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The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.
METHODS AND RESULTS:
In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].
CONCLUSION:
Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.
Background Nut consumption has increased in the US but little evidence exists on the association between changes in nut consumption and weight change. We aimed to evaluate the association between changes in total consumption of nuts and intakes of different nuts (including peanuts) and long-term weight change, in three independent cohort studies.
Methods and findings Data collected in three prospective, longitudinal cohorts among health professionals in the US were analysed. We included 27 521 men (Health Professionals Follow-up Study, 1986 to 2010), 61 680 women (Nurses’ Health Study, 1986 to 2010), and 55 684 younger women (Nurses’ Health Study II, 1991 to 2011) who were free of chronic disease at baseline in the analyses. We investigated the association between changes in nut consumption over 4-year intervals and concurrent weight change over 20–24 years of follow-up using multivariate linear models with an unstructured correlation matrix to account for within-individual repeated measures. 21 322 individuals attained a body mass index classification of obesity (BMI ≥30 kg/m2) at the end of follow-up.
Average weight gain across the three cohorts was 0.32 kg each year. Increases in nut consumption, per 0.5 servings/day (14 g), was significantly associated with less weight gain per 4-year interval (p<0.01 for all): −0.19 kg (95% CI -0.21 to -0.17) for total consumption of nuts, -0.37 kg (95% CI -0.45 to -0.30) for walnuts, -0.36 kg (95% CI -0.40 to -0.31) for other tree nuts, and -0.15 kg (95% CI -0.19 to -0.11) for peanuts.
Increasing intakes of nuts, walnuts, and other tree nuts by 0.5 servings/day was associated with a lower risk of obesity. The multivariable adjusted RR for total nuts, walnuts, and other tree nuts was 0.97 (95% CI 0.96 to 0.99, p=0.0036), 0.85 (95% CI 0.81 to 0.89, p=0.0002), and 0.89 (95% CI 0.87 to 0.91, p<0.0001), respectively. Increasing nut consumption was also associated with a lower risk of gaining ≥2 kg or ≥5 kg (RR 0.89–0.98, p<0.01 for all).
In substitution analyses, substituting 0.5 servings/day of nuts for red meat, processed meat, French fries, desserts, or potato, chips (crisps) was associated with less weight gain (p<0.05 for all).
Our cohorts were largely composed of Caucasian health professionals with relatively higher socioeconomic status; thus the results may not be generalisable to other populations.
Conclusion Increasing daily consumption of nuts is associated with less long-term weight gain and a lower risk of obesity in adults. Replacing 0.5 servings/day of less healthful foods with nuts may be a simple strategy to help prevent gradual long-term weight gain and obesity.
Morbidity from asthma is disproportionately higher among black patients than among white patients, and black patients constitute the minority of participants in trials informing treatment. Data indicate that patients with inadequately controlled asthma benefit more from addition of a long-acting beta-agonist (LABA) than from increased glucocorticoids; however, these data may not be informative for treatment in black patients.
METHODS:
We conducted two prospective, randomized, double-blind trials: one involving children and the other involving adolescents and adults. In both trials, the patients had at least one grandparent who identified as black and had asthma that was inadequately controlled with low-dose inhaled glucocorticoids. We compared combinations of therapy, which included the addition of a LABA (salmeterol) to an inhaled glucocorticoid (fluticasone propionate), a step-up to double to quintuple the dose of fluticasone, or both. The treatments were compared with the use of a composite measure that evaluated asthma exacerbations, asthma-control days, and lung function; data were stratified according to genotypic African ancestry.
