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Orthostatic hypotension (OH) based on a change from seated-to-standing blood pressure (BP) is often used interchangeably with supine-to-standing BP.The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a randomized trial of vitamin D3 supplementation and fall in adults aged ≥70 years at high risk of falls. OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mmHg, measured at pre-randomization, 3-, 12-, and 24-month visits with each of 2 protocols: seated-to-standing and supine-to-standing. Participants were asked about orthostatic symptoms, and falls were ascertained via daily fall calendar, ad hoc reporting, and scheduled interviews.Among 534 participants with 993 paired supine and seated assessments (mean age 76 ± 5 years, 42% women, 18% Black), mean baseline BP was 130 ± 19/68 ± 11 mmHg; 62% had a history of high BP or hypertension. Mean BP increased 3.5 (SE, 0.4)/2.6 (SE, 0.2) mmHg from sitting to standing, but decreased with supine to standing (mean change: -3.7 [SE, 0.5]/-0.8 [SE, 0.3] mmHg; P-value 0.001). OH was detected in 2.1% (SE, 0.5) of seated versus 15.0% (SE, 1.4) of supine assessments (P 0.001). While supine and seated OH were not associated with falls (HR: 1.55 [0.95, 2.52] vs 0.69 [0.30, 1.58]), supine systolic OH was associated with higher fall risk (HR: 1.77 [1.02, 3.05]). Supine OH was associated with self-reported fainting, blacking out, seeing spots and room spinning in the prior month (P-values 0.03), while sitting OH was not associated with any symptoms (P-values ≥ 0.40).Supine OH was more frequent, associated with orthostatic symptoms, and potentially more predictive of falls than seated OH.

Given the concern that beta-blocker use may be associated with an increased risk for heart failure (HF) in populations with normal left ventricular systolic function, we evaluated the association between beta-blocker use and incident HF events, as well as loop diuretic initiation in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT demonstrated that a blood pressure target of120 mm Hg reduced cardiovascular outcomes compared with140 mm Hg in adults with at least one cardiovascular risk factor and without HF. The lower rate of the composite primary outcome in the 120 mm Hg group was primarily driven by a reduction in HF events. Subjects on a beta blocker for the entire trial duration were compared with subjects who never received a beta blocker after 1:1 propensity score matching. A competing risk survival analysis by beta-blocker status was performed to estimate the effect of the drug on incident HF and was then repeated for a secondary end point of cardiovascular disease death. Among the 3,284 propensity score-matched subjects, beta-blocker exposure was associated with an increased HF risk (hazard ratio 5.86; 95% confidence interval 2.73 to 13.04; p0.001). A sensitivity analysis of propensity score-matched cohorts with a history of coronary artery disease or atrial fibrillation revealed the same association (hazard ratio 3.49; 95% confidence interval 1.15 to 10.06; p = 0.028). In conclusion, beta-blocker exposure in this secondary analysis was associated with increased incident HF in subjects with hypertension without HF at baseline.

Guidelines recommend 1 to 2 minutes between repeated, automated office-based blood pressure (AOBP) measures, which is a barrier to broader adoption. Patients from a single hypertension center underwent a 3-day evaluation that included a 24-hour ambulatory blood pressure (BP) monitor (ABPM) and one of two nonrandomized, unattended AOBP protocols. Half of the patients underwent 3 AOBP measurements separated by 30 seconds, and the other half underwent 3 BP measurements separated by 60 seconds. All measurements were compared with the average awake-time BP from ABPM and the first AOBP measurement. We used linear regression to assess whether the 30-second protocol was associated with individual or average AOBP measurements or awake-time ABPM and used an interaction term to determine whether interval modified the relationship between AOBP measurements (individual and mean) with awake-time ABPM. Among 102 patients (mean age, 59.2±16.2 years; 64% women; 24% Black), the average awake-time BP was 132.5±15.6/77.7±12.2 mm Hg among those who underwent the 60-second protocol and 128.6±13.6/76.5±12.5 mm Hg for the 30-second protocol. Mean systolic/diastolic BP was lower with the second and third AOBP measurement by −0.5/−1.7 mm Hg and −1.0/−2.3 mm Hg for the 60-second protocol versus −0.8/−2.0 mm Hg and −0.7/−2.7 mm Hg for the 30-second protocol; protocol did not significantly modify these differences. Differences between AOBP measurements (first, second, or third) and awake-time ABPM were nearly identical across protocols. In conclusion, a 30-second interval between AOBP measurements was as accurate and reliable as a 60-second interval. These findings support shorter time intervals between BP measurements, which would make AOBP more feasible in clinical practice.

Background The Dietary Approaches to Stop Hypertension (DASH) diet, a high-carbohydrate diet, is highly recommended based on its cardiovascular risk benefits, yet adherence remains persistently low. How subjective impressions of this diet contribute to adherence has not been thoroughly explored. The OmniCarb trial, which compared DASH-style diets varying in glycemic index (GI) and carbohydrate amount, surveyed subjective impressions of such diets. Objectives We examined the effects of GI and carbohydrate amount on qualitative aspects of diet acceptability through secondary outcomes in the OmniCarb trial. Methods OmniCarb was a randomized, crossover trial of 4 DASH-style diets varying by GI (≥65 compared with ≤45) and carbohydrate amount (40% compared with 58% kcal) in overweight or obese (BMI ≥25 kg/m2) adults (n = 163). Participants consumed each diet in random order over 5-wk periods, separated by 2-wk washouts. At baseline and the end of each feeding period, participants rated hunger, diet satisfaction, and gastrointestinal symptoms (diarrhea/loose stools, constipation, bloating, nausea, and heartburn). Results Participant mean age was 52 y, with 52% women, 51% non-Hispanic black, and 56% obese (BMI ≥30). Compared with baseline, all intervention diets decreased heartburn, increased diarrhea/loose stools, and increased bloating, but did not significantly affect constipation or nausea. Compared with lower carbohydrate diets, higher carbohydrate diets increased hunger (RR: 1.16; 95% CI: 1.04, 1.30), increased diet satisfaction (RR: 1.10; 95% CI: 1.01, 1.20), and increased heartburn (RR: 1.49; 95% CI: 1.09, 2.04). Compared with lower GI diets, higher GI diets did not affect hunger (RR: 0.92; 95% CI: 0.83, 1.02), decreased diet satisfaction (RR: 0.83; 95% CI: 0.75, 0.92), and did not affect heartburn (RR: 0.89; 95% CI: 0.70, 1.13). There were no between-diet differences for diarrhea/loose stools, constipation, bloating, and nausea. Conclusions Although a higher carbohydrate amount in DASH-style diets can increase diet satisfaction, it can also decrease satiety and increase heartburn in adults with overweight or obesity.This trial is registered at clinicaltrials.gov as NCT00608049.

Background/objectives To assess whether vitamin D supplementation prevents specific fall subtypes and sequelae (e.g., fracture). Design Secondary analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You)-a response-adaptive, randomized clinical trial. Setting Two community-based research units. Participants Six hundred and eighty-eight participants ≥70 years old with elevated fall risk and baseline serum 25-hydroxyvitamin D levels of 10-29 ng/ml. Intervention 200 IU/day (control), 1000 IU/day, 2000 IU/day, or 4000 IU/day of vitamin D3. Measurements Outcomes included repeat falls and falls that were consequential, were injurious, resulted in emergency care, resulted in fracture, and occurred either indoors or outdoors. Results After adjustment for multiple comparisons, the risk of fall-related fracture was greater in the pooled higher doses (≥1000 IU/day) group compared with the control (hazard ratio [HR] = 2.66; 95% confidence interval [CI]:1.18-6.00). Although not statistically significant after multiple comparisons adjustment, time to first outdoor fall appeared to differ between the four dose groups (unadjusted p for overall difference = 0.013; adjusted p = 0.222), with risk of a first-time outdoor fall 39% lower in the 1000 IU/day group (HR = 0.61; 95% CI: 0.38-0.97; unadjusted p = 0.036; adjusted p = 0.222) and 40% lower in the 2000 IU/day group (HR = 0.60; 95%CI 0.38-0.97; p = 0.037; adjusted p = 0.222), each versus control. Conclusion Vitamin D supplementation doses ≥1000 IU/day might have differential effects on fall risk based on fall location and fracture risk, with the most robust finding that vitamin D doses between 1000 and 4000 IU/day might increase the risk of first time falls with fractures. Replication is warranted, given the possibility of type 1 error.

Background Dietary recommendations to prevent gout emphasize a low-purine diet. Recent evidence suggests that the Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate while also improving blood pressure and lipids. Objective To compare the effects of DASH-style diets emphasizing different macronutrient proportions on serum urate reduction. Methods We conducted a secondary analysis of the Optimal Macronutrient Intake Trial to Prevent Heart Disease feeding study, a 3-period, crossover design, randomized trial of adults with prehypertension or hypertension. Participants were provided with 3 DASH-style diets in random order, each for 6 wk. Each DASH-style diet emphasized different macronutrient proportions: a carbohydrate-rich (CARB) diet, a protein-rich (PROT) diet, and an unsaturated fat-rich (UNSAT) diet. In the PROT diet, approximately half of the protein came from plant sources. We compared the effects of these diets on serum urate at weeks 4 and 6 of each feeding period. Results Of the 163 individuals included in the final analysis, the mean serum urate at baseline was 5.1 mg/dL. Only the PROT diet reduced serum urate from baseline at the end of the 6-wk feeding period (-0.16 mg/dL; 95% CI: -0.28, -0.04; P = 0.007). Neither the CARB diet (-0.03 mg/dL; 95% CI: -0.14, 0.09; P = 0.66) nor the UNSAT diet (-0.01 mg/dL; 95% CI: -0.12, 0.09; P = 0.78) reduced serum urate from baseline. The PROT diet lowered serum urate by 0.12 mg/dL (95% CI: -0.20, -0.03; P = 0.006) compared with CARB and by 0.12 mg/dL (95% CI: -0.20, -0.05; P = 0.002) compared with UNSAT. Conclusions A DASH-style diet emphasizing plant-based protein lowered serum urate compared with those emphasizing carbohydrates or unsaturated fat. Future trials should test the ability of a DASH-style diet emphasizing plant-based protein to lower serum urate and prevent gout flares in patients with gout. This trial was registered at clinicaltrials.gov as NCT00051350.

Background Clinic blood pressure (BP) when measured in the seated position, can miss meaningful BP phenotypes, including low ambulatory BP (white coat effects [WCE]) or high supine BP (nocturnal non-dipping). Orthostatic hypotension (OH) measured using both seated (or supine) and standing BP, could identify phenotypes poorly captured by seated clinic BP alone. Methods We examined the association of OH with WCE and night-to-daytime systolic BP (SBP) in a subpopulation of SPRINT, a randomized trial testing the effects of intensive or standard (1. Results Of 897 adults (mean age 71.5±9.5 years, 29% female, 28% black), 128 had OH at least once. Among those with OH, 15% had WCE (vs. 7% without OH). Moreover, 25% of those with OH demonstrated a non-dipping pattern (vs. 14% without OH). OH was positively associated with both WCE (OR=2.24; 95%CI: 1.28, 4.27) and reverse dipping (OR=2.29; 95% CI: 1.31, 3.99). Conclusions The identification of OH in clinic was associated with two BP phenotypes often missed with traditional seated BP assessments. Further studies on mechanisms of these relationships are needed. Clinical trials registration Trial Number NCT03569020.

OBJECTIVE To determine whether the Dietary Approaches to Stop Hypertension (DASH) diet or an alternative, simplified diet, emphasizing high-fiber fruits and vegetables (the FV diet), lowers serum urate levels. METHODS We conducted a secondary study of the DASH feeding study, a 3-arm, parallel-design, randomized trial of 459 adults with systolic blood pressure (BP) of

Background Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences. Objective To compare the effects of 4 doses of vitamin D3 supplements on falls. Design 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333). Setting 2 community-based research units. Participants 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L. Intervention 200 (control), 1000, 2000, or 4000 IU of vitamin D3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose. Measurements Time to first fall or death over 2 years (primary outcome). Results During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n = 308) and those randomly assigned to receive 200 IU/d (n = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46]). Limitations The control group received 200 IU of vitamin D3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached. Conclusion In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D3 doses of 1000 IU/d or higher. Primary funding source National Institute on Aging.

The mechanisms underlying the association between orthostatic hypotension (OH) and cardiovascular disease are unclear. We investigated whether OH is associated with circulating cardiovascular risk markers. This was a cross-sectional analysis of 3857 older, community-dwelling men. “Consensus OH” was defined as a sitting-tostanding decrease in systolic blood pressure ≥20 mm Hg and/or diastolic blood pressure ≥10 mm Hg that occurred within three minutes of standing. Multiple generalized linear regression and logistic models were used to examine the association between cardiovascular risk markers and OH. Consensus OH was present in 20.2%, consisting of isolated systolic OH in 12.6%, isolated diastolic OH in 4.6%, and combined systolic and diastolic OH in 3.0%. Concentration of von Willebrand factor, a marker of endothelial dysfunction, was positively associated with isolated systolic OH (OR 1.35, 95% CI 1.05-1.73) and combined systolic and diastolic OH (OR 2.27, 95% CI 1.35-3.83); high circulating phosphate concentration, which may reflect vascular calcification, was associated with isolated diastolic OH (OR 1.53, 95% CI 1.04-2.25) and combined systolic and diastolic OH (OR 2.12, 95% CI 1.31-3.44), high-sensitivity troponin T, a marker of myocardial injury, was positively associated with isolated diastolic OH (OR 1.69, 95% CI 1.07-2.65) and N-terminal pro-brain natriuretic peptide, a marker of cardiac stress, was positively associated with combined systolic and diastolic OH (OR 2.14, 95% CI 1.14-4.03). In conclusion, OH is associated with some cardiovascular risk markers implicated in endothelial dysfunction, vascular calcification, myocardial injury, and cardiac stress. Clinicians should consider assessing cardiovascular risk in patients with OH.

ObjectiveTo test the hypothesis that orthostatic hypotension (OH) might cause cerebral hypoperfusion and injury, we examined the longitudinal relationship between OH or orthostatic symptoms and incident neurologic outcomes in a community population of older adults.MethodsCardiovascular Health Study participants (≥65 years) without dementia or stroke had blood pressure (BP) measured after lying down for 20 minutes and after standing 3 for minutes. Participants reported dizziness immediately upon standing and any dizziness in the past 2 weeks. OH was defined as a drop in standing systolic/diastolic BP ≥20/≥10 mm Hg. We determined the association between OH or dizziness with (1) MRI brain findings (ventricular size, white matter hyperintensities, brain infarcts) using linear or logistic regression, (2) cognitive function (baseline and over time) using generalized estimating equations, and (3) prospective adjudicated events (dementia, stroke, death) using Cox models. Models were adjusted for demographic characteristics and OH risk factors. We used multiple imputation to account for missing OH or dizziness (n = 534).ResultsPrior to imputation, there were 5,007 participants (mean age 72.7 ± 5.5 years, 57.6% women, 10.9% Black, 16% with OH). OH was modestly associated with death (hazard ratio [HR] 1.11; 95% confidence interval 1.02–1.20), but not MRI findings, cognition, dementia, or stroke. In contrast, dizziness upon standing was associated with lower baseline cognition (β = −1.20; −1.94 to −0.47), incident dementia (HR 1.32; 1.04–1.62), incident stroke (HR 1.22; 1.06–1.41), and death (HR 1.13; 1.06–1.21). Similarly, dizziness over the past 2 weeks was associated with higher white matter grade (β = 0.16; 0.03–0.30), brain infarcts (OR 1.31; 1.06–1.63), lower baseline cognition (β = −1.18; −2.01 to −0.34), and death (HR 1.13; 1.04–1.22).ConclusionsDizziness was more consistently associated with neurologic outcomes than OH 3 minutes after standing. Delayed OH assessments may miss pathologic information related to cerebral injury.

BACKGROUND In the United States, current guidelines recommend a total sodium intake METHODS In the National Health and Nutrition Examination Survey (NHANES), we estimated the prevalence of adherence to sodium intake recommendations ( RESULTS In 2005–2006, 23.1% (95% confidence interval [CI]: 21.5, 24.9) of the US population consumed CONCLUSIONS Adherence estimated by sodium density is substantially less than adherence estimated by total sodium intake, especially among persons with lower kilocalorie intake. Further efforts to achieve population-wide reduction in sodium density intake are urgently needed.

OBJECTIVE Hypoglycemia has been postulated to contribute to falls risk in older adults with type 2 diabetes. However, few studies have prospectively examined the association between severe hypoglycemia and falls, both important causes of morbidity and mortality. RESEARCH DESIGN AND METHODS We conducted a prospective cohort analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study with diagnosed diabetes at visit 4 (1996–1998). Episodes of severe hypoglycemia requiring medical treatment were identified using ICD-9 codes from hospitalizations, emergency department visits, and ambulance calls; total falls were identified from medical claims using E-codes from 1996 to 2013. Secondary analyses examined hospitalized falls and falls with fracture. We calculated incidence rates and used Cox regression models to evaluate the independent association of severe hypoglycemia with falls occurring after visit 4 through 2013. RESULTS Among 1,162 participants with diabetes, 149 ever had a severe hypoglycemic event before baseline or during the median of 13.1 years of follow-up. The crude incidence rate of falls among persons without severe hypoglycemia was 2.17 per 100 person-years (PY) (95% CI 1.93–2.44) compared with 8.81 per 100 PY (6.73–11.53) with severe hypoglycemia. After adjustment, severe hypoglycemia was associated with a more than twofold higher risk of falls (hazard ratio 2.23, 95% CI 1.61–3.07). Associations were consistent in subgroups defined by age, sex, race, BMI, duration of diabetes, or functional difficulty. CONCLUSIONS Severe hypoglycemia was associated with a substantially higher risk of falls in this community-based population of adults with diabetes. Fall risk should be considered when individualizing glycemic treatment in older adults. Assessing hypoglycemia history and future hypoglycemia risk could also improve multifactorial fall prevention interventions for older adults with diabetes.

