Frequency of left ventricular hypertrophy in non-valvular atrial fibrillation

Left ventricular hypertrophy (LVH) is significantly related to adverse clinical outcomes in patients at high risk of cardiovascular events. In patients with atrial fibrillation (AF), data on LVH, that is, prevalence and determinants, are inconsistent mainly because of different definitions and heterogeneity of study populations. We determined echocardiographic-based LVH prevalence and clinical factors independently associated with its development in a prospective cohort of patients with non-valvular (NV) AF. From the "Atrial Fibrillation Registry for Ankle-brachial Index Prevalence Assessment: Collaborative Italian Study" (ARAPACIS) population, 1,184 patients with NVAF (mean age 72 \ub1 11 years; 56% men) with complete data to define LVH were selected. ARAPACIS is a multicenter, observational, prospective, longitudinal on-going study designed to estimate prevalence of peripheral artery disease in patients with NVAF. We found a high prevalence of LVH (52%) in patients with NVAF. Compared to those without LVH, patients with AF with LVH were older and had a higher prevalence of hypertension, diabetes, and previous myocardial infarction (MI). A higher prevalence of ankle-brachial index 640.90 was seen in patients with LVH (22 vs 17%, p = 0.0392). Patients with LVH were at significantly higher thromboembolic risk, with CHA2DS2-VASc 652 seen in 93% of LVH and in 73% of patients without LVH (p <0.05). Women with LVH had a higher prevalence of concentric hypertrophy than men (46% vs 29%, p = 0.0003). Logistic regression analysis demonstrated that female gender (odds ratio [OR] 2.80, p <0.0001), age (OR 1.03 per year, p <0.001), hypertension (OR 2.30, p <0.001), diabetes (OR 1.62, p = 0.004), and previous MI (OR 1.96, p = 0.001) were independently associated with LVH. In conclusion, patients with NVAF have a high prevalence of LVH, which is related to female gender, older age, hypertension, and previous MI. These patients are at high thromboembolic risk and deserve a holistic approach to cardiovascular prevention

Regulation of NF-kappa B nuclear activity in peripheral blood mononuclear cells: role of CD28 antigen.

The NF-kappa B/rel family of transcription factors regulates the expression of a number of genes, including interleukin 2 (IL-2), IL-2 receptor alpha chain (Tac), and others, controlling T lymphocyte activation. The CD28 antigen is involved in regulation of T cell activation. To investigate whether CD28 antigen regulates NF-kappa B factors, we analyzed the effect of an anti-CD28 monoclonal antibody (mAb), CLB-CD28/1, on the nuclear activity of NF-kappa B complexes in resting and CD3-activated peripheral blood mononuclear cells (PBMC) of 11 donors. Cells were incubated with or without the anti-CD3 mAb OKT3 and/or the mAb CLB- CD28/1. Then nuclear extracts were obtained and analyzed for their binding to a 32P-labeled oligonucleotide, corresponding to the NF-kappa B 5'-CAACGGCAGGGGAATCTCCCTCTCCTT-3' consensus sequence in electrophoretic mobility shift assays. PBMC incubated with control medium did not appear to contain significant levels of NF-kappa B nuclear activity. The anti-CD28 mAb did not induce any detectable NF-kappa B nuclear activity in PBMC when used alone, except for two cases. However, cells incubated with the anti-CD3 mAb displayed NF-kappa B nuclear activity in 7 of the 11 cases. The addition of anti-CD28 to the anti-CD3 mAb-stimulated cells enhanced the levels of NF-kappa B activity in eight PBMC, while it did not modify PBMC in one sample and partially inhibited the induction of NF-kappa B in the remaining two samples. The stimulatory effect of anti-CD28 mAb on NF-kappa B nuclear activity was detected also on CD3-stimulated purified T lymphocytes. By analysis with antisera recognizing the p50 and p65 components of the NF-kappa B/rel family, NF-kappa B complexes of CD3+CD28-stimulated PBMC were found to contain both p50 and p65 proteins. An enhanced production of IL-2 was detected in cultures of CD3+CD28-stimulated PBMC. Our results indicate that CD28 triggering can modulate the activity on NF-kappa B nuclear complexes in T lymphocytes stimulated via CD3. Such an effect appeared not to require the presence of accessory cells (AC) or AC-derived cytokines

Defect of interleukin-2 production and T cell proliferation in atopic patients: restoring ability of the CD28-mediated activation pathway

We previously reported that T lymphocytes of atopic patients displayed a defect in CD2- and CD3-mediated pathways of cell activation; that defect relied on impairment of interleukin 2 (IL-2) production (Romano, M. F., Valerio, G., Turco, M. C., Spadaro, G., Venuta, S., and Formisono, S., Cell. Immunol. 139, 91, 1992). We have subsequently analyzed T cell response to anti-CD2, -CD3, or -CD28 monoclonal antibodies (mAb) in 40 atopic individuals, including patients subjected to immunotherapy. In the latter group T cell response to anti-CD2 mAbs was normal, while IL-2 production and proliferative response in T lymphocytes stimulated via CD3 was still impaired. Costimulation with anti-CD28 mAb rescued both IL-2 production and proliferative response in all tested patients. Response to CD28-mediated stimulation was more pronounced in atopic than that in normal individuals. Our results indicated that CD28 had a major role in T cell proliferation of atopic patients and provided a model for analyzing CD3/CD28 interactions in regulation of IL-2 gene expressio