Jeffrey L. Anderson

Background: The absence of coronary artery calcium (CAC = 0) on computed tomography (CT) portends a low but not zero coronary risk. However, the frequency and prognostic significance of non-calcified plaques in CAC = 0 patients are incompletely defined, and non-coronary artery disease (CAD) causes of coronary risk have been proposed. We sought to define the ischemic burden, CAD status, and outcomes of CAC = 0 patients. Methods: The Intermountain electronic medical records were searched for CAC = 0 patients undergoing stress positron emission tomography (PET)/CT between January 2016 and July 2022. We defined definite PET abnormality as ischemic burden (IB) ≥ 10%. Patients were followed for angiographic findings, interventions, and major adverse cardiovascular events (MACE) over 3.1 ± 1.3 years. Results: Of 22,542 PET/CT studies in primary prevention patients, 5054 (22.4%) had CAC = 0. Of these, 59 (1.2%) had IB ≥ 10% on PET. Selective coronary angiography was performed within 90 days in 25 (42%) of IB ≥ 10% patients. Severe CAD was present in 11, but findings were not explained by CAD in 14. Revascularization was indicated in 10 (16.9%) of 59 with IB ≥ 10% vs. 0.04% of IB = 0% (p < 0.0001); 3-year outcomes also were lower with IB = 0%. Conclusions: In this large series of stress PET/CT study data, IB ≥ 10% in patients with CAC = 0 was rare. Most positive PET tests were not explained by obstructive CAD. While CAC does not perfectly predict an absence of coronary ischemia or obstructive CAD, it is a strong marker of prognosis. Here, we show that IB by PET supplements CAC score to importantly refine risk assessment.

Background: The low‐density lipoprotein cholesterol (LDL‐C)‐lowering effect of inclisiran, a proprotein convertase subtilisin/kexin type 9‐targeting small interfering RNA, has not been established in patients with recent acute coronary syndrome. Methods: VICTORION‐INCEPTION, a 330‐day, phase 3b, open‐label, multicenter trial, designed to mimic clinical practice, randomized 400 eligible participants (discharged following acute coronary syndrome ≤5 weeks of screening, with LDL‐C ≥70 mg/dL [or non–high‐density lipoprotein cholesterol ≥100 mg/dL], receiving statin therapy or statin intolerant) 1:1 to inclisiran sodium 300 mg (284 mg inclisiran equivalent; Days 0, 90, 270) + usual care, or usual care (clinician‐directed LDL‐C management). Coprimary end points at Day 330 were LDL‐C P P <0.001). Participants with ≥1 adverse events were comparable (inclisiran + usual care, 58.6%; usual care, 53.3%). Conclusions: VICTORION‐INCEPTION was the first inclisiran trial in participants with recent acute coronary syndrome. Early inclisiran initiation with usual care resulted in rapid, sustained attainment of guideline‐directed LDL‐C goals and was well tolerated. Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT04873934.

Background: It is unclear whether sex or age impacts the prognostic value of a zero coronary artery calcium (CAC) score. Methods: We searched our electronic medical record (eMR) database for primary prevention patients who underwent positron emission tomography/computed tomography (PET/CT) stress testing. We assessed coronary prognosis and all-cause death during 2.2 (SD 1.9) years of follow-up in women vs. men and in those ≥65 vs. 0 scores. Results: We identified 40,018 qualifying patients, of which 48.7% were women and 58.9% were ≥65. CAC = 0 was present in 7967 (19.9%), of which 67.8% were women, and 34.9% were aged ≥65. In CAC = 0 patients, 13 coronary events occurred: 7 (0.13%) in women and 6 (0.24%) in men (p = 0.28); and 6 (0.12%) in 0 subjects were 3.1% vs. 9.8% overall: 3.1% vs. 9.5% in women and 3.3% vs. 10.2% in men, 2.4% vs. 6.9% for ages p < 0.001. Conclusions: A zero CAC score predicts an excellent prognosis for not only coronary events but also all-cause mortality, both overall and in women and the elderly.

