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Marie-Pierre St-Onge,1 Gary Zammit,2 David M Reboussin,3 Samuel T Kuna,4 Mark H Sanders,8 Richard Millman,6 Anne B Newman,5 Thomas A Wadden,4 Rena R Wing,6 F Xavier Pi-Sunyer,1 Gary D Foster7 Sleep AHEAD Research Group*1New York Obesity Research Center, St Luke's/Roosevelt Hospital, New York, NY, USA; 2Clinilabs, New York, NY, USA; 3Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 4Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA; 5Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA; 6Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA; 7Center for Obesity Research and Education, Temple University, Philadelphia, PA, USA; 8Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, PA, USA*A full list of the members of the Sleep AHEAD Research Group is available in an online appendixPurpose: Some studies have found an association between sleep disturbances and metabolic risk, but none has examined this association in individuals with type 2 diabetes. The objective of this study was to determine the relationship between sleep disturbances and metabolic risk factors in obese patients with type 2 diabetes.Patients and methods: This study was a cross-sectional examination of the relationship between sleep parameters (apnea/hypopnea index [AHI], time spent in various sleep stages) and metabolic risk markers (fasting glucose, hemoglobin A1c, lipids) using baseline data of the Sleep AHEAD cohort. Subjects (n = 305) were participants in Sleep AHEAD (Action for Health in Diabetes), a four-center ancillary study of the Look AHEAD study, a 16-center clinical trial of overweight and obese participants with type 2 diabetes, designed to assess the long-term effects of an intensive lifestyle intervention on cardiovascular events. All participants underwent one night of in-home polysomnography and provided a fasting blood sample. Regression analyses estimated the relationship between sleep variables and metabolic risk factors. Models were adjusted for study center, age, sex, race/ethnicity, waist circumference, smoking, alcohol intake, diabetes duration, and relevant medications.Results: Of 60 associations tested, only one was significant: fasting glucose was associated with sleep efficiency (estimate −0.53 ± [standard error] 0.26, P = 0.041). No associations were found between any of the sleep variables and lipid profile or hemoglobin A1c.Conclusions: The present data show only weak associations between select sleep variables and metabolic risk factors and do not provide strong support for a role of sleep on metabolic abnormalities in obese patients with type 2 diabetes.Keywords: obesity, obstructive sleep apnea, metabolic risk, sleep, diabetes

We compared initial screening transferrin saturation (TfSat) and serum ferritin (SF) phenotypes and HFE C282Y and H63D genotypes of 645 Native American and 43,453 white Hemochromatosis and Iron Overload Screening Study participants who did not report a previous diagnosis of hemochromatosis or iron overload. Elevated measurements were defined as TfSat >50% in men and >45% in women and SF >300 ng/ml in men and >200 ng/ml in women. Mean TfSat was 31% in Native American men and 32% in white men (p = 0.0337) and 25% in Native American women and 27% in white women (p < 0.0001). Mean SF was 153 microg/l in Native American and 151 microg/l in white men (p = 0.8256); mean SF was 55 microg/l in Native American women and 63 microg/l in white women (p = 0.0015). The C282Y allele frequency was 0.0340 in Native Americans and 0.0683 in whites (p < 0.0001). The H63D allele frequency was 0.1150 in Native Americans and 0.1532 in whites (p = 0.0001). We conclude that the screening TfSat and SF phenotypes of Native Americans are similar to those of whites. The allele frequencies of HFE C282Y and H63D are significantly lower in Native Americans than in whites.

Objective: We examined whether a 1-year intensive lifestyle intervention (ILI) for weight loss reduced elevated high-sensitivity C-reactive protein (hs-CRP) levels in obese individuals with diabetes and identified metabolic and fitness predictors of hs-CRP change.Research Design and Methods: Look AHEAD (Action for Health in Diabetes) is an ongoing multicenter clinical trial examining the effects of weight loss achieved through ILI on cardiovascular events and overall mortality in obese/overweight adults with type 2 diabetes. We report on 1,759 Look AHEAD participants who had hs-CRP and fitness data at baseline and 1 year. Subjects were randomly assigned to ILI or to usual care (diabetes support and education [DSE]). ILI involved frequent counseling to increase moderate-intensity exercise to 175 min/week, reduce caloric and saturated fat intake, and change macronutrient composition to improve glycemic control.Results: ILI reduced median hs-CRP by 43.6% from baseline to 1 year, compared with a 16.7% reduction with DSE (P<0.001). ILI decreased weight (8.8%), A1C (0.7%), and triglycerides (17%) and increased fitness (19%) and HDL cholesterol (7.5%) (P<0.0001 vs. changes with DSE). Changes in adiposity and glucose control with ILI remained independent predictors of hs-CRP change at 1 year (P<0.0001 for each) after adjustment for demographics, smoking, cardiovascular history, statin and thiazolidinedione use, and changes in fitness and lipid control. Neither statin nor insulin therapy modified the association between ILI and hs-CRP.Conclusions: A 1-year lifestyle intervention for weight loss in obese individuals with diabetes was associated with substantial reductions in hs-CRP. Improved glycemic control and reduced adiposity had comparable effects on hs-CRP change. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study. Research Design and Methods: Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis. Results: The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center. Conclusions: Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload. [ABSTRACT FROM AUTHOR]

Background: Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. Methods: Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. Results: Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 mug per liter in 78 of 89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 microg per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. Conclusions: The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites. [ABSTRACT FROM AUTHOR]

