Coronary Calcium Is Elevated in Patients with Myocardial Infarction without Standard Modifiable Risk Factors.

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.

Intermittent fasting and changes in clinical risk scores: Secondary analysis of a randomized controlled trial.

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: Subjects (N = 71) completing the WONDERFUL trial were aged 21-70 years, had ≥1 metabolic syndrome criteria, elevated cholesterol, and no anti-diabetes medications, statins, or chronic diseases. The intermittent fasting arm underwent 24-h water-only fasting twice-per-week for 4 weeks and once-per-week for 22 weeks (26 weeks total). Analyses examined the IMRS change score at 26 weeks vs. baseline between intermittent fasting (n = 38) and ad libitum 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.

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events.

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.

Frequency and Outcomes of Patients Presenting with Non-ST Elevation Myocardial Infarction (NSTEMI) without Standard Modifiable Risk Factors: A US Healthcare Experience.

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 of our study was to identify the proportion and outcomes of SMuRF-less NSTEMI patients in a large US healthcare population. Patients with NSTEMI between 2001-2021 presenting to Intermountain Healthcare hospitals and catheterization laboratories were included. SMuRF-less status was defined as no clinical diagnosis of, or treatment for, hypertension, hyperlipidemia, diabetes, and smoking. Outcomes were assessed at 60 days and long-term for major adverse cardiovascular events (MACE: death, myocardial infarction, and heart failure hospitalization). Multivariable Cox proportional hazard regression was used to determine MACE hazard ratios (HR) for SMuRF-less versus patients with SMuRF. NSTEMI patients totaled 8196, of which 1458 (17.8%) were SMuRF-less. SMuRF-less patients were younger, more frequently male, had fewer comorbidities, and were slightly less likely to have revascularization. For SMuRF-less patients, 60-day MACE outcomes were lower (adj HR = 0.55, p < 0.0001), and this persisted for long-term MACE outcomes (adj HR = 0.64, p < 0.0001) and for each of its components. In this large US healthcare population, SMuRF-less NSTEMI presentation, as with STEMI presentation, was found to be common (17.8%). However, unlike STEMI reports, short- and long-term outcomes were better for SMuRF-less patients. Further studies to increase understanding of risk factors and preventive measures for NSTEMI in SMuRF-less patients are indicated.

Impact of Statin Therapy in Heart Failure Patients: Results of a Large Real-World Experience.

Background: The use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk, including HF-related events. However, in some large studies, no benefit was seen in statin-treated HF patients. Objectives: The purpose of this study was to determine the impact of statin therapy in HF with reduced ejection fraction (HFrEF). Methods: Intermountain Healthcare medical records identified patients with a HF diagnosis and an ejection fraction of ≤40%. Patients prescribed and not prescribed a statin were compared for major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) (median of 4.5 years follow-up). Statin use was defined as use at or after a HF diagnosis but at least 60 days before MACE or end of follow-up. Cox proportional hazards regression was used to determine the relationship between statin use and outcomes. Results: A total of 15,010 patients (n = 9,641 [64%] on statins) were studied. Statin use was associated with more frequent ASCVD risk factors yet a lower risk of MACE risk (adjusted HR: 0.53; 95% CI: 0.51-0.56; P < 0.0001). Benefit was similar for primary and secondary prevention patients and for prior and new statin prescriptions. Using time-varying hazard ratio analysis, the longer the patient was on a statin, the greater the reduction in risk of MACE (P < 0.0001). Conclusions: These results suggest a potential benefit of selective statin use in the real-world management of HFrEF patients with ASCVD or at high ASCVD risk.

Impact of Active vs Passive Statin Selection for Primary Prevention: The CorCal Vanguard Trial.

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 total of 3,770 patients ≥50 years of age without a history of ASCVD or statin use were invited to enroll in CorCal, with 601 consenting to participate. These patients were randomized 1:1 to statin initiation guided by the pooled cohort equation or by coronary artery calcium scoring (CACS). Outcomes (2.8-year follow-up) compared patients managed actively vs passively (randomly invited but declined or did not respond). Results: Patient demographics were well matched. Statin recommendation was common among enrolled patients (41.7%). During follow-up, 25.3% of active patients were taking a statin vs 9.8% managed passively (P < 0.0001). Active patients had more lipid panels (median 2.0 vs 1.0), lower low-density lipoprotein cholesterol (109 vs 117 mg/dL) (both P < 0.0001), and a low rate of major adverse cardiovascular events during follow-up (0.6% vs 1.0%, P = 0.47). Statistical comparisons included t-tests, chi-squared tests, nonparametric tests, and time-to-event tests as appropriate. Conclusions: An active approach to statin selection for primary ASCVD prevention identified a large treatment opportunity and led to over twice as many patients on statins compared to passive (usual care) management. A large CorCal Outcomes Trial is underway to more definitively assess the impact on outcomes of active management of statins for primary prevention.

