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Item Associations between affective factors and high-frequency heart rate variability in primary care patients with depression(Elsevier, 2022-10) Shell, Aubrey L.; Gonzenbach , Virgilio; Sawhney , Manisha; Crawford, Christopher A.; Stewart, Jesse C.; Psychology, School of ScienceObjective Depression is a risk factor for cardiovascular disease (CVD), and subgroups of people with depression may be at particularly elevated CVD risk. Lower high-frequency heart rate variability (HF HRV), which reflects diminished parasympathetic activation, is a candidate mechanism underlying the depression-CVD relationship and predicts cardiovascular events. Few studies have examined whether certain depression subgroups – such as those with co-occurring affective factors – exhibit lower HF HRV. The present study sought to assess associations between co-occurring affective factors and HF HRV in people with depression. Methods Utilizing baseline data from the 216 primary care patients with depression in the eIMPACT trial, we examined cross-sectional associations of depression's co-occurring affective factors (i.e., anxiety symptoms, hostility/anger, and trait positive affect) with HF HRV. HF HRV estimates were derived by spectral analysis from electrocardiographic data obtained during a supine rest period. Results Individual regression models adjusted for demographics and depressive symptoms revealed that anxiety symptoms (standardized regression coefficient β = −0.24, p = .002) were negatively associated with HF HRV; however, hostility/anger (β = 0.02, p = .78) and trait positive affect (β = −0.05, p = .49) were not. In a model further adjusted for hypercholesterolemia, hypertension, diabetes, body mass index, current smoking, CVD prevention medication use, and antidepressant medication use, anxiety symptoms remained negatively associated with HF HRV (β = −0.19, p = .02). Conclusion Our findings suggest that, in adults with depression, those with comorbid anxiety symptoms have lower HF HRV than those without. Co-occurring anxiety may indicate a depression subgroup at elevated CVD risk on account of diminished parasympathetic activation.Item Brief Report: Reduced Heart Rate Variability in Children with Autism Spectrum Disorder(SpringerLink, 2020-11) Lory, Catharine; Kadlaskar, Girija; McNally Keehn, Rebecca; Francis, Alexander L.; Keehn, Brandon; Pediatrics, School of MedicineDysregulation of the autonomic nervous system (ANS), which can be indexed by heart rate variability (HRV), has been posited to contribute to core features of autism spectrum disorder (ASD). However, the relationship between ASD and HRV remains uncertain. We assessed tonic and phasic HRV of 21 children with ASD and 21 age- and IQ-matched typically developing (TD) children and examined (1) group differences in HRV and (2) associations between HRV and ASD symptomatology. Children with ASD showed significantly lower tonic HRV, but similar phasic HRV compared to TD children. Additionally, reduced tonic HRV was associated with atypical attentional responsivity in ASD. Our findings suggest ANS dysregulation is present in ASD and may contribute to atypical attentional responses to sensory stimulation.Item Follow Your Heart: Heart Rate Variability Reveals Sex Differences in Autonomic Regulation During Anxiety-Like Behavior and During Alcohol Drinking in Rats(2024-02) Frasier, Raizel Michele; Yoder, Karmen; Hopf, Woody; McKinzie, David; Lukkes, Jodi; Conroy, SusanMental health conditions remain a substantial and costly challenge to society. Of note, women have a higher prevalence of anxiety disorders than men, and alcohol misuse in women has risen sharply in recent years. However, critical mechanisms underlying these observed sex differences remain incompletely understood. Measures of cardiac function, including heart rate (HR) and HR variability (HRV), reflect dynamic balance between the two opposing branches of the autonomic nervous system: sympathetic (SNS, “fight or flight”) and parasympathetic (PNS, “rest and digest”). Furthermore, recent evidence strongly suggests these measures are potential biomarkers for pathological states, including mental health conditions. To better understand sex differences in autonomic mechanisms related to pathological anxiety and alcohol misuse, we utilized