Joseph Brent Muhlestein

• MD
• Managing Director at Intermountain Medical Center

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....

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: In...

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....

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 Cardio...

Background Statins can improve outcomes in high-risk primary prevention populations. However, application in clinical practice has lagged. Objectives The objective of this study was to compare an active vs a passive strategy (ie, usual care) to statin prescription for primary prevention of atherosclerotic cardiovascular disease (ASCVD). Methods A...

Background: Low vitamin (vit) D serum levels in observational data are associated with increased cardiovascular (CV) events. Prevalence of vit D deficiency (≤20 ng/mL) in the USA is estimated at 40%. Meanwhile, doses for USA recommended dietary allowance (RDA) are 600-800 IU. Several randomized trials of vit D therapy did not use serum levels to ta...

Background: Many observational studies have reported associations between low 25-hydroxyvitamin D (25[OH] vit D) levels and adverse cardiovascular (CV) outcomes. Recent randomized clinical trials have not found vitamin (vit) D 3 supplementation to reduce CV risk. However, these trials gave “blanket” doses regardless of 25[OH] vit D level, with none...

Introduction: Statins are used to treat those with hyperlipidemia and at high risk for a cardiovascular event, including women of childbearing potential. Traditionally, statins have been contraindicated during pregnancy because of a theoretical risk of teratogenicity. The FDA removed the black box warning for usage during pregnancy in 2021and recen...

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...

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...

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 d...

Patients with ST-elevation myocardial infarction (STEMI), but without standard modifiable risk factors (SMuRF-less), are surprisingly common and appear to have a worse, or at best similar, short-term prognosis. However, relatively little attention has been paid to the prevalence and prognosis of SMuRF-less patients with non-STEMI (NSTEMI). The aim...

Background: Complex and incompletely understood metabolic dysfunction associated with inflammation and protein-energy wasting contribute to the increased mortality risk of older patients and those with chronic organ diseases affected by cachexia, sarcopenia, malnutrition, and frailty. However, these wasting syndromes have uncertain relevance for p...

Studies primarily outside the United States have reported that SMuRF-less STEMI patients are surprisingly common (14–27%) and have a worse in-hospital/short-term prognosis. Given potential demographic and management differences over time and in the US, we aimed to identify the proportion and outcomes of SMuRF-less STEMI patients in a large US healt...

Introduction: The clinical spectrum of COVID-19 can range from asymptomatic to severe, with severe resulting in part from an intense inflammatory response. Selective serotonin reuptake inhibitor (SSRI) is the most commonly prescribed class of antidepressants and has anti-inflammatory and anti-platelet effects. Recent studies reported greater surviv...

Introduction: Recently there has been a much-needed focus on disparity and inequity in cardiovascular disease (CVD) care. Race, ethnicity, sex, and geography are shown to impact CVD care and outcomes. Perhaps one of the reasons for this is the lack of diversity and representation in CVD research studies, especially in non-sponsored research studies...

Introduction: There has been considerable discussion regarding the value of follow-up LDL-C measurements in secondary prevention of major adverse cardiac events (MACE). We therefore set out to determine in a large healthcare system whether measurement of LDL-C after an ASCVD event was associated with a difference in MACE during follow-up and whethe...

Introduction: When patients (pts) are diagnosed with HFrEF, it is hoped that medical therapy will improve their left ventricular ejection fraction (LVEF). However, which baseline clinical characteristics may predict an improvement in LVEF after medical treatment remains unclear. Methods: Pts with a baseline LVEF ≤35% and a follow-up LVEF ≥180 days...

Introduction: Recent interest has focused on STEMI patients (pts) without standard modifiable risk factors (SMuRF-less), noting that they are surprisingly common (14-27%). These studies have reported them to have a worse, or at best similar, in-hospital/short-term prognosis. However, relatively little attention has been paid to the prevalence and p...

Introduction: Statins traditionally have been contraindicated during pregnancy because of a theoretical risk of teratogenicity. However, emerging evidence to suggest relative safety and potential harm in contraindicating statins in high cardiovascular (CV)-risk pregnancies have led the FDA in 2021 to remove the “Pregnancy Category X” label. This ha...

