Pre-treatment bone mineral density (BMD) and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA). This study used data from a large set of randomised controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into femoral neck (FN) BMD T-score subgroups (≤ -2.5, > -2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ -2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ -2.5 and > -2.5 subgroups. Compared to those with FN BMD T-score > -2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ -2.5, but only the all fracture outcome reached statistical significance (interaction p = 0.001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all and all clinical fractures in the lower BMD quintiles (all interaction p ≤ 0.03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above -2.5, though effects tended to be larger and more significant in those with baseline T-scores <-2.5.

It is important to know whether our treatments for osteoporosis are effective at reducing the risk of fracture no matter what the bone mineral density (BMD) before starting treatment. This study used data from many clinical trials to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We found that anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD, though effects tended to be larger and more significant in those with lower BMD scores.

Comparison of a person-centered pregnancy prevention question and One Key Question to assess postpartum contraceptive needs.

OBJECTIVES: To explore the relevance of pregnancy intention as a screen for contraceptive needs among postpartum individuals. STUDY DESIGN: We surveyed 234 postpartum individuals to assess the alignment between pregnancy intentions in the next year and current desire to prevent pregnancy. RESULTS: Most individuals (87%) desired pregnancy prevention now, including 73% of individuals who desired or were ambivalent about pregnancy in the next year. CONCLUSION: A majority of individuals considering pregnancy in the next year desired pregnancy prevention now. Directly assessing current desire to prevent pregnancy may be more specific for contraceptive needs in postpartum individuals. IMPLICATIONS: Our ability to ensure that all individuals who want to prevent pregnancy have access to contraception depends on the use of effective screening questions. These findings prompt consideration of broader clinical implementation of screening for desire to prevent pregnancy in lieu of questions about pregnancy intention in the next year.

HIV Viral Suppression Among Psychiatric Inpatients with Schizophrenia in San Francisco: A Retrospective Cohort Study.

People with schizophrenia are at increased risk for contracting HIV and face higher mortality rates compared with the general population. Viral suppression is key to HIV care, yet little is known about this metric among people with HIV and schizophrenia. A chart review was conducted among people with HIV/AIDS and schizophrenia living in San Francisco who had received inpatient mental health services between 2010 and 2016. Demographic, laboratory, medication, encounter, and discharge data were collected, and were compared with all people living with HIV in San Francisco (PLWH-SF). Among 153 people living with HIV and comorbid schizophrenia, 77% were virally suppressed, compared to 67% for all PLWH-SF. Viral suppression for people with comorbid HIV and schizophrenia living in San Francisco appears higher than PLWH-SF. Further research is needed to confirm the association and mechanisms behind better treatment outcomes for people living with HIV and comorbid schizophrenia.

Anti-fracture treatment efficacy by age.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on bone mineral density (BMD) differ in people ≥70 compared to those <70 years. We used individual patient data from 23 RCTs of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. We assessed the following fractures: radiographic vertebral, non-vertebral, hip, all clinical and all fractures. We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes, logistic regression for the radiographic vertebral fracture outcome and linear regression to estimate treatment effect on 24-month change in hip and spine BMD in each age subgroup. The analysis included 123,164 (99% female) participants; 43% being ≥ 70 years. Treatment with anti-osteoporosis drugs significantly and similarly reduced fractures in both subgroups [e.g. OR = 0.47 and 0.51 for vertebral fractures in those below and above 70 years, interaction p = 0.19; HR for all fractures: 0.72 vs 0.70, interaction p = 0.20)]. Results were similar when limited to bisphosphonate trials with the exception of hip fracture risk reduction which was somewhat greater in those <70 (HR = 0.44) vs ≥70 (HR = 0.79) years (interaction p = 0.02). Allocation to anti-osteoporotic drugs resulted in significantly greater increases in hip and spine BMD at 24 months in those >70 compared to those <70 years. In summary, anti-osteoporotic medications similarly reduced the risk of fractures regardless of age and the few small differences in fracture risk reduction by age were of uncertain clinical significance.

Medications used for osteoporosis maybe are less effective in older adults. This study used data from clinical trials to determine whether these medications work equally well in reducing the risk of fractures in people ≥70 compared to those <70 years. The analysis included 123,164 participants with data from 23 trials. Treatment with anti-osteoporosis drugs significantly reduced fractures in both groups in a similar way. The bone mineral density increased more in the older group.

Changes in alcohol consumption during the COVID-19 pandemic: a longitudinal cohort study using smart-breathalyzer data.

Previous studies relying on alcohol sales, alcohol-related injuries, and surveys have suggested that alcohol consumption increased during the COVID-19 pandemic. We sought to leverage over 1 million Breath Alcohol Concentration (BrAC) measurements from Bluetooth-enabled breathalyzers to conduct an objective and longitudinal assessment of alcohol use during the pandemic. Serial BrAC measurements revealed a decrease in drinking between January 1, 2020 and March 30, 2020, an increase between March 30, 2020 and May 25, 2020, a statistically insignificant decrease between May 25, 2020 and January 1, 2021, and an increase again between January 1, 2021 and June 4, 2021. No statistically significant relationships between shelter-in-place orders and alcohol consumption were detected. These findings demonstrate the complex relationship between the pandemic and alcohol consumption patterns, providing insights that may be relevant to the use of this commonly consumed substance with implications relevant to long-term effects from the patterns observed.

Acute alcohol exposure and electrocardiographic changes: Finding from the HOLIDAY trial.

BACKGROUND: Alcohol consumption is associated with a higher increased risk of atrial fibrillation (AF), but the acute effects on cardiac electrophysiology in humans remain poorly understood. The HOw ALcohol InDuces Atrial TachYarrhythmias (HOLIDAY) Trial revealed that alcohol shortened pulmonary vein atrial effective refractory periods, but more global electrophysiologic changes gleaned from the surface ECG have not yet been reported. METHODS: This was a secondary analysis of the HOLIDAY Trial. During AF ablation procedures, 100 adults were randomized to intravenous alcohol titrated to 0.08% blood alcohol concentration versus a volume and osmolarity-matched, masked, placebo. Intervals measured from 12­lead ECGs were compared between pre infusion and at infusion steady state (20 min). RESULTS: The average age was 60 years and 11% were female. No significant differences in the P-wave duration, PR, QRS or QT intervals, were present between alcohol and placebo arms. However, infusion of alcohol was associated with a statistically significant relative shortening of the JT interval (r: -14.73, p = 0.048) after multivariable adjustment. CONCLUSION: Acute exposure to alcohol was associated with a relative reduction in the JT interval, reflecting shortening of ventricular repolarization. These acute changes may reflect a more global shortening of refractoriness, suggesting immediate proarrhythmic effects pertinent to the atria and ventricles.

Bisphosphonate Use and Risk of Atypical Femoral Fractures: A Danish Case Cohort Study with Blinded Radiographic Review.

CONTEXT: Prolonged bisphosphonate (BP) treatment for osteoporosis prevents hip and other fractures but causes atypical femoral fractures (AFF). OBJECTIVE: To establish the relationship between patterns of BP use and the risk of AFF and hip fractures. Other potential risk factors for AFF were also examined. DESIGN: Population-based case-cohort study. SETTING: The Danish National Healthcare system maintains longitudinal records of medication use, healthcare utilization, and x-ray images. PARTICIPANTS: Among all 1.9 million Danish adults ≥50, those with subtrochanteric or femoral shaft fractures between 2010-2015 (n = 4,973) were identified and compared to a random sample (n = 37,021). PREDICTORS: Bisphosphonate use was collected from 1995-2015. MAIN OUTCOME MEASURES: Fracture radiographs (n = 4,769) were reviewed by blinded study radiologists to identify AFFs (n = 181) using established criteria. Traditional hip fractures in the random sample (n = 691) were identified by ICD-10. RESULTS: Compared to <1 year of BP use, 5-7 years of use was associated with a 7-fold increase in AFF [adjusted HR = 7.29 (CI: 3.07,17.30)]; the risk of AFF fell quickly after discontinuation. The 5-year number-needed-to-harm for one AFF was 1,424, while the 5-year number-needed-to-treat to prevent one hip fracture was 56. Glucocorticoid and proton pump inhibitor use were independently associated with increased AFF risk. Thirty-one percent of those with AFF had no BP exposure. CONCLUSIONS: The risk of AFF increases with duration of BP use but the beneficial effects of BP therapy in adults ≥50 dramatically exceed this increased risk. Nearly one-third of those with AFF have no BP exposure.

