Objectives The purpose of this study was to assess whether changes of major atrial fibrillation (AF) risk factors and/or intercurrent cardiovascular events could explain the relationship between type ...2 diabetes mellitus (T2D) and incident AF. Background Previous studies found an increased risk of incident AF among individuals with T2D, but few, if any, of these studies took into account changes of AF risk factors over time. Methods A total of 34,720 female health professionals who participated in the Women's Health Study, and who were free of cardiovascular disease and AF at baseline were followed for a median of 16.4 years. Cox proportional-hazards models were constructed to assess the relationship between T2D and incident AF, using either information at baseline or time-varying covariates for both T2D and potential confounders. Results At baseline, 937 (2.7 %) women had T2D. Compared with women without T2D, women with T2D had an age-adjusted hazard ratio (HR) for new-onset AF of 1.95 (95% confidence interval CI: 1.49 to 2.56; p < 0.0001). In multivariable analyses adjusting for baseline confounders, this HR was substantially attenuated, but baseline T2D remained a significant predictor of incident AF (HR: 1.37, 95% CI: 1.03 to 1.83; p = 0.03). In time-updated models that adjusted for changes in AF risk factors and intercurrent cardiovascular events, the HR for T2D was attenuated further and became nonsignificant (HR: 1.14; 95% CI: 0.93 to 1.40; p = 0.20). Conclusions Although this study confirms a significant relationship between baseline T2D and incident AF, our data suggest that the increased risk associated with T2D is mainly mediated by changes of other AF risk factors.
Premature ventricular contractions (PVCs) are associated with an increased risk of morbidity and mortality. Therefore, it was aimed to assess risk factors for the frequency of PVCs in young and ...healthy adults.
Our population-based study included 2048 healthy adults from the general population aged 25-41 years. PVC frequency was determined by 24-hour Holter ECG. We performed multivariable regression analysis using stepwise backward selection to identify factors independently associated with PVC frequency.
Median age was 37 years, 953 (46.5%) were male. At least one PVC during the 24-hour monitoring period was observed in 69% of participants. Median number of detected PVCs was 2, the 95th percentile was 193. In multivariable regression analyses, we found 17 significant risk factors for PVC frequency. Low educational status (risk ratio (RR) 3.33; 95% CI 1.98 to 5.60), body height>median (1.58, 95% CI 1.11 to 2.24) and increasing levels of waist:hip ratio (2.15, 95% CI 1.77 to 2.61), N-terminal pro brain natriuretic peptide (1.52, 95% CI 1.30 to 1.76) and Sokolow-Lyon Index (1.38, 95% CI 1.15 to 1.66) (all p≤0.01) were associated with a higher PVC frequency. Physical activity (RR fourth vs first quartile 0.51, 95% CI 0.34 to 0.76) and increasing levels of haemoglobin (0.58, 95% CI 0.47 to 0.70) and glucagon-like peptide-1 (0.72, 95% CI 0.64 to 0.82) (all p<0.001) were related to a lower PVC frequency.
PVC occurrence is common even in healthy low-risk individuals, and its frequency is associated with several covariates mainly related to cardiovascular risk factors, markers of cardiac structure and function and socioeconomic status.
Obstructive sleep apnea seems to have an important influence on the autonomic nervous system. In this study, we assessed the relations of sleep apnea–related parameters with 24-hour heart rate ...variability (HRV) in a large population of young and healthy adults. Participants aged 25 to 41 years with a body mass index <35 kg/m2 and without known obstructive sleep apnea were included in a prospective population-based cohort study. HRV was assessed using 24-hour electrocardiographic monitoring. The SD of all normal RR intervals (SDNN) was used as the main HRV variable. Apnea-Hypopnea Index (AHI) and oxygen desaturation index (ODI) were obtained from nighttime pulse oximetry with nasal airflow measurements. We defined sleep-related breathing disorders as an AHI ≥5 or an ODI ≥5. Multivariable regression models were constructed to assess the relation of HRV with either AHI or ODI. Median age of the 1,255 participants was 37 years, 47% were men, and 9.6% had an AHI ≥5. Linear inverse associations of SDNN across AHI and ODI groups were found (p for trend = 0.006 and 0.0004, respectively). The β coefficients (95% CI) for the relation between SDNN and elevated AHI were −0.20 (−0.40 to −0.11), p = 0.04 and −0.29 (−0.47 to −0.11), p = 0.002 for elevated ODI. After adjustment for 24-hour heart rate, the same β coefficients (95% CI) were −0.06 (−0.22 to 0.11), p = 0.51 and −0.14 (−0.30 to 0.01), p = 0.07, respectively. In conclusion, even early stages of sleep-related breathing disorders are inversely associated with HRV in young and healthy adults, suggesting that they are tightly linked with autonomic dysfunction. However, HRV and 24-hour heart rate seem to have common information.