BACKGROUND: The Dietary Approaches to Stop Hypertension (DASH) diet lowered blood pressure (BP) and low-density lipoprotein cholesterol. OBJECTIVE: To compare effects of diets rich in fruits and vegetables with a typical American diet on cardiovascular injury in middle-aged adults without known preexisting cardiovascular disease. DESIGN: Observational study based on a three-arm, parallel-design, randomized trial conducted in the U.S. from 1994 to 1996. (ClinicalTrials.gov:NCT00000544) SETTING: Three of the four original clinical trial centers. PARTICIPANTS: 326 of the original 459 trial participants with available stored specimens. INTERVENTIONS: Participants were randomized to 8 weeks of monitored feeding with: a control diet typical of what many Americans eat, a diet rich in fruit and vegetables but otherwise similar to control, or the DASH diet which was rich in fruit, vegetables, low-fat dairy, and fiber, and reduced in saturated fat and cholesterol. Weight was kept constant throughout feeding. MEASUREMENTS: Biomarkers collected at baseline and 8-weeks: high-sensitivity cardiac troponin I (hs-cTnI), N-terminal b-type pro natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP). RESULTS: The mean age of participants was 45.2 years, 48% were women, 49% were black, and mean baseline BP was 131/85 mmHg. Compared to control, the fruits and vegetables diet reduced hs-cTnI by 0.5 ng/L (95% CI: −0.9 to −0.2) and NT-proBNP by 0.3 pg/mL (95% CI: −0.5 to −0.1). Compared to control, DASH reduced hs-cTnI by 0.5 ng/L (95% CI: −0.9 to −0.1) and NT-proBNP by 0.3 pg/mL (95% CI: −0.5 to −0.04). Hs-CRP did not differ between diets. None of the markers differed between the fruits and vegetables and DASH diets. LIMITATIONS: Short duration, missing specimens, inability to isolate effects of specific foods or micronutrients. CONCLUSION: Diets rich in fruits and vegetables given over an 8-week period were associated with lower markers of subclinical cardiac damage and strain in adults without preexisting cardiovascular disease.

BACKGROUND: Short-term randomized trials suggest that a 500 mg/d vitamin C supplement reduces serum urate, whereas observational studies show vitamin E is inversely associated with gout risk. OBJECTIVES: We evaluated the effect of supplemental vitamin C (prespecified primary exposure) and vitamin E (prespecified secondary exposure) on new diagnoses of gout. METHODS: We performed a post hoc analysis of data from the Physicians’ Health Study II, a randomized, double-blind, placebo-controlled factorial trial of randomized vitamin C (500 mg/d) and vitamin E (400 IU every other day). The primary outcome was new gout diagnoses, self-reported at baseline and throughout the follow-up period of ≤10 y. RESULTS: Of 14,641 randomly assigned male physicians in our analysis, the mean age was 64 ± 9 y; 1% were Black, and 6.5% had gout prior to randomization. The incidence rate of new gout diagnoses during follow-up was 8.0 per 1000 person-years among those assigned vitamin C compared with 9.1 per 1000 person-years among those assigned placebo. The vitamin C assignment reduced new gout diagnoses by 12% (HR: 0.88; 95% CI: 0.77, 0.99; P = 0.04). These effects were greatest among those with a BMI

OBJECTIVE: Observational data suggest a potential for subclinical cardiac damage from intensive blood glucose or blood pressure (BP) control, particularly in adults with very low blood glucose and BP levels. However, this has not been tested in a randomized trial. METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Research Controlled Evaluation (ADVANCE) study was a factorial, randomized trial designed to test the effects of intensive blood glucose (hemoglobin A1c ≤6.5% versus usual care) and intensive BP (combination of perindopril-indapamide versus placebo) control on vascular events in adults with diabetes. Using mixed effects tobit models, we determined the effect of the randomized interventions on change in subclinical cardiac injury (high sensitivity cardiac troponin T [hs-cTnT]) and strain (N-terminal b-type pro natriuretic peptide [NT-proBNP]), 1 year after randomization. RESULTS: Among the 682 participants, mean age was 66.1 (SD, 6.5) years; 40% were women. Mean baseline hemoglobin A1c was 7.4% (SD, 1.5) and systolic/diastolic BP was 147 (SD,21)/81 (SD,11) mmHg. After 1 year, intensive versus standard glucose control did not significantly change hs-cTnT (1.5%; 95%CI:−4.9,8.2) or NT-proBNP (−10.3%; 95%CI: −20.2%,0.9%). Intensive versus standard BP control also did not affect hs-cTnT (−2.9%; 95%CI: −8.9,3.6), but did significantly lower NT-proBNP by 21.6% (95%CI: −30.2%,−11.9%). Changes in systolic BP at 1 year (versus baseline) were strongly associated with NT-proBNP (P = 0.004), but not hs-cTnT (P = 0.95). CONCLUSIONS: In adults with diabetes, intensive BP control reduced NT-proBNP without increasing hs-cTnT, supporting the benefits and safety of intensive BP control in adults with diabetes. This trial is registered at clinicaltrials.gov, number: NCT00145925.

Background Low serum 25-hydroxyvitamin D [25(OH)D] level is associated with a greater risk of frailty, but the effects of daily vitamin D supplementation on frailty are uncertain. This secondary analysis aimed to examine the effects of vitamin D supplementation on frailty using data from the Study To Understand Fall Reduction and Vitamin D in You (STURDY). Methods The STURDY trial, a two-stage Bayesian, response-adaptive, randomized controlled trial, enrolled 688 community-dwelling adults aged ≥ 70 years with a low serum 25(OH)D level (10–29 ng/mL) and elevated fall risk. Participants were initially randomized to 200 IU/d (control dose; n = 339) or a higher dose (1000 IU/d, 2000 IU/d, or 4000 IU/d; n = 349) of vitamin D3. Once the 1000 IU/d was selected as the best higher dose, other higher dose groups were reassigned to the 1000 IU/d group and new enrollees were randomized 1:1 to 1000 IU/d or control group. Data were collected at baseline, 3, 12, and 24 months. Frailty phenotype was based on number of the following conditions: unintentional weight loss, exhaustion, slowness, low activity, and weakness (≥ 3 conditions as frail, 1 or 2 as pre-frail, and 0 as robust). Cox proportional hazard models estimated the risk of developing frailty, or improving or worsening frailty status at follow-up. All models were adjusted for demographics, health conditions, and further stratified by baseline serum 25(OH)D level (insufficiency (20–29 ng/mL) vs. deficiency (10–19 ng/mL)). Results Among 687 participants (mean age 77.1 ± 5.4, 44% women) with frailty assessment at baseline, 208 (30%) were robust, 402 (59%) were pre-frail, and 77 (11%) were frail. Overall, there was no significant difference in risk of frailty outcomes comparing the pooled higher doses (PHD; ≥ 1000 IU/d) vs. 200 IU/d. When comparing each higher dose vs. 200 IU/d, the 2000 IU/d group had nearly double the risk of worsening frailty status (HR = 1.89, 95% CI: 1.13–3.16), while the 4000 IU/d group had a lower risk of developing frailty (HR = 0.22, 95% CI: 0.05–0.97). There were no significant associations between vitamin D doses and frailty status in the analyses stratified by baseline serum 25(OH)D level. Conclusions High dose vitamin D supplementation did not prevent frailty. Significant subgroup findings might be the results of type 1 error. Trial registration ClinicalTrials.gov: NCT02166333.

This cross-sectional study characterizes the prevalent use of medications that may raise BP and examine their associations with BP control and antihypertensive use.

Background/aim:Cost-efficient methods are essential for successful participant recruitment in clinical trials. Patient portal messages are an emerging means of recruiting potentially eligible patients into trials. We assessed the response rate and complaint rate from direct-to-patient, targeted recruitment through patient portals of an electronic medical record for a clinical trial, and compared response rates by differences in message content.Methods:The Study to Understand Fall Reduction and Vitamin D in You (STURDY) trial is a National Institutes of Health–sponsored, community-based study of vitamin D supplementation for fall prevention in older adults conducted at Johns Hopkins. Potential participants were identified using the Epic electronic medical record at the Johns Hopkins Health System based on age (≥70 years), ZIP code (30-mile radius of study site), and prior activation of a patient portal account. We prepared a shorter message and a longer message. Both had basic information about study participation, but the longer message also contained information about the significance of the study and a personal invitation from the STURDY principal investigator. The Hopkins Institutional Review Board did not require prior consent from the patient or their providers. We calculated the response rate and tracked the number of complaints and requests for removal from future messages. We also determined response rate according to message content.Results:Of the 5.5 million individuals receiving care at the Johns Hopkins Health System, a sample of 6896 met our inclusion criteria and were sent one patient portal recruitment message between 6 April 2017 and 3 August 2017. Assessment of enrollment by this method ended on 1 December 2017. There were 116 patients who expressed interest in the study (response rate: 1.7%). Twelve (0.2%) recipients were randomized. There were two complaints (0.03%) and one request to unsubscribe from future recruitment messages (0.01%). Response rate was higher with the longer message than the shorter message (2.1% vs 1.2%; p = 0.005).Conclusion:Patient portal messages inviting seniors to participate in a randomized controlled trial resulted in a response rate similar to commercial email marketing and resulted in very few complaints or opt-out requests. Furthermore, a longer message with more content enhanced response rate. Recruitment through patient portals might be an effective strategy to enroll trial participants.

