Lower left atrial function in young individuals with type 1 diabetes mellitus compared to healthy controls: an echocardiographic study.

In adulthood, individuals with type 1 diabetes mellitus may develop a condition of heart failure with preserved ejection fraction. However, subclinical changes to the heart in diabetes are likely to occur prior to the clinical presentation. This cross-sectional study aimed to compare left atrial function by echocardiography between 43 individuals with type 1 diabetes and 43 healthy controls, aged 10-30 years. All participants underwent echocardiography and 2D speckle tracking measurements for left atrial phase function parameters. Physical capacity was assessed by exercise test on a bicycle. Results showed that participants with type 1 diabetes had significantly lower left atrial function parameters than healthy controls (p < 0.05). There was a significant negative correlation between HbA1c means and reservoir and conduit strain (p < 0.05) and individuals with BMI < 30 showed a lower left atrial stiffness (p < 0.05). Individuals with type 1 diabetes and a higher physical capacity did not differ from their healthy peers. Results indicate that lower HbA1c levels, BMI < 30 and a higher physical capacity are favourable in terms of left atrial function in children and young adults with type 1 diabetes mellitus. Left atrial strain by echocardiography might become a new important tool in assessing heart function in T1DM.

Mind body exercise improves cognitive function more than aerobic- and resistance exercise in healthy adults aged 55 years and older - an umbrella review.

Exercise is often cited as a major factor contributing to improved cognitive functioning. As a result, the relationship between exercise and cognition has received much attention in scholarly literature. Systematic reviews and meta-analyses present varying and sometimes conflicting results about the extent to which exercise can influence cognition. The aim of this umbrella review was to summarize the effects of physical exercise on cognitive functions (global cognition, executive function, memory, attention, or processing speed) in healthy adults ≥ 55 years of age.Methods An umbrella review of systematic reviews with meta-analyses investigating the effect of exercise on cognition was performed. Databases (CINAHL, Cochrane Library, MEDLINE, PsycInfo, Scopus, and Web of Science) were searched from inception until June 2023 for reviews of randomized or non-randomised controlled trials. Full-text articles meeting the inclusion criteria were reviewed and methodological quality assessed. Overlap within included reviews was assessed using the corrected covered area method (CCA). A random effects model was used to calculate overall pooled effect size with sub-analyses for specific cognitive domains, exercise type and timing of exercise.Results Database searches identified 9227 reviews. A total of 20 met the inclusion criteria. They were based on 332 original primary studies. Overall quality of the reviews was considered moderate with most meeting 8 or more of the 16 AMSTAR 2 categories. Overall pooled effects indicated that exercise in general has a small positive effect on cognition (d = 0.22; SE = 0.04; p < 0.01). Mind-body exercise had the greatest effect with a pooled effect size of (d = 0.48; SE = 0.06; p < 0.001). Exercise had a moderate positive effect on global cognition (d = 0.43; SE = 0,11; p < 0,001) and a small positive effect on executive function, memory, attention, and processing speed. Chronic exercise was more effective than acute exercise. Variation across studies due to heterogeneity was considered very high.Conclusions Mind-body exercise has moderate positive effects on the cognitive function of people aged 55 or older. To promote healthy aging, mind-body exercise should be used over a prolonged period to complement other types of exercise. Results of this review should be used to inform the development of guidelines to promote healthy aging.Trial registration PROSPERO (CDR 42022312955).

