Linear and non-linear analysis of heart rate variability in HIV-positive patients on two different antiretroviral therapy regimens

Background Cardiac autonomic dysfunction in HIV+ patients on different antiretroviral therapy (ART) regimens has been described. We aimed to characterize parameters of heart rate variability (HRV) and correlate with different classes of ART in HIV+ patients in three experimental conditions: rest, cold face, and tilt tests. Methods Cross-sectional study with three groups of age- and gender-matched individuals: group 1, 44 HIV+ patients undergoing combination therapy, with two nucleoside reverse transcriptase inhibitors (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI); group 2, 42 HIV+ patients using two NRTI and protease inhibitors (PI’s); and group 3, 35 healthy volunteers with negative HIV serology (control group). Autonomic function at rest and during cold face- and tilt-tests was assessed through computerized analysis of HRV, via quantification of time- and frequency domains by linear and non-linear parameters in the three groups. Results Anthropometric and clinical parameters were similar between both HIV groups, except CD4+ T lymphocytes, which were significantly lower in group 2 (p = 0.039). At baseline, time-domain linear HRV parameters, RMSSD and pNN50, and the correlation dimension, a non-linear HRV parameter (p < 0.001; p = 0.018; p = 0.019, respectively), as well as response of RMSSD to cold face test were also lower in the HIV+ group than in the control individuals (p < 0.001), while no differences among groups were detected in HRV parameters during the tilt test. Conclusions Despite ART regimens, HIV+ patients presented lower cardiac vagal modulation than controls, whereas no difference was observed among the HIV groups, suggesting that higher cardiovascular risk linked to PIs may be associated with factors other than autonomic dysfunction.

Altered Cardiovascular Reactivity to and Recovery from Cold Face Test-Induced Parasympathetic Stimulation in Essential Hypertension

Essential hypertension is associated with increased sympathetic and diminished parasympathetic activity as well as impaired reactivity to sympathetic stimulation. However, reactivity and recovery from parasympathetic stimulation in hypertension are unknown. We investigated reactivity and recovery to primarily parasympathetic stimulation by Cold Face Test (CFT) in essential hypertension. Moreover, we tested whether chronic stress modulates CFT-reactivity dependent on hypertension status. The CFT was conducted by applying a cold face-mask for 2 min in 24 unmedicated, otherwise healthy hypertensive men and in 24 normotensive controls. Systolic and diastolic blood pressure (BP) and heart rate (HR) were measured repeatedly. Chronic stress was assessed with the Trier-Inventory-for-Chronic-Stress-Screening-Scale. Hypertensives did not exhibit diastolic BP decreases after CFT-cessation (p = 0.59) as did normotensives (p = 0.002) and failed to show HR decreases in immediate response to CFT (p = 0.62) when compared to normotensives (p < 0.001). Systolic BP reactivity and recovery patterns did not differ between hypertensives and normotensives (p = 0.44). Chronic stress moderated HR (p = 0.045) but not BP CFT-reactivity (p′s > 0.64) with chronically stressed normotensives showing similar HR reactivity as hypertensives. Our findings indicate impaired diastolic BP and HR reactivity to and recovery from CFT in hypertensives and a moderating effect of chronic stress on HR reactivity potentially reflecting reduced relaxation ability of the cardiovascular system.

A call to reevaluate cardiac autonomic assessment after spinal cord injury

This “Perspectives” article puts forward the notion that measuring heart rate variability, or other forms of cardiac autonomic regulation, after spinal cord injury must be performed during a test of autonomic stress. Resting values of heart rate variability are often similar to those obtained from able-bodied individuals, which may therefore be falsely interpreted as normal or healthy autonomic regulation. However, evidence shows that despite normal resting values, cardiac autonomic control is impaired when individual with spinal cord injury are subjected to a cold face test, head-up tilt, or recovery from exercise. Accordingly, examination of cardiac autonomic function must be performed during an autonomic challenge, as resting measures do not accurately reflect the state of cardiovascular regulation after spinal cord injury and can provide false information.

Cardiovascular Effects of Stress During Acutely Increased Free Fatty Acids in a Randomized, Double-Blind, Cross-Over Study in Humans

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.

Cold Face Test-Induced Increases in Heart Rate Variability Are Abolished by Engagement in a Social Cognition Task

The vagus nerve is a major constituent in the bidirectional relationship between the heart and the prefrontal cortex. This study investigated the role of the vagus in social cognition using the cold face test (facial cooling) to stimulate the vagus nerve and increase prefrontal inhibitory control. Heart Rate Variability (HRV) was measured to index parasympathetic outflow while social cognition ability was tested using the Reading the Mind in the Eyes Test (RMET). Healthy males (n = 25) completed the RMET under two conditions: with and without facial cooling. Results indicated that although facial cooling increased HRV at rest, there was no improvement in the RMET during the facial cooling condition. Interestingly, completing the RMET with facial cooling abolished this increase in HRV, suggesting interference along the vagal reflex arc. These results are consistent with the involvement of a common cortico-subcortical circuit in autonomic and cognitive processes, important for emotion recognition.