The Duke treadmill score with bicycle ergometer: Exercise capacity is the most important predictor of cardiovascular mortality.

BACKGROUND: The Duke treadmill score, a widely used treadmill testing tool, is a weighted index combining exercise time or capacity, maximum ST-segment deviation and exercise-induced angina. No previous studies have investigated whether the Duke treadmill score and its individual components based on bicycle exercise testing predict cardiovascular death. DESIGN: Two populations with a standard bicycle testing were used: 3936 patients referred for exercise testing (2371 men, age 56 ± 13 years) from the Finnish Cardiovascular Study (FINCAVAS) and a population-based sample of 2683 men (age 53 ± 5.1 years) from the Kuopio Ischaemic Heart Disease study (KIHD). METHODS: Cox regression was applied for risk prediction with cardiovascular mortality as the primary endpoint. RESULTS: In FINCAVAS, during a median 6.3-year (interquartile range (IQR) 4.5-8.2) follow-up period, 180 patients (4.6%) experienced cardiovascular mortality. In KIHD, 562 patients (21.0%) died from cardiovascular causes during the median follow-up of 24.1 (IQR 18.0-26.2) years. The Duke treadmill score was associated with cardiovascular mortality in both populations (FINCAVAS, adjusted hazard ratio (HR) 3.15 for highest vs. lowest Duke treadmill score tertile, 95% confidence interval (CI) 1.83-5.42, P < 0.001; KIHD, adjusted HR 1.71, 95% CI 1.34-2.18, P < 0.001). However, after progressive adjustment for the Duke treadmill score components, the score was not associated with cardiovascular mortality in either study population, as exercise capacity in metabolic equivalents of task was the dominant harbinger of poor prognosis. CONCLUSIONS: The Duke treadmill score is associated with cardiovascular mortality among patients who have undergone bicycle exercise testing, but metabolic equivalents of task, a component of the Duke treadmill score, proved to be a superior predictor.

Hypertonic saline-hydroxyethyl starch solution attenuates fluid accumulation in cardiac surgery patients: a randomized controlled double-blind trial.

BACKGROUND: Significant fluid retention is common after cardiac surgery with the use of cardiopulmonary bypass (CPB). The aim of the study was to evaluate the effects of hypertonic saline-hydroxyethyl starch (HS-HES) solution on fluid accumulation in patients undergoing coronary artery bypass grafting surgery (CABG). METHODS: Fifty adult male patients undergoing coronary bypass surgery were enrolled in this interventional, randomized, double-blinded study to compare HS-HES with saline solution. The study fluid (250 mL) was given into the venous reservoir of the CPB circuit at the time of aortic declamping. RESULTS: Body mass change from the baseline to the first postoperative morning was significantly less in the HS-HES group compared with the control group (3.3 ± 1.5 kg vs. 4.4 ± 1.5 kg, P = 0.022). In the extracellular water (ECW) or ECW-balance, there were no significant differences between the groups. The need for fluids and diuretic medication did not differ between the groups during the perioperative period. CONCLUSIONS: Our study shows that 250 mL of HS-HES solution can reduce perioperative fluid accumulation to some degree in patients undergoing CABG surgery with CPB.

Central wave reflection is associated with peripheral arterial resistance in addition to arterial stiffness in subjects without antihypertensive medication.

BACKGROUND: Augmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non-haemodynamic factors. METHODS: Background information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography. RESULTS: In a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (ß = 0.425, ß = 0.336), pulse wave velocity (ß = 0.409, ß = 0.400) (P < 0.001 for all), stroke volume (ß = 0.256, ß = 0.278) (P = 0.001 for both) and heart rate (ß = -0.150, ß = -0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (ß = 0.577, ß = 0.557) and systemic vascular resistance (ß = 0.437, ß = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman's correlation ≥0.617). CONCLUSION: Augmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01742702 .

Increased Cardiac Workload in the Upright Posture in Men: Noninvasive Hemodynamics in Men Versus Women.

