The effect of thyroid hormone therapy on muscle function, strength and mass in older adults with subclinical hypothyroidism-an ancillary study within two randomized placebo controlled trials.

BACKGROUND: loss of skeletal muscle function, strength and mass is common in older adults, with important socioeconomic impacts. Subclinical hypothyroidism is common with increasing age and has been associated with reduced muscle strength. Yet, no randomized placebo-controlled trial (RCT) has investigated whether treatment of subclinical hypothyroidism affects muscle function and mass. METHODS: this is an ancillary study within two RCTs conducted among adults aged ≥65 years with persistent subclinical hypothyroidism (thyrotropin (TSH) 4.60-19.99 mIU/l, normal free thyroxine). Participants received daily levothyroxine with TSH-guided dose adjustment or placebo and mock titration. Primary outcome was gait speed at final visit (median 18 months). Secondary outcomes were handgrip strength at 1-year follow-up and yearly change in muscle mass. RESULTS: we included 267 participants from Switzerland and the Netherlands. Mean age was 77.5 years (range 65.1-97.1), 129 (48.3%) were women, and their mean baseline TSH was 6.36 mIU/l (standard deviation [SD] 1.9). At final visit, mean TSH was 3.8 mIU/l (SD 2.3) in the levothyroxine group and 5.1 mIU/l (SD 1.8, P < 0.05) in the placebo group. Compared to placebo, participants in the levothyroxine group had similar gait speed at final visit (adjusted between-group mean difference [MD] 0.01 m/s, 95% confidence interval [CI] -0.06 to 0.09), similar handgrip strength at one year (MD -1.22 kg, 95% CI -2.60 to 0.15) and similar yearly change in muscle mass (MD -0.15 m2, 95% CI -0.49 to 0.18). CONCLUSIONS: in this ancillary analysis of two RCTs, treatment of subclinical hypothyroidism did not affect muscle function, strength and mass in individuals 65 years and older.

[Management of type 2 diabetes on oral nutritional supplement]. / Prise en charge du diabète de type 2 chez le patient dénutri sous supplément nutritif oral.

The management of a patient with type 2 diabetes is well known and is the subject of numerous studies. Protein-calorie malnutrition, on the other hand, is an entity that is still under-diagnosed and under-treated. When artificial nutrition is introduced, glucose homeostasis can be disturbed in case of (pre-)diabetes. To date, few recommendations based on expert opinion exist on the management of diabetes after the introduction of enteral or parenteral nutrition. This article proposes an algorithm for the management of type 2 diabetes when oral nutritional supplements are introduced.

La prise en charge d'un patient diabétique de type 2 est bien connue et fait l'objet de nombreuses études. La dénutrition protéino-calorique quant à elle est une entité encore sous-diagnostiquée et sous-traitée. Lors de la mise en place d'une nutrition artificielle, l'équilibre glycémique peut être perturbé en cas de prédiabète ou de diabète. À ce jour, quelques recommandations basées sur des avis d'experts existent sur la prise en charge du diabète après la mise en place d'une nutrition entérale ou parentérale. Cet article propose un algorithme de prise en charge du diabète de type 2, lors de l'introduction de suppléments nutritifs oraux.

[Is ketogenic diet effective against cancer ?] / Le régime cétogène : efficace contre le cancer ?

The ketogenic diet, which consists of reduced carbohydrate intake and increased fat intake, is a recognized treatment option for children with intractable epilepsy. This diet is now receiving renewed interest from physicians and researchers because of its potential therapeutic effect in other diseases, such as neurodegenerative diseases, metabolic syndrome or cancer. Since cancer is one of the major public health challenges, complementary approaches to improve the efficacy of standard anti-cancer therapies are the subject of much research. This article reviews the place of the ketogenic diet as a complementary therapy in cancer, the scientific evidence and possible practical aspects of such an approach.

