Time domain heart rate variability analysis in patients with thalassaemia major

OBJECTIVE: Cardiac complication is one of the major causes of death in patients with thalassaemia major. Heart rate variability is a non-invasive index of neuronal modulation of heart rate. In this study, autonomic functions of the heart in a preclinical stage of heart disease were evaluated in 48 thalassaemic patients with time domain heart rate variability analysis; the control group consisted of 45 healthy subjects. METHODS AND RESULTS: Mean RR time in the study and control group was 0.73 +/- 0.1, and 0.82 +/- 0.1 ms respectively (p < 0.001). In the study group; SDNN, SDNN-i, SDANN-i, RMSSD, and PNN50 were found to be 167.4 +/- 86.2 ms, 153.9 +/- 108.1 ms, 111.4 +/- 60.4 ms, 108.9 +/- 86.7 ms, and 14.5 +/- 13.4%, respectively. Time domain parameters were significantly lower in the study group than the control group (p < 0.00 1). There was a significant positive correlation between the mean RR time and SDNN, SDNN-i, SDANN-i, RMSSD, and PNN50 (for the RMSSD p < 0.05, r = 0.31; for the others p = 0.000, and r values were 0.65, 0.65, 0.38, 0.37 for the SDNN, SDNN-i, SDANN-i, and PNN50, respectively). CONCLUSION: The analysis of heart rate variability might be helpful to detect cardiac complications in the preclinical stage of the cardiac involvement.     

Cardiac autonomic functions derived from short-term heart rate variability recordings associated with heart rate recovery after treadmill exercise test in young individuals

Analysis of short-term heart rate variability (HRV) may provide useful information about autonomic nervous control of heart rate recovery. We studied 495 individuals (273 men), age range 19–85 years, submitted to treadmill exercise tests and short-term HRV evaluations over time (standard deviation of the normal-to-normal interval [SDNN], the square root of the mean squared differences of successive normal-to-normal intervals [RMSSD], the number of interval differences of successive normal-to-normal intervals greater than 50 ms [NN50 count], the proportion derived by dividing NN50 count by the total number of normal-to-normal intervals [pNN50]) and frequency (low-frequency power [LF], high-frequency power [HF], total power) domains. Among 495 patients, 106 patients (68 men) were elderly (age  ≥ 65 years). Male gender and hypertension were significantly higher in elderly patients. The young patients had higher HRR after exercise. HRR at 4 min (54 ± 13 vs 60 ± 12 beats/min; P = 0.003) was the most significant predictor for positive exercise test result. In the young group, both time domain measures (SDNN: correlation coefficient 0.34, P < 0.001; RMSSD: correlation coefficient 0.37, P < 0.001) and frequency domain measures (LF: correlation coefficient 0.21, P < 0.001; HF: correlation coefficient 0.13, P = 0.01; total power: correlation coefficient 0.22, P < 0.001) were significantly associated with HRR at 4 min. HRR at 4 min was significantly associated with short-term HRV of time and frequency domains in young individuals, but not elderly ones, receiving treadmill exercise test.     

老年急性心肌梗塞心率变异时域分析

目的分析急性心肌梗塞（ＡＭＩ）后老年患者心率变异（ＨＲＶ）时域指标，了解ＡＭＩ后ＨＲＶ变化。方法以多单位协作方式对１５７例ＡＭＩ后２周的老年患者行动态心电图检测ＨＲＶ时域法５项指标，并与健康老年组对比分析。数据经ＥｐｉＩｎｆｏ（６．０）统计软件处理。结果①ＡＭＩ患者的正常Ｒ－Ｒ间期标准差（ＳＤＮＮ）、平均值的标准差（ＳＤＡＮＮ）和标准差的平均值（ＳＤＮＮＩｎｄｅｘ）低于对照组（Ｐ＜０．０１），而相邻正常Ｒ－Ｒ间期差值的均方根（ＲＭＳＳＤ）和相邻正常Ｒ－Ｒ差值大于５０ｍｓ记数占总Ｒ－Ｒ间期数的百分比（ＰＮＮ５０）虽低于对照组，但无显著差异（Ｐ＞０．０５）。②ＡＭＩ后ＨＲＶ时域５项指标男、女性别间无显著性差异（Ｐ＞０．０５）。③ＳＤＮＮ、ＳＤＡＮＮ和ＳＤＮＮＩｎ－ｄｅｘ在心肌梗塞各部位间无显著差异（Ｐ＞０．０５），ＲＭＳＳＤ和ＰＮＮ５０前间壁低于下壁心肌梗塞（Ｐ＜０．０５）。结论老年人ＡＭＩ后ＨＲＶ降低。反映交感神经活性的ＳＤＮＮ、ＳＤＡＮＮ和ＳＤＮＮＩｎｄｅｘ和反映迷走神经活性的ＲＭＳＳＤ和ＰＮＮ５０２组指标变化不相同。     