BACKGROUND: Men and women differ in the risk of cardiovascular disease, but the underlying mechanisms are not completely understood. We examined possible sex-related differences in supine and upright cardiovascular regulation. METHODS AND RESULTS: Hemodynamics were recorded from 167 men and 167 women of matching age (≈45 years) and body mass index (≈26.5) during passive head-up tilt. None had diabetes mellitus or cardiovascular disease other than hypertension or used antihypertensive medication. Whole-body impedance cardiography, tonometric radial blood pressure, and heart rate variability were analyzed. Results were adjusted for height, smoking, alcohol intake, mean arterial pressure, plasma lipids, and glucose. Supine hemodynamic differences were minor: Men had lower heart rate (-4%) and higher stroke index (+7.5%) than women (P<0.05 for both). Upright systemic vascular resistance was lower (-10%), but stroke index (+15%), cardiac index (+16%), and left cardiac work were clearly higher (+20%) in men than in women (P<0.001 for all). Corresponding results were observed in a subgroup of men and postmenopausal women (n=76, aged >55 years). Heart rate variability analyses showed higher low:high frequency ratios in supine (P<0.001) and upright (P=0.003) positions in men. CONCLUSIONS: The foremost difference in cardiovascular regulation between sexes was higher upright hemodynamic workload for the heart in men, a finding not explained by known cardiovascular risk factors or hormonal differences before menopause. Heart rate variability analyses indicated higher sympathovagal balance in men regardless of body position. The deviations in upright hemodynamics could play a role in the differences in cardiovascular risk between men and women. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01742702.

The type of the functional cardiovascular response to upright posture is associated with arterial stiffness: a cross-sectional study in 470 volunteers.

BACKGROUND: In a cross-sectional study we examined whether the haemodynamic response to upright posture could be divided into different functional phenotypes, and whether the observed phenotypes were associated with known determinants of cardiovascular risk. METHODS: Volunteers (n = 470) without medication with cardiovascular effects were examined using radial pulse wave analysis, whole-body impedance cardiography, and heart rate variability analysis. Based on the passive head-up tilt induced changes in systemic vascular resistance and cardiac output, the principal determinants of blood pressure, a cluster analysis was performed. RESULTS: The haemodynamic response could be clustered into 3 categories: upright increase in vascular resistance and decrease in cardiac output were greatest in the first (+45 % and -27 %, respectively), smallest in the second (+2 % and -2 %, respectively), and intermediate (+22 % and -13 %, respectively) in the third group. These groups were named as 'constrictor' (n = 109), 'sustainer' (n = 222), and 'intermediate' (n = 139) phenotypes, respectively. The sustainers were characterized by male predominance, higher body mass index, blood pressure, and also by higher pulse wave velocity, an index of large arterial stiffness, than the other groups (p < 0.01 for all). Heart rate variability analysis showed higher supine and upright low frequency/high frequency (LF/HF) ratio in the sustainers than constrictors, indicating increased sympathovagal balance. Upright LF/HF ratio was also higher in the sustainer than intermediate group. In multivariate analysis, independent explanatory factors for higher pulse wave velocity were the sustainer (p < 0.022) and intermediate phenotypes (p < 0.046), age (p < 0.001), body mass index (p < 0.001), and hypertension (p < 0.001). CONCLUSIONS: The response to upright posture could be clustered to 3 functional phenotypes. The sustainer phenotype, with smallest upright decrease in cardiac output and highest sympathovagal balance, was independently associated with increased large arterial stiffness. These results indicate an association of the functional haemodynamic phenotype with an acknowledged marker of cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT01742702.