No differences in FBN1 genotype between men with and without abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an aortic enlargement in which the transverse diameter reaches at least 30 mm. Certain risk factors, such as age, male gender, and smoking, are well known; however, less is known about the genetic factors involved. Fibrillin-1 (FBN1) is a protein that coordinates the deposition of elastin fibres in the extracellular matrix and is therefore likely to affect the elastic properties in the aortic wall. Previously studies have found associations between the FBN1-2/3 genotype and arterial stiffness, but how different FBN1 genotypes, AAA, and arterial stiffness are related has been less frequently investigated. AIM: This study aimed to investigate whether there is a difference in FBN1 genotype between men with and without AAA. A further aim was to study whether the FBN1 genotype affects arterial wall stiffness differently in men with and without AAA. METHODS: Pulse wave velocity and FBN1 genotyping were performed in 229 men (159 with AAA, 70 without AAA). Participants were recruited from ultrasound AAA surveillance programs or ongoing ultrasound screening programs from 2011 to 2016. RESULTS: The distribution of the FBN1 genotype in the AAA and control groups were as follows: FBN1-2/2: 62% vs. 64%; FBN1-2/3: 8% vs. 14%; and FBN1-2/4: 30% vs. 21%, respectively. Men with AAA and FBN1-2/2 had increased central pulse wave velocity (p < 0.005) compared to the control group (those without AAA) with the FBN1-2/2 genotype. CONCLUSION: No differences were found with respect to FBN1 genotypes between men with and without AAA. The development of AAA in men does not appear to be linked to a specific FBN1 genotype. Nevertheless, men with FBN1-2/2 and AAA have increased central arterial stiffness compared to men with the same FBN1 genotype but without AAA.

Characterization of methylation patterns associated with lifestyle factors and vitamin D supplementation in a healthy elderly cohort from Southwest Sweden.

Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D3 can be monitored.

Association of IL-10 and CRP with Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm.

BACKGROUND: Markers of inflammation and arterial stiffness are predictors of cardiovascular morbidity and events, but their roles in the mechanisms and progression of abdominal aortic aneurysm (AAA) in males have not been fully investigated. This study explored possible associations between inflammatory marker levels and arterial stiffness in males with AAA. METHODS: A total of 270 males (191 AAA and 79 controls) were included in the study. Arterial stiffness was assessed using non-invasive applanation tonometry to measure the regional pulse wave velocity between the carotid and femoral arteries and the carotid and radial arteries. Blood samples were obtained, and interleukin-10 (IL-10) and CRP levels were analysed. RESULTS: Subjects with an AAA had higher levels of IL-10 (21.5 ± 14.0 ng/mL versus 16.6 ± 9.3 ng/mL) compared to controls (p = 0.007). In the AAA cohort, subjects with T2DM showed higher levels of IL-10 (26.4 ± 17.3 versus 20.4 ± 13.0, p = 0.036). We observed a positive correlation between PWVcf and CRP in the control group (r = 0.332) but not the AAA group. PWVcf and CRP were negatively correlated (r = 0.571) in the T2DM subjects treated with metformin in the AAA group. CONCLUSION: Arterial stiffness is related to the degree of inflammation reflected by CRP and IL-10 levels in males with an AAA. IL-10 is negatively correlated with arterial stiffness in these subjects. This finding suggests that IL-10 may decrease arterial stiffness in males with AAA. The negative correlation between CRP and PWVcf in males with T2DM treated with metformin may indicate that metformin influences the arterial wall to decrease stiffness in subjects with AAA.

Males with abdominal aortic aneurysm have reduced left ventricular systolic and diastolic function.

BACKGROUND: Abdominal aortic aneurysm (AAA) increases the risk of chronic heart failure and other major cardiovascular events. Knowledge about left ventricular function in patients with AAA is lacking. This echocardiographic study aimed to investigate whether AAA is associated with left ventricular systolic and diastolic dysfunction. METHODS: Echocardiography was performed in 307 males (199 AAA and 108 controls) recruited from a regional ultrasound surveillance programme of known AAA, or from an ongoing ultrasound screening programme, during 2011-2016. RESULTS: Subjects with AAA had thicker septal and posterior walls and a reduced left ventricular function compared to controls. Left ventricular ejection fraction (AAA 55 ± 8%, controls 57 ± 7%) and global longitudinal strain (AAA 19 ± 3%, controls 20 ± 3%) were lower in the group with AAA (both p < 0·05). Moreover, decreased mitral annular plane systolic excursion (12 ± 2 mm versus 13 ± 2 mm) and higher E/e' (13 ± 5 versus 11 ± 4) were observed in subjects with AAA (both p < 0·05). The aortic sinus (38 ± 4 mm versus 35 ± 2 mm) and ascending aorta (36 ± 4 mm versus 34 ± 5 mm) were also wider in the AAA group compared to controls (both p < 0·01). CONCLUSION: AAAs are associated with reduced left ventricular systolic and diastolic function in males. The larger diameter of the aortic sinus and ascending aorta among AAA patients suggests that AAA is a general aortic disease.

