Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial.

Importance: Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. Objective: To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. Design, Setting, and Participants: The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). Intervention: In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Main Outcome and Measures: Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. Results: The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P = .019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 µIU/L (HR, 0.48; 95% CI, 0.31-0.74; P = .001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P = .008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P = .84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P = .97; interaction P = .02). Conclusions and Relevance: This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia. Trial Registration: ClinicalTrials.gov Identifier: NCT01479452.

Cognitive functioning in adolescents with severe obesity undergoing bariatric surgery or intensive non-surgical treatment in Sweden (AMOS2): a multicentre, open-label, randomised controlled trial.

Background: Severe obesity during childhood is associated with cognitive deficits. Studies in adults have suggested improvements in executive functioning and memory after bariatric surgery. Our aim was to explore changes in cognitive function in adolescents over two years after bariatric surgery or intensive non-surgical treatment. Methods: The Adolescent Morbid Obesity Surgery 2 (AMOS2) is a multicentre, open-label, randomised controlled trial in which adolescents (aged 13-16 years) with severe obesity (defined as body mass index (BMI) ≥35 kg/m2) at three specialised obesity centres in Sweden, were randomly assigned to receive bariatric surgery or intensive non-surgical treatment. Herein we report the results of the prespecified exploratory endpoint of change in cognitive functioning. Inclusion in AMOS2 required Tanner pubertal stage ≥3, previous participation in lifestyle obesity treatment for at least one year, and passed assessment form a paediatrician and a paediatric psychologist. Adolescents with severe intellectual disability or other severe, pervasive developmental disorder were excluded. Participants underwent baseline assessment of general intellectual ability, executive functioning, and memory before randomisation. Tests were administrated by clinical psychologists and repeated at one- and two-year follow-up timepoints. Differences in means between groups during follow-up are provided with confidence intervals. The trial is registered at ClinicalTrials.gov, NCT02378259. Findings: Between October 28 2015 and June 7 2017, 46 adolescents (74% girls), with a mean age of 15.8 (±0.92) years and a mean BMI of 42.8 (±5.4) kg/m2, were included and randomised (23 to bariatric surgery and 23 to intensive non-surgical treatment). At baseline 23/46 (50%) of the adolescents had general intellectual functioning classified as borderline or below. For 15/18 (83%) aspects of cognitive functioning, no significant differences in change over two years were identified between groups; Immediate (average difference during follow-up 1.0 [95% CI: -2.6 to 4.6]) and Delayed (0.5 [95% CI: -0.6 to 1.6]) Verbal Recall, Category Fluency (1.1 [95% CI: -1.6 to 3.8]) and Switching (1.5 [95% CI: -0.0 to 2.9]), Number (-6.0 [95% CI: -12.3 to 0.3]) and Letter (0.1 [95% CI: -5.2 to 5.3]) Sequencing, Number-Letter Switching (-10.3 [95% CI: -26.4 to 5.8]), Motor Speed (-8.3 [95% CI: -17.5 to 0.9]), Colour Naming (-1.9 [95% CI: -4.2 to 0.3]), Inhibition (-3.6 [95% CI: -9.6 to 2.5]), Inhibition Switching (-6.7 [95% CI: -15.3 to 1.9]), Mazes (-0.5 [95% CI: -4.9 to 3.9]), Digit Span Forward (0.1 [95% CI: -0.6 to 0.9 ]) and Backward (0.6 [95% CI: -0.4 to 1.6 ]), and Estimated IQ (0.4 [95% CI: -3.9 to 4.8]; all p > 0.05). Three sub-tests assessing fundamental cognitive skills improved more over two years in operated adolescents than in intensive non-surgical treatment; Letter Fluency (average difference during follow-up 3.8 [95% CI: 0.1-7.5]; p = 0.046), Visual Scanning (-6.5 [95% CI: -11.6 to -1.5]; p = 0.011), and Word Reading (-1.9 [95% CI: -3.3 to -0.4]; p = 0.011). Interpretation: In contrast to non-randomised studies in adults, we could not demonstrate an association of bariatric surgery and its accompanying significant weight loss with overall greater improvement in executive functions and memory in adolescents over two years compared with a non-surgical group without weight loss. However, lack of statistical power is a potential limitation. The clinical relevance of greater improvements in basic cognitive skills needs to be explored. Funding: Sweden's innovation agency (VINNOVA), Swedish Research Council, Joanna Cocozza foundation for paediatric research, The Skane University Hospital Psychology Research and Development Grant, Tore Nilsson's Foundation, SUS Foundations and Donations, and Mary von Sydow's Foundation.

Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass: A Randomized Clinical Trial.

Importance: Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear. Objective: To compare perioperative outcomes in SG and RYGB. Design, Setting, and Participants: In this registry-based, multicenter randomized clinical trial (Bypass Equipoise Sleeve Trial), baseline and perioperative data for patients undergoing bariatric surgery from October 6, 2015, to March 31, 2022, were analyzed. Patients were from university, regional, county, and private hospitals in Sweden (n = 20) and Norway (n = 3). Adults (aged ≥18 years) eligible for bariatric surgery with body mass indexes (BMIs; calculated as weight in kilograms divided by height in meters squared) of 35 to 50 were studied. Interventions: Laparoscopic SG or RYGB. Main Outcomes and Measures: Perioperative complications were analyzed as all adverse events and serious adverse events (Clavien-Dindo grade >IIIb). Ninety-day mortality was also assessed. Results: A total of 1735 of 14 182 eligible patients (12%; 1282 [73.9%] female; mean (SD) age, 42.9 [11.1] years; mean [SD] BMI, 40.8 [3.7]) were included in the study. Patients were randomized and underwent SG (n = 878) or RYGB (n = 857). The mean (SD) operating time was shorter in those undergoing SG vs RYGB (47 [18] vs 68 [25] minutes; P < .001). The median (IQR) postoperative hospital stay was 1 (1-1) day in both groups. The 30-day readmission rate was 3.1% after SG and 4.0% after RYGB (P = .33). There was no 90-day mortality. The 30-day incidence of any adverse event was 40 (4.6%) and 54 (6.3%) in the SG and RYGB groups, respectively (odds ratio, 0.71; 95% CI, 0.47-1.08; P = .11). Corresponding figures for serious adverse events were 15 (1.7%) for the SG group and 23 (2.7%) for the RYGB group (odds ratio, 0.63; 95% CI, 0.33-1.22; P = .19). Conclusions and Relevance: This randomized clinical trial of 1735 patients undergoing primary bariatric surgery found that both SG and RYGB were performed with a low perioperative risk without clinically significant differences between groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02767505.

A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol.

BACKGROUND: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer's Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60-79 years) at increased risk of dementia. METHODS: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle intervention is adapted from the original FINGER trial (diet, physical activity, cognitive training, monitoring of cardiovascular/metabolic risk factors, social interaction) to be consistently delivered in three countries. Metformin is administered as Glucophage®XR/SR 500, (500 mg oral tablets). The metformin/placebo treatment will be double blinded. CONCLUSION: MET-FINGER is the first trial combining a multimodal lifestyle intervention with a putative repurposed disease-modifying drug for cognitive impairment prevention. Although preliminary, its findings will provide crucial information for innovative precision prevention strategies and form the basis for a larger phase-III trial design and future research in this field. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05109169).

Perceived Body Size in Relation to 10-Year Weight Change in the Swedish Obese Subjects Intervention Study.

INTRODUCTION: Body size underestimation in patients with obesity may be associated with long-term weight increase. In the current report, we analyse changes in body size perception in patients with obesity undergoing either bariatric surgery or usual obesity care, and in subgroups of patients who gain weight or maintain their body weight over 10 years. MATERIALS AND METHODS: A total of 2,504 patients with obesity from the prospective, controlled Swedish Obese Subjects (SOS) intervention study were included in this report, 1,370 patients underwent bariatric surgery and 1,134 patients were usual care controls. Weight was measured and body size was self-estimated using the Stunkard's figure rating scale at baseline and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years of follow-up. A body perception index (BPI) was calculated as estimated/measured BMI. Weight (re)gain was defined as ≥10% increase between 1 and 10 years of follow-up. RESULTS: Body size was underestimated by 12% in the surgery and 14% in the control group (i.e., >5 BMI units) at baseline and underestimation largely persisted over 10 years in both intervention groups. When stratified by long-term weight development, weight regainers from the surgery group underestimated their body size to a larger degree compared to weight maintainers (12 vs. 9%, p < 0.001) after 10 years. Likewise weight gainers in the control group also underestimated their body size to a larger degree (17% vs. 13%, p < 0.001). In both groups, the change in BPI was significantly different between weight regainers and maintainers during follow-up (time-BPI interactions both p < 0.001). CONCLUSION: Patients with obesity underestimate their body size and this underestimation remains long-term even after major weight loss induced by bariatric surgery. In patients with obesity who maintain their weight, regardless of treatment, underestimation of body size persists but body size perception is slightly more accurate compared to patients who gain or regain weight long-term.

