Faculty Bibliography

BACKGROUND:Acute limb ischemia (ALI) is an important clinical event and an emerging cardiovascular clinical trial outcome. Risk factors for and outcomes after ALI have not been fully evaluated. METHODS:EUCLID randomized patients with peripheral artery disease (PAD) to ticagrelor versus clopidogrel. Enrollment criteria included an ankle-brachial index (ABI) ≤0.80 or prior lower extremity revascularization. Patients were grouped according to the primary outcome, post-randomization ALI hospitalization. Baseline factors associated with ALI were identified using Cox proportional hazards modeling. Models with ALI hospitalization as a time-dependent covariate were developed for secondary outcomes of major adverse cardiovascular events (MACE: myocardial infarction, cardiovascular death, ischemic stroke), all-cause mortality, and major amputation. RESULTS:Among 13,885 patients, 1.7% (n=232) had 293 ALI hospitalizations (0.8 per 100 patient-years). Patients with versus without ALI were younger and more often had prior peripheral revascularization and lower baseline ABI. Treatment during ALI hospitalization included endovascular revascularization (39.2%, n=115), surgical bypass (24.6%, n=72), and major amputation (13.0%, n=38). After multivariable adjustment, any prior peripheral revascularization (HR 4.7, 95% CI 3.3-6.8, p<0.01), baseline atrial fibrillation (HR 1.8, 95% CI 1.1-3.2, p=0.03), and baseline ABI ≤0.60 (HR 1.3 per 0.10 decrease, 95% CI 1.1-1.5, p<0.01) were associated with higher ALI risk. Older age (HR 0.8 per 10-year increase, 95% CI 0.7-1.0, p=0.02) and baseline statin use (HR 0.7, 95% CI 0.5-0.9, p<0.01) were associated with lower risk for ALI. There was no relationship between randomized treatment to ticagrelor or clopidogrel and ALI. Among patients with prior revascularization, surgical versus endovascular procedures performed more than 6 months prior were associated with ALI (adjusted HR 2.63, 95% CI 1.75-3.96). In the overall population, ALI hospitalization was associated with subsequent MACE (adjusted HR 1.4, 95% CI 1.0-2.1, p=0.04), all-cause mortality (adjusted HR 3.3, 95% CI 2.4-4.6, p<0.01), and major amputation (adjusted HR 34.2, 95% CI 9.7-20.8, p<0.01). CONCLUSIONS:Prior peripheral revascularization, baseline atrial fibrillation, and lower ABI identify PAD patients at heightened risk for ALI, an event associated with subsequent cardiovascular and limb-related morbidity and mortality. CLINICAL TRIAL REGISTRATION/BACKGROUND:URL: https://clinicaltrials.gov Unique Identifier: NCT01732822.

OBJECTIVE:To assess the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its individual phenotypes of coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease by age and sex in a large US cohort of hospitalized patients with systemic lupus erythematosus (SLE). METHODS:A nested case-control study of adults with and without SLE was conducted from the January 1, 2008, through December 31, 2014, National Inpatient Sample. Hospitalized patients with SLE were matched (1:3) by age, sex, race, and calendar year to hospitalized patients without SLE. The prevalences of CAD, PAD, and cerebrovascular disease were evaluated, and associations with SLE were determined after adjustment for common cardiovascular risk factors. RESULTS:Among the 252,676 patients with SLE and 758,034 matched patients without SLE, the mean age was 51 years, 89% were women, and 49% were white. Patients with SLE had a higher prevalence of ASCVD vs those without SLE (25.6% vs 19.2%; OR, 1.45; 95% CI, 1.44-1.47; P<.001). After multivariable adjustment, SLE was associated with a greater odds of ASCVD (adjusted odds ratio [aOR], 1.46; 95% CI, 1.41-1.51). The association between SLE and ASCVD was observed in women and men and was attenuated with increasing age. Also, SLE was associated with increased odds of CAD (aOR, 1.42; 95% CI, 1.40-1.44), PAD (aOR, 1.25; 95% CI, 1.22-1.28), and cerebrovascular disease (aOR, 1.68; 95% CI, 1.65-1.71). CONCLUSION/CONCLUSIONS:In hospitalized US patients, SLE was associated with increased ASCVD prevalence, which was observed in both sexes and was greatest in younger patients.

