Association of Troponin T measurements with long-term outcomes in patients with coronary artery disease participating in a secondary prevention trial.

BACKGROUND AND AIMS: Identification of high-risk patients in secondary cardiovascular prevention may be challenging, although risk stratification tools are available. Cardiac troponins might have predictive value in identification of high-risk patients. The aim of this study was to investigate the association between cardiac Troponin T (cTnT) levels following a coronary event and long-term outcomes. METHODS: This study was carried out as a subanalysis from a randomized controlled trial conducted at Sørlandet Hospital, Norway, where patients hospitalized with myocardial infarction (MI) or scheduled percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) were included between 2007 and 2017. Participants were followed-up for up to 10 years after the index event through out-patient consultations. cTnT was assessed at each consultation as well as information regarding new cardiovascular events or death. RESULTS: A total of 1278 patients (18-80 years) with complete measurements of cTnT were included. cTnT was elevated (≥ 14 ng/L) one year after the primary event in 241 (19%) of participants. Median follow-up was 5.7 [SD 2.7] years. Cox regression analyses showed reduced survival (adjusted HR 0.37, 95% CI 0.19-0.72; p = 0.003) and composite endpoint-free survival (adjusted HR 0.73, 95% CI 0.55-0.98; p = 0.04) in participants with elevated cTnT versus participants with low cTnT after adjustment for risk factors at inclusion and randomization assignment. CONCLUSIONS: Assessment of cTnT after coronary heart events may help identify patients at high risk of poor outcomes and might contribute to more focused secondary preventive treatment. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov (NCT00679237).

Sex differences in secondary preventive follow-up after coronary heart events.

BACKGROUND AND AIMS: Some studies point to sex differences in cardiovascular preventive practices. The aim of this study was to investigate differences in achievement of secondary preventive targets and long-term outcome in men and women after a coronary heart event. METHODS: This study was a subanalysis from a randomized controlled trial of hospital-based versus primary care-based secondary preventive follow-up at Sorlandet Hospital, Norway, 2007-2022 and included both groups. The main outcome was achievement of treatment targets two years after the index event. Event-free survival was calculated based on the composite of mortality, coronary intervention, stroke, or myocardial infarction during follow-up. Participants were followed-up for up to 10 years after the index event through out-patient consultations. RESULTS: In total, 337 women and 1203 men were eligible for the study. Due to loss of follow-up during the first two years after the index coronary event 106 (7%) participants were excluded from further analysis (53% withdrawal of consent, 12% death, and 35% other causes) leaving 307 (21%) women and 1127 (79%) men. After two years of follow-up we found no differences between women and men in achievement of blood pressure targets (61% vs. 59%; p = 0.57), LDL-cholesterol goals (64% vs. 69%; p = 0.15), HbA1c-goal in patients with diabetes (49% vs. 45%; p = 0.57), non-smoking (79% vs. 81%; p = 0.34), healthy diets (14% vs. 13%, p = 0.89), physical activity (55% vs. 58%; p = 0.38), use of acetylsalicylic acid (93% vs. 94%; p = 0.39), and use of lipid lowering therapy (92% vs. 94%; p = 0.15). After a median follow-up time of 5.0 [SD 3.2] years there were no differences between women and men regarding composite endpoint (89 [30.0%] vs. 345 [30.6]; p = 0.58), and composite endpoint-free survival did not differ between women and men (hospital-based follow-up HR for women versus men, 0.87, 95% CI 0.62-1.23; p = 0.44 and primary care service HR for women versus men 0.95, 95% CI 0.69-1.31; p = 0.78). CONCLUSIONS: The study show no sex differences in achievement of secondary preventive targets or composite endpoint after coronary heart events. However, many women and men did not achieve treatment goals, and further improvement in secondary prevention is needed. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov (NCT00679237).

A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial.

BACKGROUND AND AIMS: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. PATIENTS AND METHODS: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. RESULTS: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. CONCLUSIONS: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Effect of smoking cessation on cardiac troponin I concentrations.

