Acute Heart Rate Responses Research Articles

Association of CETP gene polymorphisms and haplotypes with acute heart rate response to exercise

Abstract Background Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile, and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular fitness. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Methods Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892 and rs9989419) and their haplotypes (H) known to be associated with cardiovascular risk in the CETP gene with AHRR in 607 individuals from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-minute step test and was measured as the difference between resting and post-exercise heart rate, i.e. delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels were applied in the statistical analyses. Results Among the five SNPs examined, two showed a significant association with lower ΔHR (rs1532624-Cdom: B = -8.15, p < 0.001; rs708272-Gdom: B = -8.09, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-A: OR = 2.26, p < 0.001; rs708272-A: OR = 2.17, p < 0.001). Among the ten haplotypes, two showed significant association with lower ΔHR (H3 - CAGCA: B = -6.79, p = 0.003; H9 - CGGCG: B = -14.79, p = 0.014) and lower risk of adverse AHRR (H3 - CAGCA: OR = 0.58, p = 0.038; H9 - CGGCG: OR = 0.05, p = 0.008) compared to the reference haplotype (H1 - AGACG). Conclusions Our study is the first to report a significant association between polymorphisms and their haplotypes in the CETP gene and AHRR. It also confirms that the effect of the CETP gene on cardiovascular risk is expressed through the acute heart rate response to physical activity, in addition to its effect on the lipid profile. Key messages • Certain polymorphisms and haplotypes in the CETP gene show a significant association with AHRR. • The CETP gene polymorphisms exert their effect on cardiovascular risk not only by altering the lipid profile, but also by modifying the heart rate response to physical activity.

Genetic background of the acute heart rate response to physical activity

Genetic background of the acute heart rate response to physical activity

Association of CETP Gene Polymorphisms and Haplotypes with Acute Heart Rate Response to Exercise.

Polymorphisms in the cholesteryl ester transfer protein (CETP) gene are known to be strongly associated with increased cardiovascular risk, primarily through their effects on the lipid profile and consequently on atherosclerotic risk. The acute heart rate response (AHRR) to physical activity is closely related to individual cardiovascular health. This study aimed to investigate the effect of CETP gene polymorphisms on AHRR. Our analysis examines the association of five single nucleotide polymorphisms (SNPs; rs1532624, rs5882, rs708272, rs7499892, and rs9989419) and their haplotypes (H) in the CETP gene with AHRR in 607 people from the Hungarian population. Individual AHRR in the present study was assessed using the YMCA 3-min step test and was estimated as the difference between resting and post-exercise heart rate, i.e., delta heart rate (ΔHR). To exclude the direct confounding effect of the CETP gene on the lipid profile, adjustments for TG and HDL-C levels, next to conventional risk factors, were applied in the statistical analyses. Among the examined five SNPs, two showed a significant association with lower ΔHR (rs1532624-Cdominant: B = -8.41, p < 0.001; rs708272-Gdominant: B = -8.33, p < 0.001) and reduced the risk of adverse AHRR (rs1532624-Cdominant: OR = 0.44, p = 0.004; rs708272-Gdominant: OR = 0.43, p = 0.003). Among the ten haplotypes, two showed significant association with lower ΔHR (H3-CAGCA: B = -6.81, p = 0.003; H9-CGGCG: B = -14.64, p = 0.015) and lower risk of adverse AHRR (H3-CAGCA: OR = 0.58, p = 0.040; H9-CGGCG: OR = 0.05, p = 0.009) compared to the reference haplotype (H1-AGACG). Our study is the first to report a significant association between CETP gene polymorphisms and AHRR. It also confirms that the association of the CETP gene with cardiovascular risk is mediated by changes in heart rate in response to physical activity, in addition to its effect on lipid profile.

Genetic Background of Acute Heart Rate Response to Exercise.

The acute heart rate response (AHRR) to physical activity, which refers to the change in heart rate during and after exercise, has been associated with cardiovascular and all-cause mortality. Previous studies have shown that AHRR is significantly determined by genetics in addition to environmental and lifestyle factors. The aim of this study was to investigate the genetic background of AHRR by analysing ten single nucleotide polymorphisms (SNPs) associated with leisure-time physical activity (LTPA) in 620 samples from the Hungarian population. The AHRR can be characterised as the difference between post-exercise and resting heart rate, i.e., the delta heart rate (ΔHR) defined by the YMCA 3 min step test, with a lower value indicating better cardiovascular fitness. The association of SNPs with ΔHR was analysed both separately and in combination using an optimised polygenic score (oPGS). The results showed that five SNPs (rs10252228, rs459465, rs6022999, rs8097348, and rs12405556) had at least nominally significant (p < 0.05) individual associations with ΔHR. After optimizing the PGS, a cumulative effect was observed for eight SNPs (rs6022999, rs12405556, rs459465, rs10252228, rs8097348, rs10887741, rs12612420, and rs7023003) that had a strong and statistically significant association with ΔHR (B = -2.51, 95% CI: -3.46--1.76; p = 2.99 × 10-9). Of the four main domains of physical activity, the oPGS showed a significant positive association only with LTPA (B = 84.60; 95%CI: 25.23-143.98; p = 0.005). In conclusion, our results suggest that the SNPs we investigated influence individual leisure-time physical activity, mediated by their effects on the acute heart rate response.

Modeling Patient-specific Apnea-bradycardia Patterns in Preterm Newborn.

Preterm infants are particularly exposed to severe cardio-respiratory events, associating apnea with bradycardia and oxygen desaturation. A patient-specific and event-specific model-based approach is proposed in this work to analyze the acute heart rate response to apnea-bradycardia events in preterm newborn. A novel model integrating the main cardio-respiratory interactions which are specific to the neonatal period is proposed. An evolutionary algorithm is applied to estimate patient-specific model parameters from a database of 37 apnea-bradycardia episodes acquired from 10 preterm newborns. Unsupervised clustering (K-means) was applied to the identified parameters to define phenogroups of cardio-respiratory responses to apnea. A significant correspondence was observed between simulated and experimental heart rate series in all identifications (median RMSE = 8.85 bpm). Three clusters of parameters were found and were associated to three different pathophysiological dynamics related to apnea-bradycardia. The proposed method, based on patient and event-specific model parameter identification, provides a novel approach to characterize bradycardia dynamics in response to apnea, opening the way to the proposal of new personalized diagnosis and treatment possibilities in this particularly sensitive population.

Acute Response of Heart Rate of Pregnant Women to Aerobic Dance Exercise

This was a Pre-test/Post-test research designed to study the acute heart rate response of pregnant women to aerobic dance exercise. Twenty four (24) pregnant women with no complications participated in this study. HR increased significantly after 30 minutes exercise [7.292, P = 0.004 (P 0.05)]. Moderate intensity Aerobic Dance Exercise may not precipitate adverse acute cardiorespiratory response in pregnant women with no complications.

Acute Heart Rate Responses to Resistance Exercise at Different Cadences

Acute Heart Rate Responses to Resistance Exercise at Different Cadences

Biochemical, demographic, and self-reported tobacco-related predictors of the acute heart rate response to nicotine in smokers

Understanding the stimulatory effects of nicotine on cardiovascular function in humans is of great interest given the wide-spread use of different forms of combustible and smokeless products that deliver nicotine. An intravenous nicotine infusion procedure was used to evaluate factors associated with the acute heart rate (HR) response to nicotine (0.5 mg per 70 kg bodyweight) in a sample of 213 smokers. We tested for differential response to nicotine based on demographic characteristics (race [European American vs African America], sex, body mass index and age); a set of blood-based biomarkers (baseline nicotine, cotinine and cortisol levels and nicotine metabolite ratio); and a set of self-reported measures related to tobacco use. Nicotine infusion was first noted to increase HR approximately 10 beats per minute (95% CI: 7.8–12.3) one minute post-infusion, and 13 beats per minute (95% CI: 11.0–15.2) two minutes post-infusion. Higher cortisol, lower nicotine levels, higher nicotine metabolite ratio, being female and greater withdrawal symptoms were independently associated with a potentiated increase in HR 1 or 2 min after nicotine infusion. Factors associated with the acute HR effects of nicotine warrant further investigation given their potential to inform the development of nicotine delivery systems as tobacco harm reduction approaches for smokers.

