A Luminex Approach to Develop an Anti-Tumor-Associated Antigen Autoantibody Panel for the Detection of Prostate Cancer in Racially/Ethnically Diverse Populations.

(1) Background: Autoantibodies to tumor-associated antigens (TAAs) have emerged as promising cancer biomarkers. Luminex technology offers a powerful approach for the simultaneous detection of multiple anti-TAA autoantibodies. (2) Methods: We aimed to utilize Luminex technology to evaluate and optimize a panel of anti-TAAs autoantibodies for detecting prostate cancer (PCa), which included autoantibodies to fourteen TAAs. A total of 163 serum samples (91 PCa, 72 normal controls) were screened to determine the levels of the autoantibodies using the Luminex assay. (3) Results: Twelve autoantibodies exhibited significantly high frequencies ranging from 19.8% to 51.6% in the PCa group. Receiver operating characteristic (ROC) curve analysis revealed area under the curve (AUC) values ranging from 0.609 to 0.868 for the twelve autoantibodies individually. We further confirmed the performance of the HSP60 autoantibody by using an enzyme-linked immunosorbent assay (ELISA) in a larger sample comprising 200 PCa sera, 20 benign prostatic hyperplasia (BPH) sera, and 137 normal control sera. The results obtained from the Luminex assay were consistent with the ELISA findings. We developed a panel consisting of three autoantibodies (p16, IMP2, and HSP60) which achieved an impressive AUC of 0.910 with a sensitivity of 71.4% and a specificity of 95.8%. The panel was also evaluated in PCa patients from different races/ethnicities with the best performance observed in distinguishing the Hispanic American patients with PCa from normal controls. (4) Conclusions: We developed an anti-TAA autoantibody panel for the detection of PCa that exhibits promising performance. This panel holds significant potential as a high-throughput tool to facilitate PCa detection.

Rank and Tenure Amongst Faculty at Academic Medical Centers: A Study of More Than 50 Years of Gender Disparities.

PURPOSE: To investigate progress toward gender equality in academic medicine through a longitudinal analysis of gender parity among faculty at medical schools. METHOD: The authors conducted a retrospective analysis of Association of American Medical Colleges Faculty Roster data on gender, tenure status, and academic rank of faculty in basic science (BSc) and clinical science (CSc) departments from 1966 to 2019. They expressed data as whole numbers and percent female. A trend analysis projected time to gender parity across rank and tenure categories, and cross-tabulation analysis revealed the relative odds of females being in a rank and tenure position relative to males. RESULTS: A 12-fold increase in the number of faculty occurred from 1966 to 2019, driven largely by increases in non-tenure track faculty. Female tenured and tenure track numbers increased at consistent rates (121 and 174 per year; P < .001). Female non-tenure track rates mirrored those for males, both changing in 2000. Odds ratios in 2019 for BSc and CSc females to be in tenure track versus non-tenure track positions compared with males were 0.83/0.98 and to be tenured were 0.63/0.44. Odds ratios in 2019 for BSc and CSc females to be full professors versus assistant or associate professors compared with males were 0.55/0.42. BSc assistant and associate professor percent female rates increased linearly from 1966 to 2019, while full professor rates increased in 1986. Transition points between periods of linear change were seen later in CSc departments (1977, 1980, 1985, 1994). Best fit line models indicated gender parity will be reached for BSc/CSc faculty in 2034/2023, 2047/2033, and 2065/2053 for assistant, associate, and full professors, respectively. CONCLUSIONS: These findings suggest large historical changes in medical school expansion, medical education, and economics have shifted gender curves at all academic ranks. To achieve gender parity, additional national changes are needed.

Low-Frequency Transcranial Magnetic Stimulation (LF-TMS) in Treating Depression in Patients With Impaired Cognitive Functioning.

OBJECTIVE: Common methodologies for treating depressive symptoms have demonstrated decreased efficacy among individuals with impaired cognitive functioning. While transcranial magnetic stimulation (TMS) has been approved to treat major depressive disorder, few studies have analyzed the ability of TMS to treat depressive symptoms among individuals with cognitive impairments. The present study had two objectives: to determine whether low-frequency TMS (LF-TMS) might demonstrate efficacy in treating depressive symptoms among individuals with impaired cognitive functioning; and to determine whether LF-TMS might improve neurocognitive functioning above and beyond depressive symptom improvements. METHODS: Data were derived from a pre-existing database at Eastern Virginia Medical School. Fifty-three (N=53) participants completed LF-TMS treatment. The Beck Depression Inventory II (BDI-II) and CNS Vital Signs (CNS-VS) neurocognitive assessment were administered at multiple time points throughout treatment. Participants were classified as impaired cognitive functioning or average cognitive functioning based on baseline CNS-VS scores. Data were analyzed using restricted maximum likelihood (REML) measures-within-persons longitudinal hierarchical linear modeling (HLM) with time-varying covariates. RESULTS: LF-TMS produced significant reductions in depressive symptoms for individuals in both cognitive functioning groups; however, a significant group-by-time interaction indicates differential effects between these two groups. Low-frequency TMS produced significant improvements in three neurocognitive domains above and beyond improvements in depressive symptoms; however, the reliability of these changes may be questionable. CONCLUSIONS: This study adds to the growing body of empirical findings for LF-TMS treatment in improving neurocognitive functioning above and beyond other treatment-related effects.

Development and Validation of the Norfolk Quality of Life Fatigue Tool (QOL-F): A New Measure of Perception of Fatigue.

OBJECTIVES: To design a questionnaire to evaluate and distinguish between cognitive and physical aspects of fatigue in different age groups of "nondiseased" people and guide appropriate prevention and interventions for the impact of frailty occurring in normative aging. STUDY DESIGN AND PARTICIPANTS: The Norfolk QOL-Fatigue (QOL-F) with items of cognitive and physical fatigue, anxiety, and depression from validated questionnaires including items from the Patient-Reported Outcomes Measure Information System (PROMIS) databank was developed. The preliminary QOL-F was administered to 409 healthy multiethnic local participants (30-80 years old) in 5 age groups. METHODS: The authors distilled the item pool using exploratory (EFA) and confirmatory factor analysis (CFA). EFA identified 5 latent groups as possible factors related to problems due to fatigue, subjective fatigue, reduced activities, impaired activities of daily living (ADL), and depression. RESULTS: CFA demonstrated good overall fit [χ2(172) = 1094.23, P < .001; Tucker-Lewis index = 0.978; root mean square error of approximation = 0.049] with factor loadings >0.617 and strong interfactor correlations (0.69-0.83), suggesting that fatigue in each domain is closely related to other domains and to the overall scale except for ADL. The 5-factor solution displayed good internal consistency (Cronbach α = 0.78-0.94). Total and domain scores were fairly equivalent in all age groups except for the 40 to 49-year-old group with better overall scores. In addition, 70 to 79-year-olds had better ADL scores. In item response analysis, factor scores in different age groups were similar, so age may not be a significant driver of fatigue scores. Fatigue scores were significantly higher in females than in males (P < .05). CONCLUSIONS AND CLINICAL IMPLICATIONS: The developed Norfolk QOL-F tool demonstrated fatigue as a perceived cognitive phenomenon rather than an objective physical measure, suggesting mandatory inclusion of cognitive as well as physical measures in the evaluation of people as they age. QOL-F is able to distinguish QOL-F domain scores unique to different age groups, proposing clinical benefits from physical, balance, and cognitive interventions tailored to impact frailty occurring in normative aging.

