Age and Aspirin Dosing in Secondary Prevention of Atherosclerotic Cardiovascular Disease.

BACKGROUND: In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. METHODS AND RESULTS: In the ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow-up: 26.2 months; interquartile range: 19.0-34.9 months). Median age was 67.6 years (interquartile range: 60.7-73.6 years). Among participants aged <65 years (n=5841 [38.7%]), a primary end point occurred in 226 (7.54%) in the 81 mg group, and in 191 (6.80%) in the 325 mg group (adjusted hazard ratio [HR], 1.23 [95% CI, 1.01-1.49]). Among participants aged ≥65 years (n=9235 [61.3%]), a primary end point occurred in 364 (7.12%) in the 81 mg group, and in 378 (7.96%) in the 325 mg group (adjusted HR, 0.95 [95% CI, 0.82-1.10]). The age-dose interaction was not significant (P=0.559). There was no significant interaction between age and the randomized aspirin dose for the secondary effectiveness and the primary safety bleeding end points (P>0.05 for all). CONCLUSIONS: Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease: A Secondary Analysis of the ADAPTABLE Randomized Clinical Trial.

Importance: Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. Objective: To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. Design, Setting, and Participants: This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. Intervention: ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. Main Outcomes and Measures: The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Results: Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). Conclusions and Relevance: In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. Trial Registration: ClinicalTrials.gov Identifier: NCT02697916.

Surge of neurophysiological coupling and connectivity of gamma oscillations in the dying human brain.

The brain is assumed to be hypoactive during cardiac arrest. However, animal models of cardiac and respiratory arrest demonstrate a surge of gamma oscillations and functional connectivity. To investigate whether these preclinical findings translate to humans, we analyzed electroencephalogram and electrocardiogram signals in four comatose dying patients before and after the withdrawal of ventilatory support. Two of the four patients exhibited a rapid and marked surge of gamma power, surge of cross-frequency coupling of gamma waves with slower oscillations, and increased interhemispheric functional and directed connectivity in gamma bands. High-frequency oscillations paralleled the activation of beta/gamma cross-frequency coupling within the somatosensory cortices. Importantly, both patients displayed surges of functional and directed connectivity at multiple frequency bands within the posterior cortical "hot zone," a region postulated to be critical for conscious processing. This gamma activity was stimulated by global hypoxia and surged further as cardiac conditions deteriorated in the dying patients. These data demonstrate that the surge of gamma power and connectivity observed in animal models of cardiac arrest can be observed in select patients during the process of dying.

Oral hygiene and infective endocarditis: a case control study.

OBJECTIVE: To determine if oral hygiene is associated with infective endocarditis (IE) among those at moderate risk for IE. STUDY DESIGN: This is a case control study of oral hygiene among hospitalized patients with IE (cases) and outpatients with heart valve disease but without IE (controls). The primary outcome was the mean dental calculus index. Secondary outcomes included other measures of oral hygiene and periodontal disease (e.g., dental plaque, gingivitis) and categorization of blood culture bacterial species in case participants. RESULTS: The 62 case participants had 53% greater mean dental calculus index than the 119 control participants (0.84, 0.55, respectively; difference = 0.29, 95% CI: 0.11, 0.48; P = .002) and 26% greater mean dental plaque index (0.88, 0.70, respectively; difference = 0.18, 95% CI: 0.01.0.36; P = .043). Overall, cases reported fewer dentist and dental hygiene visits (P = .013) and fewer dental visits in the 12 weeks before enrollment than controls (P = .007). Common oral bacteria were identified from blood cultures in 27 of 62 cases (44%). CONCLUSIONS: These data provide evidence to support and strengthen current American Heart Association guidance that those at risk for IE can reduce potential sources of IE-related bacteremia by maintaining optimal oral health through regular professional dental care and oral hygiene procedures.

Reported obstructive sleep apnea does not diminish the cardiometabolic health benefits from a comprehensive lifestyle intervention program.

Obstructive sleep apnea (OSA) commonly coexists with the metabolic syndrome, a condition for which behavioral changes are often prescribed. Whether OSA diminishes the cardiometabolic health benefits from lifestyle interventions remains unclear. We evaluated 278 consecutive metabolic syndrome participants enrolled in a 12-week comprehensive lifestyle intervention program. The changes in blood pressure (BP), along with other metabolic health parameters, from baseline to follow-up were compared between those with and without OSA. Mean age was 52.4 ± 10.9 years and 37% were male. At enrollment, mean body mass index (BMI) was 38.2 ± 7.7 kg/m2 . OSA was reported in 126 of 269 final participants (47%). At baseline, participants with reported OSA were more likely to be male, older, have a higher BMI, waist and neck size (all P < 0.05). At program completion, participants with (-5.8 ± 16.1/-3.0 ± 10.0 mm Hg) and without OSA (-4.7 ± 13.1/-3.3 ± 8.2 mm Hg) had significant reductions in systolic and diastolic BP as well as BMI, fasting glucose, and triglyceride levels. There were no significant differences in the absolute or percentage changes in BP or other metabolic parameters between groups. Our findings support that patients with the metabolic syndrome can derive substantial health benefits, including reductions in BP, by a lifestyle intervention program regardless of the presence of OSA.