Atrial fibrillation is a risk factor for major adverse cardiovascular events in COVID-19.

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 COVID-19 patients. The present investigation sought to determine whether AF should be considered a risk factor for worse outcomes in COVID-19 illness. Methods: From March 2020-September 2021 patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n = 3623) were propensity matched to non-AF SARS-CoV-2 positive patients (n = 3610). Multivariable Cox hazard regression was used to determine subsequent MACE (all-cause death, myocardial infarction, HF and stroke) risk among patients with and without AF. Results: COVID-19 patients with a prior history of AF were more likely to be hospitalized, require ICU care, supplemental oxygen, and ventilator support compared COVID-19 patients without a history of AF. There was a 1.40 times higher rate of MACE in the COVID-19 patients with prior AF compared to patients without prior AF (p < 0.0001). The increased rate of MACE in patients with a prior AF was primarily secondary to increases in heart failure hospitalization and death. This finding was confirmed even after controlling for acute AF during COVID-19 illness (HR 1.22, p = 0.0009). Conclusion: AF history was shown to be an independent risk factor for MACE during a COVID-19 illness. Both recurrent and principally new-onset AF were associated with an increased risk of poor clinical outcomes during COVID-19 illness.

Is Alcohol Consumption Associated with a Lower Risk of Cardiovascular Events in Patients Treated with Statins? An Observational Real-World Experience.

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 for patients with a prescription history of statin use or non-use and a self-report of alcohol use or non-use. Alcohol and statin prescription data were available together with long-term (mean [SD], 4.4 [2.4] years) major adverse CV events (MACE, including death, myocardial infarction, stroke, and heart failure hospitalizations) in 1701 patients at primary and 3266 patients at secondary CV risk. MACE rates were lower for primary prevention alcohol users than non-users not on statins (adjusted hazard ratio [adj-HR] 0.50 (95% CI 0.33, 0.78, p = 0.002), but not for those on statins (adj-HR 0.84, CI 0.54, 1.32, p = 0.45). MACE rates for secondary prevention were not reduced by alcohol consumption either in statin non-users or users (adj HR 1.18, CI 0.85, 1.64, p = 0.33; adj HR 1.08, CI 0.87, 1.35, p = 0.45, respectively). These findings, together with other recent supportive studies, can help inform personal choices in alcohol consumption and professional society recommendations for CV prevention.

Intermittent fasting and changes in Galectin-3: A secondary analysis of a randomized controlled trial of disease-free subjects.

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 reduce insulin resistance. This post hoc evaluation assessed whether intermittent fasting increased galectin-3. METHODS AND RESULTS: The WONDERFUL Trial enrolled adults ages 21-70 years with ≥1 metabolic syndrome features or type 2 diabetes who were not taking anti-diabetic medication, were free of statins, and had elevated LDL-C. Subjects were randomized to water-only 24-h intermittent fasting conducted twice-per-week for 4 weeks and once-per-week for 22 weeks or to a parallel control arm with ad libitum energy intake. The study evaluated 26-week change scores of galectin-3 and other biomarkers. Overall, n = 67 subjects (intermittent fasting: n = 36; control: n = 31) completed the trial and had galectin-3 results. At 26-weeks, the galectin-3 change score was increased by intermittent fasting (median: 0.793 ng/mL, IQR: -0.538, 2.245) versus control (median: -0.332 ng/mL, IQR: -0.992, 0.776; p = 0.021). Galectin-3 changes correlated inversely with 26-week change scores of HOMA-IR (r = -0.288, p = 0.018) and MSS (r = -0.238, p = 0.052). Other HF biomarkers were unchanged by fasting. CONCLUSION: A 24-h water-only intermittent fasting regimen increased galectin-3. The fasting-triggered galectin-3 elevation was inversely correlated with declines in HOMA-IR and MSS. This may be an evolutionary adaptive survival response that protects human health by modifying disease risks, including by reducing inflammation and insulin resistance. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02770313 (registered on May 12, 2016; first subject enrolled: November 30, 2016; final subject's 26-week study visit: February 19, 2020).