Heart rate variability parameters and ventricular arrhythmia correlate with pulmonary arterial pressure in adult patients with idiopathic pulmonary arterial hypertension

ObjectiveThis aim of this study was to correlate heart rate variability (HRV) parameters to pulmonary arterial pressure (PAP) in patients with purely idiopathic pulmonary arterial hypertension (IPAH).BackgroundHRV is decreased in patients with PAH. Whether HRV indices can be used to assess PAP in IPAH patients remains unclear.MethodsHRV parameters obtained by 24-h ECG were evaluated in 26 IPAH patients and 51 controls.ResultsTime-domain HRV parameters (SDNN, p < 0.0001; SDANN, p < 0.0001; RMSSD, p = 0.006) were lower in IPAH patients. Frequency-domain indices (high-frequency power, HFP, p = 0.001; low-frequency power, LFP, p = 0.003; total power, TP, p = 0.001) were also decreased in IPAH patients. In IPAH patients, RMSSD (p = 0.001), HFP (p = 0.015), and LFP (p = 0.027) were significantly correlated with PAP. IPAH patients had longer QTc intervals (p < 0.0001) and more premature ventricular contractions (p < 0.0001) than controls.ConclusionsIPAH is associated with autonomic dysfunction. RMSSD, HFP, and LFP may be used as a supplemental tool to assess PAP in IPAH patients. IPAH patients with autonomic dysfunction are at high risk for ventricular arrhythmia.     

Evaluation of repolarization dynamics using the QT–RR regression line slope and intercept relationship during 24-h Holter ECG

QT–RR linear regression consists of two parameters, slope and intercept, and the aim of this study was to evaluate repolarization dynamics using the QT–RR linear regression slope and intercept relationship during 24-h Holter ECG. This study included 466 healthy subjects (54.6 ± 14.6 years; 200 men and 266 women) and 17 patients with ventricular arrhythmias, consisted of 10 patients with idiopathic ventricular fibrillation (IVF) and 7 patients with torsades de pointes (TDP). QT and RR intervals were measured from ECG waves based on a 15-s averaged ECG during 24-h Holter recording using an automatic QT analyzing system. The QT interval dependence on the RR interval was analyzed using a linear regression line for each subject ([QT] = A[RR] + B; where A is the slope and B is the y-intercept). The slope of the QT–RR regression line in healthy subjects was significantly greater in women than in men (0.185 ± 0.036 vs. 0.161 ± 0.033, p < 0.001) and the intercept was significantly smaller in women than in men (0.229 ± 0.028 vs. 0.240 ± 0.027, p < 0.001). A scatter diagram of the QT–RR regression line slope and intercept among healthy subjects demonstrated a statistically significant negative correlation (B = ?0.62A + 0.34, r = ?0.79). Distribution of both scatter diagrams of the slope and the intercept of the QT–RR regression line in patients with IVF and TDP was different from healthy subjects (left corner for IVF and upward shift for TDP). The slope and intercept relationship of the QT–RR linear regression line based on 24-h Holter ECG may become a simple useful marker for abnormality of ventricular repolarization dynamics.     