BACKGROUND:The impact of thrombocytopenia on revascularization and outcomes in patients presenting with acute myocardial infarction remains poorly understood. We sought to evaluate associations between thrombocytopenia, in-hospital management, bleeding, and cardiovascular outcomes in patients hospitalized for acute myocardial infarction in the United States. METHODS:Patients hospitalized from 2004 to 2014 with a primary diagnosis of acute myocardial infarction were identified from the National Inpatient Sample. Management of acute myocardial infarction was compared between patients with and without thrombocytopenia. Multivariable logistic regression models were used to estimate odds of in-hospital adverse events stratified by thrombocytopenia and adjusted for demographics, cardiovascular risk factors, comorbidities, and treatment. RESULTS:A total of 6,717,769 patients were hospitalized with a primary diagnosis of acute myocardial infarction and thrombocytopenia was reported in 219,351 (3.3%). Patients with thrombocytopenia were older, more likely to have other medical comorbidities, were more likely to undergo coronary artery bypass grafting (28.8% vs. 8.2%, p<0.001), and were less likely to receive a drug eluting stent (15.5% vs. 29.5%, p<0.001). After multivariable adjustment, thrombocytopenia was independently associated with nearly two-fold increased odds of in-hospital mortality (aOR 1.91, 95% CI 1.86-1.97). Thrombocytopenia was also independently associated with ischemic stroke, cardiogenic shock, cardiac arrest and bleeding complications. CONCLUSIONS:Patients with thrombocytopenia in the setting of acute myocardial infarction had increased odds of bleeding, cardiovascular outcomes, and mortality compared with patients without thrombocytopenia. Future investigations to mitigate the poor prognosis of patients with acute myocardial infarction and thrombocytopenia are warranted.

BACKGROUND:Prior registry data suggest that 4%-20% of patients require noncardiac surgery (NCS) within 2 years of percutaneous coronary intervention (PCI). Contemporary data on NCS after PCI in the United States among women and men are limited. We determined the rate of early hospital readmission for NCS and associated outcomes in a large cohort of patients who underwent PCI in the United States. METHODS:Adults undergoing PCI between January 1 and June 30, 2014, were identified from the Nationwide Readmission Database. Patients readmitted for NCS within 6 months of PCI were identified. Outcomes of interest were in-hospital death, myocardial infarction (MI), and bleeding defined by International Classification of Diseases, Ninth Revision, codes. RESULTS:Among 221,379 patients who underwent PCI and survived to hospital discharge, 3.5% (n = 7,696) were readmitted for NCS within 6 months post-PCI, and 41% of these hospitalizations were elective. Early NCS was complicated by MI in 4.7% of cases, and 21% of perioperative MIs were fatal. Bleeding was recorded in 32.0% of patients. All-cause mortality occurred in 4.4% of patients (n = 339) readmitted for surgery. The risk of death or MI was greatest when NCS was performed within the first month after PCI. CONCLUSIONS:Despite clear guidelines to avoid surgery early after PCI, NCS was performed in 1 of every 29 patients with recent PCI, corresponding to as many as ~30,000 patients each year nationwide. Surgical mortality and perioperative MI were high in this setting. Strategies to minimize perioperative thrombotic and bleeding risks during readmission for NCS after PCI are necessary.

