C-reactive protein as a predictor of disease in smokers and former smokers: a review

BACKGROUND:Cigarette smoking is a classical and a major risk factor in the development of several diseases with an inflammatory component, including cardiovascular disease and chronic obstructive pulmonary disease. Improvements in assays for protein markers of inflammation have led to many studies on these factors and their roles in disease.AIMS:C-reactive protein (CRP) is one such marker and this review focuses on the evidence for using CRP as a diagnostic marker and how levels of this protein are modified according to the smoking status of the patient, both in terms of the current amount of cigarettes smoked and how CRP levels change following smoking cessation.CONCLUSIONS:Assay of CRP levels may be useful in monitoring disease progression and determining risk of future cardiovascular complications. However, as this marker is also an indicator of acute inflammation and challenges to the immune system, some caution must be exercised in interpreting the available data on CRP levels in patients with different chronic comorbidities

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 associ- ated 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, I 2 = 97%) per 5 unit increment in BMI, 1.18 (95% CI: 1.12–1.25, I 2 = 73%, n = 5) and 1.32 (95% CI: 1.16–1.51, I 2 = 91%, n = 3) per 10 cm increase in waist and hip circumference, respectively, 1.09 (95% CI: 1.02–1.16, I 2 = 44%, n = 4) per 0.1 unit increase in waist- to-hip ratio, 1.09 (95% CI: 1.02–1.16, I 2 = 94%, n = 4) per 5 kg increase in fat mass, 1.10 (95% CI: 0.92–1.33, I 2 = 90%, n = 3) per 10% increase in fat percentage, 1.10 (95% CI: 1.08–1.13, I 2 = 74%, n = 10) per 5 kg increase in weight, and 1.08 (95% CI: 0.97–1.19, I 2 = 86%, n = 2) per 5% increase in weight gain. The association between BMI and atrial fibrillation was non- linear, 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

BMI and all cause mortality: systematic review and non-linear dose-response meta-analysis of 230 cohort studies with 3.74 million deaths among 30.3 million participants

 To conduct a systematic review and meta-analysis of cohort studies of body mass index (BMI) and the risk of all cause mortality, and to clarify the shape and the nadir of the dose-response curve, and the influence on the results of confounding from smoking, weight loss associated with disease, and preclinical disease. PubMed and Embase databases searched up to 23 September 2015. Cohort studies that reported adjusted risk estimates for at least three categories of BMI in relation to all cause mortality. Summary relative risks were calculated with random effects models. Non-linear associations were explored with fractional polynomial models. 230 cohort studies (207 publications) were included. The analysis of never smokers included 53 cohort studies (44 risk estimates) with >738 144 deaths and >9 976 077 participants. The analysis of all participants included 228 cohort studies (198 risk estimates) with >3 744 722 deaths among 30 233 329 participants. The summary relative risk for a 5 unit increment in BMI was 1.18 (95% confidence interval 1.15 to 1.21; I(2)=95%, n=44) among never smokers, 1.21 (1.18 to 1.25; I(2)=93%, n=25) among healthy never smokers, 1.27 (1.21 to 1.33; I(2)=89%, n=11) among healthy never smokers with exclusion of early follow-up, and 1.05 (1.04 to 1.07; I(2)=97%, n=198) among all participants. There was a J shaped dose-response relation in never smokers (Pnon-linearity <0.001), and the lowest risk was observed at BMI 23-24 in never smokers, 22-23 in healthy never smokers, and 20-22 in studies of never smokers with ≥20 years follow-up. In contrast there was a U shaped association between BMI and mortality in analyses with a greater potential for bias including all participants, current, former, or ever smokers, and in studies with a short duration of follow-up (<5 years or <10 years), or with moderate study quality scores. Overweight and obesity is associated with increased risk of all cause mortality and the nadir of the curve was observed at BMI 23-24 among never smokers, 22-23 among healthy never smokers, and 20-22 with longer durations of follow-up. The increased risk of mortality observed in underweight people could at least partly be caused by residual confounding from prediagnostic disease. Lack of exclusion of ever smokers, people with prevalent and preclinical disease, and early follow-up could bias the results towards a more U shaped association

Physical activity and the risk of gestational diabetes mellitus: a systematic review and dose-response meta-analysis of epidemiological studies

