Lower Baroreflex Sensitivity Research Articles

Load-Dependent Mechanisms Contribute to Increased Aortic Stiffness Among Women with a History of Preeclampsia: Relation with Cardiovagal Baroreflex Sensitivity.

Introduction: Preeclampsia, a hypertensive disorder of pregnancy, results in increased lifetime cardiovascular disease (CVD) risk. Total aortic stiffness, a robust risk factor for CVD, is composed of load-dependent (blood pressure load on arterial wall) and structural (intrinsic changes in arterial wall) mechanisms. Total aortic stiffness is also associated with reduced cardiovagal baroreflex sensitivity (BRS). We sought to determine 1) whether elevated total aortic stiffness among women with a history of preeclampsia (hxPE) is attributed to load-dependent or structural stiffness, and 2) whether either mechanism is associated with lower BRS. Methods: Total aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal BRS (sequence technique) were measured among women 1-5 years postpartum (n=115; age 34 ±4yrs; hxPE n=51; controls n=64). Structural aortic stiffness was calculated from participant-specific exponential models, standardizing aortic stiffness to a 'reference' blood pressure. Load-dependent stiffness was calculated as total minus structural stiffness. Results: Total (+0.8 m/sec, 95% CI (-0.99, -0.23), p=0.002) and load-dependent (+0.4 m/sec, 95% CI (-0.56, -0.22), P<0.001), but not structural (95% CI (-0.52, 0.08), p=0.16), aortic stiffness were higher among women with hxPE compared with controls. Women with a hxPE had lower BRS (p=0.042) that was negatively associated with total (B =-3.24 ms/mmHg, 95% CI (-6.35, -0.13), p=0.042) and load-dependent (B =-5.91ms/mmHg, 95% CI (-11.31, -0.51), p=0.033) aortic stiffness. Conclusion: Load-dependent, not structural, aortic stiffness mechanisms contribute to higher total aortic stiffness among women with hxPE and was associated with lower cardiovagal BRS. Postpartum BP monitoring is critical to reduce increased CVD risk in preeclampsia.

Interindividual variability in cold-pressor pain sensitivity is not explained by peripheral vascular responding and generalizes to a C-nociceptor-specific pain phenotype.

Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor-sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex-mediated microcirculatory responses. Cold-pressor-sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor-mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber-mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water-exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.

Correlation between Cardiovascular Autonomic and Pulmonary Ventilation Functions in Myasthenia Gravis Patients.

This study aimed to investigate the relationship between pulmonary function and cardiac autonomic function parameters in clinically stable myasthenia gravis (MG) patients. A total of 22 MG patients and 22 healthy controls (HCs) were evaluated. Pulmonary function test parameters, heart rate variability (HRV), baroreflex sensitivity (BRS), and cardiovascular autonomic function test parameters (the Valsalva ratio, expiration/inspiration (E/I) ratio) were assessed. Compared with the HCs, the patients demonstrated a similar diffusion capacity for carbon monoxide (DLCO); a lower forced vital capacity (FVC%pred); a lower forced expiratory volume in 1 s (FEV1%pred); lower BRS and HRV, including high-frequency and total power spectral density; and a higher percentage of abnormal cardiovagal function test results (p < 0.05). A lower BRS in the patient group was associated with worse clinical disease outcomes and reduced pulmonary function (DLCO%pred, R = 0.59; TLC%pred, R = 0.48). Age, forced vital capacity, and total lung capacity predicted the E/I ratio (R2 values ranging from 0.48 to 0.49). Our study demonstrated a significant relationship between a reduced pulmonary ventilation function and respiratory mechanics with cardiovascular autonomic parameters, including the E/I ratio, BRS, and HRV measures at rest, as shown in the MG group. Future studies should focus on the interplay between respiratory and autonomic function testing, as well as pulmonary rehabilitation, to mitigate cardiovascular risk in these patients.

Altered Cardiac Autonomic Regulation in Individuals with Myasthenia Gravis-A Systematic Review and Meta-Analysis.

The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception to 7 July 2023 for studies investigating cardiovascular autonomic parameters in MG vs. HCs. A random-effects meta-analysis was performed to compute Hedges' g ± 95% confidence intervals (CI). Out of a total of 2200 records, 8 observational studies with a sample size of 301 patients with MG and 454 HCs were included in the systematic review. Meta-analysis revealed lower values of expiration/inspiration ratio (g = -0.45, I2 = 74.7), baroreflex sensitivity (g = -0.56, 95%CI -0.80, -0.33; I2 = 0.3), percentage of adjacent NN intervals differing by more than 50 ms (g = -1.2, I2 = 82.8), square root of the mean of squared differences between successive beat intervals (g = -1.94, I2 = 95.1), mean of the standard deviations of all NN intervals (g = -0.83, 95%CI -1.37, -0.28; I2 = 55.5), and high frequency of HRV during tilt (g = -0.75, 95%CI -0.11, -0.39; I2 = 0). MG patients vs. HCs had higher systolic blood pressure (g = 0.39; I2 = 56.1), sympathovagal balance at rest/during tilt (LF/HF-RRIsupine, g = 0.44; I2 = 0; LF/HF-RRItilt, g = 0.86; I2 = 0; LF/HFtilt, g = 0.40; I2 = 0). As a group, MG patients have altered cardiac autonomic function, including decreased parasympathetic function, lower baroreflex sensitivity, and higher sympathovagal balance at rest and during orthostatic challenges.

Role of Vascular Receptors in the Development of Hypertension in the Elderly Population.

Hypertension is a disease common in adults, with many risk factors and potentially life-threatening outcomes. Blood pressure is controlled by receptors that inform the brain about the amount of pressure inside the arteries, and the amount of oxygen and carbon dioxide in the blood, respectively. Research has revealed that baroreflex sensitivity (BRS) decreases with increasing age and that there is a high correlation between hypertension and low BRS. However, various studies with differing results have indicated that high blood pressure is what causes BRS to decline, and vice versa. Several studies have shown very conflicting results on the correlation between chemoreflex and age; there have been indications of chemoreflex having a positive, negative, and zero correlation with age. In several experiments, the surgical removal of the chemoreceptors of hypertensive rats was followed by a decrease in blood pressure. These animal experiments, and an additional noninvasive human experiment in which the chemoreceptors were temporarily "shut off," are reasons why more attention should be given to chemoreceptors as a route of alleviating hypertension.

Cardiovagal baroreflex sensitivity, blood pressure and blood pressure variability - the Maastricht study.

Low baroreflex sensitivity (BRS) has been hypothesized to underlie high blood pressure (BP) and greater BP variability on the longer term, but evidence is scarce. In addition, these associations may differ by sex and (pre)diabetes. Therefore, we investigated whether cardiovagal BRS is associated with short- to mid-term mean BP and BP variability, and differs according to sex and (pre)diabetes. Cross-sectional data from the population-based Maastricht study (age 60 ± 8 years, 52% men), where office ( n = 2846), 24-h ( n = 2404) and 7-day BP measurements ( n = 2006) were performed. Spontaneous BRS was assessed by cross-correlating systolic BP and instantaneous heart rate. We used linear regression with adjustments for age, sex, BP or BP variability, and cardiovascular risk factors. With regard to BP, 1-SD (standard deviation) lower BRS (-5.75 ms/mmHg) was associated with higher office, 24-h and 7-day systolic BP (2.22 mmHg [95% confidence interval [CI]: 1.59; 2.80], 0.95 mmHg [0.54; 1.36], and 1.48 mmHg [0.99; 1.97], respectively) and diastolic BP (1.31 mmHg [0.97; 1.66], 0.57 mmHg [0.30; 0.84], and 0.86 mmHg [0.54; 1.17], respectively). Per 1-SD lower BRS, these associations were stronger in women (0.5-1.5 mmHg higher compared to men), and weaker in those with type 2 diabetes (1-1.5 mmHg lower compared to normal glucose metabolism). With regard to BP variability, BRS was not consistently associated with lower BP variability. Lower cardiovagal BRS is associated with higher mean BP from the short- to mid-term range, and not consistently with BP variability. The associations with mean BP are stronger in women and weaker in those with type 2 diabetes.

Association of Cardiac Autonomic Responses with Clinical Outcomes of Myasthenia Gravis: Short-Term Analysis of the Heart-Rate and Blood Pressure Variability.

