TAVR in Older Adults: Moving Toward a Comprehensive Geriatric Assessment and Away From Chronological Age: JACC Family Series.

Calcific aortic stenosis can be considered a model for geriatric cardiovascular conditions due to a confluence of factors. The remarkable technological development of transcatheter aortic valve replacement was studied initially on older adult populations with prohibitive or high-risk for surgical valve replacement. Through these trials, the cardiovascular community has recognized that stratification of these chronologically older adults can be improved incrementally by invoking the concept of frailty and other geriatric risks. Given the complexity of the aging process, stratification by chronological age should only be the initial step but is no longer sufficient to optimally quantify cardiovascular and noncardiovascular risk. In this review, we employ a geriatric cardiology lens to focus on the diagnosis and the comprehensive management of aortic stenosis in older adults to enhance shared decision-making with patients and their families and optimize patient-centered outcomes. Finally, we highlight knowledge gaps that are critical for future areas of study.

Global Longitudinal Strain as Predictor of Inducible Ischemia in No Obstructive Coronary Artery Disease in the CIAO-ISCHEMIA Study.

BACKGROUND: Global longitudinal strain (GLS) is a sensitive marker for identifying subclinical myocardial dysfunction in obstructive coronary artery disease (CAD). Little is known about the relationship between GLS and ischemia in patients with myocardial ischemia and no obstructive CAD (INOCA). OBJECTIVES: To investigate the relationship between resting GLS and ischemia on stress echocardiography (SE) in patients with INOCA. METHODS: Left ventricular GLS was calculated offline on resting SE images at enrollment (n = 144) and 1-year follow-up (n = 120) in the CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial screen failures with no obstructive CAD on computed tomography [CT] angiography) study, which enrolled participants with moderate or severe ischemia by local SE interpretation (≥3 segments with new or worsening wall motion abnormality and no obstructive (<50% stenosis) on coronary computed tomography angiography. RESULTS: Global longitudinal strain values were normal in 83.3% at enrollment and 94.2% at follow-up. Global longitudinal strain values were not associated with a positive SE at enrollment (GLS = -21.5% positive SE vs GLS = -19.9% negative SE, P = .443) or follow-up (GLS = -23.2% positive SE vs GLS = -23.1% negative SE, P = .859). Significant change in GLS was not associated with positive SE in follow-up (P = .401). Regional strain was not associated with colocalizing ischemia at enrollment or follow-up. Changes in GLS and number of ischemic segments from enrollment to follow-up showed a modest but not clinically meaningful correlation (ß = 0.41; 95% CI, 0.16, 0.67; P = .002). CONCLUSIONS: In this cohort of INOCA patients, resting GLS values were largely normal and did not associate with the presence, severity, or location of stress-induced ischemia. These findings may suggest the absence of subclinical myocardial dysfunction detectable by echocardiographic strain analysis at rest in INOCA.

Association of Lipoprotein Subfractions With Presence and Severity of Coronary Artery Disease in Patients Referred for Coronary Angiography.

Lipoprotein subfractions (LS) can be used for better risk stratification in subjects deemed not at high risk for coronary artery disease (CAD). In this study, we evaluated the correlation between LS with CAD presence and severity. This is a prospective case-control study of 157 patients referred for coronary angiography who were not on lipid-lowering therapy and had LS measured by nuclear magnetic resonance spectroscopy. Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores were calculated to estimate CAD severity. Univariate and multivariable regression analysis was performed to determine correlation of LS with CAD presence and severity and acute coronary syndrome (ACS). There was significant association of certain LS (positive for total low-density lipoprotein particle [LDL-P], small LDL-P and apolipoprotein B, negative for large high-density lipoprotein particle [HDL-P] and apolipoprotein A1 [ApoA1]) with the presence of obstructive CAD and CAD severity. Small LDL-P and HDL-P were still predictive for obstructive CAD after adjusting for traditional risk factors, 10-year atherosclerotic cardiovascular disease risk score and in those with low-density lipoprotein cholesterol <100 mg/100 ml. Total LDL-P and ApoA1 were predictive of CAD severity on multivariable analysis. Higher small LDL-P and lower large HDL-P were associated with ACS presence, although only large HDL-P had a significant inverse correlation with ACS on adjusted analysis (odds ratio 0.74 95% confidence interval 0.58, 0.95) In conclusion, in our cohort of patients referred for coronary angiography, total LDL-P, small LDL-P, and apolipoprotein B had significant direct correlation, and large HDL-P and ApoA1 had significant inverse correlation with obstructive CAD and CAD severity.

