To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender.
Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to ...99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale.
Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and ≥35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals.
Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.
The aim was to investigate if there is an interaction between sitting time and leisure time physical activity on blood pressure and if there are age differences and sex differences in this respect.
...Linear regression analysis on cross-sectional data was performed in more than 45 000 men and women from two Swedish cohort studies, EpiHealth (45-75 years) and LifeGene (18-45 years). Self-reported leisure time physical activity was given in five levels from low (level 1) to vigorous physical activity (level 5) and television time was used as a proxy measure of sitting time.
High physical activity was associated with lower DBP (P = 0.001), but not SBP. Active middle-aged men had lower DBP (-1.1 mmHg; 95% CI -1.7 to -0.4) compared with inactive participants. Prolonged television time was associated with higher SBP (P < 0.001) and DBP (P = 0.011) in both sexes and in most age groups. Watching 3 h instead of 1 h television per day was associated with higher SBP in middle-aged women (SBP: 1.1 mmHg; 95% CI 0.7-1.4) and men (SBP: 1.2 mmHg; 95% CI 0.8-1.6). Only in young men, a high physical activity (level 4 instead of level 1) could compensate for a prolonged television time (3 h per day) in terms of DBP.
Prolonged television time was associated with higher SBP and DBP in both sexes and at most ages, whereas an increased physical activity was mainly associated with a lower DBP. Only in young men, a high physical activity could compensate for prolonged television time regarding DBP.
Aims/hypothesis
The euglycaemic–hyperinsulinaemic clamp (EIC) is the reference standard for the measurement of whole-body insulin sensitivity but is laborious and expensive to perform. We aimed to ...assess the incremental value of high-throughput plasma proteomic profiling in developing signatures correlating with the
M
value derived from the EIC.
Methods
We measured 828 proteins in the fasting plasma of 966 participants from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study and 745 participants from the Uppsala Longitudinal Study of Adult Men (ULSAM) using a high-throughput proximity extension assay. We used the least absolute shrinkage and selection operator (LASSO) approach using clinical variables and protein measures as features. Models were tested within and across cohorts. Our primary model performance metric was the proportion of the
M
value variance explained (
R
2
).
Results
A standard LASSO model incorporating 53 proteins in addition to routinely available clinical variables increased the
M
value
R
2
from 0.237 (95% CI 0.178, 0.303) to 0.456 (0.372, 0.536) in RISC. A similar pattern was observed in ULSAM, in which the
M
value
R
2
increased from 0.443 (0.360, 0.530) to 0.632 (0.569, 0.698) with the addition of 61 proteins. Models trained in one cohort and tested in the other also demonstrated significant improvements in
R
2
despite differences in baseline cohort characteristics and clamp methodology (RISC to ULSAM: 0.491 0.433, 0.539 for 51 proteins; ULSAM to RISC: 0.369 0.331, 0.416 for 67 proteins). A randomised LASSO and stability selection algorithm selected only two proteins per cohort (three unique proteins), which improved
R
2
but to a lesser degree than in standard LASSO models: 0.352 (0.266, 0.439) in RISC and 0.495 (0.404, 0.585) in ULSAM. Reductions in improvements of
R
2
with randomised LASSO and stability selection were less marked in cross-cohort analyses (RISC to ULSAM
R
2
0.444 0.391, 0.497; ULSAM to RISC
R
2
0.348 0.300, 0.396). Models of proteins alone were as effective as models that included both clinical variables and proteins using either standard or randomised LASSO. The single most consistently selected protein across all analyses and models was IGF-binding protein 2.
Conclusions/interpretation
A plasma proteomic signature identified using a standard LASSO approach improves the cross-sectional estimation of the
M
value over routine clinical variables. However, a small subset of these proteins identified using a stability selection algorithm affords much of this improvement, especially when considering cross-cohort analyses. Our approach provides opportunities to improve the identification of insulin-resistant individuals at risk of insulin resistance-related adverse health consequences.
Graphical Abstract
Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health ...Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy.An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population.We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.
Purpose
This study is part of a larger effort aiming to expand the knowledge of brain‐enriched proteins in human cerebrospinal fluid (CSF) and to provide novel insight into the relation between such ...proteins and different neurodegenerative diseases.
