Joseph B. Muhlestein works in Interventional / Structural Cardiology affiliated with University of Utah.
J. Brent Muhlestein, MD, is Professor of Medicine in the Division of Cardiovascular Medicine at the University of Utah Spencer Fox Eccles School of Medicine and an interventional cardiologist at Intermountain Medical Center. He is Co-Director of Cardiology Research for Intermountain Healthcare and Director of the Interventional Cardiology Training Program at Intermountain Medical Center. He received his MD from the University of Utah in 1984 and completed internal medicine residency and cardiology fellowships at Duke University.
405 pubs · 17,942 cites · h-index 65
MD
University of Utah School of Medicine
1984
BS
Brigham Young University
1980
Fellowship, Cardiovascular Disease
Duke University Medical Center
1991
Co-Director of Cardiology Research
Intermountain Healthcare · 2010 - Present
Director of Interventional Cardiology Training Program
Intermountain Medical Center · 2007 - Present
Professor of Medicine
University of Utah · 1992 - Present
Director of Cardiology Research
Intermountain Healthcare · 1999 - 2010
Co-Director of Cardiac Catheterization Laboratory
LDS Hospital · 1997 - 2007
A 3-month course of azithromycin did not significantly reduce ischemic events at 2 years in patients with coronary artery disease seropositive for C pneumoniae, challenging earlier small studies.
The neutrophil/lymphocyte ratio is a strong, independent predictor of death or MI in patients with or at high risk for CAD, offering greater predictive value than total WBC count.
There is a significantly higher incidence of Chlamydia species in atherosclerotic coronary arteries compared to nonatherosclerotic controls, suggesting a potential etiologic role in coronary atherosclerosis.
MVP management remains unchanged; leaves open therapeutic target discovery from expanded genetic insights.
Professor of medicine, UCLA School of Medicine · David Geffen School of Medicine at UCLA / The Lundquist Institute
These data highlight the early and sustained impact of icosapent ethyl on the atherothrombotic burden in the high-risk population.
European Heart JournalBudoff et al.
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: 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.Clinical Trial Registration: clinicaltrials.gov, identifier NCT01059760.
Intense intermittent fasting regimens safely reduce weight to a similar extent as caloric restriction. A previous trial reported low-frequency 26-week intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) without significant weight loss. During fasting, human growth hormone (HGH) increases substantially, but whether basal HGH modifies the effect of fasting on outcomes of repeated fasting is unknown. In a post hoc analysis of a randomized controlled trial (registration: clinicaltrials.gov, NCT02770313, May 12, 2016), subjects (N = 68) were adults ages 21-70 years with modest cholesterol elevation, ≥1 metabolic syndrome component, available HGH measurements, no chronic disease, and no statin or anti-diabetes medication. Randomization was 1:1 to intermittent fasting (24-hour, water-only, twice-per-week for 4 weeks, then once-per-week for 22 weeks) or 26-week ad libitum control. General linear modeling evaluated the interaction of trial arm with baseline HGH for HOMA-IR changes. Subjects with lower baseline HGH had 26-week HOMA-IR changes (p = 0.003) of -1.04 ± 0.99 for fasting versus 0.60 ± 1.04 for controls. Subjects with higher baseline HGH had HOMA-IR changes (p = 0.26) of -0.69 ± 0.75 (fasting) and -0.42 ± 0.92 (controls). The interaction of fasting with lower baseline HGH was significant (p-interaction=0.004). Results were similar for insulin and glucose. Weight loss at 26 weeks was not significantly different between fasting and controls (-1.74 ± 4.81 kg vs. 0.21 ± 3.50 kg, p = 0.08) and was not correlated with changes in HOMA-IR, insulin, glucose, and HGH. In conclusion, lower baseline HGH modified the effect of low-frequency water-only 24-hour fasting in profoundly reducing HOMA-IR over 26 weeks compared both to controls and to fasting subjects with higher baseline HGH.
