Usefulness of hypertensive blood pressure response during a single-stage exercise test to predict long-term outcome in patients with peripheral arterial disease

The prognostic value of a hypertensive blood pressure (BP) response is still unclear. Therefore, the prognostic value of a hypertensive BP response in patients during single-stage exercise testing for peripheral arterial disease (PAD) on long-term mortality and major adverse cerebrovascular and cardiac events (MACCEs) was investigated. In addition, effects of statin, beta-blocker, and aspirin use in patients with known or suspected PAD were studied. A total of 2,109 patients were enrolled in an observational prospective study from 1993 to 2005. Hypertensive BP response was defined as an increase in systolic BP >/=55 mm Hg (95(th) percentile within our population) after a single-stage treadmill exercise test. The outcome was obtained by using the civil registries, and a questionnaire about cardiac events was sent to all survivals. Hypertensive BP response was associated with increased risk of long-term mortality (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.12 to 1.80) and MACCEs (HR 1.47, 95% CI 1.09 to 1.97). After adjustments for clinical risk factors and propensity score, baseline statin use was associated with reduced risk of long-term mortality (HR 0.59, 95% CI 0.44 to 0.79), and statin, beta-blocker, and aspirin use were associated with reduced risk of MACCEs (HR 0.59, 95% CI 0.43 to 0.81; HR 0.75, 95% CI 0.60 to 0.95; HR 0.73, 95% CI, 0.57 to 0.92, respectively). In conclusion, hypertensive BP response at exercise in patients with known or suspected PAD is an important independent risk factor for all-cause long-term mortality and MACCEs, whereas statin, beta-blocker, and aspirin use were associated with an improved outcome.     

Alterations of Granulopoiesis Following Chemotherapy

Clonal proliferation of marrow granulocytic progenitor cells (GPC) in vitro andthe daily urinary output of granulocyticcolony-stimulating factor (CSF) were determined in two patients with acutemyeloid leukemia (AML) in remission andone patient with malignant lymphoma receiving monthly pulses of chemotherapywith cytosine arabinoside and 6-thioguanine. During and immediately following therapy, a marked decrease of granulocytic colony-forming capacity (CFC)occurred, with an increase and return tobasal levels by 3-4 wk. In the AMLpatients, the proportion of GPC in DNAsynthesis (GPC-S), as determined by thethymidine suicide technique, declinedfrom basal levels (31%-39%) to 0%-26% after 2 days of treatment. This wasfollowed by a sharp rise in GPC-S to41%-75% 1-3 days posttherapy, with anoscillatory return of GPC-S to basal levelsby 3-4 wk. In all courses a marked increase of urinary CSF output occurredduring or 1 day posttherapy, concomitantwith the rise of the proportion of GPC-S.In the lymphoma patient, an initially highproportion of marrow GPC-S and low CFCanticipated the severe neutropenia whichfollowed therapy. These results provide abasis for determining the efficacy withwhich cytotoxic drugs destroy proliferativeactivity of GPC and for assessing thepotential for hemopoietic toxicity following chemotherapy.

Submitted on August 10, 1973 Accepted on February 27, 1974     

Diagnosis and mortality prediction in pulmonary hypertension: the value of the electrocardiogram-derived ventricular gradient

PurposeThe aim of this study was to investigate the use of the electrocardiogram-derived ventricular gradient, projected on the x-axis (VGx), for detection of pulmonary hypertension (PH) and for prediction of all-cause mortality in PH patients.MethodsIn patients referred for PH screening (n = 216), the VGx was calculated semiautomatically from the electrocardiogram and was defined as abnormal when less than 24 mV·ms. The VGx of PH patients was compared with the VGx of patients without PH. The association between a reduced VGx and mortality was investigated in PH patients.ResultsPatients with PH (n = 117) had a significantly reduced VGx: 14 ± 27 vs 45 ± 23 mV·ms, P < .001. Furthermore, a severely reduced VGx (<0 mV·ms) was associated with increased mortality in PH patients: hazard ratio, 1.025 (95% confidence interval, 1.006-1.045; P = .012) per mV·ms VGx decrease.ConclusionReduced VGx is associated with the presence of PH and, more importantly, within PH patients, a severely reduced VGx predicts mortality.     

Matrix production and remodeling capacity of cardiomyocyte progenitor cells during in vitro differentiation

Cell-based therapy has emerged as a treatment modality for myocardial repair. Especially cardiac resident stem cells are considered a potential cell source since they are able to differentiate into cardiomyocytes and have improved heart function after injury in a preclinical model for myocardial infarction. To avoid or repair myocardial damage it is important not only to replace the lost cardiomyocytes, but also to remodel and replace the scar tissue by "healthy" extracellular matrix (ECM). Interestingly, the role of cardiac stem cells in this facet of cardiac repair is largely unknown. Therefore, we investigated the expression and production of ECM proteins, matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in human cardiomyocyte progenitor cells (CMPCs) undergoing differentiation towards the cardiomyogenic lineage. Our data suggest that CMPCs have the capacity to synthesize and modulate their own matrix environment, especially during differentiation towards the cardiomyogenic lineage. While undifferentiated CMPCs expressed collagen I, III, IV and fibronectin, but no elastin, during the process of differentiation the expression of collagen I, III, IV and fibronectin increased and interestingly also elastin expression was induced. Furthermore, undifferentiated CMPCs express MMP-1 -2 and -9 and upon differentiation the expression of MMP-1 decreased, while the expression of MMP-2 and MMP-9, although the latter only in the early stage of differentiation, increased. Additionally, the expression of TIMP-1, -2 and -4 was induced during differentiation. This study provides new insights into the matrix production and remodeling capacity of human CMPCs, with potential beneficial effects for the treatment of cardiac injury.