Seroclearance rate of hepatitis B surface antigen in 2,112 patients with chronic hepatitis in Japan during long-term follow-up

Background

Rate of hepatitis B surface antigen (HBsAg) seroclearance was determined in 2,112 Japanese patients with chronic hepatitis B who were followed up for at least 15 years.

Methods

Patients had a median age of 37 years and included 1,431 (67.8 %) men. Median values were AST/ALT, 43/62 IU/L; platelet counts, 182 × 10³/mm³; HBsAg, 3,400 IU/mL; and hepatitis B virus (HBV) DNA, 6.2 log copies/mL. Factors influencing HBsAg seroclearance were evaluated by the Cox proportional model and annual rate of HBsAg seroclearance by the Kaplan–Meier life table method.

Results

The overall annual rate of HBsAg seroclearance was 1.75 % in 2,112 patients; it was 1.65 % in 1,130 untreated and 2.05 % in 982 treated patients (p = 0.289). In untreated patients, seroclearance was influenced by age, no HBV infections in third-degree or closer relatives, and HBsAg levels in univariate analysis. Seroclearance was influenced by a median age ≥50 years [relative risk (RR) 1.61 (p = 0.018)] and HBsAg ≤2,000 IU/mL [RR 1.77 (p = 0.014)] in multivariate analysis. In treated patients, age, male gender, no HBV infections in third-degree or closer relatives, interferon therapy, chronic hepatitis, high AST and γ-GTP levels, low platelet counts, hepatitis B e antigen (HBeAg)-negative status, low HBsAg levels and the wild-type precore sequence significantly influenced HBsAg seroclearance. In multivariate analysis, no family history [RR 2.22 (p = 0.006)], interferon treatment [RR 3.15 (p < 0.001)], and HBeAg-negative status [RR 3.75 (p < 0.001)] significantly influenced HBsAg seroclearance.

Conclusions

In this retrospective cohort study, the annual rate of HBsAg seroclearance was 1.65 % in untreated patients and 2.05 % in treated patients.     

Feasibility of multiple short, 40-s, intra-procedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias

Purpose

This study aims to evaluate a method to detect heart rate variability (HRV) changes using short ECG segments during ablation for arrhythmias.

Methods

HRV was averaged from sequentially shorter time windows from 5-min ECG recordings in 15 healthy volunteers. The 40-s window was identified as the shortest duration that yielded reproducible values in high frequency (HF) and low frequency (LF) HRV. This method was validated in patients undergoing tilt table testing to see if the expected modulation in HRV that occurs prior to syncope could be detected from multiple 40-s recordings. Lastly, this method was used to assess HRV changes in 75 patients undergoing ablation for atrial fibrillation (AF) and other arrhythmias, to see if autonomic modulation as a result of ablation could be detected. A further 14 patients had stepwise HRV measurements at different stages of the AF ablation procedure to determine whether intra-procedural HRV changes could be detected.

Results

HRV, averaged from multiple 40-s recordings, demonstrated the expected increase immediately preceding syncope compared with baseline (LF: 341?±?311?C1,536?±?1,368 ms², p?<?0.05; HF: 342?±?339?C1,628?±?1,755 ms², p?<?0.05). AF ablation, particularly following right pulmonary vein circumferential ablation, produced immediately detectable reductions in LF (153?±?251?C50?+?116 ms², p?<?0.001) and HF (86?±?195?C33?±?83 ms², p?<?0.001) without any change in RR interval (877?±?191?C843?±?220 ms, p?=?0.261). Ablation for atrial flutter did not change the mean RR interval, LF or HF HRV.

Conclusion

Averaging multiple 40-s windows give valid HF and LF HRV measurements that enable detection of intra-procedural changes. Left atrial ablation around the right-sided pulmonary veins is unique in producing reductions in HRV. This method has the potential for use as an endpoint marker for adjunctive autonomic ablation procedures.     