Chronic elevation of cardiac troponin I (cTnI) is associated with heart failure and cardiovascular death. Paradoxically, observational studies have indicated that current smokers have lower cTnI concentrations than non-smokers. We examined determinants of cTnI in smokers and the effect of smoking cessation on cTnI. Overweight or obese smokers received motivational support and varenicline to aid cessation and dietary advice to limit weight gain. Quitters were defined according to the Russell standard (≤5 cigarettes after the quit date) and validated with expired breath CO <10 ppm. Of the total 122 participants, 108 completed assessments at 12 weeks and 78 were classified as quitters versus 30 who continued smoking. cTnI was measured with a high-sensitivity assay with a limit of detection of 1.2 ng/L (Abbott Diagnostics), and concentrations (log-transformed) were compared between quitters and continuing smokers. cTnI concentrations were significantly higher in men than women and correlated with age, but not with number of cigarettes/day. Quitters had median baseline and 12-week levels of 1.4 ng/L (interquartile range [IQR] 1.2-2.5) and 1.4 ng/L (IQR 1.2-2.4), respectively, while nonquitters had baseline and 12-week levels of 1.5 ng/L (IQR 1.2-2.9) and 1.8 ng/L (IQR 1.3-3.4), respectively. The change in cTnI concentrations from baseline to 12 weeks did not differ between quitters and continuous smokers (p = .7). The results suggest that smoking cessation does not affect levels of cTnI, a marker of chronic subclinical myocardial injury, in contrast to prior observational data suggesting that tobacco smoking is associated with lower cTn concentrations.

Quality of clinical management of cardiometabolic risk factors in patients with severe mental illness in a specialist mental health care setting.

PURPOSE: Cardiometabolic disease in patients with severe mental illness is a major cause of shortened life expectancy. There is sparse evidence of real-world clinical risk prevention practice. We investigated levels of assessments of cardiometabolic risk factors and risk management interventions in patients with severe mental illness in the Norwegian mental health service according to an acknowledged international standard. METHODS: We collected data from 264 patients residing in six country-wide health trusts for: (a) assessments of cardiometabolic risk and (b) assessments of levels of risk reducing interventions. Logistic regressions were employed to investigate associations between risk and interventions. RESULTS: Complete assessments of all cardiometabolic risk variables were performed in 50% of the participants and 88% thereof had risk levels requiring intervention according to the standard. Smoking cessation advice was provided to 45% of daily smokers and 4% were referred to an intervention program. Obesity was identified in 62% and was associated with lifestyle interventions. Reassessment of psychotropic medication was done in 28% of the obese patients. Women with obesity were less likely to receive dietary advice, and use of clozapine or olanzapine reduced the chances for patients with obesity of getting weight reducing interventions. CONCLUSIONS: Nearly nine out of the ten participants were identified as being at cardiometabolic high risk and only half of the participants were adequately screened. Women with obesity and patients using antipsychotics with higher levels of cardiometabolic side effects had fewer adequate interventions. The findings underscore the need for standardized recommendations for identification and provision of cardiometabolic risk reducing interventions in all patients with severe mental illness.

Cardiovascular risk factors and body composition in adults with achondroplasia.

PURPOSE: An increased cardiovascular mortality has been reported in achondroplasia. This population-based, case-control study investigated cardiovascular risk factors and body composition in Norwegian adults with achondroplasia. METHODS: We conducted anthropometric, clinical, and laboratory assessments in 49 participants with achondroplasia, of whom 40 completed magnetic resonance imaging (MRI) for body composition analysis. Controls consisted of 98 UK Biobank participants, matched for body mass index (BMI), sex, and age. RESULTS: Participants were well matched for BMI (33.3 versus 32.5 kg/m2) and sex, but achondroplasia participants were younger than controls (mean age 41.1 versus 54.3 years). Individuals with achondroplasia had lower age-adjusted mean blood pressure, total and low-density lipoprotein (LDL) cholesterol, and triglycerides compared with controls, but similar fasting glucose and HbA1c values. Age-adjusted mean visceral fat store was 1.9 versus 5.3 L (difference -2.7, 95% confidence interval [CI] -3.6 to -1.9; P < 0.001), abdominal subcutaneous fat was 6.0 versus 11.2 L (-4.7, 95% CI -5.9 to -3.4; P < 0.001), and liver fat was 2.2 versus 6.9% (-2.8, 95% CI -5.2 to -0.4; P = 0.02). CONCLUSION: Despite a high BMI, the cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that other factors might contribute to the increased mortality observed in this condition.

Physical activity and the risk of heart failure: a systematic review and dose-response meta-analysis of prospective studies.

