Faculty Bibliography

Importance: Major adverse cardiovascular and cerebrovascular events (MACCE) are a significant source of perioperative morbidity and mortality following noncardiac surgery. Objective: To evaluate national trends in perioperative cardiovascular outcomes and mortality after major noncardiac surgery and to identify surgical subtypes associated with cardiovascular events using a large administrative database of United States hospital admissions. Design, Setting, Participants: Patients who underwent major noncardiac surgery from January 2004 to December 2013 were identified using the National Inpatient Sample. Main Outcomes and Measures: Perioperative MACCE (primary outcome), defined as in-hospital, all-cause death, acute myocardial infarction (AMI), or acute ischemic stroke, were evaluated over time. Results: Among 10581621 hospitalizations (mean [SD] patient age, 65.74 [12.32] years; 5975798 female patients 56.60%]) for major noncardiac surgery, perioperative MACCE occurred in 317479 hospitalizations (3.0%), corresponding to an annual incidence of approximately 150000 events after applying sample weights. Major adverse cardiovascular and cerebrovascular events occurred most frequently in patients undergoing vascular (7.7%), thoracic (6.5%), and transplant surgery (6.3%). Between 2004 and 2013, the frequency of MACCE declined from 3.1% to 2.6% (P for trend <.001; adjusted odds ratio [aOR], 0.95; 95% CI, 0.94-0.97) driven by a decline in frequency of perioperative death (aOR, 0.79; 95% CI, 0.77-0.81) and AMI (aOR, 0.87; 95% CI, 0.84-0.89) but an increase in perioperative ischemic stroke from 0.52% in 2004 to 0.77% in 2013 (P for trend <.001; aOR 1.79; CI 1.73-1.86). Conclusions and Relevance: Perioperative MACCE occurs in 1 of every 33 hospitalizations for noncardiac surgery. Despite reductions in the rate of death and AMI among patients undergoing major noncardiac surgery in the United States, perioperative ischemic stroke increased over time. Additional efforts are necessary to improve cardiovascular care in the perioperative period of patients undergoing noncardiac surgery.

In patients with previous myocardial infarction (MI), aggressive hypertension control and low-density lipoprotein cholesterol (LDL-C) reduction are important secondary prevention measures. However, residual risk remains despite aggressive treatment. Whether variability in blood pressure (BP) and LDL-C can explain this residual risk is not known. Patients enrolled in the Incremental Decrease in End Points Through Aggressive Lipid-Lowering trial with at least 1 post-baseline measurement of LDL-C and blood pressure (BP) were included. Visit-to-visit LDL-C and BP variabilities were evaluated using various measures of variability. Primary outcome was any coronary event with the secondary outcomes of any cardiovascular event (CV), MI, stroke, death, and CV death. Among the 8,658 patients included, each 1-SD (10.8 mg/dl) increase in LDL-C variability increased the risk of any coronary event (adjusted HR [HRadj] 1.07; 95% CI 1.04 to 1.11; p <0.0001), any CV event, MI, and death (HRadj 1.19; 95% CI 1.14 to 1.25; p <0.0001). Similarly, each 1-SD (7.2 mm Hg) increase in systolic BP variability increased the risk of any coronary event (HRadj 1.15; 95% CI 1.10 to 1.20; p <0.0001), any CV event, MI, stroke, death (HRadj 1.28; 95% CI 1.18 to 1.38; p <0.0001), and CV death. Compared with the group with low variability for both LDL-C and systolic BP, the group with high variability for both had a significant increase in any coronary event (HRadj 1.48; 95% CI 1.30 to 1.70), any CV event (HRadj 1.43; 95% CI 1.27 to 1.61), and MI (HRadj 1.87; 95% CI 1.46 to 2.41). In conclusions, in patients with a history of MI, variabilities in LDL-C and BP are powerful and independent predictors of CV events including death.

BACKGROUND: Although hypertension guidelines define treatment resistant hypertension as blood pressure uncontrolled by >/=3 antihypertensive medications, including a diuretic, it is unknown whether patient prognosis differs when a diuretic is included. METHODS: Participants in the Antihypertensive and Lipid-Lowering to Prevent Heart Attack Trial were randomly assigned to first-step therapy with chlorthalidone, amlodipine, or lisinopril. At a Year 2 follow-up visit, those with average BP>/=140 mmHg systolic or >/=90 mmHg diastolic on >/=3 antihypertensive medications, or BP<140/90 mmHg on >/=4 antihypertensive medications, were identified as having apparent treatment resistant hypertension. The prevalence of treatment resistant hypertension and its association with ALLHAT primary (combined fatal coronary heart disease or nonfatal myocardial infarction) and secondary (all-cause mortality, stroke, heart failure, combined coronary heart disease, and combined cardiovascular disease) outcomes were identified for each treatment group. RESULTS: Of participants assigned to chlorthalidone, amlodipine and lisinopril, 9.6%, 11.4% and 19.7%, respectively, had treatment resistant hypertension. During mean follow-up of 2.9 years, primary outcome incidence was similar for those assigned to chlorthalidone compared to amlodipine or lisinopril (amlodipine vs. chlorthalidone adjusted HR=0.86; 95% CI 0.53-1.39; P=0.53; lisinopril vs. chlorthalidone adjusted HR=1.06; 95% CI 0.70-1.60; P=0.78). Secondary outcome risks were similar for most comparisons except coronary revascularization, which was higher with amlodipine than with chlorthalidone (HR=1.86; 95% CI 1.11-3.11; P=0.02). An as-treated analysis based on diuretic use produced similar results. CONCLUSIONS: In this study, which titrated medications to a goal, participants assigned to chlorthalidone were less likely to develop treatment resistant hypertension. However, prognoses in those with treatment resistant hypertension were similar across treatment groups. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, NCT00000542.