Introduction: The aim of the study was to assess cardiac and autonomic function in patients with myasthenia gravis (MG) and to explore its relationship with disease outcomes. Methods: Thirty-eight patients with an MG were enrolled (median age 40.5 years; median disease duration 5.5 years). Cardiovascular parameters, baroreflex sensitivity (BRS), spectral indices of short-term heart rate (HRV), and systolic blood pressure variability (SBPV) were compared with age- and gender-matched controls (n = 30). Cardiac autonomic function was assessed during the response to standing (tilt) and deep breathing tests (expiration/inspiration ratio-E/I). Results: HR and BP responses to the tilt test were similar in both groups. MG patients, as compared to controls, were characterized by altered SBPV at rest, significantly reduced HR response to the deep breathing test (p < 0.001), increased sympathovagal balance after tilt (delta LF/HF-RRI, p = 0.037), and lower values of BRS (p = 0.007) and hemodynamic parameters, i.e., cardiac index, index contractility, left ventricular work index, at rest and during tilt. There was no association between disease duration and autonomic parameters. Disease severity, as determined by MGFA (Myasthenia Gravis Foundation of America) corrected for age and sex, was an independent predictor of diminished vagal tone (E/I ratio) and increased sympathetic response to tilt (delta LF/HF-RRI) as measured with HRV. Lower BRS was associated with greater disease severity and older age. Hemodynamic parameters were predominantly predicted by age and sex. Conclusion: Our results confirm cardiac autonomic dysfunction among MG patients with predominant parasympathetic impairment. Clinicians should consider evaluation of autonomic balance in MG patients with, or at risk for, cardiovascular disease.

ACUTE POST-DYNAMIC, ISOMETRIC AND COMBINED RESISTANCE EXERCISE HYPOTENSION IN PATIENTS WITH HYPERTENSION: A RANDOMIZED STUDY

Objective: American guidelines included dynamic resistance exercise (DRE) and isometric handgrip (IH) in hypertension treatment. A single session of DRE decreases blood pressure (BP) during the recovery period, which has been described as post-exercise hypotension (PEH). However, the occurrence of PEH after a session of IH is controversial and the post-exercise effects of the association of DRE and IH, in a combined resistance exercise (CRE), has not been evaluated. Thus, this study investigated the effects of DRE, IH and CRE on post-exercise BP and its hemodynamic, autonomic and vascular mechanisms. Design and method: Seventy medicated hypertensive men (52 ± 8 years) were randomly allocated to perform 1 of 4 interventions: DRE (8 exercises, 3 sets, 50%1RM, repetitions until moderate fatigue), IH (4 sets, 2 min-unilateral contraction, 30% MVC), CRE (DRE + IH) and control (CO - seated resting). Office BP, systemic hemodynamics (CO2 rebreathing technique), cardiovascular autonomic modulation [spectral analysis of heart rate (HR) and BP variabilities] and brachial vascular parameters (ultrasound) were evaluated before and after the interventions. Thus, the responses to interventions (post – pre-intervention values) were calculated and compared among the groups by ANOVAs with significance level set at P &lt; 0.05. Results: Responses to IH were similar to CO, showing that a single session of IH did not promote PEH, and did not affect any of the BP mechanisms. On the other hand, DRE and CRE induced responses significantly different from IH and CO. DRE and CRE significantly decreased systolic BP, diastolic BP, mean BP, stroke volume and cardiac baroreflex sensitivity, while they significantly increased HR, brachial artery diameter, blood flow and vascular conductance during the post-exercise period. Additionally, DRE significantly decreased post-exercise cardiac vagal modulation (HFR-R, nu) and increased cardiac sympathovagal balance (LF/HF). Conclusions: DRE, but not IH, elicits PEH, which is accompanied by vasodilation and increased HR, via a higher sympathovagal balance and lower baroreflex sensitivity. The addition of IH to DRE, in a CRE, does not potentiate PEH and did not change its mechanisms.

Changes in autonomic nervous system during cerebral desaturation episodes in aneurysmal subarachnoid hemorrhage.