Prognostic capacity of a clinically indicated exercise test for cardiovascular mortality is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

BACKGROUND: Exercise capacity, heart rate recovery and T-wave alternans are independent predictors of cardiovascular mortality. We tested whether these parameters contain supplementary prognostic information. METHODS: A total of 3609 consecutive patients (2157 men) referred for a routine, clinically indicated bicycle exercise test were enrolled in the Finnish Cardiovascular Study (FINCAVAS). Exercise capacity was measured in metabolic equivalents, heart rate recovery as the decrease in heart rate from maximum to one minute post-exercise, and T-wave alternans by time-domain Modified Moving Average method. RESULTS: During 57-month median follow-up (interquartile range 35-78 months), 96 patients died of cardiovascular causes (primary endpoint) and 233 from any cause. All three parameters were independent predictors of cardiovascular mortality when analysed as continuous variables. Adding metabolic equivalents (p < 0.001), heart rate recovery (p = 0.002) or T-wave alternans (p = 0.01) to the linear model improved its predictive power for cardiovascular mortality. The combination of low exercise capacity (<6 metabolic equivalents), reduced heart rate recovery (≤12 beats/min) and elevated T-wave alternans (≥60 µV) yielded the highest hazard ratio for cardiovascular mortality of 16.5 (95% confidence interval 4.0-67.7, p < 0.001). Harrell's C index was 0.719 (confidence interval 0.665-0.772) for cardiovascular mortality with previously defined cutpoints (<8 units for metabolic equivalents, ≤18 beats/min for heart rate recovery and ≥60 µV for T-wave alternans). CONCLUSION: The prognostic capacity of the clinical exercise test is enhanced by combined analysis of exercise capacity, heart rate recovery and T-wave alternans.

Lower glomerular filtration rate is associated with higher systemic vascular resistance in patients without prevalent kidney disease.

The authors examined the association between estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation, and hemodynamics in 556 normotensive or never-treated hypertensive patients without kidney disease (mean age, 46 years). Hemodynamic variables were recorded using pulse wave analysis and whole-body impedance cardiography. The mean eGFR was 98 mL/min/1.73 m(2) (range, 64-145 mL/min/1.73 m(2) and one third of the patients had values below 92, while none had proteinuria. In linear regression analyses adjusted for differences in age, weight:height ratio, low-density lipoprotein cholesterol, and sex, significant associations were found between lower eGFR and higher systolic (P=.001) and diastolic blood pressure (P<.001) and higher systemic vascular resistance (P=.001). There was no association between eGFR and cardiac output or extracellular volume. In the absence of clinical kidney disease, lower eGFR was associated with higher blood pressure and systemic vascular resistance. Therefore, early impairment in kidney function may be involved in the pathogenesis of essential hypertension.

Daily liquorice consumption for two weeks increases augmentation index and central systolic and diastolic blood pressure.

BACKGROUND: Liquorice ingestion often elevates blood pressure, but the detailed haemodynamic alterations are unknown. We studied haemodynamic changes induced by liquorice consumption in 20 subjects versus 30 controls with average blood pressures of 120/68 and 116/64 mmHg, respectively. METHODS: Haemodynamic variables were measured in supine position before and after two weeks of liquorice consumption (daily glycyrrhizin dose 290-370 mg) with tonometric recording of radial blood pressure, pulse wave analysis, and whole-body impedance cardiography. Thirty age-matched healthy subjects maintaining their normal diet were studied as controls. RESULTS: Two weeks of liquorice ingestion elevated peripheral and central systolic and diastolic blood pressure (by 7/4 and 8/4 mmHg, 95% confidence intervals [CI] 2-11/1-8 and 3-13/1-8, respectively, P<0.05), and increased extracellular volume by 0.5 litres (P<0.05 versus controls). Also augmentation index adjusted to heart rate 75/min (from 7% to 11%, 95% CI for change 0.3-7.5, P<0.05) and aortic pulse pressure (by 4 mmHg, 95% CI 1-7, P<0.05) were elevated indicating increased wave reflection from the periphery. In contrast, peripheral (-3/-0.3 mmHg) and central blood pressure (-2/-0.5 mmHg), aortic pulse pressure (-1 mmHg), and augmentation index adjusted to heart rate 75/min (from 9% to 7%) decreased numerically but not statistically significantly without changes in extracellular volume in the control group. Heart rate, systemic vascular resistance, cardiac output, and pulse wave velocity did not differ between the groups. CONCLUSIONS: Two weeks of daily liquorice consumption increased extracellular volume, amplified pressure wave reflection from the periphery, and elevated central systolic and diastolic blood pressure. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT 2006-002065-39 ClinicalTrials.gov NCT01742702.

