Prolonged PR interval, or first degree AV block, has been traditionally regarded as a benign electrocardiographic finding in healthy individuals, until recent studies have suggested that it may be ...associated with increased mortality and morbidity. The aim of this study was to further elucidate clinical and prognostic importance of prolonged PR interval in a large middle-aged population with a long follow-up.
We evaluated 12-lead electrocardiograms of 10 785 individuals aged 30-59 years (mean age 44 years, 52% males) recorded between 1966 and 1972, and followed the subjects for 30 ± 11 years. Prolonged PR interval was defined as PR >200 ms, with further analysis performed using PR ≥220 ms. Main endpoints were all-cause mortality, cardiovascular mortality, and sudden cardiac death, and other endpoints included hospitalizations due to cardiovascular causes. During the baseline examination, prolonged PR interval >200 ms was present in 2.1% of the subjects, but PR interval normalized to ≤200 ms in 30% of these individuals during the follow-up. No increase in mortality or in hospitalizations due to coronary artery disease, heart failure, atrial fibrillation, or stroke was associated with prolonged PR interval (P = non-significant for all endpoints). These results were not changed after multivariate adjustment or in several subanalyses.
In the middle-aged general population, prolonged PR interval normalizes in a substantial proportion of subjects during the time course, and it is not associated with an increased risk of all-cause or cardiovascular mortality.
Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss ...(secondary outcome) over 2 years.
A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.
A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.
From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.
Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.
Recent epidemiologic papers are presenting prevalence data suggesting breaks and decreases in obesity rates. However, before concluding that the obesity epidemic is not increasing anymore, the ...validity of the presented data should be discussed more thoroughly. We had a closer look into the literature presented in recent reviews to address the major potential biases and distortions, and to develop insights about how to interpret the presented suggestions for a potential break in the obesity epidemic. Decreasing participation rates, the use of reported rather than measured data and small sample sizes, or lack of representativeness, did not seem to explain presented breaks in the obesity epidemic. Further, available evidence does not suggest that stabilization of obesity rates is seen in higher socioeconomic groups only, or that urbanization could explain a potential break in the obesity epidemic. However, follow-ups of short duration may, in part, explain the apparent break or decrease in the obesity epidemic. On the other hand, a single focus on body mass index (BMI) ⩾25 or ⩾30 kg m(-)(2) is likely to mask a real increase in the obesity epidemic. And, in both children and adults, trends in waist circumferences were generally suggesting an increase, and were stronger than those reported for trends in BMI. Studies concluding that there is a recent break in the obesity epidemic need to be interpreted with caution. Reported studies presenting a break were mostly of short duration. Further, focusing on trends in waist circumference rather than BMI leads to a less optimistic conclusion: the public health problem of obesity is still increasing.
Objective: Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology ...has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC). Methods: The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975-1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models. Results: The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r=-0.12) and females (r=-0.18), and between physical activity and BMI in females (r=-0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC. Conclusions: Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.
Traditional lectures and exercises are good for gaining basic knowledge in STEM (Science, Technology, Engineering and Mathematics). If feasible, motivational and deeper learning experiences like ...laboratory - or work life-related field experimentation are included in studying levels, more concrete learning experiences can be reached. At the National Defence University (NDU), the theoretical part of master's level studies in STEM relies on earlier basic studies. In order to promote practical skills, a specific simulation and modelling course is aimed at learning how real-world artifacts or models work, how to acquire data, how to visualise the acquired data, and to develop one's understanding trough simulations. This course ends with a group work, where participating students are asked to produce a working simulation model either from the given list or from their professional context. This study describes two sample cases: The first one is a flight simulator that includes a lot of physics and physical phenomena. The second one illustrates time dependence and statistical nature of targeting. The course's success is estimated from reports and the feedback given by the students. Observations on motivation and learning goals are included. For military officers learning is practically oriented, while in natural sciences learning is theoretically oriented. In both cases simulation is a natural "bridge" in between theory and practice.
