: The thrombogenicity of the blood may be a major determinant of infarct severity. Smoking increases thrombogenicity and the likelihood of ST elevation, but because coronary occlusion is relatively more thrombotic in smokers, responses to both endogenous and exogenous thrombolysis are better, reducing the risk of Q wave development. Previous aspirin treatment reduces thrombogenicity, protecting against ST elevation and Q wave development.

Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues.

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.

The hypoechoic band: a normal finding on testicular sonography.

High-resolution sonograms were obtained in 119 patients in whom intrascrotal disease was suspected on the basis of history and physical findings. In 20 of these patients, a total of 22 conspicuous hypoechoic intratesticular bands (18 unilateral and four bilateral) were seen in the middle third of the testicle on scans obtained axially or slightly oblique to conventional axial scans. The bands were up to 3 mm wide and 3 cm long. The bands were on the side with suspected disease in six patients. Of these, three patients had a small epididymal cyst, one had a mild hydrocele, and two had no other sonographic finding. The remaining 16 bands were on the side opposite that with clinically suspected disease and were seen in otherwise normal testes. Follow-up examination in 11 of the 20 patients with the band showed no change. In four of eight patients examined with pulsed Doppler sonography, a normal low-resistance waveform was seen that was characteristic of intratesticular arteries (with gradual descent after peak systole and relatively high diastolic flow). In three of these patients, color Doppler imaging corroborated the presence of arterial flow, which did not fill the entire width of the band, thus suggesting an additional venous component of lower velocity in the band. Identification of flow in only half the cases may have been caused by the limitations in sensitivity of the equipment. We conclude that the hypoechoic bands noted on gray-scale testicular sonography are caused by a normal variant of intratesticular vessels, artery and vein, and that they are of no clinical significance.