Association of resting heart rate with cardiovascular function: a cross-sectional study in 522 Finnish subjects.

BACKGROUND: High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt. METHODS: Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles. RESULTS: Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright. CONCLUSIONS: Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.

Metabolic syndrome may be associated with increased arterial stiffness even in the absence of hypertension: a study in 84 cases and 82 controls.

OBJECTIVE: To evaluate the hemodynamic characteristics of metabolic syndrome (MetS) in the absence and presence of hypertension. MATERIALS/METHODS: Altogether 166 subjects without previously diagnosed cardiovascular disease, diabetes, or antihypertensive medication, were allocated to four groups: control, hypertension only, MetS without hypertension, and MetS with hypertension (mean age 44-46 years). Cut-point for hypertension was blood pressure ≥140/90 mmHg. Other criteria of MetS were as defined by Alberti et al. 2009. Hemodynamic variables were measured using whole-body impedance cardiography and pulse wave analysis. RESULTS: Pulse wave velocity was higher in hypertensive and normotensive subjects with MetS than controls (p<0.05), and in the hypertensive MetS group than subjects with hypertension only (p<0.05). Aortic pulse pressure was higher in the two hypertensive groups than the two normotensive groups (p<0.05). Systemic vascular resistance index was higher in the hypertensive than normotensive MetS group (p<0.05), and in the group with hypertension alone than in controls (p<0.05). Heart rate was higher in the hypertensive Mets group than in controls and subjects with hypertension only (p<0.05). Cardiac index did not differ, while stroke index was lower in both groups with MetS than groups without MetS. Augmentation pressure was higher in the hypertensive MetS group than in controls and normotensive MetS group (p<0.05). CONCLUSIONS: Pulse wave velocity, an acknowledged marker of arterial stiffness, was associated with MetS even in the absence of hypertension. This emphasizes the importance of the prevention and treatment of MetS.

Hemodynamic alterations in hypertensive patients at rest and during passive head-up tilt.

OBJECTIVE: Hypertension is characterized by increased vascular resistance and arterial stiffness, but information about upright hemodynamics is scarce. We compared hemodynamics in hypertensive versus normotensive patients at rest and during passive head-up tilt. METHODS: Volunteers (n = 387, 19-72 years) without antihypertensive medication were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Seated office blood pressure was 4/10  mmHg (systolic/diastolic) higher than average supine values during hemodynamic measurements. As there is no accepted cut-off for hypertension during tilt-table tests, supine level at least 135/85  mmHg defined hypertension (n = 155) versus normotension (n = 232). Age, BMI, and proportion of men were higher among hypertensives (49 vs. 42 years, 28 vs. 25, 55 vs. 38%, respectively), and analyses were adjusted for these differences. RESULTS: Both at rest and during head-up tilt radial and aortic blood pressure and pulse pressure, cardiac index (CI) and work, systemic vascular resistance (SVR), and augmentation pressure were higher in hypertensive patients (P < 0.05 for all). Adjusted linear regression analyses showed that during passive head-up tilt aortic SBP and pulse pressure, stroke index, and left cardiac work index decreased less; heart rate increased less; and aortic DBP and SVR increased more in hypertensive patients (P < 0.05 for all); whereas reduction in CI and augmentation index did not differ between the groups. CONCLUSION: Not only supine hemodynamics, but also responses to head-up tilt differed between normotensive and hypertensive patients, indicating functional alterations beyond increased vascular resistance and higher arterial stiffness in hypertension.

Comparison of the effects of esomeprazole and fundoplication on airway responsiveness in patients with gastro-oesophageal reflux disease.

