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Objectives: In observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD., Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10-29 ng/mL). Hs-cTnI and NT-proBNP levels were measured at baseline, 3-, 12-, and 24-month follow-up visits. For this ancillary study, we used data from the original trial and compared participants by treatment group: low-dose (200 IU/day) or high-dose (1000+ IU/day). The effects of vitamin D dose on biomarkers were assessed via mixed effects tobit models., Results: Among 688 participants (mean age of 76.5) hs-cTnI increased in both the low- and high-dose groups by 5.2 % and 7.0 %, respectively; likewise, NT-proBNP increased by 11.3 % and 9.3 %, respectively. Compared to the low-dose, high-dose vitamin D supplementation did not affect hs-cTnI (1.6 %-difference; 95 % CI: -5.3, 8.9) or NT-proBNP (-1.8 %-difference; 95 % CI: -9.3, 6.3)., Conclusions: Compared to low-dose vitamin D supplementation, doses ≥1,000 IU/ day did not affect markers of subclinical CVD in older adults with low serum vitamin D levels., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Background: Accurate quantification of sodium intake based on self-reported dietary assessments has been a persistent challenge. We aimed to apply machine-learning (ML) algorithms to predict 24-hour urinary sodium excretion from self-reported questionnaire information., Methods and Results: We analyzed 3454 participants from the NHS (Nurses' Health Study), NHS-II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study), with repeated measures of 24-hour urinary sodium excretion over 1 year. We used an ensemble approach to predict averaged 24-hour urinary sodium excretion using 36 characteristics. The TOHP-I (Trial of Hypertension Prevention I) was used for the external validation. The final ML algorithms were applied to 167 920 nonhypertensive adults with 30-year follow-up to estimate confounder-adjusted hazard ratio (HR) of incident hypertension for predicted sodium. Averaged 24-hour urinary sodium excretion was better predicted and calibrated with ML compared with the food frequency questionnaire (Spearman correlation coefficient, 0.51 [95% CI, 0.49-0.54] with ML; 0.19 [95% CI, 0.16-0.23] with the food frequency questionnaire; 0.46 [95% CI, 0.42-0.50] in the TOHP-I). However, the prediction heavily depended on body size, and the prediction of energy-adjusted 24-hour sodium excretion was modestly better using ML. ML-predicted sodium was modestly more strongly associated than food frequency questionnaire-based sodium in the NHS-II (HR comparing Q5 versus Q1, 1.48 [95% CI, 1.40-1.56] with ML; 1.04 [95% CI, 0.99-1.08] with the food frequency questionnaire), but no material differences were observed in the NHS or HPFS., Conclusions: The present ML algorithm improved prediction of participants' absolute 24-hour urinary sodium excretion. The present algorithms may be a generalizable approach for predicting absolute sodium intake but do not substantially reduce the bias stemming from measurement error in disease associations.

Hypertension guidelines recommend team-based care for the treatment of high blood pressure (BP). Clinical pharmacists can help patients get to goal BP with rapid medication titration in conjunction with telehealth visits. We conducted a pharmacist-led home BP monitoring pilot program from June 2020 to September 2021. Forty-two patients with a SBP ≥140 despite using ≤2 antihypertensive medications were referred for pharmacist telehealth with expedited medication titration to achieve a BP goal <130/80. The mean enrollment SBP/DBP was 155.2 (SD, 15.8)/89.7 (SD, 11.5) mm Hg, and the mean completion SBP/DBP was 132.1 (SD, 10.9)/77.6 (SD, 10). The number of hypertension medications prescribed increased from 1.3 to 1.6 with no instances of falls or hypotension. At completion, 31% of patients had an automated office blood pressure (AOBP) with SBP <130 mm Hg and DBP <80 mm Hg. A pharmacist-led, home BP monitoring telehealth pilot program helped patients safely achieve BP goals., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Abnormal orthostatic blood pressure (BP) regulation may result in cerebral hypoperfusion and brain ischemia and contribute to dementia. It may also manifest as early symptoms of the neurodegenerative process associated with dementia. The relationship between the magnitude and timing of orthostatic BP responses and dementia risk is not fully understood., Methods: We conducted a prospective cohort analysis of the associations of orthostatic BP changes and self-reported orthostatic dizziness with the risk of dementia in the Atherosclerosis Risk in Communities study (ARIC). We calculated changes in BP from the supine to the standing position at 5 measurements taken within 2 minutes after standing during the baseline visit (1987-1989). The primary outcome was adjudicated dementia ascertained through 2019., Results: Among 11 644 participants (mean [SD] age, 54.5 [5.7] years; 54.1% women; 25.9% Black), 2303 dementia cases were identified during a median follow-up of 25.9 years. Large decreases in systolic BP from the supine to standing position measured at the first 2 measurements ≈30 and 50 seconds after standing, but not afterward, were associated with orthostatic dizziness and a higher risk of dementia. Comparing a decrease in systolic BP of ≤-20 or >-20 to -10 mm Hg to stable systolic BP (>-10 to 10 mm Hg) at the first measurement, the adjusted hazard ratios were 1.22 (95% CI, 1.01-1.47) and 1.10 (95% CI, 0.97-1.25), respectively., Conclusions: Abnormal orthostatic BP regulation, especially abrupt drops in BP within the first minute, might be early risk markers for the development of dementia. Transient early orthostatic hypotension warrants more attention in clinical settings., Competing Interests: Disclosures None.

