Asymmetric Properties of the Heart Rate Microstructure in Healthy Adults during 48 h ECG Recordings.

Heart rate asymmetry reflects the different contributions of heart rate (HR) decelerations and accelerations to heart rate variability (HRV). We examined the contribution of monotonic runs of HR accelerations and decelerations to the asymmetric properties of the HR microstructure in the 48 h electrocardiograms (ECGs) of healthy adults (n = 101, 47 males, average age of 39 years) and analysed sex differences in the HR microstructure. The HR microstructure was asymmetric for runs of most lengths, except for sequences of two consecutive decelerations (DR2s) or accelerations (AR2s). Women had a higher prevalence of AR2s than men but fewer runs in the range of 4 to 11 consecutive accelerations (AR4-AR11s) and 5 to 11 consecutive decelerations (DR5-DR11s). The longest runs consisted of 47 consecutive accelerations (AR47s) and 27 consecutive decelerations (DR27s). More DR3s than AR3s and more DR4s than AR4s reveal a crossing of HR microstructure asymmetry. In conclusion, more acceleration than deceleration runs demonstrate that the HR microstructure was asymmetric in the 48 h ECGs. This phenomenon was present in both sexes but was more pronounced in men. For shorter runs of 3 and 4 consecutive heartbeats, there was a crossing of HR microstructure asymmetry, with more deceleration than acceleration runs.

Arterial Blood Pressure Features of Hypertensive Patients with Typical and Atypical 460 nm Skin Fluorescence Response to Transient Ischaemia.

Flow-mediated skin fluorescence (FMSF) at 460 nm is a non-invasive method for assessing dynamic changes in the reduced form of nicotinamide adenine dinucleotide (NADH) and microcirculation in forearm skin under varying conditions of tissue perfusion. Typically, fluorescence increases during ischaemia, but atypical cases show a temporary signal decrease instead of a constant increase. This study aimed to explore the clinical implications of atypical FMSF patterns in patients with newly diagnosed untreated hypertension. NADH fluorescence and pulse wave analysis were performed on 65 patients. Differences in peripheral and arterial pulse pressure profiles were examined based on FMSF curve courses. Patients with atypical curve courses had significantly (p < 0.05 or lower for all) higher heart rate, peripheral and central diastolic pressure, tension time index, central rate pressure product, shorter diastole duration, and reservoir pressure-time integral. Hypertensive patients with atypical FMSF signals had less advantageous blood pressure profiles. Although the underlying factors causing these symptoms are unknown, the atypical FMSF pattern may reflect increased sympathetic stimulation and vascular resistance. The visual assessment of the FMSF curve may have important clinical implications that deserve further investigation.

First-Phase Left Ventricular Ejection Fraction as an Early Sign of Left Ventricular Dysfunction in Patients with Stable Coronary Artery Disease.

Left ventricular (LV) systolic function is often measured with echocardiography using LV ejection fraction (LVEF) or global longitudinal peak systolic strain (GLPSS). Global wasted work (GWW), global work efficiency (GWE), and first-phase ejection fraction (LVEF-1) are newer LV systolic function indices. We examined these parameters in 45 healthy individuals and 50 patients with stable coronary artery disease (CAD), normal LV contractility, and LVEF > 50%. Compared to healthy individuals, CAD patients had similar LVEF but increased GLPSS and GWW and reduced GWE and LVEF-1. The highest area under the receiver operating characteristic for detecting CAD was found for LVEF-1 (0.84; 95% CI 0.75-0.91; p < 0.0001), and it was significantly larger than for GLPSS (+0.166, p = 0.0082) and LVEF (+0.283, p = 00001). For LVEF-1 < 30%, the odds ratio for the presence of CAD was 22.67 (95% CI 6.47-79.44, p < 0.0001) in the logistic regression adjusted for age, sex, and body mass index. Finding LVEF-1 < 30% in an individual with normal LV myocardial contraction and preserved LVEF strongly suggests the presence of CAD.

Comparison of Hemodynamic Response between Patients with Systolic Heart Failure Differing in Serum Aldosterone Concentrations during and after a 6-Minute Walk Test.