Prevalence estimates and evidence informing treatment targets for thyroid dysfunction largely come from studies of middle-aged adults. We conducted a cross-sectional analysis to determine the prevalence of thyroid dysfunction and risk factors for abnormal thyroid tests in participants aged ≥65 in the Atherosclerosis Risk in Communities (ARIC) study (N = 5,392). We measured serum concentrations of triiodothyronine (T3), free thyroxine (FT4), thyroid peroxidase antibody (Anti-TPO), and thyroid stimulating hormone (TSH). In this population (58% women, 22% black), 17% reported medication use for thyroid dysfunction. Among those not on treatment, the prevalence of overt and subclinical hypothyroidism was 0.82% and 6.06%, respectively. Overt and subclinical hyperthyroidism affected 0.26% and 0.78%, respectively. Multivariable adjusted TSH, FT4 and T3 levels were 25%, 1.3% and 3.9% lower in blacks compared to whites, respectively. Men were less likely to be anti-TPO positive compared to women (p

BACKGROUND Clinic-based blood pressure (BP) is a closely-tracked metric of health care quality, but is prone to inaccuracy and measurement imprecision. Recent guidelines have advocated for automated office blood pressure (AOBP) devices to improve clinic-based BP assessments. METHODS Patients from a single hypertension clinic underwent a 3-day evaluation that included a 24-hour ambulatory blood pressure monitoring (ABPM), 2 manual clinic-based BP measurements (over 2 visits), and an unattended AOBP measurement (single visit). All measurements were compared to the average wake-time systolic BP (SBP) and diastolic BP (DBP) from ABPM. RESULTS Among 103 patients (mean age 57.3 ± 14.8 years, 51% women, 29% black) the average wake-time SBP was 131.3 ± 12.3 mm Hg and DBP was 78.3 ± 9.2 mm Hg. The average of 2 manual BPs was significantly higher than wake-time ABPM with mean differences of 5.5 mm Hg (P < 0.001) for SBP and 2.7 mm Hg (P = 0.002) for DBP. In contrast, the averages of the last 2 AOBP measurements did not significantly differ from ABPM with mean differences of 1.6 mm Hg (P = 0.21) for SBP and −0.5 mm Hg (P = 0.62) for DBP. The estimated prevalence of SBP ≥ 140 or DBP ≥ 90 mm Hg based on wake-time ABPM was 27.2% vs. 49.5% based on the average of 2 manual measurements (difference 22.3%; P < 0.001) and 31.1% based on the average of the last 2 AOBP measurements (difference 3.9%; P = 0.57). CONCLUSIONS A single visit, unattended AOBP more precisely estimated BP and the prevalence of stage 2 and uncontrolled hypertension than even the average of 2 manual clinic visits, supporting guideline recommendations to use AOBP for clinic-based BP measurements.

Aims To evaluate 1,5‐anhydroglucitol (1,5‐AG) according to clinical outcomes and assess the effects of glucose‐ and blood pressure‐lowering interventions on change in 1,5‐AG levels in people with type 2 diabetes. Methods We measured 1,5‐AG in 6826 stored samples at baseline and in a random subsample of 684 participants at the 1‐year follow‐up visit in the ADVANCE trial. We examined baseline 1,5‐AG [ Results Low 1,5‐AG level [ Conclusions Our results suggest that 1,5‐AG is a marker of risk in adults with type 2 diabetes, but only for microvascular events independently of HbA1c. We found that 1,5‐AG was improved (increased) in response to an intensive glucose‐lowering intervention, although the independent effect of the blood pressure‐lowering intervention on 1,5‐AG suggests potential non‐glycaemic influences.

INTRODUCTION: Bloating is one of the most common gastrointestinal complaints. Evidence has linked fiber and sodium to bloating; however, randomized trials examining these diet components are lacking. Here, we used a randomized trial to examine the effects of the high-fiber DASH diet and dietary sodium intake on abdominal bloating. We hypothesized that both the high-fiber DASH diet and higher sodium intake would increase bloating. METHODS: The DASH–Sodium trial (1998–1999) randomized healthy adults to a high-fiber (32 g/d) DASH or low-fiber (11 g/d) Western diet (control). On their assigned diet, participants ate 3 sodium levels (50, 100, and 150 mmol/d at 2100 kcal) in 30-day periods in random order, with 5-day breaks between each period. The participants reported the presence of bloating at baseline and after each feeding period. Statistical analyses included log-binomial models to evaluate the risk of bloating. RESULTS: Of 412 participants (mean age 48 years; 57% women; 57% black), 36.7% reported bloating at baseline. Regardless of the diet, high sodium intake increased the risk of bloating (risk ratio = 1.27; 95% confidence interval: 1.06–1.52; P = 0.01). The high-fiber DASH diet also increased the risk of bloating over all sodium levels (risk ratio = 1.41; 95% confidence interval: 1.22–1.64; P < 0.001). The effect of high-fiber DASH on bloating was greater in men than in women (P for interaction = 0.001). DISCUSSION: Higher dietary sodium increased bloating, as did the high-fiber DASH diet. Although healthful high-fiber diets may increase bloating, these effects may be partially mitigated by decreasing dietary sodium intake. Future research is needed to explore mechanisms by which sodium intake and diet can influence bloating.

ImportanceClinical hyperthyroidism accelerates bone resorption without compensatory bone formation, reducing bone density and increasing the risk of fracture. The association between subclinical hyperthyroidism and fracture risk is less clear.ObjectiveTo investigate the association of endogenous subclinical thyroid dysfunction and fracture risk, independent of clinical confounders.Design, Setting, and ParticipantsThis cohort study included 10 946 participants from the Atherosclerosis Risk in Communities Study, an ongoing prospective cohort study of community-dwelling individuals conducted from 1987-1989 through December 31, 2019, in Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and the suburbs of Minneapolis, Minnesota. Participants were not taking thyroid medications and had no history of fractures.ExposuresThyrotropin and free thyroxine levels were measured at visit 2 (1990-1992). Subclinical hyperthyroidism was defined as a thyrotropin level lower than 0.56 mIU/L, subclinical hypothyroidism as a thyrotropin level higher than 5.1 mIU/L, and euthyroidism as a thyrotropin level of 0.56 to 5.1 mIU/L, with normal free thyroxine levels from 0.85 to 1.4 ng/dL.Main Outcomes and MeasuresIncident fracture was ascertained using hospitalization discharge codes through 2019 and linkage to inpatient and outpatient Medicare claims through 2018.ResultsOf 10 946 participants (54.3% women; mean [SD] age, 57 [5.7] years), 93.0% had euthyroidism, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism. During a median follow-up of 21 years (IQR, 13.0-27.3 years), there were 3556 incident fractures (167.1 per 10 000 person-years). The adjusted hazard ratios of fracture were 1.34 (95% CI, 1.09-1.65) for those with subclinical hyperthyroidism and 0.90 (95% CI, 0.77-1.05) for those with subclinical hypothyroidism compared with individuals with euthyroidism. Among those with normal free thyroxine levels, thyrotropin levels in the lower-than-normal range were significantly associated with higher fracture-related hospitalization risk; fracture risk was greater among individuals with thyrotropin concentrations below 0.56 mIU/L.Conclusions and RelevanceThis community-based cohort study suggests that subclinical hyperthyroidism was an independent risk factor associated with fracture. The increased risk for fracture among individuals with a thyrotropin level lower than 0.56 mIU/L highlights a potential role for more aggressive screening and monitoring of patients with subclinical hyperthyroidism to prevent bone mineral disease.

Background Self-reported low physical activity is a defining feature of phenotypic frailty but does not adequately capture physical activity performed throughout the day. This study examined associations between accelerometer-derived patterns of routine daily physical activity and frailty. Methods Wrist accelerometer and frailty data from 638 participants (mean age 77 [SD = 5.5] years; 44% women) were used to derive 5 physical activity metrics: active minutes/day, sedentary minutes/day, total activity counts/day, activity fragmentation (reciprocal of the average active bout length), and sedentary fragmentation (reciprocal of the average sedentary bout length). Robust, prefrail, and frail statuses were identified using the physical frailty phenotype defined as having 0, 1–2, or ≥3 of the following criterion: weight loss, exhaustion, slowness, self-reported low activity, and weakness. Frailty was collapsed into not frail (robust and prefrail) and frail, and each frailty criteria was dichotomized. Multiple logistic regression was used to model each accelerometer metric. Separate frailty criteria and interactions with age and sex were also examined. Results With higher amounts and intensity of daily activity (more active minutes, fewer sedentary minutes, higher activity counts) and lower activity fragmentation, the odds of frailty were lower compared to robust/prefrail states (p < .02 for all). For interactions, only an age by sedentary fragmentation interaction on the odds of frailty was observed (p = .01). For each separate criteria, accelerometer metrics were associated with odds of slowness, low activity, and weakness. Conclusion Less favorable patterns of objectively measured daily physical activity are associated with frailty and the components of slowness, low self-reported activity, and weakness.