Little evidence is available on the effect of regional cerebral desaturation (rCD) episodes that occur in the first days after aneurysm subarachnoid haemorrhage (aSAH) on the autonomic nervous system activity and on cardiovascular hemodynamics. In this study, we aimed to determine the impact of rCD episodes, developed within 5days of aSAH, on the autonomic nervous system based on the assessment of baroreflex sensitivity (BRS) and on cardiac output (CO) and cardiac index (CI), and on cerebral autoregulation (CA). Of 96 patients with aSAH, 36 patients (aged 57 (48-69)) met the inclusion criteria and were included in the study. Regional cerebral oxygen saturation and rCD episodes were evaluated using near-infrared spectroscopy. CA was quantified by the correlation coefficient (TOxa). Cardiac output (CO) and cardiac index (CI) were monitored using the FloTrack®/EV1000. Baroreflex sensitivity (BRS) was assessed using the cross-correlation method. Scores of 1 to 3 in Glasgow Outcome Scale were classified as a poor outcome. During episodes of rCD, BRS decreased significantly compared to baseline (p=0.027) in patients who had a total duration of rCD episodes of more than 10hours. During rCD episodes, CA improved slightly in comparison to baseline (p=0.027). The threshold associated with poor outcome was: rSO2<62% (p=0.002). BRS decreased in patients who had a total duration rCD episodes of more than 10 hours within the 5 days of aSAH. These results might partly explain the relationship between lower BRS and worse prognosis.

High‐Fat Diet and Environmentally Relevant Secondhand Smoke Co‐exposure and Cardiovascular Regulation in Mice

BACKGROUNDOver the past few decades, cardiovascular disease incidence significantly decreased by 27%. Paradoxically, the number of deaths from cardiovascular diseases increased by 42% over the same period, owing to population growth and longevity. Consequently, cardiovascular diseases remain the leading cause of global death. Cardiovascular diseases are complex, multifactorial diseases that cannot be ascribed to a single factor. High‐fat diet (HFD) and secondhand smoke (SHS) are two preventable risk factors for the development of cardiovascular diseases. Studies have shown that SHS exposure is associated with poor dietary habits, suggesting the importance of potential confounding diet effects on health effects of SHS exposure. We previously showed that, in mice, environmentally relevant SHS exposure resulted in 10% decrease in baroreflex sensitivity (BRS) and 13% decrease in measures of heart rate variability (HRV). Here, we sought to characterize how HFD interplay with SHS in inducing cardiovascular dysfunction.METHODSMale C57BL/6J mice (11 wk) implanted with BP/ECG telemetry devices were fed with either normal diet (ND, 13.6 kcal% fat) or HFD (60 kcal% fat) and exposed to either filtered air (FA) or SHS (3 mg/m3, 6 hr/d, 5 d/wk) for 11 weeks. 36‐hr continuous BP/ECG recordings were performed. Data were divided into three 12‐hour periods: the first dark cycle (dark 1) immediately after the last day of exposure, and the following light and dark (dark 2) cycles. Spontaneous baroreflex sensitivity (BRS) was determined with the sequence method. Standard time domain heart rate variability (HRV) parameters were obtained from normal‐to‐normal R‐R intervals.RESULTSHFD‐fed mice had significantly greater weight gain than ND‐fed group (+15.3 g and +2.8 g over 11 weeks, HFD and ND, respectively). SHS exposure had no effect on body weight. Compared to ND mice, HFD mice had significantly higher BP (~6.5 mmHg), HR (~98 bpm), and lower BRS (~15% decrease) in the light cycle. Furthermore, HFD significantly reduced overall and short‐term HRV (36% and 47% reduction for SDNN and rMSSD, respectively, p &lt; 0.05) across all three light cycles. The reduction in HRV is unlikely due to a higher HR in HFD mice because normalizing the HRV measures to baseline R‐R intervals did not change the results. SHS exposure did not pose additional effects on these HFD‐induced changes. While HFD alone did not affect BP variability, co‐exposure of SHS and HFD significantly increased BP variability during the first dark cycle (16.8%, 15.6%, and 17.3% higher than HFD+FA group, for systolic, diastolic, and mean BP variability, respectively, p &lt; 0.05), suggesting a co‐exposure‐induced BP dysregulation.CONCLUSIONSThis study emphasizes the importance of accounting for differences in diet when studying the cardiovascular effects of SHS.

Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH.Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal.Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50–67). WFNS scale was 2 (1–4) and the modified Fisher scale was 3 (1–3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (Rp = −0.42; p < 0.001).Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

Dynamics of the baroreflex sensitivity during combined anesthesia with sevoflurane or propofol: a randomized trial

