Peripheral arterial disease prevalence among sepsis hospitalizations and associated outcomes

Sepsis is common, deadly, and exacerbated by comorbid conditions. Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD) and peripheral artery disease (PAD), are risk factors for sepsis with minimal data on the association between PAD and outcomes. We aimed to evaluate the prevalence of ASCVD and the association between ASCVD and in-patient mortality and limb outcomes among sepsis hospitalizations.

We generated ASCVD prevalence estimates among survey-weighted adult sepsis hospitalizations within the National Inpatient Sample (2016-2020). We included hospitalizations with a primary diagnosis of sepsis and excluded nonadult patients (<18 years), and those with missing outcome data (ie, in-hospital mortality) and demographic data (ie, age, sex, and race/ethnicity). Associations between ASCVD and in-hospital mortality and major or transmetatarsal amputation among sepsis hospitalizations were evaluated using Cox regression, adjusting for demographics (age, sex, race/ethnicity, and income) and comorbidities (diabetes mellitus, end-stage renal disease, cerebrovascular disease, and hypertension). Subgroup analyses were conducted to assess moderation of the association between ASCVD and outcomes by antithrombotic therapy.

Of 174,776,160 estimated hospitalizations (age, mean ± standard error, 50 ± 0.2 years; 44% male; 65% White), 5.5% (5.5%-5.6%) had a primary diagnosis of sepsis (age 69 ± 0.1; 51% male; 70% White); of which, 9.5% (9.3%-9.6%) had a secondary diagnosis of PAD (age 73 ± 0.05; 58% male; 73% White). PAD was associated with 18% higher adjusted risk of in-hospital mortality (95% confidence interval [CI], 1.17-1.20) and 4.36 times the risk of major or transmetatarsal amputation (95% CI, 4.18-4.56). Sepsis hospitalizations with joint ASCVD had the highest risk of in-hospital mortality (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.31-1.36) compared with those with CAD alone (aHR, 1.25; 95% CI, 1.24-1.27) or PAD alone (aHR, 1.23; 95% CI, 1.21-1.26). Yet patients with PAD who were hospitalized for sepsis had a higher risk of in-hospital major or transmetatarsal amputation (aHR, 5.03; 95% CI, 4.76-5.32) compared with those with joint ASCVD (aHR, 3.89; 95% CI, 3.66-4.14); CAD was expectedly not associated with amputation (aHR, 1.05; 95% CI, 0.999-1.1). Subgroup analyses revealed significant interactions between ASCVD and antithrombotic therapy, such that, among those taking antithrombic therapy, the associations between ASCVD and in-hospital mortality (P < .001) and amputation (P < .05) were smaller when compared with the associations examined in the whole sample.

Sepsis and ASCVD are common and associated with a higher risk of adverse outcomes. PAD diagnosis occurred among 9.5% of sepsis hospitalizations and, mirroring CAD, increased the risk of in-hospital mortality by approximately 25%. Expectedly, PAD was associated with a higher risk of in-hospital amputation. Antithrombotic therapies, a staple of ASCVD medical optimization, reduced the risk of in-hospital amputation and mortality among patients with PAD hospitalized for sepsis. Medical optimization may improve outcomes in patients with sepsis and ASCVD.