Kristjan Karason

Bariatric Surgery and Long-term Cardiovascular Events

CONTEXTnObesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking.nnnOBJECTIVEnTo study the association between bariatric surgery, weight loss, and cardiovascular events.nnnDESIGN, SETTING, AND PARTICIPANTSnThe Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals.nnnMAIN OUTCOME MEASURESnThe primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined.nnnRESULTSnBariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P < .001).nnnCONCLUSIONnCompared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.

Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial

BACKGROUNDnObesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data.nnnMETHODSnThe SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years).nnnFINDINGSnBariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention.nnnINTERPRETATIONnBariatric surgery was associated with reduced cancer incidence in obese women but not in obese men.nnnFUNDINGnSwedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.

Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications.

IMPORTANCEnShort-term studies show that bariatric surgery causes remission of diabetes. The long-term outcomes for remission and diabetes-related complications are not known.nnnOBJECTIVESnTo determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery.nnnDESIGN, SETTING, AND PARTICIPANTSnThe Swedish Obese Subjects (SOS) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden. Of patients recruited between September 1, 1987, and January 31, 2001, 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline. For the current analysis, diabetes status was determined at SOS health examinations until May 22, 2013. Information on diabetes complications was obtained from national health registers until December 31, 2012. Participation rates at the 2-, 10-, and 15-year examinations were 81%, 58%, and 41% in the control group and 90%, 76%, and 47% in the surgery group. For diabetes assessment, the median follow-up time was 10 years (interquartile range [IQR], 2-15) and 10 years (IQR, 10-15) in the control and surgery groups, respectively. For diabetes complications, the median follow-up time was 17.6 years (IQR, 14.2-19.8) and 18.1 years (IQR, 15.2-21.1) in the control and surgery groups, respectively.nnnINTERVENTIONSnAdjustable or nonadjustable banding (n = 61), vertical banded gastroplasty (n = 227), or gastric bypass (n = 55) procedures were performed in the surgery group, and usual obesity and diabetes care was provided to the control group.nnnMAIN OUTCOMES AND MEASURESnDiabetes remission, relapse, and diabetes complications. Remission was defined as blood glucose <110 mg/dL and no diabetes medication.nnnRESULTSnThe diabetes remission rate 2 years after surgery was 16.4% (95% CI, 11.7%-22.2%; 34/207) for control patients and 72.3% (95% CI, 66.9%-77.2%; 219/303) for bariatric surgery patients (odds ratio [OR], 13.3; 95% CI, 8.5-20.7; P <u2009.001). At 15 years, the diabetes remission rates decreased to 6.5% (4/62) for control patients and to 30.4% (35/115) for bariatric surgery patients (OR, 6.3; 95% CI, 2.1-18.9; P <u2009.001). With long-term follow-up, the cumulative incidence of microvascular complications was 41.8 per 1000 person-years (95% CI, 35.3-49.5) for control patients and 20.6 per 1000 person-years (95% CI, 17.0-24.9) in the surgery group (hazard ratio [HR], 0.44; 95% CI, 0.34-0.56; P <u2009.001). Macrovascular complications were observed in 44.2 per 1000 person-years (95% CI, 37.5-52.1) in control patients and 31.7 per 1000 person-years (95% CI, 27.0-37.2) for the surgical group (HR, 0.68; 95% CI, 0.54-0.85; P =u2009.001).nnnCONCLUSIONS AND RELEVANCEnIn this very long-term follow-up observational study of obese patients with type 2 diabetes, bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care. These findings require confirmation in randomized trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01479452.

Effects of obesity and weight loss on left ventricular mass and relative wall thickness: survey and intervention study.