Gender Differences in Physician Burnout: Driving Factors and Potential Solutions.

Introduction Burnout among physicians has reached an epidemic level, with substantially higher rates among women. In this brief report, the authors evaluate recent literature to identify major factors leading to gender differences in physician burnout. Methods The authors review data on gender within each of the key drivers of burnout, including workload and job demands, efficiency and resources, control and flexibility, organizational culture and values, social support and community at work, work-life integration, and meaning at work. Results Women physicians face a higher workload, spending more time in electronic health records, and more time per patient. Women physicians also receive fewer resources and report less control over their workload and schedules. Organizational culture factors, such as a lack of women in leadership roles, compensation disparities, lower rates of career advancement and academic promotion, as well as gender bias, microaggressions, and harassment, also play a key role in gender disparities in burnout. Disproportionate responsibilities outside of work, including childcare and elder care, contribute to less satisfaction with work-life integration. Additionally, women physicians report lower self-compassion and perceived appreciation. These factors ultimately lead to decreased professional fulfillment and higher burnout rates among women physicians. Finally, the authors present proposals to address each of these factors at an organizational level, to effectively address the high burnout rate among women physicians. Conclusion Burnout among women physicians is substantially higher compared to men and stems from multiple factors. It is crucial for organizations to evaluate the gender differences within each burnout driver and develop sustainable strategies to reduce disparities.

Cause-Specific Mortality in Patients With Advanced Chronic Kidney Disease in the ISCHEMIA-CKD Trial.

BACKGROUND: In ISCHEMIA-CKD, 777 patients with advanced chronic kidney disease and chronic coronary disease had similar all-cause mortality with either an initial invasive or conservative strategy (27.2% vs 27.8%, respectively). OBJECTIVES: This prespecified secondary analysis from ISCHEMIA-CKD (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease) was conducted to determine whether an initial invasive strategy compared with a conservative strategy decreased the incidence of cardiovascular (CV) vs non-CV causes of death. METHODS: Three-year cumulative incidences were calculated for the adjudicated cause of death. Overall and cause-specific death by treatment strategy were analyzed using Cox models adjusted for baseline covariates. The association between cause of death, risk factors, and treatment strategy were identified. RESULTS: A total of 192 of the 777 participants died during follow-up, including 94 (12.1%) of a CV cause, 59 (7.6%) of a non-CV cause, and 39 (5.0%) of an undetermined cause. The 3-year cumulative rates of CV death were similar between the invasive and conservative strategies (14.6% vs 12.6%, respectively; HR: 1.13, 95% CI: 0.75-1.70). Non-CV death rates were also similar between the invasive and conservative arms (8.4% and 8.2%, respectively; HR: 1.25; 95% CI: 0.75-2.09). Sudden cardiac death (46.8% of CV deaths) and infection (54.2% of non-CV deaths) were the most common cause-specific deaths and did not vary by treatment strategy. CONCLUSIONS: In ISCHEMIA-CKD, CV death was more common than non-CV or undetermined death during the 3-year follow-up. The randomized treatment assignment did not affect the cause-specific incidences of death in participants with advanced CKD and moderate or severe myocardial ischemia. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches-Chronic Kidney Disease [ISCHEMIA-CKD]; NCT01985360).