Physical activity has been inconsistently associated with risk of gestational diabetes mellitus in epidemiological studies, and questions remain about the strength and shape of the dose-response relationship between the two. We therefore conducted a systematic review and meta-analysis of cohort studies and randomized trials on physical activity and gestational diabetes mellitus. PubMed, Embase and Ovid databases were searched for cohort studies, and randomized controlled trials of physical activity and risk of gestational diabetes mellitus, up to August 5th 2015. Summary relative risks (RRs) were estimated using a random effects model. Twenty-five studies (26 publications) were included. For total physical activity the summary RR for high versus low activity was 0.62 (95 % CI 0.41-0.94, I(2) = 0 %, n = 4) before pregnancy, and 0.66 (95 % CI 0.36-1.21, I(2) = 0 %, n = 3) during pregnancy. For leisure-time physical activity the respective summary RRs for high versus low activity was 0.78 (95 % CI 0.61-1.00, I(2) = 47 %, n = 8) before pregnancy, and it was 0.80 (95 % CI 0.64-1.00, I(2) = 17 %, n = 17) during pregnancy. The summary RR for pre-pregnancy activity was 0.70 (95 % CI 0.49-1.01, I(2) = 72.6 %, n = 3) per increment of 5 h/week and for activity during pregnancy was 0.98 (95 % CI 0.87-1.09, I(2) = 0 %, n = 3) per 5 h/week. There was evidence of a nonlinear association between physical activity before pregnancy and the risk of gestational diabetes mellitus, pnonlinearity = 0.005, with a slightly steeper association at lower levels of activity although further reductions in risk were observed up to 10 h/week. There was also evidence of nonlinearity for physical activity in early pregnancy, pnonlinearity = 0.008, with no further reduction in risk above 8 h/week. There was some indication of inverse associations between walking (before and during pregnancy) and vigorous activity (before pregnancy) and the risk of gestational diabetes mellitus. This meta-analysis suggests that there is a significant inverse association between physical activity before pregnancy and in early pregnancy and the risk of gestational diabetes mellitus. Further studies are needed to clarify the association between specific types and intensities of activity and gestational diabetes mellitus

Protocol for a 20-year follow-up after a randomized controlled trial of a Mediterranean diet in pregnancy:maternal and offspring risk factors for cardiovascular disease

Background: An inadequate maternal diet during pregnancy can impair offspring health and may increase the risk of cardiovascular disease later in life. The purpose of the proposed study is to assess the risk factors associated with cardiovascular disease in both mothers and their offspring 20 years following their participation in a Mediterranean diet intervention trial during pregnancy.Methods: The “Cardiovascular Risk Reduction Diet In Pregnancy” (CARRDIP) study was a randomized controlled trial performed between 1999 and 2001. The participants were randomized to adhere to either a Mediterranean diet or their regular diet during pregnancy. An extensive amount of data such as diet information, ultrasound measurements, anthropometry, and biomarkers from these mothers during pregnancy and their offspring in the neonatal period were collected. The mother–offspring pairs (n = 269) from the CARRDIP study will be invited to participate in a clinical examination and blood sample collection. This follow-up study, conducted 20 years after the original CARRDIP study, will investigate cardiovascular risk factors in mothers and offspring. The primary outcome will be the blood pressure of the offspring. In addition, the study will explore various aspects of cardiovascular health, including metabolic and inflammatory status, clinical history, and body composition of the participants.Discussion: Previous studies investigating the effects of nutrition during pregnancy on maternal and offspring health have been either observational studies, animal studies, or randomized controlled trials with a follow-up period of less than 5 years. This project aims to study the long-term effects of dietary intervention during pregnancy on maternal and offspring cardiovascular risk markers.Clinical Trial Registration: Clinicaltrials.gov, identifier (NCT05030922)

Whole grain consumption and risk of cardiovascular disease, cancer, and all cause and cause specific mortality: systematic review and dose-response meta-analysis of prospective studies

Objective To quantify the dose-response relation between consumption of whole grain and specific types of grains and the risk of cardiovascular disease, total cancer, and all cause and cause specific mortality. Data sources PubMed and Embase searched up to 3 April 2016. Study selection Prospective studies reporting adjusted relative risk estimates for the association between intake of whole grains or specific types of grains and cardiovascular disease, total cancer, all cause or cause specific mortality. Data synthesis Summary relative risks and 95% confidence intervals calculated with a random effects model. Results 45 studies (64 publications) were included. The summary relative risks per 90 g/day increase in whole grain intake (90 g is equivalent to three servings—for example, two slices of bread and one bowl of cereal or one and a half pieces of pita bread made from whole grains) was 0.81 (95% confidence interval 0.75 to 0.87; I2=9%, n=7 studies) for coronary heart disease, 0.88 (0.75 to 1.03; I2=56%, n=6) for stroke, and 0.78 (0.73 to 0.85; I2=40%, n=10) for cardiovascular disease, with similar results when studies were stratified by whether the outcome was incidence or mortality. The relative risks for morality were 0.85 (0.80 to 0.91; I2=37%, n=6) for total cancer, 0.83 (0.77 to 0.90; I2=83%, n=11) for all causes, 0.78 (0.70 to 0.87; I2=0%, n=4) for respiratory disease, 0.49 (0.23 to 1.05; I2=85%, n=4) for diabetes, 0.74 (0.56 to 0.96; I2=0%, n=3) for infectious diseases, 1.15 (0.66 to 2.02; I2=79%, n=2) for diseases of the nervous system disease, and 0.78 (0.75 to 0.82; I2=0%, n=5) for all non-cardiovascular, non-cancer causes. Reductions in risk were observed up to an intake of 210-225 g/day (seven to seven and a half servings per day) for most of the outcomes. Intakes of specific types of whole grains including whole grain bread, whole grain breakfast cereals, and added bran, as well as total bread and total breakfast cereals were also associated with reduced risks of cardiovascular disease and/or all cause mortality, but there was little evidence of an association with refined grains, white rice, total rice, or total grains. Conclusions This meta-analysis provides further evidence that whole grain intake is associated with a reduced risk of coronary heart disease, cardiovascular disease, and total cancer, and mortality from all causes, respiratory diseases, infectious diseases, diabetes, and all non-cardiovascular, non-cancer causes. These findings support dietary guidelines that recommend increased intake of whole grain to reduce the risk of chronic diseases and premature mortality