Background Vitamin D3 supplementation is considered a potential intervention to prevent orthostatic hypotension (OH) based on observational evidence that vitamin D levels are inversely associated with OH. With data from The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a double-blind, randomized, response-adaptive trial, we determined if higher doses of vitamin D3 reduced risk of OH. Methods STURDY tested the effects of higher (1,000+ IU/day, i.e., 1,000, 2,000, and 4,000 IU/day combined) vs. lower-dose vitamin D3 (200 IU/day, comparison) on fall risk in adults ages 70 years and older with low serum 25-hydroxyvitamin D (25(OH)D, 10–29 ng/ml). OH was determined at baseline, 3, 12, and 24 months by taking the difference between seated and standing blood pressure (BP). OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mm Hg after 1 minute of standing. Participants were also asked about OH symptoms during the assessment and the preceding month. Results Among 688 participants (mean age 77 [SD, 5] years; 44% women; 18% Black), the mean baseline systolic/diastolic BP was 130 (19)/67 (11) mm Hg, serum 25(OH)D was 22.1 (5.1) ng/ml, and 2.8% had OH. There were 2,136 OH assessments over the maximum 2-year follow-up period. Compared with 200 IU/day, 1,000+ IU/day was not associated with seated, standing, or orthostatic BP, and it did not lower risk of OH or orthostatic symptoms. Conclusions These findings do not support use of higher doses of vitamin D3 supplementation as an intervention to prevent OH. Clinical trials registration Trial Number NCT02166333.

Background The Trial of Nonpharmacologic Interventions in the Elderly (TONE) demonstrated the efficacy of weight loss and sodium reduction to reduce hypertension medication use in older adults. However, the longer-term effects of drug withdrawal (DW) on blood pressure (BP), adverse events, and orthostatic symptoms were not reported. Methods TONE enrolled adults, ages 60–80 years, receiving treatment with a single antihypertensive and systolic BP (SBP)/diastolic BP Results Among the 975 participants (mean age 66 years, 48% women, 24% black), mean (±SD) BP was 128 ± 9/71 ± 7 mm Hg. Independent of assignment, DW increased SBP by 4.59 mm Hg (95% confidence interval [CI]: 3.89, 5.28) compared with baseline. There were 113 adverse events (84 symptomatic, 29 clinical), primarily during DW. Compared with usual care, combined weight loss and sodium reduction mitigated the effects of DW on BP (β = −4.33 mm Hg; 95% CI: −6.48, −2.17) and reduced orthostatic symptoms long term (odds ratio = 0.62; 95% CI: 0.41, 0.92), without affecting adverse events (hazard ratio = 1.81; 95% CI: 0.90, 3.65). In contrast, sodium reduction alone increased risk of adverse events (hazard ratio = 1.75; 95% CI: 1.04, 2.95), mainly during DW. Conclusions In older adults, antihypertensive DW may increase risk of symptomatic adverse events, highlighting the need for caution in withdrawing their antihypertensive medications. Clinical trials registration Trial Number NCT00000535.

While cardiorespiratory fitness is strongly associated with mortality and diverse outcomes, routine measurement is limited. We used smartphone-derived physical activity data to estimate fitness among 50 older adults. We recruited iPhone owners undergoing cardiac stress testing and collected recent iPhone physical activity data. Cardiorespiratory fitness was measured as peak metabolic equivalents of task (METs) achieved on cardiac stress test. We then estimated peak METs using multivariable regression models incorporating iPhone physical activity data, and validated with bootstrapping. Individual smartphone variables most significantly correlated with peak METs (p-values both

In the general population, an increased potassium (K) intake lowers blood pressure (BP). The effects of K have not been well-studied in individuals with chronic kidney disease (CKD). This randomized feeding trial with a 2-period crossover design compared the effects of diets containing 100 and 40 mmol K/day on BP in 29 adults with stage 3 CKD and treated or untreated systolic BP (SBP) 120–159 mmHg and diastolic BP (DBP) &lt, 100 mmHg. The primary outcome was 24 hour ambulatory systolic BP. The higher- versus lower-K diet had no significant effect on 24 hour SBP (−2.12 mm Hg, p = 0.16) and DBP (−0.70 mm Hg, p = 0.44). Corresponding differences in clinic BP were −4.21 mm Hg for SBP (p = 0.054) and −0.08 mm Hg for DBP (p = 0.94). On the higher-K diet, mean serum K increased by 0.21 mmol/L (p = 0.003) compared to the lower-K diet, two participants had confirmed hyperkalemia (serum K ≥ 5.5 mmol/L). In conclusion, a higher dietary intake of K did not lower 24 hour SBP, while clinic SBP reduction was of borderline statistical significance. Additional trials are warranted to understand the health effects of increased K intake in individuals with CKD.

Background: Lower body mass index (BMI) has been associated with lower serum urate (SU), but only in observational studies. We sought to determine the effects of behavioral weight loss and metformin treatment on SU in a randomized trial. Methods and Findings: The Survivorship Promotion In Reducing IGF-1 Trial (SPIRIT) was a parallel three-arm randomized controlled trial of overweight/obese adult cancer survivors without gout at a single center in Maryland, United States. Participants were randomized to: (1) coach-directed weight loss (behavioral telephonic coaching), (2) metformin (up to 2000 mg daily), or (3) self-directed weight loss (informational brochures, reference group). SU and BMI were assessed at baseline and at 3, 6, and 12 months post-randomization. The 121 participants had a mean ± standard deviation (SD) age of 60 ± 9 years, 79% were female, and 45% were Black. At baseline, BMI was 35 ± 5 kg/m2, and SU was 5.6 ± 1.3 mg/dL. Compared to the self-directed group, at 12 months, the coach-directed group reduced BMI by 0.9 kg/m2 (95% confidence interval (CI): −1.5, −0.4) and metformin reduced BMI by 0.6 kg/m2 (95% CI: −1.1, −0.1). However, compared to the self-directed group, the coach-directed group unexpectedly increased SU by 0.3 mg/dL (95% CI: 0.05, 0.6), and metformin non-significantly increased SU by 0.2 mg/dL (95% CI: −0.04, 0.5), these effects were attenuated when analyses included change in estimated glomerular filtration rate (eGFR). Conclusions: In this randomized trial of cancer survivors without gout, reductions in BMI either increased or did not change SU, potentially due to effects on eGFR. These results do not support a focus on BMI reduction for SU reduction, however, long-term studies are needed. ClinicalTrials.gov Registration: NCT02431676.

Lipopolysaccharide-binding protein (LBP), a biomarker of gut barrier permeability to lipopolysaccharides, is higher in adults with obesity and type 2 diabetes. Behavioral weight loss and metformin have distinct effects on the gut microbiome, but their impact on gut permeability to lipopolysaccharides is unknown. This study's objective was to determine the effects of a behavioral weight-loss intervention or metformin treatment on plasma LBP.SPIRIT was a randomized trial of adults with overweight or obesity. Participants were randomized to one of three arms: metformin treatment, coach-directed behavioral weight loss on a DASH diet, or self-directed care (control). Of 121 participants, a random subset (n = 88) was selected to have LBP measured at baseline, 6 months, and 12 months post intervention. Intervention effects on LBP over time were assessed using generalized estimating equations (GEE). We also examined whether the intervention effects were modified by change in diet and weight.Arms were balanced by sex (83% female), race (51% white), and age (mean 60 years), with no differences in baseline LBP (median 4.23 μg/mL). At 1 year, mean weight change was -3.00% in the metformin arm, -3.02% in the coach-directed behavioral weight-loss arm, and +0.33% in the self-directed (control) arm. The corresponding change in LBP was +1.03, -0.98, +1.03 μg/mL. The behavioral weight-loss intervention reduced LBP compared to self-directed care (β = -0.17, 95% CI: -0.33 to -0.01); no other between-arm comparisons were significant. Behavioral weight-loss participants who reduced dietary fat showed the greatest reductions in 6-month LBP (β = -2.84, 95% CI: -5.17 to -0.50).Despite similar weight loss in the behavioral weight loss arm and the metformin arm, only the behavioral weight-loss intervention reduced LBP compared to control. Lifestyle weight-loss interventions that promote a DASH diet may be effective at reducing gut barrier permeability to lipopolysaccharides.NCT02431676, https://clinicaltrials.gov.

Context Higher levels of insulin-like growth factor-1 (IGF-1) are associated with increased risk of cancers and higher mortality. Therapies that reduce IGF-1 have considerable appeal as means to prevent recurrence. Design Randomized, 3-parallel-arm controlled clinical trial. Interventions and Outcomes Cancer survivors with overweight or obesity were randomized to (1) self-directed weight loss (comparison), (2) coach-directed weight loss, or (3) metformin treatment. Main outcomes were changes in IGF-1 and IGF-1:IGFBP3 molar ratio at 6 months. The trial duration was 12 months. Results Of the 121 randomized participants, 79% were women, 46% were African Americans, and the mean age was 60 years. At baseline, the average body mass index was 35 kg/m2; mean IGF-1 was 72.9 (SD, 21.7) ng/mL; and mean IGF1:IGFBP3 molar ratio was 0.17 (SD, 0.05). At 6 months, weight changes were -1.0% (P = 0.07), -4.2% (P Conclusions In cancer survivors with obesity, metformin may have a short-term effect on IGF-1 reduction that wanes over time.

