Somers, Virend K.

Abstract Background The ACC/AHA Pooled Cohort Equation (PCE) for atherosclerotic cardiovascular disease (ASCVD) has been recommended as the initial step in cardiovascular risk assessment. The sensitivity of this tool to detect those who will develop ASCVD within 10-years, while considering age and sex groups, has not been extensively studied. Methods Using the Rochester Epidemiology Project (REP) we evaluated a community-based cohort of consecutive patients that sought primary care in Olmsted County, MN, between the years 1998–2000 and were followed up through March 1st 2016. Inclusion criteria were ages 40–79 and complete data to calculate the PCE. We excluded those with known ASCVD, atrial fibrillation or heart failure. Criteria were similar to those used to derive the PCE. Events were validated in duplicate and included fatal and non-fatal myocardial infarction and ischemic stroke. Patient information was ascertained using the record linkage system of the REP. Follow-up was truncated at 10 years. We assessed the ASCVD predicted risk (categorized as low <5%, intermediate 5–9.9%, high 10–19.9%, and very high ≥20% risk) at baseline, in subjects having an ASCVD event within 10-years in the community across age (<65 years) and sex categories. We also categorized ideal cardiovascular health as ≥4 metrics [non-smoker, body mass index <25 kg/m2, and not having of elevated blood pressure (≥130/80 mmHg), LDL cholesterol (>100 mg/dL), or fasting blood glucose (>100 mg/dL), in the absence of a medical diagnosis or treatment]. Results We included 30,042 adults, mean ± SD age 48.5±12.2 years, 54% women, with a median follow-up of 16.5±5.3 years. There were 1,555 ASCVD events (5.2%) at 10 years of follow-up. The performance of the PCE was similar to what was described in the original report (0.78 vs 0.79). Overall, among those who suffered an ASCVD, 54% of women and 41% of men were not high risk as predicted by PCE (Figure 1A). Most women (73%) <65 years of age would had been considered low risk within 10-years before the event, and only 10% would have been considered to be high risks (Figure 1B). Nonetheless, women <65 years who had an ASCVD event and low 10-year predicted ASCVD risk by PCE were less likely to have ideal cardiovascular health [55 (0.40%) vs 3884 (28.39%), p-value<0.0001], when compared to women in the low risk category without an event. Conclusion The PCE fails to identify most women who will develop an ASCVD event, particularly women <65 years of age. These results underscore the importance of using additional information when estimating ASCVD risk among women and the need for better cardiovascular risk prediction tools. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic

Introduction: Obstructive sleep apnea (OSA) is associated with increased rates of atrial fibrillation (AF). Recent randomized data suggest that traditional scoring of OSA needs to evolve to improve cardiovascular outcomes. Traditional scoring of OSA does not fully reflect pathophysiological links between OSA and AF, particularly regarding OSA-induced prolongation of p-wave duration (PWD), which is the most powerful predictor of AF occurrence. Hypothesis: We hypothesized that OSA episodes that closely follow each other (serially stacked apneas, ssOSA) exert greater effect on PWD compared to isolated OSA (iOSA) episodes. Methods: Sleeping patients (adults with mild-moderate OSA and presence of both iOSA and ssOSA, but without other cardiovascular comorbidities) undergoing diagnostic polysomnography were recorded by continuous 8-lead ECG. iOSA was defined as OSA episodes with no other episode within 30 seconds. ssOSA consisted of ≥3 consecutive apneas with inter-OSA intervals <30 seconds. PWD was defined from onset of p-wave in any ECG lead to termination in any lead (measured by digital calipers, averaged over 3 beats from first half of OSA and 3 beats from second half of OSA). Wilcoxon rank-sum test was used. Results: We analyzed 208 OSA episodes (51.0% iOSA, 49.0% ssOSA) which occurred in 12 patients (7 women; age 63.1±11.5 years; apnea hypopnea index 16.8±5.4). PWD was longer during ssOSA compared to iOSA (median 117.7ms vs 109.6ms; p<0.0001). The following variables did not differ between ssOSA and iOSA: PR interval (p=0.3139), RR interval (p=0.7531), peripheral oxygen saturation (p=0.7776). Conclusions: The impact of OSA on atrial conduction delay is exacerbated by the phenomenon of OSA stacking, which seems independent of oxygen desaturation and heart rate. Stacking of OSA episodes may be an underused and cost-efficient variable in evaluating the severity of OSA and the effectiveness of OSA treatments with the ultimate goal of reducing occurrence of AF.