Background: Management of orthostatic hypotension (OH) prioritizes prevention of standing hypotension, sometimes at the expense of supine hypertension. It is unclear whether supine hypertension is associated with adverse outcomes relative to standing hypotension., Objectives: To compare the long-term clinical consequences of supine hypertension and standing hypotension among middle-aged adults with and without OH., Methods: The ARIC study (Atherosclerosis Risk in Communities) measured supine and standing blood pressure (BP) in adults aged 45 to 64 years, without neurogenic OH, between 1987 and 1989. We defined OH as a positional drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg, supine hypertension as supine BP≥140/≥90 mm Hg, and standing hypotension as standing BP≤105/≤65 mm Hg. Participants were followed for >30 years. We used Cox regression models to examine associations with cardiovascular disease events, all-cause mortality, falls, and syncope., Results: Of 12 489 participants (55% female, 26% Black, mean age 54 years, SD 6), 4.4% had OH. Among those without OH (N=11 943), 19% had supine hypertension and 21% had standing hypotension, while among those with OH (N=546), 58% had supine hypertension and 38% had standing hypotension. Associations with outcomes did not differ by OH status ( P -interactions >0.25). Supine hypertension was associated with heart failure (hazard ratio, 1.83 [95% CI, 1.68-1.99]), falls (hazard ratio, 1.12 [95% CI, 1.02-1.22]), and all-cause mortality (hazard ratio, 1.45 [95% CI, 1.37-1.54]), while standing hypotension was only significantly associated with mortality (hazard ratio, 1.06 [95% CI, 1.00-1.14])., Conclusions: Supine hypertension was associated with higher risk of adverse events than standing hypotension, regardless of OH status. This challenges conventional OH management, which prioritizes standing hypotension over supine hypertension., Competing Interests: Disclosures None.

The benefits of plant-based diets may depend on the type of plant. To determine the associations of healthy and unhealthy plant-based diet types on risk of hospitalization with respiratory infections or any infection, we used dietary intake data reported in a food frequency questionnaire from the Atherosclerosis Risk in Communities Study to calculate a plant-based diet index (PDI), a healthy PDI (HPDI), and an unhealthy PDI (UPDI). Cox regression was used to calculate hazard ratios for the associations of the three plant-based diet indices with the risk of hospitalization with respiratory infections and any infection-related hospitalization. Comparing the highest to lowest quintiles, HPDI was associated with a lower risk of hospitalization with respiratory infections (HR 0.86, 95% CI: 0.75, 0.99), and a lower risk of hospitalization with any infections (HR 0.87, 95% CI: 0.78, 0.97). The PDI was associated with a lower risk of hospitalization with any infections (HR 0.86, 95% CI: 0.76, 0.96). Significant associations were not observed with the UPDI. Adults with a high PDI and HPDI had a lower risk of hospitalization with any infections, whereas adults with a high HPDI had lower risk of hospitalizations with respiratory infections.

Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post-hoc analysis of the DASH-losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American diet (control) and in crossover fashion to 4-week losartan or placebo. Serum urate was measured at baseline and after each 4-week period. Diets were designed to maintain weight constant. We examined the effects of DASH (vs control) and/or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Of 55 participants (mean age 52 years, 58% women, 64% Black), mean (±SD) baseline ambulatory SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. The DASH diet did not significantly reduce urate levels overall (mean difference -0.05 mg/dL; 95%CI: -0.39, 0.28), but did decrease levels among participants with baseline hyperuricemia (-0.33 mg/dL; 95%CI: -0.87, 0.21; P-interaction=0.007 across hyperuricemia groups). Losartan significantly decreased serum urate (-0.23 mg/dL; 95%CI: -0.40, -0.05) with greater effects on serum urate among adults <60 years old versus adults ≥60 years old (-0.33 mg/dL vs 0.16 mg/dL, P interaction = 0.003). In summary, the DASH diet significantly decreased serum urate among participants with higher urate at baseline, while losartan significantly reduced serum urate, especially among younger adults. Future research should examine the effects of these interventions in patients with hyperuricemia or gout., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: The associations of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) with dual energy x-ray absorptiometry (DEXA)-derived measures of body mass and composition are largely unknown., Methods: We included participants aged ≥20 years from the 1999-2004 National Health and Nutrition Examination Survey with NT-pro-BNP and DEXA-derived body composition (fat and lean mass) measures. We used linear and logistic regression to characterize the associations of measures of body mass and composition (body mass index [BMI], waist circumference [WC], fat mass, and lean mass) with NT-pro-BNP, adjusting for cardiovascular risk factors., Results: We conducted sex-specific analyses among 9134 adults without cardiovascular disease (mean age 44.4 years, 50.8% women, and 72% White adults). The adjusted mean NT-proBNP values were lowest in the highest quartiles of BMI, WC, fat mass, and lean mass. There were large adjusted absolute differences in NT-pro-BNP between the highest and lowest quartiles of DEXA-derived lean mass, -6.26 pg/mL (95% confidence interval [CI], -8.99 to -3.52) among men and -22.96 pg/mL (95% CI, -26.83 to -19.09) among women. Lean mass exhibited a strong inverse association with elevated NT-pro-BNP ≥ 81.4 pg/mL (highest quartile) - odds ratio (OR) 0.58 (95% CI, 0.39-0.86) in men and OR 0.59 (95% CI, 0.47-0.73) in women for highest lean mass quartile vs. lowest quartile. Further adjustment for fat mass, BMI, or WC did not appreciably alter the inverse association of lean mass with NT-pro-BNP., Conclusions: In a national sample of US adults, lean mass was inversely associated with NT-pro-BNP., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Disclosures None.

