Abdominal aortic aneurysm is a life-threatening condition due to the risk of aneurysm growth and rupture. There are no approved diagnostic or prognostic biomarkers for abdominal aortic aneurysm. We ...aimed to identify diagnostic and prognostic biomarkers for abdominal aortic aneurysm and to investigate their relationship with abdominal aortic aneurysm diameter and growth.
In this case-control study, patients were included from an abdominal aortic aneurysm screening study on men aged ≥65 years. Of 24,589 examined men, 415 had abdominal aortic aneurysm, out of whom 134 consented to participate in the present study. One hundred and thirty-six screened men with aortic diameter <30 mm, matched for comorbidities and time of sampling were included as non-abdominal aortic aneurysm patients. Ninety-one cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III
panel.
After Bonferroni correction, plasma levels of 21 proteins associated with proteolysis, oxidative-stress, lipid metabolism, and inflammation were significantly increased, whereas levels of paraoxonase 3, associated with high-density lipoprotein metabolism, were decreased in abdominal aortic aneurysm patients. Combination of growth/differentiation factor 15 and cystatin B had the best ability to discriminate abdominal aortic aneurysm from non-abdominal aortic aneurysm (area under the curve, 0.76; sensitivity, 80% and specificity, 52%). Myeloperoxidase showed the best prognostic value (area under the curve, 0.71; sensitivity, 80% and specificity, 59%) and higher baseline levels of myeloperoxidase were significantly associated with faster abdominal aortic aneurysm growth compared with lower levels, independent of baseline diameter.
We have identified multiple proteins associated with abdominal aortic aneurysm diameter and growth with a potential to become novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.
Summary Background Polyglutamine (polyQ) diseases are characterised by the expansion of CAG triplet repeats in specific genes. The accumulated encoded proteins affect the transcription of numerous ...transcription factors. We investigated whether polyQ diseases reduce the risk of cancer development. Methods Data on patients with the polyQ diseases Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), and hereditary ataxia (HA) in Sweden were linked to the Swedish Cancer Registry. We calculated standardised incidence ratios for cancers at specific sites or of specific types and the risks were compared with those in the general population. We also analysed risks in the unaffected parents of patients. Findings In the period January, 1969, to December, 2008, we identified 1510 patients with HD, 471 with SBMA, and 3425 with HA. Cancer was diagnosed in 91 (6·0%) HD patients, 34 (7·2%) SBMA patients, and 421 (12·3%) HA patients. The standardised incidence ratios were 0·47 (95% CI 0·38–0·58), 0·65 (0·45–0·91), and 0·77 (0·70–0·85), respectively. Before diagnosis of polyQ disease, the risk of cancer was even lower. Cancer incidence and risk in the unaffected parents of patients with polyQ diseases were similar to those in the general population. Interpretation The consistently decreased incidence of cancer in patients with polyQ diseases suggests that a common mechanism protects against the development of cancer. This feature could be related to the polyQ-tract expansion seen in these diseases. Further studies are warranted to investigate the underlying mechanisms linking cancer and polyQ diseases. Funding Swedish Cancer Society, Swedish Council for Working Life and Social Research.
The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the ...evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR.
We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium.
A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 95% confidence interval (CI), 0.29-0.61. Genetically-predicted GLP1R expression (the target of GLP-1 RAs) showed an inverse association with background odds ratio (OR)=0.83, 95% CI, 0.71-0.97 and severe nonproliferative DR (OR=0.72, 95% CI, 0.53-0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92-1.03) and proliferative DR (OR=0.98, 95% CI, 0.91-1.05).
Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings.
Exercise facilities may have the potential to promote physical activity among residents, and to support an active lifestyle throughout the year. We investigated the association between objectively ...assessed availability of exercise facilities and objectively assessed physical activity outcomes, and whether time of year had a modifying effect on these associations.
A total of 2,037 adults (55% females) wore an accelerometer for seven days. Time spent in moderate to vigorous physical activity (minutes per day) and meeting the physical activity recommendations (yes/no) were used as outcome variables. Availability of exercise facilities was measured within 1,000-meter line-based road network buffers around participants' residential addresses using Geographic Information Systems. Socio-demographic variables and time of year were included as covariates in the analyses.
Participants with ≥4 exercise facilities within their buffer zones spent 5.4 (confidence interval (CI) = 2.3-8.5) more minutes in moderate to vigorous physical activity per day, and had 69% higher odds (OR = 1.69; CI = 1.39-2.05) of meeting the physical activity recommendations, compared to those with no exercise facilities within their buffer zones. Time of year had no modifying effect on these associations.