Real-world clinical burden and economic assessment associated with hyperkalaemia in a large integrated healthcare system: a retrospective analysis.

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 facilities with a serum potassium (sK) result between January 1, 2003 and December 31, 2018 were retrospectively studied. Descriptive assessment of a population with detected HK, defined by any sK > 5.0 mmol/L and HK frequency and severity to associated resource use and characteristics of HK predictors were made. Multivariable Cox hazard regression was used to evaluate HK to outcomes. RESULTS: Of 1,208,815 patients included, 13% had HK. Compared to no-HK, HK patients were older (60 ± 18 vs 43 ± 18 years, P < 0.001), male (51% vs 41%, P < 0.001), and had greater disease burden (Charlson Comorbidity Index 3.5 ± 2.8 vs 1.7 ± 1.4, P < 0.001). At 3 years, more HK patients experienced major adverse cardiovascular events (MACEs) (19 vs 3%, P < 0.001), persisting post-adjustment (multivariable hazard ratio = 1.60, P < 0.001). They incurred higher costs for emergency department services ($552 ± 7,574 vs $207 ± 1,930, P < 0.001) and inpatient stays ($10,956 ± 93,026 vs $1,477 ± 21,423, P < 0.001). HyperK Risk Scores for the derivation and validation cohorts were: 44% low-risk, 45% moderate-risk, 11% high-risk. Strongest HK predictors were renal failure, dialysis, aldosterone blockers, diabetes, and smoking. CONCLUSION: Within this large system, HK was associated with a large clinical burden, affecting over 1 in 10 patients; HK was also associated with increased 3-year MACE risk and higher medical costs. Although risk worsened with more severe or persistently recurring HK, even mild or intermittent HK episodes were associated with significantly greater adverse clinical outcomes and medical costs. The HyperK Score predicted patients who may benefit from closer management to reduce HK risk and associated costs. It should be remembered that our assumptions are valid only for detected HK and not HK per se.

Association of the Intermountain Risk Score with major adverse health events in patients positive for COVID-19: an observational evaluation of a US cohort.

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 results tested at COVID-19 diagnosis is also predictive. DESIGN: Prospective observational cohort study. SETTING: Primary, secondary, urgent and emergent care, and drive-through testing locations across Utah and in sections of adjacent US states. Viral RNA testing for SARS-CoV-2 was conducted from 3 March to 2 November 2020. PARTICIPANTS: Patients aged ≥18 years were evaluated if they had CBC and BMP measured in 2019 and tested positive for COVID-19 in 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was a composite of hospitalisation or mortality, with secondary outcomes being hospitalisation and mortality separately. RESULTS: Among 3883 patients, 8.2% were hospitalised and 1.6% died. Subjects with low, mild, moderate and high-risk IMRS had the composite endpoint in 3.5% (52/1502), 8.6% (108/1256), 15.5% (152/979) and 28.1% (41/146) of patients, respectively. Compared with low-risk, subjects in mild-risk, moderate-risk and high-risk groups had HR=2.33 (95% CI 1.67 to 3.24), HR=4.01 (95% CI 2.93 to 5.50) and HR=8.34 (95% CI 5.54 to 12.57), respectively. Subjects aged <60 years had HR=3.06 (95% CI 2.01 to 4.65) and HR=7.38 (95% CI 3.14 to 17.34) for moderate and high risks versus low risk, respectively; those ≥60 years had HR=1.95 (95% CI 0.99 to 3.86) and HR=3.40 (95% CI 1.63 to 7.07). In multivariable analyses, IMRS was independently predictive and was shown to capture substantial risk variation of comorbidities. CONCLUSIONS: IMRS, a simple risk score using very basic laboratory results, predicted COVID-19 hospitalisation and mortality. This included important abilities to identify risk in younger adults with few diagnosed comorbidities and to predict risk prior to SARS-CoV-2 infection.

Spectrum of radionuclide perfusion study abnormalities in takotsubo cardiomyopathy.