Introduction: Health, wellness, and healthcare are most effectively and efficiently managed when health status is quantitatively measured. The Intermountain Mortality Risk Score (IMRS) is a well-validated low-cost decision tool calculated from the complete blood count and basic metabolic profile that can be electronically deployed to inform clinici...

Introduction: Statins play a critical role in primary and secondary ASCVD prevention. Although uncommon, myalgias and abnormal liver function tests (LFTs) may limit statin use. Alcohol consumption also is a common cause of LFT elevations. It is unknown whether or to what extent concurrent alcohol and statin use may alter elevated LFT risk and impac...

Background: Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials. Methods: The cognitive decline and dementia in patients with non-v...

Background New-onset atrial fibrillation (AF) during COVID-19 infection is associated with worse cardiovascular outcomes and mortality, with new-onset AF being associated with worse clinical outcomes than recurrent AF. However, it is not known whether a prior history of AF is an independent cardiovascular risk factor predicting worse outcomes in CO...

Alcohol consumption has long been associated with cardiovascular (CV) benefit, but it also has adverse potential. Statins are currently widely used for CV prevention. We evaluated whether alcohol use is associated with lower CV risk in patients on statins. We searched Intermountain Medical Center cardiac catheterization laboratory medical records f...

Objectives Intermittent fasting boosts some host defence mechanisms while modulating the inflammatory response. Lower-frequency fasting is associated with greater survival and lower risk from COVID-19-related comorbidities. This study evaluated associations of periodic fasting with COVID-19 severity and, secondarily, initial infection by SARS-CoV-2...

Objectives: To support development of a robust postmarket device evaluation system using real-world data (RWD) from electronic health records (EHRs) and other sources, employing unique device identifiers (UDIs) to link to device information. Methods: To create consistent device-related EHR RWD across 3 institutions, we established a distributed...

Background Hyperkalaemia (HK) is a serious and potentially life-threatening condition. Both acute and chronic conditions may alter potassium homeostasis. Our aim is to describe HK incidence, clinical outcomes, and associated resource use within a large, integrated healthcare system. Methods Adult patients seen at Intermountain Healthcare facilitie...

Objectives: The Intermountain Risk Score (IMRS), composed using published sex-specific weightings of parameters in the complete blood count (CBC) and basic metabolic profile (BMP), is a validated predictor of mortality. We hypothesised that IMRS calculated from prepandemic CBC and BMP predicts COVID-19 outcomes and that IMRS using laboratory resul...

Objectives Intermittent fasting boosts some mechanisms of host defense against infection while modulating the inflammatory response. Lower-frequency periodic fasting is associated with greater survival and lower risk of comorbidities that exacerbate COVID-19. This study evaluated the association of periodic fasting with COVID-19 severity and, secon...

Aims: Mitral valve prolapse (MVP) is a common valvular heart disease with a prevalence of >2% in the general adult population. Despite this high incidence, there is a limited understanding of the molecular mechanism of this disease, and no medical therapy is available for this disease. We aimed to elucidate the genetic basis of MVP in order to bet...

Background and Aims Intermittent fasting reduces risk of interrelated cardiometabolic diseases, including type 2 diabetes and heart failure (HF). Previously, we reported that intermittent fasting reduced homeostasis model assessment of insulin resistance (HOMA-IR) and Metabolic Syndrome Score (MSS) in the WONDERFUL Trial. Galectin-3 may act to redu...

Background SARS-CoV-2 vaccines are being administered on an unprecedented scale. Assessing the risks of side effects is needed to aid clinicians in early detection and treatment. This study examined the risk of inflammatory heart disease, including pericarditis and myocarditis, following SARS-CoV-2 vaccination. Methods Intermountain Healthcare pat...

Red cell distribution width (RDW) predicts cardiovascular outcomes, but it is unstudied with regard to intermittent fasting. In WONDERFUL trial subjects, the effect of the interaction between baseline RDW and intermittent fasting on changes in insulin and other cardiometabolic endpoints and the effect of fasting on changes in RDW were evaluated. Th...