Efficacy of Sleep Tool Education During Hospitalization: A Randomized Controlled Trial.

BACKGROUND: Patients are commonly provided tools in the hospital to overcome poor sleep. Whether education on use of sleep tools can impact health outcomes from a patient perspective is not known. METHODS: We recruited 120 adults admitted to a nonintensive care unit cardiac-monitored floor. All patients received a set of sleep-enhancing tools (eye mask, ear plugs, and a white noise machine) and were randomized to receive direct education on use of and benefit of these sleep-enhancing tools (intervention), or an equal amount of time was spent discussing general benefits of sleep (control). Measurement of several symptom domains was assessed daily by health outcome survey responses, and change from baseline was assessed for differences between groups. Inpatient opioid use and length of stay were also measured. RESULTS: Participants randomized to receive the education intervention had a significantly greater decrease in fatigue scores over the 3 days, compared with controls (5.30 ± 6.93 vs 1.81 ± 6.96, t = 2.32, P = .028). There was a trend toward improvements in multiple other sleep-related domains, including sleep disturbance, sleep-related impairment, physical functioning, pain severity, or pain interference (all P >.140). There was no difference in length of stay between intervention and control groups (7.40 ± 7.29 vs 7.71 ± 6.06 days, P = .996). The change in number of opioid equivalents taken did not differ use between the groups (P = .688). CONCLUSION: In a randomized trial of education in the use of sleep-enhancing tools while hospitalized, patient fatigue was significantly improved, whereas several other patient-reported outcomes showed a trend toward improvements. Implementation of this very low-cost approach to improving sleep and well-being could substantially improve the patient care experience.

Occult obstructive sleep apnea and clinical outcomes of radiofrequency catheter ablation in patients with atrial fibrillation.

BACKGROUND: Recurrent atrial fibrillation (AF) after successful cardioversion can be predicted by obstructive sleep apnea (OSA) diagnosed by polysomnography. However, it is not known whether the validated STOP-BANG questionnaire can predict AF recurrence after radiofrequency ablation (RFA). Our objective is to determine the prevalence of unrecognized OSA in patients with AF and its relation to freedom from AF after RFA. METHODS: Validated surveys were administered to 247 consecutive AF patients following radiofrequency ablation from January to October 2011. OSA status was assessed at baseline RFA. Clinical follow up occurred at 3-6 month intervals. RESULTS: OSA had been previously diagnosed in 94/247 (38%). Among 153 patients without prior diagnosis of OSA, 121 (79%) had high risk STOP-BANG scores for OSA. Probability of maintaining sinus rhythm after RFA was similar among patients with known OSA (66/94, 70%) and high risk OSA scores (95/124, 77%) and higher than among patients with low risk OSA scores (29/32, 91%, P=0.03). Among patients without prior OSA, a high risk STOP-BANG score did predict recurrent AF (OR = 3.7, 95 % CI 1.4-11.4, P = 0.0005). Multivariate analysis showed a higher risk of atrial arrhythmia recurrence for non-paroxysmal AF patients (OR = 3.1, ± 95 % CI 1.4-7.1, P = 0.005). CONCLUSIONS: The majority of AF patients undergoing RFA have high risk OSA scores, suggesting that OSA is vastly underdiagnosed in this population. STOP-BANG independently predicted recurrent AF in patients without a prior diagnosis of OSA.

Frequency of negative coronary arteriographic findings in patients with chest pain is related to community practice patterns.

OBJECTIVE: To determine factors contributing to the relatively high frequency and variability (10% to 30%) of finding no significant coronary disease by coronary angiography in patients with chest pain. STUDY DESIGN: Retrospective, comparative analysis of practice patterns at 3 southeastern Michigan hospitals and a composite sample from New York State. PATIENTS AND METHODS: Medical records for 7668 patients were reviewed to determine the frequency of negative coronary arteriographic findings in patients undergoing chest pain evaluation. A private practice allopathic community hospital with interventional cardiologists and a private practice osteopathic community hospital with diagnostic facilities (DiagCommunity) were compared with a university hospital with full-time salaried interventional cardiologists and a sample of 17 New York hospitals. RESULTS: Of the 7668 coronary angiograms at all centers, 39.7% were performed to assess patients with stable chest pain. There was no significant obstruction found in 16.5%, and the frequency was not different between the Michigan (17.8%+/-3.8%) and New York (14.2%) hospitals. The DiagCommunity had the highest proportion (22%; P < .001 vs others). On review of the negative coronary arteriographic findings, normal or near normal coronary arteriographic findings were infrequent (range, 2.4%-6.6%) but higher in the DiagCommunity (6.6% vs 2.9%+/-1.6%; P < .0001). CONCLUSIONS: The frequency of finding no significant coronary disease by arteriography in patients with chest pain is similar in southeastern Michigan hospitals and comparable to an established external database. Cardiology self-referral and personal gain does not seem to be a major factor in selection of patients for invasive studies.