Aldosterone regulates hemodynamics, including blood pressure (BP), and is involved in the development and progression of cardiovascular diseases, including systolic heart failure (HF). While exercise intolerance is typical for HF, neither BP nor heart rate (HR) have specific characteristics in HF patients. This study compares BP and HR profiles during and after standardized exercise between patients with systolic HF with either lower or higher aldosterone concentrations. We measured BP and HR in 306 ambulatory adults with systolic HF (left ventricular ejection fraction (LVEF) <50%) during and after a 6 min walk test (6MWT). All patients underwent a resting transthoracic echocardiography, and venous blood samples were collected for biochemical analyses. The patients were also divided into tertiles of serum aldosterone concentration: T1 (<106 pg/mL), T2 (106 and 263 pg/mL) and T3 (>263 pg/mL), respectively. Individuals from T1 and T2 were combined into T1-T2 as the reference group for comparisons with patients from T3. The individuals from T3 had significantly lower systolic, mean and diastolic BPs at rest, at the end and at 1 and 3 min post-6MWT recovery, as well as a more dilated left atrium and right ventricle alongside a higher concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Higher serum aldosterone concentration in HF patients with an LVEF < 50% is associated with a lower 6MWT BP but not an HR profile.

Heart Rate Asymmetry, Its Compensation, and Heart Rate Variability in Healthy Adults during 48-h Holter ECG Recordings.

Heart rate asymmetry (HRA) reflects different contributions of heart rate (HR) decelerations and accelerations to heart rate variability (HRV). In this study, we examined various properties of HRA, including its compensation and HRV, in 48-h electrocardiogram (ECG) recordings in healthy adults. Furthermore, we compared sex differences in parameters used to quantify HRA and HRV. Variance-based and relative HRA and HRV parameters were computed for Holter ECG recordings lasting up to 48 h in 101 healthy volunteers. The median age of the subjects was 39 years, with 47 of them being men. The prevalence of all forms of HRA was statistically different from randomness (p < 0.0001). Specifically, HR decelerations contributed >50% (C1d) to short-term HRA in 98.02% of subjects, while HR decelerations contributed <50% to long-term HRA in 89.11% of recordings and to total HRA in 88.12% of recordings. Additionally, decelerations accounted for <50% of all changing heartbeats (Porta's index) in 74.26% of subjects, and HRA compensation was present in 88.12% of volunteers. Our findings suggest that various HRA features are present in most healthy adults. While men had more pronounced HRA expression, the prevalence of short-, long-term, and total HRA and its compensation was similar in both sexes. For HRV, values of variance-based indices were higher in men than in women, but no differences were found for relative measures. In conclusion, our study references HRA and HRV for longer ECG recordings of up to 48 h, which have become increasingly important in clinical ECG monitoring. The findings can help understand and compare the characteristics of HRA and HRV in patients with different diseases.

Investigating the Ischaemic Phase of Skin NADH Fluorescence Dynamics in Recently Diagnosed Primary Hypertension: A Time Series Analysis.

The reduced form of nicotinamide adenine dinucleotide (NADH) is crucial in cellular metabolism. During hypoxia, NADH accumulation results from anaerobic cytoplasmic glycolysis and impaired mitochondrial function. This study aimed to compare the dynamic changes in the 460-nm forearm skin fluorescence, which reflects cellular NADH content, during transient ischaemia between healthy individuals and patients with newly diagnosed, untreated essential hypertension (HA). Sixteen healthy volunteers and sixty-five patients with HA underwent non-invasive measurement of forearm skin NADH content using the Flow Mediated Skin Fluorescence (FMSF) method at rest and during a 100-s transient ischaemia induced by inflation of the brachial cuff. The fluorescent signal was sampled at 25 Hz. All samples were normalised to the end of the ischaemic phase, which is the most stable phase of the whole recording. Slope values of 1 s linear regressions were determined for every 25-sample neighbouring set. The 1-s slopes in the early phase of skin ischaemia, indicating quicker hypoxia-induced NADH accumulation in skin, were significantly higher in patients with HA than in healthy individuals. These findings suggest that some protecting mechanisms postponing the early consequences of early cellular hypoxia and premature NADH accumulation during skin ischaemia are impaired in patients with untreated HA. Further studies are needed to investigate this phenomenon.

Cardiovascular Function in Different Phases of the Menstrual Cycle in Healthy Women of Reproductive Age.

Background: Sex hormones influence the cardiovascular (CV) function in women. However, it is uncertain whether their physiological variation related to the regular menstrual cycle affects the CV system. We studied changes in the hemodynamic profile and body's water content and their relation to sex hormone concentration in healthy women during the menstrual cycle. Material and methods: Forty-five adult women were examined during the early follicular, late follicular, and mid-luteal phases of the same menstrual cycle. The hemodynamic profile was estimated non-invasively by cardiac impedance while water content was estimated by total body impedance. Results were compared with repeated measures ANOVA with post-test, if applicable. Results: There were no significant changes in most hemodynamic and water content parameters between the menstrual cycle phases in healthy women. Left ventricular ejection time differed significantly among phases of the menstrual cycle, with shorter values in the mid-luteal phase (308.4 vs. 313.52 ms, p < 0.05) compared to the late follicular phase. However, the clinical relevance of such small differences is negligible. Conclusions: Changes in sex hormones during the physiological menstrual cycle appear to have no considerable effect on healthy women's hemodynamic function and water accumulation.