Objectives This study sought to determine the feasibility of performing an extensive randomized outcomes trial comparing a coronary artery calcium (CAC)- versus a pooled cohort equations (PCE) risk score–based strategy for initiating statin therapy for primary atherosclerotic cardiovascular disease (ASCVD) prevention. Background Statin therapy is...

Background The insulin like growth factor (IGF) axis emerged as an important pathway in heart failure with preserved ejection (HFpEF). We aimed to identify IGF phenotypes associated with HFpEF in the context high-dimensional proteomic profiling. Methods From the Intermountain INSPIRE Registry, we identified 96 patients with HFpEF and matched contr...

Introduction: The use of statins in patients (pts) with heart failure (HF) is controversial. In patients without HF, statins reduce the risk of atherosclerotic cardiovascular disease (ASCVD), including HF-related events. In contrast, no benefit was observed in statin-treated HF pts in the CORONA and GISSI-HF trials. However, issues with generalizab...

Introduction: Intermittent fasting decreases cardiometabolic risk factors, heart failure (HF) risk, and type 2 diabetes risk. Sodium-glucose transport 2 (SGLT-2) inhibitors reduce diabetes and HF risk and a study of canagliflozin reported that it raised galectin-3 levels (Januzzi 2017). Previously in the WONDERFUL trial (NCT02770313), intermittent...

Background: Dealing with statin intolerance represents a major clinical challenge. Controlled clinical trials suggest that a large percentage of statin intolerance may be due to a “nocebo effect”, wherein adverse reactions are linked to pill ingestion irrespective of actual pill content (e.g., SAMSON trial). We tested whether statin intolerance was...

Background: As SARS-CoV-2 vaccines are being administered on an unprecedented scale, it is critical to carefully assess risks to aid clinicians in the early detection and treatment of potential side effects. Here we examine increases in the risk of pericarditis following SARS-CoV-2 vaccination. Methods: We examined pericarditis cases from December...

Introduction: Intermittent fasting reduces weight and cardiometabolic risk factors. In the WONDERFUL Trial (NCT02770313), intermittent fasting reduced homeostatic model assessment of insulin resistance (HOMA-IR) and the Metabolic Syndrome Score (MSS), with insulin having the largest decline. The red cell distribution width (RDW) measures the disper...

Introduction: Adults <40-yrs (20-39) may have elevated cardiovascular risk based on higher LDL-C (e.g., ≥160 mg/dL). We sought to compare the risk of MACE (all-cause death, MI, ischemic stroke, heart failure hospitalization, and peripheral vascular disease [PVD]) in adults <40-yrs and LDL-C ≥160 to 189 compared with LDL-C <160 mg/dL. Hypothesis: Ad...

Introduction: Mitochondrial DNA copy number (mtDNA-CN) is associated with cardiovascular disease (CVD) and mortality. Here we examine, in a high-risk CVD population, the association with prevalent coronary artery disease (CAD) and subsequent major adverse events (MACE) at 1-,5- and 10-year follow-up of mtDNA-CN. Methods: Consecutive subjects (n=226...

Background: Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor remains standard treatment for patients undergoing PCI, and clopidogrel remains the most used agent. Many patients (pts) are genetically resistant to clopidogrel and may not receive its full benefit. However, the use of platelet function testing to provide individualize...

Background: The COVID-19 pandemic has affected nearly every aspect of daily life. The interpersonal loss due to quarantining and social distancing, compounded with societal disruption has negatively affected mental health. Once established, mental health conditions can become chronic with having subsequent effects on additional risk factors and dis...

Background: In the presence of comorbid conditions, COVID-19 infections are known to require more advanced treatment, poorer outcomes and have longer-term sequelae. New-onset atrial fibrillation (AF) during COVID-19 infection has been associated with worse cardiovascular outcomes but not mortality. However, it remains unclear whether a prior histor...

Sinus of Valsalva aneurysm (SoVA) is an uncommon clinical entity, which is present in roughly 0. 09% of the general population. The cause can either be acquired or congenital. Clinically the SoVA of unruptured status are rarely captured or even diagnosed due to atypical clinical presentations. Here, we present a rare case of exertional angina pecto...