INTRODUCTION: Gastro-oesophageal reflux disease (GORD) is suggested to cause or aggravate several respiratory conditions. Studies with proton pump inhibitors have resulted in only minor improvements in pulmonary outcomes in patients with GORD. It has been speculated that operative treatment of GORD might be more efficient as it also diminishes non-acidic reflux. OBJECTIVES: To compare the effects of esomeprazole 40 mg bid and fundoplication on airway responsiveness, forced expiratory volume in 1 s (FEV1), exhaled nitric oxide (NO) and respiratory symptoms in patients with moderate-to-severe GORD. METHODS: Sixty-nine GORD patients had methacholine inhalation challenge performed on them, and FEV1, exhaled NO and respiratory symptoms were measured at baseline, after a 3-month treatment with esomeprazole and 3 months after fundoplication. Primary outcome variable was dose-response slope (DRS), i.e. decline in FEV1 during methacholine challenge divided with the amount of methacholine administered (%/µmol). Pre-defined subgroup analysis was performed among those with concomitant asthma (n = 12). RESULTS: There was no improvement in DRS, FEV1 or exhaled NO after esomeprazole treatment or fundoplication. Cough and dyspnoea measured with visual analog scale improved with esomeprazole treatment (P < 0.001), and further after fundoplication (P < 0.001). Among those with concomitant asthma, significant improvements in St George Respiratory Questionnaire (SGRQ) scores could be seen after fundoplication. CONCLUSIONS: Neither esomeprazole treatment nor fundoplication diminishes airway responsiveness or exhaled NO, or improves FEV1 in patients with GORD. Improvements in respiratory symptoms and SGRQ scores after GORD treatments could be detected. However, as this was not a placebo-controlled study, the findings in these secondary endpoints should not be emphasised. ClinicalTrials.cov: NCT00994708.

Supine and upright haemodynamic effects of sublingual nitroglycerin and inhaled salbutamol: a double-blind, placebo-controlled, randomized study.

OBJECTIVES: Pulse wave analysis is widely applied to measure the haemodynamic effects of nitroglycerin and salbutamol as an endothelium-independent and endothelium-dependent vasodilator, respectively. The recordings are usually performed in supine position from 10 to 20 successive heartbeats without simultaneous measurement of vascular resistance and cardiac function. Our objective was to examine the effects of nitroglycerin and salbutamol on central haemodynamics, arterial stiffness, cardiac function, and vascular resistance in supine and upright positions. METHODS: A placebo-controlled, randomized and double-blinded passive head-up tilt protocol was performed after sublingual nitroglycerin (0.25 mg) or inhaled salbutamol (400 µg) in 35 healthy volunteers. Continuous tonometric pulse wave analysis, whole-body impedance cardiography, and plethysmographic finger blood pressure recordings were applied. RESULTS: Nitroglycerin decreased aortic and finger blood pressure, radial DBP, vascular resistance, augmentation index and pulse wave velocity, and increased heart rate, cardiac index, stroke index and aortic reflection time (P < 0.030 for all). Salbutamol moderately decreased radial and aortic blood pressure and finger DBP, augmentation index and vascular resistance, but increased heart rate and cardiac index (P < 0.030 for all). Almost all of the strong haemodynamic effects of nitroglycerin were emphasized during the head-up tilt, whereas the effects of salbutamol on heart rate and cardiac index were more pronounced in the supine position. CONCLUSION: The haemodynamic changes induced by nitroglycerin and salbutamol were dependent on body position: the effects of nitroglycerin were accentuated during the head-up tilt, whereas those of salbutamol were more evident in the supine position.

Allelic variant of NOS1AP effects on cardiac alternans of repolarization during exercise testing.