Le régime cétogène vise à réduire l'apport nutritionnel d'hydrates de carbone en augmentant les lipides. Ce régime est une option thérapeutique reconnue, en particulier chez les enfants souffrant d'épilepsie réfractaire. Il fait aujourd'hui l'objet d'un regain d'intérêt de la part des médecins et des chercheurs, en raison de son potentiel effet thérapeutique dans d'autres pathologies comme certaines maladies neurodégénératives, le syndrome métabolique ou même le cancer. Le cancer étant l'un des grands défis de santé publique, les approches complémentaires pour améliorer l'efficacité des thérapies anticancéreuses standards font l'objet de nombreuses recherches. Cet article fait le point sur la place du régime cétogène comme thérapie complémentaire dans le cancer, les évidences scientifiques et les éventuels aspects pratiques d'une telle approche.

Lowering blood cholesterol does not affect neuroinflammation in experimental autoimmune encephalomyelitis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disabling disease of the central nervous system (CNS) commonly affecting young adults. There is increasing evidence that environmental factors are important in the development and course of MS. The metabolic syndrome (MetS) which comprises dyslipidemia has been associated with a worse outcome in MS disease. Furthermore, the lipid-lowering drug class of statins has been proposed to improve MS disease course. However, cholesterol is also rate-limiting for myelin biogenesis and promotes remyelination in MS animal models. Thus, the impact of circulating blood cholesterol levels during the disease remains debated and controversial. METHODS: We assessed the role of circulating cholesterol on the murine model of MS, the experimental autoimmune encephalomyelitis (EAE) disease using two different approaches: (1) the mouse model of familial hypercholesterolemia induced by low-density lipoprotein receptor (LDLr) deficiency, and (2) the use of the monoclonal anti-PCSK9 neutralizing antibody alirocumab, which reduces LDLr degradation and consequently lowers blood levels of cholesterol. RESULTS: Elevated blood cholesterol levels induced by LDLr deficiency did not worsen clinical symptoms of mice during EAE. In addition, we observed that the anti-PCSK9 antibody alirocumab did not influence EAE disease course, nor modulate the immune response in EAE. CONCLUSIONS: These findings suggest that blood cholesterol level has no direct role in neuro-inflammatory diseases and that the previously shown protective effects of statins in MS are not related to circulating cholesterol.

Thyroid antibodies and levothyroxine effects in subclinical hypothyroidism: A pooled analysis of two randomized controlled trials.

BACKGROUND: Antithyroid antibodies increase the likelihood of developing overt hypothyroidism, but their clinical utility remains unclear. No large randomized controlled trial (RCT) has assessed whether older adults with subclinical hypothyroidism (SHypo) caused by autoimmune thyroid disease derive more benefits from levothyroxine treatment (LT4). OBJECTIVE: To determine whether older adults with SHypo and positive antibodies derive more clinical benefits from LT4 than those with negative antibodies. METHODS: We pooled individual participant data from two RCTs, Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism and IEMO 80+. Participants with persistent SHypo were randomly assigned to receive LT4 or placebo. We compared the effects of LT4 versus placebo in participants with and without anti-thyroid peroxidase (TPO) at baseline. The two primary outcomes were 1-year change in Hypothyroid Symptoms and Tiredness scores on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire. RESULTS: Among 660 participants (54% women) ≥65 years, 188 (28.5%) had positive anti-TPO. LT4 versus placebo on Hypothyroid Symptoms lead to an adjusted between-group difference of -2.07 (95% confidence interval: -6.04 to 1.90) for positive antibodies versus 0.89 (-1.76 to 3.54) for negative antibodies (p for interaction = 0.31). Similarly, there was no treatment effect modification by baseline antibody status for Tiredness scores-adjusted between-group difference 1.75 (-3.60 to 7.09) for positive antibodies versus 1.14 (-1.90 to 4.19) for negative antibodies (p for interaction = 0.98). Positive anti-TPO were not associated with better quality of life, improvement in handgrip strength, or fewer cardiovascular outcomes with levothyroxine treatment. CONCLUSIONS: Among older adults with SHypo, positive antithyroid antibodies are not associated with more benefits on clinical outcomes with LT4.

[Vitamin deficiencies in the adult outpatient setting]. / Carences vitaminiques chez l'adulte en médecine ambulatoire.

Since their discovery more than a century ago to this day, vitamins went from misunderstood molecules with mysterious properties to fundamental components with undoubted clinical implications. Despite the scientific progresses in the understanding of their physiopathological role, vitamins raise to this day multiple interrogations in clinical practice. This article aims at answering questions that are frequently encountered in the outpatient setting regarding vitamin deficiencies: who to screen ? At what moment ? By which test ? How to interpret the results ? How to supplement ? By answering these questions, we hope to provide the general practitioners with a pragmatic tool to guide them in the management of issues related to vitamins.

