Effect of Smoking on Blood Pressure and Resting Heart Rate: A Mendelian Randomization Meta-Analysis in the CARTA Consortium.

BACKGROUND: Smoking is an important cardiovascular disease risk factor, but the mechanisms linking smoking to blood pressure are poorly understood. METHODS AND RESULTS: Data on 141 317 participants (62 666 never, 40 669 former, 37 982 current smokers) from 23 population-based studies were included in observational and Mendelian randomization meta-analyses of the associations of smoking status and smoking heaviness with systolic and diastolic blood pressure, hypertension, and resting heart rate. For the Mendelian randomization analyses, a genetic variant rs16969968/rs1051730 was used as a proxy for smoking heaviness in current smokers. In observational analyses, current as compared with never smoking was associated with lower systolic blood pressure and diastolic blood pressure and lower hypertension risk, but with higher resting heart rate. In observational analyses among current smokers, 1 cigarette/day higher level of smoking heaviness was associated with higher (0.21 bpm; 95% confidence interval 0.19; 0.24) resting heart rate and slightly higher diastolic blood pressure (0.05 mm Hg; 95% confidence interval 0.02; 0.08) and systolic blood pressure (0.08 mm Hg; 95% confidence interval 0.03; 0.13). However, in Mendelian randomization analyses among current smokers, although each smoking increasing allele of rs16969968/rs1051730 was associated with higher resting heart rate (0.36 bpm/allele; 95% confidence interval 0.18; 0.54), there was no strong association with diastolic blood pressure, systolic blood pressure, or hypertension. This would suggest a 7 bpm higher heart rate in those who smoke 20 cigarettes/day. CONCLUSIONS: This Mendelian randomization meta-analysis supports a causal association of smoking heaviness with higher level of resting heart rate, but not with blood pressure. These findings suggest that part of the cardiovascular risk of smoking may operate through increasing resting heart rate.

Typology of "Fatigue" by Heart Rate Variability Analysis in Elite Nordic-skiers.

This study investigated changes in heart rate variability (HRV) in elite Nordic-skiers to characterize different types of "fatigue" in 27 men and 30 women surveyed from 2004 to 2008. R-R intervals were recorded at rest during 8 min supine (SU) followed by 7 min standing (ST). HRV parameters analysed were powers of low (LF), high (HF) frequencies, (LF+HF) (ms(2)) and heart rate (HR, bpm). In the 1 063 HRV tests performed, 172 corresponded to a "fatigue" state and the first were considered for analysis. 4 types of "fatigue" (F) were identified: 1. F(HF(-)LF(-))SU_ST for 42 tests: decrease in LFSU (- 46%), HFSU (- 70%), LFST (- 43%), HFST (- 53%) and increase in HRSU (+ 15%), HRST (+ 14%). 2. F(LF(+) SULF(-) ST) for 8 tests: increase in LFSU (+ 190%) decrease in LFST (- 84%) and increase in HRST (+ 21%). 3. F(HF(-) SUHF(+) ST) for 6 tests: decrease in HFSU (- 72%) and increase in HFST (+ 501%). 4. F(HF(+) SU) for only 1 test with an increase in HFSU (+ 2161%) and decrease in HRSU (- 15%). Supine and standing HRV patterns were independently modified by "fatigue". 4 "fatigue"-shifted HRV patterns were statistically sorted according to differently paired changes in the 2 postures. This characterization might be useful for further understanding autonomic rearrangements in different "fatigue" conditions.

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

BACKGROUND: The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. AIM: The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. DESIGN: Case control study. POPULATION: Eleven stroke survivors with spastic hemiplegia. METHODS: Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. RESULTS: None of the variable considered showed statistically significant changes after BoNT-A injection. CONCLUSION: The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. CLINICAL REHABILITATION IMPACT: The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

Intrapartum hypoxia and power spectral analysis of fetal heart rate variability

Reliable detection of intrapartum fetal acidosis is crucial for preventing morbidity. Hypoxia-related changes of fetal heart rate variability (FHRV) are controlled by the autonomic nervous system. Subtle changes in FHRV that cannot be identified by inspection can be detected and quantified by power spectral analysis. Sympathetic activity relates to low-frequency FHRV and parasympathetic activity to both low- and high-frequency FHRV. The aim was to study whether intra partum fetal acidosis can be detected by analyzing spectral powers of FHRV, and whether spectral powers associate with hypoxia-induced changes in the fetal electrocardiogram and with the pH of fetal blood samples taken intrapartum. The FHRV of 817 R-R interval recordings, collected as a part of European multicenter studies, were analyzed. Acidosis was defined as cord pH ≤ 7.05 or scalp pH ≤ 7.20, and metabolic acidosis as cord pH ≤ 7.05 and base deficit ≥ 12 mmol/l. Intrapartum hypoxia increased the spectral powers of FHRV. As fetal acidosis deepened, FHRV decreased: fetuses with significant birth acidosis had, after an initial increase, a drop in spectral powers near delivery, suggesting a breakdown of fetal compensation. Furthermore, a change in excess of 30% of the low-to-high frequency ratio of FHRV was associated with fetal metabolic acidosis. The results suggest that a decrease in the spectral powers of FHRV signals concern for fetal wellbeing. A single measure alone cannot be used to reveal fetal hypoxia since the spectral powers vary widely intra-individually. With technical developments, continuous assessment of intra-individual changes in spectral powers of FHRV might aid in the detection of fetal compromise due to hypoxia.