cardiac telemetry to measure HR and HRV. This allowed observation of real-time autonomic tone in awake, freely behaving Wistar rats of both sexes. At baseline, female rats had greater HR and lower SNS influence than males, which concords with human studies. In both anxiety-like behavior and alcohol drinking studies, we observed that females tend to utilize a higher PNS influence to overcome challenge, whereas males tend to utilize higher SNS. Furthermore, female (but not male) baseline HR and HRV are related to within-task behavior, suggesting that baseline state impacts drinking and anxiety-like behavior in a sex-specific way. Again, these data concord with human research suggesting a similar PNS bias in women and SNS bias in men when responding, especially under challenge. Taken together, these data have contributed new knowledge to sex differences in autonomic engagement, especially for anxiety states and alcohol drinking. Importantly, these findings are likely translationally relevant for the development of novel, and more personalized, therapies.Item Heart Rate Variability Declines with Increasing Age and CTG Repeat Length in Patients with Myotonic Dystrophy Type 1(Wiley, 2003-07) Hardin, Bradley A.; Lowe, Miriam R.; Bhakta, Deepak; Groh, William J.; Medicine, School of MedicineBackground: Cardiac myopathy manifesting as arrhythmias is common in the neurological disease, myotonic dystrophy type 1 (DM1). The purpose of the present study was to evaluate heart rate variability (HRV) in patients with DM1. Methods: In a multicenter study, history, ECG, and genetic testing were performed in DM1 patients. Results: In 289 patients in whom the diagnosis of DM1 was confirmed by a prolonged cytosine-thymine-guanine (CTG) repeat length the most common ambulatory ECG abnormality was frequent ventricular ectopy (16.3%). The 24-hour time domain parameters of SDNN (SD of the NN interval) and SDANN (SD of the mean NN, 5-minute interval) declined as age and CTG repeat length increased (SDNN: −8.5 ms per decade, 95% confidence intervals [CI]−12.9, −4.2, −8.7 ms per 500 CTG repeats, CI −15.7, −1.8, r = 0.24, P < 0.001; SDANN: −8.1 ms per decade, CI −12.4, −3.8, −8.8 ms per 500 CTG repeats, CI −15.7, −1.9, r = 0.23, P < 0.001). Short-term frequency domain parameters declined with age only (total power: −658 ms2 per decade, CI: −984, −331, r = 0.23, P < 0.001; low frequency (LF) power −287 ms2 per decade, CI: −397, −178, r = 0.30, P < 0.001; high frequency (HF) power: −267 ms2 per decade, CI: −386, −144, r = 0.25, P < 0.001). The LF/HF ratio increased as the patient aged (0.5 per decade, CI: 0.1, 0.9, r = 0.13, P = 0.03). Conclusions: In DM1 patients a decline in HRV is observed as the patient ages and CTG repeat length increases.Item Heart rate variability measures indicating sex differences in autonomic regulation during anxiety-like behavior in rats(Frontiers Media, 2023-10-31) Frasier, Raizel M.; De Oliveira Sergio, Thatiane; Starski, Phillip A.; Grippo, Angela J.; Hopf, F. Woodward; Psychiatry, School of MedicineIntroduction: Mental health conditions remain a substantial and costly challenge to society, especially in women since they have nearly twice the prevalence of anxiety disorders. However, critical mechanisms underlying sex differences remain incompletely understood. Measures of cardiac function, including heart rate (HR) and HR variability (HRV), reflect balance between sympathetic (SNS) and parasympathetic (PNS) systems and are potential biomarkers for pathological states. Methods: To better understand sex differences in anxiety-related autonomic mechanisms, we examined HR/HRV telemetry in food-restricted adult rats during novelty suppression of feeding (NSF), with conflict between food under bright light in the arena center. To assess HRV, we calculated the SDNN (reflective of both SNS and PNS contribution) and rMSSD (reflective of PNS contribution) and compared these metrics to behaviors within the anxiety task. Results: Females had greater HR and lower SNS indicators at baseline, as in humans. Further, females (but not males) with higher basal HR carried this state into NSF, delaying first approach to center. In contrast, males with lower SNS measures approached and spent more time in the brightly-lit center. Further, females with lower SNS indicators consumed significantly more food. In