Toward a Cardio-Environmental Risk Model: Environmental Determinants of Cardiovascular Disease.

It is increasingly recognized that strong geographic variations in cardiovascular risk cannot be explained using traditional cardiovascular risk factors alone. Indeed, it is highly unlikely that heredity and classic risk factors such as hypertension, diabetes, dyslipidemia, and tobacco use can explain the tenfold variation observed in cardiovascular mortality among men in Russia and those in Switzerland. Since the advent of industrialization and resultant changes to our climate, it is now clear that environmental stressors also influence cardiovascular health and our thinking around cardiovascular risk prediction is in need of a paradigm shift. Herein, we review the basis for this shift in our understanding of the interplay of environmental factors with cardiovascular health. We illustrate how air pollution, hyperprocessed foods, the amount of green space, and population activity levels are now considered the 4 major environmental determinants of cardiovascular health and provide a framework for how these considerations might be incorporated into clinical risk assessment. We also outline the clinical and socioeconomic effects of the environment on cardiovascular health and review key recommendations from major medical societies.

Analysis of the COMPARE-AMI trial: First report of long-term safety of CD133+ cells.

BACKGROUND: Data related to long-term safety of intracoronary (IC) injection of CD133+ bone marrow stem cells (BMSC) following an acute myocardial infarction (MI) are still lacking. METHODS: COMPARE-AMI is a double-blind, placebo-controlled phase II clinical trial evaluating the safety and efficacy of IC injection of CD133+ enriched hematopoietic BMSC in patients with ST-elevation myocardial infarction (STEMI) and persistent left ventricular (LV) dysfunction following successful primary percutaneous coronary intervention (PCI). Herein, we report outcomes up to ten years of follow-up. RESULTS: Between November 2007 and July 2012, we enrolled 38 patients in our study. Males were 89% and the median age was 50.5 years. Baseline left ventricular ejection fraction (LVEF) was 40.0%, and 90% of lesions were located in the left anterior descending (LAD) artery. The median follow-up time was 8.5 years IQR [7.9, 10.0]. Using Kaplan-Meier methods, MACE-free survival up to 10 years was 77.3% overall. IC injection of CD133+ BMSC was associated with a similar event-free survival rate compared to placebo (87.8% vs. 66.3%, p = .37). Two cancer cases in each group were recorded. No malignant arrhythmias were observed. CONCLUSIONS: IC injection of CD133+ BMSC is safe up to 10 years of follow-up. The long-term efficacy needs to be confirmed by a larger randomized trial.

Impact of intracoronary injection of CD133+ bone marrow stem cells on coronary atherosclerotic progression in patients with STEMI: a COMPARE-AMI IVUS substudy.

OBJECTIVES: Adverse effects of intracoronary injection of stem cells on in-stent restenosis and atherosclerotic progression remain unclear. We sought to evaluate the adverse effects of intracoronary injection of CD133 cells on in-stent restenosis and atherosclerotic progression in the infarct-related and contralateral arteries using serial intravascular ultrasound (IVUS) analysis. METHODS: Baseline and 4-month follow-up IVUS images were obtained from 17 patients treated with intracoronary stem cell injection and 20 placebo patients after primary percutaneous coronary intervention in the COMPARE-AMI trial. In the infarct-related artery, the stented segment, 5 mm proximal and distal reference segments, and proximal and distal nonstented segments were analyzed every 1 mm; the entire segment of a contralateral artery was also analyzed every 1 mm. RESULTS: In the infarct-related artery analysis, the median percentage of in-stent neointimal hyperplasia (12.1 vs. 7.6%, P=0.95), the reduction in the minimum lumen area (MLA; -1.6 vs. -1.5 mm(2), P=0.97), and the MLA at follow-up (4.3 vs. 5.3 mm(2), P=0.21) were found to be similar between the stem cell and placebo groups. Changes in proximal and distal nonstented segment lumen areas and plaque burden were also similar between the stem cell and placebo groups; however, there was a decrease in the maximum arc of the attenuated plaque behind the stent from baseline to follow-up in the placebo group (P=0.004), but not in the stem cell group. In the contralateral artery, there were no differences in changes in MLA, plaque burden, or attenuated plaque between stem cell and placebo patients. CONCLUSION: Intracoronary injection of CD133(+) bone marrow stem cells has no IVUS-detectable effect on neointimal hyperplasia or atherosclerosis progression in either infarct-related or contralateral arteries.

One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133 Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction.

Bone marrow stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium. Despite initial excitement, recent clinical trials using non-homogenous stem cells preparations showed variable and mixed results. Selected CD133(+) hematopoietic stem cells are candidate cells with high potential. Herein, we report the one-year safety analysis on the initial 20 patients enrolled in the COMPARE-AMI trial, the first double-blind randomized controlled trial comparing the safety, efficacy, and functional effect of intracoronary injection of selected CD133(+) cells to placebo following acute myocardial infarction with persistent left ventricular dysfunction. At one year, there is no protocol-related complication to report such as death, myocardial infarction, stroke, or sustained ventricular arrhythmia. In addition, the left ventricular ejection fraction significantly improved at four months as compared to baseline and remained significantly higher at one year. These data indicate that in the setting of the COMPARE-AMI trial, the intracoronary injection of selected CD133(+) stem cells is secure and feasible in patients with left ventricle dysfunction following acute myocardial infarction.

COMPARE-AMI trial: comparison of intracoronary injection of CD133+ bone marrow stem cells to placebo in patients after acute myocardial infarction and left ventricular dysfunction: study rationale and design.

Stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium, to treat or prevent cardiac failure, and to restore lost cardiac function. Despite initial excitement, recent clinical trials using nonhomogenous human stem cells preparations showed variable results, raising concerns about the best cell type to transplant. Selected CD133(+) hematopoietic stem cells are promising candidate cells with great potential. COMPARE-acute myocardial infarction (AMI) study is a phase II, randomized, double-blind, placebo-controlled trial evaluating the safety and effectiveness of intracoronary CD133(+)-enriched hematopoietic bone marrow stem cells in patients with acute myocardial infarction and persistent left ventricular dysfunction. Patients who underwent successful percutaneous coronary intervention and present a persistent left ventricular ejection fraction <50% will be eligible to have bone marrow aspiration and randomized for intracoronary injection of selected CD 133(+) bone marrow cells vs placebo. The primary end point is a composite of a safety and efficacy end points evaluating the change at 4 months in the coronary atherosclerotic burden progression proximal and distal to the coronary stent in the infarct related artery; and the change in global left ventricular ejection fraction at 4 months relative to baseline as measured by magnetic resonance imaging. The secondary end point will be the occurrence of a major adverse cardiac event. To date, 14 patients were successfully randomized and treated without any protocol-related complication. COMPARE-AMI trial will help identify the effect of a selected population of the bone marrow stem cells on cardiac recovery of infarcted myocardium.