Our results show that objective availability of exercise facilities was associated with accelerometer-assessed time spent in moderate to vigorous physical activity and the odds of meeting the recommended levels of physical activity. Neighborhoods may be a logical and potentially significant venue for policy interventions aimed at increasing physical activity in the overall population.
OBJECTIVE: Our aim was to characterize familial risks for type 2 diabetes by the type and number of affected family members, including half-siblings, adoptees, and spouses, to quantify risks and ...estimate the contribution of environmental effect. RESEARCH DESIGN AND METHODS: Families were identified from the Multigeneration Register, and type 2 diabetic patients were obtained from the Hospital Discharge Register. Standardized incidence ratios were calculated for offspring with type 2 diabetes whose family members were hospitalized for type 2 diabetes at ages >39 years compared with those lacking affected family members. RESULTS: The number of hospitalized type 2 diabetic patients was 157,549. Among 27,895 offspring, 27.9% had a parent or sibling also hospitalized for type 2 diabetes. The familial relative risk (RR) ranged from 2.0 to >30, depending on the number and type of probands. The highest RRs of type 2 diabetes were found in individuals who had at least two siblings affected by type 2 diabetes, irrespective of the parental disease. Adoptees showed no risk from adopted parents. CONCLUSIONS: The study, the largest yet published, showed that familial RRs varied by the number and type of affected family member. However, much of the familial clustering remains yet to be genetically explained. The high risk should be recognized in clinical genetic counseling. The data from adoptees confirmed the genetic basis of the familial associations, but those from half siblings and spouses suggested that a smaller part of familial clustering may be accounted for by environmental factors.
Low academic achievement (AA) in childhood and adolescence is associated with increased substance use. Empirical evidence, using longitudinal epidemiologic data, may provide support for interventions ...to improve AA as a means to reduce risk of drug abuse (DA).
To clarify the nature of the association between adolescent AA and risk of DA by using instrumental variable and co-relative analysis designs.
This study, assessing nationwide data from individuals born in Sweden between 1971 and 1982, used instrumental variable and co-relative analyses of the association between AA and DA. The instrument was month of birth. Co-relative analyses were conducted in pairs of cousins (263 222 pairs), full siblings (154 295), and monozygotic twins (1623) discordant for AA, with raw results fitted to a genetic model. The AA-DA association was modeled using Cox regression. Data analysis was conducted from October 2017 to January 2018.
Academic achievement assessed at 16 years of age (for instrumental variable analyses), and estimated discordance in AA in pairs of monozygotic twins (for co-relative analyses).
Drug abuse registration in national medical, criminal, or pharmacy registries.
This instrumental variable analysis included 934 462 participants (478 341 males and 456 121 females) with a mean (SD) age of 34.7 (4.3) years at a mean follow-up of 19 years. Earlier month of birth was associated with a linear effect on AA, with the regression coefficient per month equaling -0.0225 SDs (95% CI, -0.0231 to -0.0219). Controlling for AA, month of birth had no association with risk of DA (hazard ratio HR, 1.000; 95% CI, 0.997-1.004). Lower AA had a significant association with risk of subsequent DA registration (HR per SD, 2.33; 95% CI, 2.30-2.35). Instrumental variable analysis produced a substantial but modestly attenuated association (HR, 2.04; 95% CI, 1.75-2.33). Controlling for modest associations between month of birth and parental educational status and DA risk reduced the association to a HR of 1.92 (95% CI, 1.67-2.22). The genetic model applied to the results of co-relative analyses fitted the observed data well and estimated the AA-DA association in monozygotic twins discordant for AA to equal a HR of 1.79 (95% CI, 1.64-1.92).
Two different methodological approaches with divergent assumptions both produced results consistent with the hypothesis that the significant association observed between AA at 16 years of age and risk of DA into middle adulthood may be causal. These results provide empirical support for efforts to improve AA as a means to reduce risk of DA.
Abstract
Tall stature and obesity have been associated with a higher risk of atrial fibrillation (AF), but there have been conflicting reports of the effects of aerobic fitness. We conducted a ...national cohort study to examine interactions between height or weight and level of aerobic fitness among 1,547,478 Swedish military conscripts during 1969–1997 (97%–98% of all 18-year-old men) in relation to AF identified from nationwide inpatient and outpatient diagnoses through 2012 (maximal age, 62 years). Increased height, weight, and aerobic fitness level (but not muscular strength) at age 18 years were all associated with a higher AF risk in adulthood. Positive additive and multiplicative interactions were found between height or weight and aerobic fitness level (for the highest tertiles of height and aerobic fitness level vs. the lowest, relative excess risk = 0.51, 95% confidence interval (CI): 0.40, 0.62; ratio of hazard ratios = 1.50, 95% CI: 1.34, 1.65). High aerobic fitness levels were associated with higher risk among men who were at least 186 cm (6 feet, 1 inch) tall but were protective among shorter men. Men with the combination of tall stature and high aerobic fitness level had the highest risk (for the highest tertiles vs. the lowest, adjusted hazard ratio = 1.70, 95% CI: 1.61, 1.80). These findings suggest important interactions between body size and aerobic fitness level in relation to AF and may help identify high-risk subgroups.