Hypertension is among the most prevalent medical conditions globally and a major contributor to chronic kidney disease, cardiovascular disease, and death. Prevention through nonpharmacological, population-level interventions is critically needed to halt this worldwide epidemic. However, there are ongoing disagreements as to where public policy efforts should focus. Recently the Salt Substitute and Stroke Study demonstrated the efficacy of substituting table salt with potassium salt to reduce the risk of stroke, major cardiovascular events, and death. However, this sparked debate over whether sodium or potassium should be prioritized in countries where table salt substitution was less feasible. In this commentary, we summarize arguments in favor of either strategy: reduced sodium or increased potassium intake. Moreover, we discuss evidence and policy approaches related to either or combined approaches relevant to cultural context. Ultimately, there is an urgent need for policies that both reduce sodium and increase potassium intake; however, identifying a strategy that fits cultural context will be key to improve population-wide blood pressures.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) is strongly associated with mortality in patients with heart failure. Prior studies, primarily in middle-aged and older populations, have suggested that NT-proBNP has prognostic value in ambulatory adults. Methods and Results We conducted a prospective cohort analysis of adults, aged ≥20 years, in the nationally representative 1999 to 2004 National Health and Nutrition Examination Survey, to characterize the association of NT-proBNP with mortality in the general US adult population overall and by age, race and ethnicity, and body mass index. We used Cox regression to characterize associations of NT-proBNP with all-cause and cardiovascular disease (CVD) mortality through 2019, adjusting for demographics and cardiovascular risk factors. We included 10 645 individuals (mean age, 45.7 years; 50.8% women; 72.8% White adults; 8.5% with a self-reported history of CVD). There were 3155 deaths (1009 CVD-related) over a median 17.3 years of follow-up. Among individuals without prior CVD, elevated NT-proBNP (≥75th percentile [81.5 pg/mL] versus <25th percentile [20.5 pg/mL]) was associated with a significantly higher risk of all-cause (hazard ratio [HR], 1.67 [95% CI, 1.39-2.00]) and CVD mortality (HR, 2.87 [95% CI, 1.61-5.11]). Associations of NT-proBNP with all-cause and CVD mortality were generally similar across subgroups defined by age, sex, race and ethnicity, or body mass index (all P interaction >0.05). Conclusions In a representative sample of the US adult population, NT-proBNP was an important independent risk factor for all-cause and CVD mortality. NT-proBNP may be useful for monitoring risk in the general adult population.

Background: We recently demonstrated that more intensive blood pressure (BP) treatment lowered risk of orthostatic hypotension (OH) measured with a seated-to-standing protocol. However, seated-to-standing OH assessments are less sensitive than supine-to-standing and could miss clinically relevant OH., Objectives: Using data from the Syst-Eur trial (Systolic Hypertension in Europe), we examined the effect of hypertension treatment on incidence of OH based on the difference in BP from 3 body positions., Methods: Syst-Eur was a multi-center, randomized trial that enrolled adults with isolated systolic hypertension to investigate whether active hypertension treatment could reduce cardiovascular events. Participants underwent BP measurement in supine, seated, and standing positions. Using differences in BP between the 3 body positions (seated minus supine, standing minus seated, and standing minus supine), we defined OH as a drop in systolic BP ≥20 mm Hg or diastolic BP ≥10 mm Hg. We included measurements from baseline and follow-up visits., Results: Among 4695 participants (mean age, 70.2±6.7 years; 66.9% female) with 42 636 BP measurements, OH was present in 4.9% of measures with supine-to-seated, 7.9% with seated-to-standing, and 11.4% with supine-to-standing protocols, respectively. Compared with placebo, BP treatment did not increase OH with any set of maneuvers, OR, 0.79 (95% CI, 0.65-0.95) with seated-to standing, 1.03 (95% CI, 0.86-1.24) with supine-to-seated, and 0.99 (95% CI, 0.86-1.15) with supine-to-standing., Conclusions: Regardless of protocol, active hypertension treatment did not increase the risk of OH, reinforcing evidence that OH should not be viewed as a complication of hypertension treatment., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02088450.

Background Hypertension is an important modifiable risk factor of serious maternal morbidity and mortality. Social determinants of health (SDoH) influence hypertension outcomes and may contribute to racial and ethnic differences in hypertension control. Our objective was to assess SDoH and blood pressure (BP) control by race and ethnicity in US women of childbearing age with hypertension. Methods and Results We studied women (aged 20-50 years) with hypertension (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg or use of antihypertensive medication) in the National Health and Nutrition Examination Surveys 2001 to 2018. SDoH and BP control (systolic BP <140 mm Hg and diastolic BP <90 mm Hg) were examined by race and ethnicity (White race, Black race, Hispanic ethnicity, and Asian race). Using multivariable logistic regression, odds of uncontrolled BP by race and ethnicity were modeled, adjusting for SDoH, health factors, and modifiable health behaviors. Responses on hunger and affording food determined food insecurity status. Across women of childbearing age with hypertension (N=1293), 59.2% were White race, 23.4% were Black race, 15.8% were Hispanic ethnicity, and 1.7% were Asian race. More Hispanic and Black women experienced food insecurity than White women (32% and 25% versus 13%; both P <0.001). After SDoH, health factor, and modifiable health behavior adjustment, Black women maintained higher odds of uncontrolled BP than White women (odds ratio, 2.31 [95% CI, 1.08-4.92]), whereas Asian and Hispanic women showed no difference. Conclusions We identified racial inequities in uncontrolled BP and food insecurity among women of childbearing age with hypertension. Further exploration beyond the SDoH measured is needed to understand the inequity in hypertension control in Black women.