Neuromotor and cognitive responses of adults with autism spectrum disorder compared to neurotypical adults.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, whose core symptom domains include impaired social communication and narrowed interests and/or repetitive behaviors; in addition, deficits of general cognition, neuromotor function, and movement ability can be observed. This study was designed to examine differences in neuromotor and cognitive functions for a group of young adults with ASD and age-matched controls. It was also of interest to assess whether changes in the intra-individual variability (IIV) of these selected neuromotor and cognitive tasks also occurred. Increased IIV in persons with ASD may reveal important organizational features of their neuromotor system that differ from neurotypical controls. Twenty neurotypical adult individuals (24.3 ± 2.8 years) and twenty adults with a clinician-assigned diagnosis of ASD (21.2 ± 4.4 years) participated in this study. Specific cognitive and motor assessments included Trails Making Tests A&B, Symbol Digit Modalities Test, Purdue Pegboard Test, simple reaction time, finger tapping, hand grip strength, balance, and gait. Results revealed that the ASD adults exhibited decreased upper limb strength and slower responses for finger tapping, hand dexterity, reaction times, and gait compared to the non-ASD controls. The general slowing of motor responses for the persons with ASD was also associated with increased within-subject variability during the reaction time, finger tapping, hand grip, and gait assessments compared to neurotypical adults, illustrating that IIV measures may be a useful marker of widespread neuromotor dysfunction for adults with ASD. Overall, these findings are consistent with clinical observations that abnormalities of movement performance and cognitive performance are an associated feature of ASD in young adults.

Rehabilitation procedures in the management of gait disorders in the elderly.

Gait disorders are common and very disabling in elderly people, leading to an increase of risk of falling and reductions in quality of life. So far, many clinical classifications of gait disorders in the elderly population have been proposed. Here we suggest a novel categorization of gait disorders in elderly people, which takes into account the several resources required during gait. The biomechanical constraints, movement and sensory strategies, orientation in space, control of dynamics and cognitive processing are essential to perform safely gait. Moreover, the strictly connection between gait and balance has been discussed. According to this perspective, a literature search was performed including studies investigating the rehabilitation procedures in the management of balance and gait disorders in elderly people. Training aimed at improving muscle strength and flexibility, movement strategies, sensorimotor integration and sensory reweighting processes, balance in static and dynamic conditions and cognitive strategies have been proposed as possible therapeutic approaches in elderly people affected by gait disorders. Moreover, the role of new technological devices in improving balance and gait control has been also described. A multidisciplinary and interdisciplinary approach is fundamental for the management of gait disorders in elderly people. Rehabilitation procedures should take into consideration all the potential constraints involved in gait disorders in order to select the most appropriate intervention.

A double-blind, randomized, neoadjuvant study of the tissue effects of POMx pills in men with prostate cancer before radical prostatectomy.

Pomegranates slow prostate cancer xenograft growth and prolong prostate-specific antigen (PSA) doubling times in single-arm human studies. Pomegranates' effects on human prostate tissue are understudied. We hypothesized that orally administered pomegranate extract (POMx; Pom Wonderful) would lower tissue 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress biomarker. Seventy men were randomized to two tablets, POMx or placebo, daily up to four weeks before radical prostatectomy. Tissue was analyzed for intraprostatic urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NF-κB, and Ki67. Primary endpoint was differences in 8-OHdG, and the study was powered to detect 35% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (P = 0.095), which was not statistically significant. POMx was well tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21 of the 33 patients in the POMx group versus 12 of the 35 in the placebo group (P = 0.031). Cancer pS6 kinase, NF-κB, Ki67, and serum PSA changes were similar between arms. POMx before surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary endpoint in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitively test whether POMx reduces prostate oxidative stress, as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology.

Polymorphic variation in choline transporter gene (CHT1) is associated with early, subclinical measures of carotid atherosclerosis in humans.

Atherosclerosis is a heritable trait with little known about specific genetic influences on preclinical measures of plaque formation. Based on relations of parasympathetic-cholinergic function to atherosclerosis and to a choline transporter gene [CHT1 (G/T)] polymorphism, we investigated whether the same allelic variant predicts variation in carotid intima-media thickness (IMT) and plaque formation. Carotid IMT and plaque occurrence as well as genotyping for the CHT1 (G/T) variant were measured in a sample (N = 264) of generally healthy adults (age 30-55) of European ancestry. CHT1 GG homozygotes had greater IMT (P < 0.005) and plaque occurrence (P < 0.020) than T allele carriers. This is the first study showing polymorphic variation in the CHT1 gene to predict early, subclinical measures of carotid atherosclerosis which may aid in understanding cholinergic-vagal processes potentially underlying atherosclerotic risk.

