Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.

BACKGROUND: Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association. METHODS: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis. FINDINGS: Of 21 eligible studies, 16 with 36,984 participants were included. During a mean follow-up of 7·0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0·97 (95% CI 0·94-1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95-1·01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1·16, 95% CI 1·10-1·22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0·06 and r=-0·02). INTERPRETATION: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials. FUNDING: Deutsche Forschungsgemeinschaft.

Current trends in hematopoietic stem cell transplantation in Europe.

Major changes have occurred in the transplantation of hematopoietic stem cells (HSCs) during the last decade. This report reveals the changes, reflects current status, and provides medium-term projections of HSC transplantation (HSCT) development in Europe. Data on 132 963 patients, 44 165 with allogeneic HSC transplant (33%) and 88 798 with an autologous HSC transplant (67%), collected prospectively from 619 centers by the European Group for Blood and Marrow Transplantation (EBMT) in 35 European countries between 1990 (4234 HSCTs) and 2000 (19 136 HSCTs) illustrate utilization of HSCT. HSCT increased in all European countries and for all indications. There were major differences depending on disease indication and donor type. Transplantation rates (numbers of HSCTs per 10 million inhabitants) varied from less than 1 for some rare indications to 37.7 +/- 4.1 for acute myeloid leukemia in allogeneic HSCT or 95.5 +/- 13.5 for non-Hodgkin lymphoma in autologous HSCT. There were indications with a steady, continuing increase and others with initial increase but subsequent decrease. Projections on medium-term development for each disease based on a weighted sensitivity analysis predict an ongoing increase in allogeneic HSCT except for chronic myeloid leukemia. In autologous HSCT they predict an increase for lymphoproliferative disorders, acute myeloid leukemia, myelodysplastic syndromes, and some solid tumors but a decrease for most solid tumors, acute lymphoid leukemia, and chronic myeloid leukemia. Transplantation rates can be predicted with reasonable sensitivity for most disease indications. Despite marked changes in the rapidly developing field of HSCT, this information on current use, trends, and midterm predictions forms a rational basis for patient counseling and health care planning.