Introduction: Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty and possibly modified by chronic inflammation-a pathway often underlying frailty-remains unexplored., Methods: Using the Study to Understand Fall Reduction and Vitamin D in You data from 477 robust/prefrail adults (mean age = 76 ± 5 yr; 42% women), we examined whether accelerometer patterns (activity counts per day, active minutes per day, and activity fragmentation [broken accumulation]) were associated with incident frailty using Cox proportional hazard regression. Baseline interactions between each accelerometer metric and markers of inflammation that include interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor 1 were also examined., Results: Over an average of 1.3 yr, 42 participants (9%) developed frailty. In Cox regression models adjusted for demographics, medical conditions, and device wear days, every 30 min·d -1 higher baseline active time, 100,000 more activity counts per day, and 1% lower activity fragmentation was associated with a 16% ( P = 0.003), 13% ( P = 0.001), and 8% ( P < 0.001) lower risk of frailty, respectively. No interactions between accelerometer metrics and baseline interleukin-6, C-reactive protein, or tumor necrosis factor-alpha receptor 1 were detected (interaction P > 0.06 for all)., Conclusions: Among older adults who are either robust or prefrail, constricted patterns of daily physical activity (i.e., lower total activity minutes and counts, and higher activity fragmentation) were prospectively associated with higher risk of frailty but not modified by frailty-related chronic inflammation. Additional studies, particularly trials, are needed to understand if this association is causal., (Copyright © 2022 by the American College of Sports Medicine.)

Background The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce biomarkers of cardiovascular disease. We aimed to characterize the time course of change in biomarkers of cardiac injury (high-sensitivity cardiac troponin I), cardiac strain (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and inflammation (hs-CRP [high-sensitivity C-reactive protein]) while consuming the DASH diet. Methods and Results The DASH-Sodium trial was a randomized controlled trial of 412 adults with elevated blood pressure or hypertension. Participants were randomly assigned to 12 weeks of the DASH diet or a typical American diet. Energy intake was adjusted to maintain body weight. Measurements of high-sensitivity cardiac troponin I, NT-proBNP, and hs-CRP were performed in stored serum specimens, collected at baseline and ≈4, 8, and 12 weeks after randomization. In both the control diet and DASH diet, levels of NT-proBNP decreased; however, there was no difference between diets ( P -trend compared with control=0.22). On the DASH diet versus control, levels of high-sensitivity cardiac troponin I decreased progressively during follow-up ( P- trend compared with control=0.025), but a statistically significant between-diet difference in change from baseline levels was not observed until week 12 (% difference, 17.78% [95% CI, -29.51% to -4.09%]). A similar pattern was evident for hs-CRP ( P- trend compared with control=0.01; % difference at week 12, 19.97% [95% CI, -31.94% to -5.89%]). Conclusions In comparison with a typical American diet, the DASH diet reduced high-sensitivity cardiac troponin I and hs-CRP progressively over 12 weeks. These results suggest that the DASH diet has cumulative benefits over time on biomarkers of subclinical cardiac injury and inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000608.

Cuff-based home blood pressure (BP) devices, which have been the standard for BP monitoring for decades, are limited by physical discomfort, convenience, and their ability to capture BP variability and patterns between intermittent readings. In recent years, cuffless BP devices, which do not require cuff inflation around a limb, have entered the market, offering the promise of continuous beat-to-beat measurement of BP. These devices take advantage of a variety of principles to determine BP, including (1) pulse arrival time, (2) pulse transit time, (3) pulse wave analysis, (4) volume clamping, and (5) applanation tonometry. Because BP is calculated indirectly, these devices require calibration with cuff-based devices at regular intervals. Unfortunately, the pace of regulation of these devices has failed to match the speed of innovation and direct availability to patient consumers. There is an urgent need to develop a consensus on standards by which cuffless BP devices can be tested for accuracy. In this narrative review, we describe the landscape of cuffless BP devices, summarize the current status of validation protocols, and provide recommendations for an ideal validation process for these devices., (© 2023 Published by Elsevier Inc. on behalf of Heart Rhythm Society.)

Importance: Clinical 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., Objective: To investigate the association of endogenous subclinical thyroid dysfunction and fracture risk, independent of clinical confounders., Design, Setting, and Participants: This 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., Exposures: Thyrotropin 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 Measures: Incident fracture was ascertained using hospitalization discharge codes through 2019 and linkage to inpatient and outpatient Medicare claims through 2018., Results: Of 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 Relevance: This 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.