TV Viewing From Young Adulthood to Middle Age and Cardiovascular Disease Risk.

INTRODUCTION: Few studies have longitudinally examined TV viewing trajectories and cardiovascular disease risk factors. The objective of this study was to determine the association between level and annualized changes in young adult TV viewing and the incidence of cardiovascular disease risk factors from young adulthood to middle age. METHODS: In 2023, prospective community-based cohort data of 4,318 Coronary Artery Risk Development in Young Adults study participants (1990-1991 to 2015-2016) were analyzed. Individualized daily TV viewing trajectories for each participant were developed using linear mixed models. RESULTS: Every additional hour of TV viewing at age 23 years was associated with higher odds of incident hypertension (AOR=1.16; 95% CI=1.11, 1.22), diabetes (AOR=1.19; 95% CI=1.11, 1.28), high triglycerides (AOR=1.17; 95% CI=1.08, 1.26), dyslipidemia (AOR=1.10; 95% CI=1.03, 1.16), and obesity (AOR=1.12; 95% CI=1.06, 1.17). In addition, each hourly increase in daily TV viewing was associated with higher annual odds of incident hypertension (AOR=1.26; 95% CI=1.16, 1.37), low high-density lipoprotein cholesterol (AOR=1.15; 95% CI=1.03, 1.30), high triglycerides (AOR=1.32; 95% CI=1.15, 1.51), dyslipidemia (AOR=1.22; 95% CI=1.11, 1.34), and obesity (AOR=1.17; 95% CI=1.07, 1.27) over the follow-up period. CONCLUSIONS: In this prospective cohort study, higher TV viewing in young adulthood and annual increases in TV viewing were associated with incident hypertension, high triglycerides, and obesity. Young adulthood as well as behaviors across midlife may be important time periods to promote healthful TV viewing behavior patterns.

Effect of Personalized Risk-Reduction Strategies on Cognition and Dementia Risk Profile Among Older Adults: The SMARRT Randomized Clinical Trial.

Importance: Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious. Objective: To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults. Design, Setting, and Participants: The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023. Intervention: Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control. Main Outcomes and Measures: The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote. Results: The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, -0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P < .001). Conclusions and Relevance: In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia. Trial Registration: ClinicalTrials.gov Identifier: NCT03683394.

Association of urine biomarkers of kidney health with subclinical cardiovascular disease among men with and without HIV.

OBJECTIVE: The aim of this study was to determine whether urine biomarkers of kidney health are associated with subclinical cardiovascular disease among men with and without HIV. DESIGN: A cross-sectional study within the Multicenter AIDS Cohort Study (MACS) among 504 men with and without HIV infection who underwent cardiac computed tomography scans and had urine biomarkers measured within the preceding 2 years. METHODS: Our primary predictors were four urine biomarkers of endothelial (albuminuria), proximal tubule dysfunction (alpha-1-microglobulin [A1 M] and injury (kidney injury molecule-1 [KIM-1]) and tubulointerstitial fibrosis (pro-collagen-III N-terminal peptide [PIIINP]). These were evaluated for association with coronary artery calcium (CAC) prevalence, CAC extent, total plaque score, and total segment stenosis using multivariable regression. RESULTS: Of the 504 participants, 384 were men with HIV (MWH) and 120 were men without HIV. In models adjusted for sociodemographic factors, cardiovascular disease risk factors, eGFR, and HIV-related factors, each two-fold higher concentration of albuminuria was associated with a greater extent of CAC (1.35-fold higher, 95% confidence interval 1.11-1.65), and segment stenosis (1.08-fold greater, 95% confidence interval 1.01-1.16). Associations were similar between MWH and men without HIV in stratified analyses. The third quartile of A1 M showed an association with greater CAC extent, total plaque score, and total segment stenosis, compared with the lowest quartile. CONCLUSION: Worse endothelial and proximal tubule dysfunction, as reflected by higher urine albumin and A1 M, were associated with greater CAC extent and coronary artery stenosis.