The extent of heart rate reduction during hospitalization using beta-blockers,not the achieved heart rate itself at discharge,predicts the clinical outcome in patients with acute heart failure syndromes

AimIt has been uncertain whether patients with acute heart failure syndromes (AHFSs) benefit from a lower heart rate (HR) itself or from treatment for heart failure (HF) that reduces sympathetic tone with consequent HR reduction (HRR). The present study investigated the influence of HRR during hospitalization on the prognosis of AHFS patients.Methods and resultsIn 421 AHFS patients, we analyzed the relationship between HRR during hospitalization and the prognosis after discharge. During a mean follow-up period of 1.9 years, 76 and 55 patients died or were re-hospitalized for HF, respectively. Although HR at discharge did not influence cardiac events (hazard ratio [HR]: 1.00 [95% CI; 0.99–1.02], p = 0.22), the extent of HRR was a predictor of cardiac events (HR: 0.89 [0.84–0.96], p < 0.001). Kaplan–Meier analysis revealed that the cardiac event rate of the HRR-positive group (≥27 bpm reduction of HR from 114 ± 24 at admission to 65 ± 11 bpm at discharge) was significantly lower than that of the HRR-negative group (≤26 bpm (=median value) reduction of HR from 74 ± 14 to 71 ± 14 bpm). In the HRR-positive group, the cardiac event rate was significantly lower in patients receiving beta-blockers. Furthermore, the extent of HR change was an important predictor of cardiac events among other markers, compared with the change in systolic blood pressure or B-type natriuretic peptide.ConclusionThe HR itself at discharge was not associated with the prognosis, but the extent of HRR achieved by treatment of HF with beta-blockers was a strong predictor for the clinical outcome in AHFS patients.     

Heart rate variability and heart rate turbulence in hypothyroidism before and after treatment

Background: Cardiac autonomic dysfunction may develop in patients with clinical or subclinical thyroid hormone deficiency. Heart rate variability (HRV) and heart rate turbulence (HRT) are used for evaluating changes in cardiac autonomic functions and also used to provide risk stratification in cardiac and noncardiac diseases. The aim of this study is to evaluate cardiac autonomic functions before and 6 months after thyroid replacement therapy in patients with thyroid hormone deficiency. Methods: Forty hypothyroid patients (mean age 48 ± 13, four male) and 31 healthy controls (mean age 51 ± 12, three male) were included in the study. Twenty‐four hour ambulatory electrocardiogram recordings were taken using Pathfinder Software Version V8.255 (Reynolds Medical). The time domain parameters of HRV analysis were performed using the Heart Rate Variability Software (version 4.2.0, Norav Medical Ltd, Israel). HRT parameters, Turbulence Onset (TO), and Turbulence Slope (TS) were calculated with HRT! View Version 0.60‐0.1 software. Results: HRV and HRT parameters were decreased in the patient group (SDNN; P < 0.001, SDANN; P < 0.009, RMSSD; P = 0.049, TO; P = 0.035, TS; P < 0.001). After 6 months of thyroid replacement therapy, there were no significant changes observed in either HRV or HRT. Conclusions: Hypothyroidism may cause cardiac autonomic dysfunction. Treating hypothyroidism with L‐thyroxine therapy does not effectively restore cardiac autonomic function. HRV and HRT can be used as to help monitor cardiovascular‐related risk in this population. Ann Noninvasive Electrocardiol 2011;16(4):344–350     

Insulin-like growth factor-I correlates more closely than growth hormone with insulin resistance and glucose intolerance in patients with acromegaly