Abstract Objectives: To investigate the consequences of longstanding obesity on left ventricular mass and structure and to examine the effects of weight loss on these variables. Design: Cross sectional survey and controlled intervention study. Setting: City of Gothenburg and surrounding areas, Sweden. Subjects: 41 obese patients treated with weight reducing gastric surgery, 31 obese patients treated conventionally, and 43 non-obese subjects. Main outcome measures: Changes in left ventricular mass and relative wall thickness. Results: Obese patients had higher blood pressure, greater left ventricular mass, and increased relative wall thickness than did matched non-obese control subjects. Obese subjects treated with gastric surgery had a substantial weight loss and a significant reduction in all variables when compared with conventionally treated obese subjects. Univariate and multivariate analysis of pooled data from the two groups of obese subjects showed that changes in relative wall thickness and left ventricular mass were more closely related to the change in weight than to the concomitant change in blood pressure. Conclusions: Structural heart abnormalities occurring in conjunction with obesity diminish after weight loss. The regression in these structural aberrations is better predicted by the weight loss than by the accompanying reduction in blood pressure. To prevent or improve abnormalities of heart structure in obese people, weight control should be the primary goal; it should be regarded as at least as important as regulating blood pressure. Key messages Obesity and hypertension often coexist, leading to various degrees of eccentric and concentric left ventricular hypertrophy These structural heart changes are in turn powerful risk factors for cardiovascular morbidity and mortality Weight loss is followed by a reduction in left ventricular mass and relative wall thickness Changes in left ventricular structure are better predicted by the weight loss than by the accompanying reduction in blood pressure To prevent or improve abnormal heart structure in obese people, weight control should be the primary goal and should be regarded as at least as important as regulating blood pressure

Evidence for obesity paradox in patients with acute coronary syndromes: a report from the Swedish Coronary Angiography and Angioplasty Registry.

AIMSnThe obesity paradox refers to the epidemiological evidence that obesity compared with normal weight is associated with counter-intuitive improved health in a variety of disease conditions. The aim of this study was to investigate the relationship between body mass index (BMI) and mortality in patients with acute coronary syndromes (ACSs).nnnMETHODS AND RESULTSnWe extracted data from the Swedish Coronary Angiography and Angioplasty Registry and identified 64 436 patients who underwent coronary angiography due to ACSs. In 54 419 (84.4%) patients, a significant coronary stenosis was identified, whereas 10 017 (15.6%) patients had no significant stenosis. Patients were divided into nine different BMI categories. The patients with significant stenosis were further subdivided according to treatment received such as medical therapy, percutaneous coronary intervention (PCI), or coronary artery by-pass grafting. Mortality for the different subgroups during a maximum of 3 years was compared using Cox proportional hazards regression with the lean BMI category (21.0 to <23.5 kg/m(2)) as the reference group. Regardless of angiographic findings [significant or no significant coronary artery disease (CAD)] and treatment decision, the underweight group (BMI <18.5 kg/m(2)) had the greatest risk for mortality. Medical therapy and PCI-treated patients with modest overweight (BMI category 26.5-<28 kg/m(2)) had the lowest risk of mortality [hazard ratio (HR) 0.52; 95% CI 0.34-0.80 and HR 0.64; 95% CI 0.50-0.81, respectively]. When studying BMI as a continuous variable in patients with significant CAD, the adjusted risk for mortality decreased with increasing BMI up to ~35 kg/m(2) and then increased. In patients with significant CAD undergoing coronary artery by-pass grafting and in patients with no significant CAD, there was no difference in mortality risk in the overweight groups compared with the normal weight group.nnnCONCLUSIONnIn this large and unselected group of patients with ACSs, the relation between BMI and mortality was U-shaped, with the nadir among overweight or obese patients and underweight and normal-weight patients having the highest risk. These data strengthen the concept of the obesity paradox substantially.