Depuis leur découverte il y a plus d'un siècle à aujourd'hui, les vitamines sont passées de molécules méconnues et aux propriétés mystérieuses à des composants primordiaux et aux implications cliniques certaines. Malgré les progrès scientifiques dans la compréhension de leur rôle physiopathologique, les vitamines suscitent encore de nombreuses interrogations en pratique clinique. Cet article s'efforce de répondre aux questions fréquem ment rencontrées en médecine ambulatoire portant sur les carences vitaminiques: qui dépister ? À quel moment ? Par quel test ? Comment interpréter les résultats ? Comment supplémenter ? En répondant à ces questions, nous espérons fournir au médecin de premier recours un outil pragmatique pour l'orienter dans la prise en charge des problématiques vitaminiques.

Peripheral Volumetric Muscle Area and Total Body Volume in Postmenopausal Women With Rheumatoid Arthritis.

The effect of rheumatoid arthritis (RA) on peripheral muscle parameters is not completely understood. This study aimed to elucidate the influence of RA on peripheral muscle area and whole body skeletal muscle mass index (SMI) using peripheral quantitative computed tomography and dual-energy X-ray absorptiometry in postmenopausal women. This cross-sectional study included 54 postmenopausal women with RA and 86 healthy controls. Peripheral quantitative computed tomography and dual-energy X-ray absorptiometry were used to measure the muscle cross-sectional area and skeletal muscle mass. Muscle strength was assessed using a handheld dynamometer. Additionally, the effects of RA on muscle area and density as well as the bone / muscle area ratio were analyzed using multivariate models. The muscle area index of the thigh and forearm were correlated between both groups (RA: r = 0.357, p = 0.030; and healthy controls: r = 0.608, p < 0.001) and each index correlated with SMI in RA and healthy controls (p < 0.001). Bone / muscle area ratio correlated between forearms and thighs in health controls only (r = 0.547, p < 0.001). The RA group had a decreased thigh muscle area (p = 0.014); the fat area and fat muscle area ratio at the thigh and forearm were significantly increased (all p < 0.001), as well as thigh bone / muscle area ratio (p = 0.015). The RA group also had significantly lower forearm muscle density (p < 0.001). A sensitivity analysis excluding those on bisphosphonates led to similar results. Independent of RA, the thigh and forearm muscle area correlate with each other and with SMI. Differences in the bone / muscle ratio between RA and healthy controls may indicate regional muscle effects of inflammation and inactivity.

L-Thyroxine Therapy for Older Adults With Subclinical Hypothyroidism and Hypothyroid Symptoms: Secondary Analysis of a Randomized Trial.

BACKGROUND: L-thyroxine does not improve hypothyroid symptoms among adults with subclinical hypothyroidism (SCH). However, those with greater symptom burden before treatment may still benefit. OBJECTIVE: To determine whether L-thyroxine improves hypothyroid symptoms and tiredness among older adults with SCH and greater symptom burden. DESIGN: Secondary analysis of the randomized, placebo-controlled trial TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial). (ClinicalTrials.gov: NCT01660126). SETTING: Switzerland, Ireland, the Netherlands, and Scotland. PARTICIPANTS: 638 persons aged 65 years or older with persistent SCH (thyroid-stimulating hormone level of 4.60 to 19.9 mIU/L for >3 months and normal free thyroxine level) and complete outcome data. INTERVENTION: L-thyroxine or matching placebo with mock dose titration. MEASUREMENTS: 1-year change in Hypothyroid Symptoms and Tiredness scores (range, 0 to 100; higher scores indicate more symptoms) on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire among participants with high symptom burden (baseline Hypothyroid Symptoms score >30 or Tiredness score >40) versus lower symptom burden. RESULTS: 132 participants had Hypothyroid Symptoms scores greater than 30, and 133 had Tiredness scores greater than 40. Among the group with high symptom burden, the Hypothyroid Symptoms score improved similarly between those receiving L-thyroxine (mean within-group change, -12.3 [95% CI, -16.6 to -8.0]) and those receiving placebo (mean within-group change, -10.4 [CI, -15.3 to -5.4]) at 1 year; the adjusted between-group difference was -2.0 (CI, -5.5 to 1.5; P = 0.27). Improvements in Tiredness scores were also similar between those receiving L-thyroxine (mean within-group change, -8.9 [CI, -14.5 to -3.3]) and those receiving placebo (mean within-group change, -10.9 [CI, -16.0 to -5.8]); the adjusted between-group difference was 0.0 (CI, -4.1 to 4.0; P = 0.99). There was no evidence that baseline Hypothyroid Symptoms score or Tiredness score modified the effects of L-thyroxine versus placebo (P for interaction = 0.20 and 0.82, respectively). LIMITATION: Post hoc analysis, small sample size, and examination of only patients with 1-year outcome data. CONCLUSION: In older adults with SCH and high symptom burden at baseline, L-thyroxine did not improve hypothyroid symptoms or tiredness compared with placebo. PRIMARY FUNDING SOURCE: European Union FP7.