Increased arterial stiffness in males with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA), a localized dilatation of the abdominal aorta, has a prevalence of about 1.5%-3% among 65- to 70-year-old males in Europe. AAA confers an increased risk of developing major cardiovascular events in addition to the risk of aneurysm rupture. The aim of this study was to evaluate whether the arterial wall distensibility is altered in subjects with AAA. METHODS: Two hundred and eighty-four male subjects (182 with AAA and 102 controls) were enrolled in the study. Arterial wall distensibility was evaluated using non-invasive applanation tonometry to measure regional pulse wave velocity between the carotid and femoral arteries and the carotid and radial arteries. In addition, blood pressure was measured, and the pulse pressure waveform was analysed. RESULTS: Higher aortic augmentation index (25.1% versus 20.6%; p < .001) and higher aortic pulse wave velocity (12.3 m/s versus 10.9 m/s; p < .001) were demonstrated in the AAA cohort. The slightly higher arm pulse wave velocity in the AAA group (9.4 m/s versus 9.1 m/s; p < .05) was abolished after adjusting for mean arterial blood pressure. CONCLUSIONS: Males with AAA have decreased aortic wall distensibility and enhanced reflection waves in central aorta during systole. These results imply that increased arterial wall stiffness may be a contributing factor to the overall higher cardiovascular risk seen in patients with AAA.

Assessing heart rate variability in type 1 diabetes mellitus-Psychosocial stress a possible confounder.

BACKGROUND: Autonomic neuropathy (AN) commonly arises as a long-term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context. METHODS: A total of 167 individuals 6-60 years old (113 with T1DM and 54 healthy controls) underwent 24-hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary. RESULTS: Heart rate variability (high-frequency power during sleep) was reduced (p < .05) with older age, longer diabetes duration, higher mean glucose levels, physical inactivity, and perceived psychosocial stress. Salivary cortisol levels in the evening were increased (p < .05) in women in ovulation phase, in individuals with preceding hypoglycemia or with hyperglycemia. The amplitude of salivary cortisol was reduced (p < .05) with the presence of perceived psychosocial stress, but only in adult healthy controls, not in individuals with diabetes. CONCLUSION: Psychosocial stress might be a confounder for reduced HRV when diagnosing cardiac AN in T1DM. Salivary cortisol is, however, not a useful biomarker for psychosocial stress in diabetes since the physiological stress of both hypoglycemia and hyperglycemia seems to overrule the effect of psychosocial stress on cortisol.

Higher blood pressure in elderly hypertensive females, with increased arterial stiffness and blood pressure in females with the Fibrillin-1 2/3 genotype.

BACKGROUND: Elderly patients have a relatively high cardiovascular risk due to increased arterial stiffness, elevated blood pressure and decreased amounts of elastin in the arteries. The composition of the media layer in the arterial wall, comprising elastin, collagen, smooth muscle cells, proteoglycans, fibronectin and fibrillin-1, influences its mechanical properties. Mutations in the fibrillin-1 gene leads to increased aortic stiffness, elevated pulse pressure and aortic root dilatation. This study investigates whether there is a sex difference among hypertensive elderly patients regarding blood pressure, arterial stiffness and fibrillin-1 genotypes. METHODS: A total of 315 hypertensive subjects (systolic blood pressure > 140 mmHg) were included in this study (155 men and 160 women aged 71-88 years). Aortic pulse wave velocity and augmentation index were determined using SphygmoCor, and brachial blood pressure was measured using an oscillometric technique. Fibrillin-1 was genotyped by polymerase chain reaction and with a capillary electrophoresis system. RESULTS: Females showed a significantly higher peripheral mean arterial pressure (females; 107.20 mmHg, males 101.6 mmHg, p = 0.008), central mean arterial pressure (females; 107.2 mmHg, males 101.6 mmHg p = 0.008), central systolic blood pressure (females; 148.1 mmHg, males 139.2 mmHg, p <  0.001) and central pulse pressure (females; 68.9 mmHg, males 61.6 mmHg, p = 0.035) than males. Females with the Fibrillin-1 2/3 genotype showed a significantly higher augmentation index (FBN1 2/3; 39.9%, FBN1 2/2 35.0%, FBN1 2/4 35.8, p = 0.029) and systolic blood pressure (FBN1 2/3; 174.6 mmHg, FBN1 2/2168.9 mmHg, FBN1 2/4169.9 mmHg, p = 0.025) than females with the 2/2 and 2/4 genotypes. CONCLUSION: The findings of this study may indicate that hypertensive elderly females, especially elderly females with Fibrillin-1 2/3, have increased systolic blood pressure and arterial stiffness.