Impact of blood pressure and insulin on the relationship between body fat and left ventricular structure

AIMSnObesity leads to hypertension and metabolic disturbances, as well as left ventricular hypertrophy and altered left ventricular geometry. However, the underlying mechanisms behind these relationships are not clear. The aim of this study was to investigate how body composition, blood pressure and metabolic factors relate to left ventricular mass and geometry.nnnMETHODS AND RESULTSnWe included 60 patients with obesity (BMI 31-52) and 43 non-obese subjects (BMI 18-27). Body weight, blood pressure and metabolic parameters were measured and echocardiography was performed. Body composition was determined by gender-specific anthropometric equations. Multivariate analyses showed that both body fat and lean body mass were independently and positively associated with left ventricular mass, whereas adipose tissue alone was related to relative wall thickness. When blood pressure was added to the model, the associations between body fat and left ventricular mass and geometry were weakened. Further adjustment for insulin levels eliminated the relationship between adipose tissue and relative wall thickness.nnnCONCLUSIONSnBoth total adipose tissue and lean body mass predict an increase in myocardial mass, while adipose tissue alone is related to a rise in relative wall thickness. The concentric left ventricular geometry associated with body fat accumulation appears to be mediated, at least in part, by blood pressure and insulin levels.

Incidence and remission of type 2 diabetes in relation to degree of obesity at baseline and 2 year weight change: the Swedish Obese Subjects (SOS) study.

AbstractAims/hypothesisThe aim of this work was to analyse the rates of incidence and remission of type 2 diabetes in relation to baseline BMI and weight change in the prospective, controlled Swedish Obese Subjects (SOS) study.MethodsThree-thousand four-hundred and eighty-five obese individuals receiving bariatric surgery or conventional treatment were grouped into four baseline BMI categories (<35, 35–40, 40–45 or ≥45xa0kg/m2) and five weight-change categories according to their BMI at 2xa0years (increase [≥1 BMI unit increase], no change [less than 1 BMI unit change], minor reduction [−1 to −9 BMI units], medium reduction [−10 to −14 BMI units] and major reduction [< −15 BMI units]). The incidence and remission of diabetes at 2xa0years was assessed.ResultsAmong individuals with no weight change, diabetes incidence rates were 5.5%, 7.4%, 8.3% and 5.2%, in the four baseline BMI categories, respectively. In those with an initial BMI of 35–40, 40–45 and ≥45xa0kg/m2 who attained a minor reduction in weight, the corresponding rates were 1.3%, 1.2% and 3.4%, respectively. In both the medium- and major-weight-reduction groups, diabetes incidence was ≤0.5%. Among individuals with diabetes at baseline, the remission rates were 15.3–26.9% in the no-weight-change groups, and 48.1–70% for individuals who attained a minor weight reduction. In the medium- and major-weight-reduction groups, the remission rate was 77–97%. There were no differences in 2xa0year incidence and remission rates between different baseline BMI groups that achieved the same degree of weight reduction.Conclusions/interpretationIn obese individuals, the favourable effect of weight reduction on type 2 diabetes incidence and remission is independent of initial BMI.n Trial registration ClinicalTrials.gov number NCT01479452

Bariatric Surgery and the Risk of New-Onset Atrial Fibrillation in Swedish Obese Subjects

BACKGROUNDnObesity is a risk factor for atrial fibrillation, which in turn is associated with stroke, heart failure, and increased all-cause mortality.nnnOBJECTIVESnThe authors investigated whether weight loss through bariatric surgery may reduce the risk of new-onset atrial fibrillation.nnnMETHODSnSOS (Swedish Obese Subjects) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary healthcare centers in Sweden. The cohort was recruited between 1987 and 2001. Among 4,021 obesexa0individuals with sinus rhythm and no history of atrial fibrillation, 2,000 underwent bariatric surgery (surgery group), and 2,021 matched obese control subjects received usual care (control group). The outcome, first-time atrial fibrillation, was ascertained by crosschecking the SOS database with the Swedish National Patient Register on inpatientxa0and outpatient diagnosis codes.nnnRESULTSnDuring a median follow-up of 19 years, first time atrial fibrillation occurred in 247 patients (12.4%) in the surgical group, and in 340 (16.8%) control subjects. The risk of developing atrial fibrillation was 29% lower in the surgery group versus the control group (hazard ratio: 0.71; 95% confidence interval: 0.60 to 0.83; pxa0< 0.001). Younger individuals benefited more from surgical intervention than those who were older (p value for interaction 0.001). Also, those with a high diastolic blood pressure benefitted more from surgery than did those with a low diastolic blood pressure (p for interactionxa0= 0.028).nnnCONCLUSIONSnCompared with usual care, weight loss through bariatric surgery reduced the risk of atrial fibrillationxa0among persons being treated for severe obesity. The risk reduction was more apparent in younger people and in thosexa0with higher blood pressure.

