Overweight, obesity and risk of cardiometabolic multimorbidity: pooled analysis of individual-level data for 120,813 adults from 16 cohort studies from the USA and Europe

Background Although overweight and obesity have been studied in relation to individual cardiometabolic diseases, their association with risk of cardiometabolic multimorbidity is poorly understood. Here we aimed to establish the risk of incident cardiometabolic multimorbidity (ie, at least two from: type 2 diabetes, coronary heart disease, and stroke) in adults who are overweight and obese compared with those who are a healthy weight. Methods We pooled individual-participant data for BMI and incident cardiometabolic multimorbidity from 16 prospective cohort studies from the USA and Europe. Participants included in the analyses were 35 years or older and had data available for BMI at baseline and for type 2 diabetes, coronary heart disease, and stroke at baseline and follow-up. We excluded participants with a diagnosis of diabetes, coronary heart disease, or stroke at or before study baseline. According to WHO recommendations, we classified BMI into categories of healthy (20·0–24·9 kg/m²), overweight (25·0–29·9 kg/m²), class I (mild) obesity (30·0–34·9 kg/m²), and class II and III (severe) obesity (≥35·0 kg/m²). We used an inclusive definition of underweight (<20 kg/m²) to achieve sufficient case numbers for analysis. The main outcome was cardiometabolic multimorbidity (ie, developing at least two from: type 2 diabetes, coronary heart disease, and stroke). Incident cardiometabolic multimorbidity was ascertained via resurvey or linkage to electronic medical records (including hospital admissions and death). We analysed data from each cohort separately using logistic regression and then pooled cohort-specific estimates using random-effects meta-analysis. Findings Participants were 120 813 adults (mean age 51·4 years, range 35–103; 71445 women) who did not have diabetes, coronary heart disease, or stroke at study baseline (1973–2012). During a mean follow-up of 10·7 years (1995–2014), we identified 1627 cases of multimorbidity. After adjustment for sociodemographic and lifestyle factors, compared with individuals with a healthy weight, the risk of developing cardiometabolic multimorbidity in overweight individuals was twice as high (odds ratio [OR] 2·0, 95% CI 1·7–2·4; p<0·0001), almost five times higher for individuals with class I obesity (4·5, 3·5–5·8; p<0·0001), and almost 15 times higher for individuals with classes II and III obesity combined (14·5, 10·1–21·0; p<0·0001). This association was noted in men and women, young and old, and white and non-white participants, and was not dependent on the method of exposure assessment or outcome ascertainment. In analyses of different combinations of cardiometabolic conditions, odds ratios associated with classes II and III obesity were 2·2 (95% CI 1·9–2·6) for vascular disease only (coronary heart disease or stroke), 12·0 (8·1–17·9) for vascular disease followed by diabetes, 18·6 (16·6–20·9) for diabetes only, and 29·8 (21·7–40·8) for diabetes followed by vascular disease. Interpretation The risk of cardiometabolic multimorbidity increases as BMI increases; from double in overweight people to more than ten times in severely obese people compared with individuals with a healthy BMI. Our findings highlight the need for clinicians to actively screen for diabetes in overweight and obese patients with vascular disease, and pay increased attention to prevention of vascular disease in obese individuals with diabetes

Long working hours as a risk factor for atrial fibrillation: A multi-cohort study

Aims Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working long hours (>55 per week) and those working standard 35-40 hours per week. Methods In this prospective multi-cohort study from the Individual-Participant-Data Meta-analysis in and results Working Populations (IPD-Work) Consortium, the study population was 85,494 working men and women (mean age 43.4 years) with no recorded atrial fibrillation. Working hours were assessed at study baseline (1991-2004). Mean follow-up for incident atrial fibrillation was 10 years and cases were defined using data on electrocardiograms, hospital records, drug reimbursement registers, and death certificates. We identified 1061 new cases of atrial fibrillation (10-year cumulative incidence 12.4 per 1000). After adjustment for age, sex and socioeconomic status, individuals working long hours had a 1.4-fold increased risk of atrial fibrillation compared to those working standard hours (hazard ratio=1.42, 95%CI=1.13-1.80, P=0.003). There was no significant heterogeneity between the cohortspecific effect estimates (I2=0%, P=0.66) and the finding remained after excluding participants with coronary heart disease or stroke at baseline or during the follow-up (N=2006, hazard ratio=1.36, 95%CI=1.05-1.76, P=0. 0180). Adjustment for potential confounding factors, such as obesity, risky alcohol use and high blood pressure, had little impact on this association. Conclusion Individuals who worked long hours were more likely to develop atrial fibrillation than those working standard hours

Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data

Background Adverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression. Methods We identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individuallevel data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) consortium. Summary estimates of the association were obtained using random effects models. Individual-level data analyses were based on a pre-published study protocol (F1000Res 2013;2:233). Results We included 6 published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published (Relative Risk [RR]= 1.77, 95% confidence interval [CI] 1.47-2.13) and unpublished datasets (RR=1.27, 95% CI 1.04-1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR=1.25, 95% CI: 0.94-1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR=1.03, 95% CI: 0.81- 1.32). Conclusion Job strain may precipitate clinical depression among employees. Future intervention studies

Picture and illustration of the set up.

<p>(a) Photo of the acoustophoresis microfluidic system first presented by Augustsson <i>et al. </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064233#pone.0064233-Augustsson3" target="_blank">[27]</a>. (b) Cross sectional view of cell distribution in the microchannel without ultrasound (left) and with ultrasound forming an ultrasound standing wave (right). (c) Illustration of acouscoustophoresis chip. For the present study, only one of the channel segments was used allowing cells to be exposed to ultrasound.</p

Unaltered viability of BV2 microglial cell line following acoustophoretic processing (10V_pp and 20V_pp).

<p>BV2 cells were passed through the acoustophoresis chip with the function generator set at 0, 10 and 20 V_pp. After going through the chip, the BV2 cells were seeded again for 24 and 48 h. Cell viability was measured by XTT (a), apoptotic nuclei appearance (b) and decrease of mitochondrial potential -Ψm- (c), showing no difference between experimental groups. Similar, no difference was detected by clonogenic assay (d) used to study survival and proliferation at 7 days following acoustophoretic processing. The graphs show the results from at least three separate experiments and the data are shown as means ± SD. Significance value <i>P</i><0.05, ns denotes non-significant.</p

Mitochondrial respiratory function in human leukocytes and thrombocytes are not altered following acoustophoresis.

<p>Leukocytes and thrombocytes were passed through the acoustophoresis chip run at 0, 10 and 20 V_pp. Maximal respiration during using both complex I- and complex II-linked substrates for thrombocytes (a) and leukotcytes (b) was unaltered after acoustophoresis, supporting that acoustophoresis does not affect metabolic pathways important for respiration. The remaining respiratory activity following inhibition of ATP synthase with oligomycin, so called Leak or state 4 respiration, was also unaffected by acoustophoresis, in thrombocytes (c) and leukocytes (d). This data confirm no effect of acoustophoresis on inner mitochondrial membrane integrity or changed utilization of proton motive force for other purposes than ADP phosphorylation. Unprocessed cells were used as control cells. The graphs show the results from three separate experiments and the data are shown as means ± SD. Significance value <i>P</i><0.05, ns denotes non-significant.</p

Inflammatory response of BV2 cells upon LPS challenge following acoustophoresis is not changed.

<p>After acoustophoretic processing, BV2 cells were seeded and stimulated the next day with LPS for 24 h. We observed no alteration due to acoustophoretic processing in the expression of iNOS (inducible nitric oxide synthase)(a,b), the release of proinflammatory cytokines IL-1β (χ), IL-12 (d), TNF-α (e) or the anti-inflammatory cytokine IL-10 (f). The graphs show the results from at least three separate experiments and the data are shown as means ± SD. Significance value <i>P</i><0.05, ns denotes non-significant.</p

Adjusted Odds Ratios (95% CI) for the Association Between Job Strain and Diabetes (N = 44,818 in All Models), the IPD-Work Consortium, 1984–2003.

<p>Adjusted Odds Ratios (95% CI) for the Association Between Job Strain and Diabetes (N  =  44,818 in All Models), the IPD-Work Consortium, 1984–2003.</p

Participant Characteristics According to Study, the IPD-Work Consortium, 1984–2003.

<p>Participant Characteristics According to Study, the IPD-Work Consortium, 1984–2003.</p