Resting Level of Insulin-Like Growth Factor-1 Is Not at Play in Cardiac Enlargement in Endurance-Trained Adolescents.

PURPOSE: The study aimed to investigate resting levels of several selected growth and metabolic hormones in a group of 24 endurance-trained adolescents (aged 13-19 years) compared with 24 untrained age- and sex-matched controls, and to investigate if increased cardiac dimensions were related to these hormones at rest with emphasis on insulin-like growth factor-1 (IGF-1). METHODS: The hormones (cortisol, IGF-1, IGF-2, follicle-stimulating hormone, growth hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone) were analysed with chemiluminescence microparticle immunoassay (CMIA) or multiplex fluorochrome (Luminex) technique. Cardiac dimensions were assessed by echocardiographic examination at rest. Peak oxygen uptake was obtained by a maximal cardiopulmonary exercise test on a treadmill. RESULTS: Circulating levels of analysed hormones at rest did not differ between the groups. A correlation was found between increased cardiac dimensions and IGF-1 in the controls, but not in the active group. This correlation declined also among the controls when the cardiac parameters were indexed for body surface area. CONCLUSION: Increased cardiac dimensions in endurance-trained adolescents could not be related to resting levels of hormones associated with growth and metabolism, including IGF-1 and GH. In addition, the resting levels of these hormones seem not to be affected by intense regular endurance exercise in adolescents. These findings may contribute to the knowledge about cellular signaling that trigger growth as well as cardiac adaptation to endurance training in young athletes.

Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain.

AIMS: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. METHODS: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight < 25 kg/m2, overweight 25-29 kg/m2, and obesity ≥ 30 kg/m2). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. RESULTS: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/é (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05). Corresponding results in the control group were 58% (6%) vs. - 22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p < 0.05 vs. p < 0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n = 187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n = 179) (p < 0.05). CONCLUSION: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons. Trial registration ClinicalTrials.gov identifier NCT 01049737.

Left ventricular diastolic function is enhanced after peak exercise in endurance-trained adolescents as well as in their non-trained controls.

The aims of the study were to explore the temporal change of cardiac function after peak exercise in adolescents, and to investigate how these functional changes relate to maximal oxygen uptake (VO2max ). The cohort consisted of 27 endurance-trained adolescents aged 13-19 years, and 27 controls individually matched by age and gender. Standard echocardiography and colour tissue Doppler were performed at rest, and immediately after as well as 15 min after a maximal cardio pulmonary exercise test (CPET) on a treadmill. The changes in systolic and diastolic parameters after exercise compared to baseline were similar in both groups. The septal E/e'-ratio increased immediately after exercise in both the active and the control groups (from 9·2 to 11·0; P<0·001, and from 8·7 to 10·2; P = 0·008, respectively). In a comparison between the two groups after CPET, the septal E/e'-ratio was higher in the active group both immediately after exercise and 15 min later compared to the control group (P = 0·007 and P = 0·006, respectively). We demonstrated a positive correlation between VO2max and cardiac function including LVEF and E/e' immediately after CPET, but the strongest correlation was found between VO2max and LVEDV (r = 0·67, P<0·001) as well as septal E/e' (r = 0·34, P = 0·013). Enhanced diastolic function was found in both groups, but this was more pronounced in active adolescents. The cardiac functional response to exercise, in terms of LVEF and E/e', correlates with the increase in VO2 uptake. These findings in trained as well as un-trained teenagers have practical implications when assessing cardiac function.