Bupropion SR for smoking cessation in smokers with cardiovascular disease: a multicentre, randomised study

Aim To investigate the safety and efficacy of bupropion sustained release (bupropion SR) in promoting abstinence from smoking in subjects with cardiovascular disease (CVD). Methods Six hundred twenty-nine subjects with CVD who smoked ≥10 cigarettes/day were randomised in a double-blind, multicentre study to receive bupropion SR (150mg twice daily) or placebo for 7 weeks, with a follow-up of 52 weeks. Primary efficacy endpoint: continuous abstinence from smoking from weeks 4 to 7. Secondary endpoints: continuous abstinence (weeks 4-12, 4-26 and 4-52) and weekly point prevalence abstinence. All participants received brief motivational support. Safety was evaluated throughout the study. Results Continuous smoking abstinence rates from weeks 4 to 7 were significantly higher in subjects receiving bupropion SR compared with placebo (43 vs. 19%, odds ratio [OR]=3.27, 95% confidence interval [CI] 2.24-4.84; \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $P{<}0.001$ \end{document}). Continuous abstinence rates from weeks 4 to 26 and 4 to 52 continued to be more than double for bupropion SR compared with placebo (27 vs. 11%; 22 vs. 9%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $P{<}0.001$ \end{document}). Weekly point prevalence abstinence was significantly higher for participants who received bupropion SR compared with placebo at weeks 3, 7, 26 and 52 \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(P{<}0.001)$ \end{document}. In both groups, there were no clinically significant changes in blood pressure and heart rate throughout the treatment phase. Overall, 6% of the participants \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $(n=36)$ \end{document} discontinued study medication due to an adverse event (bupropion SR, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $n=17$ \end{document}; placebo, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} $n=19$ \end{document}). Conclusions After 7 weeks of bupropion SR treatment, more than twice as many smokers with CVD had quit smoking at 1 year compared with placebo. The safety profile of bupropion SR was similar to that previously observed in general smoking population

Smoking and Risk for Diabetes Incidence and Mortality in Korean Men and Women

This is an uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association, publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care in print and online a

Effectiveness of individualized training based on force–velocity profiling on physical function in older men

The study aimed to investigate the effectiveness of an individualized power training program based on force–velocity (FV) profiling on physical function, muscle morphology, and neuromuscular adaptations in older men. Forty-nine healthy men (68 ± 5 years) completed a 10-week training period to enhance muscular power. They were randomized to either a generic power training group (GPT) or an individualized power training group (IPT). Unlike generic training, individualized training was based on low- or high-resistance exercises, from an initial force–velocity profile. Lower-limb FV profile was measured in a pneumatic leg-press, and physical function was assessed as timed up-and-go time (TUG), sit-to-stand power, grip strength, and stair-climbing time (loaded [20kg] and unloaded). Vastus lateralis morphology was measured with ultrasonography. Rate of force development (RFD) and rate of myoelectric activity (RMA) were measured during an isometric knee extension. The GPT group improved loaded stair-climbing time (6.3 ± 3.8 vs. 2.3% ± 7.3%, p = 0.04) more than IPT. Both groups improved stair-climbing time, sit to stand, and leg press power, grip strength, muscle thickness, pennation angle, fascicle length, and RMA from baseline (p < 0.05). Only GPT increased loaded stair-climbing time and RFD (p < 0.05). An individualized power training program based on FV profiling did not improve physical function to a greater degree than generic power training. A generic power training approach combining both heavy and low loads might be advantageous through eliciting both force- and velocity-related neuromuscular adaptions with a concomitant increase in muscular power and physical function in older men.publishedVersio

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