Background Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, because of ventricular proarrhythmia risk, a history of myocardial infarction (MI) or coronary artery disease (CAD) is a flecainide exclusion, and stress testing is used to exclude ischemia. We assessed whether absent/mild coronary artery calcium (CAC) can suppl...

Background Medication adherence is generally low and challenging to address because patient actions control healthcare delivery outside of medical environments. Behavioral nudging changes clinician behavior, but nudging patient decision-making requires further testing. This trial evaluated whether behavioral nudges can increase statin adherence, me...

Vertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQT...

Background Low-density lipoprotein cholesterol (LDL-C) predicts heart disease onset and may be reduced by intermittent fasting. Some studies, though, reported that fasting increased LDL-C; however, no study evaluated LDL-C as the primary endpoint. This randomized controlled trial evaluated the effect of low-frequency intermittent fasting on LDL-C a...

Background: Class 1C antiarrhythmic drugs(AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction(MI). Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease(CAD). However, long-term data are lacking to know if unique risks exis...

Both time in therapeutic range (TTR) for anticoagulation and depression are associated with dementia risk. The purposes of this study were to examine the impact of depression on TTR and to describe the partitioned contribution of depression and TTR on long-term dementia risk. We studied 14,953 patients anticoagulated with warfarin (target INR 2-3)...

Background Several recent trials have evaluated invasive versus medical therapy for stable ischemic heart disease. Importantly, patients with significant left main coronary stenosis (LMCS) were excluded from these trials. In the ISCHEMIA trial, these patients were identified by a coronary CT angiogram (CCTA), which adds time, expense, and contrast...

This case-control study examined the association of sociodemographic factors and blood group type with risk of SARS-CoV-2 infection and severity of COVID-19.

Aims: Despite proven benefits of LDL-C lowering among those with atherosclerotic cardiovascular disease (ASCVD), statin adherence remains low. Very little real-world data exist on the effect of long-term statin adherence on cardiovascular outcomes. Methods and results: A total of 7,339 patients ≥18 years first diagnosed with ASCVD with a statin...

Background: Hyperkalaemia (HK) is a serious and potentially life-threatening condition. Both acute and chronic conditions may alter potassium homeostasis. Our aim is to describe HK incidence, clinical outcomes, and associated resource use within a large, integrated healthcare system. Methods: Adult patients seen at Intermountain Healthcare faciliti...

Low vitamin D (serum or plasma 25‐hydroxyvitamin D (25(OH)D)) is a global pandemic and associates with a greater prevalence in all‐cause and cardiovascular mortality and morbidity. Open‐heart surgery is a form of acute stress that decreases circulating 25(OH)D concentrations and exacerbates the preponderance of low vitamin D in a patient population...

Aims This analysis qualitatively describes the impact of hyperkalaemia (HK) and renin‐angiotensin‐aldosterone system inhibitor (RAASi) use on clinical outcomes in patients with heart failure (HF). Methods and results Patients were included if they were ≥18 years old; had a serum potassium result between 1 January 2003 and 3 December 2018; had ≥2 s...

Introduction: It is well-documented that COVID-19 patients with pre-existing cardiovascular-related disorders are at higher risk of a complicated course. It would be valuable to integrate individual risk factors into overall risk scores for hospitalization and death from COVID-19. Methods: The Intermountain Healthcare medical record database was se...

Introduction: High-frequency intermittent fasting (IF) diets reduce weight similarly to continuous calorie restriction (CR). In patients with type 2 diabetes, twice-weekly IF and CR equivalently reduced HbA1c. IF may improve chronic disease risk factors, but no controlled trial has evaluated whether IF reduces low-density lipoprotein cholesterol (L...

Background: Treatment for COVID-19 has created surges in hospitalizations, intensive care unit (ICU) admissions, and the need for advanced medical therapy and equipment, including ventilators. Identifying patients early on who are at risk for more intensive hospital resource use and poor outcomes could result in shorter hospital stays, lower costs,...

Introduction: Studies have previously shown that atrial fibrillation (AF) is associated with dementia. The mechanisms are likely multifactorial, but may involve treatment strategies that include anticoagulation use and rhythm management, particularly when used early. Patients that have earlier-life depression are at risk of dementia. However, depre...