Preceding Night Sleep Quality and Atrial Fibrillation Episodes in the I-STOP-AFIB Randomized Trial.

BACKGROUND: Chronic sleep disruption is associated with incident atrial fibrillation (AF), but it is unclear whether poor sleep quality acutely triggers AF. OBJECTIVES: The aim of this study was to characterize the relationship between a given night's sleep quality and the risk of a discrete AF episode. METHODS: Patients with symptomatic paroxysmal AF in the I-STOP-AFIB (Individualized Studies of Triggers of Paroxysmal Atrial Fibrillation) trial reported sleep quality on a daily basis. Participants were also queried daily regarding AF episodes and were provided smartphone-based mobile electrocardiograms (ECGs) (KardiaMobile, AliveCor). RESULTS: Using 15,755 days of data from 419 patients, worse sleep quality on any given night was associated with a 15% greater odds of a self-reported AF episode the next day (OR: 1.15; 95% CI: 1.10-1.20; P < 0.0001) after adjustment for the day of the week. No statistically significant associations between worsening sleep quality and mobile ECG-confirmed AF events were observed (OR: 1.04; 95% CI: 0.95-1.13; P = 0.43), although substantially fewer of these mobile ECG-confirmed events may have limited statistical power. Poor sleep was also associated with longer self-reported AF episodes, with each progressive category of worsening sleep associated with 16 (95% CI: 12-21; P < 0.001) more minutes of AF the next day. CONCLUSIONS: Poor sleep was associated with an immediately heightened risk for self-reported AF episodes, and a dose-response relationship existed such that progressively worse sleep was associated with longer episodes of AF the next day. These data suggest that sleep quality may be a potentially modifiable trigger relevant to the near-term risk of a discrete AF episode.

Cannabis use and incident atrial fibrillation in a longitudinal cohort.

BACKGROUND: Cannabis use is increasing worldwide. While prior studies have reported an association between cannabis use and a higher risk of atrial fibrillation (AF), most were cross-sectional and generally relied on diagnostic coding to identify cannabis users, which may not be representative of the typical recreational cannabis user. OBJECTIVE: The purpose of this study was to examine the association between recreational cannabis use and lifetime AF risk. METHODS: We evaluated the AF risk of participants of the UK Biobank cohort who completed the cannabis use lifestyle questionnaire. Cannabis exposure was categorized as "Occasional Use" for less than 100 times used, "Frequent Use" for more than 100 times used, and "Never" users. AF events were identified using International Classification of Diseases codes. Cox models were used to estimate the hazard ratios (HRs) between cannabis use and incident AF and were subsequently adjusted for age, sex, race, alcohol, coffee, smoking, education, and baseline cardiovascular comorbidities. RESULTS: A total of 150,554 participants (mean age 63.4 ± 7.7 years; 86,487 (57.4%) female; and 33,442 (22.2%) using cannabis at least once) were followed for a mean period of 6.1 ± 0.6 years. After multivariable adjustment, there were no statistically significant differences in incident AF among occasional users (HR 0.98; 95% confidence interval 0.89-1.08) nor frequent users (HR 1.03; 95% confidence interval 0.81-1.32) as compared with never users. CONCLUSION: In a large prospective cohort study, there was no evidence that cannabis use was associated with a higher risk of incident AF. An evaluation of cannabis ingestion methods and quantification was not possible using the current data set.

Brief Report: The Role of Substance Use in Structural Heart Disease Among Women Living With HIV.