Orthostatic hypotension affects roughly 10% of individuals with hypertension and is associated with several adverse health outcomes, including dementia, cardiovascular disease, stroke, and death. Among adults with hypertension, orthostatic hypotension has also been shown to predict patterns of blood pressure dysregulation that may not be appreciated in the office setting, including nocturnal nondipping. Individuals with uncontrolled hypertension are at particular risk of orthostatic hypotension and may meet diagnostic criteria for the condition with a smaller relative reduction in blood pressure compared with normotensive individuals. Antihypertensive medications are commonly de-prescribed to address orthostatic hypotension; however, this approach may worsen supine or seated hypertension, which may be an important driver of adverse events in this population. There is significant variability between guidelines for the diagnosis of orthostatic hypotension with regards to timing and position of blood pressure measurements. Clinically relevant orthostatic hypotension may be missed when standing measurements are delayed or when taken after a seated rather than supine position. The treatment of orthostatic hypotension in patients with hypertension poses a significant management challenge for clinicians; however, recent evidence suggests that intensive blood pressure control may reduce the risk of orthostatic hypotension. A detailed characterization of blood pressure variability is essential to tailoring a treatment plan and can be accomplished using both in-office and out-of-office monitoring.

Background Limited data exist on the benefits of lifestyle behavior change delivered using telehealth and web-based applications with varied support on blood pressure (BP). Methods and Results We conducted a 2-site randomized controlled trial at Geisinger (January 2019-March 2021) to compare the efficacy of 2 remotely delivered strategies using web-based applications in participants with 24-hour systolic BP 120-160 mm Hg and body mass index ≥25 kg/m 2 . Both arms received access to web-based applications and the same lifestyle guidance per American Heart Association guidelines. One arm received minimal nonclinical staff support, and the other arm received dietitian support with motivational interviewing during weekly calls. The primary outcome was 12-week change in 24-hour systolic BP. A total of 187 participants were randomly assigned, with 156 (83.4%) completing the trial. In both arms, 24-hour systolic BP was reduced at follow-up, but the difference in BP change was not significant (dietitian-led arm, -6.73 mm Hg [95% CI, -8.64 to -4.82]; minimal-support arm, -4.92 [95% CI, -7.01 to -2.77]; P comparing groups=0.2). The dietitian-support arm had greater 12-week improvements in the secondary outcomes sleep systolic BP (mean, -6.92 versus -1.45; P =0.004), sleep diastolic BP (-3.31 versus 0.73; P =0.001), and self-reported physical activity (866 versus -243 metabolic equivalent task minutes per week; P =0.01) and tended to have improvements in weight loss (-5.11 versus -3.89 kg; P =0.1) and Healthy Eating Index-2015 score (9.23 versus 6.43 units; P =0.09). Conclusions Both the dietitian- and minimal-support interventions reduced 24-hour systolic BP similarly, although the dietitian-led intervention led to greater improvements in several secondary cardiometabolic outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03700710.

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 <25 kg/m 2 (P-interaction = 0.01). Vitamin E was not associated with new gout diagnoses (HR: 1.05; 95% CI: 0.92, 1.19; P = 0.48)., Conclusions: Vitamin C modestly reduced the risk of new gout diagnoses in middle-aged male physicians. Additional research is needed to determine the effects of higher doses of vitamin C supplementation on serum urate and gout flares in adults with established gout.The Physicians' Health Study II is registered at clinicaltrials.gov (identifier: NCT00270647)., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background Short chain fatty acids (SCFAs) are microbially derived end products of dietary fiber fermentation. The SCFA butyrate reduces blood pressure (BP) in mouse models. The association of SCFAs, including butyrate, with BP in humans is unclear, due in part to predominantly cross-sectional analyses and different biospecimens (blood versus fecal) for SCFA measurement. Longitudinal studies including both circulating and fecal SCFAs are lacking. Methods and Results We leveraged existing data from the SPIRIT (Survivorship Promotion In Reducing IGF-1 Trial), which randomized 121 adult cancer survivors with overweight/obesity to a behavioral weight-loss intervention, metformin, or self-directed weight-loss. Of participants with baseline serum and fecal SCFAs measured (n=111), a subset had serum (n=93) and fecal (n=89) SCFA measurements 12 months later. We used Poisson regression with robust error variance to estimate baseline associations of SCFAs with hypertension, and we assessed the percent change in SCFAs from baseline with corresponding 12-month changes in BP using multiple linear regression. Baseline fecal butyrate was inversely associated with prevalent hypertension (standardized PR [95%CI]: 0.71 [0.54, 0.92]). A 10% increase in fecal butyrate from baseline was associated with decreased systolic BP (β [95%CI]: -0.56 [-1.01, -0.10] mm Hg), and a 10% increase in serum butyrate was associated with decreased systolic (β [95%CI]: -1.39 [-2.15, -0.63] mm Hg) and diastolic (β [95%CI]: -0.55 [-1.03, -0.08] mm Hg) BPs. Butyrate associations with systolic BP were linear and not modified by sex, race, or intervention arm. Conclusions Increased serum or fecal butyrate is associated with lowered BP. Butyrate may be a target for SCFA-centered BP-lowering interventions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02431676.

