Faculty Bibliography

: A physiologically lower heart rate, such as that seen in athletes, has been associated with better survival in epidemiological studies. In patients with coronary artery disease, heart rate is considered an independent risk factor for adverse outcomes. Higher heart rate increases cardiac work load and oxygen demand and reduces coronary perfusion by decreasing the amount of time spent in diastole, which in patients with obstructive coronary artery disease can trigger angina and myocardial infarction. Whether pharmacological reduction in heart rate by using a beta-blocker or ivabradine improves prognosis has been debated. In this review, we explore the effect of pharmacological heart rate lowering with a beta-blocker or ivabradine on cardiovascular outcomes in patients with cardiovascular disease and address the question as to whether pharmacological heart rate reduction is ready for prime time in the management of patients with coronary artery disease. Although physiologically lower heart rates are associated with improved survival, the effect of pharmacological heart rate reduction with beta-blockers (in patients without heart failure or postmyocardial infarction) or ivabradine on improvement in survival is weak at best.

Until recently, intraindividual visit-to-visit variability of cardiovascular risk factors has been dismissed as random fluctuation. This simplistic concept was challenged by demonstrating that visit-to-visit blood pressure variability, independent of average blood pressure, was a powerful risk factor for stroke. Subsequently, variability of other cardiovascular risk factors such as cholesterol, glycemia, and body weight was documented to increase risk independent of their absolute values. Variability of these risk factors has been demonstrated to be a powerful predictor for all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia. With the notable exception of heart rate, cardiovascular risk factors must now be defined by 2 components: the magnitude and duration of sustained risk factor elevation and, equally important, the variability of the same risk factor over time.

Background Kidney function decreases during the lifetime, and this decline is a powerful predictor of both kidney and cardiovascular outcomes. Statins lower cardiovascular risk, which may relate to beneficial effects on kidney function. We studied whether atorvastatin influences kidney function decline and assessed the association between individual kidney function slopes and cardiovascular outcome. Methods and Results Data were collected from 6 large atorvastatin cardiovascular outcome trials conducted in patients not selected for having kidney disease. Slopes of serum creatinine reciprocals representing measures of kidney function change ([mg/dL]^-1/y), were analyzed in 30 621 patients. Based on treatment arms, patients were categorized into 3 groups: placebo (n=10 057), atorvastatin 10 mg daily (n=12 763), and 80 mg daily (n=7801). To assess slopes, mixed-model analyses were performed for each treatment separately, including time in years and adjustment for study. These slopes displayed linear improvement over time in all 3 groups. Slope estimates for patients randomized to placebo or atorvastatin 10 mg and 80 mg were 0.009 (0.0008), 0.011 (0.0006), and 0.014 (0.0006) (mg/dL)^-1/y, respectively. A head-to-head comparison of atorvastatin 10 and 80 mg based on data from 1 study ( TNT [Treating to New Targets]; n=10 001) showed a statistically significant difference in slope between the 2 doses ( P=0.0009). From a Cox proportional hazards model using slope as a predictor, a significant ( P<0.0001) negative association between kidney function and cardiovascular outcomes was found. Conclusions In patients at risk of or with cardiovascular disease, atorvastatin improved kidney function over time in a dose-dependent manner. In the 3 treatment groups, kidney function improvement was strongly associated with lower cardiovascular risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifiers: NCT00327418; NCT00147602; NCT00327691.

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.

Kidney transplantation (KT) is the optimal therapy for end-stage kidney disease (ESKD), resulting in significant improvement in survival as well as quality of life when compared with maintenance dialysis. The burden of cardiovascular disease (CVD) in ESKD is reduced after KT; however, it still remains the leading cause of premature patient and allograft loss, as well as a source of significant morbidity and healthcare costs. All major phenotypes of CVD including coronary artery disease, heart failure, valvular heart disease, arrhythmias and pulmonary hypertension are represented in the KT recipient population. Pre-existing risk factors for CVD in the KT recipient are amplified by superimposed cardio-metabolic derangements after transplantation such as the metabolic effects of immunosuppressive regimens, obesity, posttransplant diabetes, hypertension, dyslipidemia and allograft dysfunction. This review summarizes the major risk factors for CVD in KT recipients and describes the individual phenotypes of overt CVD in this population. It highlights gaps in the existing literature to emphasize the need for future studies in those areas and optimize cardiovascular outcomes after KT. Finally, it outlines the need for a joint 'cardio-nephrology' clinical care model to ensure continuity, multidisciplinary collaboration and implementation of best clinical practices toward reducing CVD after KT.

The association between admission blood pressure (BP) and outcomes in patients with transient ischemic attack (TIA) is not well defined. Patients in the United States national Get With The Guidelines-Stroke registry with a TIA were included. Admission systolic and diastolic BP was used to compute mean arterial pressure and pulse pressure (PP). A subset of this cohort was linked to Centers for Medicare and Medicaid claims data for postdischarge outcomes. The in-hospital outcomes of interest were: mortality, not discharged home, and inability to ambulate independently at discharge. Postdischarge, 30-day and 90-day outcomes of interest were mortality, readmission for stroke, and readmission for major cardiovascular event-composite of death, cerebrovascular, or cardiovascular readmission. Among the 218,803 patients with TIA, lower admission systolic blood pressure (SBP) was associated with worse in-hospital outcomes. Compared with patients with SBP of 150 mm Hg, a lower SBP of 120 mm Hg was associated with higher risk of in-hospital death (adjusted OR = 1.79; 95% CI = 1.50 to 2.12), not being discharged home (adjusted OR = 1.31; 95% CI = 1.27 to 1.36), or inability to ambulate independently at discharge (adjusted OR = 1.27; 95% CI = 1.23 to 1.31). Similarly, among the 64,352 patients in the Centers for Medicare and Medicaid-linked cohort, an inverse association between systolic BP and postdischarge mortality (p <0.0001), and major cardiovascular event (p = 0.0001) was observed at 30-days and at 90-days postdischarge. However, there was no relation between SBP and readmission for stroke either at 30-days (p = 0.35) or at 90-days (p = 0.11). Results were largely similar for diastolic BP, mean arterial pressure, PP, and outcomes. In conclusion, in patients with a transient ischemic attack, a BP paradox was observed, with higher admission BP associated with improved in-hospital, 30-day, and 90-day postdischarge outcomes.

Importance/UNASSIGNED:It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia. Objective/UNASSIGNED:To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles. Design, Setting, and Participants/UNASSIGNED:The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (<50% for imaging stress test and <70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018. Main Outcomes and Measures/UNASSIGNED:Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported. Results/UNASSIGNED:A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging. Conclusions and Relevance/UNASSIGNED:The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD. Trial Registration/UNASSIGNED:ClinicalTrials.gov Identifier: NCT01471522.