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. Radionuclide perfusion study (RPS) findings in TCM, including by positron emission tomography (PET), have been poorly characterized. METHODS AND RESULTS: Intermountain Healthcare electronic medical records were searched from 2009 to 2019 for patients with a discharge diagnosis of TCM, stress CM, or takotsubo syndrome. 16 TCM patients with an RPS, including by PET in 8, were identified: 13 (81%) were women; age averaged 72 years (50-89 years); 14 had an identified stressor. TCM diagnosis was definite in 11 and probable/possible in 5. RPS was abnormal in 11, with 9 showing an apical perfusion deficit, whereas angiography in 14 showed normal coronaries in 12 and non-obstructive disease in 2. Echo ejection fraction averaged 41% (29%-60%); an apical wall motion abnormality was present in 14 (88%). Troponin elevations were noted in 14/15. The presenting ECG was abnormal is 14, frequently showing ST-T-wave abnormalities. 13 patients were discharged on a beta-blocker. Follow-up echo (in 12) showed recovered ejection fraction in 9 and recovered apical wall motion in 11. CONCLUSIONS: Despite having normal or non-obstructive epicardial coronary arteries on angiography, TCM patients frequently present with apical wall motion abnormalities and matching RPS perfusion defects. These findings suggest microvascular abnormalities, whose pathophysiology, temporal course, and clinical implications should be the subject of further investigation.

Association of periodic fasting lifestyles with survival and incident major adverse cardiovascular events in patients undergoing cardiac catheterization.

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 longitudinal cohort (n = 2785) during 2013-2015 were followed through March 2019. A fasting survey was completed in n = 2025 (73%) of this cohort and 1957 were included in the final data analysis after 68 participants were removed (24 for data issues and 44 for fasting less than 5 years). Self-reported routine fasting behaviour, years of participation in fasting, and other fasting characteristics were surveyed. Mortality was the primary outcome and incident myocardial infarction (MI), stroke, and heart failure (HF) were secondary. Routine fasters (n = 389, mean age 64 ± 14 years, 34% female) averaged 42 ± 18 years of routine fasting (minimum 5 years). Non-fasters (n = 1568, aged 63 ± 14 years, 36% female) included never fasters (n = 1120 with 0 years of fasting) and previous fasters (n = 448 who averaged 32 ± 21 years of prior fasting but had stopped prior to enrolment). Routine fasters had greater survival vs. non-fasters [adjusted hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.36-0.80; P = 0.002] and lower incidence of HF (adjusted HR = 0.31, CI = 0.12-0.78; P = 0.013), but not MI or stroke after adjustment. CONCLUSIONS: Routine fasting followed during two-thirds of the lifespan was associated with higher survival after cardiac catheterization. This may in part be explained by an association of routine fasting with a lower incidence of HF. CLINICAL STUDY REGISTRATION: The Intermountain INSPIRE registry https://clinicaltrials.gov/, NCT02450006.

High-statin adherence over 5 years of follow-up is associated with improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease: results from the IMPRES study.

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 7339 patients ≥18 years first diagnosed with ASCVD with a statin prescription within 12 months of diagnosis who had 5 years of continuous Select Health insurance or died during Years 2-5, while a member was studied. The proportion of days covered (PDC) was calculated using pharmacy claims for statin use by year, and patients were stratified into pre-defined categories: fully adherent [PDC ≥ 80% for Years 1-5 or until death, n = 353 (4.8%)], short-term-adherent [PDC ≥ 80% for Years 1-3, n = 330 (4.5%)], early-adherent only [PDC ≥ 80% for Year 1, n = 890 (12.1%)], complex-adherent (PDC ≥ 80% in any of Years 2-5, but not Year 1, n = 1292 [17.6%]), and non-adherent [PDC < 80% for Years 1-5 or until death, n = 3942 (72.1%)]. Patients were followed for major adverse clinical events (MACE = death, myocardial infarction, and stroke). Patients averaged 56.4 ± 9.6 years and 76.5% were male. During Year 1, statin adherence was poor, with PDC < 20% in 4007 (54.6%) patients and PDC ≥80% in 1573 (21.4%) patients, which dropped to 16.9% by Year 5. Increased adherence was associated with significantly fewer MACE (11.6%, 17.9%, 21.9%, 21.1%, and 26.4% for those fully adherent, short-term adherent, early-adherent only, complex-adherent, and non-adherent, respectively, P-trend < 0.0001). After adjustment, fully adherent was associated with a significant decrease in MACE (hazard ratio = 0.51, 0.37-0.71). CONCLUSION: Among ASCVD patients with at least 5 years of continuous pharmacy benefits, long-term adherence to statins was associated with decreased long-term MACE in a linear-fashion.