Objective: To examine usual marine omega-3 fatty acid (mO-3FA) intake in individuals with diabetes; its association with adiposity, lipid, and glucose control; and its changes with behavioral lifestyle intervention for weight loss.Research Design and Methods: Cross-sectional and 1-year longitudinal analyses were performed on 2,397 Look AHEAD (Action for Health in Diabetes) participants. Look AHEAD is a cardiovascular outcome trial evaluating the effects of intensive lifestyle intervention for weight loss in overweight/obese subjects with type 2 diabetes.Results: Baseline mO-3FA intake was 162 +/- 138 mg/day. It was inversely associated with triglycerides (beta = -0.41, P < 0.001) and weakly with HDL (beta = 4.14, P = 0.050), after multiple covariate adjustment. One-year mO-3FA and fried/sandwich fish intake decreased with intensive lifestyle intervention (P < 0.001).Conclusions: mO-3FA intake in Look AHEAD participants was low but associated favorably with lipids. These results encourage investigation on the potential benefits of increasing mO-3FA intake in lifestyle interventions for weight loss in individuals with diabetes. [ABSTRACT FROM AUTHOR]

Background: Avocado intake improves dietary fat quality, but the subsequent impact on red blood cell (RBC) saturated (SFA), monounsaturated (MUFA), polyunsaturated (PUFA), and trans-fatty acid (TFA) composition and association with cardiometabolic health, has not been elucidated., Objectives: To compare the effect of consuming 1 avocado/d relative to habitual diet (HAB) on RBC-FA profiles, and their association with visceral adiposity and cardiometabolic risk factors (CMRFs) in individuals with abdominal obesity., Methods: RBC-FA profiling at baseline, 3- and 6 mo was conducted in participants (n = 994) from the Habitual Diet and Avocado Trial (HAT). HAT was a multisite, free-living, parallel-arm intervention study in which participants were randomly assigned to either the avocado-supplemented group (AVO, usual diet with 1 avocado/d) or the HAB group (usual diet with limited avocado intake) for 6 mo. Changes in RBC-FA profiles, a secondary outcome measure, were determined within and between groups using linear regression and mixed effect models, adjusting for age, sex, BMI, clinical site, smoking status, and percentage of energy intake from fat at baseline. The association between changes in RBC-FAs with visceral adiposity measures and CMRFs was assessed after covariate and False Discovery Rate (FDR <0.05) adjustment., Results: No major differences in RBC-FA profiles were observed between groups, with the exception of MUFA cis-vaccenic [18:1n-7c], which was significantly higher in AVO (β: 0.11 [0.05, 0.17]) compared with the HAB (β: 0.03 [-0.03, 0.08]) participants. In the HAB but not AVO group, increases in MUFA cis (18:1n-7c, oleic [18;1n-9c], erucic [22:1n-9c]) and MUFA trans (palmitelaidic [16:1n-7t], vaccenic [18:1n-7t], elaidic [18:1n-9t], and petroselaidic [18;1n-10-12t), as well as PUFA γ-linolenic [18:3n-6], dihomo-γ-linolenic [20:3n-6], arachidonic [20:4n-6], and α-linolenic [18:3n-3] were associated with unfavorable changes in visceral adiposity measures, lipid profiles, glucose, insulin and high sensitivity C-reactive protein concentrations., Conclusions: Daily avocado intake over 6-mo modified RBC-MUFA composition, notably 18:1n-7c, and potentially mitigated some of the unfavorable individual RBC-FA-CMRF associations observed over time in the HAB group. This trial was registered at https://clinicaltrials.gov/study as NCT03528031., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Adolescents and young adults continue to use e-cigarettes, and communication campaigns are needed to decrease use among these populations. We developed and tested a point-of-sale communication campaign focused on e-cigarette chemical exposure. We developed messages based on formative research and tested them (versus text-only messages) in a nationally-representative online survey among adolescents and young adults (16-25) (Phase 1). Based on survey findings, we selected a message focused on nicotine and brain development for the point-of-sale trial (Phase 2). We then conducted a cluster-randomized trial at six gas stations with convenience stores, randomly assigned to the intervention (messages displayed) or no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 participants (ages 16-25) per store, at baseline and a four-week follow-up. Phase 1 included 1,636 participants in the online study. Intervention messages were rated as more attention grabbing than plain text messages ( p  < .05), though were rated similarly on other outcomes. Exposure to intervention messages resulted in larger changes from pre- to posttest for beliefs about addiction and relative harms versus cigarettes ( p  < .05). Phase 2 included 586 participants in the point-of-sale study. Real-world campaign exposure was low (31.8%), and no differences were found between conditions. E-cigarette prevention messages focused on nicotine's impact on brain development show promise. However, garnering attention for communication campaigns in saturated point-of-sale environments, often dominated by tobacco advertising, is challenging. Future efforts should utilize additional communication channels to directly target adolescents and young adults.