Evaluation of CXCL9 and CXCL10 as circulating biomarkers of human cardiac allograft rejection

BackgroundCardiac allograft rejection remains a significant clinical problem in the early phase after heart transplantation and requires frequent surveillance with endomyocardial biopsy. However, this is an invasive procedure, which is unpleasant for the patient and carries a certain risk. Therefore, a sensitive non-invasive biomarker of acute rejection would be desirable.MethodsEndomyocardial tissue samples and serum were obtained in connection with clinical biopsies from twenty consecutive heart transplant patients followed for six months. A rejection episode was observed in 14 patients (11 men and 3 women) and biopsies obtained before, during and after the episode were identified. Endomyocardial RNA, from three patients, matching these three points in time were analysed with DNA microarray. Genes showing up-regulation during rejection followed by normalization after the rejection episode were evaluated further with real-time RT-PCR. Finally, ELISA was performed to investigate whether change in gene-regulation during graft rejection was reflected in altered concentrations of the encoded protein in serum.ResultsThree potential cardiac allograft rejection biomarker genes, chemokine (C-X-C motif) ligand 9 (CXCL9), chemokine (C-X-C motif) ligand 10 (CXCL10) and Natriuretic peptide precursor A (NPPA), from the DNA microarray analysis were selected for further evaluation. CXCL9 was significantly upregulated during rejection (p < 0.05) and CXCL10 displayed a similar pattern without reaching statistical significance. Serum levels of CXCL9 and CXCL10 were measured by ELISA in samples from 10 patients before, during and after cardiac rejection. There were no changes in CXCL9 and CXCL10 serum concentrations during cardiac rejection. Both chemokines displayed large individual variations in the selected samples, but the serum levels between the two chemokines correlated (p < 0.001).ConclusionWe conclude, that despite a distinct up-regulation of CXCL9 mRNA in human hearts during cardiac allograft rejection, this was not reflected in the serum levels of the encoded protein. Thus, in contrast to previous suggestions, serum CXCL9 does not appear to be a promising serum biomarker for cardiac allograft rejection.

Impact of body composition, fat distribution and sustained weight loss on cardiac function in obesity

BACKGROUNDnObesity is associated with alterations in left ventricular function varying along with the degree of fatness, but the mechanisms underlying this co-variation are not clear. In a case-control study we examined how sustained weight losses affect cardiac function and report on how body composition and fat distribution relate to the left ventricular performance.nnnMETHODSnAt the 10-year follow-up of the Swedish obese subjects (SOS) study cohort we identified 44 patients with sustained weight losses after bariatric surgery (surgery group) and 44 matched obese control patients who remained weight stable (obese group). We also recruited 44 matched normal weight subjects (lean group). Dual-energy X-ray absorptiometry, computed tomography and echocardiography were performed to evaluate body composition, fat distribution and cardiac function.nnnRESULTSnBMI was 42.5 kg/m(2), 31.5 kg/m(2) and 24.4 kg/m(2) for the obese, surgery and lean groups respectively. Increasing degree of obesity was associated with larger left ventricular volumes (p < 0.001), higher cardiac output (p < 0.001), reduced systolic myocardial velocity (p<0.001) and impaired ventricular relaxation (p = 0.015). In multivariate analyses, left ventricular volume, stroke volume and cardiac output primarily associated with lean body mass, whereas blood pressure, heart rate and variables reflecting cardiac dysfunction were more related to total body fat and visceral adiposity.nnnCONCLUSIONnObesity is associated with discrete but distinct disturbances in the left ventricular performance appearing to be related to both the total amount of body fat and degree of visceral adiposity. Patients with sustained weight losses display superior left ventricular systolic and diastolic functions as compared with their obese counterparts remaining weight stable.