BACKGROUND: Chronic kidney disease (CKD) is associated with cardiovascular disease and acute myocardial infarction (AMI). Contemporary management and outcomes of AMI in patients with CKD have not been reported. METHODS: We analyzed United States National Inpatient Sample data for patients admitted with AMI with or without CKD from 2007 to 2012. Propensity score matching was used to identify patients with AMI and CKD with similar baseline characteristics who were managed invasively (cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft surgery [CABG]) or conservatively. The primary outcome was in-hospital all-cause mortality. RESULTS: Among 753,782 patients admitted with AMI, 17.8% had a diagnosis of CKD. Patients with CKD had lower odds of invasive management (49.9% vs. 73.1%; adjusted OR 0.57, 95% CI 0.57-0.58), were less likely to undergo revascularization (adjusted OR 0.60, 95% CI 0.59-0.61), and had higher in-hospital mortality (8.4% vs. 5.0%; adjusted OR 1.55, 95% CI 1.51-1.59) than those without CKD. In a propensity-matched cohort of 89,630 CKD patients treated for AMI with invasive vs. conservative management, invasive management was associated with lower in-hospital mortality overall (5.9% vs. 10.9%, p<0.001; OR=0.51 (0.49-0.54)) as well as in subgroups by MI type and severity of CKD. CONCLUSIONS: Patients with AMI and CKD are less likely to receive invasive management, coronary revascularization, and have higher in-hospital mortality than patients without CKD. Invasive management of AMI was associated with lower in-hospital mortality versus conservative management in all patients, regardless of CKD severity.

BACKGROUND: Patients with chronic kidney disease (CKD) undergoing coronary angiography (CA), adequate hydration and minimizing volume of contrast media (CM) are class 1b recommendations for preventing contrast induced nephropathy (CIN). Current data are insufficient to justify specific recommendations about isoosmolar vs. low-osmolar contrast media by the ACCF/AHA/SCAI guidelines. METHODS: Randomized trials comparing IOCM to LOCM in CKD stage 3 and above patients undergoing CA, and reporting incidence of CIN (defined by a rise in creatinine of 25% from baseline) were included in the analysis. The secondary outcome of the study was the incidence of serum creatinine increase by >1mg/dl. RESULTS: A total of 2839 patients were included in 10 trials, in which 1430 patients received IOCM and 1393 received LOCM. When compared to LOCM, IOCM was not associated with significant benefit in preventing CIN (OR=0.72, [CI: 0.50-1.04], P=0.08, I2=59%). Subgroup analysis revealed non-significant difference in incidence of CIN based on baseline use of N-acetylcystine (NAC), diabetes status, ejection fraction, and whether percutaneous coronary intervention vs coronary angiography alone was performed. The difference between IOCM and LOCM was further attenuated when restricted to studies with larger sample size (>250 patients) (OR=0.93; [CI: 0.66-1.30]) or when compared with non-ionic LOCM (OR=0.79, [CI: 0.52-1.21]). CONCLUSION: In patients with CKD stage 3 and above undergoing coronary angiography, use of IOCM showed overall non-significant difference in incidence of CIN compared to LOCM. The difference was further attenuated when IOCM was compared with non-ionic LOCM.

OBJECTIVE:To evaluate the outcomes with use of renin angiotensin system (RAS) blockers compared with other antihypertensive agents in people with diabetes. DESIGN/METHODS:Meta-analysis. DATA SOURCES AND STUDY SELECTION/METHODS:PubMed, Embase, and the Cochrane central register of controlled trials databases for randomized trials of RAS blockers versus other antihypertensive agents in people with diabetes mellitus. Outcomes were death, cardiovascular death, myocardial infarction, angina, stroke, heart failure, revascularization, and end stage renal disease. RESULTS:The search yielded 19 randomized controlled trials that enrolled 25,414 participants with diabetes for a total of 95,910 patient years of follow-up. When compared with other antihypertensive agents, RAS blockers were associated with a similar risk of death (relative risk 0.99, 95% confidence interval 0.93 to 1.05), cardiovascular death (1.02, 0.83 to 1.24), myocardial infarction (0.87, 0.64 to 1.18), angina pectoris (0.80, 0.58 to 1.11), stroke (1.04, 0.92 to 1.17), heart failure (0.90, 0.76 to 1.07), and revascularization (0.97, 0.77 to 1.22). There was also no difference in the hard renal outcome of end stage renal disease (0.99, 0.78 to 1.28) (power of 94% to show a 23% reduction in end stage renal disease). CONCLUSIONS:In people with diabetes, RAS blockers are not superior to other antihypertensive drug classes such as thiazides, calcium channel blockers, and β blockers at reducing the risk of hard cardiovascular and renal endpoints. These findings support the recommendations of the guidelines of the European Society of Cardiology/European Society of Hypertension and eighth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure to also use other antihypertensive agents in people with diabetes but without kidney disease.