Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.

Funder: Department of HealthFunder: Medical Research CouncilBackgroundTargeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).MethodsIn this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions.FindingsWe included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4·22 [95% CI 3·86-4·62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4·60 (4·06-5·22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5·87 (5·23-6·59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1·23 (1·18-1·27), for men versus women was 1·12 (1·08-1·16), and for Black individuals versus White individuals was 1·13 (1·04-1·24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period.InterpretationA radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care.FundingThe British Hearth Foundation, Health Data Research UK, the UK Medical Research Council, and the National Institute for Health Research

Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations:a nested case-control study

Objective To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations

Epidemiological study of the relationship between dietary and soclo-economic factors and the risk of stroke in a sample of the greek population

The present study aimed to evaluate the association of the traditional Mediterranean dietand major food groups with incidence of and mortality from cerebrovascular disease (CBVD)in a Mediterranean population, taking into account various socio-demographic factors. Thestudy population was a cohort of 23,601 participants from the Greek segment of the EPICStudy (European Prospec- tive Investigation into Cancer and Nutrition) who were free ofcardiovascular diseases and cancer at baseline (1994–1999). Diet was assessed by meansof a validated semi-quantitative food frequency questionnaire. A 10-point scale integratingkey Mediterranean diet characteristics was used to assess the participants’ degree ofadherence to this diet. During a median follow-up period of 10.6 years (1994–2009), 395confirmed incident cases and 196 deaths from CBVD were recorded. Using Cox proportionalhazards regression and adjusting for potential confounders, increased adherence to theMediterranean diet, as measured by 2-point increments in score, was inversely associatedwith CBVD incidence (adjusted hazard ratio = 0.85, 95% confidence interval: 0.74, 0.96) andmortality (adjusted hazard ratio = 0.88, 95% CI: 0.73, 1.06). These inverse trends weremostly evident among women and with respect to ischemic rather than hemorrhagic CBVDand were largely driven by consumption of vegetables, legumes, and olive oil. These dataprovide support for an inverse association of adherence to the Mediterranean diet withCBVD incidence and mortality.Η παρούσα μελέτη έχει ως σκoπό να διερευνήσει τη συσχέτιση των διατροφικών συνηθειώνμε την επίπτωση και τη θνησιμότητα από αγγειακά εγκεφαλικά επείσοδια (ΑΕΕ), σεσυνάρτηση με διάφορους κοινωνικο-οικονομικούς παράγοντες. Ο πληθυσμός της μελέτηςαποτελείται από 23.601 άτομα τα οποία συμμέτεχουν στο ελληνικό τμήμα της προοπτικήςμελέτης ΕΠΙΚ (Ευρωπαικό Πρόγραμμα συνεργασίας Ιατρικής και Κοινωνίας), η οποίαξεκίνησε το 1994. Η εκτίμηση της διατροφής έγινε με την χρήση ενός σταθμισμένουημιποσοτικού διατροφικού ερωτηματολογίου συχνότητας και για την εκτίμηση τηςπροσκόλλησης στη παραδοσιακή Μεσογειακή διατροφή χρησιμοποιήθηκε μια κλίμακα 10μονάδων, η οποία ενσωματώνει τα χαρακτηριστικά του συγκεκριμένου διατροφικούπροτύπου. Κατά τη διάρκεια διάμεσης παρακολούθησης 10,6 ετών, παρατηρήθηκαν 395επιβεβαιωμένα νέα περιστατικά και 196 θάνατοι από ΑΕΕ. Μετά από ανάλυση επιβίωσης μεμοντέλα αναλογικών κινδύνων και σταθμίζοντας για συγχυτικούς παράγοντες, η αύξηση κατάδύο μονάδες στη κλίμακα της προσκόλλησης στη παραδοσιακή Μεσογειακή διατροφήσχετίστηκε με ελλατωμένο κίνδυνο για εμφάνιση πρώτου ΑΕΕ κατά 15% (αναλογία κινδύνου0,85, 95% διάστημα εμπιστοσύνης: 0,74- 0,96) και θανάτου από ΑΕΕ κατά 12% (αναλογίακινδύνου 0,88, 95% διάστημα εμπιστοσύνης: 0,73-1,06). Οι σχέσεις αυτές ήταν πιο ισχυρέςστις γυναίκες και για τα ισχαιμικά ΑΕΕ και σε μεγάλο βαθμό υποκινούνταν από τηνκατανάλωση λαχανικών, οσπρίων και ελαιόλαδου