Reduced sodium meal plans are recommended by the Centers of Disease Control to lower blood pressure in older adults, however, this strategy has not been tested in a clinical trial. The Satter House Trial of Reduced Sodium Meals (SOTRUE) was an individual-level, double-blind, randomized controlled pilot study of adults living in a congregate living facility subsidized by the Federal Department of Housing and Urban Development (HUD). Adults over age 60 years ate 3 isocaloric meals with two snacks daily for 14 days. The meal plans differed in sodium density (&lt, 0.95 vs. &gt, 2 mg/kcal), but were equivalent in potassium and macronutrients. Seated systolic BP (SBP) was the primary outcome, while urine sodium-creatinine ratio was used to measure compliance. Twenty participants were randomized (95% women, 95% white, mean age 78 ± 8 years), beginning in 7 October 2019. Retention was 100% with the last participant ending November 4, 2019. Mean baseline SBP changed from 121 to 116 mmHg with the typical sodium diet (−5 mmHg, 95%CI: −18, 8) and from 123 to 112 mmHg with the low sodium diet (−11 mmHg, 95%CI: −15.2, −7.7). Compared to the typical sodium meal plan, the low sodium meal plan lowered SBP by 4.8 mmHg (95%CI: −14.4, 4.9, p = 0.31) and urine sodium-creatinine ratio by 36% (−36.0, 95%CI: −60.3, 3.4, p = 0.07), both non-significant. SOTRUE demonstrates the feasibility of sodium reduction in federally mandated meal plans. A longer and larger study is needed to establish the efficacy and safety of low sodium meals in older adults.

The Dietary Approaches to Stop Hypertension (DASH) diet reduces serum urate (SU), however, the impact of the DASH diet has not been previously evaluated among patients with gout. We conducted a randomized, controlled, crossover pilot study to test the effects of ~$105/week ($15/day) of dietitian-directed groceries (DDG), patterned after the DASH diet, on SU, compared with self-directed grocery shopping (SDG). Participants had gout and were not taking urate lowering therapy. Each intervention period lasted 4 weeks, crossover occurred without a washout period. The primary endpoint was SU. Compliance was assessed by end-of-period fasting spot urine potassium and sodium measurements and self-reported consumption of daily servings of fruit and vegetables. We randomized 43 participants (19% women, 49% black, mean age 59 years) with 100% follow-up. Mean baseline SU was 8.1 mg/dL (SD, 0.8). During Period 1, DDG lowered SU by 0.55 mg/dL (95% CI: 0.07, 1.04) compared to SDG by 0.0 mg/dL (95% CI: −0.44, 0.44). However, after crossover (Period 2), the SU difference between groups was the opposite: SDG reduced SU by −0.48 mg/dL (95% CI: −0.98, 0.01) compared to DDG by −0.05 mg/dL (95% CI: −0.48, 0.38, P for interaction by period = 0.11). Nevertheless, DDG improved self-reported intake of fruit and vegetables (3.1 servings/day, 95% CI: 1.5, 4.8) and significantly reduced total spot urine sodium excretion by 22 percentage points (95% CI: −34.0, −8.6). Though relatively small in scale, this pilot study suggests that dietitian-directed, DASH-patterned groceries may lower SU among gout patients not on urate-lowering drugs. However, behavior intervention crossover trials without a washout period are likely vulnerable to strong carryover effects. Definitive evaluation of the DASH diet as a treatment for gout will require a controlled feeding trial, ideally with a parallel-design.

The DASH (Dietary Approaches to Stop Hypertension) diet has been determined to have beneficial effects on cardiac biomarkers. The effects of sodium reduction on cardiac biomarkers, alone or combined with the DASH diet, are unknown.The purpose of this study was to determine the effects of sodium reduction and the DASH diet, alone or combined, on biomarkers of cardiac injury, strain, and inflammation.DASH-Sodium was a controlled feeding study in adults with systolic blood pressure (BP) 120 to 159 mm Hg and diastolic BP 80 to 95 mm Hg, randomly assigned to the DASH diet or a control diet. On their assigned diet, participants consumed each of three sodium levels for 4 weeks. Body weight was kept constant. At the 2,100 kcal level, the 3 sodium levels were low (50 mmol/day), medium (100 mmol/day), and high (150 mmol/day). Outcomes were 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) (measure of cardiac injury), N-terminal pro-B-type natriuretic peptide (NT-proBNP) (measure of strain), and high-sensitivity C-reactive protein (hs-CRP) (measure of inflammation), collected at baseline and at the end of each feeding period.Of the original 412 participants, the mean age was 48 years; 56% were women, and 56% were Black. Mean baseline systolic/diastolic BP was 135/86 mm Hg. DASH (vs. control) reduced hs-cTnI by 18% (95% confidence interval [CI]: -27% to -7%) and hs-CRP by 13% (95% CI: -24% to -1%), but not NT-proBNP. In contrast, lowering sodium from high to low levels reduced NT-proBNP independently of diet (19%; 95% CI: -24% to -14%), but did not alter hs-cTnI and mildly increased hs-CRP (9%; 95% CI: 0.4% to 18%). Combining DASH with sodium reduction lowered hs-cTnI by 20% (95% CI: -31% to -7%) and NT-proBNP by 23% (95% CI: -32% to -12%), whereas hs-CRP was not significantly changed (-7%; 95% CI: -22% to 9%) compared with the high sodium-control diet.Combining a DASH dietary pattern with sodium reduction can lower 2 distinct mechanisms of subclinical cardiac damage: injury and strain, whereas DASH alone reduced inflammation. (Dietary Patterns, Sodium Intake and Blood Pressure [DASH - Sodium]; NCT00000608).

Background Decreased kidney function is commonly caused by hypovolemia. When hypovolemic, the kidney reabsorbs water resulting in concentrated urine. Osmolality is a measure of urine concentration which is more objective than self-reported fluid intake. It has a positive association with hypovolemia. However, it remains controversial whether osmolality is associated with decreased kidney function and/or albuminuria. Methods We conducted a cross-sectional analysis of the 2009–2012 National Health and Nutrition Examination Survey, a standardized survey in the U.S. population. Participants aged 18–70 years old with random urine osmolality were included. Osmolality was categorized as quartiles. Decreased kidney function was defined by estimated glomerular filtration rate (eGFR) 2 and albuminuria was defined by albumin-to-creatinine ratio ≥ 30 mg/gm. We performed multivariable regression via four sequential models. Results Our study sample included 7,373 participants. The mean age was 42.9 ± 0.4 years. Overall, 51.4% were male and 67.3% were white. The mean osmolality was 603.8 mOsm/kg and 629.1 mOsm/kg in those with and without decreased eGFR and/or albuminuria, respectively. The number of cases was 610 (6.7%). The prevalence from the lowest to highest quartiles of osmolality was 116 (6.2%), 213 (8.6%), 179 (7.5%), and 102 (4.3%), respectively (p-value for trend = 0.02). The relationship between osmolality and eGFR appeared nonlinear. After adjustment for demographic, social, cardiovascular, and dietary risk factors, there was no significant association of osmolality quartiles with decreased eGFR and/or albuminuria (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.56, 1.07). In sensitivity analyses, osmolality ≥ 500 mOsm/kg was associated with lower eGFR (adjusted ß -1.13, 95% CI -1.98, -0.28). In pre-specified subgroup analyses, osmolality had a statistically significant negative correlation with eGFR among individuals with eGFR ≥ 60 mL/min/1.73m2, but a positive correlation among those with eGFR 2 (adjusted ß -0.19, 95% CI -0.36, -0.01 versus adjusted ß 0.50, 95% CI 0.05, 0.96; p-value for interaction = 0.016). Conclusions Higher osmolality was significantly associated with lower eGFR among adults with eGFR ≥ 60 mL/min/1.73m2 Future research should examine the relationship between osmolality and change in kidney function over time among adults with normal eGFR.

Background/aims:Electronic-based recruitment methods are increasingly utilized in clinical trials to recruit and enroll research participants. The cost-effectiveness of electronic-based methods and impact on sample generalizability is unknown. We compared recruitment yields, cost-effectiveness, and demographic characteristics across several electronic and traditional recruitment methods.Methods:We analyzed data from the diet gout trial recruitment campaign. The diet gout trial was a randomized, controlled, cross-over trial that examined the effects of a dietary approaches to stop hypertension (DASH)–like diet on uric acid levels in adults with gout. We used four electronic medical record and four non-electronic medical record–based recruitment methods to identify and recruit potentially eligible participants. We calculated the response rate, screening visit completion rate, and randomization rate for each method. We also determined cost per response, the screening, and randomization for each method. Finally, we compared the demographic characteristics among individuals who completed the screening visit by recruitment method.Results:Of the 294 adults who responded to the recruitment campaign, 51% were identified from electronic medical record–based methods. Patient portal messaging, an electronic medical record–based method, resulted in the highest response rate (4%), screening visit completion rate (37%), and randomization rate (21%) among these eight methods. Electronic medical record–based methods ($60) were more cost-effective per response than non-electronic medical record–based methods ($107). Electronic-based methods, including patient portal messaging and Facebook, had the highest proportion of White individuals screened (52% and 60%). Direct mail to non-active patient portal increased enrollment of traditionally under-represented groups, including both women and African Americans.Conclusion:An electronic medical record–based recruitment strategy that utilized the electronic medical record for participant identification and postal mailing for participant outreach was cost-effective and increased participation of under-represented groups. This hybrid strategy represents a promising approach to improve the timely execution and broad generalizability of future clinical trials.