Regular endurance training in adolescents impacts atrial and ventricular size and function.

AIMS: The aims of the study were to explore the effects of long-term endurance exercise on atrial and ventricular size and function in adolescents and to examine whether these changes are related to maximal oxygen uptake (VO2max). METHODS AND RESULTS: Twenty-seven long-term endurance-trained adolescents aged 13-19 years were individually matched by age and gender with 27 controls. All participants, 22 girls and 32 boys, underwent an echocardiographic examination at rest, including standard and colour tissue Doppler investigation. VO2max was assessed during treadmill exercise. All heart dimensions indexed for body size were larger in the physically active group compared with controls: left ventricular end-diastolic volume 60 vs. 50 mL/m2 (P <0.001), left atrial volume 27 vs. 19 mL/m2 (P < 0.001), and right ventricular (RV) and right atrial area 15 vs. 13 and 9 vs. 7 cm2/m2, respectively (P <0.001 for both). There were strong associations between the size of the cardiac chambers and VO2max. Further, we found improved systolic function in the active group compared with controls: left ventricular ejection fraction 61 vs. 59% (P= 0.036), tricuspid annular plane systolic excursion 12 vs. 10 mm/m2 (P= 0.008), and RV early peak systolic velocity s' 11 vs. 10 cm/s (P = 0.031). CONCLUSION: Cardiac remodelling to long-term endurance exercise in adolescents is manifested by an increase in atrial as well as ventricular dimensions. The physically active group also demonstrated functional remodelling with an increase in TAPSE and systolic RV wall velocity. These findings have practical implications when assessing cardiac enlargement and function in physically active youngsters.

Left ventricular diastolic function, assessed by echocardiography and tissue Doppler imaging, is a strong predictor of cardiovascular events, superior to global left ventricular longitudinal strain, in patients with type 2 diabetes.

AIMS: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2. METHODS AND RESULTS: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 ± 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' ≤15, P = 0.011. CONCLUSION: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.

Serum lysozyme - a surrogate marker of pulmonary microvascular injury in smokers?

Progression rate of disease processes in smoke-induced lung injuries varies greatly. Diverse pathophysiological mechanisms may trigger these divergences. The aim of this study was to evaluate whether circulating markers of monocytes/macrophages and/or neutrophil [i.e. lysozyme (LZM) or myeloperoxidase (MPO)] were associated with reduced values of diffusion capacity (DL,CO), which is considered to serve as a mirror of pulmonary microvascular derangement and an early sign of tissue remodelling in smokers. Data obtained from 134 smokers (GOLD stage ≤1) and 24 matched healthy non-smoking volunteers were evaluated in a cross-sectional study design. Lung function tests as well as single breath test of DL,CO were assessed according to ATS/ERS guidelines. Biomarkers were measured in serum by means of sensitive immunoassays. A subgroup of smokers with normal lung function was created to minimize confounding, by excluding datasets showing significant airflow limitation and abnormally high values of carboxy haemoglobin (COHb), the latter indicating recent smoking. The capacity of serum lysozyme to correctly identify abnormally low values of DL,CO (i.e. <1·9SD units), tended to be higher than that of Myeloperoxidase as assessed by analyses of receiver operated curves (ROC; AUC 0·81, 95%CI: 0·69-0·89 versus AUC 0·67, 95%CI: 0·60-0·81). It is concluded that serum levels of lysozyme, reflecting mainly activated monocytes/macrophages but also neutrophils, were significantly associated with isolated decrements of DL,CO in smokers with normal lung function tests. This suggests monocytes/macrophages to have a significant mechanistic role in early phases of the disease process and/or pulmonary microvascular damage.

Bronchial responsiveness to dry air hyperventilation in smokers may predict decline in airway status using indirect methods.