INTRODUCTION: A repolarization abnormality manifested as T-wave alternans (TWA) in electrocardiogram (ECG) predicts cardiovascular mortality. A common variant in the NOS1AP gene is associated with mortality and QT interval duration, possibly in a gender-specific manner, but data is lacking on potential association with TWA. This study tested association between rs10494366 in NOS1AP and both TWA and 4-year mortality. MATERIAL AND METHODS: A total of 1963 Finnish Cardiovascular Study participants (36.6% female, 57.1 ± 13.0 years) were genotyped and their maximal TWA values were measured from continuous ECG recordings during clinical exercise test at rest, exercise and recovery. RESULTS: We observed a significant gender-specific effect of NOS1AP genotype on TWA. In all subjects, there was no statistically significant difference between the three genotypes (TT, TG, GG) in the responses of TWA over the entire exercise test (time-by-genotype interaction p = 0.057). In women, after adjustment for age, coronary heart disease and ß-blocker medication status, changes of TWA over different phases of exercise test were significantly associated with NOS1AP genotype (time-by-genotype interaction p = 0.001). In men, NOS1AP rs10494366 was not associated with TWA. During follow-up (mean 47 months), 113 patients died. NOS1AP rs10494366 was not a statistically significant predictor of mortality. CONCLUSION: The NOSIAP variant rs10494366 influences TWA and TWA response during clinical exercise test in females. Gender-specific effects have also been previously reported for the influence of the variant on QT interval. If replicated, these findings should prompt studies to further elucidate the mechanisms underlying the gender differences in NOS1AP effects on repolarization.

Arterial tension time reflects subclinical atherosclerosis, arterial stiffness and stroke volume.

OBJECTIVE: To introduce and evaluate a new haemodynamic parameter known as arterial tension time (ATT) and study whether ATT is associated with traditional cardiovascular risk factors as well as with indices of arterial stiffness, cardiac pump function and subclinical atherosclerosis. METHODS: Arterial tension time was measured from the whole-body impedance cardiography (ICG) signal and defined as the time difference between the onset of arterial distension induced by stroke volume (SV) and maximal integrated arterial distension. As measures of subclinical atherosclerosis and arterial stiffness, carotid artery intima-media thickness (IMT), Young's elastic modulus (YEM), arterial stiffness index (ASI) and carotid artery compliance (CAC) were assessed with ultrasound in 336 Finnish adults (aged 46-76 years, 43·2% men) participating in the Health 2000 Survey. In addition, pulse wave velocity (PWV) and stroke volume index (SI), as indices of arterial stiffness and cardiac pump function, were assessed with ICG. RESULTS: Arterial tension time was associated inversely with PWV, IMT, YEM and ASI (P<0·002 for all) and directly with SI and CAC (P<0·001 for both). Age, systolic blood pressure, diastolic blood pressure and fasting glucose were independent determinants of decreased ATT (P<0·04 for all). Moreover, accumulation of cardiovascular risk factors was associated with the decrease in ATT (P for trend <0·001). CONCLUSION: Decreased ATT was associated with increased arterial stiffness, increased subclinical atherosclerosis and decreased SV. Current results suggest that ATT provides simultaneous information on several aspects of cardiovascular structure and function and could possibly serve as a new integrated parameter for cardiovascular risk stratification.

Metabolic syndrome in childhood and increased arterial stiffness in adulthood: the Cardiovascular Risk In Young Finns Study.

OBJECTIVE. We conducted the present study to examine the associations of two different paediatric metabolic syndrome (MetS) definitions and recovery from childhood MetS with arterial pulse wave velocity (PWV), an index of arterial stiffness, measured in adulthood. METHODS. A total of 945 subjects participated in the base-line study in 1986 (then aged 9-18 years) and the adult follow-up in 2007 (then aged 30-39 years). Cardiovascular risk factor data were available at both base-line and follow-up. In the follow-up study, arterial PWV was measured using a whole-body impedance cardiography device. RESULTS. Subjects suffering from MetS in childhood (prevalence 11.1%-14.1%) had higher arterial PWV after 21-year follow-up when compared with those not afflicted by the syndrome in childhood (P < 0.007). An increasing number of the MetS components in childhood were associated with increased PWV in adulthood (P for trend = 0.005). Subjects who recovered from the MetS during the 21-year follow-up period had lower PWV than those with persistent MetS (P < 0.001). CONCLUSION. MetS in childhood predicted increased arterial stiffness in adulthood, and recovery from childhood MetS was associated with decreased arterial PWV in adulthood. The current results emphasize the importance of the prevention and controlling of MetS risk factors both in childhood and adulthood.