BACKGROUND: People living with HIV have increased risk of cardiovascular disease, but few studies focus on women with HIV (WWH) and few account for the use of multiple substances. SETTING: We recruited WWH from San Francisco shelters, free meal programs, street encampments, and a safety net HIV clinic. METHODS: Between 2016 and 2019, participants completed 6 monthly interviews, specimen collection, and a transthoracic echocardiogram. We assessed associations between 3 echocardiographic indices of cardiac hypertrophy (concentric hypertrophy, concentric remodeling, and eccentric hypertrophy) and study factors, including cardiovascular risk factors, substance use, and HIV-specific factors (CD4 + count, viral load, HIV medication). RESULTS: Among 62 participants, the average age was 53 years and 70% were ethnic minority women. Just over 70% had elevated blood pressure. Toxicology-confirmed substance use included tobacco (63%), cannabis (52%), cocaine (51%), methamphetamine (29%), and alcohol (26%). Concentric hypertrophy was detected in 26% of participants. It was positively associated with cocaine use [adjusted relative risk (aRR) = 32.5, P < 0.01] and negatively associated with cannabis use (aRR = 0.07, P < 0.01). Concentric remodeling was detected in 40% of participants. It was positively associated with cocaine use (aRR = 11.2, P < 0.01) and negatively associated with cannabis use (aRR = 0.17, P = 0.02). Eccentric hypertrophy was not significantly associated with factors studied here. CONCLUSIONS: Routine evaluation of stimulant use as a contributing factor to cardiovascular risk may improve risk assessment in WWH. Whether cannabis use mitigates the impact of cocaine use on structural heart disease among WWH merits further investigation.

Housing Instability Associated with Return to Stimulant Use among Previously Abstaining Women.

Stimulant use among unstably housed individuals is associated with increased risks of psychiatric co-morbidity, violence, HIV transmission, and overdose. Due to a lack of highly effective treatments, evidence-based policies targeting the prevention of stimulant use disorder are of critical importance. However, little empirical evidence exists on risks associated with initiating or returning to stimulant use among at-risk populations. In a longitudinal cohort of unstably housed women in San Francisco (2016-2019), self-reported data on stimulant use, housing status, and mental health were collected monthly for up to 6 months, and factors associated with initiating stimulants after a period of non-use were identified through logistic regression. Among 245 participants, 42 (17.1%) started using cocaine and 46 (18.8%) started using methamphetamine. In analyses adjusting for demographics and socio-structural exposures over the preceding month, experiencing street homelessness was associated with initiating cocaine use (AOR: 2.10; 95% CI: 1.04, 4.25) and sheltered homelessness with initiating methamphetamine use (AOR: 2.57; 95% CI: 1.37, 4.79). Other factors-including race, income, unmet subsistence needs, mental health, and treatment adherence-did not reach levels of significance, suggesting the paramount importance of policies directed toward improving access to permanent supportive housing to prevent stimulant use among unstably housed women.

Cocaine Use is Associated With Increased LVMI in Unstably Housed Women With Polysubstance Use.

BACKGROUND: While substance use is known to influence cardiovascular health, most prior studies only consider one substance at a time. We examined associations between the concurrent use of multiple substances and left ventricular mass index (LVMI) in unhoused and unstably housed women. METHODS: Between 2016 and 2019, we conducted a cohort study of unstably housed women in which measurements included an interview, serum/urine collection, vital sign assessment, and a single transthoracic echocardiogram at baseline. We evaluated independent associations between 39 separate substances confirmed through toxicology and echocardiography-confirmed LVMI. RESULTS: The study included 194 participants with a median age of 53.5 years and a high proportion of women of color (72.6%). Toxicology-confirmed substance use included: 69.1% nicotine, 56.2% cocaine, 28.9% methamphetamines, 28.9% alcohol, 23.2% opioid analgesics, and 9.8% opioids with catecholaminergic effects. In adjusted analysis, cocaine was independently associated with higher LVMI (Adjusted linear effect: 18%; 95% CI 9.9, 26.6). Associations with other substances did not reach levels of significance and did not significantly interact with cocaine. CONCLUSION: In a population of vulnerable women where the use of multiple substances is common, cocaine stands out as having particularly detrimental influences on cardiac structure. Blood pressure did not attenuate the association appreciably, suggesting direct effects of cocaine on LVMI. Routinely evaluating stimulant use as a chronic risk factor during risk assessment and preventive clinical care planning may reduce end organ damage, particularly in highly vulnerable women.