[Intermittent fasting†: A solution for metabolic disorders?] / Nutrition-obésité - Jeûne intermittent†: une solution pour les maladies métaboliques†?

The management of obesity comprises lifestyle changes targeting nutrient content, eating behavior and regular physical activity. Medication (orlistat, liraglutide) and bariatric surgery can later be used, but they require a clear indication and a close follow-up. Studies in chronobiology are now exploring the metabolic benefits of intermittent fasting, which restricts food intake and calorie-containing beverages to a certain window of the 24h cycle, or to certain days of the week/month, thus reinstating the alternance between anabolism and catabolism. However, the current scientific evidence is limited by the sample size and duration of the studies. It is therefore too early for a blanket strategy based on intermittent fasting in all patients with metabolic disorders.

Le traitement de l'obésité repose sur la modification des habitudes et du comportement alimentaire, ainsi que la mise en place d'une activité physique régulière. Les médicaments (orlistat, liraglutide) et la chirurgie bariatrique peuvent être envisagés, mais nécessitent une indication claire et un suivi clinique rapproché. La recherche en chronobiologie explore les bénéfices métaboliques du jeûne intermittent, qui restreint l'alimentation et les boissons caloriques à certaines heures du cycle de 24 heures, ou à certains jours de la semaine ou du mois, pour réinstaurer l'alternance entre anabolisme et catabolisme. Toutefois, les études jusqu'à présent sont limitées par la taille de l'échantillon et la durée du suivi. Il est donc trop tôt pour proposer le jeûne intermittent à tous les patients avec des maladies métaboliques.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 µg daily, or 25 µg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 µg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).

[The management of hypertriglyceridemia and the risk of pancreatitis]. / Prise en charge des hypertriglycéridémies et du risque de pancréatite.

In the face of hypertriglyceridemia, the potential causes must be assessed to choose the best medical therapeutic option. In cases of secondary hypertriglyceridemia, physicians should use treatments targeting the pathophysiological mechanisms underlying the lipid disorder. Lifestyle interventions are the cornerstone of an effective treatment, to achieve controlled glycemia, blood pressure and weight loss. Only in cases where these measures are insufficient, fibrates can be trialed although their clinical benefit is controversial, with special caution when combined with statins (risk of rhabdomyolysis). Plasmapheresis or intravenous insulin therapy are only used in severe situations after a multidisciplinary decision process in the hospital setting. The clinical case presented here reminds us to assess hypertriglyceridemia in the face of any acute pancreatitis.

Les causes d'une hypertriglycéridémie doivent être explorées pour choisir la meilleure approche thérapeutique. En cas d'hypertriglycéridémie secondaire, il est préférable de cibler le mécanisme physiopathologique du désordre lipidique. Les mesures hygiéno-diététiques restent la clé de voûte du traitement, pour atteindre un bon contrôle glycémique, tensionnel et pondéral. Uniquement en cas d'échec, les fibrates peuvent être évoqués bien que leur bénéfice clinique soit controversé, avec une attention particulière en cas de bithérapie par statine et fibrate (risque de rhabdomyolyse). La plasmaphérèse ou l'insulinothérapie intraveineuse sont réservées aux situations sévères et décidées avec les différents spécialistes en milieu hospitalier. Le cas clinique présenté ici est un rappel que l'hypertriglycéridémie devrait être recherchée devant toute pancréatite aiguë.