BACKGROUND: Disabling respiratory symptoms and rapid decline of lung function may occur in susceptible tobacco smokers. Bronchial hyperresponsiveness (BHR) elicited by direct challenge methods predicts worse lung function outcomes. The aim of this study was to evaluate whether BHR to isocapnic hyperventilation of dry air (IHDA) was associated with rapid deterioration in airway status and respiratory symptoms. METHODS: One hundred twenty-eight smokers and 26 age- and sex-matched healthy individuals with no history of smoking were investigated. All subjects completed a questionnaire. Spirometry and impulse oscillometry (IOS) measurements were recorded before and after 4 min of IHDA. The tests were repeated after 3 years in 102 smokers and 11 controls. RESULTS: Eighty-five smokers (66 %) responded to the challenge with a ≥2.4-Hz increase in resonant frequency (F res), the cutoff limit defining BHR, as recorded by IOS. They had higher F res at baseline compared to nonresponding smokers [12.8 ± 3.2 vs. 11.5 ± 3.4 Hz (p < 0.05)] and lower FEV1 [83 ± 13 vs. 89 ± 13 % predicted (p < 0.05)]. Multivariable logistic regression analysis indicated that wheezing (odds ratio = 3.7, p < 0.01) and coughing (odds ratio = 8.1, p < 0.05) were significantly associated with hyperresponsiveness. An increase in F res was recorded after 3 years in responding smokers but not in nonresponders or controls. The difference remained when subjects with COPD were excluded. CONCLUSIONS: The proportion of hyperresponsive smokers was unexpectedly high and there was a close association between wheezing and coughing and BHR. Only BHR could discriminate smokers with rapid deterioration of airway status from others.

Fibroblast growth factor 10 haploinsufficiency causes chronic obstructive pulmonary disease.

BACKGROUND: Genetic factors influencing lung function may predispose to chronic obstructive pulmonary disease (COPD). The fibroblast growth factor 10 (FGF10) signalling pathway is critical for lung development and lung epithelial renewal. The hypothesis behind this study was that constitutive FGF10 insufficiency may lead to pulmonary disorder. Therefore investigation of the pulmonary functions of patients heterozygous for loss of function mutations in the FGF10 gene was performed. METHODS: The spirometric measures of lung function from patients and non-carrier siblings were compared and both groups were related to matched reference data for normal human lung function. RESULTS: The patients show a significant decrease in lung function parameters when compared to control values. The average FEV1/IVC quota (FEV1%) for the patients is 0.65 (80% of predicted) and reversibility test using Terbutalin resulted in a 3.7% increase in FEV1. Patients with FGF10 haploinsufficiency have lung function parameters indicating COPD. A modest response to Terbutalin confirms an irreversible obstructive lung disease. CONCLUSION: These findings support the idea that genetic variants affecting the FGF10 signalling pathway are important determinants of lung function that may ultimately contribute to COPD. Specifically, the results show that FGF10 haploinsufficiency affects lung function measures providing a model for a dosage sensitive effect of FGF10 in the development of COPD.

Longitudinal peak strain detects a smaller risk area than visual assessment of wall motion in acute myocardial infarction.

BACKGROUND: Opening of an occluded infarct related artery reduces infarct size and improves survival in acute ST-elevation myocardial infarction (STEMI). In this study we performed tissue Doppler analysis (peak strain, displacement, mitral annular movement (MAM)) and compared with visual assessment for the study of the correlation of measurements of global, regional and segmental function with final infarct size and transmurality. In addition, myocardial risk area was determined and a prediction sought for the development of infarct transmurality >or=50%. METHODS: Twenty six patients with STEMI submitted for primary percutaneous coronary intervention (PCI) were examined with echocardiography on the catheterization table. Four to eight weeks later repeat echocardiography was performed for reassessment of function and magnetic resonance imaging for the determination of final infarct size and transmurality. RESULTS: On a global level, wall motion score index (WMSI), ejection fraction (EF), strain, and displacement all showed significant differences (p or=50%, but strain added no significant information to that obtained with WMSI in a logistic regression analysis. CONCLUSIONS: In patients with acute STEMI, WMSI, EF, strain, and displacement showed significant changes between the pre- and post PCI exam. In a ROC-analysis, strain had 64% sensitivity at 80% specificity and WMSI around 90% sensitivity at 80% specificity for the detection of scar with transmurality >or=50% at follow-up.