Little is known about epigenetic alterations associated with subcutaneous adipose tissue (SAT) in obesity. Our aim was to study genome-wide DNA methylation and gene expression differences in SAT in ...monozygotic (MZ) twin pairs who are discordant for body mass index (BMI). This design completely matches lean and obese groups for genetic background, age, gender and shared environment.
14We analyzed DNA methylome and gene expression from SAT, together with body composition (magnetic resonance imaging/spectroscopy) and glucose tolerance test, lipids and C-reactive protein from 26 rare BMI-discordant (intrapair difference in BMI ⩾3 kg m(-2)) MZ twin pairs identified from 10 birth cohorts of young adult Finnish twins.
We found 17 novel obesity-associated genes that were differentially methylated across the genome between heavy and lean co-twins. Nine of them were also differentially expressed. Pathway analyses indicated that dysregulation of SAT in obesity includes a paradoxical downregulation of lipo/adipogenesis and upregulation of inflammation and extracellular matrix remodeling. Furthermore, CpG sites whose methylation correlated with metabolically harmful fat depots (intra-abdominal and liver fat) also correlated with measures of insulin resistance, dyslipidemia and low-grade inflammation, thus suggesting that epigenetic alterations in SAT are associated with the development of unhealthy obesity.
This is the first study in BMI-discordant MZ twin pairs reporting genome-wide DNA methylation and expression profiles in SAT. We found a number of novel genes and pathways whose methylation and expression patterns differ within the twin pairs, suggesting that the pathological adaptation of SAT to obesity is, at least in part, epigenetically regulated.
Objectives: To determine the long term survival and predictors of death in patients with primary intracerebral haemorrhage (ICH) in Central Finland. Methods: Data were collected retrospectively on ...all adult patients with first ever ICH in Central Finland county between September 1985 and December 1991. The survival of all patients at the end of December 2002 was investigated. Kaplan–Meier survival curves were constructed and factors associated with both early (⩽28 days) and late deaths determined. Long term survival was compared with the general Finnish population of the same age and sex distribution. The causes of death were compared with those of the population of Central Finland. Results: 411 patients with first ever ICH were identified, 199 men (mean age 64.9 years) and 212 women (mean age 69.5); 30 died before hospital admission, and 208 (50.6%) within the first 28 days. In Kaplan–Meier analysis, at 16 years the cumulative survival was 3.2% for men and 9.8% for women. The 28 day survivors had a 4.5-fold increased annual risk of dying during the first year after ICH, and 2.2-fold during years 2 to 6. On admission, significant independent predictors of death within the first four weeks were unconsciousness, lateral shift of cerebral midline structures, mean arterial pressure ⩾134 mm Hg, hyperglycaemia, anticoagulant treatment, and ventricular extrasystoles. Predictors of late death for the 28 day survivors were old age, male sex, and heart failure. Conclusions: Primary intracerebral haemorrhage has a poor short and long term outcome. The results emphasise the importance of primary and secondary prevention for ICH.
Does dieting make you fat? A twin study PIETILÄINEN, K. H; SAARNI, S. E; KAPRIO, J ...
International Journal of Obesity,
03/2012, Letnik:
36, Številka:
3
Journal Article
Recenzirano
Odprti dostop
To investigate whether the paradoxical weight gain associated with dieting is better related to genetic propensity to weight gain than to the weight loss episodes themselves.
Subjects included 4129 ...individual twins from the population-based FinnTwin16 study (90% of twins born in Finland 1975-1979). Weight and height were obtained from longitudinal surveys at 16, 17, 18 and 25 years, and number of lifetime intentional weight loss (IWL) episodes of more than 5 kg at 25 years.
IWLs predicted accelerated weight gain and risk of overweight. The odds of becoming overweight (body mass index (BMI)≥ 25 kg m(-2)) by 25 years were significantly greater in subjects with one (OR 1.8, 95% CI 1.3-2.6, and OR 2.7, 1.7-4.3 in males and females, respectively), or two or more (OR 2.0, 1.3-3.3, and OR 5.2, 3.2-8.6, in males and females, respectively), IWLs compared with subjects with no IWL. In MZ pairs discordant for IWL, co-twins with at least one IWL were 0.4 kg m(-2) (P=0.041) heavier at 25 years than their non-dieting co-twins (no differences in baseline BMIs). In DZ pairs, co-twins with IWLs gained progressively more weight than non-dieting co-twins (BMI difference 1.7 kg m(-2) at 16 years and 2.2 kg m(-2) at 25 years, P<0.001).