RESULTS:
When quintupling the dose of fluticasone (to 250 μg twice a day) was compared with adding salmeterol (50 μg twice a day) and doubling the fluticasone (to 100 μg twice a day), a superior response occurred in 46% of the children with quintupling the fluticasone and in 46% of the children with doubling the fluticasone and adding salmeterol (P = 0.99). In contrast, more adolescents and adults had a superior response to added salmeterol than to an increase in fluticasone (salmeterol-low-dose fluticasone vs. medium-dose fluticasone, 49% vs. 28% [P = 0.003]; salmeterol-medium-dose fluticasone vs. high-dose fluticasone, 49% vs. 31% [P = 0.02]). Neither the degree of African ancestry nor baseline biomarkers predicted a superior response to specific treatments. The increased dose of inhaled glucocorticoids was associated with a decrease in the ratio of urinary cortisol to creatinine in children younger than 8 years of age.
CONCLUSIONS:
In contrast to black adolescents and adults, almost half the black children with poorly controlled asthma had a superior response to an increase in the dose of an inhaled glucocorticoid and almost half had a superior response to the addition of a LABA. (Funded by the National Heart, Lung, and Blood Institute; BARD ClinicalTrials.gov number, NCT01967173.).
Whether physical activity attenuates the association of total daily sitting time with cardiovascular disease and diabetes incidence is unclear. This systematic review and meta-analysis examined the association of total daily sitting time with cardiovascular disease and diabetes with and without adjustment for physical activity.
EVIDENCE ACQUISITION:
PubMed, Web of Science, BASE, MEDLINE, Academic Search Elite, and ScienceDirect were searched for prospective studies, published between January 1, 1989, and February 15, 2019, examining the association of total daily sitting time with cardiovascular disease or diabetes outcomes. Data extraction and study quality assessments were conducted by 2 independent reviewers. Pooled hazard ratios (HRs) were calculated using a fixed-effects model. The quality assessment and meta-analysis procedures were completed in 2018.
EVIDENCE SYNTHESIS:
Nine studies with 448,285 participants were included. A higher total daily sitting time was associated with a significantly increased risk of cardiovascular disease (HR=1.29, 95% CI=1.27, 1.30, p<0.001) and diabetes (HR=1.13, 95% CI=1.04, 1.22, p<0.001) incidence when not adjusted for physical activity. The increased risk for diabetes was unaffected when adjusting for physical activity (HR=1.11, 95% CI=1.01, 1.19, p<0.001). For cardiovascular disease, the increased risk was attenuated but remained significant (HR=1.14, 95% CI=1.04, 1.23, p<0.001).
CONCLUSIONS:
Higher levels of total daily sitting time are associated with an increased risk of cardiovascular disease and diabetes, independent of physical activity. Reductions in total daily sitting may be recommended in public health guidelines.
Stroke continues to be a major cause of morbidity and mortality in atrial fibrillation (AF) patients. Oral anticoagulation (OAC) provides protection against stroke and peripheral embolization in AF but significant proportion of patients could not be started on anticoagulation because of bleeding complications. Left atrial appendage harbors clot in about 90% of nonvalvular AF. The advent of left atrial appendage occlusion (LAAO) techniques has provided these patients with alternative to OAC for stroke prophylaxis. Multiple LAAO devices are currently available with Watchman and Amulet being the most commonly used in clinical practice. Randomized studies are available for Watchman device only. Data on Amplatzer Cardiac Plug, Amulet and Lariat devices are limited by the paucity of randomized data. Long-term data on different LAAO techniques are showing promising results. Device related thrombosis continues to be a serious complication associated with LAAO. Future studies should look into comparative effectiveness between different LAAO techniques, optimal patient selection, risk of complications, and anticoagulant treatment after LAAO. This article aims to provide current available evidence on efficacy and safety of different LAAO devices and future prospective.
Purpose
To review the evidence and provide clinical recommendations for the pharmacologic management of atrial fibrillation.
Methods
This guideline is based on two systematic reviews of published randomized controlled trials (RCTs) and prospective and retrospective observational studies from 2000 to 2012. An updated literature search was performed to identify new studies from 2012 to December 31, 2015. The target audience for the guideline includes all primary care clinicians, and the target patient population includes adults who have nonvalvular atrial fibrillation that is not due to a reversible cause. This guideline was developed using a modified version of GRADE to evaluate the quality of the evidence and make recommendations based on the balance of benefits and harms.
