Date of Award

January 2022

Document Type


Degree Name

Medical Doctor (MD)



First Advisor

Carlos Mena-Hurtado


ABSTRACTBackground: Previous studies on select populations have shown worsened limb outcomes among patients with comorbid Peripheral artery disease (PAD) and Microvascular disease (MVD), however this connection has not been studied in larger populations. Using a national database, we aimed to analyze the frequency of Major Adverse Limb Events (MALE), as well as Major Adverse Cardiac Events (MACE), Mortality, and other comorbidities for patients with comorbid PAD/MVD, as compared to patients with PAD or MVD alone. Methods: Using 2011 to 2018 National Readmission Database (NRD) data, we identified the frequency of PAD and MVD-related admissions based on ICD-9/10 codes. The primary outcomes of interest were MALE, MACE, and mortality, while secondary outcomes were length of stay and hospitalization cost. Patient socio-demographic characteristics, including age, gender, insurance and household income; and comorbidities were compared by disease group using standardized differences, with values of d≥0.20 equivalent to a small effect size or larger highlighted. Outcomes were stratified by disease status (PAD-only, MVD-only, and comorbid PAD+MVD), with MVD-only patients serving as the reference group. Results: There were 21,270,666 MVD-only, 9,133,256 PAD-only, and 3,568,847 comorbid PAD/MVD-related hospitalizations from 2011 to 2018. There were no significant differences in age or sex between all three groups (d<0.20). Patients with MVD-only had rates of 7.71%, 67.44%, 55.70%, 2.22% for CLI, Diabetes, Renal failure, and prior amputation respectively. Compared to them, PAD-only patients’ rates were 15.35%, 38.59%, 25.08%, and 7.62% (d=0.43, -0.66, -0.73, 0.71 respectively). Comorbid patients’ rates were 29.81%, 80.38%, 62.72%, and 16.17% (d=0.90, 0.38, 0.16, 1.18 for MVD-only vs PAD+MVD, while for PAD-only vs PAD+MVD d=0.47, 1.03, 0.89, 0.47). From 2011 to 2018 there was a 20% increase in MVD-only admissions from 2,478,490 to 2,968,604. Similarly, PAD-only rose by 29% from 1,028,521 to 1,353,793, while the PAD+MVD group increased by 28% from 397,326 to 507,404 (Ptrend <.0001). Conclusion: Patients with comorbid PAD/MVD have higher rates of comorbidities such as diabetes, renal disease, and CLI. They also have significantly worse rates of limb amputation, and slightly worse rates of MACE. We have shown that the diagnosis of MVD significantly increases the chances of minor and major amputation for PAD patients. Moreover, MVD also results in small but significant increase in the risk of MACE, and in an increased likelihood of hospital readmission. Identifying this subgroup of patients could be critical in improving limb outcomes. Future efforts in screening PAD patients for microvascular disease could help decrease amputation rates and potentially have a modest improvement in major adverse cardiovascular events as well.


This thesis is restricted to Yale network users only. It will be made publicly available on 06/16/2023