Chronic stress and the introduction to captivity: How wild house sparrows (Passer domesticus) adjust to laboratory conditions

The conditions of captivity can cause chronic stress in wild animals. Newly-captured animals may experience weight loss, elevated glucocorticoid hormones, increased heart rate, increased resting adrenomedullary activation, and an altered heart rate response to acute stressors. As captivity conditions persist, chronic stress may decrease as animals adjust to the stressors of captivity. In this study, house sparrows (Passer domesticus) were captured from the wild, fitted with heart rate transmitters in a minor surgical process, and individually housed in an indoor bird facility. Mass, baseline corticosterone, resting heart rate, resting adrenomedullary activation, and the acute heart rate response to a sudden noise were measured over the course of the first 6 weeks of captivity. Birds lost weight during the first weeks of captivity, which was regained by week 5. Baseline corticosterone peaked at day 7, decreased sharply by day 11, and continued to decrease throughout the 6 weeks. Although heart rate in the first 24 h could not be collected, daytime heart rate decreased from day 1 through day 20, where it reached a stable plateau. Daytime heart rate variability decreased through the entire 6 weeks, which may indicate a gradual shift from sympathetic to parasympathetic nervous system regulation of heart rate. The acute heart rate response to a sudden noise lasted longer at day 6 than earlier or later in captivity. In conclusion, the data indicate that the different physiological systems associated with chronic stress adjust to captivity over different timelines.

Long-term vagal stimulation for heart failure: Eighteen month results from the NEural Cardiac TherApy foR Heart Failure (NECTAR-HF) trial

BackgroundThe NECTAR-HF study evaluated safety and feasibility of vagal nerve stimulation (VNS) for the treatment of heart failure patients. The first six-month randomized phase of the study did not show improvement in left ventricular remodelling in response to VNS. This study reports the 18-month results and provides novel findings aiming to understand the lack of efficacy of VNS, including a new technique assessing the effects of VNS. MethodsNinety-six patients were randomized 2:1 to active or inactive VNS for 6months, thereafter VNS was activated for all patients. The primary safety endpoint was 18-month all-cause mortality. ResultsNinety-one patients continued in the long-term evaluation with active VNS. The on-therapy survival estimate at 18months was 95% with a 95% one-sided lower confidence limit of 91%, (better than the predefined criterion).Left ventricular systolic volume decreased in the crossover group (VNS OFF→ON; 144±37 to 139±40, p<0.05) after VNS activation; LVESD (5.02±0.77 to 4.96±0.82, p>0.05) and LVEF (33.2±4.9 to 33.3±6.5, p>0.05) did not change.A new technique to detect subtle heart rate changes during Holter recordings, i.e. “heat maps”, revealed that VNS evoked heart rate response in only 13/106 studies (12%) at 6 and 12months with active VNS. ConclusionsAlthough a favourable long-term safety profile was found, improvements in the efficacy endpoints were not seen with VNS. A new technique for detecting acute heart rate responses to VNS suggests that the recruitment of nerve fibres responsible for heart rate changes were substantially lower in NECTAR-HF than in pre-clinical models.

Vagal Nerve Stimulation Evoked Heart Rate Changes and Protection from Cardiac Remodeling.