Image quality and myocardial scar size determined with magnetic resonance imaging in patients with permanent atrial fibrillation: a comparison of two imaging protocols.

BACKGROUND: Magnetic resonance imaging (MRI) of the heart generally requires breath holding and a regular rhythm. Single shot 2D steady-state free precession (SS_SSFP) is a fast sequence insensitive to arrhythmia as well as breath holding. Our purpose was to determine image quality, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios and infarct size with a fast single shot and a standard segmented MRI sequence in patients with permanent atrial fibrillation and chronic myocardial infarction. METHODS: Twenty patients with chronic myocardial infarction and ongoing atrial fibrillation were examined with inversion recovery SS_SSFP and segmented inversion recovery 2D fast gradient echo (IR_FGRE). Image quality was assessed in four categories: delineation of infarcted and non-infarcted myocardium, occurrence of artefacts and overall image quality. SNR and CNR were calculated. Myocardial volume (ml) and infarct size, expressed as volume (ml) and extent (%), were calculated, and the methodological error was assessed. RESULTS: SS_SSFP had significantly better quality scores in all categories (P = 0.037, P = 0.014, P = 0.021, P = 0.03). SNR(infarct) and SNR(blood) were significantly better for IR_FGRE than for SS_SSFP (P = 0.048, P = 0.018). No significant difference was found in SNR(myocardium) and CNR. The myocardial volume was significantly larger with SS_SSFP (170.7 versus 159.2 ml, P<0.001), but no significant difference was found in infarct volume and infarct extent. CONCLUSION: SS_SSFP displayed significantly better image quality than IR_FGRE. The infarct size and the error in its determination were equal for both sequences, and the examination time was shorter with SS_SSFP.

Late gadolinium uptake demonstrated with magnetic resonance in patients where automated PERFIT analysis of myocardial SPECT suggests irreversible perfusion defect.

BACKGROUND: Myocardial perfusion single photon emission computed tomography (MPS) is frequently used as the reference method for the determination of myocardial infarct size. PERFIT(R) is a software utilizing a three-dimensional gender specific, averaged heart model for the automatic evaluation of myocardial perfusion. The purpose of this study was to compare the perfusion defect size on MPS, assessed with PERFIT, with the hyperenhanced volume assessed by late gadolinium enhancement magnetic resonance imaging (LGE) and to relate their effect on the wall motion score index (WMSI) assessed with cine magnetic resonance imaging (cine-MRI) and echocardiography (echo). METHODS: LGE was performed in 40 patients where clinical MPS showed an irreversible uptake reduction suggesting a myocardial scar. Infarct volume, extent and major coronary supply were compared between MPS and LGE as well as the relationship between infarct size from both methods and WMSI. RESULTS: MPS showed a slightly larger infarct volume than LGE (MPS 29.6 +/- 23.2 ml, LGE 22.1 +/- 16.9 ml, p = 0.01), while no significant difference was found in infarct extent (MPS 11.7 +/- 9.4%, LGE 13.0 +/- 9.6%). The correlation coefficients between methods in respect to infarct size and infarct extent were 0.71 and 0.63 respectively. WMSI determined with cine-MRI correlated moderately with infarct volume and infarct extent (cine-MRI vs MPS volume r = 0.71, extent r = 0.71, cine-MRI vs LGE volume r = 0.62, extent r = 0.60). Similar results were achieved when wall motion was determined with echo. Both MPS and LGE showed the same major coronary supply to the infarct area in a majority of patients, Kappa = 0.84. CONCLUSION: MPS and LGE agree moderately in the determination of infarct size in both absolute and relative terms, although infarct volume is slightly larger with MPS. The correlation between WMSI and infarct size is moderate.