Long-term outcomes in patients treated with flecainide for atrial fibrillation with stable coronary artery disease.

BACKGROUND: Class 1C antiarrhythmic drugs (AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction. 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 exist when these drugs are used for atrial fibrillation (AF) in patients with CAD without a prior myocardial infarction. METHODS: In 24,315 patients treated with the initiation of AADs, two populations were evaluated: (1) propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n = 1,114, vs class-3 AAD, n = 1,114) and (2) AF patients who had undergone a percutaneous coronary intervention or coronary artery bypass graft (flecainide, n = 150, and class-3 AAD, n = 1,453). Outcomes at 3 years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups. RESULTS: At 3 years, mortality (9.1% vs 19.3%, P < .0001), HF hospitalization (12.5% vs 18.3%, P < .0001), MACE (22.9% vs 36.6%, P < .0001), and VT (5.8% vs 8.5%, P = .02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs 25.8%, P = .26), HF hospitalization (24.5% vs 26.1%, P = .73), VT (10.9% vs 14.7%, P = .28) and MACE (44.5% vs 49.5%, P = .32). CONCLUSIONS: Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.

Behavioral Nudges as Patient Decision Support for Medication Adherence: The ENCOURAGE Randomized Controlled Trial.

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, measured as the proportion of days covered (PDC). METHODS: In a 12-month parallel-group, unblinded, randomized controlled trial, adult patients in Intermountain Healthcare cardiology clinics were enrolled. Inclusion required an indication for statins and membership in SelectHealth insurance. Subjects were randomized 1:1 to control or nudges. Nudge content, timing, frequency, and delivery route were personalized by CareCentra using machine learning of subject motivations and abilities from psychographic assessment, demographics, social determinants, and the Intermountain Mortality Risk Score. PDC calculation used SelectHealth claims data. RESULTS: Among 182 subjects, age averaged 63.2±8.5 years, 25.8% were female, baseline LDL-C was 82.5±32.7 mg/dL, and 93.4% had coronary disease. Characteristics were balanced between nudge (n = 89) and control arms (n = 93). The statin PDC was greater at 12 months in the nudge group (PDC: 0.742±0.318) compared to controls (PDC: 0.639±0.358, P = 0.042). Adherent subjects (PDC ≥80%) were more concentrated in the nudge group (66.3% vs controls: 50.5%, P = 0.036) while a composite of death, myocardial infarction, stroke, and revascularization was non-significant (nudges: 6.7% vs control: 10.8%, P = 0.44). CONCLUSIONS: Persuasive behavioral nudges driven by artificial intelligence resulted in a clinically important increase in statin adherence in general cardiology patients. This precision patient decision support utilized computerized nudge design and delivery with minimal on-going human input.

Coronary Artery Calcium Versus Pooled Cohort Equations Score for Primary Prevention Guidance: Randomized Feasibility Trial.

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 standard for the primary prevention of ASCVD in subjects at increased risk. National guidelines recommend using the American College of Cardiology/American Heart Association PCE risk score to guide a statin recommendation. Whether guidance by a CAC score is equivalent or superior is unknown. METHODS: CorCal (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events) was a randomized trial consenting 601 patients without known ASCVD, diabetes, or prior statin therapy recruited from primary care clinics and randomized to CAC- (n = 302) or PCE guidance (n = 299) of statin initiation for primary prevention. Enrolled subjects and their physicians made final treatment decisions. Primary outcomes compared the proportion of statin recommendations received and subject adherence over 1 year between CAC- and PCE-arm subjects. Modeled medical costs, adverse effects, and low-density lipoprotein-cholesterol (LDL-C) were additional measures of interest. RESULTS: Subjects were well matched, and 540 (89.9%) completed entry testing and received a protocol-based recommendation. A statin was recommended in 101 (35.9%) CAC-arm and 124 (47.9%) PCE-arm subjects (P = 0.005). Compared to PCE-based recommendations, CAC-arm subjects were reclassified from statin to no statin in 36.0% and from no statin to statin in 5.6% of cases, resulting in a total reclassification of 20.6%. Physicians accepted the study-dictated recommendation to start a statin in 88.1% of CAC-arm vs 75.0% of PCE-arm subjects (P = 0.01). Patient-reported adherence to this recommendation at 3 months was 62.2% vs 42.2%, respectively (P = 0.009). At 1 year, statin adherence remained superior, LDL-C levels were lower, estimated costs were similar or reduced in CAC subjects, and few events occurred. CONCLUSIONS: CAC guidance may be a more efficient, personalized, cost-effective, and motivating approach to statin initiation and maintenance in primary prevention. This feasibility phase of CorCal should be regarded as hypothesis-generating with respect to cardiovascular outcomes, which is being addressed in a large, longer-term outcomes trial. (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events [CorCal]; NCT03439267).