Objective: Subclinical brain infarcts (SBI) increase the risk for stroke and dementia, but whether they should be considered equivalent to symptomatic stroke when determining blood pressure targets remains unclear. We tested whether intensive systolic blood pressure (SBP) treatment reduced the risk of new SBI or stroke and determined the association between SBI and cognitive impairment., Methods: In this secondary analysis of SPRINT (Systolic Pressure Intervention Trial), participants ≥50 years old, with SBP 130-180mmHg and elevated cardiovascular risk but without known clinical stroke, dementia, or diabetes, were randomized to intensive (<120mmHg) or standard (<140mmHg) SBP treatment. Brain magnetic resonance images collected at baseline and follow-up were read for SBI. The occurrence of mild cognitive impairment (MCI) or probable dementia (PD) was evaluated., Results: For 667 participants at baseline, SBI were identified in 75 (11%). At median 3.9 years follow-up, 12 of 457 had new SBI on magnetic resonance imaging (5 intensive, 7 standard), whereas 8 had clinical stroke (4 per group). Baseline SBI (subhazard ratio [sHR] = 3.90; 95% CI 1.49 to 10.24; p = 0.006), but not treatment group, was associated with new SBI or stroke. For participants with baseline SBI, intensive treatment reduced their risk for recurrent SBI or stroke (sHR = 0.050; 95% CI 0.0031 to 0.79; p = 0.033). Baseline SBI also increased risk for MCI or PD during follow-up (sHR = 2.38; 95% CI 1.23 to 4.61; p = 0.010)., Interpretation: New cerebral ischemic events were infrequent, but intensive treatment mitigated the increased risk for participants with baseline SBI, indicating primary prevention SBP goals are still appropriate when SBI are present. ANN NEUROL 2024;95:866-875., (© 2024 American Neurological Association. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: Few clinical trials have evaluated diet quality change as a predictor of intervention effectiveness., Objectives: The aim of this study was to examine changes in the Healthy Eating Index (HEI)-2015 after a food-based intervention, and assess the associations between HEI-2015 change and intervention effects on cardiometabolic risk-related outcomes., Methods: The Habitual Diet and Avocado Trial was a 26-wk, multicenter, randomized, controlled parallel-arm study. Participants were 1008 individuals aged ≥25 y with abdominal obesity (females ≥ 35 inches; males ≥ 40 inches). The avocado-supplemented diet group was provided 1 avocado per day, and the habitual diet group maintained their usual diet. Change in diet quality was assessed using the HEI-2015 from a single 24-h recall conducted at 4 time points. Mixed models were used for analysis., Results: The avocado-supplemented diet group had a greater increase in the HEI-2015 (4.74 points; 95% CI: 2.93, 6.55) at 26 wk than the habitual diet group. Compared with the habitual diet group, the avocado-supplemented diet group had greater increases in the following HEI-2015 components from baseline: total vegetables (0.99 points; 95% CI: 0.77, 1.21), fatty acid ratio (2.25 points; 95% CI: 1.74, 2.77), sodium (1.03 points; 95% CI: 0.52, 1.55), refined grains (0.82 points; 95% CI: 0.32, 1.31), and added sugars (0.84 points; 95% CI: 0.49, 1.19). No differences in HEI-2015 improvements were observed by race, ethnicity, study site, body mass index, or age category. In the avocado-supplemented diet compared with the habitual diet group, the HEI-2015 increased in females (6.50 points; 95% CI: 4.39, 8.62) but not in males (0.02 points; 95% CI: -3.44, 3.48). Median HEI-2015 change was not associated with intervention-related changes in cardiometabolic disease risk factors., Conclusions: Intake of 1 avocado per day for 26 wk in adults with abdominal obesity increased adherence to the Dietary Guidelines for Americans. Changes in diet quality did not predict changes in risk factors for cardiometabolic disease.This trial was registered at clinicaltrials.gov as NCT03528031 (https://clinicaltrials.gov/study/NCT03528031)., (© 2024 The Author(s).)

Many adolescents and young adults hold erroneous beliefs that cigarillos and waterpipe tobacco (WT) are safer than cigarettes, contributing to use. Communication campaigns can correct misperceptions and increase risk beliefs. We tested point-of-sale (POS) communication campaigns focused on chemical exposure for cigarillos and WT. We conducted two cluster randomized trials at 20 gas stations with convenience stores (10 stores for cigarillos, 10 for WT) in North Carolina between June and November 2017. Within each trial, stores were randomly assigned to either the intervention (campaign messages displayed) or a no message control condition. We conducted intercept surveys with repeated cross-sectional samples of 50 adolescents and young adults (ages 16-25) per store, at baseline and follow-up. There were 978 participants (mean age = 20.9 years) in the cigarillo trial, and 998 participants (mean age = 21.0 years) in the WT trial. Rates of campaign exposure were low (26% for cigarillos; 24.3% for WT). The cigarillo campaign increased knowledge that ammonia is in cigarillo smoke ( p < .01). There were also significant increases in knowledge about ammonia and cyanide in cigarillo smoke and arsenic in WT smoke ( p < .05) in the sub-sample who reported exposure to the campaign. No differences were found in outcome expectancies, product attitudes, worry about chemical exposure, or behavioral intentions in either campaign. Garnering attention for communication campaigns in saturated POS environments, often dominated by tobacco advertising, is challenging. Our study demonstrates the feasibility of anti-tobacco campaigns at the POS and points to several lessons learned for future POS campaigns.

Background: Brain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure., Methods: This is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130-180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, Black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH)., Results: For 610 participants with sufficient quality MRI at baseline (mean age 67 ± 8, 40 % female, 32 % Black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median ± IQR = 3.9 ± 0.4 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: -0.029 [-0.055 to -0.0029] p = 0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB)., Conclusions: PVS enlargement was partially reversed in the intensive SBP treatment group. The association with CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance. Clincaltrials.gov: NCT01206062., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Clinton B. Wright reports a relationship with Wolters Kluwer UpToDate that includes: consulting or advisory.]., (Copyright © 2023. Published by Elsevier Inc.)