Our results suggest that frequent IWLs reflect susceptibility to weight gain, rendering dieters prone to future weight gain. The results from the MZ pairs discordant for IWLs suggest that dieting itself may induce a small subsequent weight gain, independent of genetic factors.
BACKGROUND—Prolonged duration of QRS complex in a 12-lead ECG is associated with adverse prognosis in patients with cardiac disease, but its significance is not well established in the general ...population. In particular, there is a paucity of data on the prognostic significance of nonspecific intraventricular conduction delay in apparently healthy subjects.
METHODS AND RESULTS—We evaluated the 12-lead ECGs of 10 899 Finnish middle-aged subjects from the general population (52% of whom were men; mean age 44±8.5 years) between 1966 and 1972 and followed them for 30±11 years. Primary end points were all-cause mortality, cardiac mortality, and arrhythmic death. Prolonged QRS duration was defined as QRS ≥110 ms and intraventricular conduction delay as QRS ≥110 ms, without the criteria of complete or incomplete bundle-branch block. QRS duration ≥110 ms was present in 1.3% (n=147) and intraventricular conduction delay in 0.6% (n=67) of the subjects. Prolonged QRS duration predicted all-cause mortality (multivariate-adjusted relative risk RR 1.48; 95% confidence interval CI 1.22–1.81; P<0.001), cardiac mortality (RR 1.94; CI 1.44–2.63; P<0.001), and sudden arrhythmic death (RR 2.14; CI 1.38–3.33; P=0.002). Subjects with intraventricular conduction delay had increased all-cause mortality (RR 2.01; CI 1.52–2.66; P<0.001), increased cardiac mortality (RR 2.53; CI 1.64–3.90; P<0.001), and an elevated risk of arrhythmic death (RR 3.11; CI 1.74–5.54; P=0.001). Left bundle-branch block also weakly predicted arrhythmic death (P=0.04), but right bundle-branch block was not associated with increased mortality.
CONCLUSIONS—Prolonged QRS duration in a standard 12-lead ECG is associated with increased mortality in a general population, with intraventricular conduction delay being most strongly associated with an increased risk of arrhythmic death.
We wanted to evaluate the prevalence and prognostic value of the fragmented QRS (fQRS) complex, defined as changes in QRS morphology with various RSR′-patterns in 12-lead electrocardiogram (ECG) in a ...middle-aged general population. We evaluated the 12-lead ECGs of 10,904 Finnish middle-aged subjects (52% men, mean age 44 ± 8.5 years) with (n = 2,543) and without (n = 8,361) an evidence of cardiac disease drawn from general population and followed them for 30 ± 11 years. Fragmentation of the QRS complex was defined as various RSR′-patterns in at least 2 consecutive leads within the same territory (inferior II, III, aVF; lateral I, aVL, V4 to V6; anterior V1 to V3). Primary end points were death from any cause, cardiac, and arrhythmic deaths. In the total population, fQRS was present in 19.7% (n = 2,147) of subjects, including 15.7% (n = 1714) in inferior leads, 0.8% (n = 84) in lateral leads, and 2.9% (n = 314) in anterior leads. Fragmentation was not associated with increased mortality in subjects without a known cardiac disease. However, fQRS observed in lateral leads in subjects with an evidence of cardiac disease was associated with an increased risk of all-cause (p = 0.001), cardiac (p = 0.001), and arrhythmic (p = 0.004) mortalities. In conclusion, fQRS reflecting minor intraventricular conduction defect is a common finding, especially in the inferior leads, but it is not a sign of increased risk of mortality in subjects without a known cardiac disease. Lateral fQRS, which is less commonly observed in the ECG, is associated with a worse outcome in patients with a known cardiac disease.
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