Background and Purpose- Perioperative stroke is associated with significant morbidity and mortality. Conventional cardiovascular risk scores have not been compared to predict acute stroke after noncardiac surgery. Methods- Patients undergoing noncardiac surgery between 2009 and 2010 were identified from the US National Surgical Quality Improvement Program (n=540 717). Patients were prospectively followed for 30 days postoperatively for the primary outcome of stroke. Established cardiovascular and perioperative risk scores (CHADS₂, CHA₂DS₂-VASc, Revised Cardiac Risk Index, Mashour et al risk score, Myocardial Infarction or Cardiac Arrest risk score, and National Quality Improvement Project American College of Surgeons surgical risk calculator) were assessed to predict perioperative stroke. Results- Stroke occurred in the perioperative period of 1474 noncardiac surgeries (0.27%). Patients with perioperative stroke were older, more frequently male, had lower body mass index, and were more likely to have undergone vascular surgery or neurosurgery than patients without stroke ( P<0.001 for each comparison). All risk prediction models were associated with increased risk of perioperative stroke (C statistic [AUC] range, 0.743-0.836). The Myocardial Infarction or Cardiac Arrest risk score (AUC, 0.833) and American College of Surgeons surgical risk calculator (AUC, 0.836) had the most favorable test characteristics and a greater ability to discriminate perioperative stroke when compared with Revised Cardiac Risk Index, CHADS₂, CHA₂DS₂-VASc, and Mashour risk scores ( P for comparison, <0.001; Delong). Risk scores did not provide consistent discriminative ability across surgery types and were least predictive in vascular surgery (AUC range, 0.588-0.672). Conclusions- The Myocardial Infarction or Cardiac Arrest risk score and American College of Surgeons surgical risk calculator surgical risk scores provide excellent risk discrimination for perioperative stroke in most patients undergoing noncardiac surgery. Stroke prediction was less optimal in patients undergoing vascular surgery.

Chronic coronary artery disease (CAD) and peripheral artery disease (PAD) are both associated with elevated risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). The frequency of these events in patients with CAD or PAD, and their corresponding costs, are not well understood. Accordingly, we describe the incidence and cost of both MACE and MALE in patients with CAD or PAD. Using a database that included healthcare claims linked to electronic medical records, we identified patients with evidence of chronic CAD and PAD, respectively, between January 1, 2009, and September 30, 2016. We assessed the occurrence of MACE (defined as myocardial infarction, stroke, or cardiovascular-related death) and MALE (critical limb ischemia, amputation, or peripheral artery disease-related revascularization). A total of 99,730 patients met all selection criteria: 86.0% had CAD, 25.8% had PAD, and 11.8% had both. Mean (±standard deviation) age was 67.7 (±11.5) years and 59.8% were male. During follow-up (mean: 1.8 years), 13.6% experienced MACE or MALE (6.3 per 100 person-years [PYs]), predominantly MACE (9.6% [4.3 per 100 PYs]). Adjusted 1-year healthcare costs were $44,495 greater in patients who experienced MACE or MALE (mean [95% confidence interval]: $64,099 [$33,254 to $123,557] vs $19,604 [$10,175 to $37,771]; p < 0.001). In conclusion, approximately 1 in 7 patients with chronic CAD or PAD experiences additional MACE or MALE within approximately 2 years of follow-up; the relatively high risk and cost of these events highlight the need for new secondary prevention therapies that may improve outcomes in these patients.

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01732822.