Early treatment response evaluation in patients with diffuse large B-cell lymphoma--a pilot study comparing volumetric MRI and PET/CT.

PURPOSE: The purpose of this study is to evaluate the time course of early chemotherapy response in patients with aggressive non-Hodgkin's lymphoma (NHL) by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). PROCEDURES: Eight patients with histologically proven aggressive NHL were imaged by MRI and PET/CT before treatment (E1), 1 week (E2), and two cycles (E3) after chemotherapy. RESULTS: The mean tumor volume on MRI was 276 mL at baseline; it decreased 58% at E2 (p < 0.05) and 65% further at E3 (p < 0.05), giving a total decrease of 84% (p < 0.05). All the imaged pre-therapy tumors were strongly positive on PET/CT, with a mean maximum standardized uptake value (SUV(max)) of 20. The SUV(max) decreased 60% at E2 (p < 0.05) and 59% further at E3 (p < 0.05), giving a total decrease of 83% (p < 0.05). The active tumor burden (mean 229 mL) decreased 66% at E2 (p < 0.05). The tumor volume on MRI correlated with the active tumor volume on fused PET/CT images in the same region of interest at both E1 and E2 (r = 0.88, p < 0.01, respectively). CONCLUSIONS: Standard chemotherapy causes rapid decrease of both tumor metabolic activity and volume as early as 1 week, which continues to decline during therapy. Both volumetric MRI and PET/CT are valuable tools for early treatment response evaluation of aggressive NHL.

Reduced systemic vascular resistance in healthy volunteers with presyncopal symptoms during a nitrate-stimulated tilt-table test.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Nitrates may facilitate syncope through various pathways, but the precise mechanism of nitrate-induced syncope is still under debate. The purpose of the present study was to compare the underlying haemodynamic mechanisms in subjects without and with presyncopal symptoms during a nitroglycerin-stimulated tilt-table test. WHAT THIS STUDY ADDS: A major decrease in systemic vascular resistance was documented in subjects with presyncope during 0.25 mg nitroglycerin-stimulated tilt-table test, in the absence of changes in cardiac output. These findings indicated that even a small dose of nitroglycerin significantly decreased arterial resistance and cardiac afterload. AIMS The mechanism of nitrate-induced syncope remains controversial. We examined the haemodynamic changes in healthy volunteers during nitroglycerin-stimulated tilt-table test. METHODS: Continuous radial pulse wave analysis, whole-body impedance cardiography and plethysmographic finger blood pressure were recorded in a supine position and during head-up tilt in 21 subjects with presyncopal symptoms (6 male/15 female, age 43 ± 3 years) after 0.25 mg sublingual nitroglycerin and 21 control subjects (6 male/15 female, age 43 ± 2 years). The drug was administered in the supine position and a passive head-up tilt followed 5 min later. Additionally, nitroglycerin was only administered during head-up tilt in 19 subjects and the haemodynamics were recorded. RESULTS: Supine and upright haemodynamics were similar before nitroglycerin administration in the two groups. During the nitroglycerin-stimulated tilt test, aortic and radial mean blood pressure decreased significantly more in the presyncope group when compared with the controls (P= 0.0006 and P= 0.0004, respectively). The decreases in systemic vascular resistance (P= 0.0008) and heart rate (P= 0.002), and increase in aortic reflection time (P= 0.0002) were greater in the presyncope group, while the change in cardiac index was not different between the groups (P= 0.14). If nitroglycerin was administered during the upright tilt and not in supine position, the haemodynamic changes were quite corresponding. CONCLUSIONS: Presyncopal symptoms during nitrate-stimulated tilt test were explained by decreased systemic vascular resistance and increased aortic reflection time, while cardiac output remained unchanged. These findings indicated reduced arterial resistance in nitroglycerin-induced presyncope.