Subclinical thyroid dysfunction and cardiovascular diseases: 2016 update.

Subclinical thyroid dysfunction comprises subclinical hypothyroidism (SHypo), defined as elevated thyroid-stimulating hormone (TSH) by normal free thyroxine (FT4), and subclinical hyperthyroidism (SHyper) with decreased or undetectable TSH and normal FT4. Up to 10% of the elderly have SHypo, which is usually asymptomatic. Individual participant data (IPD) analyses of prospective cohort studies from the international Thyroid Studies Collaboration show that SHypo is associated with increased coronary heart disease (CHD) mortality [hazard ratio (HR) 1,58 for TSH ≥ 10 mIU/L, 95% CI 1.10-2.27), as well as increased risk of stroke, and heart failure (HF) for both higher and lower TSH. Small studies found that SHypo affects carotid intima media thickness (CIMT), diastolic function, peripheral vascular resistance, endothelial function, and lipid profile. SHyper is associated with increased risk of atrial fibrillation (AF) (HR 1.68, 95% CI 1.16-2.43) and CHD events (HR 1.21, 95% CI 0.99-1.46). The TSH threshold for initiating treatment is unclear. In the absence of large randomized controlled trials, the best evidence suggests SHypo therapy should be started at TSH ≥ 10 mIU/L, and SHyper therapy at TSH < 0.1 mIU/L. Recommendations on screening are discordant, but most guidelines advocate that thyroid function should be checked in those at risk for hypothyroidism, those over 60, and those with known CHD and HF. This review updates current evidence on the association between thyroid dysfunction and cardiovascular disease, as well as on screening and treatment of subclinical thyroid dysfunction.

Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism.

IMPORTANCE: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. OBJECTIVE: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. DESIGN, SETTING, AND PARTICIPANTS: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. EXPOSURES: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). RESULTS: Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). CONCLUSIONS AND RELEVANCE: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.

[Should patients with type 2 diabetes be screened for lower extremity arterial disease?] / Faut-il dépister l'artériopathie oblitérante des membres inférieurs chez les patients avec diabète de type.

Lower extremity arterial disease (LEAD) is a serious and invalidating disease with a relatively high prevalence in the diabetic population. Patients suffering from both conditions have a less favourable prognosis of affected limbs compared to non-diabetic patients, with more frequent adverse limb events such as amputations. Nevertheless, awareness of LEAD remains sub-optimal in the diabetic population. Regular and appropriate screening for this condition is therefore recommended. Affected individuals should receive optimal medical treatment, including intensive management of the various cardiovascular risk factors and strict blood glucose control.

L'artériopathie oblitérante des membres inférieurs (AOMI) est une pathologie souvent sévère et invalidante, relativement fréquente dans la population diabétique. Les patients atteints des deux maladies ont un pronostic moins favorable au niveau des membres inférieurs par rapport aux patients non diabétiques, et souffrent plus fréquemment de complications graves comme des amputations. Néanmoins, la sensibilisation à l'AOMI chez les médecins prenant en charge les patients diabétiques reste sous-optimale. Un dépistage régulier et approprié de cette condition est donc recommandé. Les patients affectés doivent recevoir un traitement médical optimal, incluant une prise en charge intensive des différents facteurs de risque cardiovasculaire et un contrôle strict des glycémies.

Thyroid Function Within the Normal Range, Subclinical Hypothyroidism, and the Risk of Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. METHODS: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. RESULTS: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26-1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. CONCLUSIONS: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

Energy expenditure in frontotemporal dementia: a behavioural and imaging study.