BACKGROUND:Heart failure (HF) is associated with an incremental risk of ischemic stroke, but limited real-world data exist in Patients with HF without atrial fibrillation (AF). OBJECTIVES/OBJECTIVE:This study quantified the incremental risk of ischemic stroke among newly diagnosed patients with HF and without AF. METHODS:Adult patients with an HF-related claim and ≥18 months of enrollment before their index HF (i.e., baseline period) were identified in Truven Health Analytics MarketScan Databases (01/2010-04/2015). Patients without an AF diagnosis during the baseline period and without an ischemic stroke within 14 days of the index date were propensity score matched 1:1 to individuals with neither HF nor AF and observed for ischemic stroke. A similar analysis was performed for the overall HF population (regardless of AF status). Incidence rates (calculated using Poisson regression models) were compared using incidence rate ratios (IRRs) between HF and non-HF cohorts; Kaplan-Meier analyses with log-rank tests were used to compare incidence rates over time. RESULTS:A total of 66,414 patients with HF were identified of which 52,005 did not have AF. Patients with HF without AF had significantly higher rates of ischemic stroke than patients without HF without AF during follow-up (IRR=1.91 [95%CI: 1.75-2.09], p<0.001). Ischemic stroke rates remained significantly higher for patients with HF over time among individuals without AF (p<0.001 for log-rank test at 12, 24, and 36 months).Similar results were found for the overall HF population. CONCLUSIONS:Even in the absence of AF, Patients with HF are at heightened risk of ischemic stroke compared to patients without HF.

BACKGROUND:While progress in the prevention of cardiovascular disease (CVD) has been noted over the past several decades, there are still those who develop CVD earlier in life than others. OBJECTIVE:We investigated traditional and lifestyle CVD risk factors in young to middle-aged patients compared to older ones with obstructive coronary artery disease (CAD). METHODS:A retrospective analysis of patients with a new diagnosis of obstructive CAD undergoing coronary intervention was performed. Young to middle-aged patients were defined as those in the youngest quartile (n = 281, mean age 50 ± 6 years, 81% male) compared to the other three older quartiles combined (n = 799, mean age 69 ± 7.5 years, 71% male). Obstructive CAD was determined by angiography. RESULTS:Young to middle-aged patients compared to older ones were more likely to be male (p < 0.01), smokers (21 vs. 9%, p < 0.001), and have a higher body mass index (31 ± 6 vs. 29 ± 6 kg/m2, p < 0.001). Younger patients were less likely to eat fruits, vegetables, and fish and had fewer controlled CVD risk factors (2.7 ± 1.2 vs. 3.0 ± 1.0, p < 0.001). Compared to older patients, higher levels of psychological stress (aOR 1.6, 95% CI 1.1-2.4), financial stress (aOR 1.8, 95% CI 1.3-2.5), and low functional capacity (aOR 3.3, 95% CI 2.4-4.5) were noted in the young to middle-aged population as well. CONCLUSION/CONCLUSIONS:Lifestyle in addition to traditional CVD risk factors should be taken into account when evaluating risk for development of CVD in a younger population.

Pulmonary hypertension (PH), defined by a mean pulmonary artery pressure of >25mm Hg at rest, is strongly associated with morbidity and mortality in the perioperative period. The prevalence and outcomes of PH among patients referred for major noncardiac surgery in the United States are unknown. Patients ≥18 years of age hospitalized for noncardiac surgery were identified from Healthcare Cost and Utilization Project's National Inpatient Sample data from 2004 to 2014. Pulmonary hypertension was defined by International Classification of Diseases, Ninth Revision diagnosis codes. The primary outcome was perioperative major adverse cardiovascular events (MACCE), defined as in-hospital death, myocardial infarction, or ischemic stroke. Among 17,853,194 hospitalizations for major noncardiac surgery, 143,846 (0.81%) had PH. MACCE occurred in 8.3% of hospitalizations with any diagnosis of PH in comparison to 2.0% of those without PH (p <0.001), driven by an increased frequency of death (4.4% vs 1.1%, p <0.001) and nonfatal myocardial infarction (3.2% vs 0.6%, p <0.001). After adjusting for demographics, clinical covariates, and surgery type, PH remained independently associated with MACCE (aOR 1.43, 95% CI 1.40 to 1.46). In conclusion, PH is associated with perioperative major adverse cardiovascular events. Careful patient selection, recognition of perioperative risks, and appropriate intraoperative hemodynamic monitoring may improve perioperative cardiovascular outcomes.