males, a high-SNS subpopulation consumed no food. Among consumers, males with greater SNS ate more food. Discussion: Together, these are congruent with human findings suggesting women engage PNS more, and men SNS more. Our previous behavior-only work also observed female differences from males during initial movement and food intake. Thus, high basal SNS in females reduced behavior early in NSF, while subsequent reduced SNS allowed greater food intake. In males, lower SNS increased engagement with arena center, but greater SNS predicted higher consumption. Our findings show novel and likely clinically relevant sex differences in HRV-behavior relationships.Item Heart rate variability parameters indicate altered autonomic tone in subjects with COVID-19(Springer Nature, 2024-12-28) Gruionu, Gabriel; Aktaruzzaman, Md; Gupta, Anita; Nowak, Thomas V.; Ward, Matthew; Everett, Thomas H., IV; Medicine, School of MedicineCOVID-19 is associated with long-term cardiovascular complications. Heart Rate Variability (HRV), a measure of sympathetic (SNS) and parasympathetic (PNS) control, has been shown to predict COVID-19 outcomes and correlate with disease progression but a comprehensive analysis that includes demographic influences has been lacking. The objective of this study was to determine the balance between SNS, PNS and heart rhythm regulation in hospitalized COVID-19 patients and compare it with similar measurements in healthy volunteers and individuals with cardiovascular diseases (CVD), while also investigating the effects of age, Body Mass Index (BMI), gender and race. Lead I ECG recordings were acquired from 50 COVID-19 patients, 31 healthy volunteers, and 51 individuals with cardiovascular diseases (CVD) without COVID-19. Fourteen HRV parameters were calculated, including time-domain, frequency-domain, nonlinear, and regularity metrics. The study population included a balanced demographic profile, with 55% of participants being under 65 years of age, 54% identifying as male, and 68% identifying as White. Among the COVID-19 patients, 52% had a BMI ≥ 30 compared to 29% of healthy volunteers and 33% of CVD patients. COVID-19 and CVD patients exhibited significantly reduced time-domain HRV parameters, including SDNN and RMSSD, compared to healthy volunteers (SDNN: 0.02 ± 0.02 s vs. 0.06 ± 0.03 s, p < 0.001; RMSSD: 0.02 ± 0.02 s vs. 0.05 ± 0.03 s, p = 0.08). In the frequency domain, both COVID-19 and CVD patients showed increased low-frequency (LF) power and lower high-frequency (HF) power compared to healthy volunteers (COVID-19 LF: 18.47 ± 18.18%, HF: 13.69 ± 25.80%; Healthy LF: 23.30 ± 11.79%, HF: 22.91 ± 21.86%, p < 0.01). The LF/HF ratio was similar in COVID-19 patients (1.038 ± 1.54) and healthy volunteers (1.03 ± 0.78). Nonlinear parameters such as SD1 were significantly lower in COVID-19 patients (0.04 ± 0.04 s vs. 0.08 ± 0.05 s, p < 0.01), indicating altered autonomic regulation. Variations in HRV were observed based on demographic factors, with younger patients, females, and non-white individuals showing more pronounced autonomic dysfunction. COVID-19 patients exhibit significant alterations in HRV, indicating autonomic dysfunction, characterized by decreased vagal tone and sympathetic dominance, similar to patients with severe cardiovascular comorbidities. Despite higher heart rates, the HRV analysis suggests COVID-19 is associated with substantial disruption in autonomic regulation, particularly in patients with specific demographic risk factors.Item Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study(BMC, 2020-05-11) Poon, Anna K.; Whitsel, Eric A.; Heiss, Gerardo; Soliman, Elsayed Z.; Wagenknecht, Lynne E.; Suzuki, Takeki; Loehr, Laura; Medicine, School of MedicineBackground: Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities. Methods: We examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by <25th percentile for four measures: 1) standard deviation of normal-to-normal R-R intervals (SDNN), a measure of total variability; 2) root mean square of successive differences in normal-to-normal R-R intervals (RMSSD), a measure of vagal activity; 3) low frequency spectral component (LF), a measure of sympathetic and vagal activity; and 4) high frequency spectral component (HF), a measure of vagal activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals weighted