In normal subjects growth hormone (GH) and insulin-like growth factor-I (IGF-I) have opposing effects on glucose metabolism. Active acromegaly is associated with insulin resistance (IR) and glucose intolerance although both GH and IGF-I are elevated. Our objective was to compare whether GH or IGF-I correlates more closely with IR and glucose intolerance in acromegaly. Basal serum IGF-I and GH, glucose and insulin during an oral glucose tolerance test were measured in 70 normoglycemic and 44 hyperglycemic acromegalic patients (21 impaired fasting glucose, 11 impaired glucose tolerance and 12 diabetes mellitus) according to American Diabetes Association criteria. 55 patients were assessed before any treatment for acromegaly and 59 after surgery and/or radiotherapy (15 patients had normal IGF-I after treatment). Patients treated with somatostatin analogs, GH-receptor antagonists or antidiabetic drugs were excluded. IR was assessed by various basal and stimulated indices. Homeostatic Model Assessment 2-Insulin Resistance (HOMA2-IR) index correlated more closely with IGF-I (r = 0.65, p < 0.0001) than nadir (r = 0.23, p = 0.008) or random GH (r = 0.26, p = 0.002). HOMA2-IR correlated better with IGF-I than nadir or random GH also in normoglycemic (n = 70; r = 0.74, p < 0.0001 vs. r = 0.36, p = 0.001 vs. r = 0.39, p < 0.001) and hyperglycemic patients (n = 44; r = 0.54, p = 0.0002 vs. r = 0.09, p = 0.4 vs. r = 0.14, p = 0.26). In multivariate logistic regression analysis IGF-I but not GH was a significant risk factor for glucose intolerance after adjusting for age, sex, weight and acromegaly duration (OR = 1.56, p = 0.01). In acromegaly IGF-I correlates more closely than GH with IR. IGF-I levels but not GH are associated with glucose intolerance.     

Immunoglobulin subtypes predict therapy response to the biologics in patients with rheumatoid arthritis

To analyze the effectiveness of rituximab (RTX) versus alternative TNF antagonists (aTNFs) on rheumatoid arthritis (RA) disease activity in different subgroups of patients and relation with extraarticular manifestations of RA and to assess that RF-subsets have potential as predictors of clinical response to RTX. Patients with RA (n = 40, M/F: 3/37) who received aTNFs at least 6 months with good response (group I; n = 20) or discontinued at least one aTNFs because of the ineffectiveness and subsequently received RTX at least one course (group II; n = 20) were retrospectively evaluated. IgM-, IgA-, IgG-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) levels were measured by ELISA technique. Extraarticular manifestations and radiological scores were also recorded. The mean (SD) age was 51.7 ± 6.5 years in group I and 52.1 ± 6.1 years in group II patients (p > 0.05). The median disease durations were higher in group II than group I [8.0 (2–30) vs. 13 (3–35) years, respectively, p = 0.04]. Presence of RF [13(61.9 %) vs. 20(100 %) p = 0.001] and extraarticular involvement [5(25 %) vs. 13(65 %) p = 0.01] were higher in group II patients. When Ig-RF subgroups analyzed, all subgroup (IgA, IgM, IgG) levels were higher in group II (p = 0.001, p = 0.05, p = 0.001). IgA-RF levels were significantly high in patients with extraarticular involvement (p = 0.04). Association between high RF levels and having extraarticular manifestations in RA patients may largely be attributed to the IgA isotype.     

Evaluation of central corneal and central retinal thicknesses and intraocular pressure in acromegaly patients

Introduction

Acromegaly is a disorder with increased morbidity which can involve many organs and the eye can be one of them which was investigated in few reports. Herein, we aimed to evaluate CCT, IOP and retinal thickness (RT), and their relationships with serum GH and IGF-1 levels and disease duration, in acromegaly patients. We compared the ocular parameters with those of a control group. This study included the largest number of patients of any comparable investigation to date.

Material and Method

We enrolled 30 acromegaly patients (15 male, 15 female and age: 48.4 ± 12.8 years) and 21 age and gender matched controls. All participants underwent complete hormonal and ophtalmological evaluation including central corneal thickness (CCT), retinal thickness (RT) and intraocular pressure (IOP) values.

Results

There were no significant differences in median right and left CCTs and mean CCT (p = 0.646, p = 0.667 and p = 0.384, respectively). Nor were there statistically significant differences in median right and left RT, or mean central RT, between the acromegaly and control groups (p = 0.977, p = 0.738 and p = 0.811, respectively). However median right, left and mean IOPs were found to be significantly higher in the acromegaly group, despite there being no difference in the CCT values (p = 0.011, p = 0.028 and p = 0.047, respectively). When we analyzed two subgroups of acromegaly patients (active/inactive), we found that the median right, left and mean CCTs and RTs, were not significantly different between the groups. Although there was a significant difference in IOP between the acromegaly and control groups, the two subgroups of acromegaly patients had similar IOPs (p = 0.400, p = 0.621 and p = 0.451 for right, left and mean IOPs, respectively). IOP was not found to be correlated with serum IGF-I, GH or disease duration in acromegaly patients.