Safety and Efficacy of CYP2C19 Genotype-Guided Escalation of P2Y12 Inhibitor Therapy After Percutaneous Coronary Intervention in Chronic Kidney Disease: a Post Hoc Analysis of the TAILOR-PCI Study.

PURPOSE: Chronic kidney disease (CKD) is a risk factor for ischemic and bleeding events with dual antiplatelet therapy after percutaneous coronary intervention (PCI). Whether the presence of CYP2C19 loss of function (LOF) alleles modifies this risk, and whether a genotype-guided (GG) escalation of P2Y12 inhibitor therapy post PCI is safe in this population is unclear. METHODS: This was a post hoc analysis of randomized patients in TAILOR PCI. Patients were divided into two groups based on estimated glomerular filtration rate (eGFR) threshold of < 60 ml/min/1.73 m2 for CKD (n = 539) and non-CKD (n = 4276). The aggregate of cardiovascular death, stroke, myocardial infarction, stent thrombosis, and severe recurrent coronary ischemia at 12-months post-PCI was assessed as the primary endpoint. Secondary endpoint was major or minor bleeding. RESULTS: Mean (standard deviation) eGFR among patients with CKD was 49.5 (8.4) ml/min/1.72 m2. Among all patients, there was no significant interaction between randomized strategy and CKD status for any endpoint. Among LOF carriers, the interaction between randomized strategy and CKD status on composite ischemic outcome was not significant (p = 0.2). GG strategy was not associated with an increased risk of bleeding in either CKD group. CONCLUSIONS: In this exploratory analysis, escalation of P2Y12 inhibitor therapy following a GG strategy did not reduce the primary outcome in CKD. However, P2Y12 inhibitor escalation following a GG strategy was not associated with increased bleeding risk in CKD. Larger studies in CKD are needed. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT01742117?term=TAILOR-PCI&draw=2&rank=1 . NCT01742117.

Management of Atrial Fibrillation in Patients 75 Years and Older: JACC State-of-the-Art Review.

The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use. Beyond rate and rhythm control considerations, stroke prophylaxis is critical to AF management, and the benefits of direct OACs, compared with warfarin, extend to older adults. Invasive procedures such as AF catheter ablation, pacemaker implantation/atrioventricular junction ablation, and left atrial appendage occlusion may be useful in appropriately selected cases. However, older adults have generally been under-represented in clinical trials.

Challenges in Optimizing Lipid Management in Women.

While there are physiologic differences in lipid metabolism in men and women, pharmacologic therapy is very effective in both with similar management strategies recommended in the current guidelines for the management of dyslipidemia. Despite similar guidelines for treatment, studies have shown that women have worse control of dyslipidemia than their male counterparts. This may stem from multiple contributing factors including underestimation of cardiovascular disease risk in women, decreased prescription and utilization of lipid-lowering therapies, decreased medication adherence, and higher risk of statin intolerance, all of which may contribute to lower attainment of lipid targets. Furthermore, heart disease is the leading cause of mortality in women, with heart disease noted an average of 7-10 years later than in men. This has historically led to the misperception that women are protected from heart disease and can be treated less aggressively. In fact, traditional risk factors for atherosclerotic cardiovascular disease often impact risk in women to a greater extent than they do in men. Unique risk factors such as pregnancy-related disorders also contribute to the level of risk and therefore warrant consideration in risk stratification. This review summarizes the efficacy of contemporary lipid-lowering therapies in women versus men and discusses the challenges that arise with lipid management in women along with potential ways to tackle these obstacles.

Challenges of long-term dual antiplatelet therapy use following acute coronary syndromes.

An acute coronary syndrome (ACS) event is associated with a high risk of recurrent ACS, stroke, and death. To ameliorate the risk of subsequent events, current guidelines for ST-segment elevation myocardial infarction and non-ST-segment elevation ACS recommend long-term management strategies for secondary prevention including risk factor modification and anti-ischemic and antiplatelet therapies. Dual antiplatelet therapy (DAPT), comprising aspirin plus a P2Y12 inhibitor, is a critical component of secondary prevention therapy following ACS. However, despite the importance of DAPT for secondary prevention after ACS, questions remain over the optimal duration of therapy. Clinical evidence is emerging that maintenance DAPT >12 months lowers the risk of recurrent ACS events; however, this benefit must be considered against any potential risks of prolonged DAPT such as bleeding. Several tools for bleeding risk assessment have shown promise; however, their limited accuracy and discriminative power necessitates further development. Assessment of patient ischemic risk should consider the complexity of the percutaneous coronary intervention (PCI) procedure, anatomic burden of coronary artery disease, and additional underlying risk factors. Consequently, identifying patients in whom the risk:benefit ratio favors prolonged DAPT may prove invaluable for clinicians in deciding which patients should continue or stop taking DAPT at 12 months after PCI, or consider P2Y12 inhibitor monotherapy as an option. This article reviews the most recent information about the risks and benefits of DAPT continued for >12 months after ACS and provides critical guidance to assist physicians in identifying patients most likely to benefit from a secondary prevention strategy with DAPT.

Adequate enrollment of women in cardiovascular drug trials and the need for sex-specific assessment and reporting.

Cardiovascular disease (CVD) is the leading cause of death for women in the United States and globally. There is an abundance of evidence-based trials evaluating the efficacy of drug therapies to reduce morbidity and mortality in CVD. Additionally, there are well-established influences of sex, through a variety of mechanisms, on pharmacologic treatments in CVD. Despite this, the majority of drug trials are not powered to evaluate sex-specific outcomes, and much of the data that exists is gathered post hoc and through meta-analysis. The FDA established a committee in 1993 to increase the enrollment of women in clinical trials to improve this situation. Several authors, reviewing committees, and professional societies have highlighted the importance of sex-specific analysis and reporting. Despite these statements, there has not been a major improvement in representation or reporting. There are ongoing efforts to assess trial design, female representation on steering committees, and clinical trial processes to improve the representation of women. This review will describe the pharmacologic basis for the need for sex-specific assessment of cardiovascular drug therapies. It will also review the sex-specific reporting of landmark drug trials in hypertension, coronary artery disease (CAD), hyperlipidemia, and heart failure (HF). In reporting enrollment of women, several therapeutic areas like antihypertensives and newer anticoagulation trials fare better than therapeutics for HF and acute coronary syndromes. Further, drug trials and cardiometabolic or lifestyle intervention trials had a higher percentage of female participants than the device or procedural trials.

Pericardial Effusion After Renal Transplantation: Timing and Clinical Characteristics.

BACKGROUND: Pericardial effusion and tamponade have been recognized as potentially serious complications in patients who have undergone renal transplantation. Our study aims to analyze the association between sirolimus and the development of pericardial effusion in renal transplant recipients. METHODS: This is a single-center retrospective study of 585 consecutive patients who underwent renal transplantation between 2005 and 2016. The study included 82 patients (14%) who developed new pericardial effusion after transplantation. Baseline demographics, medical comorbidities, medication use, echocardiographic parameters, and time to occurrence of effusion were assessed. Patients were divided into 2 groups based on timing of effusion development: early onset, ≤4 years after transplantation (51%); and late onset, >4 years after transplantation (49%). We examined the likelihood of immunosuppressant use and timing of effusion development using univariate and multivariate logistic regression analysis. RESULTS: The mean age of the cohort was 55.1 ± 11.5 years, 58.5% were men, 81.7% were white, and mean time from transplantation to the development of effusion was 4 ± 3.1 years. There were no significant differences between the early and late effusion groups in the demographic characteristics and medical comorbidities. However, sirolimus therapy was more common in the late effusion group. Furthermore, after adjusting for comorbidities, sirolimus use was associated with greater risk for developing late-onset effusion, adjusted odds ratio of 3.58 (95% confidence interval 1.25-10.20, P = .017). CONCLUSION: Pericardial effusion is prevalent in renal transplant recipients. In our cohort, treatment with sirolimus was associated with late-onset pericardial effusion. Awareness of pericardial disease in this population is important, and further studies are needed to identify predisposing factors.

Geographical Differences in Cardiovascular Comorbidities and Outcomes of COVID-19 Hospitalized Patients in the USA.

INTRODUCTION: Cardiovascular comorbidities may predispose to adverse outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). However, across the USA, the burden of cardiovascular comorbidities varies significantly. Whether clinical outcomes of hospitalized patients with COVID-19 differ between regions has not yet been studied systematically. Here, we report differences in underlying cardiovascular comorbidities and clinical outcomes of patients hospitalized with COVID-19 in Texas and in New York state. METHODS: We established a multicenter retrospective registry including patients hospitalized with COVID-19 between March 15 and July 12, 2020. Demographic and clinical data were manually retrieved from electronic medical records. We focused on the following outcomes: mortality, need for pharmacologic circulatory support, need for mechanical ventilation, and need for hemodialysis. Univariate and multivariate logistic regression analyses were performed. RESULTS: Patients in the Texas cohort (n = 296) were younger (57 vs. 63 years, p value <0.001), they had a higher BMI (30.3 kg/m2 vs. 28.5 kg/m2, p = 0.015), and they had higher rates of diabetes mellitus (41 vs. 30%; p = 0.014). In contrast, patients in the New York state cohort (n = 218) had higher rates of coronary artery disease (19 vs. 10%, p = 0.005) and atrial fibrillation (11 vs. 5%, p = 0.012). Pharmacologic circulatory support, mechanical ventilation, and hemodialysis were more frequent in the Texas cohort (21 vs. 13%, p = 0.020; 30 vs. 12%, p < 0.001; and 11 vs. 5%, p = 0.009, respectively). In-hospital mortality was similar between the 2 cohorts (16 vs. 18%, p = 0.469). After adjusting for differences in underlying comorbidities, only the use of mechanical ventilation remained significantly higher in the participating Texas hospitals (odds ratios [95% CI]: 3.88 [1.23, 12.24]). Median time to pharmacologic circulatory support was 8 days (interquartile range: 2, 13.8) in the Texas cohort compared to 1 day (0, 3) in the New York state cohort, while median time to in-hospital mortality was 16 days (10, 25.5) and 7 days (4, 14), respectively (both p < 0.001). In-hospital mortality was higher in the late versus the early study phase in the New York state cohort (24 vs. 14%, p = 0.050), while it was similar between the 2 phases in the Texas cohort (16 vs. 15%, p = 0.741). CONCLUSIONS: Geographical differences, including practice pattern variations and the impact of disease burden on provision of health care, are important for the evaluation of COVID-19 outcomes. Unadjusted data may cause bias affecting future regulatory policies and proper allocation of resources.

Sex Differences Remain Under-Reported in Cardiovascular Publications.

Background: For the past two decades, there has been increased interest from medical journals and calls to action from various organizations such as the National Institutes of Health to study sex differences in cardiovascular (CV) disease. It is unknown whether this emphasis has translated to a growth in publications addressing sex differences in CV disease. Materials and Methods: We performed a bibliometric analysis of all CV publications from 2006 to 2015. The National Library of Medicine's PubMed database was searched for articles containing the phrases "cardiac," "cardiovascular" or "cardiology," in the first author affiliation field. This was followed by a subsequent search for publications containing any of the following phrases in the title and/or abstract: "woman," "women," "female," "females," "gender," or "sex." The presence of such terms defined the publication as sex-specific. Trends over time were analyzed for specified subgroups, including publication category and funding source. Results: A total of 189,543 CV publications were identified, out of which there were 24,615 (12.99%) sex-specific publications. For the 10-year period, there were no significant changes in the relative proportion of sex-specific publications. When specific publication categories were analyzed, there were significant proportional increase of sex-specific publications in general articles category, but not for reviews, clinical trials, meta-analysis, or letters. Conclusion: Despite calls for greater attention, only a small fraction of publications for the past decade have reported on sex differences. There was no significant proportional growth of sex-specific publications for a recent 10-year period, except for the general research articles.

