Higher Anxiety Is Associated with Lower Cardiovascular Autonomic Function in Female Twins

Anxiety symptoms co-occur with cardiovascular health problems, with increasing evidence suggesting the role of autonomic dysfunction. Yet, there is limited behavior genetic research on underlying mechanisms. In this twin study, we investigated the phenotypic, genetic and environmental associations between a latent anxiety factor and three cardiovascular autonomic function factors: interbeat interval (IBI, time between heart beats), heart rate variability (HRV, overall fluctuation of heart-beat intervals) and baroreflex sensitivity (BRS, efficiency in regulating blood pressure [BP]). Multivariate twin models were fit using data of female twins (N = 250) of the Twin Interdisciplinary Neuroticism Study (TWINS). A significant negative association was identified between latent anxiety and BRS factors (r = -.24, 95% CI [-.40, -.07]). Findings suggest that this relationship was mostly explained by correlated shared environmental influences, and there was no evidence for pleiotropic genetic or unique environmental effects. We also identified negative relationships between anxiety symptoms and HRV (r = -.17, 95% CI [-.34, .00]) and IBI factors (r = -.13, 95% CI [-.29, .04]), though these associations did not reach statistical significance. Findings implicate that higher anxiety scores are associated with decreased efficiency in short-term BP regulation, providing support for autonomic dysfunction with anxiety symptomatology. The baroreflex system may be a key mechanism underlying the anxiety-cardiovascular health relationship

Cross-instrument feasibility, validity, and reproducibility of wireless heart rate monitors:Novel opportunities for extended daily life monitoring

Wired ambulatory monitoring of the electrocardiogram (ECG) is an established method used by researchers and clinicians. Recently, a new generation of wireless, compact, and relatively inexpensive heart rate monitors have become available. However, before these monitors can be used in scientific research and clinical practice, their feasibility, validity, and reproducibility characteristics have to be investigated. Therefore, we tested how two wireless heart rate monitors (i.e., the Ithlete photoplethysmography (PPG) finger sensor and the Cortrium C3 ECG monitor perform against an established wired reference method (the VU-AMS ambulatory ECG monitor). Monitors were tested on cross-instrument and test-retest reproducibility in a controlled laboratory setting, while feasibility was evaluated in protocolled ambulatory settings at home. We found that the Cortrium and the Ithlete monitors showed acceptable agreement with the VU-AMS reference in laboratory setting. In ambulatory settings, assessments were feasible with both wireless devices although more valid data were obtained with the Cortrium than with the Ithlete. We conclude that both monitors have their merits under controlled laboratory settings where motion artefacts are minimized and stationarity of the ECG signal is optimized by design. These findings are promising for long-term ambulatory ECG measurements, although more research is needed to test whether the wireless devices' feasibility, validity, and reproducibility characteristics also hold in unprotocolled daily life settings with natural variations in posture and activities

Abnormal Nailfold Capillaroscopy Is Common in Patients with Connective Tissue Disease and Associated with Abnormal Pulmonary Function Tests

Objective. To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT). Methods. NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity <70%. Patients were classified as primary RP (n = 245), or secondary: no definite diagnosis (n = 391), SSc (n = 40), primary Sjogren syndrome (pSS; n = 30), systemic lupus erythematosus (SLE; n = 30), mixed connective tissue disease (MCTD; n = 7), rheumatoid arthritis (RA; n = 15). Results. An SSc pattern on NCM was frequently observed in most patients with a definite diagnosis: SSc (88%), pSS (33%), SLE (17%), MCTD (71%), and RA (13%). In patients without definite diagnosis, 17% had a normal NCM pattern, 35% nonspecific, and 48% SSc pattern. Abnormal PFT was more frequent in patients with an SSc pattern (35.9% vs 19.5%, p = 0.002), even when corrected for SSc diagnosis (p = 0.003). Absence of an SSc pattern had high negative predictive value (88%); positive predictive values were low. Conclusion. SSc pattern on NCM is common in patients with RP, and in those with connective tissue diseases other than SSc. It is associated with a higher prevalence of abnormal PFT, independent of the presence of an SSc diagnosis. Although these data need validation in a prospective setting, they underline the importance of NCM in RP and putative value to stratify the risk of pulmonary involvement in early stages of disease

The genetic relationship between neuroticism and autonomic function in female twins

Background. Neuroticism is widely used as an explanatory concept in etiological research of psychopathology. In order to clarify what neuroticism actually represents, we investigated the genetic association between neuroticism and cardiovascular measures. Method. In 125 female twin pairs (18-30 years), electrocardiogram and continuous finger blood pressure were assessed during two rest and two mental stress conditions. Mean values for baroreflex sensitivity (BRS), heart rate variability (HRV) and inter-beat interval (IBI) were calculated for each condition. Neuroticism was assessed by multiple questionnaires. Multivariate genetic model-fitting analyses were used to investigate the genetic correlation between latent neuroticism and the cardiovascular autonomic nervous system (ANS) measures. Results. Neuroticism was negatively correlated to BRS and HRV. Neuroticism was not correlated to IBI. For BRS, this phenotypical relation was entirely determined by shared genetic influences. For HRV, the genetic contribution to the phenotypical correlation was not significant, but the proportions of explained covariance showed a trend of more genetic than environmental influences on the phenotypical relationship. Conclusions. High neuroticism is associated with a deregulated ANS. Pleiotropic genetic effects may be partly responsible for this effect