Background: Aging of the population has resulted in more patients living with atrial fibrillation (AF) and age‐related macular degeneration (AMD). AF is associated with macro‐ and micro‐thromboembolism, microvascular dysfunction, and system inflammation. Organ systems sensitive to the long‐term systemic and vascular disease associations of AF will likely develop dysfunction over time. There is also an increase in age‐related macular degeneration (AMD), which shares many pathophysiologic risk factors of AF. We hypothesized that AF will increase the risk of AMD. Methods: A total of 38 746 consecutive patients from the large ongoing prospective angiography INSPIRE Study database without a history of AMD were evaluated for the development of AMD. Long‐term incidence of AMD was assessed at 1 and 5 years and at last follow‐up to determine its association with AF. Results: Over a mean follow‐up of 2159.4 ± 1851.7 days, 11 787 (30.4%) had or developed AF. Patients with AF were older (67.7 ± 12.2 vs. 57.5 ± 15.5 years, p < 0.0001), and had higher rates of hypertension (50.0% vs. 44.0%, p < 0.0001), renal failure (1.7% vs. 1.1%, p < 0.0001), stroke (4.6% vs. 3.1%, p < 0.0001), and heart failure (27.3% vs. 11.5%, p < 0.0001). AF patients were more likely to be treated with a statin, ACE/ARB, diuretic, and warfarin. The overall incidence of AMD over the follow‐up period was higher in patients with AF (2.1% vs. 1.2%, p < 0.0001). Compared with no AF, the risk of AMD in patients with AF was increased at 1 year (hazard ratio [HR] = 1.92 [1.26–2.93], p = 0.003), 5 years (HR = 1.83 [1.46–2.29], p < 0.0001), and long‐term (1.80 [1.52–2.12], p < 0.0001). The association of AF with AMD was attenuated after adjustment by baseline characteristics, comorbidities, and medications. All AMD risks were mitigated in multivariable modeling that included baseline characteristics (i.e., CHA2DS2‐Vasc) and drug therapies for AF. Conclusion: Patients with AF are at elevated risk of developing AMD that increases over time when compared to patients without AF. In this cohort of patients, the risk of AMD is due to risk factors that drive the presence of AF itself and its progression. Comprehensive treatment of AF that focuses on its underlying risk factors, including dynamic reassessment of risk factors during follow‐up, may impact risk of AMD in patients with AF.

Background: Periodic fasting was previously associated with greater longevity and a lower incidence of heart failure (HF) in a pre-pandemic population. In patients with coronavirus disease 2019 (COVID-19), periodic fasting was associated with a lower risk of death or hospitalization. This study evaluated the association between periodic fasting and HF hospitalization and major adverse cardiovascular events (MACEs). Methods: Patients enrolled in the INSPIRE registry from February 2013 to March 2020 provided periodic fasting information and were followed into the pandemic (n = 5227). Between March 2020 and February 2023, N = 2373 patients were studied, with n = 601 COVID-positive patients being the primary study population (2836 had no COVID-19 test; 18 were excluded due to fasting n = 117, 19.5%) occurred in 13.3% of fasters and 22.1% of non-fasters [adjusted hazard ratio (aHR) = 0.63, CI = 0.40, 0.99; p = 0.044]. Most HF admissions were exacerbations, with a prior HF diagnosis in 111 (94.9%) patients hospitalized for HF. Fasting was also associated with a lower MACE risk (aHR = 0.64, CI = 0.43, 0.96; p = 0.030). In n = 1772 COVID-negative patients (29.7% fasters), fasting was not associated with HF hospitalization (aHR = 0.82, CI = 0.64, 1.05; p = 0.12). In COVID-positive and negative patients combined, periodic fasting was associated with lower mortality (aHR = 0.60, CI = 0.39, 0.93; p = 0.021). Conclusions: Routine periodic fasting was associated with less HF hospitalization in patients positive for COVID-19.