More knowledge concerning the association between physical activity and objectively measured attributes of the built environment is needed. Previous studies on the association between objectively ...measured neighborhood walkability, physical activity, and walking have been conducted in the U.S. or Australia and research findings are available from only one country in Europe – Belgium. The first aim of this Swedish study of 2269 adults was to examine the associations between neighborhood walkability and walking for active transportation or leisure, and moderate-to-vigorous physical activity (MVPA) and whether these hypothesized associations are moderated by age, gender, income, marital status and neighborhood-level socioeconomic status. The second aim was to determine how much of the total variance of the walking and physical activity outcomes can be attributed to neighborhood-level differences. Neighborhood walkability was objectively measured by GIS methods. An index consisting of residential density, street connectivity, and land use mix was constructed to define 32 highly and less walkable neighborhoods in Stockholm City. MVPA was measured objectively during 7 days with an accelerometer and walking was assessed using the validated International Physical Activity Questionnaire (IPAQ). Multilevel linear as well as logistic models (mixed-effects, mixed-distribution models) were used in the analysis. The statistically significant and “adjusted” results for individuals living in highly walkable neighborhoods, as compared to those living in less walkable neighborhoods, were: (1) 77% and 28% higher odds for walking for active transportation and walking for leisure, respectively, (2) 50 min more walking for active transportation/week, and (3) 3.1 min more MVPA/day. The proportion of the total variance at the neighborhood level was low and ranged between 0.0% and 2.1% in the adjusted models. The findings of the present study stress that future policies concerning the built environment must be based on context-specific evidence, particularly in the light of the fact that neighborhood redevelopments are time-consuming and expensive.
Aim
To investigate an association between autoimmune disorders (AID) and hospitalization for dementia and Alzheimer's disease, and to study whether the risk is associated with follow‐up time and age.
...Methods
We followed up all individuals in Sweden without previous hospital admission for dementia and Alzheimer's disease, and with a primary or secondary diagnosis of an AID between 1 January 1964 and 31 December 2010, in the Swedish National Patient Register for dementia and Alzheimer's disease. The Swedish National Patient Register includes both inpatients and outpatients. We calculated standardized incidence ratios (SIR) for dementia and Alzheimer's disease, adjusted for individual variables, including age, sex and comorbidities.
Results
A total of 788 103 individuals were admitted to hospital because of an autoimmune disorder without previous dementia and Alzheimer's disease. Among a total of 42 conditions of AID, 9998 dementia and Alzheimer's disease patients were identified with a SIR of 1.28 (95% CI 1.26–1.31). A total of 17 showed an increased risk, and of those the remaining, 14 conditions were still at risk, when dementia and Alzheimer's disease diagnosed in the year of AID diagnosed were excluded. The risks depended on the age at hospitalization for dementia and Alzheimer's disease.
Conclusions
The present large study quantified the increased risks of dementia and Alzheimer's disease in patients with many types of AID. Geriatr Gerontol Int 2018; 18: 1350–1355.
Background: Early-term birth (gestational age, 37—38 weeks) has been associated with increased infant mortality relative to later-term birth, but mortality beyond infancy has not been studied. We ...examined the association between early-term birth and mortality through young adulthood. Methods: We conducted a national cohort study of 679,981 singleton births in Sweden in 1973—1979, followed up for all-cause and cause-specific mortality through 2008 (ages 29—36 years). Results: There were 10,656 deaths in 21.5 million person-years of follow-up. Among those still alive at the beginning of each age range, early-term birth relative to those born at 39—42 weeks was associated with increased mortality in the neonatal period (0—27 days: adjusted hazard ratio = 2.18 95% confidence interval = 1.89—2.51), post-neonatal period (28—364 days: 1.66 1.44—1.92), early childhood (1—5 years: 1.29 1.10—1.51), and young adulthood (18—36 years: 1.14 1.05—1.24), but not in late childhood/adolescence (6—17 years: 0.97 0.84—1.12). In young adulthood, early-term birth was strongly associated with death from congenital anomalies and endocrine disorders, especially diabetes (2.89 1.54—5.43). Conclusions: In this large national cohort study, early-term birth was independently associated with increased mortality in infancy, early childhood, and young adulthood. Lowest short-term and long-term mortality was among those born at 39—42 weeks.
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