Importance: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive blood pressure control reduced cardiovascular morbidity and mortality. However, the legacy effect of intensive treatment is unknown., Objective: To evaluate the long-term effects of randomization to intensive treatment with the incidence of cardiovascular and all-cause mortality approximately 4.5 years after the trial ended., Design, Setting, and Participants: In this secondary analysis of a multicenter randomized clinical trial, randomization began on November 8, 2010, the trial intervention ended on August 20, 2015, and trial close-out visits occurred through July 2016. Patients 50 years and older with hypertension and increased cardiovascular risk but without diabetes or history of stroke were included from 102 clinic sites in the US and Puerto Rico. Analyses were conducted between October 2021 and February 2022., Interventions: Randomization to systolic blood pressure (SBP) goal of less than 120 mm Hg (intensive treatment group; n = 4678) vs less than 140 mm Hg (standard treatment group; n = 4683)., Main Outcomes and Measures: Extended observational follow-up for mortality via the US National Death Index from 2016 through 2020. In a subset of 2944 trial participants, outpatient SBP from electronic health records during and after the trial were examined., Results: Among 9361 randomized participants, the mean (SD) age was 67.9 (9.4) years, and 3332 (35.6%) were women. Over a median (IQR) intervention period of 3.3 (2.9-3.9) years, intensive treatment was beneficial for both cardiovascular mortality (hazard ratio [HR], 0.66; 95% CI, 0.49-0.89) and all-cause mortality (HR, 0.83; 95% CI, 0.68-1.01). However, at the median (IQR) total follow-up of 8.8 (8.3-9.3) years, there was no longer evidence of benefit for cardiovascular mortality (HR, 1.02; 95% CI, 0.84-1.24) or all-cause mortality (HR, 1.08; 95% CI, 0.94-1.23). In a subgroup of participants, the estimated mean outpatient SBP among participants randomized to intensive treatment increased from 132.8 mm Hg (95% CI, 132.0-133.7) at 5 years to 140.4 mm Hg (95% CI, 137.8-143.0) at 10 years following randomization., Conclusions and Relevance: The beneficial effect of intensive treatment on cardiovascular and all-cause mortality did not persist after the trial. Given increasing outpatient SBP levels in participants randomized to intensive treatment following the trial, these results highlight the importance of consistent long-term management of hypertension., Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Introduction: Lowering blood pressure (BP) reduces the risk for cognitive impairment and the progression of cerebral white matter lesions. It is unclear whether hypertension control also influences plasma biomarkers related to Alzheimer's disease and non-disease-specific neurodegeneration., Methods: We examined the effect of intensive (< 120 mm Hg) versus standard (< 140 mm Hg) BP control on longitudinal changes in plasma amyloid beta (Aβ) 40 and Aβ 42 , total tau, and neurofilament light chain (NfL) in a subgroup of participants from the Systolic Blood Pressure Intervention Trial (N = 517)., Results: Over 3.8 years, there were no significant between-group differences for Aβ 40, Aβ 42, Aβ 42 /Aβ 40, or total tau. Intensive treatment was associated with larger increases in NfL compared to standard treatment. Adjusting for kidney function, but not BP, attenuated the association between intensive treatment and NfL., Discussion: Intensive BP treatment was associated with changes in NfL, which were correlated with changes in kidney function associated with intensive treatment., Trial Registration: clinicaltrials.gov Identifier: NCT01206062., (© 2021 the Alzheimer's Association.)

Background Excess visceral adiposity is associated with increased risk of cardiometabolic disorders. Short-term well-controlled clinical trials suggest that regular avocado consumption favorably affects body weight, visceral adiposity, and satiety. Methods and Results The HAT Trial (Habitual Diet and Avocado Trial) was a multicenter, randomized, controlled parallel-arm trial designed to test whether consuming 1 large avocado per day for 6 months in a diverse group of free-living individuals (N=1008) with an elevated waist circumference compared with a habitual diet would decrease visceral adiposity as measured by magnetic resonance imaging. Secondary and additional end points related to risk factors associated with cardiometabolic disorders were assessed. The primary outcome, change in visceral adipose tissue volume during the intervention period, was not significantly different between the Avocado Supplemented and Habitual Diet Groups (estimated mean difference (0.017 L [-0.024 L, 0.058 L], P =0.405). No significant group differences were observed for the secondary outcomes of hepatic fat fraction, hsCRP (high-sensitivity C-reactive protein), and components of the metabolic syndrome. Of the additional outcome measures, modest but nominally significant reductions in total and low-density lipoprotein cholesterol were observed in the Avocado Supplemented compared with the Habitual Diet Group. Changes in the other additional and post hoc measures (body weight, body mass index, insulin, very low-density lipoprotein concentrations, and total cholesterol:high-density lipoprotein cholesterol ratio) were similar between the 2 groups. Conclusions Addition of 1 avocado per day to the habitual diet for 6 months in free-living individuals with elevated waist circumference did not reduce visceral adipose tissue volume and had minimal effect on risk factors associated with cardiometabolic disorders. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03528031.

Background: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death., Methods: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of <120 mm Hg (intensive treatment; n = 4678) or <140 mm Hg (Standard treatment; n = 4683). Outcomes included adjudicated MCI, MCI subtype (amnestic, non-amnestic, multi-domain, single domain), and probable dementia. Multistate survival models were used to examine transitions in cognitive status accounting for the competing risk of death., Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 640 participants met the protocol definition for MCI, with intensive treatment reducing the risk of MCI overall (hazard ratio [HR], 0.81 [95% confidence interval {CI}, 0.69-0.94]), as previously reported. This effect was largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66-0.92]) and multi-domain subtypes (HR, 0.78 [95% CI, 0.65-0.93]). An adjudication of MCI, as compared with normal cognitive function, substantially increased the probability of progressing to probable dementia (5.9% [95% CI: 4.5%-7.7%] vs. 0.6% [95% CI: 0.3%-0.9%]) and to death (10.0% [95% CI: 8.3%-11.9%] vs. 2.3% [95% CI: 2.0%-2.7%]) within 2 years., Conclusions: Intensive treatment reduced the risk for amnestic and multi-domain subtypes of MCI. An adjudication of MCI was associated with increased risk of progression to dementia and death, highlighting the relevance of MCI as a primary outcome in clinical and research settings., (© 2021 The American Geriatrics Society.)