INTRODUCTION: A significant number of complications is still a serious problem in abdominal surgery. It is known that patients with low baroreflex sensitivity are more prone to hemodynamic instability during general anesthesia, which allows them to be identified as a risk group. OBJECTIVE: To evaluate the dynamics of baroreflex sensitivity (BRS) during major abdominal surgery in patients with different risk of critical incidents under combined anesthesia with propofol or sevoflurane. MATERIALS AND METHODS: A randomized study was conducted in 160 patients (80 high-risk and 80 low-risk patients), who were randomized into subgroups according to the type of anesthesia (propofol or sevoflurane) to assess the effect of the type of anesthesia critical incidents and baroreflex dynamics. RESULTS: After the induction there was a trend towards a decrease in BRS, while in subgroups with initially low values of BRS, it decreased below 3 ms/mmHg. After the end of operation and 6 hours after extubation, there were no significant changes in comparison with intraoperative values. Evaluation of BRS after 24 hours showed that BRS in all subgroups was significantly higher than at previous time points, but did not return to baseline values. At 6 hours postoperatively, in low-risk patients, BRS values were below 3 ms/mmHg in 12.5 % with propofol, and in 10 % with sevoflurane, in high-risk patients — in 45 % and 42.5 % of cases, respectively. At 24 hours, in the low-risk group, only two patients in the propofol anesthesia group and one in the sevoflurane anesthesia subgroup experienced this dysfunction. CONCLUSIONS: Both anesthesia with propofol and anesthesia with sevoflurane lead to a decrease in the sensitivity of the arterial baroreflex, which is not fully restored 24 hours after the end of the operation. High-risk patients with initially reduced baroreflex sensitivity show more frequent postoperative baroreflex dysfunction.

Is the Association Between Education and Sympathovagal Balance Mediated by Chronic Stressors?

BackgroundThis study investigated whether raised chronic stress in low education groups contributes to education differences in cardiovascular disease by altering sympathovagal balance.MethodsThis study included cross-sectional data of 10,202 participants from the multi-ethnic, population-based HELIUS-study. Sympathovagal balance was measured by baroreflex sensitivity (BRS), the standard deviation of the inter-beat interval (SDNN) and the root mean square of successive differences between normal heartbeats (RMSSD). The associations between chronic stressors (work, home, psychiatric, financial, negative life events, lack of job control and perceived discrimination) in a variety of domains and BRS, SDNN and RMSSD were assessed using linear regression, adjusted for age, ethnicity, waist-to-hip ratio and pack-years smoked. Mediation analysis was used to assess the contribution of chronic stress to the association between education and sympathovagal balance.ResultsModest but significant associations were observed between financial stress and BRS and SDNN in women, but not in RMSSD nor for any outcome measure in men. Women with the highest category of financial stress had 0.55% lower BRS (ms/mmHg; β = -0.055; CI = -0.098, -0.011) and 0.61% lower SDNN (ms; β = -0.061; CI = -0.099, -0.024) than those in the lowest category. Financial stress in women contributed 7.1% to the association between education and BRS, and 13.8% to the association between education and SDNN.ConclusionNo evidence was found for the hypothesized pathway in which sympathovagal balance is altered by chronic stress, except for a small contribution of financial stress in women.

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

Low baroreflex sensitivity (BRS) was an established risk factor for cardiovascular disorders. We investigated determinants of BRS in a large sample from general population. In a population-based study (n = 901), data were collected on BRS, arm cuff blood pressure (BP), and obesity indices including body mass index, waist-to-hip ratio, 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 10-15 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). In multivariable analysis, age, sex, %BF, and hypertension were independently associated with BRS. BRS decreased with -0.10 (95% confidence interval: -0.15 to -0.06) ms/mm Hg with each year of increase in age. Women had -1.55 (95% confidence interval: -2.28 to -0.73) ms/mm Hg lower mean BRS than men. The effects of %BF (per 10% increase) and hypertension on BRS were -0.55 (95% confidence interval: -0.97 to -0.13) ms/mm Hg and -1.23 (95% confidence interval: -1.92 to -0.46) ms/mm Hg, respectively. There was no evidence of associations between BRS and lifestyle factors. Age, age2, sex, and their interactions plus %BF and hypertension contributed 16.9% of total variance of BRS. In this large general population study, we confirmed prior findings that age and sex were important factors associated with BRS and found %BF was more strongly related to less favorable BRS levels than body mass index.

