Prognostic Significance of Impaired Baroreflex Sensitivity Assessed from Phase IV of the Valsalva Maneuver in a Population-Based Sample of Middle-Aged Subjects

doi:10.1016/j.amjcard.2014.05.032

The American Journal of Cardiology

Volume 114, Issue 4, 15 August 2014, Pages 571-576

https://doi.org/10.1016/j.amjcard.2014.05.032 Get rights and content

Depressed baroreflex sensitivity (BRS) is associated with an increased risk of mortality in patients with a known cardiac disease. The prognostic significance of BRS in subjects without history of major cardiovascular (CV) events is unknown. The present study tested the hypothesis that impaired BRS predicts the CV mortality in a population-based sample of middle-aged subjects. The present study is a part of the Oulu Project Elucidating Risk of Atherosclerosis study, where middle-aged hypertensive and age- and gender-matched control subjects were randomly selected. Along with clinical and laboratory assessments, BRS was measured from the blood pressure overshoot of Valsalva maneuver in 559 subjects (age 51 ± 6 years; 300 men). The causes of death (n = 72) were registered during a follow-up of up to 19 years. CV death (n = 23) was defined as the primary end point. CV death was predicted by smoking status, alcohol consumption, high-sensitivity C-reactive protein, use of diuretics, waist circumference, and fasting glucose. Among all measured risk factors, impaired Valsalva BRS (<3 ms/mm Hg) was the most potent predictor of CV death (hazard ratio 9.1, 95% confidence interval 3.8 to 21.7, p <0.001) and remained so after adjustments for the other significant predictors (hazard ratio 5.3, 95% confidence interval 2.1 to 13.3, p <0.001). In conclusion, impaired Valsalva BRS is a potent and independent predictor of CV death in a population-based sample of middle-aged subjects without history of major CV complications and may have important clinical implications in early risk stratification.

Section snippets

Methods

The present study is a part of the Oulu Project Elucidating Risk of Atherosclerosis (OPERA) study, where middle-aged hypertensive subjects and age- and gender-matched control subjects were randomly selected in the early 1990s from the national registry for reimbursement of medications for the purpose of assessing the prognostic significance of risk factors in predicting atherosclerotic CV diseases.⁷ Subjects with previous myocardial infarction or stroke were excluded. A total of 559 subjects

Results

Hypertension (p <0.001), current smoking (p = 0.001), female gender (p = 0.003), and advanced age (p = 0.019) were the most significant determinants of abnormal BRS. Impaired Valsalva BRS involved ninefold univariate risk for CV death (Table 2; Figure 2), positive and negative predictive accuracies and sensitivity and specificity being 19% and 97%, and 35% and 94%, respectively. In multivariate analysis without impaired Valsalva BRS in the model, advanced age, current smoking, larger alcohol

Discussion

The principal finding of the present study was that impaired BRS, as measured from the BP overshoot phase of the Valsalva maneuver, is a significant and independent predictor of CV death in a population-based sample of middle-aged subjects. The present findings support the hypothesis, tested previously in healthy animals,⁶ that depressed baroreflex is a powerful predictor of CV death also in subjects without history of major CV complications.

Depressed BRS has proved to be an evident predictor

Acknowledgment

The OPERA investigators and staff are gratefully acknowledged.