Conclusion

Our study results suggest that acromegaly is associated with increased ocular pressures irrespective of disease activity. Therefore detailed ocular evaluation should be a routine component of the follow up visits of acromegaly patients.     

Intracranial internal carotid artery changes in acromegaly: a quantitative magnetic resonance angiography study

Purpose

Although cerebrovascular mortality is increased up to eightfold in acromegaly, intracranial internal carotid artery (ICA) changes have not been well investigated. This is a magnetic resonance angiography (MRA) quantitative cross-sectional study of ICA tortuosity, ectasia and intercarotid distance in acromegalic patients with subsequent analysis of concomitant clinical, laboratory and neuroimaging findings.

Methods

One hundred seventy six acromegalic patients (mean-age 55 ± 14 years, age range 21–88, 92 females) and 104 subjects with headache or transient neurological deficits underwent MRA with the same 1.5 T scanner. Clinical data, laboratory and pituitary adenoma imaging findings were recorded. Using a commercially available software, we measured the tortuosity index [(curved/linear ICA length from C3-midpoint to intracranial bifurcation) ? 1], ICA ectasia index (intracavernous/petrous ICA diameter) and intercarotid distance at C3 and C4 levels.

Results

Mean ICA tortuosity and ectasia indices were increased in acromegalic patients compared with controls (1.06 ± 0.29 vs 0.93 ± 0.26, p < 0.001; 1.02 ± 0.10 vs 0.92 ± 0.09, p < 0.001). Mean intercarotid distance was reduced at C3 and increased at C4 in acromegalic patients (16.7 ± 3.4 vs 17.9 ± 2.5 mm, p < 0.001; 16.7 ± 4.6 vs 15.4 ± 4.1 mm, p < 0.05; t test). ICA tortuosity and ectasia correlated neither with laboratory findings nor with previous or current treatment. On multivariate analysis, C3 intercarotid distance was reduced in patients on dopamine agonist treatment (p < 0.01) and increased in patients with GH-deficit (p = 0.01), while C4 intercarotid distance was increased with macroadenoma (p = 0.01) and reduced in patients under dopamine agonist (p < 0.01) or somatostatin analogue (p < 0.05) treatment.

Conclusions

Intracranial ICA changes are common findings in acromegaly, and further studies focused on their possible clinical impact are needed.     

Urinary excretion of high molecular weight adiponectin is an independent predictor of decline of renal function in type 2 diabetes

Adiponectin and urinary adiponectin excretions have been ascribed a function in glomerular physiology and seem to indicate vascular disease in diabetes. The aim of this study was to compare the urinary excretion of albumin and adiponectin as predictors for decline of renal function in patients with type 2 diabetes and early kidney disease. Over 141 patients were screened for renal function (estimated GFR, ml/min*1.73 m²), albumin excretion rate (AER, mg/24 h), total as well as high molecular weight (HMW) urinary adiponectin excretion (ng/mol u-creatinine). AER and adiponectin excretion were studied as predictors of renal function after 1 year. After 1 year, 36 patients were in the upper quartile of eGFR decline and defined as progressors (delta eGFR = ? 12.3 ± 6.3) while the remaining 105 patients were defined as non-progressors (delta eGFR = 1.4 ± 6.0). At baseline, HMW-adiponectin excretion was positively correlated with HbA_1c (p < 0.001) and negatively with eGFR (p < 0.001), but not with AER (p = 0.14). Progressors showed increased urinary HMW-adiponectin at baseline (158[IQR41/479] vs. 65[24/168] ng/mol; p < 0.01), while total adiponectin (182[101/1534] vs. 345[118/1361] ng/mol) and AER (48[23/109] vs. 46[25/108] mg/24 h) excretion showed no differences between the groups. Multivariate logistic regression showed that HMW-adiponectin excretion was an independent predictor of renal progression in all patients (OR 1.86 [95 % CI 1.34–2.59]; p < 0.01), especially in those (n = 45) with normal AER at baseline (OR 2.16 [95 % CI 1.1–4.56]; p < 0.05). Urinary HMW-adiponectin but not AER improved the prediction of progressors in ROC analysis (AUC 0.72 [95 % CI 0.63–0.81] vs. 0.80 [95 % CI 0.71–0.90], p < 0.05). In conclusion, urinary HMW-adiponectin excretion may identify diabetes patients at increased risk for progression of kidney disease.     