Concepts and Controversies: Lipid Management in Patients with Chronic Kidney Disease.

Atherosclerotic cardiovascular disease (ASCVD) remains an important contributor of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is recognized as an important risk enhancer that identifies patients as candidates for more intensive low-density lipoprotein (LDL) cholesterol lowering. However, there is controversy regarding the efficacy of lipid-lowering therapy, especially in patients on dialysis. Among patients with CKD, not yet on dialysis, there is clinical trial evidence for the use of statins with or without ezetimibe to reduce ASCVD events. Newer cholesterol lowering agents have been introduced for the management of hyperlipidemia to reduce ASCVD, but these therapies have not been tested in the CKD population except in secondary analyses of patients with primarily CKD stage 3. This review summarizes the role of hyperlipidemia in ASCVD and treatment strategies for hyperlipidemia in the CKD population.

Cardiovascular Biomarkers and Imaging in Older Adults: JACC Council Perspectives.

Whereas the burgeoning population of older adults is intrinsically vulnerable to cardiovascular disease, the utility of many management precepts that were validated in younger adults is often unclear. Whereas biomarker- and imaging-based tests are a major part of cardiovascular disease care, basic assumptions about their use and efficacy cannot be simply extrapolated to many older adults. Biology, physiology, and body composition change with aging, with important influences on cardiovascular disease testing procedures and their interpretation. Furthermore, clinical priorities of older adults are more heterogeneous, potentially undercutting the utility of testing data that are collected. The American College of Cardiology and the National Institutes on Aging, in collaboration with the American Geriatrics Society, convened, at the American College of Cardiology Heart House, a 2-day multidisciplinary workshop, "Diagnostic Testing in Older Adults with Cardiovascular Disease," to address these issues. This review summarizes key concepts, clinical limitations, and important opportunities for research.

Is our initial evaluation of patients admitted for syncope guideline-directed and cost-effective?

INTRODUCTION: Recent American College of Cardiology and European Society of Cardiology guidelines for syncope evaluation help distinguish high-cardiac risk patients from those with low-risk orthostatic and neurogenic syncope. Inpatient evaluation is recommended if at least one high-risk feature is present. OBJECTIVE: To assess guideline adherence and its impact on hospitalization in patients who presented with syncope before and after the introduction of guideline-based syncope protocol in the emergency department (ED). METHODS: All adult patients admitted to general medicine from the ED with the primary diagnosis of syncope in the months of October 2016 and October 2018 (before and after the introduction of syncope protocol in 2017). Electronic charts were retrospectively reviewed for high-risk cardiac features and orthostatic blood pressure measurement. RESULTS: Sixty patients were admitted for syncope in October 2016 (n = 32) and October 2018 (n = 28), out of which 33 (55%) were female and 47 (78.3%) were over age 50. Forty-five patients had at least one high-risk feature. Excluding one patient with an alternate diagnosis at discharge, 14 out of 60 patients (23.3%) admitted for syncope did not have any high-risk feature. Orthostatic blood pressure was measured in 3 patients (5%) in the ED and 27 patients (45%) later in the hospitalization. Six out of eight patients with implanted cardioverter-defibrillator or pacemaker had their devices interrogated. After the introduction of syncope protocol, there was an improvement in the proportion of high-risk patients admitted [68.7% (22/32) in October 2016 vs. 82.1% (23/28) in October 2018]. CONCLUSION: Utilizing syncope protocol in the ED may improve guideline adherence, direct appropriate disposition, and reduce healthcare expenses.