Exaggerated Exercise Blood Pressure as a Marker of Baroreflex Dysfunction in Normotensive Metabolic Syndrome Patients

IntroductionExaggerated blood pressure response to exercise (EEBP = SBP ≥ 190 mmHg for women and ≥210 mmHg for men) during cardiopulmonary exercise test (CPET) is a predictor of cardiovascular risk. Sympathetic hyperactivation and decreased baroreflex sensitivity (BRS) seem to be involved in the progression of metabolic syndrome (MetS) to cardiovascular disease.ObjectiveTo test the hypotheses: (1) MetS patients within normal clinical blood pressure (BP) may present EEBP response to maximal exercise and (2) increased muscle sympathetic nerve activity (MSNA) and reduced BRS are associated with this impairment.MethodsWe selected MetS (ATP III) patients with normal BP (MetS_NT, n = 27, 59.3% males, 46.1 ± 7.2 years) and a control group without MetS (C, n = 19, 48.4 ± 7.4 years). We evaluated BRS for increases (BRS+) and decreases (BRS−) in spontaneous BP and HR fluctuations, MSNA (microneurography), BP from ambulatory blood pressure monitoring (ABPM), and auscultatory BP during CPET.ResultsNormotensive MetS (MetS_NT) had higher body mass index and impairment in all MetS risk factors when compared to the C group. MetS_NT had higher peak systolic BP (SBP) (195 ± 17 vs. 177 ± 24 mmHg, P = 0.007) and diastolic BP (91 ± 11 vs. 79 ± 10 mmHg, P = 0.001) during CPET than C. Additionally, we found that MetS patients with normal BP had lower spontaneous BRS− (9.6 ± 3.3 vs. 12.2 ± 4.9 ms/mmHg, P = 0.044) and higher levels of MSNA (29 ± 6 vs. 18 ± 4 bursts/min, P < 0.001) compared to C. Interestingly, 10 out of 27 MetS_NT (37%) showed EEBP (MetS_NT+), whereas 2 out of 19 C (10.5%) presented (P = 0.044). The subgroup of MetS_NT with EEBP (MetS_NT+, n = 10) had similar MSNA (P = 0.437), but lower BRS+ (P = 0.039) and BRS− (P = 0.039) compared with the subgroup without EEBP (MetS_NT−, n = 17). Either office BP or BP from ABPM was similar between subgroups MetS_NT+ and MetS_NT−, regardless of EEBP response. In the MetS_NT+ subgroup, there was an association of peak SBP with BRS− (R = −0.70; P = 0.02), triglycerides with peak SBP during CPET (R = 0.66; P = 0.039), and of triglycerides with BRS− (R = 0.71; P = 0.022).ConclusionNormotensive MetS patients already presented higher peak systolic and diastolic BP during maximal exercise, in addition to sympathetic hyperactivation and decreased baroreflex sensitivity. The EEBP in MetS_NT with apparent well-controlled BP may indicate a potential depressed neural baroreflex function, predisposing these patients to increased cardiovascular risk.

Hypoglycemia Impairs Baroreflex Sensitivity: Implications for Autonomic Control of Cardiovascular Function in Diabetes

Background: Iatrogenic hypoglycemia is an unintended, though common, occurrence in individuals with diabetes. There is a clear association between hypoglycemia exposure and an increase in mortality in individuals with type 2 diabetes (T2DM). It is well-established that recurrent hypoglycemic episodes impair the counterregulatory hormone responses; however, it is yet to be determined if in T2DM there are more global effects of hypoglycemia on autonomic control of cardiovascular function (baroreflex sensitivity, BRS), as has been shown in healthy individuals. This is a clinically relevant knowledge gap as decreases in BRS are pro-arrhythmogenic and associated with decreases in mortality in individuals with diabetes. Objective: We tested the hypothesis that in individuals with T2DM, hypoglycemia impairs baroreflex sensitivity (BRS), a robust measure of cardiovascular autonomic control. Methods: Individuals with well-controlled T2DM and without known cardiovascular disease were exposed to two 90-minute episodes of experimental hypoglycemia (50 mg/dl) in the same day. All individuals experienced a hypoglycemic-hyperinsulinemic clamp in the morning (AM clamp) and again in the afternoon (PM clamp). BRS was assessed using the modified Oxford method (sequential administration of nitroprusside and phenylephrine) before the initiation of each hypoglycemic-hyperinsulinemic clamp, during the last 30 minutes of hypoglycemia, and the following day. Results: The study included 16 individuals with a diagnosis of T2DM (6 men and 10 women) with the following characteristics (mean ± SD): age 45 ± 11 years, BMI 32 ± 6 kg/m2, hemoglobin A1c 6.4 ± 0.9%, and diabetes duration 8 ± 5 years. At baseline, individuals with T2DM had a BRS of 7.7 ± 3.6 ms/mmHg, which is reduced compared to a BRS of 21.3 ± 13.8 ms/mmHg in a historical healthy control group of 54 subjects (p<0.001). A mixed effects model adjusting for sex, age, BMI, and insulin level, demonstrated a significant effect of hypoglycemia on BRS (p=0.008). Pairwise comparisons revealed a significant decrease in BRS during the PM clamp as compared with BRS assessed at baseline (5.5 ± 5.0 vs 7.7 ± 3.6 ms/mmHg, p=0.045), during the AM clamp (5.5 ± 5.0 vs 10.5 ± 5.6 ms/mmHg, p=0.43), and the following day (5.5 ± 5.0 vs 8.6 ± 3.8 ms/mmHg, p=0.33). Of note, there was no significant difference between BRS at baseline and during the AM clamp (p=0.44). Additionally, insulin levels positively and strongly correlated with BRS at baseline (R2 0.52) and during the AM clamp (R2 0.67). Discussion: Insulin may have a stimulatory effect on BRS during a hyperinsulinemic hypoglycemic clamp that counters the inhibitory effect of hypoglycemia during the first episode of hypoglycemia. However, with exposure to a second hypoglycemic clamp, BRS decreases. Conclusion: Individuals with T2DM have low BRS at baseline, which is further reduced after 2 episodes of hypoglycemia.