The SPRINT (Systolic Blood Pressure Intervention Trial) results have influenced clinical practice but have also generated discussion regarding the validity, generalizability, and importance of the findings. Following the SPRINT primary results manuscript in 2015, additional results and analyses of the data have addressed these concerns. The primary objective of this article is to respond to key questions that have been raised.

Excess visceral adiposity is associated with increased risk of diabetes and cardiovascular disease. In the U.S. approximately 60% of adults have visceral obesity. Despite high calorie and fat, small, well-controlled clinical studies suggest that avocado consumption has favorable effects on body weight and visceral adiposity. Additionally, short-term studies also suggest that consuming avocados increases satiety, hence, may decrease overall energy intake. The Habitual Diet and Avocado Trial HAT is a multi-center, randomized, controlled trial designed to test whether in a large, diverse cohort providing one avocado per day for consumption for six months compared to a habitual diet essentially devoid of avocados, will result in a decrease in visceral adiposity as measured by magnetic resonance imaging (MRI) in individuals with an increased waist circumference (WC). Additional outcome measures include hepatic lipid content, plasma lipid profiles, blood pressure and high sensitivity C-reactive protein. Inclusion criteria were increased WC and not currently eating more than two avocados per month. Major exclusion criteria were not eating or being allergic to avocados, and not willing or able to undergo MRI scans. From June 27, 2018 to March 4, 2020, 1008 participants were randomized at 4 clinics. The cohort was 72% women, 53% Non-Hispanic White, and had a mean age of 50 years. Follow-up was completed in October 2020 when 936 participants had final MRI scans. HAT will provide information on the effects of avocado consumption on visceral fat adiposity and cardiometabolic disease risk in a diverse sample of participants., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected., Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016., Results: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups., Conclusions: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.)., (Copyright © 2021 Massachusetts Medical Society.)

Cigarillo use has increased among adolescents and young adults and has remained high. Public education efforts are needed to communicate with these populations about cigarillo use risks, but little is known about the implications of using the term "cigarillo" in such efforts. The study goal was to assess adolescent and young adult perceptions of the term "cigarillo". We conducted a nationally representative online survey of 3517 adolescents and young adults (ages 13-25). We asked participants "what is a cigarillo?" with several response options. Participants were 49.6% female, 69.8% white, 5.2% reported past 30-day cigarillo use, and 11.6% reported lifetime cigarillo use. The most common response to the question "what is a cigarillo" was "I don't know" (51% of participants), followed by "a thinner and smaller version of a traditional cigar" (30.1% of participants), which was chosen by 19.4% of adolescents and 36.8% of young adults. Among past 30-day cigarillo users, the most common response was "I don't know" (54.9%) followed by "a thinner and smaller version of a traditional cigar" (45.1%). Cigarillo users were more likely to select the "a thinner and smaller version of a traditional cigar" response than nonusers. Findings suggest that many adolescents and young adults have varied understandings of the term "cigarillo". Researchers and practitioners need to ensure that terminology used in health communication campaigns is clearly understood by the target audience to maximize effectiveness.

Rationale: Weight loss is recommended to treat obstructive sleep apnea (OSA). Objectives: To determine whether the initial benefit of intensive lifestyle intervention (ILI) for weight loss on OSA severity is maintained at 10 years. Methods: Ten-year follow-up polysomnograms of 134 of 264 adults in Sleep AHEAD (Action for Health in Diabetes) with overweight/obesity, type 2 diabetes mellitus, and OSA were randomized to ILI for weight loss or diabetes support and education (DSE). Measurements and Main Results: Change in apnea-hypopnea index (AHI) was measured. Mean ± SE weight losses of ILI participants of 10.7 ± 0.7, 7.4 ± 0.7, 5.1 ± 0.7, and 7.1 ± 0.8 kg at 1, 2, 4, and 10 years, respectively, were significantly greater than the 1-kg weight loss at 1, 2, and 4 years and 3.5 ± 0.8 kg weight loss at 10 years for the DSE group ( P values ≤ 0.0001). AHI was lower with ILI than DSE by 9.7, 8.0, and 7.9 events/h at 1, 2, and 4 years, respectively ( P values ≤ 0.0004), and 4.0 events/h at 10 years ( P  = 0.109). Change in AHI over time was related to amount of weight loss, baseline AHI, visit year ( P values < 0.0001), and intervention independent of weight change ( P  = 0.01). OSA remission at 10 years was more common with ILI (34.4%) than DSE (22.2%). Conclusions: Participants with OSA and type 2 diabetes mellitus receiving ILI for weight loss had reduced OSA severity at 10 years. No difference in OSA severity was present between ILI and DSE groups at 10 years. Improvement in OSA severity over the 10-year period with ILI was related to change in body weight, baseline AHI, and intervention independent of weight change.