SEE FINGER DOI101093/AWW312 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Abnormal eating behaviour and metabolic parameters including insulin resistance, dyslipidaemia and body mass index are increasingly recognized as important components of neurodegenerative disease and may contribute to survival. It has previously been established that behavioural variant frontotemporal dementia is associated with abnormal eating behaviour characterized by increased sweet preference. In this study, it was hypothesized that behavioural variant frontotemporal dementia might also be associated with altered energy expenditure. A cohort of 19 patients with behavioural variant frontotemporal dementia, 13 with Alzheimer's disease and 16 (age- and sex-matched) healthy control subjects were studied using Actiheart devices (CamNtech) to assess resting and stressed heart rate. Actiheart devices were fitted for 7 days to measure sleeping heart rate, activity levels, and resting, active and total energy expenditure. Using high resolution structural magnetic resonance imaging the neural correlates of increased resting heart rate were investigated including cortical thickness and region of interest analyses. In behavioural variant frontotemporal dementia, resting (P = 0.001), stressed (P = 0.037) and sleeping heart rate (P = 0.038) were increased compared to control subjects, and resting heart rate (P = 0.020) compared to Alzheimer disease patients. Behavioural variant frontotemporal dementia was associated with decreased activity levels compared to controls (P = 0.002) and increased resting energy expenditure (P = 0.045) and total energy expenditure (P = 0.035). Increased resting heart rate correlated with behavioural (Cambridge Behavioural Inventory) and cognitive measures (Addenbrooke's Cognitive Examination). Increased resting heart rate in behavioural variant frontotemporal dementia correlated with atrophy involving the mesial temporal cortex, insula, and amygdala, regions previously suggested to be involved exclusively in social and emotion processing in frontotemporal dementia. These neural correlates overlap the network involved in eating behaviour in frontotemporal dementia, suggesting a complex interaction between eating behaviour, autonomic function and energy homeostasis. As such the present study suggests that increased heart rate and autonomic changes are prevalent in behavioural variant frontotemporal dementia, and are associated with changes in energy expenditure. An understanding of these changes and neural correlates may have potential relevance to disease progression and prognosis.

[Management of obesity-associated dyslipidemia : an approach based on food choices]. / Prise en charge de la dyslipidémie liée à l'obésité : une approche centrée sur l'alimentation.

Obesity is associated with elevated levels of triglycerides, sometimes LDL-cholesterol, and lower levels of HDL-cholesterol. Management should first focus on dietary advices and increased physical activity, while lipid-lowering drugs are indicated only in patients at intermediate or high cardiovascular risk. We summarize nutritional recommendations from scientific societies: although they do not always overlap, they agree on lowering consumption of dietary fat (20-35 % of total energy intake) and favoring non-saturated fatty acids. Physicians must review the intake of carbohydrates as well, by limiting added sugars and increasing dietary fibers (vegetables, wholegrain cereals, legumes and nuts). Multidisciplinary management shared between physicians and trained dieticians improves long-term healthy lifestyle.

L'obésité est associée à une élévation des triglycérides, parfois du LDL-cholestérol, et une diminution du HDL-cholestérol. La prise en charge se concentre d'abord sur les conseils nutritionnels et l'activité physique, alors qu'un traitement hypolipémiant n'est indiqué que pour un risque cardiovasculaire intermédiaire ou élevé. Nous résumons ici les recommandations des sociétés savantes, qui ne sont pas toujours congruentes, mais s'accordent sur une consommation modérée de graisses (20­35 % de l'apport énergétique) privilégiant les acides gras insaturés. Il faut aussi s'intéresser à l'apport en glucides, limiter les sucres ajoutés et augmenter les fibres (légumes, céréales complètes, légumineuses et oléagineux). Une prise en charge multidisciplinaire avec une diététicienne diplômée améliore le maintien de bonnes habitudes de vie à long terme.

[Statin-associated muscle symptoms : Current management in 2018]. / Symptômes musculaires associés aux statines : quelle prise en charge en 2018 ?

Statins are the first line treatment in hyperlipidemia, either in primary or secondary prevention of cardiovascular diseases. One of the most prescribed drug class worldwide, this drug class is often the focus of highly publicized drug controversies. Various adverse effects have been attributed to statins, in particular statin-associated muscle symptoms (SAMS). This condition varies in severity (from frequent isolated myalgia to rare severe myositis, even rhabdomyolysis) and often leads to treatment termination. Because SAMS are a daily challenge in clinical practice, we review here the recent medical literature on this topic and suggest a management strategy to be shared with the patient as an active partner.