Although physical activity is an established protective factor for cardiovascular diseases such as ischemic heart disease and stroke, less is known with regard to the association between specific domains of physical activity and heart failure, as well as the association between cardiorespiratory fitness and heart failure. We conducted a systematic review and meta-analysis of prospective observational studies to clarify the relations of total physical activity, domains of physical activity and cardiorespiratory fitness to risk of heart failure. PubMed and Embase databases were searched up to January 14th, 2020. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine prospective studies (36 publications) were included in the review. The summary RRs for high versus low levels were 0.77 (95% CI 0.70-0.85, I2 = 49%, n = 7) for total physical activity, 0.74 (95% CI 0.68-0.81, I2 = 88.1%, n = 16) for leisure-time activity, 0.66 (95% CI 0.59-0.74, I2 = 0%, n = 2) for vigorous activity, 0.81 (95% CI 0.69-0.94, I2 = 86%, n = 3) for walking and bicycling combined, 0.90 (95% CI 0.86-0.95, I2 = 0%, n = 3) for occupational activity, and 0.31 (95% CI 0.19-0.49, I2 = 96%, n = 6) for cardiorespiratory fitness. In dose-response analyses, the summary RRs were 0.89 (95% CI 0.83-0.95, I2 = 67%, n = 4) per 20 MET-hours per day of total activity and 0.71 (95% CI 0.65-0.78, I2 = 85%, n = 11) per 20 MET-hours per week of leisure-time activity. Nonlinear associations were observed in both analyses with a flattening of the dose-response curve at 15-20 MET-hours/week for leisure-time activity. These findings suggest that high levels of total physical activity, leisure-time activity, vigorous activity, occupational activity, walking and bicycling combined and cardiorespiratory fitness are associated with reduced risk of developing heart failure.

Long-term hospital-based secondary prevention of coronary artery disease: a randomized controlled trial.

BACKGROUND AND AIMS: Despite established guidelines on secondary prevention of cardiovascular disease, practical implementation of treatment targets is deficient even in high-income countries. This study compared long-term hospital-based treatment with follow-up at primary health care regarding new cardiovascular events and achievement of treatment targets. METHODS: This randomized controlled trial at Sørlandet Hospital, Norway 2007-2021 included patients hospitalized due to myocardial infarction (n = 760) or after scheduled percutaneous coronary intervention (PCI) (n = 677) or coronary artery bypass grafting (n = 103). Patients were randomized to hospital-based secondary preventive care with consultations 2 weeks, 3 months, 6 months and 1 year after the index event and annually for up to 5 years, or follow-up at primary health care. Final data was collected after 10 years and hazard ratios were calculated using Cox regression analyses. RESULTS: Composite endpoint-free survival due to a lower rate of PCI improved in patients with hospital-based follow-up (n = 788) compared to patients followed-up at primary health care (n = 752) (HR 0.80, 95% CI 0.66-0.96; p = 0.02) but all-cause mortality was not reduced (HR 0.96, 95% CI 0.59-1.56; p = 0.86). At 1 year, LDL-cholesterol (2.1 [SD 0.7] versus 2.3 [SD 0.8] mmol/l; p < 0.001) and systolic blood pressure (132 [SD 16] versus 142 [SD 20] mm/Hg; p < 0.001) were lower in the hospital-based group, and the differences remained significant during the first 5 years. Other secondary preventive measures (smoking cessation, physical activity, body weight, glucose control, drug adherence) did not differ. CONCLUSIONS: Long-term hospital-based secondary preventive follow-up improved composite endpoint-free survival, but not mortality. Substantial risk factors remained unaddressed. The beneficial effects on blood pressure and LDL-cholesterol disappeared after annual consultations ceased. TRIAL REGISTRATION: The study is registered in ClinicalTrials.gov (NCT00679237) May 16, 2008.

Effect of intermittent and continuous caloric restriction on Sirtuin1 concentration depends on sex and body mass index.

BACKGROUND & AIMS: The favorable effect of caloric restriction (CR) on health span is well known and partly mediated by the sirtuin system. Sirtuin1, a regulator of energy homeostasis in response to nutrient availability, is activated by CR. We therefore investigated effects of two different CR regimens on Sirtuin1 concentrations. METHODS & RESULTS: The study included 112 abdominally obese subjects, randomized to intermittent or continuous CR for 1 year. Blood samples and anthropometric measures were collected at baseline and after 12 months. Sirtuin1 concentrations were measured by ELISA. Sirtuin1 correlated significantly to BMI at baseline (r = .232, p = 0.019). Mean reduction in body-weight was 8.0 and 9.0 kg after intermittent and continuous CR, respectively. After 1 year, no significant between-group differences in Sirtuin1 levels were observed according to regimen (p = 0.98) and sex (p = 0.41). An increase in median Sirtuin1 concentrations (pg/mL) [25, 75 percentiles] from baseline was observed after intermittent CR in the total population (884 [624, 1285] vs.762 [530, 1135]; p = 0.041), most marked in men (820 [623, 1250] vs. 633 [524, 926]; p = 0.016). Improvement in BMI after 1 year correlated to Sirtuin1 changes, but varied according to sex. In women, Spearman's rho = .298, p = 0.034, with stronger correlation in the intermittent CR group (r = .424, p = 0.049). In men, there was an inverse relation to Sirtuin1 changes, only in the intermittent CR group (r = -.396, p = 0.045). CONCLUSIONS: Effects on Sirtuin1 concentrations after 1 year of CR are sex and BMI-related. Intermittent CR regimen affected Sirtuin1 to a stronger extent than continuous CR, suggesting individualized dietary intervention.