The heart rate response to adenosine: A simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes

Background

The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk.

Methods

In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR < 20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death.

Results

During 4.7 ± 0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR < 20% (n = 79), 20–39% (n = 182) and ≥ 40% (n = 257), respectively, p = 0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model < 0.001). HRR < 20% was associated with 9-fold increased risk (p = 0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p = 0.004). Participants with both abnormal MPI and HRR (n = 8) were at highest risk for cardiac events (38%) whereas those with HRR ≥ 40%, irrespective of MPI abnormalities (n = 234), were at extremely low risk (≤ 1%, log-rank p < 0.001).

Conclusions

In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management.     

Potassium excretion and blood pressure are associated with heart rate variability in healthy black adults: The African-PREDICT study

Background and aimsHeart rate variability (HRV) is a main determinant of autonomic function and related to the development of hypertension and cardiovascular (CV) disease. Hypertension develops in black populations at an earlier age, which could be due to differences in the autonomic nervous system activity and sodium/potassium handling in black and white populations. We investigated whether HRV is associated with 24 h urinary sodium and potassium excretion and blood pressure (BP) in a young bi-ethnic cohort.Methods and resultsWe examined 423 black and 483 white healthy adults (aged 24.5 ± 3.1 years) for 24 h HRV, including standard deviation of normal RR intervals (SDNN) reflecting autonomic variations over time, and root mean square of successive differences (RMSSD) reflecting parasympathetic activity. We measured 24 h urinary sodium and potassium concentration and BP. The black group had lower SDNN and potassium excretion as well as higher RMSSD, sodium and Na/k ratio compared to the white group (all p < 0.05). Only in black individuals, urinary potassium excretion was independently and negatively associated with SDNN (β[95% CI];-0.26[-0.50;-0.02]ms) and RMSSD (?0.14[-0.27;-0.01]ms, p < 0.05). One unit increase in sodium/potassium (Na/K) ratio was associated with higher SDNN (β[95% CI]; 3.04[0.89; 5.19]ms) and RMSSD (1.60[0.41; 2.78]ms) in the black cohort only (both p < 0.001). In both groups elevated 24 h diastolic BP was associated with lower RMSSD (p < 0.05).ConclusionLower potassium excretion and higher Na/K ratio related independently to higher HRV in young and healthy black adults. A better ethnic-specific understanding of sodium and potassium handling is required as part of preventive cardiology, especially in black individuals.Clinical trial registrationClinicalTrials.gov Identifier: NCT03292094; URL: https://clinicaltrials.gov/ct2/show/NCT03292094.     

Pegvisomant and cabergoline combination therapy in acromegaly

Combination with cabergoline may offer additional benefits to acromegalic patients on pegvisomant monotherapy. We evaluated the safety and efficacy profile of this combination and investigated the determinants of response. An observational, retrospective, cross-sectional study. Fourteen acromegalic patients (9 females), who were partially resistant to somatostatin analogs and on pegvisomant monotherapy. Cabergoline was added because of the presence of persistent mildly increased IGF-I. The mean follow-up time was 18.3 ± 10.4 months. The efficacy and safety profile was assessed. The influence of clinical and biochemical characteristics on treatment efficacy was studied. IGF-I levels returned to normal in 4 patients (28%) at the end of the study. In addition, some decline in IGF-I levels was observed in a further 5 patients. The % IGF-I decreased from 158 ± 64% to 124 ± 44% (p = 0.001). The average change in IGF-I was ?18 ± 27% (range ?67 to +24%). Lower baseline IGF-I (p = 0.007), female gender (p = 0.013), lower body weight (p = 0.031), and higher prolactin (PRL) levels (p = 0.007) were associated with a better response to combination therapy. There were no significant severe adverse events. Significant tumour shrinkage was observed in 1 patient. Combination therapy with pegvisomant and cabergoline could provide better control of IGF-I in some patients with acromegaly. Baseline IGF-I levels, female gender, body weight, and PRL levels affect the response to this combination therapy.     