Background An estimated two-thirds of heart failure (HF) patients with reduced ejection fraction (HFrEF) hospitalized in the United States have a severely reduced left ventricular ejection fraction (LVEF < 30%). Few studies have categorized patients according to their severity of left ventricular dysfunction beyond an LVEF of < 30%. Methods Intermountain Health patients (≥18 years), with a primary HF diagnosis, ≥1 inpatient hospitalization with a primary discharge diagnosis of HF, a documented LVEF of < 30%, and a BNP > 100 pg/mL within one year of hospitalization were studied. Patients were stratified by LVEF levels (≤15%, 16–25%, and 26–29%) and evaluated for death, HF hospitalization, healthcare resource utilization, and medical costs. Results Overall, 2 184 patients (mean age 64.2 ± 15.5 years, 72.5% male) were stratified by LVEF (≤15%, n = 468 [21.4%]; 16–25%, n = 1399 [64.1%]; and 26–29%, n = 317 [14.5%]). Lower LVEF was associated with younger age, male sex, and fewer comorbidities. Although one-year mortality differed significantly between LVEF stratifications, which remained after adjustment by risk factors (vs. LVEF 26–29% [referent]): ≤15%, hazard ratio (HR)=1.92, p < 0.0001; and 16–25%, HR = 1.42, p = 0.01), mortality was similar by 3-years. HF hospitalizations at 1- and 3-years were similar among LVEF groups. Total HF costs—driven by increased HF outpatient costs—were significantly higher among LVEF of ≤ 15%. Conclusions Patients with an LVEF of ≤ 15% had a modestly increased risk of 1-year mortality, as well as significantly higher total HF costs. Patients with HFrEF and a severely reduced LVEF continue to face an increased clinicoeconomic burden, and novel therapies to treat this unmet medical need are warranted.
Although fasting is increasingly applied for disease prevention and treatment, consensus on terminology is lacking. Using Delphi methodology, an international, multidisciplinary panel of researchers and clinicians standardized definitions of various fasting approaches in humans. Five online surveys and a live online conference were conducted with 38 experts, 25 of whom completed all 5 surveys. Consensus was achieved for the following terms: "fasting" (voluntary abstinence from some or all foods or foods and beverages), "modified fasting" (restriction of energy intake to max. 25% of energy needs), "fluid-only fasting," "alternate-day fasting," "short-term fasting" (lasting 2-3 days), "prolonged fasting" (≥4 consecutive days), and "religious fasting." "Intermittent fasting" (repetitive fasting periods lasting ≤48 h), "time-restricted eating," and "fasting-mimicking diet" were discussed most. This study provides expert recommendations on fasting terminology for future research and clinical applications, facilitating communication and cross-referencing in the field.
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.
An active approach to statin selection for primary ASCVD prevention significantly increases statin utilization and lowers LDL-C compared to passive usual care.
Background: Intermittent fasting may increase longevity and lower cardiometabolic risk. This study evaluated whether fasting modifies clinical risk scores for mortality [i.e., Intermountain Mortality Risk Score (IMRS)] or chronic diseases [e.g., Pooled Cohort Risk Equations (PCRE), Intermountain Chronic Disease score (ICHRON)]. Methods and results: controls (n = 33), and change scores for PCRE, ICHRON, HOMA-IR, and a metabolic syndrome score (MSS). Age averaged 49 years; 65% were female. Intermittent fasting increased IMRS (0.78 ± 2.14 vs. controls: -0.61 ± 2.56; p = 0.010) but interacted with baseline IMRS (p-interaction = 0.010) to reduce HOMA-IR (but not MSS) more in subjects with higher baseline IMRS (median HOMA-IR change: fasters, -0.95; controls, +0.05) vs. lower baseline IMRS (-0.29 vs. -0.32, respectively). Intermittent fasting reduced ICHRON (-0.92 ± 2.96 vs. 0.58 ± 3.07; p = 0.035) and tended to reduce PCRE (-0.20 ± 0.22 vs. -0.14 ± 0.21; p = 0.054). Conclusions: Intermittent fasting increased 1-year IMRS mortality risk, but decreased 10-year chronic disease risk (PCRE and ICHRON). It also reduced HOMA-IR more in subjects with higher baseline IMRS. Increased IMRS suggests fasting may elevate short-term mortality risk as a central trigger for myriad physiological responses that elicit long-term health improvements. Increased IMRS may also reveal short-term fasting-induced safety concerns.
Introduction Long-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE. Methods We studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization). Results The average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p -value = 0.013). Conclusions Higher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials.
Aims Residual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result. Methods and Results EVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm 3 vs. an increase of 41 mm 3 , p = 0.008), widening at 18 months (6 mm 3 vs. 58 mm 3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p < 0.01 (sustained at 18 months), generalizing well to a validation cohort. Conclusion Plaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response.
Should not yet change HFrEF statin practice; leaves open causal MACE benefit pending randomized trials.
May inform NSTEMI prognosis by SMuRF status; hypothesis-generating and contrasts with STEMI observations, needing prospective confirmation.
May aid mortality stratification after catheterisation; hypothesis-generating for clinical integration pending trials.
SMuRF-less STEMI was associated with lower long-term MACE; leaves open whether this reflects true benefit or unmeasured confounding versus prior reports.
Prior AF independently predicts worse COVID-19 outcomes; confirms it as a prognostic factor in acute viral illness.