Les statines représentent la première ligne de traitement en cas d'hypercholestérolémie, que ce soit en prévention primaire ou secondaire des maladies cardiovasculaires. C'est l'une des classes médicamenteuses les plus prescrites au monde, mais qui fait l'objet de controverses médiatisées. De nombreux effets indésirables ont été attribués à la prise de statines, notamment les symptômes musculaires associés aux statines (SMAS). On relève différents types d'atteinte, d'intensité croissante (de myalgies fréquentes à une myosite sévère mais rare, voire une rhabdomyolyse), pouvant mener à l'arrêt du traitement. Au vu du défi que représentent les SMAS dans la pratique courante ambulatoire, cet article donne au praticien un aperçu de la littérature récente, ainsi qu'une proposition de prise en charge à partager avec le patient.

[Current update on PCKS9 inhibitors]. / Etat des connaissances en 2018 sur les anticorps anti-PCSK9.

PCSK9 (proprotein convertase subtilisin kexin 9) monoclonal antibodies (mAb) are new therapeutic agents to lower efficiently LDL-cholesterol levels. New data from large clinical trials suggest that the addition of PCSK9 mAb to statins can reduce the incidence of major adverse cardiovascular events in very high risk patients. Alirocumab and evolocumab are two agents available in Switzerland with specific limitations for reimbursement. PCSK9 mAb should be considered in patients with clinical atherosclerotic cardiovascular disease (ASCVD), as well as in patients with familial hypercholesterolemia without ASCVD who have substantially high LDL-cholesterol levels despite the use of statin at maximally tolerated dose with or without ezetimibe, or intolerance to appropriate doses of several statins.

Les anticorps anti-PCSK9 (proprotéine convertase subtilisine/kexine de type 9) sont une nouvelle classe de molécules qui permettent d'abaisser efficacement les taux sanguins de LDL-cholestérol. Une récente étude a montré leur efficacité en ajout aux statines pour réduire les événements cardiovasculaires chez les patients à très haut risque. L'alirocumab et l'évolocumab sont disponibles sur le marché en Suisse avec des limitations spécifiques pour le remboursement. L'utilisation des anticorps anti-PCSK9 peut être considérée chez les patients avec une maladie cardiovasculaire clinique ou les patients avec hypercholestérolémie familiale qui ont un taux de LDL-cholestérol élevé malgré un traitement de statines à la dose maximale tolérée en association ou non avec l'ézétimibe.

[Subclinical hypothyroidism : should we still treat elderly patients? Clinical implications of a new trial in primary care]. / Hypothyroïdie infraclinique : faut-il encore traiter les personnes âgées ? Implications cliniques d'une nouvelle étude en médecine de famille.

Subclinical hypothyroidism, defined as an elevated level of thyrotropin hormone (TSH) and normal thyroxin, is more frequent in women and above 65 years old. This condition is associated with an increased cardiovascular risk, in particular with TSH > 10,0 mIU/L. Although overt hypothyroidism is rare (prevalence of 0,3 %), levothyroxine has become the most prescribed medication in the US, while its indications are still debated. The European-funded TRUST trial showed no improvement in Hypothyroid Symptoms and Tiredness scores among patients ≥ 65 years with subclinical hypothyroidism treated with levothyroxine, and no improvement in blood pressure, weight, muscle strength and cognition. The results of this study call for a revision of the current international recommendations on the treatment of subclinical hypothyroidism.

L'hypothyroïdie infraclinique, soit un taux élevé d'hormone thyréotrope (TSH) et une thyroxine normale, est plus fréquente chez les femmes et après 65 ans. Cette condition est associée à une élévation du risque cardiovasculaire, en particulier lors de TSH > 10,0 mUl/l. Bien que l'hypothyroïdie franche soit peu fréquente (prévalence de 0,3 %), la lévothyroxine est devenue le médicament le plus prescrit aux Etats-Unis, alors que ses indications restent controversées. L'étude européenne TRUST a montré l'absence d'amélioration des scores de fatigue et d'hypothyroïdie chez des personnes âgées ≥ 65 ans avec hypothyroïdie infraclinique sous lévothyroxine, ainsi qu'une absence de bénéfice pour la tension artérielle, le poids, la force et la cognition. Nous proposons ici d'adapter les recommandations internationales sur l'hypothyroïdie infraclinique.