Background: Results from the Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive control of systolic blood pressure significantly reduced the occurrence of mild cognitive impairment, but not probable dementia. We investigated the effects of intensive lowering of systolic blood pressure on specific cognitive functions in a preplanned substudy of participants from SPRINT., Methods: SPRINT was an open-label, multicentre, randomised controlled trial undertaken at 102 sites, including academic medical centres, Veterans Affairs medical centres, hospitals, and independent clinics, in the USA and Puerto Rico. Participants were adults aged 50 years or older with systolic blood pressure higher than 130 mm Hg, but without diabetes, history of stroke, or dementia. Participants were randomly assigned (1:1) to a systolic blood pressure goal of less than 120 mm Hg (intensive treatment) versus less than 140 mm Hg (standard treatment). All major classes of antihypertensive agents were included. A subgroup of randomly assigned participants including, but not limited to, participants enrolled in an MRI substudy was then selected for a concurrent substudy of cognitive function (target 2800 participants). Each individual was assessed with a screening cognitive test battery and an extended cognitive test battery at baseline and biennially during the planned 4-year follow-up. The primary outcomes for this substudy were standardised composite scores for memory (Logical Memory I and II, Modified Rey-Osterrieth Complex Figure [immediate recall], and Hopkins Verbal Learning Test-Revised [delayed recall]) and processing speed (Trail Making Test and Digit Symbol Coding). SPRINT was registered with ClinicalTrials.gov, NCT01206062., Findings: From Nov 23, 2010, to Dec 28, 2012, 2921 participants (mean age 68·4 years [SD 8·6], 1080 [37%] women) who had been randomly assigned in SPRINT were enrolled in the substudy (1448 received intensive treatment and 1473 received standard treatment). SPRINT was terminated early due to benefit observed in the primary outcome (composite of cardiovascular events). After a median follow-up of 4·1 years (IQR 3·7-5·8), there was no between-group difference in memory, with an annual decline in mean standardised domain score of -0·005 (95% CI -0·010 to 0·001) in the intensive treatment group and -0·001 (-0·006 to 0·005) in the standard treatment group (between-group difference -0·004, 95% CI -0·012 to 0·004; p=0·33). Mean standardised processing speed domain scores declined more in the intensive treatment group (between-group difference -0·010, 95% CI -0·017 to -0·002; p=0·02), with an annual decline of -0·025 (-0·030 to -0·019) for the intensive treatment group and -0·015 (-0·021 to 0·009) for the standard treatment group., Interpretation: Intensive treatment to lower systolic blood pressure did not result in a clinically relevant difference compared with standard treatment in memory or processing speed in a subgroup of participants from SPRINT. The effect of blood pressure lowering might not be evident in specific domains of cognitive function, but instead distributed across multiple domains., Funding: National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Aging, National Institute of Neurological Disorders and Stroke, and the Alzheimer's Association., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Few cross-sectional studies report iron deficiency (ID) prevalence in women of different race/ethnicity and ages in US or Canada., Materials and Methods: We evaluated screening observations on women who participated between 2001-2003 in a cross-sectional, primary care-based sample of adults ages ≥25 y whose observations were complete: race/ethnicity; age; transferrin saturation; serum ferritin; and HFE p.C282Y and p.H63D alleles. We defined ID using a stringent criterion: combined transferrin saturation <10% and serum ferritin <33.7 pmol/L (<15 μg/L). We compared ID prevalence in women of different race/ethnicity subgrouped by age and determined associations of p.C282Y and p.H63D to ID overall, and to ID in women ages 25-44 y with or without self-reported pregnancy., Results: These 62,685 women included 27,079 whites, 17,272 blacks, 8,566 Hispanics, 7,615 Asians, 449 Pacific Islanders, 441 Native Americans, and 1,263 participants of other race/ethnicity. Proportions of women with ID were higher in Hispanics and blacks than whites and Asians. Prevalence of ID was significantly greater in women ages 25-54 y of all race/ethnicity groups than women ages ≥55 y of corresponding race/ethnicity. In women ages ≥55 y, ID prevalence did not differ significantly across race/ethnicity. p.C282Y and p.H63D prevalence did not differ significantly in women with or without ID, regardless of race/ethnicity, age subgroup, or pregnancy., Conclusions: ID prevalence was greater in Hispanic and black than white and Asian women ages 25-54 y. p.C282Y and p.H63D prevalence did not differ significantly in women with or without ID, regardless of race/ethnicity, age subgroup, or pregnancy., Competing Interests: The authors have declared that no competing interests exist.

Objectives: To evaluate the effect of intensive systolic blood pressure (SBP) control in older adults with hypertension, considering cognitive and physical function., Design: Secondary analysis., Setting: Systolic Blood Pressure Intervention Trial (SPRINT) PARTICIPANTS: Adults 80 years or older., Intervention: Participants with hypertension but without diabetes (N = 1167) were randomized to an SBP target below 120 mm Hg (intensive treatment) vs a target below 140 mm Hg (standard treatment)., Measurements: We measured the incidence of cardiovascular disease (CVD), mortality, changes in renal function, mild cognitive impairment (MCI), probable dementia, and serious adverse events. Gait speed was assessed via a 4-m walk test, and the Montreal Cognitive Assessment (MoCA) was used to quantify baseline cognitive function., Results: Intensive treatment led to significant reductions in cardiovascular events (hazard ratio [HR] = .66; 95% confidence interval [CI] = .49-.90), mortality (HR = .67; 95% CI = .48-.93), and MCI (HR = .70; 95% CI = .51-.96). There was a significant interaction (P < .001) whereby participants with higher baseline scores on the MoCA derived strong benefit from intensive treatment for a composite of CVD and mortality (HR = .40; 95% CI = .28-.57), with no appreciable benefit in participants with lower scores on the MoCA (HR = 1.33 = 95% CI = .87-2.03). There was no evidence of heterogeneity of treatment effects with respect to gait speed. Rates of acute kidney injury and declines of at least 30% in estimated glomerular filtration rate were increased in the intensive treatment group with no between-group differences in the rate of injurious falls., Conclusion: In adults aged 80 years or older, intensive SBP control lowers the risk of major cardiovascular events, MCI, and death, with increased risk of changes to kidney function. The cardiovascular and mortality benefits of intensive SBP control may not extend to older adults with lower baseline cognitive function., Trial Registration: Clinicaltrials.gov identifier: NCT01206062. J Am Geriatr Soc 68:496-504, 2020., (© 2019 The American Geriatrics Society.)

