Elevated levels of homocysteine predict cardiovascular death, nonfatal myocardial infarction, and symptomatic bypass graft disease at 2-year follow-up following coronary artery bypass surgery

Severe graft disease occurs in patients at a rate of approximately 15% within the first year of coronary artery bypass grafting (CABG). In this study, the authors examined predictors of the combined end point of death, nonfatal myocardial infarction (MI), and bypass graft disease at 2-year follow-up after CABG. One hundred twenty-one consecutive patients were included in this study after informed consent was obtained. In univariate analysis, there was a significantly (P<.05) higher homocysteine level (11.0 ng/mol vs 9.7 ng/mol, P=.04) in patients who met the combined end point vs those who did not. There were no statistically significant differences in the following: low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and lipoprotein(a) values; age; body mass index; smoking and diabetes status; statin or aspirin use; creatinine level; hematologic markers; left ventricular ejection fraction; number of bypass grafts; and distribution of coronary artery disease. Logistic regression analysis modeling for low-density lipoprotein cholesterol, lipoprotein(a), fibrinogen, and homocysteine showed that homocysteine value (P=.016) was an independent predictor of the primary combined end point.     

Alcohol and dietary factors in cirrhosis. An epidemiological study of 304 alcoholic patients.

Alcohol intakes and dietary habits of 304 alcoholic, hospitalized patients were evaluated. There were 195 patients with hepatic cirrhosis, 40 precirrhotics, and 69 noncirrhotics. Alcohol contributed 50% to 58% of total calories. Two thirds of the patients drank excessively for more than 20 years. There were no statistically significant differences between the three groups in the duration or degree of alcohol excess. Dietary intakes were assessed for a period of at least two years before the presenting illness. Noncirrhotics had higher food caloric intakes and higher protein intakes than the cirrhotics (P less than .05). The findings suggest that dietary factors may be involved in the pathogenesis of the disease.     

Thrombin‐Induced Platelet‐Fibrin Clot Strength Identified by Thrombelastography

Background and Objective

In‐stent restenosis (ISR) is a limitation of percutaneous coronary intervention and has been linked to specific clinical and angiographic variables. We aimed to simultaneously assess thrombosis biomarkers and lipid levels in patients with and without ISR.

Methods

Consecutive patients (n = 170) with a history of coronary stenting undergoing elective angiography were studied. Blood samples for thrombelastography, light transmittance aggregometry, and lipid levels were obtained prior to cardiac catheterization.

Results

Sixty‐nine patients (41%) had ISR (>50% luminal diameter stenosis). Among patients with ISR, 40 (58%) had ISR in more than one stent bed. Patients with ISR were more often female (37.7% vs. 21.8%, P = 0.04), had higher thrombin‐induced platelet‐fibrin clot strength (TIP‐FCS) (69.9 mm vs. 65.6 mm, P < 0.001), and a higher ApoB/A1 ratio (0.65 vs. 0.59, P = 0.03). In patients on dual antiplatelet therapy (n = 86), there were no differences in ADP‐, arachidonic acid‐, and collagen‐induced platelet aggregation between groups. The frequency of patients with ISR increased with TIP‐FCS quartiles and by ROC analysis, TIP‐FCS = 67.0 mm was the cutpoint for identification of ISR (AUC = 0.80 (95%CI 0.73–0.87, P < 0.0001). By multivariate analysis, TIP‐FCS ≥67.0 mm strongly associated with ISR (OR = 7.3, P = 0.004).

Conclusion

Patients with ISR identified at the time of cardiac catheterization have a prothrombotic phenotype indicated by high TIP‐FCS, a novel marker. Studies to confirm the prognostic utility of high TIP‐FCS for the development of ISR are ongoing. (J Interven Cardiol 2016;29:168–178)

     

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by beta-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