Cell migration in wound healing and disease is critically dependent on integration with the extracellular matrix, but the receptors that couple matrix topography to migratory behavior remain obscure. ...Using nano-engineered fibronectin surfaces and cell-derived matrices, we identify syndecan-4 as a key signaling receptor determining directional migration. In wild-type fibroblasts, syndecan-4 mediates the matrix-induced protein kinase Cα (PKCα)-dependent activation of Rac1 and localizes Rac1 activity and membrane protrusion to the leading edge of the cell, resulting in persistent migration. In contrast, syndecan-4-null fibroblasts migrate randomly as a result of high delocalized Rac1 activity, whereas cells expressing a syndecan-4 cytodomain mutant deficient in PKCα regulation fail to localize active Rac1 to points of matrix engagement and consequently fail to recognize and respond to topographical changes in the matrix.
We aimed to determine the association of a comprehensive healthy lifestyle with heart rate variability (HRV), a validated measure of autonomic function.
This was a prospective cohort study.
A ...population-based sample of 2079 individuals aged 25-41 years without prevalent cardiovascular disease was investigated. The standard deviation of all normal RR intervals (SDNN) during 24-hour electrocardiography was used as main HRV marker. Healthy lifestyle metrics were summed to a validated lifestyle-score ranging from 0 = most unhealthy to 7 = most healthy. One point was given for each of the following items: never smoking cigarettes; consuming a healthy diet; performing moderate (≥150 min/week) or vigorous (≥75 min/week) physical activity; body mass index (BMI)<25 kg/m(2); total cholesterol<200 mg/dl; glycated haemoglobin A1c<5.7%; and blood pressure<120 (systolic) and <80 mm Hg (diastolic).
Median age of the participants (47% males) was 37 years. Mean SDNN was 153 ms and median lifestyle-score was four. A score of 0/1 or 6/7 was found in 5.2% and 11.0%, respectively. In multivariable linear regression analysis with SDNN as the outcome variable, the β-estimate (95% confidence interval (CI)) for a one-point increase of the lifestyle-score was 0.14 (0.11-0.17), p < 0.0001. This relationship was attenuated but remained significant after additional adjustment for resting heart rate (HR) (β-estimate (95% CI) 0.07 (0.07-0.10), p < 0.0001) or 24-hour HR (0.04 (0.01-0.07), p = 0.003).
Few individuals adopted a healthy lifestyle in this large contemporary cohort of young adults from the general population. Adopting a healthy lifestyle has an important effect on autonomic function.
BACKGROUND
The aim of this study was to evaluate the relationship of cardiac troponin (cTn) levels with conventional and ambulatory blood pressure (BP) in young and healthy adults.
METHODS
We ...performed a population based cross-sectional analysis among 2,072 young and healthy adults aged 25–41 years free of cardiovascular disease and diabetes mellitus. cTnI was measured using a highly sensitive (hs) assay. The relationships of high sensitivity cardiac tropononin I (hs-cTnI) with office and 24-hour BP were assessed using multivariable regression analyses.
RESULTS
Median age was 37 years and 975 (47%) participants were male. hs-cTnI levels were detectable in 2,061 (99.5%) individuals. Median (interquartile range) hs-cTnI levels were 0.98 (0.71; 1.64) ng/L among men and 0.48 (0.33; 0.71) ng/L among women. Systolic BP, but not diastolic BP, gradually increased across hs-cTnI quartiles (118, 120, 121, and 122 mm Hg for conventional BP; P = 0.0002; 122, 123, 124, and 124 mm Hg for 24-hour BP, P = 0.0001). In multivariable linear regression analyses, the β estimates for systolic BP per 1-unit increase in log transformed hs-cTnI were 2.52 for conventional BP (P = 0.0001); 2.75 for 24-hour BP (P < 0.0001); 2.71 and 2.41 (P < 0.0001 and P = 0.0002) for day and nighttime BP, respectively. There was a significant relationship between hs-cTnI and the Sokolow–Lyon Index (odds ratio (95% confidence interval): 2.09 (1.37; 3.18), P < 0.001).
CONCLUSION
Using a hs assay, hs-cTnI was detectable in virtually all participants of a young and healthy population. hs-cTnI was independently associated with systolic BP and left ventricular hypertrophy.
Abstract Background The role of tachycardia-induced cardiomyopathy vs tachycardia-related short diastolic filling period and reduced atrial contraction in decline of left ventricular ejection ...fraction (LVEF) in atrial fibrillation (AF) is uncertain. We aimed to characterize left heart changes over time in patients with AF who undergo electrical cardioversion (ECV). Methods Consecutive AF patients who were to undergo ECV were enrolled. Patients with unstable or acute heart failure, severe valvular diseases, recent open-heart surgery, major disorders, or an unsuccessful ECV were excluded. Transthoracic echocardiography, including 3-dimensional left atrial and ventricular volume acquisitions, was performed 1-2 hours before and after ECV, and 4-6 weeks later. Results In 73 patients (77% male, 66 ± 11 years), ECV resulted in an immediate increase in LVEF (from 43 interquartile range (IQR), 33-50% to 48 IQR, 40-53%; P < 0.0001). Four to 6 weeks after ECV, ejection fraction increased further in patients who remained in sinus rhythm (SR) (n = 55) to 55 (IQR, 44-62)%; P < 0.001. In patients with AF relapse, LVEF returned to values comparable to pre-ECV (n = 18) (44 IQR, 32-51%; P = 0.03). The atrial emptying fraction did not significantly change immediately after ECV (n = 69; from 20 IQR, 13-25% to 20 IQR, 15-28%; P = 0.14). Only patients who remained in SR showed an increase in atrial emptying fraction after 4-6 weeks (n = 51; to 37 IQR, 26-48%; P < 0.0001 vs post-ECV). Conclusions Immediate improvement in LVEF after ECV explains approximately 50% of total LVEF increase over time. However, in SR, LVEF, and atrial function continuously increase over 4-6 weeks after ECV. This might be attributable to recovery of tachycardia-induced cardiomyopathy.