Long-term incidence of haematological cancer after bariatric surgery or usual care in the Swedish Obese Subjects study: a prospective cohort study.

BACKGROUND: Bariatric surgery in people with obesity is associated with a reduced overall cancer risk. Retrospective studies indicate that bariatric surgery specifically might reduce the risk of haematological cancers, but there is an absence of data from long-term, prospective studies. We therefore studied the association between bariatric surgery and haematological cancer in the Swedish Obese Subjects study. METHODS: The prospective controlled Swedish Obese Subjects study was designed to compare overall mortality in people who underwent bariatric surgery (n=2007) and usual care (n=2040). Participants were recruited through campaigns in mass media and at 480 primary health-care centres all over Sweden. The inclusion criteria were an age of 37-60 years and a BMI of 34 kg/m2 or more in men and 38 kg/m2 or more in women before or at the time of the examination. Haematological cancer events, including malignant lymphoma, myeloma, myeloproliferative neoplasms, as well as acute and chronic leukaemias, were captured from the Swedish Cancer Registry. The main outcome of this study was haematological cancer incidence and mortality. This study is registered with ClinicalTrials.gov (NCT01479452) and is ongoing. FINDINGS: A total of 4047 individuals with obesity were enrolled between Sept 1, 1987, and Jan 31, 2001. Overall, 34 participants in the surgery group and 51 participants in the usual care control group were diagnosed with haematological cancer during follow-up (hazard ratio [HR] 0·60; 95% CI 0·39-0·92; p=0·020). Moreover, there were three deaths by haematological cancer in the surgery group and 13 deaths in the control group (0·22; 0·06-0·76; p=0·017). Surgery was also associated with a reduced incidence of lymphoma (0·45; 0·23-0·88; p=0·020). A significant difference in treatment effect between men and women was found; bariatric surgery was associated with reduced incidence of haematological cancer in women (0·44; 0·26-0·74; p=0·002), but not in men (1·35; 0·58-3·17; p=0·489; interaction p=0·031). INTERPRETATION: Bariatric surgery is associated with a reduced incidence of haematological cancer, specifically in women. Health-care providers and policy makers working in the field of cancer prevention should consider bariatric surgery a primary prevention resource for people with obesity. FUNDING: The Swedish Research Council, the Swedish State under the agreement between the Swedish Government and the county councils, the Avtal om Läkarutbildning och Forskning agreement, the Health & Medical Care Committee of the Region Västra Götaland, the Swedish Heart Lung Foundation, Gothenburg Medical Society, and the Adlerbert Research Foundation. TRANSLATION: For the Swedish translation of the abstract see Supplementary Material section.

Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study.

OBJECTIVE: The goal of this study was to investigate whether bariatric surgery is associated with substance use disorder (SUD) with substances other than alcohol. METHODS: The prospective, controlled Swedish Obese Subjects study enrolled 2010 patients with obesity who underwent bariatric surgery (gastric bypass n = 265; vertical banded gastroplasty n = 1369; gastric banding n = 376) and 2037 matched control individuals receiving usual obesity care. Participants with SUD other than alcohol use disorder were identified using International Statistical Classification of Diseases (ICD) codes from the Swedish National Patient Register (covering treatment in hospital but not primary care). Those with a history of non-alcohol SUD were excluded. Median follow-up was 23.8 years. RESULTS: During follow-up, non-alcohol SUD incidence rates per 1000 person-years with 95% CI were 1.6 (0.8-3.1), 0.8 (0.5-1.2), 1.1 (0.5-2.2), and 0.6 (0.4-0.8) for gastric bypass, vertical banded gastroplasty, gastric banding, and control individuals, respectively. Only gastric bypass was associated with increased incidence of non-alcohol SUD (adjusted hazard ratio 2.54 [95% CI: 1.14-5.65], p = 0.022) compared with control participants. CONCLUSIONS: Gastric bypass surgery was associated with increased risk of non-alcohol SUD, and this should be considered in long-term postoperative care.

Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.

OBJECTIVES: To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study. METHODS: The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n = 265), banding (n = 376), or vertical banded gastroplasty (n = 1369). The control group (n = 2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n = 392 surgery patients/n = 305 controls) or non-T2D (n = 1609 surgery patients/n = 1726 controls) during a median follow-up 26 years. RESULTS: In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR) = 0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p = 0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR = 0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p = 0.516)). CONCLUSIONS: Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.

Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity.

BACKGROUND: Haematopoietic clones caused by somatic mutations with ≥2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years. METHODS: Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care. FINDINGS: In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04). INTERPRETATION: Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care. FUNDING: The Swedish Research Council, The Swedish state under an agreement between the Swedish government and the county councils, the ALF (Avtal om Läkarutbildning och Forskning) agreement, The Swedish Heart-Lung Foundation, The Novo Nordisk Foundation, The European Research Council, The Netherlands Organisation for Scientific Research.

Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

BACKGROUND: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. METHODS: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. FINDINGS: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. INTERPRETATION: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. FUNDING: Sweden's Innovation Agency, Swedish Research Council Health.

Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.

BACKGROUND: Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. METHODS: We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. RESULTS: A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity. CONCLUSION: Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.

Dementia prevention: The potential long-term cost-effectiveness of the FINGER prevention program.

INTRODUCTION: The aim of this study was to estimate the potential cost-effectiveness of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) program. METHODS: A life-time Markov model with societal perspective, simulating a cohort of people at risk of dementia reflecting usual care and the FINGER program. RESULTS: Costs were 1,653,275 and 1,635,346 SEK and quality-adjusted life years (QALYs) were 8.636 and 8.679 for usual care and the FINGER program, respectively, resulting in savings of 16,928 SEK (2023 US$) and 0.043 QALY gains per person, supporting extended dominance for the FINGER program. A total of 1623 dementia cases were avoided with 0.17 fewer person-years living with dementia. The sensitivity analysis confirmed the conclusions in most scenarios. DISCUSSION: The model provides support that programs like FINGER have the potential to be cost-effective in preventing dementia. Results at the individual level are rather modest, but the societal benefits can be substantial because of the large potential target population.

Risk factors for major gastrointestinal bleeding in the general population in Finland.

BACKGROUND: Data on non-drug related risk-factors for gastrointestinal bleeding (GIB) in the general population are limited, especially for life-style factors, clinical measurements and laboratory parameters. AIM: To identify and investigate non-drug risk factors for major GIB in the general population of Finland. METHODS: We performed a retrospective cohort study using data from the FINRISK health examination surveys, which have been conducted every 5 years across Finland from 1987 to 2007. Participants were adults aged 25 years to 74 years, excluding those with a previous hospitalization for GIB. Follow-up from enrollment was performed through linkage to national electronic health registers and ended at an event of GIB that led to hospitalization/death, death due to any other cause, or after 10 years. Covariates included demographics, socioeconomic and lifestyle factors, clinical measurements, laboratory parameters and comorbidities. Variable selection was undertaken using Least Absolute Shrinkage and Selection Operator (LASSO) and factors associated with GIB were identified using Cox regression. RESULTS: Among 33,508 participants, 403 (1.2%) experienced GIB [256 men (63.5%); mean age, 56.0 years (standard deviation (SD) ± 12.1)] and 33105 who did not experience GIB [15768 men (47.6%); mean age, 46.8 (SD ± 13) years], within 10 years of follow-up. Factors associated with a significantly increased risk of GIB were baseline age [per 10-year increase; hazard ratio (HR) 1.62, 95% confidence interval (CI): 1.42-1.86], unemployment (HR: 1.70, 95%CI: 1.11-2.59), body mass index (BMI) (HR: 1.15, 95%CI: 1.01-1.32), gamma-glutamyl transferase (GGT) (HR: 1.05, 95%CI: 1.02-1.09), precursors of GIB (HR: 1.90, 95%CI: 1.37-2.63), cancer (HR: 1.47, 95%CI: 1.10-1.97), psychiatric disorders (HR: 1.32, 95%CI: 1.01-1.71), heart failure (HR: 1.46, 95%CI: 1.04-2.05), and liver disorders (HR: 3.20, 95%CI: 2.06-4.97). Factors associated with a significantly decreased risk of GIB were systolic blood pressure (SBP) (HR: 0.78, 95%CI: 0.64-0.96), 6-10 cups of coffee a day (HR: 0.67, 95%CI: 0.46-0.99), or > 10 cups (HR: 0.43, 95%CI: 0.23-0.81). CONCLUSION: Our study confirms established risk-factors for GIB and identifies potential risk-factors not previously reported such as unemployment, BMI, GGT, SBP and coffee consumption.