Importance of regional specificity of T-wave alternans in assessing risk for cardiovascular mortality and sudden cardiac death during routine exercise testing.

BACKGROUND: T-wave alternans (TWA) indicates increased risk for life-threatening arrhythmias. However, the regional distribution and predictivity of TWA among precordial leads remain unknown. OBJECTIVE: We analyzed the magnitude and prognostic power of TWA in precordial leads separately and in combination during routine exercise stress testing in the largest TWA study conducted to date. METHODS: The Finnish Cardiovascular Study (FINCAVAS) enrolled consecutive patients (n = 3,598, 56 ± 13 [mean ± standard deviation] years old, 2,164 men, 1,434 women) with a clinically indicated exercise test with bicycle ergometer. TWA was analyzed with the time-domain modified moving average method. RESULTS: During a follow-up of 55 months (interquartile range of 35-78 months), 231 patients died; 97 deaths were cardiovascular, and 46 were classified as sudden cardiac deaths (SCDs). In Cox analysis after adjustment for common coronary risk factors, each 20-µV increase in TWA in leads V1-V6 multiplied the hazard ratio for cardiovascular mortality by 1.486-fold (95% confidence interval [CI] 1.127-1.952; P = .005). Each 20-µV increase in TWA in lead V5 amplified the hazard ratio for cardiovascular mortality by 1.545 (95% CI 1.150-2.108; P = .004) and for SCD by 1.576 (95% CI 1.041-2.412; P = .033). CONCLUSIONS: Maximum TWA monitored from anterolateral precordial lead V5 is the strongest predictor of cardiovascular mortality and SCD during routine exercise testing in our analysis. Higher TWA values indicate greater cardiovascular mortality and SCD risk, supporting the concept that quantification of TWA should receive more attention.

Systemic hemodynamics in relation to glucose tolerance: the Health 2000 Survey.

The influence of impaired glucose metabolism--that is, impaired fasting glucose, impaired glucose tolerance (IGT), and type 2 diabetes mellitus diabetes (DM2)--on systemic hemodynamics is largely unknown. Therefore, we investigated the associations of glucose metabolism disturbances with stroke index (SI), cardiac index, systemic vascular resistance index (SVRI), arterial pulse wave velocity (PWV), and heart rate among Finnish adults (N = 389; mean age, 58.3 ± 7.9 years) participating in the Health 2000 Survey. Systemic hemodynamic parameters were measured using the whole-body impedance cardiography device, and an oral glucose tolerance test (OGTT) was performed to evaluate glucose tolerance status. We found a decreasing trend for SI and increasing trends for SVRI and PWV according to the worsening of glucose tolerance (P for trend < .003 for all). In pairwise comparisons, SI was lower in the impaired fasting glucose group (P = .041) and the IGT group (P < .001) as compared with the normal glucose tolerance (NGT) group. Systemic vascular resistance index was higher in the IGT group (P = .045) and the DM2 group (P = .043) than in the NGT group. Subjects with IGT or DM2 had higher arterial PWV (10.7 ± 0.2 m/s, P < .001 and 11.7 ± 0.5 m/s, P = .001, respectively) than subjects with NGT (9.5 ± 0.1 m/s). Moreover, 2-hour glucose in OGTT was an independent determinant of SVRI and PWV (P < .001 and P = .005, respectively) in multivariable linear regression models. In conclusion, the present study demonstrates that glucose intolerance, even without DM2, associates with several adverse changes in systemic hemodynamics and that 2-hour glucose in OGTT is an independent determinant of SVRI and PWV. These findings support the systematic evaluation of glucose tolerance status in the estimation of cardiovascular risk among the middle-aged population.