Context: The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a randomized trial enrolling older adults with low 25-hydroxyvitamin D [25(OH)D], demonstrated vitamin D supplementation ≥ 1000 IU/day did not prevent falls compared with 200 IU/day, with doses ≥ 2000 IU/day potentially showing safety concerns., Objective: To examine associations of achieved and change in 25(OH)D concentrations after 3 months of vitamin D supplementation with fall risk., Design: Observational analysis of trial data., Setting: General community., Participants: A total of 637 adults aged ≥ 70 with baseline 25(OH)D concentrations 10 to 29 ng/mL and elevated fall risk. Three-month on-treatment absolute 25(OH)D; absolute and relative changes from baseline., Main Outcome Measures: Incident first fall (primary) and first consequential fall (injury or sought medical care) up to 24 months. Cox models were adjusted for sociodemographics, season, Short Physical Performance Battery, and body mass index., Results: At baseline, mean (SD) age was 77.1 (5.4) years and 25(OH)D was 22.1 (5.1) ng/mL; 43.0% were women and 21.5% non-White. A total of 395 participants experienced ≥ 1 fall; 294 experienced ≥ 1 consequential fall. There was no association between absolute achieved 25(OH)D and incident first fall (30-39 vs < 30 ng/mL hazard ratio [HR], 0.93; 95% CI, 0.74-1.16; ≥40 vs < 30 ng/mL HR, 1.09; 95% CI, 0.82-1.46; adjusted overall P  = 0.67), nor absolute or relative change in 25(OH)D. For incident consequential first fall, the HR (95% CI) comparing absolute 25(OH)D ≥ 40 vs < 30 ng/mL was 1.38 (0.99-1.90)., Conclusion: Achieved 25(OH)D concentration after supplementation was not associated with reduction in falls. Risk of consequential falls may be increased with achieved concentrations ≥ 40 ng/mL., Trial Registration: ClinicalTrials.gov: NCT02166333., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

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 ., (© 2022. The Author(s).)

In this cross-sectional population-based study, we used the baseline data of the Prospective Epidemiologic Research Studies in IrAN cohort study collected in Iran from 2014 to 2020. The main outcomes were the prevalence of hypertension and proportion of awareness, treatment, and control based on the 2017 ACC/AHA guideline compared to the seventh report of the Joint National Committee (JNC7). Of the total of 163,770 participants, aged 35-70 years, 55.2% were female. The sex-age standardized prevalence of hypertension was 22.3% (95% CI 20.6, 24.1) based on the JNC7 guideline and 36.5% (31.1, 41.8) based on the ACC/AHA guideline. A total of 24,312 participants [14.1% (10.1, 18.1)] were newly diagnosed based on the ACC/AHA guideline. Compared to adults diagnosed with hypertension based on the JNC7 guideline, the newly diagnosed participants were mainly young literate males who had low levels of risk factors and were free from conventional comorbidities of hypertension. About 30.7% (25.9, 35.4) of them (4.3% of the entire population) were eligible for pharmacologic intervention based on the ACC/AHA guideline. Implementation of the new guideline may impose additional burden on health systems. However, early detection and management of elevated blood pressure may reduce the ultimate burden of hypertension in Iran., (© 2022. The Author(s).)

Background: Understanding health care experiences during the COVID-19 pandemic may provide insights into patient needs and inform policy. The objective of this study was to describe health care experiences by race and social determinants of health., Methods: We conducted a telephone survey (July 6, 2020-September 4, 2021) among 9492 Black and White participants in the longitudinal REasons for Geographic And Racial Differences in Stroke cohort study, age 58-105 years, from the continental United States. Among participants with symptoms of COVID-19, outcomes were: 1. Sought care or advice for the illness; 2. Received a SARS-CoV-2 test for the illness; and 3. Tested positive. Among participants without symptoms of COVID-19, outcomes were: 1. Wanted a test; 2. Wanted and received a test; 3. Did not want but received a test; and 4. Tested positive. We examined these outcomes overall and in subgroups defined by race, household income, marital status, education, area-level poverty, rural residence, Medicaid expansion, public health infrastructure ranking, and residential segregation., Results: The average age of participants was 76.8 years, 36% were Black, and 57% were female. Among participants with COVID-19 symptoms (n = 697), 74% sought care or advice for the illness, 50% received a SARS-CoV-2 test, and 25% had a positive test (50% of those tested). Among participants without potential COVID-19 symptoms (n = 8795), 29% wanted a SARS-CoV-2 test, 22% wanted and received a test, 8% did not want but received a test, and 1% tested positive; a greater percentage of participants who were Black compared to White wanted (38% vs 23%, p < 0.001) and received tests (30% vs 18%, p < 0.001) and tested positive (1.4% vs 0.8%, p = 0.005)., Conclusions: In this national study of older US adults, many participants with potential COVID-19 symptoms and asymptomatic participants who desired testing did not receive COVID-19 testing., (© 2021. The Author(s).)

[Figure: see text].

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) < 60 mL/min/1.73m 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/1.73m 2 , but a positive correlation among those with eGFR < 60 mL/min/1.73m 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/1.73m 2 Future research should examine the relationship between osmolality and change in kidney function over time among adults with normal eGFR., (© 2021. The Author(s).)