Experimental design
Here 280 brain‐enriched proteins in CSF from patients with Alzheimer's disease (AD), Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are profiled. In total, 441 human samples of ventricular CSF collected post mortem and lumbar CSF collected ante mortem are analyzed using 376 antibodies in a suspension bead array setup, utilizing a direct labelling approach.
Results
Among several proteins displaying differentiated profiles between sample groups, we focus here on two synaptic proteins, neuromodulin (GAP43) and neurogranin (NRGN). They are both found at elevated levels in CSF from AD patients in two independent cohorts, providing disease‐associated profiles in addition to verifying and strengthening previously observed patterns. Increased levels are also observed for patients for whom the AD diagnosis was not established at the time of sampling.
Conclusions and clinical relevance
These findings indicate that analyzing the brain‐enriched proteins in CSF is of particular interest to increase the understanding of the CSF proteome and its relation to neurodegenerative disorders. In addition, this study lends support to the notion that measurements of these synaptic proteins could potentially be of great relevance in future diagnostic tests for AD.
Abstract
Background
Copy number (CN) variation (CNV) of the salivary amylase gene (
AMY1
) influences the ability to digest starch and may influence glucose homeostasis, obesity and gut microbiota ...composition. Hence, the aim was to examine the association of
AMY1
CNV with fasting glucose, BMI, and gut microbiota composition considering habitual starch intake and to investigate the effect of
AMY1
CNV on the postprandial response after two different starch doses.
Methods
The Malmö Offspring Study (
n
= 1764, 18–71 years) was used to assess interaction effects between
AMY1
CNV (genotyped by digital droplet polymerase chain reaction) and starch intake (assessed by 4-day food records) on fasting glucose, BMI, and 64 gut bacteria (16S rRNA sequencing). Participants with low (≤ 4 copies,
n
= 9) and high (≥ 10 copies,
n
= 10)
AMY1
CN were recruited for a crossover meal study to compare postprandial glycemic and insulinemic responses to 40 g and 80 g starch from white wheat bread.
Results
In the observational study, no overall associations were found between
AMY1
CNV and fasting glucose, BMI, or gut microbiota composition. However, interaction effects between
AMY1
CNV and habitual starch intake on fasting glucose (
P
= 0.03) and BMI (
P
= 0.05) were observed, suggesting inverse associations between
AMY1
CNV and fasting glucose and BMI at high starch intake levels and positive association at low starch intake levels. No associations with the gut microbiota were observed. In the meal study, increased postprandial glucose (
P
= 0.02) and insulin (
P
= 0.05) were observed in those with high
AMY1
CN after consuming 40 g starch. This difference was smaller and nonsignificant after consuming 80 g starch.
Conclusions
Starch intake modified the observed association between
AMY1
CNV and fasting glucose and BMI. Furthermore, depending on the starch dose, a higher postprandial glucose and insulin response was observed in individuals with high
AMY1
CN than in those with low
AMY1
CN.
Trial registration
ClinicalTrials.gov
,
NCT03974126
. Registered 4 June 2019—retrospectively registered.
Purpose
Intrauterine undernutrition is associated with increased risk of type 2 diabetes. Children born premature or small for gestational age were reported to have abnormal retinal vascularization. ...However, whether intrauterine famine act as a trigger for diabetes complications, including retinopathy, is unknown. The aim of the current study was to evaluate long‐term effects of perinatal famine on the risk of proliferative diabetic retinopathy (PDR).
Methods
We studied the risk for PDR among type 2 diabetes patients exposed to perinatal famine in two independent cohorts: the Ukrainian National Diabetes Registry (UNDR) and the Hong Kong Diabetes Registry (HKDR). We analysed individuals born during the Great Famine (the Holodomor, 1932–1933) and the WWII (1941–1945) famine in 101 095 (3601 had PDR) UNDR participants. Among 3021 (251 had PDR) HKDR participants, we studied type 2 diabetes patients exposed to perinatal famine during the WWII Japanese invasion in 1942–1945.
Results
During the Holodomor and WWII, perinatal famine was associated with a 1.76‐fold (p = 0.019) and 3.02‐fold (p = 0.001) increased risk of severe PDR in the UNDR. The risk for PDR was 1.66‐fold elevated among individuals born in 1942 in the HKDR (p < 0.05). The associations between perinatal famine and PDR remained statistically significant after corrections for HbA1c in available 18 507 UNDR (padditive interaction < 0.001) and in 3021 HKDR type 2 diabetes patients (p < 0.05).