Background Psychological stress and insufficient sleep are both associated with an increased risk of developing hypertension. While the underlying mechanisms are not well defined, it has been postulated that this may be facilitated by modulation of baroreflex control of sympathetic activity. Short periods (<5 min) of mental stress attenuate sympathetic baroreflex sensitivity (sBRS), but it is currently unclear whether this holds true for longer bouts of stress. As such, we sought to examine the effect of 10 min of mental stress on sBRS. Additionally, we evaluated the impact of experimental sleep restriction on baroreflex control of blood pressure during mental stress. We hypothesized that mental stress would attenuate sBRS, and that prolonged exposure to restricted sleep would result in a greater reduction in sBRS during mental stress. Methods Fourteen healthy adults (10M/4F, 25±1 yrs) underwent 10 min of mental stress consisting of a 5‐min mental arithmetic task, followed immediately by a 5‐min Stroop color‐word conflict test. Heart rate (electrocardiography), blood pressure (finger photoplethysmography), and muscle sympathetic nerve activity (microneurography of the common peroneal nerve) were continuously measured to determine sBRS at baseline and during mental stress. A subset of participants (n=9) completed the mental stress protocol under both experimental sleep restriction (4 hr/night) and control sleep conditions (8–9 hr/night) while inpatient at a hospital‐based clinical research unit. Subjects underwent a 3‐night acclimation period, followed by 9 or 14 nights of either sleep restriction or control sleep. Data from Day 2/1 or Day 13/15 (during control sleep only) were used to assess the effect of mental stress alone, and data from Day 13/15 (under both conditions) were used to assess the effect of sleep restriction. Results Acute mental stress resulted in a marked blunting of sBRS from baseline (−2.7±0.5 to −1.5±0.4 bursts·100hb −1 ·mmHg −1 , p=0.04). Examining the mental stress interventions individually revealed a significant decrease in sBRS during the initial 5 min of stress (mental arithmetic, p=0.03), but not during the subsequent 5 min of testing (Stroop test, p=0.75). Mental stress also reduced baroreflex function following sleep restriction (main effect of condition, p<0.01); however, the reduction in sBRS was not significantly different in restricted sleep compared to control (main effect of visit, p=0.78). There was no significant interaction effect between sleep restriction and mental stress (p=0.81). Conclusions These data provide further support that, in young healthy individuals, sBRS is attenuated early in mental stress but quickly returns to baseline values. In contrast, prolonged sleep restriction does not appear to alter sympathetic control of blood pressure. Support or Funding Information NIH HL114024 (VKS), NIH HL114676 (VKS), NIH HL083947 (MJJ), FAER Medical Student Anesthesia Research Fellowship (NMP)

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and sleep disordered breathing (SDB) is a treatable risk factor that has been seen to occur concurrently, and is known to propagate mortality and morbidity in a number of cardiovascular disease states including heart failure, and indeed hypertrophic cardiomyopathy. In this review, we summarize past studies that explored the simultaneous occurrence of HCM and SDB, and the pathophysiology of SDB in relation to heart failure, arrhythmias, cardiac ischemia and pulmonary hypertension in HCM. The current therapeutic modalities, with the effect of obstructive sleep apnea (OSA) treatment on HCM, are then discussed along with potential future directions.

Sleep apnea is very common in patients with cardiovascular disease, especially in patients with hypertension. Over the last few decades a number of discoveries have helped support a causal relationship between the two and even resistant hypertension. The role neurogenic mechanisms play has gathered more attention in the recent past due to their immediate bedside utility. Several innovative discoveries in pathogenesis including those exploring the role of baroreflex gain, cardiovascular variability, chemoreceptor reflex activation and the sympathetic nervous system have emerged. In this review, we discuss the epidemiology of sleep apnea and hypertension and the pathogenic mechanisms contributing to neurogenic hypertension. Furthermore, recent management strategies in addition to continuous positive airway pressure (CPAP), such as upper airway stimulation and renal denervation that target these pathogenic mechanisms, are also discussed.