for sampling/non-response, adjusted for age at ancillary visit, sex, and race/study-site. Insulin resistance quartiles 4, 3, and 2 were compared to quartile 1; high indexes refer to quartile 4 versus quartile 1. Results: The average age was 78 years, 66% (n = 497) were women, and 58% (n = 438) were African American. Estimates of association were not robust at all levels of HOMA-IR, TyG, and TG/HDL-C, but suggest that high indexes were associated consistently with indicators of vagal activity. High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low RMSSD (OR: 1.68 (1.00, 2.81), OR: 2.03 (1.21, 3.39), and OR: 1.73 (1.01, 2.91), respectively). High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low HF (OR: 1.90 (1.14, 3.18), OR: 1.98 (1.21, 3.25), and OR: 1.76 (1.07, 2.90), respectively). Conclusions: In older adults without diabetes, insulin resistance was associated with reduced cardiac autonomic function - specifically and consistently for indicators of vagal activity - measured during daily activities. Primary prevention of insulin resistance may reduce the related risk of cardiac autonomic dysfunction.Item Sex differences in heart rate variability measures that predict alcohol drinking in rats(Wiley, 2024) Frasier, Raizel M.; Starski, Phillip A.; de Oliveira Sergio, Thatiane; Grippo, Angela J.; Hopf, F. Woodward; Psychiatry, School of MedicineProblem alcohol drinking continues to be a substantial cost and burden. In addition, alcohol consumption in women has increased in recent decades, and women can have greater alcohol problems and comorbidities. Thus, there is a significant need for novel therapeutics to enhance sex-specific, individualized treatment. Heart rate (HR) and HR variability (HRV) are of broad interest because they may be both biomarkers for and drivers of pathological states. HRV reflects the dynamic balance between sympathetic (SNS, 'fight or flight') and parasympathetic (PNS, 'rest and digest') systems. Evidence from human studies suggest PNS predominance in women and SNS in men during autonomic regulation, indicating the possibility of sex differences in risk factors and physiological drivers of problem drinking. To better understand the association between HRV sex differences and alcohol drinking, we examined whether alcohol consumption levels correlated with time domain HRV measures (SDNN and rMSSD) at baseline, at alcohol drinking onset, and across 10 min of drinking, in adult female and male Wistar rats. In particular, we compared both HRV and HR measures under alcohol-only and compulsion-like conditions (alcohol + 10 mg/L quinine), because compulsion can often be a significant barrier to treatment of alcohol misuse. Importantly, previous work supports the possibility that different HRV measures could be interpreted to reflect PNS versus SNS influences. Here, we show that females with higher putative PNS indicators at baseline and at drinking onset had greater alcohol consumption. In contrast, male intake levels related to increased potential SNS measures at drinking onset. Once alcohol was consumed, HR predicted intake level in females, perhaps a pharmacological effect of alcohol. However, HRV changes were greater during compulsion-like intake versus alcohol-only, suggesting HRV changes (reduced SNS in females, reduced PNS and increased HR in males) specifically related to aversion-resistant intake. We find novel and likely clinically relevant autonomic differences associated with biological sex and alcohol drinking, suggesting that different autonomic mechanisms may promote differing aspects of female and male alcohol consumption.Item Skin Sympathetic Nerve Activity as a Biomarker for Syncopal Episodes during a Tilt Table Test(Elsevier, 2020-05) Kumar, Awaneesh; Wright, Keith; Uceda, Domingo E.; Vasallo, Peter A., III.; Rabin, Perry L.; Adams, David; Wong, Johnson; Das, Mithilesh; Lin, Shien-Fong; Chen, Peng-Sheng; Everett, Thomas H., IV.; Medicine, School of MedicineBackground: Autonomic imbalance is the proposed mechanism of syncope during a tilt table test (TTT). We have recently demonstrated that skin sympathetic nerve activity (SKNA) can be noninvasively recorded using electrocardiographic electrodes. Objective: The purpose of this study was to test the hypothesis that increased SKNA activation precedes tilt-induced syncope. Methods: We