BACKGROUND Hypertension guidelines recommend home blood pressure monitoring (HBPM) to help achieve blood pressure (BP) control. We hypothesized that HBPM use with a physician recommendation would be associated with lower BP and greater medication adherence. METHODS We used data from 6,320 adults with hypertension in the National Health and Nutrition Examination Survey 2009–2014 to characterize the association of (i) provider recommendation for HBPM and (ii) HBPM use on 2 outcomes: measured BP (linear regression) and medication adherence (logistic regression). Provider recommendation, HBPM use, and medication use were self-reported. RESULTS Among adults with hypertension, 30.1% reported a physician recommendation for HBPM, among whom 82.0% reported using HBPM. Among those who did not report a physician recommendation for HBPM, 28.3% used HBPM. Factors associated with a physician recommendation were having health insurance, higher education attainment, hypertension awareness, and having a prescription for antihypertensive medication. Among those who reported receiving a physician recommendation, those who used HBPM had a mean BP that was 3.1/4.5 mm Hg lower than those who did not. Those who reported having a physician recommendation and using HBPM were more likely to report hypertension medication adherence (odds ratio 2.9; 95% confidence interval: 2.0, 4.4). CONCLUSIONS HBPM use was associated with lower BP and higher medication adherence. Use of HBPM was higher among those with a physician recommendation. These results support a role for physicians in counseling and partnering with patients on HBPM use for BP management.

IMPORTANCE: High blood pressure (BP) is a leading contributor to premature mortality worldwide. The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause death with intensive (vs standard) BP control. However, traditional reporting of survival benefits is not readily interpretable outside medical communities. OBJECTIVE: To estimate residual life span and potential survival gains with intensive compared with standard BP control in the SPRINT trial using validated nonparametric age-based methods. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of data from an open-label randomized clinical trial included data from 102 enrolling clinical sites in the United States. Adults who were 50 years or older, were at high cardiovascular risk but without diabetes, and had a screening systolic BP between 130 and 180 mm Hg were enrolled between November 2010 and March 2013. Data analysis occurred from May 2019 to December 2019. INTERVENTIONS: A 1:1 randomization to intensive (target

Lightheadedness after standing contributes to adverse clinical events, including falls. Recommendations for higher sodium intake to treat postural lightheadedness have not been evaluated in a trial setting. The Dietary Approaches to Stop Hypertension (DASH)-Sodium trial (1998-1999) tested the effects of the DASH diet and sodium reduction on blood pressure (BP). Participants were randomly assigned to DASH or a typical Western diet (control). During either diet, participants ate three sodium levels (50, 100, 150 meq/d at 2100 kcal) in random order for 30-days, separated by 5-day breaks. Participants reported the presence and severity of postural lightheadedness at baseline and after each feeding period. There were 412 participants (mean age 48 years; 57% women; 57% black). Mean baseline SBP/DBP was 135/86 mm Hg; 9.5% reported baseline lightheadedness. Among those consuming the DASH diet, high vs low sodium increased lightheadedness (OR 1.71; 95% CI: 1.01, 2.90; P = 0.047) and severity of lightheadedness (P = 0.02), but did not affect lightheadedness in those consuming the control diet (OR 0.77; 95% CI: 0.46, 1.29; P = 0.32). Among those consuming high vs low sodium in the context of the DASH diet, adults

Although orthostatic hypotension (OH) is often considered a contraindication to blood pressure (BP) treatment, evidence is lacking. We examined the effect of BP goal or initial medication choice on OH in AASK (African American Study of Kidney Disease and Hypertension), a 2×3 factorial trial. Blacks with chronic kidney disease attributed to hypertension were randomly assigned 1 of 2 BP goals: intensive (mean arterial pressure, ≤92 mm Hg) or standard (mean arterial pressure, 102–107 mm Hg) and 1 of 3 initial medications (ramipril, metoprolol, and amlodipine). Postural changes in systolic BP, diastolic BP, or heart rate (HR) were determined after 2 minutes and 45 seconds of standing. OH was assessed each visit and defined using the consensus definition (drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg). Median follow-up was 4 years. Outcomes were congestive heart failure, stroke, nonfatal cardiovascular disease (CVD), fatal CVD, any CVD (composite of preceding events), and all-cause mortality. There were 1094 participants (mean age, 54.5±10.7 years; 38.8% female; OH was assessed at 52 864 visits). Mean seated systolic BP, diastolic BP, and HR were 150.3±23.9 mm Hg, 95.5±14.2 mm Hg, and 72.0±12.6 bpm, respectively. A more intensive BP goal did not alter the distributions of standing BP and was not associated with OH, but metoprolol was associated with systolic OH compared with ramipril (odds ratio, 1.68; 95% CI, 1.15–2.46) and amlodipine (odds ratio, 1.94; 95% CI, 1.09–3.44). Although consensus OH was associated with stroke (HR, 5.01; 95% CI, 1.80–13.92), nonfatal CVD (HR, 2.28; 95% CI, 1.21–4.30), and any CVD event (HR, 2.12; 95% CI, 1.12–3.98), neither BP goal or medication altered this risk. Concerns about causing OH or its CVD consequences should not deter a lower BP goal among adults with chronic kidney disease attributed to hypertension.

Objective To examine whether partial replacement of a diet typical of the average American diet with Dietary Approaches to Stop Hypertension (DASH)-related foods in the home environment lowers the serum uric acid (UA) level in individuals with hypertension. Methods We conducted an ancillary study of a randomized trial of African American adults with controlled hypertension from an urban clinic. Participants were assigned to either a control group or an intervention (DASH-Plus) group. DASH-Plus participants received coach-directed dietary advice, assistance with purchasing DASH-related foods ($30/week), and home delivery of food via a community supermarket. Participants in the control group received a DASH diet brochure and a debit card account ($30/week) to purchase foods. Serum UA levels were measured at baseline and after 8 weeks. Results Of the original 123 randomized participants, 117 had available serum UA measurements. Seventy percent of the participants were women, the mean ± SD age was 59 ± 9.5 years, and the mean ± SD serum UA level was 6.4 ± 1.7 mg/dl. The DASH-Plus diet did not reduce serum UA levels compared with the control diet (difference in difference -0.01 mg/dl [95% confidence interval -0.39, 0.38]). However, there was a significant trend toward a greater reduction in the serum UA level in participants with higher baseline serum UA levels (P for trend = 0.008). Baseline changes in the serum UA level were inversely associated with changes in systolic blood pressure (P = 0.002), diastolic blood pressure (P = 0.001), and urinary sodium excretion (P = 0.05). Conclusion Overall, in African American individuals, partial replacement of a typical diet with DASH foods did not lower serum UA levels compared with a control diet. However, there was a significant trend toward a greater reduction in serum UA levels in subjects with higher baseline serum UA levels. Furthermore, changes in serum UA levels were associated with known correlates, suggesting heterogeneity of effects in the treatment and control arms. Future pragmatic studies of consumption of the DASH diet to lower serum UA levels should optimize replacement strategies and enroll individuals with hyperuricemia or gout.

ObjectiveTo examine associations of orthostatic hypotension (OH) with dementia and long-term cognitive decline and to update previously published results in the same cohort for stroke with an additional 16 years of follow-up.MethodsWe analyzed data from 11,709 participants without a history of coronary heart disease or stroke who attended the baseline examination (1987–1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study. OH was defined as a drop in systolic blood pressure (BP) of at least 20 mm Hg or a drop in diastolic BP of at least 10 mm Hg on standing. Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance. Ischemic stroke was ascertained via cohort surveillance of hospitalizations, cohort follow-up, and linkage with registries. Both outcomes were adjudicated. Cognitive function was ascertained via 3 neuropsychological tests administered in 1990 to 1992 and 1996 to 1998 and a full battery of tests in 2011 to 2013. Scores were summarized and reported as SDs. We used adjusted Cox regression and linear mixed models.ResultsOver ≈25 years, 1,068 participants developed dementia and 842 had an ischemic stroke. Compared to persons without OH at baseline, those with OH had a higher risk of dementia (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.20–1.97) and ischemic stroke (HR 2.08, 95% CI 1.65–2.62). Persons with OH had greater, although nonsignificant, cognitive decline over 20 years (SD 0.09, 95% CI −0.02 to 0.21).ConclusionsOH assessed in midlife was independently associated with incident dementia and ischemic stroke. Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention.