Summary
Objective
Glucagon‐like peptide 1 (GLP‐1)‐related pathways may partially explain the strong relationship between obesity and type 2 diabetes. We therefore aimed to evaluate the relationships ...between fasting GLP‐1 levels, body fat mass and other obesity markers in a large sample of young and healthy adults.
Design and Patients
Our population‐based study included 2096 individuals aged 24–44. Exclusion criteria were prevalent cardiovascular disease, diabetes or a body mass index (BMI) >35 kg/m2. Body fat mass was obtained by bioelectrical impedance analysis. Multivariable linear regression models were constructed to assess the relationships of GLP‐1 with various measures of body composition.
Results
Median age of our population was 37 years, median BMI 24·1 kg/m2 and median body fat 25·1%. A strong positive correlation was observed in age‐adjusted models between GLP‐1 and fat mass in men (β (95% confidence interval) 1·38 (0·69; 2·07), P < 0·001) and women (1·27 (0·65; 1·89), P < 0·001) as well as fully adjusted models including BMI in men 0·87 (0·27; 1·46), P < 0·01 but not women 0·29 (−0·07; 0·64), P = 0·11. The relationships of GLP‐1 with BMI for men and women 0·00 (−0·34; 0·34), P = 0·99 −0·02 (−0·28; 0·25), P = 0·91 and waist circumference 0·43 (−0·45; 1·30), P = 0·34 0·37 (−0·44; 1·18), P = 0·37, respectively, were not significant after multivariable adjustment including fat mass.
Conclusion
Among young and healthy adults, GLP‐1 levels are strongly and independently related to body fat mass especially in men but not BMI or waist circumference. These results raise the hypothesis that GLP‐1 may be implicated in body fat mass regulation.
Several studies have shown an increased risk of type 2 diabetes among smokers. Therefore, the aim of this analysis was to assess the relationship between smoking, cumulative smoking exposure and ...nicotine dependence with pre-diabetes.
We performed a cross-sectional analysis of healthy adults aged 25-41 in the Principality of Liechtenstein. Individuals with known diabetes, Body Mass Index (BMI) >35 kg/m² and prevalent cardiovascular disease were excluded. Smoking behaviour was assessed by self-report. Pre-diabetes was defined as glycosylated haemoglobin between 5.7% and 6.4%. Multivariable logistic regression models were done.
Of the 2142 participants (median age 37 years), 499 (23.3%) had pre-diabetes. There were 1,168 (55%) never smokers, 503 (23%) past smokers and 471 (22%) current smokers, with a prevalence of pre-diabetes of 21.2%, 20.9% and 31.2%, respectively (p <0.0001). In multivariable regression models, current smokers had an odds ratio (OR) of pre-diabetes of 1.82 (95% confidential interval (CI) 1.39; 2.38, p <0.0001). Individuals with a smoking exposure of <5, 5-10 and >10 pack-years had an OR (95% CI) for pre-diabetes of 1.34 (0.90; 2.00), 1.80 (1.07; 3.01) and 2.51 (1.80; 3.59) (p linear trend <0.0001) compared with never smokers. A Fagerström score of 2, 3-5 and >5 among current smokers was associated with an OR (95% CI) for pre-diabetes of 1.27 (0.89; 1.82), 2.15 (1.48; 3.13) and 3.35 (1.73; 6.48) (p linear trend <0.0001).
Smoking is strongly associated with pre-diabetes in young adults with a low burden of smoking exposure. Nicotine dependence could be a potential mechanism of this relationship.
Cellular response to both surface topography and surface chemistry has been studied for several years. However, most of the studies focus on only one of the two parameters and do not consider their ...possible synergistic effects. Here, we report on a fabrication method for nanostructured surfaces composed of highly ordered arrays of silica nanocones with gold tips. By using a combination of block copolymer nanolithography, electroless deposition, and reactive ion etching several parameters such as structure height and structure distance could easily be adjusted to the desired values. The gold tips allow for easy functionalization of the substrates through a thiol linker system. Improved neural cell adhesion can be obtained and is dependent on the nature of the nanocone surface, thus illustrating the influence of different surface topographies on the nanometer length scale, on a complex cellular behavior such as cell adhesion. Substrate and surface functionality are shown to last over several days, leading to the conclusion that the features of our substrates can also be used for longer term experiments. Finally, initial neural cell adhesion is found to be more prominent on substrates with short intercone distances, which is an important finding for research dealing with the reactions of neuron-like tissue in the immediate moments after direct contact with an implanted surface.
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