studied 50 patients with a history of neurocardiogenic syncope undergoing a TTT. The recorded signals were band-pass filtered at 500-1000 Hz to analyze nerve activity. Results: The average SKNA (aSKNA) value at baseline was 1.38 ± 0.38 μV in patients without syncope and 1.42 ± 0.52 μV in patients with syncope (P = .77). On upright tilt, aSKNA was 1.34 ± 0.40 μV in patients who did not have syncope and 1.39 ± 0.43 μV in patients who had syncope (P = .65). In all 14 patients with syncope, there was a surge of SKNA before an initial increase in heart rate followed by bradycardia, hypotension, and syncope. The peak aSKNA immediately (<1 minute) before syncope was significantly higher than baseline aSKNA (2.63 ± 1.22 vs 1.39 ± 0.43 μV; P = .0005). After syncope, patients were immediately placed in the supine position and aSKNA dropped significantly to 1.26 ± 0.43 μV; (P = .0004). The heart rate variability during the TTT shows a significant increase in parasympathetic tone during syncope (low-frequency/high-frequency ratio: 7.15 vs 2.21; P = .04). Conclusion: Patients with syncope do not have elevated sympathetic tone at baseline or during the TTT except immediately before syncope when there is a transient surge of SKNA followed by sympathetic withdrawal along with parasympathetic surge.Item The St. Louis African American health-heart study: methodology for the study of cardiovascular disease and depression in young-old African Americans(Springer Nature, 2013-09-08) Bruchas, Robin R.; de las Fuentes, Lisa; Carney, Robert M.; Reagan, Joann L.; Bernal-Mizrachi, Carlos; Riek, Amy E.; Gu, Chi Charles; Bierhals, Andrew; Schootman, Mario; Malmstrom, Theodore K.; Burroughs, Thomas E.; Stein, Phyllis K.; Miller, Douglas K.; Dávila-Román, Victor G.; Medicine, School of MedicineBackground: Coronary artery disease (CAD) is a major cause of death and disability worldwide. Depression has complex bidirectional adverse associations with CAD, although the mechanisms mediating these relationships remain unclear. Compared to European Americans, African Americans (AAs) have higher rates of morbidity and mortality from CAD. Although depression is common in AAs, its role in the development and features of CAD in this group has not been well examined. This project hypothesizes that the relationships between depression and CAD can be explained by common physiological pathways and gene-environment interactions. Thus, the primary aims of this ongoing project are to: a) determine the prevalence of CAD and depression phenotypes in a population-based sample of community-dwelling older AAs; b) examine the relationships between CAD and depression phenotypes in this population; and c) evaluate genetic variants from serotoninP and inflammatory pathways to discover potential gene-depression interactions that contribute significantly to the presence of CAD in AAs. Methods/design: The St. Louis African American Health (AAH) cohort is a population-based panel study of community-dwelling AAs born in 1936-1950 (inclusive) who have been followed from 2000/2001 through 2010. The AAH-Heart study group is a subset of AAH participants recruited in 2009-11 to examine the inter-relationships between depression and CAD in this population. State-of-the-art CAD phenotyping is based on cardiovascular characterizations (coronary artery calcium, carotid intima-media thickness, cardiac structure and function, and autonomic function). Depression phenotyping is based on standardized questionnaires and detailed interviews. Single nucleotide polymorphisms of selected genes in inflammatory and serotonin-signaling pathways are being examined to provide information for investigating potential gene-depression interactions as modifiers of CAD traits. Information from the parent AAH study is being used to provide population-based prevalence estimates. Inflammatory and other biomarkers provide information about potential pathways. Discussion: This population-based investigation will provide valuable information on the prevalence of both depression and CAD phenotypes in this population. The study will examine interactions between depression and genetic variants as modulators of CAD, with the intent of detecting mechanistic pathways linking these diseases to identify potential therapeutic targets. Analytic results will be reported as they become available.