Occupational complexity and cognition in the FINGER multidomain intervention trial.

INTRODUCTION: Lifetime exposure to occupational complexity is linked to late-life cognition, and may affect benefits of preventive interventions. METHODS: In the 2-year multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), we investigated, through post hoc analyses (N = 1026), the association of occupational complexity with cognition. Occupational complexity with data, people, and substantive complexity were classified through the Dictionary of Occupational Titles. RESULTS: Higher levels of occupational complexity were associated with better baseline cognition. Measures of occupational complexity had no association with intervention effects on cognition, except for occupational complexity with data, which was associated with the degree of intervention-related gains for executive function. DISCUSSION: In older adults at increased risk for dementia, higher occupational complexity is associated with better cognition. The cognitive benefit of the FINGER intervention did not vary significantly among participants with different levels of occupational complexity. These exploratory findings require further testing in larger studies.

Effect of a multi-domain lifestyle intervention on cardiovascular risk in older people: the FINGER trial.

AIMS: Joint prevention of cardiovascular disease (CVD) and dementia could reduce the burden of both conditions. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) demonstrated a beneficial effect on cognition (primary outcome) and we assessed the effect of this lifestyle intervention on incident CVD (pre-specified secondary outcome). METHODS AND RESULTS: FINGER enrolled 1259 individuals aged 60-77 years (ClinicalTrials.gov NCT01041989). They were randomized (1:1) to a 2-year multi-domain intervention with diet, physical and cognitive activity, and vascular monitoring (n = 631), or general health advice (n = 628). National registries provided data on CVD including stroke, transient ischaemic attack (TIA), or coronary heart event. During an average of 7.4 years, 229 participants (18%) had at least one CVD diagnosis: 107 in the intervention group and 122 in the control group. The incidence of cerebrovascular events was lower in the intervention than the control group: hazard ratio (HR) for combined stroke/TIA was 0.71 [95% confidence interval (CI): 0.51-0.99] after adjusting for background characteristics. Hazard ratio for coronary events was 0.84 (CI: 0.56-1.26) and total CVD events 0.80 (95% CI: 0.61-1.04). Among those with history of CVD (n = 145), the incidence of both total CVD events (HR: 0.50, 95% CI: 0.28-0.90) and stroke/TIA (HR: 0.40, 95% CI: 0.20-0.81) was lower in the intervention than the control group. CONCLUSION: A 2-year multi-domain lifestyle intervention among older adults was effective in preventing cerebrovascular events and also total CVD events among those who had history of CVD.

The effect of adherence on cognition in a multidomain lifestyle intervention (FINGER).

INTRODUCTION: Lifestyle interventions may prevent cognitive decline, but the sufficient dose of intervention activities and lifestyle changes is unknown. We investigated how intervention adherence affects cognition in the FINGER trial (pre-specified subgroup analyses). METHODS: FINGER is a multicenter randomized controlled trial examining the efficacy of multidomain lifestyle intervention (ClinicalTrials.gov NCT01041989). A total of 1260 participants aged 60 to 77 with increased dementia risk were randomized to a lifestyle intervention and control groups. Percentage of completed intervention sessions, and change in multidomain lifestyle score (self-reported diet; physical, cognitive, and social activity; vascular risk) were examined in relation to change in Neuropsychological Test Battery (NTB) scores. RESULTS: Active participation was associated with better trajectories in NTB total and all cognitive subdomains. Improvement in lifestyle was associated with improvement in NTB total and executive function. DISCUSSION: Multidomain lifestyle changes are beneficial for cognitive functioning, but future interventions should be intensive enough, and supporting adherence is essential.