Sibutramine is a serotonin-noradrenaline reuptake inhibitor that is effective for long-term weight reduction and maintenance in obese patients when used as an adjunct to dietary and behavioural measures. Because the inhibition of noradrenaline reuptake may be expected to increase systolic and diastolic blood pressure (SBP and DBP) and pulse rate (PR), a 12-week multi-centre, placebo-controlled, double-blind study was designed to evaluate the efficacy and tolerability of sibutramine for weight loss in obese patients whose hypertension was well controlled (DBP < or = 95 mm Hg) by beta-adrenergic blocking agents (beta-blockers), with or without concomitant thiazide diuretics. Of the 61 patients randomised to sibutramine 20 mg once daily or placebo, 55 patients (90%) completed the study. After 12 weeks, sibutramine-treated patients lost significantly more weight than placebo-treated patients: mean weight reductions were 4.2 kg (4.5%) in the sibutramine group vs 0.3 kg (0.4%) in the placebo group (P<0.001). Greater weight reduction on sibutramine was accompanied by trends for greater mean reductions in serum triglycerides and very low density lipoprotein cholesterol. Sibutramine was well tolerated, and most adverse events were mild or moderate in severity. No sibutramine patient discontinued treatment because of an adverse event. Mean supine and standing DBP and SBP were not statistically significantly different between the sibutramine group and the placebo group at any post-baseline visit during the 12-week trial. At week 12, mean increases from baseline supine SBP and DBP, respectively, were 1.6 and 1.7 mm Hg for the sibutramine group vs increases of 0.4 and 1.3 mm Hg for the placebo group. At week 12, mean increases from baseline standing SBP and DBP, respectively, were 1.5 and 1.8 mm Hg for the sibutramine group vs an increase of 0.3 and a decrease of 0.8 mm Hg for the placebo group (P > 0.05 for treatment comparison). A statistically significant mean increase of 5.6 bpm (+/-8.25, s.d.) in supine PR from a baseline of 62 bpm was reported in sibutramine-treated patients at week 12, whereas placebo-treated patients had a mean supine PR decrease of 2.2 bpm (+/-6.43) (P < 0.001). In summary, sibutramine was well tolerated and effective in weight reduction. The addition of sibutramine did not result in an increase in BP in obese patients whose hypertension was well controlled by a beta-blocker. However, based on the potential for changes in BP and PR, obese patients being treated with sibutramine should be monitored periodically for changes in BP and PR and managed appropriately.     

Prevention,management and extent of adverse pregnancy outcomes in women with hereditary antithrombin deficiency

Antithrombin (AT) deficiency is a rare hereditary thrombophilia with a mean prevalence of 0.02 % in the general population, associated with a more than ten-fold increased risk of venous thromboembolism (VTE). Within this multicenter retrospective clinical analysis, female patients with inherited AT deficiency were evaluated concerning the type of inheritance and extent of AT deficiency, medical treatment during pregnancy and postpartally, VTE risk as well as maternal and neonatal outcome. Statistical analysis was performed with SPPS for Windows (19.0). A total of 18 pregnancies in 7 patients were evaluated, including 11 healthy newborns ≥37th gestational weeks (gw), one small for gestational age premature infant (25th gw), two late-pregnancy losses (21st and 28th gw) and four early miscarriages. Despite low molecular weight heparin (LMWH) administration, three VTE occurred during pregnancy and one postpartally. Several adverse pregnancy outcomes occurred including fetal and neonatal death, as well as severe maternal neurologic disorders occurred. Patients with substitution of AT during pregnancy in addition to LMWH showed the best maternal and neonatal outcome. Close monitoring with appropriate anticoagulant treatment including surveillance of AT levels might help to optimize maternal and fetal outcome in patients with hereditary AT deficiency.     

Risk factors associated with anaphylaxis and other allergic-like events following receipt of 2009 monovalent AS03-adjuvanted pandemic influenza vaccine in Quebec,Canada

Introduction

In Quebec, Canada, receipt of the 2009 AS03-adjuvanted pandemic H1N1 vaccine was associated with increased risk of anaphylaxis and other allergic-like events (ALE), especially among women of childbearing age. In response to this safety signal, a case–control study was conducted to identify potential risk factors.

Methods

A total of 435 ALE (50 anaphylaxis) occurring <24 h following pandemic vaccination were compared to 849 age-gender matched controls randomly selected from the provincial Pandemic Influenza Vaccination Registry. More than 60 potential risk factors were evaluated through phone interviews and included demographic information, medical history, medication use or acute respiratory illnesses (ARI) concurrent with vaccination and other risk factors associated with general allergy. Odds ratios (ORs) with 95% confidence intervals were estimated with unconditional logistic regression.

Results

Factors associated with increased risk of anaphylaxis included concurrent ARI (18% cases vs. 4% controls, ORadj 7.67, 95%CI: 3.04–13.37), food allergy (26% cases vs. 4% controls, ORadj 3.84, 95%CI: 1.51–9.74) and vaccination during the first four weeks of the campaign (66% cases vs. 50% controls, ORadj 2.16, 95%CI: 1.10–4.25) whereas alcohol exposure (≥1 drink/week) was associated with reduced risk (29% cases vs. 42% controls, ORadj 0.26, 95%CI: 0.13–0.57). These factors were also significantly associated with any ALE but the strength of association was weaker. Allergy to components found in the vaccine (e.g., egg, thimerosal) was infrequent and did not significantly differ between cases and controls.

Conclusion

Increased anaphylaxis and other allergic-like events observed in association with AS03-adjuvanted pandemic H1N1 vaccine remain mostly unexplained despite extensive risk factor review. However, prior to mass vaccination with similar formulations this safety signal warrants further consideration and better understanding. In particular, the predominance among women of childbearing age may be a clue to underlying biological or hormonal influences on adverse immunological responses to vaccine.     

Molecular Mechanisms Underlying the Nephroprotective Effects of PACAP in Diabetes

Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30–40 % of patients entering renal transplant programmes. The nephroprotective effects of the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP38) against diabetes have been shown previously, but the molecular mechanisms responsible for these effects remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2, showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-β1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect.