Faculty Bibliography

Mechanisms explaining the link between psoriasis, a proinflammatory condition, and cardiovascular disease are not fully known. PCSK9 is predominantly expressed in hepatocytes as a critical regulator of lipid metabolism, and clinical trials targeting PCSK9 reduce cardiovascular disease. Independent of its role in lipid metabolism, PCSK9 levels associate with endothelial dysfunction and predict cardiovascular events. We used two separate human psoriasis cohorts and the K14-Rac1V12^-/+ murine model of psoriasis to investigate PCSK9 and cardiovascular risk in psoriasis. In both psoriasis cohorts (n = 88 and n = 20), PCSK9 levels were 20% and 13% higher than in age-, sex-, and cholesterol-matched controls, respectively (P < 0.05 for each comparison) and correlated with PASI (r = 0.43, P < 0.05). Despite no difference in hepatocyte expression, K14-Rac1V12^-/+ mice demonstrated skin-specific PCSK9 staining, which was confirmed in human psoriatic lesional skin. In patients with psoriasis, PCSK9 levels correlated with impaired endothelial vascular health (e.g., early atherosclerosis, β = 4.5, P < 0.01) and log converted coronary artery calcium score (β = 0.30, P = 0.01), which remained significant after adjustment for Framingham risk, body mass index, and active biologic use. Taken together, these findings suggest, independent of cholesterol, an association between circulating PCSK9 and early as well as advanced stages of atherosclerosis in psoriasis.

BACKGROUND:Perioperative cardiovascular events are a leading cause of morbidity and mortality after non-cardiac surgery. We propose a simplified method for perioperative risk stratification. METHODS:A retrospective cohort study identified patients undergoing non-cardiac surgery between 2009-2015 in the United States National Surgical Quality Improvement Program. Multivariable logistic regression models adjusted for age, sex, race and surgery type were generated to estimate the impact of traditional cardiovascular risk factors (hypertension, diabetes mellitus, current smoking) on odds of perioperative myocardial infarction (MI). Time to event analysis was conducted using competing risk analysis, with MI as the outcome event and death as the competing risk. RESULTS:A total of 3,848,501 non-cardiac surgeries were identified. Post-operative MI occurred in 0.37% of patients and 1.04% of patients died. The 30-day event rate of perioperative MI increased in a stepwise fashion with additional risk factors (0.41% for one, 0.81% for two, and 1.07% for three; P-for-trend < 0.001) after accounting for the competing risk of death. In comparison to those with no risk factors, patients with one, two and three risk factors had increased odds of MI (aOR 2.07; 95% CI 1.96-2.19; aOR 3.63 95% CI 3.43-3.85; aOR 5.54 95% CI 5.09-6.04). Perioperative MI was rare (0.10%) in patients without risk factors. CONCLUSIONS:Patients with cardiovascular risk factors are at increased risk of perioperative MI, those without risk factors are at low risk. Further evaluation is needed to determine the impact of a simplified risk score in the perioperative setting.

BACKGROUND:Heart failure (HF) affects ∼5.7 million United States adults and many of these patients develop non-cardiac disease that requires surgery. The aim of this study was to determine perioperative outcomes associated with HF in a large cohort of patients undergoing in-hospital non-cardiac surgery. METHODS:Adults ≥18 years old undergoing non-cardiac surgery between 2012-2014 were identified using the HCUP National Inpatient Sample. Patients with HF were identified by ICD-9 diagnosis codes. The primary outcome was all-cause in-hospital mortality. Multivariable logistic regression models were used to estimate associations between HF and outcomes. RESULTS:A total of 21,560,996 surgical hospitalizations were identified, of which 1,063,405 (4.9%) had a diagnosis of HF. Among hospitalizations with HF, 4.7% had acute HF, 11.3% had acute on chronic HF, 27.8% had chronic HF, and 56.2% had an indeterminate diagnosis code that did not specify temporality. In-hospital perioperative mortality was more common with a diagnosis of any HF compared to without HF (4.8% vs. 0.78%, p < 0.001; adjusted OR [aOR] 2.15 [95% CI 2.09-2.22]), and the association between HF and mortality was greatest at small and non-teaching hospitals. Acute HF without chronic HF was associated with 8.0% mortality. Among patients with a chronic HF diagnosis, perioperative mortality was greater in those with acute on chronic HF compared to chronic HF alone (7.8% vs. 3.9%, p < 0.001; aOR 1.78, 95% CI 1.67-1.90). CONCLUSION/CONCLUSIONS:In patients hospitalized for non-cardiac surgery, HF was common and was associated with increased risk of perioperative mortality. The greatest risks were in patients with acute HF.

Contemporary approaches to cardiovascular risk stratification before noncardiac surgery focus on macrovascular atherosclerotic disease and risk factors. We sought to determine the prevalence of microvascular disease (MVD) and its associated perioperative outcomes. Adults ≥18 years old undergoing noncardiac surgery between 2004 and 2014 were identified using the Nationwide Inpatient Sample (NIS). Prevalent MVD (retinopathy, neuropathy, and nephropathy) was identified by ICD-9 diagnosis codes. The primary outcomes were all-cause in-hospital mortality and the composite of major adverse cardiac events (MACE; death, myocardial infarction, and ischemic stroke). Multivariable logistic regression models were used to estimate associations between MVD and outcomes after adjusting for demographics and clinical covariates. Among 81,297,003 hospitalizations for noncardiac surgery, 4,236,932 (5.0%) had a diagnosis of MVD. Patients with MVD were older and more likely to have traditional cardiovascular risk factors. In-hospital perioperative MACE (4.1% vs. 1.9%; adjusted odds ratio [aOR] 1.15, 95% confidence interval [CI] 1.13 to 1.17) and mortality (2.0% vs. 1.1%; aOR 1.15, 95% CI 1.12 to 1.17) were greater in hospitalizations with MVD compared with those without. Microvascular disease was associated with postoperative outcomes in when stratified by age, sex, and coronary artery disease (CAD). Compared with surgical hospitalizations without CAD or MVD, MVD alone (aOR 1.12; 95% CI 1.11 to 1.14), CAD alone (aOR 1.44; 95% CI 1.42 to 1.46), and MVD with CAD (aOR 2.01; 95% CI 1.96 to 2.06) were associated with perioperative MACE. In conclusion, microvascular disease was present in 1 in 20 hospitalizations for noncardiac surgery, and was associated with perioperative mortality and MACE independent of macrovascular disease and traditional risk factors.

Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, particularly in patients with coronary artery disease (CAD). Although preoperative cardiac risk assessment can facilitate the identification of vulnerable patients and implementation of adequate preventive measures, excessive evaluation might lead to undue resource utilization and surgical delay. Owing to conflicting data, there remains some uncertainty regarding the most beneficial perioperative strategy for patients with CAD. Antithrombotic agents are the cornerstone of secondary prevention of ischaemic events but substantially increase the risk of bleeding. Given that 5-25% of patients undergoing coronary stent implantation require non-cardiac surgery within 2 years, surgery is the most common reason for premature cessation of dual antiplatelet therapy. Perioperative management of antiplatelet therapy, which necessitates concomitant evaluation of the individual thrombotic and bleeding risks related to both clinical and procedural factors, poses a recurring dilemma in clinical practice. Current guidelines do not provide detailed recommendations on this topic, and the optimal approach in these patients is yet to be determined. This Review summarizes the current data guiding preoperative risk stratification as well as periprocedural management of patients with CAD undergoing non-cardiac surgery, including those treated with stents.

AIM/UNASSIGNED:To assess the real-world healthcare resource utilization (HRU) and costs of patients with non-valvular atrial fibrillation (NVAF) and obesity newly initiated on rivaroxaban or warfarin in the US. METHODS/UNASSIGNED:values generated using non-parametric bootstrap procedures. RESULTS/UNASSIGNED: < .05). The rivaroxaban cohort also had lower NVAF-related HRU and medical costs driven by lower hospitalization at 12 months post-treatment initiation. HRU and cost reductions associated with rivaroxaban persisted up to 36 months of follow-up. LIMITATIONS/UNASSIGNED:Claims data may have contained inaccuracies and obesity was classified based on ICD diagnosis codes given that patient BMI values were not available. CONCLUSIONS/UNASSIGNED:Rivaroxaban was associated with reduced HRU and costs compared to warfarin among NVAF patients with obesity in a real-world US setting.

Background/UNASSIGNED:Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lower extremity peripheral artery disease (PAD) and suffering PAD-related morbidity and mortality. However, the effect and burden of COPD on patients with PAD is less well defined. This post hoc analysis from EUCLID aimed to analyze the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with PAD and concomitant COPD compared with those without COPD, and to describe the adverse events specific to patients with COPD. Methods/UNASSIGNED:EUCLID randomized 13,885 patients with symptomatic PAD to monotherapy with either ticagrelor or clopidogrel for the prevention of MACE. In this analysis, MACE, MALE, mortality, and adverse events were compared between groups with and without COPD using unadjusted and adjusted Cox proportional hazards model. Results/UNASSIGNED:Of the 13,883 patients with COPD status available at baseline, 11% (n=1538) had COPD. Patients with COPD had a higher risk of MACE (6.02 vs 4.29 events/100 patient-years; p<0.001) due to a significantly higher risk of myocardial infarction (MI) (3.55 vs 1.85 events/100 patient-years; p<0.001) when compared with patients without COPD. These risks persisted after adjustment (MACE: adjusted hazard ratio (aHR) 1.30, 95% confidence interval [CI] 1.11-1.52; p<0.001; MI: aHR 1.45, 95% CI 1.18-1.77; p<0.001). However, patients with COPD did not have an increased risk of MALE or major bleeding. Patients with COPD were more frequently hospitalized for dyspnea and pneumonia (2.66 vs 0.9 events/100 patient-years; aHR 2.77, 95% CI 2.12-3.63; p<0.001) and more frequently discontinued study drug prematurely (19.36 vs 12.54 events/100 patient-years; p<0.001; aHR 1.34, 95% CI 1.22-1.47; p<0.001). Conclusion/UNASSIGNED:In patients with comorbid PAD and COPD, the risks of MACE, respiratory-related adverse events, and premature study drug discontinuation were higher when compared with patients without COPD. Registration/UNASSIGNED:ClinicalTrials.gov: NCT01732822.