Negative association between lipoprotein associated phospholipase A2 activity and baroreflex sensitivity in subjects with high normal blood pressure and a positive family history of hypertension.

The relationship between baroreflex sensitivity (BRS) and inflammatory vascular biomarker Lipoprotein associated phospholipase A2 (Lp-PLA2) in subjects with high normal blood pressure (HNBP, prehypertensives) with a positive family history of hypertension (FHH+) and hypertension history free control subjects (FHH-) was evaluated. A total of 24 HNBP participants (age 39.5 ± 2.5 years, 18 male/ 6 female) were studied. 14 HNBP subjects FHH+ were compared to 10 HNBP participants FHH-, being of similar age and body mass index. BRS (ms/mmHg) was determined by the sequence and spectral methods (five-minute non-invasive beat-to-beat recording of blood pressure and RR interval, controlled breathing at a frequency of 0.33 Hz). Venous blood was analyzed for Lp-PLA2 biomarker of vascular inflammation and atherothrombotic activity. A significant negative correlation between spontaneous BRS obtained by both methods and systolic blood pressure (BP) was present (BRS spect r = -0.54, P<0.001, BRS seq r = -0.59, P<0.001). BRS obtained by sequence and spectral methods were reduced in HNBP FHH+ compared to the group of HNBP FHH- (P = 0.0317 BRS seq, P = 0.0395 BRS spect). Lp-PLA2 was significantly higher in HNBP FHH+ compared to FHH- controls (P<0.05). Lp-PLA2 was negatively correlated with BRS obtained by sequence method (r = -0.798, R2 = 0.636, P<0.001) in the HNBP FHH+ subjects. These findings demonstrate that reduced baroreflex sensitivity, as a marker of autonomic dysfunction, is associated with vascular inflammation, predominantly in otherwise healthy participants with a positive family history of hypertension who could predispose to increased risk of hypertension. We conclude that our transversal study suggests that a lowbaroreflex sensitivity could be an early sign of autonomic dysfunction even in the prehypertensive period, and to corroborate these findings, a longitudinal study is needed.

Peat smoke inhalation alters blood pressure, baroreflex sensitivity, and cardiac arrhythmia risk in rats

ABSTRACT Wildland fires (WF) are linked to adverse health impacts related to poor air quality. The cardiovascular impacts of emissions from specific biomass sources are however unknown. The purpose of this study was to assess the cardiovascular impacts of a single exposure to peat smoke, a key regional WF air pollution source, and relate these to baroreceptor sensitivity and inflammation. Three-month-old male Wistar-Kyoto rats, implanted with radiotelemeters for continuous monitoring of heart rate (HR), blood pressure (BP), and spontaneous baroreflex sensitivity (BRS), were exposed once, for 1-hr, to filtered air or low (0.38 mg/m3 PM) or high (4.04 mg/m3) concentrations of peat smoke. Systemic markers of inflammation and sensitivity to aconitine-induced cardiac arrhythmias, a measure of latent myocardial vulnerability, were assessed in separate cohorts of rats 24 hr after exposure. PM size (low peat = 0.4–0.5 microns vs. high peat = 0.8–1.2 microns) and proportion of organic carbon (low peat = 77% vs. high peat = 65%) varied with exposure level. Exposure to high peat and to a lesser extent low peat increased systolic and diastolic BP relative to filtered air. In contrast, only exposure to low peat elevated BRS and aconitine-induced arrhythmogenesis relative to filtered air and increased circulating levels of low-density lipoprotein cholesterol, complement components C3 and C4, angiotensin-converting enzyme (ACE), and white blood cells. Taken together, exposure to peat smoke produced overt and latent cardiovascular consequences that were likely influenced by physicochemical characteristics of the smoke and associated adaptive homeostatic mechanisms.