Objective: To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02])., Methods: This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes., Results: Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group., Conclusions: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design., (© 2020 The Obesity Society.)

Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene ( APOL1 ). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)-sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes., Methods: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys., Results: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses., Conclusion: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation., (© 2019 International Society of Nephrology. Published by Elsevier Inc.)

Importance: The effect of intensive blood pressure lowering on brain health remains uncertain., Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes., Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016., Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315)., Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome., Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1])., Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small., Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Little is known about differences between adolescents' and adults' exposure to e-cigarette advertising in various media channels, such as retail establishments, print, television, radio, and digital marketing. We examined the exposure to e-cigarette advertising in these channels amongst adolescents (13-17), young adults (18-25), and older adults (26+). Adolescents ( N = 1124), young adults ( N = 809), and adults ( N = 4186) were recruited through two nationally representative phone surveys from 2014-2015. Lifetime e-cigarette advertising exposure was prevalent (84.5%). Overall, older adult males and older adult cigarette smokers reported the highest exposure to e-cigarette advertising ( p < 0.001). Television was the largest source of exposure for all age groups. Adolescents and young adults had higher odds than older adults of exposure through television and digital marketing. However, adolescents had lower odds than young adults and older adults of exposure through retailers and print media. Although e-cigarette advertising appears to be reaching the intended audience of adult smokers, vulnerable populations are being exposed at high rates via television and digital marketing. Regulations aimed at curbing exposure through these media channels are needed, as are counter advertising and prevention campaigns.

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia., Objective: To evaluate the effect of intensive blood pressure control on risk of dementia., Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018., Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683)., Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia., Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97)., Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point., Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Objective To review the literature systematically and perform meta-analyses to address these questions: 1) Is there evidence that self-measured blood pressure (BP) without other augmentation is superior to office-based measurement of BP for achieving better BP control or for preventing adverse clinical outcomes that are related to elevated BP? 2) What is the optimal target for BP lowering during antihypertensive therapy in adults? 3) In adults with hypertension, how do various antihypertensive drug classes differ in their benefits and harms compared with each other as first-line therapy? Methods Electronic literature searches were performed by Doctor Evidence, a global medical evidence software and services company, across PubMed and EMBASE from 1966 to 2015 using key words and relevant subject headings for randomized controlled trials that met eligibility criteria defined for each question. We performed analyses using traditional frequentist statistical and Bayesian approaches, including random-effects Bayesian network meta-analyses. Results Our results suggest that: 1) There is a modest but significant improvement in systolic BP in randomized controlled trials of self-measured BP versus usual care at 6 but not 12 months, and for selected patients and their providers self-measured BP may be a helpful adjunct to routine office care. 2) systolic BP lowering to a target of <130 mm Hg may reduce the risk of several important outcomes including risk of myocardial infarction, stroke, heart failure, and major cardiovascular events. No class of medications (ie, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers, or beta blockers) was significantly better than thiazides and thiazide-like diuretics as a first-line therapy for any outcome.

Recent publications have stated that the blood pressure (BP) measurement technique used in SPRINT (Systolic Blood Pressure Intervention Trial) was unattended. However, the SPRINT protocol does not address the issue of attendance. A survey was conducted immediately after SPRINT closeout visits were completed to inquire whether BP measurements were usually attended or unattended by staff. There were 4082 participants at 38 sites that measured BP after leaving the participant alone the entire time (always alone), 2247 at 25 sites that had personnel in the room the entire time (never alone), 1746 at 19 sites that left the participant alone only during the rest period (alone for rest), and 570 at 6 sites that left the participant alone only during the BP readings (alone for BP measurement). Similar systolic and diastolic BPs within randomized groups were noted during follow-up at the majority of visits in all 4 measurement categories. In the always alone and never alone categories, the intensive group had a similarly reduced risk for the primary outcome compared with the standard group (hazard ratio, 0.62; 95% confidence interval, 0.51-0.76 and hazard ratio, 0.64; 95% confidence interval, 0.46-0.91, respectively; pairwise interaction P value, 0.88); risk was not significantly reduced for the intensive group in the smaller alone-for-rest and the alone-for-BP-measurement categories. Similar BP levels and cardiovascular disease risk reduction were observed in the intensive group in SPRINT participants whether the measurement technique used was primarily attended or unattended., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062., (© 2018 American Heart Association, Inc.)

Background: Treating to a lower blood pressure (BP) may increase acute kidney injury (AKI) events., Study Design: Data for AKI resulting in or during hospitalization or emergency department visits were collected as part of the serious adverse events reporting process of the Systolic Blood Pressure Intervention Trial (SPRINT)., Setting & Participants: 9,361 participants 50 years or older with 1 or more risk factors for cardiovascular disease., Interventions: Participants were randomly assigned to a systolic BP target of <120 (intensive arm) or <140mmHg (standard arm)., Outcomes & Measurements: Primary outcome was the number of adjudicated AKI events. Secondary outcomes included severity of AKI and degree of recovery of kidney function after an AKI event. Baseline creatinine concentration was defined as the most recent SPRINT outpatient creatinine value before the date of the AKI event., Results: There were 179 participants with AKI events in the intensive arm and 109 in the standard arm (3.8% vs 2.3%; HR, 1.64; 95% CI, 1.30-2.10; P<0.001). Of 288 participants with an AKI event, 248 (86.1%) had a single AKI event during the trial. Based on modified KDIGO (Kidney Disease: Improving Global Outcomes) criteria for severity of AKI, the number of AKI events in the intensive versus standard arm by KDIGO stage was 128 (58.5%) versus 81 (62.8%) for AKI stage 1, 42 (19.2%) versus 18 (14.0%) for AKI stage 2, and 42 (19.2%) versus 25 (19.4%) for AKI stage 3 (P=0.5). For participants with sufficient data, complete or partial resolution of AKI was seen for 169 (90.4%) and 9 (4.8%) of 187 AKI events in the intensive arm and 86 (86.9%) and 4 (4.0%) of 99 AKI events in the standard arm, respectively., Limitations: Trial results are not generalizable to patients with diabetes mellitus or without risk factors for cardiovascular disease., Conclusions: More intensive BP lowering resulted in more frequent episodes of AKI. Most cases were mild and most participants had complete recovery of kidney function., Trial Registration: Registered at ClinicalTrials.gov with study number NCT01206062., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