Background Although disproportionately affected by cardiovascular disease, Black adults remain underrepresented in clinical trials. The National Institutes of Health recommends that studies define goals for recruitment of underrepresented populations. However, the extent to which cardiovascular trials incorporate evidence-based recruitment strategies in their protocols is understudied. Methods and Results We systematically reviewed National Institutes of Health-funded cardiovascular clinical trials registered in ClinicalTrials.gov between 2000 and 2019. Based on publicly available or requested protocols, we focused on enrollment of Black adults as well as the following recruitment strategies: community-based, electronic medical record-based, and provider-based recruitment. A total of 100 clinical trials focused on cardiovascular disease were included in our analysis, of which 62% had published protocols, and 46% of trials had enrolled populations that were <25% Black. In our analysis of available trial protocols, 21% of trials defined a recruitment target for underrepresented groups; however, only one study reported achieving its enrollment goal. While 13% of trial protocols referenced community-based recruitment strategies, 5% explicitly mentioned involving community members in the trial design process. Defining recruitment targets was associated with higher enrollment of Black participants. Conclusions Black adults are underrepresented in National Institutes of Health-funded cardiovascular trials, and the majority of these trials did not specify a Black enrollment target, did not meet targets, and largely did not report specific plans to enroll Black adults in their studies. Future interventions should target trial design and planning phases before study initiation to address these enrollment disparities.

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., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

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) <100 mmHg. The primary outcome was 24 h ambulatory systolic BP. The higher-versus lower-K diet had no significant effect on 24 h 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 h 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/m 2 , 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/m 2 (95% confidence interval (CI): -1.5, -0.4) and metformin reduced BMI by 0.6 kg/m 2 (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.

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 < 0.001) included daily peak gait speed averaged over the preceding 30 days (r = 0.63) and root mean square of the successive differences of daily distance averaged over 365 days (r = 0.57). The best-performing multivariable regression model included the latter variable, as well as age and body mass index. This model explained 68% of variability in observed METs (95% CI 46%, 81%), and estimated peak METs with a bootstrapped mean absolute error of 1.28 METs (95% CI 0.98, 1.60). Our model using smartphone physical activity estimated cardiorespiratory fitness with high performance. Our results suggest larger, independent samples might yield estimates accurate and precise for risk stratification and disease prognostication., (© 2021. The Author(s).)

Objective: To determine the longer-term effects of metformin treatment and behavioral weight loss on gut microbiota and short-chain fatty acids (SCFAs)., Research Design and Methods: We conducted a 3-parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them ( n = 121) to either 1 ) metformin (up to 2,000 mg), 2 ) coach-directed behavioral weight loss, or 3 ) self-directed care (control) for 12 months. We collected stool and serum at baseline ( n = 114), 6 months ( n = 109), and 12 months ( n = 105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum., Results: Of the 121 participants, 79% were female and 46% were Black, and the mean age was 60 years. Only metformin treatment significantly altered microbiota composition. Compared with control, metformin treatment increased amplicon sequence variants for Escherichia (confirmed as Escherichia coli by metagenomic sequencing) and Ruminococcus torques and decreased Intestinibacter bartlettii at both 6 and 12 months and decreased the genus Roseburia , including R. faecis and R. intestinalis, at 12 months. Effects were similar in comparison of the metformin group with the behavioral weight loss group. Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months). Behavioral weight loss versus control did not significantly alter microbiota composition but did increase acetate at 6 months (but not at 12 months). Increases in acetate were associated with decreases in fasting insulin. Additional whole-genome metagenomic sequencing of a subset of the metformin group showed that metformin altered 62 metagenomic functional pathways, including an acetate-producing pathway and three pathways in glucose metabolism., Conclusions: Metformin, but not behavioral weight loss, impacted gut microbiota composition at 6 months and 12 months. Both metformin and behavioral weight loss altered circulating SCFAs at 6 months, including increasing acetate, which correlated with lower fasting insulin. Future research is needed to elucidate whether the gut microboime mediates or modifies metformin's health effects., (© 2021 by the American Diabetes Association.)

Background: 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., Objectives: 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., Methods: 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., Results: 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., Conclusions: 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)., Competing Interests: Funding Support and Author Disclosures The measurement of cardiac biomarkers was supported by the National Institutes of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) R21HL144876. The original DASH trial was supported by grants (HL50981, HL50968, HL50972, HL50977, HL50982, HL02642, RR02635, and RR00722) from the NHLBI, the Office of Research on Minority Health, and the National Center for Research Resources of the NIH. Siemens (Siemens Healthineers, Malvern, Pennsylvania) donated test assays and kits for the 3 cardiac biomarkers measured in this study. Dr. Juraschek is supported by a NIH/NHLBI K23HL135273. The funding source of the present study played no role in the study’s design, conduct, analysis, and decision to submit the manuscript for publication. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Prescription stimulants are an important cause of secondary hypertension and their use is increasing in adult patients who are also at risk for essential hypertension. Although stimulants increase blood pressure, a systematic approach for assessing their impact in individual patients is lacking. We developed a protocol using ambulatory blood pressure monitoring for up to 36 h to compare blood pressure over two sequential days. Average blood pressure on the first day (without stimulant medication) was compared to average blood pressure on the second day (after re-starting stimulant medication). We describe the outcomes of this protocol for a case series of eleven adults. Patients demonstrated one of three outcomes: normal blood pressure on both days, hypertension on both days, or hypertension only on the day patients received their stimulant medications. This novel protocol provides valuable information on the blood pressure effects of stimulant medications and allows clinicians to make personalized decisions regarding treatment., (© 2021 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