The serum concentration of brain­derived neurotrophic factor is lower in ambulatory and clinically stable patients with more advanced systolic heart failure.

INTRODUCTION: Brain­derived neurotrophic factor (BDNF) is decreased in heart failure (HF), but whether serum BDNF concentration is related to the severity of HF with reduced left ventricular (LV) ejection fraction (LVEF) below 50% is uncertain. OBJECTIVES: We aimed to compare cardiac structure and function in ambulatory and clinically stable patients with HF and LVEF below 50% for lower and higher BDNF serum concentrations. PATIENTS AND METHODS: A total of 361 ambulatory patients with a compensated HF and LVEF below 50% underwent cardiac evaluation and measurement of serum BDNF and N­terminal pro-B­type natriuretic peptide (NT­proBNP). Patients from the lower (below median) and higher (equal to or above median) BDNF serum concentration groups were compared by analysis of covariance (ANCOVA) adjusted for age, sex, body mass index, resting heart rate, and systolic blood pressure. RESULTS: The patients were at a median age of 63.8 (interquartile range [IQR], 57.7-71.5) years and had a median LVEF of 31.0% (IQR, 23.0-37.4). Individuals with lower BDNF (<23.5 ng/ml) had significantly (P ≤0.05) more dilated right and left atria both before and after emptying, larger right ventricular end-diastolic diameter, LV end-systolic diameter, lower tricuspid annulus plane systolic excursion, shorter pulmonary acceleration time, higher mitral E to A waves ratio and mitral E wave to tissue Doppler e' wave ratio, and higher concentration of NT­proBNP. CONCLUSIONS: HF patients with LVEF below 50% and lower serum BDNF concentration present more advanced cardiac remodeling and dysfunction than individuals with higher BDNF. Potential mechanisms and clinical consequences of these findings require further investigation.

The Effect of Antihypertensive Drugs on NADH in Newly Diagnosed Primary Hypertension.

Background: Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF). Methods: In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women). Results: There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion (P at most <0.05), indicating an increase in the total NADH skin content. Conclusion: Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation.

Preclinical atherosclerosis in cystic fibrosis: Two distinct presentations are related to pancreatic status.

BACKGROUND: Patients with cystic fibrosis (CF) are exposed to overlapping cardiovascular risk factors. We hypothesized that CF is characterized by increased arterial stiffness and greater intima-media thickness (IMT). METHODS: This cross-sectional study assessed the digital volume pulse arterial stiffness index (SIDVP) using photopletysmography, measured intima-media complex thickness (IMT) at the common carotid artery, and obtained an extended set of clinical and atherosclerosis-related laboratory parameters. RESULTS: Fifty-five patients with moderate-to-severe CF (mean age 26.3±8.6 years, BMI 20.3±3.1 kg/m2, FEV1 62±26%) and 51 healthy controls (25.1±4.4 years, BMI 21.7±3.0 kg/m2) entered the study. SIDVP was greater in pancreatic insufficient (PI), but not pancreatic sufficient (PS) CF patients compared with control (7.3±1.8 m/s vs 6.0±1.2 m/s; p=7.1 × 10-5). IMT was increased in PS (but not PI) participants relative to control (552±69 µm vs 456±95 µm, p=0.0011). SIDVP was also greater in PI than in PS patients (7.3±1.8 m/s vs 6.3±1.7 m/s, p=0.0232) and IMT was higher in PS compared with PI (552±69 µm vs 453±82 µm, p=0.0002). SIDVP independently associated with age, PI, the lack of liver cirrhosis, and with Pseudomonas aeruginosa colonization. PS was the only independent correlate of IMT in CF. CONCLUSIONS: PI patients are at risk of developing general arterial stiffness. PS may relate to carotid IMT thickening, which underscores the need for further study that could lead to reconsideration of dietary guidance in PS CF.

Non-invasive in vivo human model of post-ischaemic skin preconditioning by measurement of flow-mediated 460-nm autofluorescence.