Fetal heart rate responses during maternal resistance exercise: a pilot study

PURPOSE: To determine fetal heart rate (FHR) responses to maternal resistance exercise for the upper and lower body at two different volumes, and after 25 minutes post-exercise.METHODS: Ten pregnant women (22-24 weeks gestation, 25.2±4.4 years of age, 69.8±9.5 kg, 161.6±5.2 cm tall) performed, at 22-24, 28-32 and 34-36 weeks, the following experimental sessions: Session 1 was a familiarization with the equipment and the determination of one estimated maximum repetition. For sessions 2, 3, 4 and 5,FHR was determined during the execution of resistance exercise on bilateral leg extension and pec-deck fly machines, with 1 and 3 sets of 15 repetitions; 50% of the weight load and an estimated repetition maximum. FHR was assessed with a portable digital cardiotocograph. Results were analyzed using Student's ttest, ANOVA with repeated measures and Bonferroni (α=0.05; SPSS 17.0).RESULTS: FHR showed no significant differences between the exercises at 22-24 weeks (bilateral leg extension=143.8±9.4 bpm, pec-deck fly=140.2±10.2 bpm, p=0.34), 28-30 weeks (bilateral leg extension=138.4±12.2 bpm, pec-deck fly=137.6±14.0 bpm, p=0.75) and 34-36 weeks (bilateral leg extension=135.7±5.8 bpm, pec-deck fly=139.7±13.3 bpm, p=0.38), between the volumes(bilateral leg extension at 22-24 weeks: p=0.36, at 28-30 weeks: p=0.19 and at 34-36 weeks: p=0.87; pec-deck fly at 22-24 weeks: p=0.43, at 28-30 weeks: p=0.61 and at 34-36 weeks: p=0.49) and after 25 minutes post-exercise.CONCLUSION: Results of this pilot study would suggest that maternal resistance exercise is safe for the fetus.

Heart rate variability in young adults - Reference values and associations with cardiometabolic risk factors and vascular properties. The Cardiovascular Risk in Young Finns Study.

Background: The function of the autonomic nervous system (ANS) can be evaluated with heart rate variability (HRV). Decreased HRV is associated with aging, the male sex, increased heart rate, and overall increased cardiometabolic risk. It has been hypothesized that early atherosclerotic vascular changes and ANS function are related. Aims: The aims were to assess reference values on HRV in young adults, and examine associations with HRV and cardiometabolic risk factors and metabolic syndrome (MetS) and to study relations between HRV and ultrasonographically measured vascular properties. Participants and methods: The present thesis is part of the Cardiovascular Risk in Young Finns Study. The thesis is based on the follow-up study in 2001, when the study individuals were 24-39 years of age. HRV data were available on 1 956 individuals. Results: HRV was inversely associated with age and heart rate (for all p<0.001). Highfrequency HRV (HF) was higher, and low-frequency HRV (LF) lower in women than men (p<0.0001 for both). MetS was associated with 11% decreased HF and 12% increased LF/HF-ratio in women, and 8% decreased HF and 4% increased LF/HF-ratio in men. Carotid artery distensibility was independently associated with HF and total HRV (for both p<0.05). Conclusions: The reference values in young adults were generated. Decreased HRV was associated with age, the male sex and increased heart rate. Women had higher HF and lower LF variability than men. MetS was related to decrease in HRV. The observed associations between carotid elasticity and HRV, supports the hypothesis that reduction in carotid elasticity may lead to decrease in autonomic cardiac control.

Heart rate changes during the Valsalva maneuver in patients with isolated aortic insufficiency

To determine the possible relationship between left ventricular dilatation and heart rate changes provoked by the Valsalva maneuver (Valsalva ratio), we studied 9 patients with isolated chronic aortic insufficiency. Left ventricular systolic function was assessed by two-dimensional echocardiography and cardiac catheterization. All patients were asymptomatic (functional class I of the New York Heart Association). The left ventricular internal diameters and volumes were significantly increased in all patients. The asymptomatic patients had either normal or slightly depressed ejection fraction (EF>0.40). The Valsalva ratio of these asymptomatic patients showed no significant correlation with the left ventricular volumes or with the left ventricular ejection fraction. In other words, parasympathetic heart rate control, as expressed by the Valsalva ratio, was normal in the asymptomatic patients with left ventricular dilatation and preserved left ventricular ejection fraction. Therefore, left ventricular dilatation may not be the major mechanism responsible for the abnormal parasympathetic heart rate control of patients with acquired heart disease

Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 ± 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1) - (MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10-3. STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 ± 12.9 to 319.2 ± 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 ± 1.67 to 19.87 ± 2.60 ms, did not change MAP, and reduced P1 from 61.0 ± 5.3 to 51.5 ± 1.8 arbitrary units (AU), P2 from 41.3 ± 0.3 to 29.0 ± 1.8 AU, and MN from 171.1 ± 30.2 to 77.2 ± 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r = -0.76, P = 0.03) as well as with the MN index (r = -0.83, P = 0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence these results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability