Cardiovascular disease remains the number one cause of death in the United States and its incidence is increasing worldwide. Incident cardiovascular disease events differ amongst different geographical regions despite adjustments for many confounders including patient level characteristics and concomitant co-morbidities. While the exact mechanism for such geographical variations is unclear, a potential cause could be related to some feature or features of the environment in which one lives. More recently, neighborhood socioeconomic status and pollution have been linked to cardiovascular disease and outcomes. However, the potential mechanisms by which these contextual risk factors lead to adverse cardiovascular outcomes in unknown. The overall goal of this project is to identify potential pathways by which these two distinct environmental factors are associated with all-cause mortality. Specific Aim 1 is to investigate the association between neighborhood of residence, physiological measures (functional capacity and heart rate recovery) and all-cause mortality. Specifically, I hypothesized that functional capacity would explain a significant portion of the attributed mortality risk from Neighborhood SES. Aim 2 is to examine the association between pollution, Neighborhood SES and all-cause mortality. I hypothesized that Neighborhood SES would fully or partially mediate the association between pollution and all-cause mortality. Aim 3 is to investigate the association between levels of pollutant PM2.5 (independent variable) and functional capacity (dependent variable), while accounting for Neighborhood and individual level of SES as confounders. I hypothesized that Neighborhood SES would fully or partially mediate the association between pollution and functional capacity. Additionally, I studied the interrelationship between pollution, Neighborhood SES, functional capacity, and all-cause mortality. Taken together, these studies may identify potentially distinct mediating pathways by which environmental risk factors lead to all-cause mortality. Such findings could potentially enhance our current ability to explain income-related disparities in cardiovascular disease outcomes. More importantly, however, such insights will provide even greater justification for interventions that interrupt these pathways both at the individual level (i.e., improving functional status) and at the community level (e.g., through the reduction of environmental stimuli).

Abstract: Objectives The goal of this study was to evaluate the 5-year follow-up data of the IN.PACT DEEP (Randomized IN.PACT Amphirion Drug-Coated Balloon [DCB] vs. Standard Percutaneous Transluminal Angioplasty [PTA] for the Treatment of Below-the-Knee Critical Limb Ischemia [CLI]) trial. Background Initial studies from randomized controlled trials have shown comparable short-term outcomes of DCB angioplasty versus PTA in patients with CLI with infrapopliteal disease. However, the long-term safety and effectiveness of DCB angioplasty remain unknown in this patient population. Methods IN.PACT DEEP was an independently adjudicated prospective, multicenter, randomized controlled trial that enrolled 358 subjects with CLI. Subjects were randomized 2:1 to DCB angioplasty or PTA. Assessments through 5 years included freedom from clinically driven target lesion revascularization, amputation, and all-cause death. Additional assessments were conducted to identify risk factors for death and major amputation, including paclitaxel dose tercile. Results Freedom from clinically driven target lesion revascularization through 5 years was 70.9% and 76.0% (log-rank p = 0.406), and the incidence of the safety composite endpoint was 59.8% and 57.5% (log-rank p = 0.309) in the DCB angioplasty and PTA groups, respectively. The rate of major amputation was 15.4% for DCB angioplasty compared with 10.6% for PTA (log-rank p = 0.108). Given the recent concern regarding a late mortality signal in patients treated with paclitaxel-coated devices, additional analyses from this study showed no increase in all-cause mortality with DCB angioplasty (39.4%) compared with PTA (44.9%) (log-rank p = 0.727). Predictors of mortality included age, Rutherford category >4, and previous revascularization but not paclitaxel by dose tercile. Conclusions Tibial artery revascularization in patients with CLI using DCB angioplasty resulted in comparable long-term safety and effectiveness as PTA. Paclitaxel exposure was not related to increased risk for amputation or all-cause mortality at 5-year follow-up. (Study of IN.PACT AmphirionTM Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733)