Introduction: SARS-CoV-2 requires the ACE-2 receptor to gain cellular entry, leading to concerns as to whether the use of ACEIs/ARBs may adversely affect patients (pts) exposed to the virus. Because of the potential for multiple confounding variables, determining their real impact through observational study may require the use of a carefully adjus...

Objective: Both time in therapeutic range (TTR) for anticoagulation and depression are associated with dementia risk. However, it is unknown if depression impacts TTR or their combined effect on dementia risk. Methods: We studied 14,953 patients who were chronically anticoagulated with warfarin (target INR 2-3) for atrial fibrillation (AF), venous...

Background: Class IC antiarrhythmic drugs (AAD) are a standard treatment of cardiac arrhythmias but are associated with harm in patients with prior myocardial infarction (MI)). Consensus guidelines have advocated that these drugs not be used in patients with coronary artery disease (CAD). However, the risk of Class IC AAD in patients with stable CA...

Background: Atrial Fibrillation (AF) is a significant risk factor for multiple forms of dementia. Although late-life depression may be a manifestation of dementia, earlier-life depression is a risk factor for dementia. The influence of earlier-life depression in patients with AF as a risk factor for dementia is unknown. Methods: AF patients (Januar...

Background: Inpatient initiation of sotalol (STL) and dofetilide (DFL) for patients with symptomatic atrial fibrillation (AF) can be variable, more so for STL. Objective: Define the impact of inpatient initiation of STL and DFL approaches on patient in-hospital costs and outcomes. Methods: AF patients that were admitted for STL (n=133) or DFL (n=38...

Background: Residual cardiovascular (CV) risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total CV events by 30%, but the mechanisms of benefit are not fully understood. The EVAPORATE trial evaluated the effects of IPE as adjunct to statins on adverse atherosclerotic plaque characteristics by CCTA. Here we use a nov...

Introduction: Generating real-world evidence for regulatory and research purposes is a fundamental transformation of healthcare. To develop and demonstrate the operational components, we created the BUILD network, a framework for the longitudinal follow-up of all patients undergoing PCI at three large health systems, Mercy, Geisinger, and Intermoun...

Background: Over the past decade, the FDA has approved several new medications that are highly effective when added to existing standard therapy in the treatment of heart failure with reduced ejection fraction (HFrEF). It is possible that, despite the presence of substantial evidence regarding the clinical effectiveness of these new medications, th...

Introduction: The ISCHEMIA trial tested an invasive vs. an initial medical strategy in patients (pts) with stable coronary disease and evidence of ischemia. No significant difference between strategies in cardiovascular events was found at 3.2 years. However, pts were screened before randomization by coronary CT angiography (CCTA) to exclude ≥50% l...

Background: The Intermountain Risk Sore (IMRS) is a general health clinical decision tool based on the complete blood count (CBC) and basic metabolic profile (BMP). IMRS was developed to predict all-cause mortality. IMRS was validated previously in patients from the US and elsewhere, including in general medical and surgical patients and in diagnos...

Background: Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, the Cardiac Arrhythmia Suppression Trial (CAST) showed an increased risk of fatal ventricular arrhythmia with flecainide use after myocardial infarction (MI). Thus, a history of MI or coronary artery disease (CAD) is a flecainide exclusion, and stress testing i...

Background: Takotsubo (stress) cardiomyopathy (TCM) is characterized by transient apical left ventricular dysfunction precipitated by emotional or physical stress. Its presentation makes it difficult to differentiate from an acute coronary syndrome. A suggestive echocardiogram plus normal coronary angiography most often are used for diagnosis. Rad...

Aims Animal models repeatedly show fasting increases longevity. Human data, though, are limited to anecdotal claims. This study evaluated the association of routine fasting with survival and, secondarily, with incident major adverse cardiovascular events. Methods and results Cardiac catheterization patients enrolled in the Intermountain INSPIRE lo...

Genetic factors play an important role in nonischemic dilated cardiomyopathy (NIDC). However, prime opportunities remain for genetic discovery and prognostic understanding. TITIN gene truncating variant mutations (TTNtv) are of interest because of their frequent appearance in NIDC series. We sought to discover known and novel TTNtv mutations in a N...