Cardiovascular Outcomes of ST-Elevation Myocardial Infarction (STEMI) Patients without Standard Modifiable Risk Factors (SMuRF-Less): The Intermountain Healthcare Experience.

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 healthcare population. Patients with a first STEMI presenting to Intermountain Healthcare catheterization laboratories between 2001-2021 were included. SMuRF included a clinical diagnosis of, or treatment for, hypertension, hyperlipidemia, diabetes, and smoking. Follow-up MACE were defined as death, MI, and heart failure hospitalization (HFH) by 60 days and long-term. Qualifying STEMI patients totaled 3510, 26.2% (919) with no SMuRF. SMuRF-less patients were younger, more frequently male, and had fewer comorbidities. Neither total MACE (adj HR 0.95, p = 0.72) nor death (adj HR 1.06, p = 0.69) differed by SMuRF status at 60 days. Long-term outcomes were more frequent in SMuRF patients, which remained significant for total MACE (adj HR 0.83, p = 0.02) and HFH (HR 0.36, p = 0.0005) after adjustment for baseline differences other than SMuRF. Results were consistent through subgroup and sensitivity analyses. In this moderately large US healthcare population, SMuRF-less STEMI presentation was confirmed to be common (26.2%). However, unlike earlier, mostly non-US reports, adjusted short-term outcomes were similar, and long-term outcomes were more favorable. Further studies to increase understanding, recognition, and treatment of risk factors in SMuRF-less subjects and to optimize STEMI management are indicated.

Association of periodic fasting with lower severity of COVID-19 outcomes in the SARS-CoV-2 prevaccine era: an observational cohort from the INSPIRE registry.

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. Design: Prospective longitudinal observational cohort study. Setting: Single-centre secondary care facility in Salt Lake City, Utah, USA with follow-up across a 24-hospital integrated healthcare system. Participants: Patients enrolled in the INSPIRE registry in 2013-2020 were studied for the primary outcome if they tested positive for SARS-CoV-2 during March 2020 to February 2021 (n=205) or, for the secondary outcome, if they had any SARS-CoV-2 test result (n=1524). Interventions: No treatment assignments were made; individuals reported their personal history of routine periodic fasting across their life span. Main outcome measures: A composite of mortality or hospitalisation was the primary outcome and evaluated by Cox regression through February 2021 with multivariable analyses considering 36 covariables. The secondary outcome was whether a patient tested positive for SARS-CoV-2. Results: Subjects engaging in periodic fasting (n=73, 35.6%) did so for 40.4±20.6 years (max: 81.9 years) prior to COVID-19 diagnosis. The composite outcome occurred in 11.0% of periodic fasters and 28.8% of non-fasters (p=0.013), with HR=0.61 (95% CI 0.42 to 0.90) favouring fasting. Multivariable analyses confirmed this association. Other predictors of hospitalisation/mortality were age, Hispanic ethnicity, prior MI, prior TIA and renal failure, with trends for race, smoking, hyperlipidaemia, coronary disease, diabetes, heart failure and anxiety, but not alcohol use. In secondary analysis, COVID-19 was diagnosed in 14.3% of fasters and 13.0% of non-fasters (p=0.51). Conclusions: Routine periodic fasting was associated with a lower risk of hospitalisation or mortality in patients with COVID-19. Fasting may be a complementary therapy to vaccination that could provide immune support and hyperinflammation control during and beyond the pandemic. Trial registration: Clinicaltrials.gov, NCT02450006 (the INSPIRE registry).