Cardiovascular and psychological reactivity and recovery from harassment in a biracial sample of high and low hostile men and women.

BACKGROUND: This study emphasizes the importance of studying the emotional, motivational, and cognitive characteristics accompanying and the potential hemodynamic mechanisms underlying cardiovascular reactivity to and recovery from interpersonal conflict. PURPOSE: The relation of dispositional hostility to cardiovascular reactivity during a frustrating anagram task and post-task recovery was investigated. METHODS: The sample was composed of 99 healthy participants (age, 18-30 years; 53% women; 51% Caucasian; 49% African American)-half randomly assigned to a harassment condition. High and low hostility groups were created by a median split specific to sex and race subgroup score distributions on the Cook-Medley Hostility Scale. It was hypothesized that hostility would interact with harassment such that harassed, high hostile individuals would display the greatest cardiovascular and emotional reactivity and slowest recovery of the four groups. Participants completed a 10-min baseline, a 6-min anagram task, and a 5-min recovery period with blood pressure, heart rate, pre-ejection period, stroke index, cardiac index, and total peripheral resistance index measured. RESULTS: Harassed participants displayed significantly greater cardiovascular responses and lower positive affect to the task and slower systolic blood pressure (SBP) recovery than did nonharassed participants. The high hostile group, irrespective of harassment, showed blunted cardiovascular responses during the task and delayed SBP recovery than the low hostile group. CONCLUSION: Although the predicted interaction between hostility and harassment was not supported in the context of cardiovascular responses, such an interaction was observed in the context of blame attributions, whereby harassed hostile participants were found to blame others for their task performance than the other subgroups.

Cholinergic abnormalities in autism: is there a rationale for selective nicotinic agonist interventions?

The core dysfunctions of autism spectrum disorders, which include autistic disorder, Asperger disorder, and pervasive developmental disorder not otherwise specified, include deficits in socialization and communication and a need for the preservation of "sameness;" intellectual impairment and epilepsy are common comorbidities. Data suggest that pathological involvement of cholinergic nuclei and altered expression of acetylcholine receptors, particularly nicotinic acetylcholine receptors, occur in brain of persons with autistic disorder. However, many of these studies involved postmortem tissue from small samples of primarily adult persons. Thus, the findings may reflect compensatory changes and may relate more closely to intellectual impairment and the confounding effects of seizures and medications, as opposed to the core dysfunctions of autism. Nonetheless, because of the roles played by acetylcholine receptors in general, and nicotinic acetylcholine receptors in particular, in normal processes of attention, cognition, and memory, selective cholinergic interventions should be explored for possible therapeutic effects. Additionally, there are electrophysiological data that complement the clinical observations of frequent comorbid seizure disorders in these patients, suggesting a disturbance in the balance of excitatory and inhibitory tone in the brains of persons with autistic disorders. Conceivably, because the alpha7 nicotinic acetylcholine receptor is located on the surface of gamma-aminobutyric acid inhibitory neurons, selective stimulation of this receptor would promote gamma-aminobutyric acid's release and restore diminished inhibitory tone. The development of agonists and partial agonists for nicotinic acetylcholine receptors and positive allosteric modulators that enhance the efficiency of coupling between the binding of agonist and channel opening should facilitate consideration of clinical trials.

AKAP10 (I646V) functional polymorphism predicts heart rate and heart rate variability in apparently healthy, middle-aged European-Americans.

Previous evidence suggests that the dual-specific A kinase-anchoring protein 2 functional polymorphism (AKAP10 (A/G) I646V) influences heart rate (HR) and heart rate variability (HRV) in mice and humans (N=122) with cardiovascular disease. Here, we asked whether this AKAP10 variant predicts HR and HRV in a large sample of healthy humans. Resting HR and short-term time and frequency domain measures of HRV (5 min during paced and unpaced respiration conditions) were assessed in a U.S. community sample (N=1,033) of generally healthy men and women (age 30-54) of European ancestry. Each person was genotyped for the AKAP10 variant. As with previous work, the AKAP10 Val allele predicted greater resting HR (Paced p<.01; Unpaced p<.03) and diminished HRV (Paced ps <.05) suggesting that this variant may modulate the sensitivity of cardiac pacemaker cells to autonomic inputs, possibly conferring risk for arrhythmias and sudden cardiac death.

Normative variation in self-reported sleep quality and sleep debt is associated with stimulated pro-inflammatory cytokine production.

Activation of innate inflammatory pathways, marked by increased production of pro-inflammatory cytokines, has been proposed as a potential mechanism linking poor sleep and inflammatory disease risk. In the present study, we examined associations of self-reported sleep quality and duration, and a calculated measure of sleep debt with the production of pro-inflammatory cytokines, interleukin (IL)-6, IL-1beta, and tumor necrosis factor (TNF)-alpha among a community sample of 156 healthy adults. Bivariate correlations revealed an inverse association between sleep quality and production of all the three pro-inflammatory cytokines that was retained for IL-1beta after controlling for demographic and health characteristics. Hierarchical linear regressions also revealed that higher sleep debt scores predicted greater production of IL-1beta and IL-6 after adjusting for covariates. Secondary analyses showed an interaction between sleep debt and body mass index (BMI) in the prediction IL-1beta, suggesting that the impact of sleep debt on cytokine production is greater among participants with lower BMI scores. Further exploration of this potential psychophysiological pathway linking sleep difficulty and inflammatory disease susceptibility is warranted.

Silent myocardial ischemia and cardiovascular responses to anger provocation in older adults.

To determine if older, asymptomatic individuals with no prior history of coronary heart disease with exercise-induced silent myocardial ischemia (SI) during graded exercise treadmill testing exhibit exaggerated cardiovascular reactivity to anger provocation, we compared 42 SI participants and 95 controls. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) changes from baseline to three tasks--anger recall, speech role-play, and mental arithmetic with harassment--were assessed. Compared to controls, SI displayed greater HR responses for the speech role-play task only. The SI group was significantly older, had higher levels of fasting glucose and triglycerides, and had lower HDL-cholesterol. In multiple regression analyses, after controlling for these differences, SI was significantly associated with greater HR responses to the speech role-play. In sum, the SI group significantly exaggerated HR responses to the speech role-play task, whereas SBP and DBP reactivity were comparable between groups. This suggests minimally enhanced cardiovascular reactivity among older SI patients that may nonetheless increase risk for cardiac events.

Stimulated production of proinflammatory cytokines covaries inversely with heart rate variability.

OBJECTIVE: To examine whether high-frequency heart rate variability, an indirect measure of parasympathetic (vagal) control over variations in heart rate, is associated with immune reactivity to an in vitro inflammatory challenge. Convergent evidence from the animal literature shows that the autonomic nervous system plays a key role in regulating the magnitude of immune responses to inflammatory stimuli. Signaling by the parasympathetic system inhibits the production of proinflammatory cytokines by activated monocytes/macrophages and thus decreases local and systemic inflammation. As yet, no direct human evidence links parasympathetic activity to inflammatory competence. METHODS: We examined the relationship of variations in heart rate, recorded during paced respiration, to lipopolysaccharide-induced production of the inflammatory cytokines interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-10 among a community sample of 183 healthy adults (mean age = 45 years; 59% male; 92% White, 7% African-American). RESULTS: Consistent with animal findings, higher derived estimates of vagal activity measured during paced respiration were associated with lower production of the proinflammatory cytokines TNF-alpha and IL-6 (r = -.18 to -.30), but were not related to production of the anti-inflammatory cytokine IL-10. These associations persisted after controlling for demographic and health characteristics, including age, gender, race, years of education, smoking, hypertension, and white blood cell count. CONCLUSIONS: These data provide initial human evidence that vagal activity is inversely related to inflammatory competence, raising the possibility that vagal regulation of immune reactivity may represent a pathway linking psychosocial factors to risk for inflammatory disease.

Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers.

OBJECTIVE: Recent evidence suggests that higher peripheral levels of interleukin 6 (IL-6) are associated with poorer cognitive function and predict future cognitive decline among the elderly. The current investigation extends the study of relationships between plasma IL-6 and cognitive performance to healthy middle-aged adults and to an examination of more specific cognitive domains. METHODS: Five hundred relatively healthy community volunteers aged 30 to 54 had blood drawn for the determination of plasma IL-6 levels and completed a battery of neuropsychological tests evaluating memory and executive function. RESULTS: After controlling for age, gender, race, and education, hierarchical regression analyses revealed an inverse relationship between circulating levels of IL-6 and performance on clusters of tests assessing auditory recognition memory, attention/working memory, and executive function. In contrast, there was no association between IL-6 and performance on tests of general memory. Secondary analyses demonstrated that relationships between IL-6 and auditory recognition and working memory and executive function were independent of a number of health factors, including body mass index, smoking, and hypertension. CONCLUSIONS: These findings contribute to a growing body of evidence linking chronic inflammation to poorer cognitive functioning and extend these findings to a midlife community sample, raising the possibility that IL-6 may represent a biomarker for risk of future cognitive decline.

Human choline transporter gene variation is associated with corticolimbic reactivity and autonomic-cholinergic function.

BACKGROUND: Our previous work has shown genetic variation in the human choline transporter gene (CHT1) to be associated with depressive symptoms and autonomic cardiac (cholinergic) dysregulation. Here, functional magnetic resonance imaging (fMRI) was used to examine the relation between a single nucleotide polymorphism (SNP) in CHT1 on regional brain reactivity relevant to autonomic (cholinergic) function. METHODS: Thirty-two participants of European ancestry (18 men, 14 women; age: 33-54 years) completed an fMRI protocol using corticolimbic reactivity and prefrontal inhibitory control paradigms. Resting cholinergic function, as measured by heart rate variability (HRV), was quantified from electrocardiogram. Subjects were genotyped for a CHT1 G/T SNP. RESULTS: GG homozygotes had greater right (R) dorsal amygdala (p < .008), bilateral anterior cingulate (p < .009), and R caudate reactivity (p < .015) than T-allele carriers. Heart rate variability was related to R frontal cortex (Brodmann Areas 6, 9, and 46), R hippocampal formation, bilateral caudate, and bilateral anterior cingulate reactivity (p's < .007). CONCLUSIONS: CHT1 variation is related to differences in a distributed corticolimbic circuitry mediating behavioral and physiologic arousal. These relations may contribute to a biological mechanism by which genetic variation in cholinergic neurotransmission affects cognition, mood, and autonomic cardiac function.

A walking program's attenuation of cardiovascular reactivity in older adults with silent myocardial ischemia.

Silent myocardial ischemia (SI) has been linked to increased risk of future coronary events. Enhanced systolic and diastolic blood pressure (SBP and DBP, respectively) and heart-rate (HR) reactions to stress (cardiovascular reactivity [CVR]) have been associated with greater severity of SI and are related prospectively to coronary-artery-disease endpoints. The authors examined the potential attenuating effects of 6 months of walking (aerobic exercise) versus control on CVR to three laboratory stressors in 25 older adults with exercise-induced SI. Maximal aerobic capacity was significantly improved by 12% for the exercise group and decreased by 8% for controls (p < .001). Groups had similar biomedical profiles pre- and postintervention. Walkers had significantly reduced DBP reactivity (pre, 12 +/- 2; post, 4 +/- 2 mm Hg) compared with controls (pre, 10 +/- 2; post, 11 +/- 2 mm Hg; p = .05), but no differences between groups were found for SBP or HR reactivity. These findings are the first to suggest that increased physical activity (via walking) can attenuate BP reactivity to emotional stressors in apparently healthy older adults with SI.

White-coat hypertension and autonomic nervous system dysregulation.

BACKGROUND: White-coat hypertension, defined as high blood pressure (BP) on clinical assessment but normal BP elsewhere or on ambulatory measurement, is a common but poorly understood phenomenon. The current study asks whether individuals with white-coat hypertension have abnormal autonomic-cardiac regulation, similar to that observed in sustained or persistent hypertension. METHODS: Participants were men (ages 40 to 70 years; 63% white, 37% African American) not receiving any cardiovascular medications who were classified as persistent hypertensive (n = 40), white-coat hypertensive (n = 40), or normotensive (n = 40) on the basis of clinic and daytime ambulatory BP, using a threshold criterion for hypertension of 140/90 mmHg. Persistent and white-coat hypertensive subjects were matched on ethnicity and clinic BP, and white-coat hypertensive subjects and normotensive subjects were matched on race and daytime ambulatory BP. Frequency domain analysis of resting beat-to-beat heart rate variability (HRV) was used to estimate parasympathetic and sympathetic control of the heart. RESULTS: Relative to normotensive subjects, both persistent and white-coat hypertensive subjects had lower high-frequency (HF) (P < .03) and low-frequency (LF) power (P < .051) and thus less parasympathetic activity. In addition, white-coat and persistent hypertensive subjects had significantly greater LF/HF ratios, indicating greater sympathetic-to-parasympathetic activity, as compared with normotensive subjects (P < .03). CONCLUSIONS: These findings suggest similarities between persistent and white-coat hypertensive subjects reflecting attenuated parasympathetic control of the heart. In addition, the association between white-coat hypertension and autonomic dysregulation, particularly diminished parasympathetic tone, may serve as a mechanism for increased risk for cardiovascular events in affected individuals.

Heart rate variability is associated with polymorphic variation in the choline transporter gene.

OBJECTIVE: The objective of this study was to determine whether interindividual variation in parasympathetic (cholinergic) and sympathetic (adrenergic) regulation of heart rate (as estimated by frequency components of heart rate variability [HRV]) may be accounted for, in part, by genetic variation in the choline transporter, a component of acetylcholine neurotransmission. METHODS: Resting HRV estimates of high- (HF) and low-frequency (LF) power and LF/HF ratio were determined from electrocardiogram recordings collected continuously over 5 minutes in 413 white individuals of European ancestry (49% men; aged 30-54 years [mean, 44 years]). Subjects were genotyped for a single nucleotide polymorphism (SNP) located in the 3' untranslated region of the choline transporter gene (CHT1). Frequencies of the alternate CHT1 alleles, labeled G and T, were 76% and 24%. RESULTS: Compared with GG homozygotes, participants having any T allele had greater HF power (p <.02), lower LF power (p <.02), and lower LF/HF ratios (p <.005). Relative to men, women had lower LF power (p <.001) and lower LF/HF ratios (p <.005). CONCLUSIONS: These findings show that polymorphic variation in the CHT1 gene is associated significantly with interindividual variability in HRV indices related to parasympathetic (cholinergic) activity.

Alexithymia predicts attenuated autonomic reactivity, but prolonged recovery to anger recall in young women.

Alexithymia has been prospectively associated with all-cause mortality and with cardiovascular morbidity. Here, stress-induced autonomic reactivity and recovery were examined as potential pathways linking alexithymia to cardiovascular disease. The relation of alexithymia to blood pressure, heart rate, and other cardiovascular parameters derived from impedance cardiography (N = 80) and heart rate variability (N = 40) was evaluated during rest, an anger recall task and recovery in women (ages 18-30). During anger recall, alexithymia was associated with significantly attenuated heart rate and stroke index reactivity, greater low frequency power, and with marginally dampened blood pressure and high frequency power reactivity. Overall, this response pattern suggests blunted sympathetic activation and diminished vagal withdrawal. Alexithymia was also related to slower diastolic blood pressure and quicker preejection period recovery implying abbreviated sympathetic arousal and possibly greater vagal modulation. These results impart some evidence for the hypoarousal model of alexithymia during reactivity, but the hyperarousal model during recovery. Autonomic dysregulation during and following acute emotional stress is suggested as a possible physiological pathway connecting alexithymia to cardiovascular disease.