Risk of cardiovascular disease after preventive salpingo-oophorectomy.

INTRODUCTION: Breast cancer susceptibility gene (BRCA) mutation carriers are recommended to undergo early oophorectomy to prevent ovarian cancer. Premature loss of ovarian hormones may increase the risk of cardiovascular disease. Because women with preventive oophorectomy are mainly young and healthy, they rarely undergo specialized cardiological surveillance. We compared the risk of cardiovascular disease in women after preventive oophorectomy with reference women. METHODS: In an historical cohort study, we included 134 women aged ≤52 years after preventive oophorectomy and 268 age matched premenopausal reference women, aged 52 years or less, from the general population, excluding participants with diabetes or cardiovascular disease. The Norwegian risk assessment tool (NORRISK 2) was used to estimate 10 year cardiovascular risk. This algorithm was validated in a large Norwegian population and is based on age, smoking, systolic blood pressure, total and high density lipoprotein cholesterol, antihypertensive medication, and family history of cardiovascular disease. We also examined cardiometabolic factors (levels of triglycerides and high sensitivity C reactive protein, as well as body mass index and waist circumference) not included in the NORRISK 2 calculation. RESULTS: Median age in the preventive oophorectomy and reference groups were 47 (range 33-52) and 46 (31-52) years, respectively. Mean time since surgery in the preventive oophorectomy group was 4.2 years (standard deviation (SD) 2.8). Ten year cardiovascular risk was similar in women after preventive oophorectomy and reference women (mean 1.15% (SD 1.00) vs 1.25 (1.09), respectively, p=0.4). Women in the preventive oophorectomy group had a lower body mass index (24.7 kg/m2 (4.0) vs 26.2 (4.8), p=0.003) and waist circumference (86 cm vs 89, p=0.006). The overall cardiovascular risk estimation was comparable among hormone therapy users and non-users, but hormone therapy users had lower total cholesterol and waist circumference. DISCUSSION: Women who underwent preventive oophorectomy had a similar risk of cardiovascular disease as population based reference women, estimated according to risk factors easily measured in general practice. Cardiometabolic risks were not increased in the preventive oophorectomy group.

Effect of fatty fish or nut consumption on concentrations of persistent organic pollutants in overweight or obese men and women: A randomized controlled clinical trial.

BACKGROUND AND AIMS: While excess energy intake and physical inactivity constitute the obvious causes of body fat accumulation, persistent organic pollutants (POPs) are novel factors that have been linked to cardiometabolic disorders. Major sources of POPs are animal fats including fatty fish. Given the putative protective effects of fish on cardiovascular disease, we explored whether high consumption of fatty fish increased serum concentrations of POPs. METHODS AND RESULTS: Men and women aged 35-70 years with body mass index between 25 and 38 kg/m2 and at least 1 cardiometabolic component were randomized to high intakes of fatty fish (mostly farmed salmon, ∼630 g/week; n = 45), high intakes of nuts (∼200 g/week; n = 42) or a control group following their usual diet but restricting fatty fish and nuts for 6 months (n = 44). Concentrations of 15 POPs (5 organochlorinated compounds, 2 dioxin-like polychlorinated biphenyls and 8 non-dioxin-like polychlorinated biphenyls) and cardiometabolic risk factors were measured at baseline and end of the study. Results showed that changes in concentrations of individual and classes of POPs did not differ between the dietary groups and controls (p > 0.05). Among cardiometabolic risk factors HDL-cholesterol increased in the fatty fish group compared to controls (+0.10 mmol/L, CI (0.05-0.20); p = 0.005) while no changes were observed in the group consuming nuts. CONCLUSION: Fatty fish consumption for 6 months did not increase the serum concentrations of POPs in individuals with overweight or obesity and metabolic risk. While this finding appears reassuring regarding short-term intakes of farmed salmon, long term variations in POPs in adipose stores require further study.

Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. OBJECTIVES: To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019. SELECTION CRITERIA: Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication. AUTHORS' CONCLUSIONS: Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

Prevalence of diabetes before and after first diagnosis of coronary artery disease. / Forekomst av diabetes før og etter første gangs koronarsykdom.

BAKGRUNN: Diabetes er assosiert med koronarsykdom, og kardiovaskulær sykdom er viktigste dødsårsak hos mennesker med sykdommen. I denne studien har vi undersøkt forekomsten av kjent diabetes og ikke-erkjent diabetes hos pasienter ved første gangs hjerteinfarkt, perkutan koronar intervensjon eller koronar bypasskirurgi samt forekomsten av nye kardiovaskulære hendelser i inntil fem år etterpå. MATERIALE OG METODE: Alle pasienter < 80 år uten tidligere kjent koronarsykdom innlagt ved Sørlandet sykehus Arendal i forbindelse med første gangs hjerteinfarkt, perkutan koronar intervensjon eller koronar bypasskirurgi i perioden 2007-16 ble fortløpende inkludert i studien og fulgt i inntil fem år (median oppfølgingstid tre år). RESULTATER: Av totalt 1 259 inkluderte pasienter hadde 178 (14 %) kjent diabetes ved innleggelsestidspunktet og 49 (4 %) ikke-erkjent diabetes. I løpet av oppfølgingsperioden utviklet ytterligere 102 pasienter (8 %) diabetes. Omtrent halvparten av dem med diabetes hadde en HbA1c-verdi ≤ 7 %. Risikoen for utvikling av nye kardiovaskulære hendelser var høyere hos pasienter med diabetes enn hos pasienter uten diabetes (alders- og kjønnsjustert hasardratio 1,5; 95 % konfidensintervall: 1,1-2,1, p = 0,005). FORTOLKNING: Studien viser at det er høy forekomst av diabetes hos pasienter med første gangs koronarsykdom og høy risiko for nye kardiovaskulære hendelser hos pasienter med diabetes. Regelmessig undersøkelse med tanke på utvikling av diabetes og god forebyggende behandling av pasienter med diabetes og koronarsykdom er viktig.

Body Mass Index, Abdominal Fatness, and Heart Failure Incidence and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Studies.

BACKGROUND: Obesity has been associated with increased risk of heart failure, but whether overweight also increases risk is unclear. It is also unclear whether abdominal adiposity is more strongly associated with heart failure risk than general adiposity. We conducted a systematic review and meta-analysis of prospective studies to clarify the strength and shape of the dose-response relationship between general and abdominal adiposity and the risk of heart failure. METHODS AND RESULTS: PubMed and Embase databases were searched up to October 10, 2014. Summary relative risks were calculated using random-effects models. A total of 28 studies (27 publications) were included. Twenty-three prospective studies with >15 905 incident cases among 647 388 participants were included in the analysis of body mass index and heart failure incidence, and 4 studies were included for heart failure mortality. The summary relative risk for a 5-unit increment in body mass index was 1.41 (95% confidence interval, 1.34-1.47; I(2)=83%) for heart failure incidence and 1.26 (95% confidence interval, 0.85-1.87; I(2)=95%) heart failure mortality. Although the test for nonlinearity was significant (P<0.0001), this appeared to be attributable to a threshold at a body mass index of ≈23 to 24 kg/m(2); however, there was evidence of increased risk even in the overweight body mass index range. The summary relative risk for a 10-cm increase in waist circumference was 1.29 (95% confidence interval, 1.21-1.37; I(2)=89%) and per 0.1-unit increase in waist-to-hip ratio was 1.29 (95% confidence interval, 1.13-1.47; I(2)=82%). CONCLUSION: Overweight and obesity and abdominal adiposity are associated with increased risk of heart failure.

Body mass index, abdominal fatness, fat mass and the risk of atrial fibrillation: a systematic review and dose-response meta-analysis of prospective studies.