Spontaneous baroreflex sensitivity and its association with age, sex, obesity indices and hypertension:a population study

BACKGROUND: Low baroreflex sensitivity (BRS) is an established risk factor for cardiovascular disorders. We investigated determinants of BRS in a large sample from general population. METHODS: In a population-based study (n=901) data were collected on BRS, arm cuff blood pressure (BP) and obesity indices including body mass index (BMI), waist-to-hip ratio (WHR), waist circumference and percentage body fat (%BF). BRS was calculated by spectral analysis software based on continuously recorded spontaneous fluctuations in beat-to-beat finger BP for 10 to 15 minutes. Correlations and multivariable regression analyses were used to test associations of age, sex, obesity indices and hypertension with BRS while considering effects of lifestyle factors (smoking, alcohol consumption and physical activity). RESULTS: In multivariable analysis, age, sex, %BF, and hypertension were independently associated with BRS. BRS decreased with -0.10 (95% confidence interval [CI]: -0.15 to -0.06) ms/mmHg with each year of increase in age. Women had -1.55 (95% CI: -2.28 to -0.73) ms/mmHg lower mean BRS than men. The effects of %BF (per 10% increase) and hypertension on BRS were -0.55 (95% CI: -0.97 to -0.13) ms/mmHg and -1.23 (95% CI: -1.92 to -0.46) ms/mmHg, respectively. There was no evidence of associations between BRS and lifestyle factors. Age, age 2, sex, and their interactions plus %BF and hypertension contributed 16.9% of total variance of BRS. CONCLUSIONS: In this large general population study, we confirm prior findings that age and sex are important factors associated with BRS and find %BF is more strongly related to less favorable BRS levels than BMI

Heritability and the Genetic Correlation of Heart Rate Variability and Blood Pressure in &gt;29 000 Families The Lifelines Cohort Study:The Lifelines Cohort Study

Dysregulation of the cardiac autonomic nervous system, as indexed by reduced heart rate variability (HRV), has been associated with the development of high blood pressure (BP). However, the underlying pathological mechanisms are not yet fully understood. This study aimed to estimate heritability of HRV and BP and to determine their genetic overlap. We used baseline data of the 3-generation Lifelines population-based cohort study (n=149 067; mean age, 44.5). In-house software was used to calculate root mean square of successive differences and SD of normal-to-normal intervals as indices of HRV based on 10-second resting ECGs. BP was recorded with an automatic BP monitor. We estimated heritabilities and genetic correlations with variance components methods in ASReml software. We additionally estimated genetic correlations with bivariate linkage disequilibrium score regression using publicly available genome-wide association study data. The heritability (SE) estimates were 15.6% (0.90%) for SD of normal-to-normal intervals and 17.9% (0.90%) for root mean square of successive differences. For BP measures, they ranged from 24.4% (0.90%) for pulse pressure to 30.3% (0.90%) for diastolic BP. Significant negative genetic correlations (all P<0.0001) of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (-0.20/-0.16) and with diastolic BP (-0.15/-0.13) were observed. LD score regression showed largely consistent genetic correlation estimates of root mean square of successive differences/SD of normal-to-normal intervals with systolic BP (range, -0.08 to -0.23) and diastolic BP (range, -0.20 to -0.27). Our study shows a substantial contribution of genetic factors in explaining the variance of HRV and BP measures in the general population. The significant negative genetic correlations between HRV and BP indicate that genetic pathways for HRV and BP partially overlap

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy:One-year follow-up

Objective: Follow-up of patients with treatment-resistant Raynaud's phenomenon (RP) one-year after single-port thoracoscopic sympathicotomy (SPTS). Methods: Eight patients (six males, two females, median age of 45 years) with treatment-resistant RP underwent left-sided SPTS at the third rib (R3), unilaterally. Questionnaires were taken, and number and duration of RP attacks were reported over a 2-week period. Perfusion was assessed with a cooling and recovery procedure at baseline and one year after SPTS. Furthermore, laser speckle contrast analysis, pulse wave velocity, heart rate variability and nailfold capillary microscopy were performed. Results: One year after SPTS the duration of the attacks of was reduced with 1.9 h in the left hand versus 0.3 h in the right hand. Furthermore, three aspects of the questionnaire showed a significant improvement (role limitations due to physical health (p = 0.017), pain (p = 0.027) and physical functioning (p = 0.025)). The total area under the curve of the total cooling and recovery procedure of the left hand was larger one year after surgery (101 (75–140) at baseline versus 118 (95–190) one year post-operatively, p = 0.012), implying a better perfusion in the fingers. This was mainly due to the improvement during the recovery phase (21 (1–41) at baseline versus 38 (24–43) one year post-operatively, p = 0.028). Conclusion: One year after unilateral R3 SPTS the benefit with regard to the majority of outcome variables persisted, though some effects seem to attenuate. Long-term effects and long-term follow-up results will be investigated in an on-going study. Clinical trial registration number: NCT02680509

Predicting recurrence of depression using cardiac complexity in individuals tapering antidepressants

Funding Information: We would like to thank GM Bloem, D Sloohof, G Arts, and E van den Kieboom for their work on (pre-)processing the physiological data. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (ERC-CoG-2015; No. 681466 to M Wichers). The Cortrium monitors were kindly provided by the iLab of the Department of Psychiatry of the University Medical Center Groningen (UMCG, http://www.ilab-psychiatry.nl ).Peer reviewe