AIMS: Transient ischaemia and reperfusion (TIAR) induce early ischaemic preconditioning (IPC) in different tissues and organs, including the skin. IPC protects tissues by modifying the mitochondrial function and decreasing the amount of the reduced form of nicotinamide adenine dinucleotide (NADH). Skin 460-nm autofluorescence is proportional to the NADH content and can be non-invasively measured during TIAR. We propose a non-invasive in vivo human model of skin IPC for studying the effects of repeated TIARs on the NADH content. METHODS: Fifty-one apparently healthy volunteers (36 women) underwent three 100-second forearm ischaemia episodes induced by inflation of brachial pressure cuff to the pressure of 60 mmHg above systolic blood pressure, followed by 500-second long reperfusion episodes. Changes in skin NADH content were measured using 460-nm fluorescence before and during each of the three TIARs. RESULTS: The first two TIARs caused a significant reduction in the skin NADH content before (P = .0065) and during the third ischaemia (P = .0011) and reperfusion (P = .0003) up to 3.0%. During the third TIAR, the increase in skin NADH was 20% lower than during the first ischaemia (P = .0474). CONCLUSIONS: The measurement of the 460-nm fluorescence during repeated TIARs allows for a non-invasive in vivo investigation of human skin IPC. Although IPC reduces the overall NADH skin content, the most noticeable NADH reduction appears during ischaemia after earlier TIARs. Studying the skin model of IPC may provide new avenues for in vivo physiological, clinical and pharmacological research on mitochondrial metabolism.

Cardiovascular, anthropometric, metabolic and hormonal profiling of normotensive women with polycystic ovary syndrome with and without biochemical hyperandrogenism.

PURPOSE: Women with polycystic ovary syndrome (PCOS) present with or without biochemical hyperandrogenism (HAPCOS or non-HAPCOS, respectively). Cardiometabolic and hormonal abnormalities have been reported in women with PCOS, particularly those with hypertension. However, no direct comparison between normotensive (blood pressure <140/90 mmHg) patients with HAPCOS and non-HAPCOS has been made. This study compared different cardiovascular (CV), anthropometric, metabolic and hormonal features between normotensive patients with HAPCOS and non-HAPCOS and healthy women. METHODS: We consecutively recruited 249 normotensive patients with PCOS and 85 healthy eumenorrheic women to a case-control observational study. Based on blood androgen concentration, patients with PCOS were divided into HAPCOS (n = 69) or non-HAPCOS (n = 180) groups. RESULTS: Although within normal ranges, patients with HAPCOS had significantly (p < 0.05) higher peripheral and central systolic blood pressure and pulse pressure, C-reactive protein, low-density lipoprotein cholesterol, triglycerides, glucose, and insulin than subjects with non-HAPCOS, and healthy women. They also had lower N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration. In contrast, their body mass index (BMI) was higher of over 4 kg/m2 than patients with non-HAPCOS and nearly 6 kg/m2 than in healthy participants. Except for BMI, statistical differences in the cardiometabolic profile were of little clinical relevance. CONCLUSIONS: Young normotensive women with HAPCOS have a worse cardiometabolic profile but lower NT-proBNP concentration than patients with non-HAPCOS. Features of this profile in both PCOS groups are within ranges typical for healthy women. Increased BMI is the only clinically relevant feature differentiating hyperandrogenic from non-hyperandrogenic patients with PCOS, and healthy women.

Titin and dystrophin serum concentration changes in patients affected by thyroid disorders.

INTRODUCTION: It is well established that thyroid hormones significantly affect skeletal muscle function, causing symptoms like myalgia and muscle weakness. Hypothyroid patients present increased levels of creatine kinase (CK), indicating muscle destruction. Lately, we proposed new serum markers of muscle disturbances in thyroid disorders: titin (TTN) and dystrophin (DMD). The aim of this study is to determine the association between thyroid status, muscle metabolism, and serum levels of TTN and DMD in patients affected by hypoand hyperthyroidism, before and after the treatment. MATERIAL AND METHODS: In the study 56 subjects were enrolled. The studied group consisted of 16 patients with newly diagnosed overt hypothyroidism and 20 patients with hyperthyroidism. Twenty healthy controls were also included in the study. Body composition, thyroid hormones, and biochemical markers of muscle deterioration levels were evaluated before and after restoration of euthyroidism. RESULTS: Dystrophin and TTN levels were noticeably lower in the hypothyroid group and hyperthyroid group in comparison with controls, at the border of statistical significance. Along with the thyroid hormones and CK normalisation, DMD levels increased in the hypothyroid group, with no significant lowering of TTN levels. However, TTN concentrations and the fT3/fT4 ratio became significantly lower than in controls. Hyperthyroid patients experienced no significant changes in TTN and DMD. CONCLUSIONS: The presented data indicate that TTN and DMD are potential new markers of musculoskeletal deterioration in thyroid disorders. In addition, the shift in TTN and DMD serum concentrations after the treatment of hypothyroidism accompanied by decreased fT3/fT4 ratio suggest the influence of the chosen therapeutic approach on muscle metabolism.