Attainment of Guideline-Directed Medical Treatment in Stable Ischemic Heart Disease Patients With and Without Chronic Kidney Disease.

BACKGROUND: Stable ischemic heart disease (SIHD) is prevalent in patients with chronic kidney disease (CKD); however, whether guideline-directed medical therapy (GDMT) is adequately implemented in patients with SIHD and CKD is unknown. HYPOTHESIS: Use of GDMT and achievement of treatment targets would be higher in SIHD patients without CKD than in patients with CKD. METHODS: This was a retrospective study of 563 consecutive patients with SIHD (mean age 67.8 years, 84% Caucasians, 40% females). CKD was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73m2 using the four-variable MDRD Study equation. We examined the likelihood of achieving GDMT targets (prescription of high-intensity statins, antiplatelet agents, renin-angiotensin-aldosterone system inhibitors (RAASi), and low-density lipoprotein cholesterol levels < 70 mg/dL, blood pressure < 140/90 mmHg, and hemoglobin A1C < 7% if diabetes) in patients with (n = 166) and without CKD (n = 397). RESULTS: Compared with the non-CKD group, CKD patients were significantly older (72 vs 66 years; p < 0.001), more commonly female (49 vs 36%; p = 0.002), had a higher prevalence of diabetes (46 vs 34%; p = 0.004), and left ventricular systolic ejection fraction (LVEF) < 40% (23 vs. 10%, p < 0.001). All GDMT goals were achieved in 26% and 24% of patients with and without CKD, respectively (p = 0.712). There were no between-group differences in achieving individual GDMT goals with the exception of RAASi (CKD vs non-CKD: adjusted risk ratio 0.73, 95% CI 0.62-0.87; p < 0.001). CONCLUSIONS: Attainment of GDMT goals in SIHD patients with CKD was similar to patients without CKD, with the exception of lower rates of RAASi use in the CKD group.

Effects of Extended-Release Niacin on Quartile Lp-PLA2 Levels and Clinical Outcomes in Statin-treated Patients with Established Cardiovascular Disease and Low Baseline Levels of HDL-Cholesterol: Post Hoc Analysis of the AIM HIGH Trial.

BACKGROUND: Lipoprotein-associated phospholipase A2 (LpPLA2) is an inflammatory marker that has been associated with the presence of vulnerable plaque and increased risk of cardiovascular (CV) events. OBJECTIVE: To assess the effect of extended-release niacin (ERN) on Lp-PLA2 activity and clinical outcomes. METHODS: We performed a post hoc analysis in 3196 AIM-HIGH patients with established CV disease and low baseline levels of high-density lipoprotein cholesterol (HDL-C) who were randomized to ERN versus placebo on a background of simvastatin therapy (with or without ezetimibe) to assess the association between baseline Lp-PLA2 activity and the rate of the composite primary end point (CV death, myocardial infarction, stroke, hospitalization for unstable angina, and symptom-driven revascularization). RESULTS: Participants randomized to ERN, but not those randomized to placebo, experienced a significant 8.9% decrease in LpPLA2. In univariate analysis, the highest quartile of LpPLA2 activity (>208 nmol/min/mL, Q4) was associated with higher event rates compared to the lower quartiles in the placebo group (log rank P = .032), but not in the ERN treated participants (log rank P = .718). However, in multivariate analysis, adjusting for sex, diabetes, baseline LDL-C, HDL-C, and triglycerides, there was no significant difference in outcomes between the highest Lp-PLA2 activity quartile versus the lower quartiles in both the placebo and the ERN groups. CONCLUSION: Among participants with stable CV disease on optimal medical therapy, elevated Lp-PLA2 was associated with higher CV events; however, addition of ERN mitigates this effect. This association in the placebo group was attenuated after multivariable adjustment, which suggests that Lp-PLA2 does not improve risk assessment beyond traditional risk factors.