Aims: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE...

Aims: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular(CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have no...

Background The Intermountain Chronic Disease Risk Score (ICHRON) is a primary prevention risk prediction tool that uses commonly ordered blood tests and is designed to be calculated by the electronic health record. ICHRON was highly predictive of 3-year chronic disease (ChrD) diagnosis in an internal validation; however, external validation is need...

Statins are among the most prescribed medications due to well-documented benefits of safely lowering LDL cholesterol. However, many patients are unable or unwilling to continue statin therapy because of real or perceived adverse effects. This study sought to increase understanding about which patients are unlikely to tolerate statin therapy. The In...

Hyperkalemia (HK) can be a life-threatening condition. Chronic kidney disease and treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin II receptor blockers (ARB) are key predictors of HK risk. Other medications (e.g. beta-blockers, immunosuppressants, non-steroidal anti-inflammatory drug [NSAIDs], potassium [K + ] suppl...

Atherosclerotic cardiovascular disease (ASCVD) is the most important cause of morbidity and mortality nationally and internationally. Improving ASCVD risk prediction is a high clinical priority. We sought to determine which of 3 ASCVD risk scores best predicts the need for revascularization and incident major adverse coronary events (MACE) in sympt...

Background MicroRNAs (miRNA)s regulate expression of genes involved in various processes including cardiac automaticity, conduction, excitability, and fibrosis and therefore may provide a diagnostic utility to identify high-risk patients for atrial fibrillation (AF). In this study, we tested the hypothesis that specific profiles of circulating miRN...

Atrial fibrillation (AF) is a source of altered brain perfusion and ischemia, potentially leading to cerebral injury and blood brain barrier (BBB) disruption, which may result in the permeation of neurospecific molecules into the bloodstream. We retrospectively analyzed circulating levels of biomarkers of cerebral injury: Astrocyte-specific glial a...

Introduction: Hyperthyroidism is a known precipitating factor for atrial fibrillation (AF). However, recent reports have suggested an increased risk of AF with free thyroxine (fT4) levels even within the upper reference ('normal') range. We sought to test whether higher fT4 levels within the reference range are associated with an increased risk of...

Objective: Oxidative stress is associated with several cardiovascular risk factors and cardiovascular disease. Damaged cells release cell-free DNA (cfDNA) into the circulation; oxidized cfDNA presence in the plasma indicates a pathological process in the context of oxidative stress. We hypothesized that biomarker of oxidative DNA damage 8-hydroxy-...

Background: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subseq...

Background: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 parti...

Introduction The apolipoprotein A1 (apoA1) remnant ratio has been identified as an independent cardiovascular (CV) risk factor. Higher apoA1 remnant ratios may predict lower CV risk in some patients. This analysis aimed to evaluate the effects of evolocumab on the change from baseline in the apoA1 remnant ratio compared with placebo. Methods This...

Glycoprotein IIb/IIIa inhibitors, used as a standard intravenous bolus followed by a prolonged infusion for 12 to 18 hours, reduces ischemic complications during percutaneous coronary interventions (PCI) but often at a cost of increased bleeding. Today, when dual oral antiplatelet therapy is routine, heparin use plus short-term (bolus alone or with...

Intermittent fasting (IF) has been connected with health benefits such as weight loss, lower risk of coronary artery disease (CAD) and diabetes, increased longevity, and improved quality of life. However, the mechanisms of these IF benefits in humans require further investigation. This study sought to elucidate some of these mechanisms through seco...

Objective: To apply the practical parsimonious modeling method of the Intermountain Mortality Risk Score in a primary care environment to predict chronic disease (ChrD) onset. Patients and methods: Primary care patients free of ChrD (women: n=98,711; men: n=45,543) were evaluated to develop (70% [n=95,882] of patients) and validate (the other 30...

Background Oral anticoagulation (OAC) therapy guidelines recommend using CHA 2 DS 2 -VASc to determine OAC need in atrial fibrillation (AF). A usable tool, CHA 2 DS 2 -VASc is challenged by its predictive ability. Applying components of the complete blood count and basic metabolic profile, the Intermountain Mortality Risk Score (IMRS) has been exte...