Introduction: Water-only fasting for one day or more may provide health benefits independent of weight loss. Human growth hormone (HGH) may play a key role in multiple fasting-triggered mechanisms. Whether HGH changes during fasting are independent of weight loss and how basal HGH and HGH change relate to other fasting-induced changes are unknown. Methods: Apparently healthy individuals (N=30) were randomized by Latin square to begin two days with either 24-hour water-only fasting or a control of 24-hour ad libitum eating. On day 2, subjects were crossed over to control (if day 1 was fasting) or fasting (if they ate on day 1). HGH, weight, and other parameters were measured at baseline and at the end of the first and second days. Results: Baseline HGH had median 0.50 ng/mL for females (n=20) and 0.04 ng/mL for males (n=10), and correlated inversely with weight, glucose, insulin, and triglycerides and positively with changes in insulin and HOMA-IR. The 24-hour fasting-induced HGH change was uncorrelated with weight loss (r= 0.01, p=0.98), but correlated with changes in glucose, HGB, and IGF-1. The percent increase in HGH was greater (p<0.001) for lower (females ≤0.15 ng/mL, males ≤0.05 ng/mL) vs. higher baseline HGH (median: 1,225% vs. 50.3%, respectively). Subjects with lower baseline HGH had a trend to greater reduction of HOMA-IR (median: −6.15 vs. −1.35 for lower vs. higher HGH, respectively, p=0.08). Conclusions: Fasting increased HGH and the HGH changes were independent of weight loss. Basal HGH and fasting-induced HGH changes correlated inversely with cardiometabolic risk factors.

Background: Patient outcomes after percutaneous coronary intervention (PCI) have improved over the last 30 years due to better techniques, therapies, and care processes. This study evaluated contemporary predictors of post-PCI major adverse cardiovascular events (MACE) and summarized risk in a parsimonious risk prediction model. Methods: The Cardiovascular Patient-Level Analytical Platform (CLiPPeR) is an observational dataset of baseline variables and longitudinal outcomes from the American College of Cardiology’s CathPCI Registry^® and national claims data. Cox regression was used to evaluate 2–6 years of patient follow-up (mean: 2.56 years), ending in December 2017, after index PCI between 2012 and 2015 (N = 1,450,787), to examine clinical and procedural predictors of MACE (first myocardial infarction, stroke, repeat PCI, coronary artery bypass grafting, and mortality). Cox analyses of post-PCI MACE were landmarked 28 days after index PCI. Results: Overall, 12.4% (n = 179,849) experienced MACE. All variables predicted MACE, with cardiogenic shock, cardiac arrest, four diseased coronary vessels, and chronic kidney disease having hazard ratios (HRs) ≥ 1.50. Other major predictors of MACE were in-hospital stroke, three-vessel disease, anemia, heart failure, and STEMI presentation. The index revascularization and discharge prescription of aspirin, P2Y₁₂ inhibitor, and lipid-lowering medication had HR ≤ 0.67. The primary Cox model had c-statistic c = 0.761 for MACE versus c = 0.701 for the parsimonious model and c = 0.752 for the parsimonious model plus treatment variables. Conclusions: In a nationally representative US sample of post-PCI patients, predictors of longitudinal MACE risk were identified, and a parsimonious model efficiently encapsulated them. These findings may aid in assessing care processes to further improve care post-PCI outcomes.

Objectives: Recent reports have highlighted myocardial infarction (MI) patients without standard modifiable risk factors (SMRF), noting them to be surprisingly common and to have a substantial risk of adverse outcomes. The objective of this study was to address the challenge of identifying at-risk patients without SMRF and providing preventive therapy. Methods: Patients presenting between 2001 and 2021 to Intermountain Health catheterization laboratories with a diagnosis of MI were included if they also had a coronary artery calcium (CAC) scan by computed tomography within 2 years. SMRF were defined as a clinical diagnosis or treatment of hypertension, hyperlipidemia, diabetes, or smoking. The co-primary endpoints in SMRF-less patients were: (1) proportion of patients with an elevated (>50%ile) CAC score, and (2) an indication for statin therapy (i.e., CAC ≥ 100 AU or ≥75%ile). The 60-day and long-term major adverse cardiovascular events were determined. A comparison set included MI patients with SMRF. Results: We identified 429 MI patients with a concurrent CAC scan, of which 60 had no SMRF. SMRF status did not distinguish most risk factors or interventions. No-SMRF patients had a high CAC prevalence and percentile (82% ≥ 50%ile; median, 80%ile), and 77% met criteria for preventive therapy. As expected, patients with SMRF had high CAC scores and percentiles. Outcomes were more favorable for No-SMRF status and for lower CAC scores. Conclusions: Patients without SMRF presenting with an MI have a high prevalence and percentile of CAC. Wider application of CAC scans, including in those without SMRF, is promising as a method to identify an additional at-risk population for MI and to provide primary preventive therapy.