Tobias Schoen

Type 2 Diabetes Mellitus and Risk of Incident Atrial Fibrillation in Women

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 Womens 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.

Age-specific differences between conventional and ambulatory daytime blood pressure values.

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

Healthy lifestyle and heart rate variability in young adults

Background We aimed to determine the association of a comprehensive healthy lifestyle with heart rate variability (HRV), a validated measure of autonomic function. Design This was a prospective cohort study. Methods 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/m2; total cholesterol<200 mg/dl; glycated haemoglobin A1c<5.7%; and blood pressure<120 (systolic) and <80 mm Hg (diastolic). Results 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). Conclusions 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.

Relationship Between High-Sensitivity Cardiac Troponin I and Blood Pressure Among Young and Healthy Adults

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.

Effects of Sinus Rhythm Maintenance on Left Heart Function After Electrical Cardioversion of Atrial Fibrillation: Implications for Tachycardia-Induced Cardiomyopathy

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.

Plasma copeptin levels and ambulatory blood pressure characteristics in healthy adults.

Objective: We investigated whether copeptin – a well characterized vasopressin-related stress hormone – is associated with circadian ambulatory blood pressure (BP) variability and/or mean BP levels in young adults. Method and results: We studied a population-based sample of healthy adults aged 25–41 years. Individuals with diabetes, treated hypertension, and cardiovascular disease were excluded. Ambulatory 24-h BP monitoring was performed using validated devices. To evaluate the relationships of copeptin with mean ambulatory BP levels and BP variability during daytime and night-time, multivariable adjusted regression models were constructed. BP variability was defined as SD of all intraindividual BP values. Of the 2012 individuals included in this study, 53% were women and the median age was 37 years. Median plasma copeptin levels were 3.9 (interquartile range 2.7, 5.8) in men and 2.3 pmol/l (interquartile range 1.6, 3.6) in women (P < 0.0001). In multivariable linear regression models, log-transformed copeptin was significantly associated with systolic and diastolic night-time BP levels among men [&bgr; = 1.9, 95% confidence interval (CI) 0.6, 3.1, P = 0.003; and &bgr; = 1.4, 95% CI 0.6, 2.3, P = 0.001, respectively], but not among women. In addition, copeptin was strongly associated with an increased systolic and diastolic daytime (&bgr; = 0.5, 95% CI 0.2, 0.7, P = 0.001; &bgr; = 0.5, 95% CI 0.3, 0.8, P < 0.0001, respectively) and night-time BP variability (&bgr; = 0.6, 95% CI 0.3, 0.9, P = 0.0002; &bgr; = 0.4, 95% CI 0.2, 0.7, P = 0.002, respectively). Conclusion: In this large population-based study of young and healthy adults, plasma levels of copeptin were significantly associated with an increased BP variability in both sexes and an elevated night-time BP among men.

Glucagon-Like Peptide-1 and Blood Pressure in Young and Healthy Adults from the General Population

Hypertension and diabetes mellitus are highly correlated, but the underlying mechanisms are only partly understood. Therefore, the aim of our study was to investigate the relationships between plasma levels of glucagon-like peptide-1, a key factor in the regulation of glucose homeostasis, and various blood pressure indices. Healthy adults aged 25 to 41 years were enrolled in a population-based study. Established cardiovascular disease, diabetes mellitus, or a body mass index >35 kg/m2 were exclusion criteria. Fasting plasma glucagon-like peptide-1 levels as determined with a novel high-sensitive assay and ambulatory blood pressure data were available in 1479 participants not using antihypertensive treatment. Median age of our population was 38 years. Mean systolic and diastolic blood pressure across increasing glucagon-like peptide-1 quartiles were 120.6, 122.8, 123.2, and 124.9 mm Hg and 77.1, 78.7, 78.9, and 79.9 mm Hg, respectively. We found a linear relationship of glucagon-like peptide-1 with 24-hour ambulatory blood pressure after multivariable adjustment (&bgr; per 1 log-unit increase 2.01; 95% confidence interval, 1.02–3.00; P<0.0001 for systolic and 1.22; 0.47–1.97; P=0.002 for diastolic blood pressure). In separate analyses, glucagon-like peptide-1 was significantly related to both awake (&bgr; per 1 log-unit increase 2.05; 1.02–3.09; P=0.0001 for systolic and 1.15; 0.35–1.96; P=0.005 for diastolic blood pressure) and asleep blood pressure (&bgr; per 1 log-unit increase 1.34; 0.26–2.42; P=0.01 for systolic and 1.05; 0.26–1.84; P=0.009 for diastolic blood pressure). In conclusion, plasma levels of glucagon-like peptide-1 are significantly associated with both systolic and diastolic blood pressure levels.

Heart rate, heart rate variability and inflammatory biomarkers among young and healthy adults

Abstract Background: Heart rate (HR), heart rate variability (HRV), and inflammation are all associated with cardiovascular morbidity and mortality. The aim of this study was to assess potential interrelationships between these parameters in a young and healthy population. Methods: Healthy individuals aged 25–41 years were included in a prospective population-based study. All participants underwent 24-h electrocardiography using a validated device. The standard deviation of all normal RR intervals (SDNN) was pre-defined as the main HRV outcome variable. High-sensitivity C-reactive protein (hs-CRP), total leukocyte (LC) count and LC subtypes were obtained from venous blood samples. Results: A total of 2064 participants (47% men, 37 years) were included in this analysis. In multivariable linear regression analyses using SDNN as the outcome variable, β-coefficients (95% confidence intervals) per 1 standard deviation (SD) increase on the log-scale were −0.11 (−0.16; −0.07), p < .0001 for hs-CRP, −0.13 (−0.17; −0.09), p < .0001 for total LC count, −0.12 (−0.16; −0.08), p < .0001 for neutrophils, −0.04 (−0.09; 0.00), p = .05 for lymphocytes and −0.08 (−0.09; −0.02), p = .005 for monocytes. There were positive relationships between resting and ambulatory HR and inflammatory biomarkers, except for lymphocytes. Conclusion: In this large cohort of young and healthy adults, inflammatory parameters were strongly associated with increased HR and decreased HRV, suggesting an important interaction between inflammatory pathways and the autonomic nervous system. Key message Inflammatory biomarkers, such as high-sensitivity C-reactive protein and leukocyte cell count with its subtypes were inversely associated with HRV and positively associated with HR. Our findings suggest important interrelationships between inflammatory pathways and the ANS.

Plasma levels of glucagon‐like peptide 1 and markers of obesity among young and healthy adults

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.

Association of smoking and nicotine dependence with pre-diabetes in young and healthy adults

INTRODUCTION 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. METHODS 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. RESULTS 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). DISCUSSION 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.