Conclusion
In conclusion, type 2 diabetes patients, exposed to perinatal famine, have increased risk of PDR compared to those without perinatal famine exposure. Further studies are needed to understand the underlying mechanisms and to extend this finding to other diabetes complications.
IntroductionOsteoarthritis (OA) of the first carpometacarpal (CMC-1) joint is a common hand disorder with symptoms including pain and weakness of the thumb. Previous studies have associated high BMI ...with OA of weight-bearing joints, whereas studies regarding non-weight-bearing joints have shown conflicting results. Thus, the aim of this study was to investigate the influence of overweight and obesity on incident OA of the CMC-1 joint.MethodDuring 1974 to 1992, 33 346 participants aged 26–61 years were included in the population-based cohort Malmö Preventive Project. Endpoint data were retrieved from Swedish national registers until end of 2018. Sex-stratified Cox regression models adjusted for potential confounders were calculated using BMI as a continuous variable and stratified for normal weight, overweight and obesity.ResultsMedian follow-up was 36 years for men and 32 years for women. A one-unit increment of BMI was independently associated with incident OA of the CMC-1 joint in men (HR 1.12; 95% CI 1.09 to 1.15, p<0.001) and women (HR 1.05; 95% CI 1.03 to 1.08, p<0.001). Stratifying for BMI groups, obesity was independently associated with OA of the CMC-1 joint in men (HR 3.57; 95% CI 2.68 to 4.77, p<0.001) and women (HR 1.98; 95% CI 1.44 to 2.73, p<0.001).ConclusionHigh BMI and obesity are major risk factors for OA of the CMC-1 joint. The association was stronger among men but could be demonstrated also among women. Future studies are warranted to clarify underlying pathophysiological mechanisms for this association, enabling identification of potential therapeutic targets related to obesity in order to prevent the development of OA of the CMC-1 joint.
Abstract Background and aims We aimed to identify clusters of metabolic syndrome (MetS) components, risky for extremely high intima-media thickness. Methods We studied 41,513 volunteers (men and ...women) from eleven cohorts worldwide, participating in the MARE (Metabolic syndrome and Artery REsearch) Consortium. Results Specific clusters of MetS components - high triglycerides-high blood pressure-abdominal obesity (TBW), low HDL cholesterol-high blood pressure-abdominal obesity (HBW), high glucose-high blood pressure-abdominal obesity (GBW) - were accompanied by a 50–90% significantly greater likelihood of presenting extremely high intima-media thickness (via ultrasound of carotid artery, CCA IMT), after controlling for age, sex, smoking, non-HDL cholesterol, and presence of diabetes mellitus. This likelihood is comparable to the effect of being 7–8 years older or of being a cigarette smoker or of having non-HDL cholesterol 50 mg/dl higher. Conclusions The consistent association of specific clusters of MetS components with extremely thick (older) large artery cross-culturally suggests that identification of those clusters in clinical practice will facilitate a personalized health care and a better – i.e. more healthy and cost-effective - prevention of major cardiovascular (CV) events.
Job strain (high demands and low decision latitude) has been associated with hypertension and cardiovascular disease, especially in men. Most studies on job strain and hypertension have been ...cross-sectional, and prospective data are inconsistent.
To prospectively describe the effects of different psychosocial work characteristics on office blood pressure changes.
In total, 448 men and women, mean age 55 years, were followed for a mean of 6.5 years. At baseline, work characteristics and cardiovascular risk factors were assessed. Only employed subjects aged 63 years or younger were eligible for participation.
Men with baseline job strain had a significantly greater increase in both systolic blood pressure (7.7 mmHg, P = 0.02), and diastolic blood pressure (5.6 mmHg, P = 0.003), compared to the group with low work demands and high decision latitude ('relaxed'). These findings were significant also after adjustments for age, follow-up time, baseline blood pressure, blood pressure treatment at baseline and follow-up, and length of education. Work demands were more strongly correlated with blood pressure increase than decision latitude. For women, no significant associations between psychosocial work characteristics and blood pressure changes were found, apart from a weak trend of association between increasing decision latitude and increasing blood pressure.
Job strain significantly predicts an increase in office blood pressure in middle-aged men, but not in women. Work demands were more strongly correlated with blood pressure increase than decision latitude in men.
PDF