4 Statin-Induced myotoxicity: An overview of the risk factors

Statins are well tolerated and particularly safe medicines. The most important clinical side effect of statins is myotoxicity. Rhabdomyolysis is the most rare, but most serious of myotoxicity. Clinically it is characterized by proximal or diffuse muscle pain, weakness and myoglobinuria. CPK usually exceeds by far 10 times the upper limit of normal. Factors, which increase the risk of myotoxicity, are: advanced age and female gender (for unknown reasons), genetic polymorphism (low hepatic or intestinal expression of the isoenzyme CYP3A4), hereditary myopathy, lipophilicity of some statins, high doses of statins (dose-dependent side effect), medicines and foods that are metabolized by CYP3A4, renal failure and hepatic dysfunction, as well as the conditions that worsen them

The syndrome of rhabdomyolysis: complications and treatment

Rhabdomyolysis is a syndrome of skeletal muscle cell damage that leads to the release of toxic intracellular material into the systemic circulation. The pathogenesis of rhabdomyolysis is based on an increase in free ionized calcium in the cytoplasm. Its main complications include (a) acute renal failure, which is triggered by renal vasoconstriction and ischemia, (b) myoglobin cast formation in the distal convoluted tubules, and (c) direct renal toxic effect of myoglobin on the epithelial cells of proximal convoluted tubules. Other major complications include electrolyte disorders, such as hyperkalemia, which may cause cardiac arrhythmias, metabolic acidosis, hyperphosphatemia, early hypocalcemia, and late hypercalcemia. Compartmental syndrome and disseminated intravascular coagulopathy may also emerge. The management of myoglobinuric acute renal failure includes aggressive fluid administration to restore the hypovolemia and urine alkalization. The concomitant electrolyte and metabolic disorders should also be treated appropriately; hemodialysis should be considered when life-threatening hyperkalemia and metabolic acidosis exist. In the case of compartmental syndrome, it is important to monitor the intra-compartmental pressure and to perform fasciotomy, if required. When diagnosed early and if the appropriate treatment is initiated promptly, the complications of rhabdomyolysis are preventable and the syndrome has a good prognosis

Risk factors and drug interactions predisposing to statin-induced myopathy: implications for risk assessment, prevention and treatment

HMG-CoA reductase inhibitors ('statins') represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical. The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant interindividual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available combinations are summarized. Finally, we provide an update of current guidelines for the prevention and management of statin myopathy. The identification of patients with an increased proclivity to statin-induced myopathy could allow more cost-effective approaches of monitoring and screening, facilitate targeted prevention of potential complications, and further improve the already overwhelmingly positive benefit-risk ratio of statins

In vivo comparative study of linear versus geometrically correct three-dimensional reconstruction of coronary arteries

Although conventional linear 3-dimensional (3D) reconstruction of coronary arteries by intravascular ultrasound has been widely used for the assessment of plaque volume and progression; the volumetric error (VE) that is produced has not been adequately studied. Linear and geometrically correct 3D reconstruction was applied in 16 coronary arterial segments from 9 patients. Using geometrically correct reconstruction as reference, VE was assessed in 1-mm-long arterial slices. Although for the entire length of the coronary arteries VEs for lumen, external elastic membrane (EEM), and intima-media volumes were minimal (lumen VE 0.4%, -0.8 to 1.8; EEM VE 0.3%, -0.9 to 1.9; intima-media VE 0.4%, -1.4 to 2.2), the VE in each arterial slice exhibited a large variation from -15.6% to 36.2% for lumen volume, from -12.9% to 33.1% for EEM volume, and from -17.2% to 46.7% for intima-media volume, suggesting that linear reconstruction over- or underestimates the true arterial volumes. Lumen VE, EEM VE, and intima-media VE were also significantly higher in curved arterial subsegments than in relatively straight arterial subsegments (p <0.05). In conclusion, in highly curved arterial subsegments, the VE that is produced by linearly stacking the intravascular ultrasound images may be not negligible. Geometrically correct reconstruction of coronary arteries provides more reliable arterial reconstructions and plaque volume measurements. It is anticipated that clinical application of this technique will contribute to more accurate follow-up of the progression of atherosclerosis and assessment of arterial remodeling

Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records

Background Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR). Methods In this longitudinal, population-based cohort study we used linked EHR data from 400 primary care practices (via the Clinical Practice Research Datalink) in England, accessed via the CALIBER programme. Eligible participants were aged 18-74 years, were registered at a general practice clinic, and had BMI and weight measurements recorded between Jan 1, 1998, and June 30, 2016, during the period when they had eligible linked data with at least 1 year of follow-up time. We calculated longitudinal changes in BMI over 1, 5, and 10 years, and investigated the absolute risk and odds ratios (ORs) of transitioning between BMI categories (underweight, normal weight, overweight, obesity class 1 and 2, and severe obesity [class 3]), as defined by WHO. The associations of demographic factors with BMI transitions were estimated by use of logistic regression analysis, adjusting for baseline BMI, family history of cardiovascular disease, use of diuretics, and prevalent chronic conditions. Findings We included 2 092 260 eligible individuals with more than 9 million BMI measurements in our study. Young adult age was the strongest risk factor for weight gain at 1, 5, and 10 years of follow-up. Compared with the oldest age group (65-74 years), adults in the youngest age group (18-24 years) had the highest OR (4.22 [95% CI 3.86-4.62]) and greatest absolute risk (37% vs 24%) of transitioning from normal weight to overweight or obesity at 10 years. Likewise, adults in the youngest age group with overweight or obesity at baseline were also at highest risk to transition to a higher BMI category; OR 4.60 (4.06-5.22) and absolute risk (42% vs 18%) of transitioning from overweight to class 1 and 2 obesity, and OR 5.87 (5.23-6.59) and absolute risk (22% vs 5%) of transitioning from class 1 and 2 obesity to class 3 obesity. Other demographic factors were consistently less strongly associated with these transitions; for example, the OR of transitioning from normal weight to overweight or obesity in people living in the most socially deprived versus least deprived areas was 1.23 (1.18-1.27), for men versus women was 1.12 (1.08-1.16), and for Black individuals versus White individuals was 1.13 (1.04-1.24). We provide an open access online risk calculator, and present high-resolution obesity risk charts over a 1-year, 5-year, and 10-year follow-up period. Interpretation A radical shift in policy is required to focus on individuals at the highest risk of weight gain (ie, young adults aged 18-24 years) for individual-level and population-level prevention of obesity and its long-term consequences for health and health care. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

A prospective analysis of the association between dietary fiber intake and prostate cancer risk in EPIC

Few studies have examined the association between dietary fiber intake and prostate cancer risk. We evaluated the association between dietary fiber intake and the risk of prostate cancer among 142,590 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Consumption of dietary fiber (total, cereal, fruit and vegetable fiber) seas estimated by validated dietary questionnaires and calibrated using 24-hr dietary recalls. Incidence rate ratios were estimated using Cox regression and adjusted for potential confounding factors. During all average of 8.7 years follow-up, prostate cancer was diagnosed in 2,747 men. Overall, there was no association between dietary fiber intake (total, cereal, fruit or vegetable fiber) and prostate cancer risk, although calibrated intakes of total fiber and fruit fiber were associated with nonstatistically significant reductions in risk. There was no association between fiber derived from cereals or vegetables and risk and no evidence for heterogeneity in any of the risk estimates by stage or grade of disease. Our results suggest that dietary fiber intake is not associated with prostate cancer risk. (C) 2008 Wiley-Liss, Inc