Background/Aims:Despite widespread Internet adoption, online advertising remains an underutilized tool to recruit participants into clinical trials. Whether online advertising is a cost-effective method to enroll participants compared to other traditional forms of recruitment is not known.Methods:Recruitment for the Survivorship Promotion In Reducing IGF-1 Trial, a community-based study of cancer survivors, was conducted from June 2015 through December 2016 via in-person community fairs, advertisements in periodicals, and direct postal mailings. In addition, “Right Column” banner ads were purchased from Facebook to direct participants to the Survivorship Promotion In Reducing IGF-1 Trial website. Response rates, costs of traditional and online advertisements, and demographic data were determined and compared across different online and traditional recruitment strategies. Micro-trials optimizing features of online advertisements were also explored.Results:Of the 406 respondents to our overall outreach efforts, 6% (24 of 406) were referred from online advertising. Facebook advertisements were shown over 3 million times (impressions) to 124,476 people, which resulted in 4401 clicks on our advertisement. Of these, 24 people ultimately contacted study staff, 6 underwent prescreening, and 4 enrolled in the study. The cost of online advertising per enrollee was $794 when targeting a general population versus $1426 when accounting for strategies that specifically targeted African Americans or men. By contrast, community fairs, direct mail, or periodicals cost $917, $799, or $436 per enrollee, respectively. Utilization of micro-trials to assess online ads identified subtleties (e.g. use of an advertisement title) that substantially impacted viewer interest in our trial.Conclusion:Online advertisements effectively directed a relevant population to our website, which resulted in new enrollees in the Survivorship Promotion In Reducing IGF-1 Trial at a cost comparable to traditional methods. Costs were substantially greater with online recruitment when targeting under-represented populations, however. Additional research using online micro-trial tools is needed to evaluate means of more precise recruitment to improve yields in under-represented groups. Potential gains from faster recruitment speed remain to be determined.

Background Multiple definitions are used to characterize orthostatic hypotension (OH), but the degree to which these definitions correspond with orthostatic symptoms is unknown. Methods We analyzed data from African American Study of Kidney Disease and Hypertension (AASK), a randomized trial of African Americans with hypertension and kidney disease, to characterize the relationship between OH definitions and self-reported syncope, dizziness, or light-headedness. Orthostatic changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), or heart rate (HR) were determined each visit after standing 2:45 minutes. OH was defined using the consensus definition (a drop in SBP ≥20 mm Hg or DBP ≥10 mm Hg) or an often used clinical substitute based on HR (an increase ≥20 bpm). Results Among 1,094 participants (mean age 54.5 ± 10.7 years, 38.9% female), there were 52,636 visits (mean 48/person). Mean resting SBP, DBP, and HR at baseline were 147.7 ± 22.3 mm Hg, 92.2 ± 13.4 mm Hg, and 71.1 ± 11.7 bpm, respectively. While the OH consensus definition was associated with syncope (odds ratio 2.49; 95% confidence interval: 1.13, 5.51), dizziness (1.89; 1.53, 2.33), and light-headedness (1.84; 1.52, 2.23), the clinical HR definition was only associated with dizziness (1.28; 1.07, 1.52). None of the OH components (SBP, DBP, or HR) reflected a natural threshold in the prevalence of symptoms; definitions using each of the 3 components were highly specific (≥96%) with low sensitivity (1-5%). Conclusions While the consensus definition was more strongly associated with symptoms, OH definitions did not reflect natural thresholds in symptoms and were insensitive. This implies that the absence of OH using either consensus or clinical definitions does not exclude orthostatic symptoms, which has implications for evaluating clinical events like falls. Clinical trials registration Trial Number: NCT01206062 (clinicaltrials.gov).

The decision to initiate insulin in patients with type 2 diabetes is a challenging escalation of care that requires an individualized approach. However, the sociodemographic and clinical factors affecting insulin initiation are not well understood. We sought to identify patient factors that were independent predictors of insulin initiation among participants in the Look AHEAD (Action for Health in Diabetes) clinical trial. Retrospective analysis of a randomized clinical trial. Beginning in 2001, Look AHEAD enrolled ambulatory U.S. adults with type 2 diabetes who were overweight or obese and had a primary healthcare provider. Participants were randomized (1:1) to an intensive lifestyle intervention, or diabetes support and education. This study examined 3913 participants across the two trial arms who were not using insulin at baseline. We used Cox proportional hazards models to estimate the association between participant characteristics and time to insulin initiation. We performed time-varying adjustment for HbA1c measured eight times over the 10-year study period, as well as for multiple clinical and socioeconomic factors. A total of 1087 participants (27.8%) initiated insulin during a median follow-up of 8.0 years. Age was inversely associated with insulin initiation (adjusted hazard ratio [aHR] 0.88 per 10 years, P = 0.025). The risk of insulin initiation was greater with a higher number of diabetes complications (P

Aims To characterize the determinants of 1,5-anhydroglucitol in people without diabetes and to determine the effects of dietary changes in amount and type of carbohydrate on 1,5-anhydroglucitol levels. Methods We conducted an ancillary study to a completed, randomized clinical trial in overweight and obese adults without diabetes (N=159). Using a crossover design, participants were fed each one of four diets in turn for 5 weeks, with 2-week washout periods inbetween. The four diets were: high glycaemic index (≥65) with high proportion of carbohydrate (58% kcal) (GC); low glycaemic index (GI≤45) with low proportion of carbohydrate (40% kcal) (gc); low glycaemic index with high proportion of carbohydrate (gC); and high glycaemic index with low proportion of carbohydrate (Gc). Plasma 1,5-anhydroglucitol levels were measured at baseline and after each feeding period. Results At baseline, participants had a mean age of 53 years (53% women, 52% non-Hispanic black, 50% obese). Their mean fasting glucose and 1,5-anhydroglucitol levels were 97 mg/dl (5.4 mmol/l) and 18.6 μg/mL (113.3 μmol/l), respectively. Compared with baseline, each of the four diets reduced 1,5-anhydroglucitol by a range of –2.4 to –3.7 μg/mL (–14.6 to –22.5 μmol/l); all P

Orthostatic hypotension (OH) is frequently observed with hypertension treatment, but its contribution to adverse outcomes is unknown. The SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized trial of adults, age ≥50 years at high risk for cardiovascular disease with a seated systolic blood pressure (BP) of 130 to 180 mm Hg and a standing systolic BP ≥110 mm Hg. Participants were randomized to a systolic BP treatment goal of either Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT01206062.

Objectives Gout is a common complication of blood pressure management and a frequently cited cause of medication nonadherence. Little trial evidence exists to inform antihypertensive selection with regard to gout risk. Methods The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized clinical trial on the effects of first-step hypertension therapy with amlodipine, chlorthalidone, or lisinopril on fatal coronary heart disease or nonfatal myocardial infarction (1994-2002). Trial participants were linked to CMS and VA gout claims (ICD9 274.XX). We determined the effect of drug assignment on gout with Cox regression models. We also determined the adjusted association of self-reported atenolol use (ascertained at the 1-month visit for indications other than hypertension) with gout. Results Claims were linked to 23 964 participants (mean age 69.8 ± 6.8 years, 45% women, 31% black). Atenolol use was reported by 928 participants at the 1-month visit. Over a mean follow-up of 4.9 years, we documented 597 gout claims. Amlodipine reduced the risk of gout by 37% (hazard ratio 0.63; 95% CI 0.51--0.78) compared with chlorthalidone and by 26% (hazard ratio 0.74; 95% CI 0.58--0.94) compared with lisinopril. Lisinopril nonsignificantly lowered gout risk compared with chlorthalidone (hazard ratio 0.85; 95% CI 0.70--1.03). Atenolol use was not associated with gout risk (adjusted hazard ratio 1.18; 95% CI 0.78--1.80). Gout risk reduction was primarily observed after 1 year of follow-up. Conclusion Amlodipine lowered long-term gout risk compared with lisinopril or chlorthalidone. This finding may be useful in cases where gout risk is a principal concern among patients being treated for hypertension.This trial is registered at clinicaltrials.gov, number: NCT00000542.

Objectives To examine the effects of high-fiber, isocaloric, macronutrient substitutions on bloating. Methods The OmniHeart study is a randomized 3-period crossover feeding trial conducted from April 2003 to June 2005. Participants were provided 3 isocaloric versions of high-fiber (∼30 g per 2,100 kcal) diet, each different in carbohydrate, protein, and unsaturated fat composition. Each feeding period lasted for 6 weeks with a 2- to 4-week washout period between diets. Participants reported the presence and severity of bloating at baseline (participants were eating their own diet) and at the end of each feeding period. Results One hundred sixty-four participants were included in the analysis (mean age: 53.1 years; 45% women; 55% black). The prevalence of bloating at baseline and at the end of the carbohydrate-rich, protein-rich, and unsaturated fat-rich diet period was 18%, 24%, 33%, and 30%, respectively. Compared with baseline, the relative risk of bloating for the carbohydrate-rich, protein-rich, and unsaturated fat-rich high-fiber diet was 1.34 (95% confidence interval [CI]: 0.93, 1.92), 1.78 (95% CI: 1.32, 2.40), and 1.63 (95% CI: 1.17, 2.26), respectively. The protein-rich diet increased the risk of bloating more than the carbohydrate-rich diet (relative risk = 1.40; 95% CI: 1.03, 1.88). Bloating did not significantly vary between protein-rich vs unsaturated fat-rich or unsaturated fat-rich vs carbohydrate-rich diets. Black participants compared with non-black participants had a higher risk of bloating after all 3 versions of the high-fiber OmniHeart diet (P-value for interaction = 0.012). Discussion Substitution of protein with carbohydrate may be an effective strategy to decrease bloating among individuals experiencing gastrointestinal bloating from a high-fiber diet.