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 <160 mm Hg and diastolic BP of 80-95 mm Hg, who were not receiving BP medications. Participants were randomized to receive 8 weeks of monitored feeding and ate 1 of 3 diets: 1) a typical American diet (control), 2) the FV diet, a diet rich in fruits and vegetables but otherwise similar to the control diet, or 3) the DASH diet, which was rich in fruits, vegetables, and low-fat dairy products, and reduced in fat, saturated fat, and cholesterol. Body weight was kept constant throughout the study. Serum urate levels were measured at baseline and after 8 weeks of feeding., Results: For the 327 participants with available specimens (mean ± SD age 45.4 ± 11.0 years, 47% women, 50% African American), the mean ± SD baseline serum urate level was 5.7 ± 1.5 mg/dl. Compared to the control diet, the FV diet reduced the mean serum urate level by 0.17 mg/dl (95% confidence interval [95% CI] -0.34, 0.00; P = 0.051) and the DASH diet reduced the mean serum urate level by 0.25 mg/dl (95% CI -0.43, -0.08; P = 0.004). These effects increased with increasing baseline serum urate levels (<5, 5-5.9, 6-6.9, 7-7.9, and ≥8 mg/dl) for those receiving the DASH diet (a reduction of 0.08, 0.12, 0.42, 0.44, and 0.73 mg/dl, respectively; P for trend = 0.04), but not for those receiving the FV diet., Conclusion: Our findings indicate that the DASH diet reduces serum urate levels, particularly among those with hyperuricemia. These findings support the growing need for a dedicated trial to test the DASH diet among patients with hyperuricemia and gout., (© 2020, American College of Rheumatology.)

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 (<0.95 vs. >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 4 November 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.

Introduction: Weight loss, consumption of a Dietary Approaches to Stop Hypertension dietary pattern, reduced sodium intake and increased physical activity have been shown to lower blood pressure (BP). Use of web-based tools and telehealth to deliver lifestyle counselling could be potentially scalable solutions to improve BP through behavioural modification though limited data exists to support these approaches in clinical practice., Methods and Analysis: This randomised controlled trial will compare the efficacy of a telehealth versus self-directed lifestyle intervention in lowering 24-hour SBP in patients with overweight/obesity (body mass index ≥25 kg/m 2 ) and 24-hour SBP 120-160 mm Hg. All participants receive personalised recommendations to improve dietary quality based on a web-based Food Frequency Questionnaire, access to an online comprehensive weight management programme and a smartphone dietary app. The telehealth arm additionally includes weekly calls with registered dietitian nutritionists who use motivational interviewing. The primary outcome is change from baseline to 12 weeks in 24-hour SBP. Secondary outcomes include changes from baseline in 24-hour diastolic BP, daytime SBP, nighttime SP, daytime diastolic BP, nighttime diastolic BP, total Healthy Eating Index-2015 score, weight, waist circumference and physical activity. Other prespecified outcomes will include change in individual components of the Healthy Eating Index-2015 score, and satisfaction with the Healthy BP research study measured on a 5-point Likert scale., Ethics and Dissemination: The study has been approved by the Geisinger Institutional Review Board. Results will be disseminated through peer-reviewed publications and conference presentations., Trial Registration Number: NCT03700710., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Elevated blood pressure and blood pressure-related morbidity are extraordinarily common in persons with diabetes. The Dietary Approaches to Stop Hypertension dietary pattern and dietary sodium reduction are recommended as lifestyle interventions in individuals with diabetes. However, these recommendations have largely been based on studies conducted in persons without diabetes. In this review, we summarize available evidence from trials that tested the effects of these 2 dietary interventions on blood pressure in people with diabetes. Overall, of the 3 trials (total n=151) that tested the effects of the Dietary Approaches to Stop Hypertension dietary pattern in persons with diabetes, 2 trials documented that the Dietary Approaches to Stop Hypertension dietary pattern lowered blood pressure. While 16 trials (total n=445) tested the effects of sodium reduction in persons with diabetes, results were inconsistent, likely because of design limitations, for example, brief duration, small sample size, and low baseline blood pressure levels, as well as differences in the mode of intervention delivery (behavioral interventions, feeding studies, and sodium supplements). In conclusion, there is a substantial need for additional research on the blood pressure lowering effects of the Dietary Approaches to Stop Hypertension diet and sodium reduction in people with diabetes and hypertension, given the high prevalence of hypertension and the dearth of high-quality trials in this population.

We evaluated the feasibility of using Computrition to design and implement a low vs. typical sodium meal plan intervention for older adults. Dietitians used Computrition to design a 7-day meal plan with three caloric levels (≤1750, 2000, ≥2250 kcals/day) and two sodium densities (low = 0.9 mg/kcal; n = 11 or typical = 2 mg/kcal; n = 9). Feasibility was determined by post-hoc definitions of effectiveness, sodium compliance, palatability of diet, sustainability, and safety. Given the low number of participants in one of the three calorie groups, the higher calorie groups were combined. Thus, comparisons are between low vs. typical meal plans at two calorie levels (≤1750 or ≥2000 kcals/day). Overall, regardless of the calorie group, the meal plans created with Computrition were effective in reaching the targeted sodium density and were safe for participants. Furthermore, individuals appeared to be equally compliant and reported similar palatability across meal plans. However, one of the three criteria for the sustainability definition was not met. In conclusion, we successfully used Computrition to design low and typical sodium meal plans that were effective, compliable, and safe. Future studies of older adults in similar settings should focus on improving the palatability of the meal plans and scaling this protocol to larger studies in older adults.