The aim of this study was to determine if an intensive lifestyle intervention (ILI) reduces the severity of obstructive sleep apnea (OSA) in rapid-eye movement (REM) sleep, and to determine if longitudinal changes in glycaemic control are related to changes in OSA severity during REM sleep over a 4-year follow-up. This was a randomized controlled trial including 264 overweight/obese adults with type 2 diabetes (T2D) and OSA. Participants were randomized to an ILI targeted to weight loss or a diabetes support and education (DSE) control group. Measures included anthropometry, apnea-hypopnea index (AHI) during REM sleep (REM-AHI) and non-REM sleep (NREM-AHI) and glycated haemoglobin (HbA1c) at baseline and year 1, year 2 and year 4 follow-ups. Mean baseline values of REM-AHI were significantly higher than NREM-AHI in both groups. Both REM-AHI and NREM-AHI were reduced significantly more in ILI versus DSE, but these differences were attenuated slightly after adjustment for weight changes. Repeated-measure mixed-model analyses including data to year 4 demonstrated that changes in HbA1c were related significantly to changes in weight, but not to changes in REM-AHI and NREM-AHI. Compared to control, the ILI reduced REM-AHI and NREM-AHI during the 4-year follow-up. Weight, as opposed to REM-AHI and NREM-AHI, was related to changes in HbA1c. The findings imply that weight loss from a lifestyle intervention is more important than reductions in AHI for improving glycaemic control in T2D patients with OSA., (© 2017 European Sleep Research Society.)

Studies of visit-to-visit office blood pressure (BP) variability (OBPV) as a predictor of cardiovascular events and death in high-risk patients treated to lower BP targets are lacking. We conducted a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a well-characterized cohort of participants randomized to intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP targets. We defined OBPV as the coefficient of variation of the systolic BP using measurements taken during the 3-,6-, 9-, and 12-month study visits. In our cohort of 7879 participants, older age, female sex, black race, current smoking, chronic kidney disease, and coronary disease were independent determinants of higher OBPV. Use of thiazide-type diuretics or dihydropyridine calcium channel blockers was associated with lower OBPV whereas angiotensin-converting enzyme inhibitors or angiotensin receptor blocker use was associated with higher OBPV. There was no difference in OBPV in participants randomized to standard or intensive treatment groups. We found that OBPV had no significant associations with the composite end point of fatal and nonfatal cardiovascular events (n=324 primary end points; adjusted hazard ratio, 1.20; 95% confidence interval, 0.85-1.69, highest versus lowest quintile) nor with heart failure or stroke. The highest quintile of OBPV (versus lowest) was associated with all-cause mortality (adjusted hazard ratio, 1.92; confidence interval, 1.22-3.03) although the association of OBPV overall with all-cause mortality was marginal ( P =0.07). Our results suggest that clinicians should continue to focus on office BP control rather than on OBPV unless definitive benefits of reducing OBPV are shown in prospective trials., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062., (© 2017 American Heart Association, Inc.)

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n =1330) or <140 mm Hg (standard group; n =1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD ( P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (-0.47 versus -0.32 ml/min per 1.73 m 2 per year; P <0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome., (Copyright © 2017 by the American Society of Nephrology.)

Objective: To determine whether the effects of intensive (<120 mmHg) compared with standard (<140 mmHg) systolic blood pressure (SBP) treatment are different among those with prediabetes versus those with fasting normoglycemia at baseline in the Systolic Blood Pressure Intervention Trial (SPRINT)., Research Design and Methods: This was a post hoc analysis of SPRINT. SPRINT participants were categorized by prediabetes status, defined as baseline fasting serum glucose ≥100 mg/dL versus those with normoglycemia (fasting serum glucose <100 mg/dL). The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment among those with prediabetes and normoglycemia., Results: Among 9,361 participants randomized (age 67.9 ± 9.4 years; 35.5% female), 3,898 and 5,425 had baseline prediabetes and normoglycemia, respectively. After a median follow-up of 3.26 years, the hazard ratio for the primary outcome was 0.69 (95% CI 0.53, 0.89) and 0.83 (95% CI 0.66, 1.03) among those with prediabetes and normoglycemia, respectively ( P value for interaction 0.30). For all-cause mortality, the hazard ratio with intensive SBP treatment was 0.77 (95% CI 0.55, 1.06) for prediabetes and 0.71 (95% CI 0.54, 0.94) for normoglycemia ( P value for interaction 0.74). Effects of intensive versus standard SBP treatment on prespecified renal outcomes and serious adverse events were similar for prediabetes and normoglycemia (all interaction P > 0.05)., Conclusions: In SPRINT, the beneficial effects of intensive SBP treatment were similar among those with prediabetes and fasting normoglycemia., (© 2017 by the American Diabetes Association.)