Resting heart rate predicts metabolic syndrome in apparently healthy non-obese Japanese men

Autonomic nervous dysfunction is considered to be one of the mechanisms of metabolic syndrome (MetS). The aim of this study is to investigate whether resting heart rate, a marker of autonomic nervous dysfunction, is a predictor of MetS in apparently healthy non-obese [body mass index (BMI) <25 kg/m²] Japanese men. This is an observational study through 3 years in apparently healthy Japanese 1,265 men and 793 women without MetS and with no history of cardiovascular disease and no use of antihypertensive, antidiabetic, or antihyperlipidemic medication at baseline. Hazard ratios (HRs) of incident MetS were calculated for each 1 SD increase in heart rate stratified by gender and obesity. Incidence of MetS for each tertile of heart rate and HRs of MetS for the highest tertile (T3) compared with the lowest tertile (T1) were calculated stratified by gender and obesity. The HRs [95 % confidence intervals (CIs)] of MetS for each 1 SD increase in heart rate were 1.319 (1.035–1.681) (p = 0.025) in non-obese men, 1.172 (0.825–1.665) (p = 0.377) in obese men, 1.115 (0.773–1.608) (p = 0.560) in non-obese women, and 1.401 (0.944–2.078) (p = 0.094) in obese women adjusted for BMI, age, smoking, alcohol drinking, and physical activity. The HRs (95 % CIs) of MetS for T3 were 2.138 (1.071–4.269) (p = 0.031) in non-obese men and 1.341 (0.565–3.180) (p = 0.506) in obese men adjusted for pre-existing five components of MetS, age, smoking, alcohol drinking, and physical activity. In conclusion, an increase in resting heart rate was a significant predictor of MetS in non-obese Japanese men.     

Arterial properties in acromegaly: relation to disease activity and associated cardiovascular risk factors

Purpose

Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function.

Methods

Twenty-nine subjects with acromegaly (11 males, 52 ± 14 year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD).

Results

IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2 ± 1.1 in patients with active disease versus 0.7 ± 0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4 ± 2.7 % in active acromegaly, 4.4 ± 3.3 % in controlled acromegaly and 7.5 ± 3.8 % in controls; p = 0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r = 0.4; P = 0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r = 0.46; p = 0.017) and negatively with small vessel compliance (r = ?0.44, p = 0.02).

Conclusions

Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.

     

高血压合并冠心病患者心率减速力与心率变异性的相关性

目的：探讨心率变异性（HRV）和心率减速力（DC）在高血压合并冠心病患者中的相关性。方法：选择81例高血压合并冠心病患者（研究组）和80例健康志愿者（健康对照组）为研究对象,分别监测 DC和 HRV。结果：与健康对照组比较,高血压合并冠心病患者DC [（11.99±4.93）ms 比（6.62±1.83）ms]及心率变异性的24h正常 R-R间期标准差[SDNN,（129.94±15.22）ms比（63.66±12.13）ms]、相邻正常 R-R间期差值的均方根[rMSSD,（55.52±9.03）ms比（28.25±8.81）ms]和相邻正常 R-R间期差值＞50ms的心搏数占24h总 R-R间期数的百分比[PNN50,（13.99±5.63）％比（7.29±1.11）％]明显降低,P 均＜0.05;Pearson相关分析显示,高血压合并冠心病患者中 DC 与 SDNN、rMSSD和 PNN50均呈正相关（r＝0.571、0.662、0.763,P 均＜0.05）。结论：高血压合并冠心病患者心率减速力与心率变异性呈正相关,可协同作为诊治依据。