0461 Blunted Baroreflex Sensitivity and Reduced Morning Parasympathetic Activity in Sleep-Onset Insomnia

Abstract Introduction Insomnia is a risk factor for hypertension and cardiovascular events, and this association is strongest for sleep-onset insomnia. However, little is known about insomnia on cardiovascular modulation, especially soon after morning awakening, the peak period of time for cardiovascular incidents. This study explored morning cardiovascular function in individuals with sleep-onset insomnia by analysing heart rate variability, blood pressure variability, and baroreflex sensitivity. Methods Sleep structure of the participants (15 good sleepers and 13 individuals with sleep-onset insomnia) was measured by laboratory polysomnography, followed by continuous recordings of the participant’s blood pressure and heart rate for 10 min in the morning. Results When compared to the good sleepers, the insomnia group showed significant reductions in total sleep time, a longer sleep-onset latency, and reduced sleep efficiency. The sleep structure, including durations of sleep stages, numbers of awakenings and arousal index did not differ between the groups. After morning awakening (averaged time: 12.33 ± 10.48 min), the shorter R-R intervals, lower total power, and lower high-frequency power of heart rate variability were observed among individuals with sleep-onset insomnia, compared with good sleepers. Elevated slopes of systolic and diastolic blood pressure, as well as lower baroreflex sensitivity, were also shown in the insomnia group. Indices of sympathetic activity, including low-frequency percentage of heart rate variability or low-frequency power of blood pressure variability, did not differ between the groups. Conclusion Weak vagal activity and blunted baroreflex sensitivity were evident among sleep-onset insomnia. These findings indicate difficulty in initiating sleep, without significant sleep fragmentation, can independently affect morning cardiovascular function. This study provides a possible link between sleep-onset insomnia and risk of cardiovascular events. Support N/A

Transient Orthostatic Hypertension During Head-Up Tilt Test in Young Adults: A Phenotype of Blood Pressure Variability.

The mechanisms underlying orthostatic hypertension (OHT) remain poorly understood. The authors evaluated the cardiovascular, cerebrovascular dynamics, and autonomic response to head-up tilt test (HUTT) in young adults with symptoms of orthostatic intolerance and transient OHT. Forty-four female subjects were included (34 ± 13 years old) and categorized in three groups after a 30-minute 70° passive HUTT: symptomatic patients with OHT (surge of systolic blood pressure ≥20 mm Hg for at least 5 minutes at any given time during HUTT), orthostatic intolerance (symptomatic patients without orthostatic blood pressure changes), and healthy asymptomatic control subjects. At baseline, OHT patients had lower systolic blood pressure than orthostatic intolerance patients (103 ± 8 vs. 116 ± 10 mm Hg, p < 0.01) and lower baroreflex sensitivity than control subjects (15.8 ± 8.3 vs. 27.1 ± 11.7 ms/mm Hg, p = 0.01). On tilt, cardiac output decreased in OHT patients from 6.1 ± 1.4 L/minute during baseline to 5.2 ± 0.8 L/minute after 10 minutes of HUTT (p = 0.01). In OHT patients at 30 minutes of HUTT, sympathetic efferent heart activity was higher (77.4 ± 14.9 normalized units or nu) than orthostatic intolerant patients (63.5 ± 11.8 nu, p = 0.02) and control subjects (65.8 ± 11.2 nu, p = 0.05). Cerebrovascular resistance in OHT was higher than control subjects after 30 minutes (2.2 ± 0.8 vs. 1.6 ± 0.3 cm/second, respectively, p = 0.02). This study demonstrates that transient OHT can occur at any given time during HUTT. These patients exhibit a decrease in cardiac output and a hyperadrenergic response to tilt.