Association of muscular strength with pulsatile and steady hemodynamics in patients with acute myocardial infarction.

INTRODUCTION: Grip strength and blood pressure are strongly interrelated. Blood pressure is an essential component of arterial load, which modulates cardiac output. OBJECTIVES: We aimed to asses the correlation between grip strength and both steady and pulsatile components of arterial load in patients with acute myocardial infarction. PATIENTS AND METHODS: We included 295 participants (mean age, 63 years) with acute myocardial infarction. The following data were assessed: grip strength, echocardiography, local arterial stiffness, arterial tonometry, continuous arterial pulse, and beat­to­beat wave. RESULTS: In univariable analyses, grip strength correlated with arterial stiffness (pulse wave velocity), ventricular-arterial coupling, and measures of pulsatile arterial load: aortic characteristic impedance (Zao), total arterial compliance (TAC), and central fractional arterial pulse pressure (cFPP). In a multivariable model including age, grip strength, body mass index, systolic blood pressure, sex, and descriptors of pulsatile load, the following remained associated with grip strength: Zao (R2 for the model = 0.58; P <0.001), TAC (R2 = 0.23 for the model; P <0.001), and cFPP (R2 for the model = 0.2; P <0.001). In the second model that included sex, only Zao remained associated with grip strength (R2 for the model = 0.67). Comparisons between men and women of the adjusted mean value demonstrated that Zao and cFPP were considerably higher (P <0.001 and P = 0.02, respectively) and TAC was lower in women (P <0.001). CONCLUSIONS: In a cohort of patients with acute myocardial infarction, grip strength correlated independently and significantly with descriptors of the pulsatile arterial load. The role of sex in these interrelations needs further study.

Grip strength is associated with markers of central hemodynamics.

Objectives. Reduced muscular strength (measured by grip strength) has been associated with an increased risk of cardiovascular complications. Further research is needed to identify how muscular strength is associated with various markers of cardiovascular function to provide at least some mechanistic explanation for observed interrelations. We, therefore, addressed the question of whether handgrip (HG) strength is associated with descriptors of peripheral and central hemodynamics in the population of healthy individuals. Design. Two hundred thirty-one healthy volunteers (90 men and 141 women, mean age 54 years) were studied. Patients were asked to perform the maximum handgrip trial in the standing position with the dominant arm, using hydraulic hand dynamometer. Applanation tonometry was used to execute the non-invasive assessment of the pressure waveform. Results. HG strength was associated with various markers of hemodynamics and clinical characteristics, e.g. correlated significantly and positively with BMI [body mass index, r = 0.21, p = .001], PPA [pulse pressure amplification, r = 0.43, p < .0001], Tr [time to return of pressure wave, r = 0.43, p < .0001] and significantly and negatively with AP [augmentation pressure, r = -0.45, p < .0001]. Multiple linear regression showed that sex, handgrip and mean blood pressure were independently associated with AP (R2 = 0.38), PPA (R2 = 0.21) and Tr (R2 = 0.29). Conclusions. Our study demonstrated the association between handgrip strength and central hemodynamic metrics. These interactions may add a mechanistic explanation for the role of muscle strength as a risk marker for incident cardiovascular complications.

Cardiovascular Function in Obstructive Sleep Apnea Patients with Controlled Hypertension.

This study investigated hemodynamic characteristics of obstructive sleep apnea (OSA) accompanied by hypertensive disease in obese men, in whom blood pressure was pharmacologically controlled within the normal range, not exceeding 140/90 mmHg. There were 21 severe OSA patients (mean age 54.1 ± 9.3 years, apnea-hypopnea index of 47.1 ± 18.8 episodes per hour) included in the study, in whom OSA was diagnosed with polysomnography. The control group consisted of healthy normotensive age-matched subjects. Hemodynamic profile was recorded nonivasively with impedance cardiography. Brachial blood pressure and radial artery tonometry were performed to capture and reconstruct peripheral radial and central aortic pressure waveforms in both groups of subjects. Compared to healthy men, OSA patients had a significantly higher body mass index (BMI); the mean increase in BMI amounted to 6.4 ± 1.2 kg/m2. The patients also presented significant differences in the hemodynamic profile. The difference consisted of a faster heart rate, higher peripheral pulse pressure, and reduced blood flow acceleration and velocity indices, describing myocardial contractility. Notably, the significance of hemodynamic differences in OSA patients disappeared in the analysis adjusted for the outstanding increase in BMI. In conclusion, the findings strongly suggest that obesity rather than the hypertensive disease per se is a source of hemodynamic consequences in OSA patients.