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Baroreflex sensitivity derived from the Valsalva manoeuvre: A physiological protective factor for anxiety induced by breathing CO<inf>2</inf>-enriched air
2022, International Journal of Psychophysiology
Citation Excerpt :
BRS measured from changes in systolic blood pressure and heartbeat interval during this fourth phase is frequently used to quantify sensitivity of the vagal baroreflex loop (vagal baroreflex sensitivity, BRS_v) (Kautzner et al., 1996; Palmero et al., 1981; Pstras et al., 2016). Impaired BRS derived from phase IV of the Valsalva manoeuvre appears to be a strong and independent predictor of cardiovascular mortality (Kiviniemi et al., 2014). It is important to note that even though the compensatory bradycardic reflex induced by the Valsalva manoeuvre is predominantly mediated by the baroreceptors, the manoeuvre also triggers alterations in chemoreceptor and cardiopulmonary receptor activity.
This study aimed to determine the capacity of baroreflex sensitivity, derived from the Valsalva manoeuvre (BRS_v), to predict state anxiety induced by a biological stressor (CO₂ inhalation). Healthy adults (n = 50) breathed 7.5 % CO₂-enriched air for 8 min, preceded and followed by breathing medical air for 5 min. State anxiety was evaluated with a visual analogue scale. Anxiety sensitivity (Anxiety Sensitivity Index-3; ASI-3) and trait anxiety (Trait form of the State-Trait Anxiety Inventory; STAI_T) served as cognitive-affective predictors. BRS_v was adopted as a physiological predictor. Multiple regression analysis revealed that BRS_v predicted lower anxiety during CO₂ exposure, and attenuated the effect of ASI-3 in increasing anxiety. No significant effects were found for STAI_T. This is the first study to identify baroreflex sensitivity as a strong protective physiological factor for anxiety beyond the effect of anxiety sensitivity.
Valsalva-derived Measures and Phenylephrine Test in Patients With Heart Failure With Reduced Ejection Fraction Receiving Comprehensive Neurohormonal Blockade Drug Therapy: A 5-year Event-free Survival Analysis
2022, Journal of Cardiac Failure
Citation Excerpt :
Regarding the Valsava test as a measure of cBRS, Rostagno et al12 reported no relation between the cBRS as assessed from the overshoot period of phase IV and mortality in 52 patients with HF during a mean follow-up of 26 months, although the patients in New York Heart Association functional class I were characterized by significantly higher cBRS as compared with patients in classes II and III. More recently, however, the cBRS calculated from the overshoot period was shown to be a powerful predictor of cardiovascular death in a population-based sample of middle-aged hypertensive and healthy subjects in a study by Kiviniemi et al.23 We failed to find any relations between the cBRS as assessed with the Valsalva test and event-free survival, and our results corroborate the study by Rostagno et al,12 although important differences between these studies, including different computational procedure (slope calculated from the overshoot of phase IV in Rostagno et al vs from the whole phase IV in our study), the clinical status of the examined patients (37% vs 5% patients in New York Heart Association functional classes III and IV in Rostagno et al vs the current study, respectively), and HF treatment (none of the Rostagno's patients received beta-blocker therapy) need to be underlined. Few studies have investigated the non–cBRS-related indices of Valsalva maneuver (eg, PAR) in terms of their prognostic usefulness.
To assess the relationships between Valsalva- and phenylephrine test-derived measures and outcome in patients with heart failure with reduced ejection fraction (HFrEF) receiving comprehensive neurohormonal blockade pharmacotherapy.
Data from 56 patients with HFrEF (mean left ventricle ejection fraction of 32 ± 6%) subjected to Valsalva and phenylephrine tests were analyzed retrospectively. Baroreflex-related (Valsalva-ratio and blood pressure–RR interval slope from phase IV) and non–baroreflex-related measures (systolic blood pressure rise in phase IV [ΔSBP_{PHASE_IV}], and pulse amplitude ratio [PAR]) were calculated from Valsalva. Short-term outcomes (HF-related hospitalization, implantable cardioverter-defibrillator shock or all-cause death within 24 months from examination) and long-term outcomes (implantable cardioverter-defibrillator shock or all-cause death within 60 months) were analyzed. The end point occurred in 16 and 18 patients, for the short- and long-term outcomes, respectively. A low ΔSBP_{PHASE_IV} identified patients at risk in the long term, as evidenced by a low vs high ΔSBP_{PHASE_IV} comparison (square-wave response patients assigned to low ΔSBP_{PHASE_IV} group, P = .002), and Cox model (hazard ratio 0.91, 95% confidence interval 0.86–0.96, P < .001), and tended to identify patients at risk in the short term outcome (hazard ratio 0.95, 95% confidence interval 0.91–1.00, P = .055). There was a tendency toward a higher event-free survival in the low PAR group (low vs high PAR; hazard ratio 0.44, 95% CI 0.17–1.18, P = .104).
Non–baroreflex-related measures obtained from Valsalva—namely, ΔSBP_{PHASE_IV} and PAR—might carry prognostic value in patients with HFrEF receiving neurohormonal blockade pharmacotherapy.
Physical demands of overhead crane operation
2021, International Journal of Industrial Ergonomics
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Electrode placement for each muscle was verified by instructing the participant to perform a muscle specific contraction designed to maximally activate that particular muscle. Given that the cardiovascular risk status of participants was not known coupled with the fact that four of the seven participants were smokers, maximum voluntary contractions (MVC) for EMG normalization were contraindicated (Hallstrom et al., 1986; Kiviniemi et al., 2014; Piha, 1994). MVC studies typically involve young, fit, and athletic university students.
Recent studies have suggested that ergonomic factors may contribute to risks experienced by overhead crane operators. However, there are few studies that provide a comprehensive overview of the physical demands of overhead crane operation. This study aimed to provide this information by quantifying muscular, postural, and upper limb movement demands of overhead crane operation including examination of muscle activation and trunk posture by task. Trunk posture, upper limb movement demands and muscle activation in the trunk and upper limbs were quantified for seven overhead crane operators. Trunk posture was quantified using trunk angle and joystick motion requirements were determined using camera data. Muscle activation was measured bilaterally using surface EMG for the upper trapezii, anterior deltoids, posterior deltoids, biceps brachii, triceps brachii, flexor carpi radialis and erector spinae. Lastly, joystick force requirements were assessed using a spring scale. High upper limb and trunk muscle loading were observed when compared to joystick use in other heavy machinery, in part due to the forward, trunk-flexed position required to adequately view the workspace, and the increased force requirements of the joysticks. Joystick input force requirements were 9–31 N for the right-hand joystick and 11–40 N for the left-hand joystick. Operators maintained a forward trunk flexion (>20°) for all subtasks which suggests that trunk posture might play a role in sustained trunk muscle activation. Results suggest that the primary issue with overhead crane cab operation is upper limb and trunk muscle loading. Results confirm the need to investigate muscle load reduction strategies such as camera systems to help reduce the need for trunk flexion. Other design modification suggestions include reducing the joystick input force and displacement requirements coupled with potentially distributing the machine functions more evenly across the right and left controllers.
Long-term caregiving is associated with impaired cardiovagal baroreflex
2017, Journal of Psychosomatic Research
Citation Excerpt :
Notably, patients with recent myocardial infarction tend to have a lower cBRS and higher risk of developing fatal arrhythmias [11]. Even without history of cardiac events, middle aged people with cBRS lower then 3 ms/mm Hg have nine times greater risk of cardiac death compared to those with cBRS > 3 ms/mm Hg [12,13]. Given the studies that caregiving stress is associated with increased cardiovascular risk, a blunted cBRS may help explain higher risk of cardiovascular events in caregivers.
Caregiving stress is associated with increased risk of cardiovascular disease (CVD). Inability to adequately regulate blood pressure is a possible underlying mechanism explaining this risk. We examined the relationship between length of caregiving and cardiovagal baroreflex sensitivity (cBRS) to better understand the link between caregiving and CVD risk.
A total of 146 elderly individuals (≥ 55 years) participated in this study, of whom 96 were providing in-home care to a spouse with dementia and 50 were healthy controls married to a non-demented spouse (i.e., non-caregivers). Among the caregivers, 56 were short-term caregivers (caring < 4 years) and 40 were long-term caregivers (caring ≥ 4 years). A multiple linear regression model, with contrast codes comparing short and long-term caregivers with non-caregivers was used to understand relationships between chronic caregiving and cBRS.
After controlling for relevant demographic and health characteristics, mean ± SE log transformed cBRS for non-caregivers was 0.971 ± 0.029. Relative to non-caregivers, the long-term caregivers had significantly impaired cBRS (0.860 ± 0.033; p = 0.013). However, mean cBRS for short-term caregivers did not significant differ from non-caregivers (0.911 ± 0.028; p = 0.144).
These results suggest that long-term caregiving stress is associated with an impaired cBRS. Accumulation of stress from years of caregiving could result in worse cBRS function, which could be a mechanistic explanation for the correlation between caregiving stress and the increased risk of CVD.
Epidemiological evidence of increased waist circumference, but not body mass index, associated with impaired baroreflex sensitivity
2020, Obesity Research and Clinical Practice
Citation Excerpt :
Autonomic function has been shown to be involved in energy metabolism and the regulation of the cardiovascular system [1,2]. Clinically, impaired baroreflex sensitivity (BRS), one indicator of autonomic function, is associated with adverse cardiovascular event, including hypertension, coronary arterial disease, heart failure, and mortality in population with and without cardiovascular diseases [3–6]. Thus, BRS may have important clinical implications in early risk stratification of cardiovascular outcomes [6].
Although an inverse relationship between body mass index (BMI) and baroreflex sensitivity (BRS) was found, the effect of waist circumference (WC) on BRS is still inconclusive. The contradictory results of previous studies may be related to the heterogeneity and relatively small sample size of the subjects examined. The aim of this population-based study was to investigate whether the influence of increased WC is more detrimental to BRS than BMI. A total of 760 community dwellers were recruited and they were classified into Q1 (n = 189), Q2 (n = 183), Q3 (n = 192) and Q4 (n = 196) groups, based on WC quartiles. Spontaneous BRS was determined by spectral α coefficient method. Valsalva ratio was the longest RR interval after release of Valsalva maneuver divided by the shortest RR interval during maneuver. Cardiac autonomic function was calculated by power spectrum of heart rate in low and high frequency (LF, 0.04–0.15 Hz; HF, 0.15–0.40 Hz), and LF/HF ratio in supine position for five minutes. There were significant differences in spontaneous BRS and Valsalva ratio among different WC groups. In multivariate analysis, obesity was inversely associated with spontaneous BRS and Valsalva ratio. However, these inverse relationships became insignificant after further adjustment for WC quartiles. In contrast, Q4 vs. Q1, Q3 vs. Q1 and Q2 vs. Q1 of WC were inversely related to spontaneous BRS. Q4 vs. Q1 and Q3 vs. Q1 of WC were negatively associated with the Valsalva ratio. In conclusion, increased and even high-normal WC had a stronger adverse effect on BRS than BMI, independent of cardio-metabolic risk factors.
Lower hemoglobin levels associate with higher baroreflex sensitivity and heart rate variability
2023, American Journal of Physiology - Endocrinology and Metabolism

View all citing articles on Scopus

: This study was supported by grants from the Sigrid Juselius Foundation, Helsinki, Finland, and The Finnish Foundation for Cardiovascular Research, Helsinki, Finland.

: See page 575 for disclosure information.

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Preventive CardiologyPrognostic Significance of Impaired Baroreflex Sensitivity Assessed from Phase IV of the Valsalva Maneuver in a Population-Based Sample of Middle-Aged Subjects

Section snippets

Methods

Results

Discussion

Acknowledgment

Am J Cardiol

Am Heart J

Am J Cardiol

J Am Soc Echocardiogr

Am J Hypertens

J Am Coll Cardiol

J Am Coll Cardiol

Baroreflex sensitivity, clinical correlates, and cardiovascular mortality among patients with a first myocardial infarction. A prospective study

Circulation

Prognostic value of baroreflex sensitivity testing after acute myocardial infarction

Br Heart J

Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators

Lancet

Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials

Circulation

Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure

J Hypertens

Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction

Circulation

Metabolic syndrome in the prediction of cardiovascular events: the potential additive role of hsCRP and adiponectin

Eur J Prev Cardiol

General cardiovascular risk profile for use in primary care: the Framingham Heart Study

Circulation

Preventive Cardiology
Prognostic Significance of Impaired Baroreflex Sensitivity Assessed from Phase IV of the Valsalva Maneuver in a Population-Based Sample of Middle-Aged Subjects