This study investigated whether vagal nerve stimulation (VNS) leads to improvements in ischemic heart failure via heart rate modulation. At 7 ± 1 days post left anterior descending artery (LAD) ligation, 63 rats with myocardial infarctions (MI) were implanted with ECG transmitters and VNS devices (MI + VNS, N = 44) or just ECG transmitters (MI, N = 17). VNS stimulation was active from 14 ± 1 days to 8 ± 1 weeks post MI. The average left ventricular (LV) end diastolic volumes at 8 ± 1 weeks were MI = 672.40 μl and MI + VNS = 519.35 μl, p = 0.03. The average heart weights, normalized to body weight (± std) at 14 ± 1 weeks were MI = 3.2 ± 0.6 g*kg(-1) and MI + VNS = 2.9 ± 0.3 g*kg(-1), p = 0.03. The degree of cardiac remodeling was correlated with the magnitude of acute VNS-evoked heart rate (HR) changes. Further research is required to determine if the acute heart rate response to VNS activation is useful as a heart failure biomarker or as a tool for VNS therapy characterization.

Pushing the limits: exercise stress in the healthy human heart.

Pushing the limits: exercise stress in the healthy human heart.

Immunohistochemical Evidence of a Melanopsin Cone in Human Retina

Melanopsin, expressed in a subset of intrinsically photosensitive ganglion cells that project to the suprachiasmatic nucleus (SCN), is involved in the photic entrainment of circadian rhythms and other non-image-forming functions (pupil light reflex, masking, acute heart rate response, and alertness). Melanopsin has recently been shown to be a "bireactive" photopigment that functions as a photosensory opsin using 11-cis retinaldehyde as a chromophore and has intrinsic photoisomerase activity. Melanopsin is widely distributed in the retina of vertebrates and, depending on the species, is expressed in ganglion, amacrine, horizontal, and photoreceptor cells. The present study was conducted to determine the distribution of this opsin in the human retina. Human donor eyes were obtained from donors and fixed shortly after death. Immunohistochemistry was used to determine melanopsin expression in the retinas of three donors. The possible coexpression of this photopigment with other opsins was studied by double-labeling immunocytochemistry and confocal analysis. In addition to the expected labeling in ganglion cells of the inner retinal layers, an unexpected finding showed melanopsin-immunopositive label in the outer segments of cones that did not coexpress other known opsins. These melanopsin-expressing cones are extremely sparse (5-25 cones/mm2; 0.1%-0.5% of the entire cone population) and are located in the peripheral retina. The presence of melanopsin in human cones suggests image and non-image-forming roles in visual responses at both the cone input and ganglion cell output stages and their involvement in a broad spectrum of irradiance detection functions in the visual system.

A Technique for Dorsal Subcutaneous Implantation of Heart Rate Biotelemetry Transmitters in Black Ducks: Application in an Aircraft Noise Response Study

A technique for heart rate biotelemetry transmitter implantation was developed to monitor heart rate fluctuations of Black Ducks (Anas rubripes) in response to simulated aircraft noise in a large outdoor enclosure. A dorsal subcutaneous approach, with subcutaneous tunneling of lead wires, was employed for placement of the 32 g transmitters. A base-apex lead configuration, with leads anchored at the dorsal cervico-thoracic junction and the caudal keel, yielded the maximal ECG wave-form deflection for triggering the transmitter. Heart rates of six Black Ducks (three in each of two separate trials) were monitored for 3 days pre-noise to establish a baseline, and then for 4 days of simulated aircraft noise. The noise stimulus replicated an FB-111 military jet, and was played 48 times per day at a peak volume of 110 dB. Daily mean heart rates, used as indicators of metabolic rates, did not increase in response to noise. Recognizable acute heart rate increases corresponding with a noise event occurred with increased frequency during the first day of noise presentation, but on subsequent days the responses did not differ significantly from baseline. Acute heart rate responses to aircraft noise diminished rapidly, indicating the ability of Black Ducks to habituate to the auditory component of low altitude aircraft overflights.