Different adiposity measures have been associated with increased risk of atrial fibrillation, however, results have previously only been summarized for BMI. We therefore conducted a systematic review and meta-analysis of prospective studies to clarify the association between different adiposity measures and risk of atrial fibrillation. PubMed and Embase databases were searched up to October 24th 2016. Summary relative risks (RRs) were calculated using random effects models. Twenty-nine unique prospective studies (32 publications) were included. Twenty-five studies (83,006 cases, 2,405,381 participants) were included in the analysis of BMI and atrial fibrillation. The summary RR was 1.28 (95% confidence interval: 1.20-1.38, I2 = 97%) per 5 unit increment in BMI, 1.18 (95% CI: 1.12-1.25, I2 = 73%, n = 5) and 1.32 (95% CI: 1.16-1.51, I2 = 91%, n = 3) per 10 cm increase in waist and hip circumference, respectively, 1.09 (95% CI: 1.02-1.16, I2 = 44%, n = 4) per 0.1 unit increase in waist-to-hip ratio, 1.09 (95% CI: 1.02-1.16, I2 = 94%, n = 4) per 5 kg increase in fat mass, 1.10 (95% CI: 0.92-1.33, I2 = 90%, n = 3) per 10% increase in fat percentage, 1.10 (95% CI: 1.08-1.13, I2 = 74%, n = 10) per 5 kg increase in weight, and 1.08 (95% CI: 0.97-1.19, I2 = 86%, n = 2) per 5% increase in weight gain. The association between BMI and atrial fibrillation was nonlinear, p nonlinearity < 0.0001, with a stronger association at higher BMI levels, however, increased risk was observed even at a BMI of 22-24 compared to 20. In conclusion, general and abdominal adiposity and higher body fat mass increase the risk of atrial fibrillation.

Body mass index and physical activity and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies.

PURPOSE: We conducted a systematic review and meta-analysis of prospective studies of the association between body mass index (BMI) and physical activity and diverticular disease risk. METHODS: PubMed and Embase databases were searched up to February 7, 2017. Summary relative risks and 95% confidence intervals (95% CIs) were calculated using a random effects model and nonlinear associations were modeled using fractional polynomial models. RESULTS: Six cohort studies of BMI and diverticular disease risk (28,915 cases, 1,636,777 participants) and five cohort studies of physical activity and diverticular disease risk (2080 cases, 147,869 participants) were included. The summary relative risk (RR) of incident diverticular disease for a 5 unit BMI increment was 1.28 (95% CI: 1.18-1.40, I 2 = 77%, n = 6) for diverticular disease, 1.31 (95% CI: 1.09-1.56, I 2 = 74%, n = 2) for diverticulitis, and 1.20 (95% CI: 1.04-1.40, I 2 = 56%, n = 3) for diverticular disease complications. There was no evidence of a nonlinear association between BMI and diverticular disease risk (p nonlinearity = 0.22), and risk increased even within the normal weight range. Compared to a BMI of 20, the summary RR for a BMI of 22.5, 25.0, 27.5, 30.0, 32.5, 35.0, 37.5, and 40.0 was 1.15 (1.07-1.23), 1.31 (1.17-1.47), 1.50 (1.31-1.71), 1.71 (1.52-1.94), 1.96 (1.77-2.18), 2.26 (2.00-2.54), 2.60 (2.11-3.21), and 3.01 (2.06-4.39), respectively. The summary RR was 0.76 (95% CI: 0.63-0.93, I 2 = 54%, n = 5) for high vs. low physical activity and 0.74 (95% CI: 0.57-0.97, I 2 = 39.5%, p heterogeneity = 0.20, n = 2) for high vs. low vigorous physical activity. CONCLUSIONS: These results suggest that even moderate increases in BMI may increase the risk of diverticular disease as well as diverticular disease complications and that a higher level of physical activity may reduce the risk.

Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review. OBJECTIVES: To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia. SEARCH METHODS: Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline.Date of most recent search: 20 February 2017. SELECTION CRITERIA: Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed studies for inclusion and extracted data. MAIN RESULTS: We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (moderate quality evidence). Serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations, did not differ between treated and placebo groups at any time point (low quality evidence). The risks of myopathy (low quality evidence) and clinical adverse events (moderate quality evidence) were very low and also similar in both groups. In one study simvastatin was shown to improve flow-mediated dilatation of the brachial artery (low quality evidence), and in another study treatment with pravastatin for two years induced a significant regression in carotid intima media thickness (low quality evidence). AUTHORS' CONCLUSIONS: Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. No significant safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.

[Statin intolerance]. / Statinintoleranse.

In 2015, more than 530 000 people were prescribed statins in Norway. Adverse effects from the musculoskeletal system as well as less specific side effects are frequently reported. The extent of these contrasts with observations made in randomised controlled studies which report the prevalence of such adverse effects as being in line with placebo. Breaks from drug treatment, low doses, switching medication and use of other lipid-lowering drugs are the most relevant approaches to dealing with adverse effects.