Ambulatory urine biomarkers associations with acute kidney injury and hospitalization in people with HIV.

BACKGROUND: People with HIV (PWH) generally have worse ambulatory levels of kidney injury biomarkers and excess risk of acute kidney injury (AKI) compared to persons without HIV. We evaluated whether ambulatory measures of subclinical kidney injury among PWH are associated with subsequent AKI. METHODS: In the Predictors of Acute Renal Injury Study (PARIS), which enrolled 468 PWH from April 2016 to August 2019, we measured 10 urine biomarkers of kidney health (albumin, a1m, b2M, NGAL, IL18, KIM-1, EGF, UMOD, MCP-1, YKL40) at baseline and annually during follow-up. Using multivariable Cox regression models, we evaluated baseline and time-updated biomarker associations with the primary outcome of AKI (≥0.3 mg/dl or ≥1.5-times increase in serum creatinine from baseline) and secondary outcome of all-cause hospitalization. RESULTS: At baseline, the mean age was 53 years old, and 45% self-identified as female. In time-updated models adjusting for sociodemographic factors, comorbidities, albuminuria, estimated glomerular filtration rate, and HIV-associated factors, higher KIM-1 [hazard ratio (HR) = 1.30 per twofold higher; 95% confidence interval (CI) 1.03-1.63] and NGAL concentrations (HR = 1.24, 95% CI 1.06-1.44) were associated with higher risk of hospitalized AKI. Additionally, in multivariable, time-updated models, higher levels of KIM-1 (HR = 1.19, 95% CI 1.00, 1.41), NGAL (HR = 1.13, 95% CI 1.01-1.26), and MCP-1 (HR = 1.20, 95% CI 1.00, 1.45) were associated with higher risk of hospitalization. CONCLUSIONS: Urine biomarkers of kidney tubular injury, such as KIM-1 and NGAL, are strongly associated with AKI among PWH, and may hold potential for risk stratification of future AKI.

A Randomized Trial of High vs Standard Power Radiofrequency Ablation for Pulmonary Vein Isolation: SHORT-AF.

BACKGROUND: High-power, short duration (HPSD) radiofrequency ablation (RFA) is a commonly used strategy for pulmonary vein isolation (PVI). OBJECTIVES: This study sought to compare HPSD with standard power, standard duration (SPSD) RFA in patients undergoing PVI. METHODS: Patients with paroxysmal or persistent (<1 year) atrial fibrillation (AF) were randomized to HPSD (50 W) or SPSD (25-30 W) RFA to achieve PVI. Outcomes assessed included time to achieve PVI (primary), left atrial dwell time, total procedure time, first-pass isolation, PV reconnection with adenosine, procedure complications including asymptomatic cerebral emboli (ACE), and freedom from atrial arrhythmias. RESULTS: Sixty patients (median age 66 years; 75% male) with paroxysmal (57%) or persistent (43%) AF were randomized to HPSD (n = 29) or SPSD (n = 31). Median time to achieve PVI was shorter with HPSD vs SPSD (87 minutes vs 126 minutes; P = 0.003), as was left atrial dwell time (157 minutes vs 180 minutes; P = 0.04). There were no differences in first-pass isolation (79% vs 76%; P = 0.65) or PV reconnection with adenosine (12% vs 20%; P = 0.26) between groups. At 12 months, recurrent atrial arrhythmias occurred less in the HPSD group compared with the SPSD group (n = 3 of 29 [10%] vs n = 11 of 31 [35%]; HR: 0.26; P = 0.027). There was a trend toward more ACE with HPSD RFA (40% HPSD vs 17% SPSD; P = 0.053). CONCLUSIONS: In patients undergoing AF ablation, HPSD compared with SPSD RFA results in shorter time to achieve PVI, greater freedom from AF at 12 months, and a trend toward increased ACE.

Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal Women: A Randomized Clinical Trial.

Importance: Due to the potential risks of long-term systemic estrogen therapy, many menopausal women are interested in nonhormonal treatments for vasomotor symptoms. Physiologic studies indicate that nitric oxide plays a key role in mediating hot flash-related vasodilation, suggesting that nonhormonal medications that induce nitrate tolerance in the vasculature may offer therapeutic benefit for vasomotor symptoms. Objective: To determine whether uninterrupted administration of transdermal nitroglycerin (NTG) to induce nitrate cross-tolerance decreased the frequency or severity of menopause-related hot flashes. Design, Setting, and Participants: This randomized, double-blinded, placebo-controlled clinical trial included perimenopausal or postmenopausal women reporting 7 or more hot flashes per day who were recruited from northern California by study personnel at a single academic center. Patients were randomized between July 2017 and December 2021, and the trial ended in April 2022 when the last randomized participant completed follow-up. Interventions: Uninterrupted daily use of transdermal NTG (participant-directed dose titration from 0.2-0.6 mg/h) or identical placebo patches. Main Outcome Measures: Validated symptom diaries assessing changes in any hot flash frequency (primary outcome) and moderate-to-severe hot flash frequency over 5 and 12 weeks. Results: Among the 141 randomized participants (70 NTG [49.6%], 71 placebo [50.4%]; 12 [85.8%] Asian, 16 [11.3%] Black or African American, 15 [10.6%] Hispanic or Latina, 3 [2.1%] multiracial, 1 [0.7%] Native Hawaiian or Pacific Islander, and 100 [70.9%] White or Caucasian individuals), a mean (SD) of 10.8 (3.5) hot flashes and 8.4 (3.6) moderate-to-severe hot flashes daily was reported at baseline. Sixty-five participants assigned to NTG (92.9%) and 69 assigned to placebo (97.2%) completed 12-week follow-up (P = .27). Over 5 weeks, the estimated change in any hot flash frequency associated with NTG vs placebo was -0.9 (95% CI, -2.1 to 0.3) episodes per day (P = .10), and change in moderate-to-severe hot flash frequency with NTG vs placebo was -1.1 (95% CI, -2.2 to 0) episodes per day (P = .05). At 12 weeks, treatment with NTG did not significantly decrease the frequency of any hot flashes (-0.1 episodes per day; 95% CI, -1.2 to 0.4) or moderate-to-severe hot flashes (-0.5 episodes per day; 95% CI, -1.6 to 0.7) relative to placebo. In analyses combining 5-week and 12-week data, no significant differences in change in the frequency of any hot flashes (-0.5 episodes per day; 95% CI, -1.6 to 0.6; P = .25) or moderate-to-severe hot flashes (-0.8 episodes per day; 95% CI, -1.9 to 0.2; P = .12) were detected with NTG vs placebo. At 1 week, 47 NTG (67.1%) and 4 placebo participants (5.6%) reported headache (P < .001), but only 1 participant in each group reported headache at 12 weeks. Conclusions and Relevance: This randomized clinical trial found that continuous use of NTG did not result in sustained improvements in hot flash frequency or severity relative to placebo and was associated with more early but not persistent headache. Trial Registration: Clinicaltrials.gov Identifier: NCT02714205.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Association Between Intensive vs Standard Blood Pressure Control and Incident Left Ventricular Conduction Disease: A Post Hoc Analysis of the SPRINT Randomized Clinical Trial.

Importance: Left ventricular conduction disease predicts heart failure and death, and the only strategies to mitigate its effects involve implantation of a permanent pacemaker. There are currently no proven preventive strategies for this common condition. Objective: To determine the association between targeting intensive blood pressure (BP) control and the risk of developing left ventricular conduction disease. Design, Setting, and Participants: This was a post hoc analysis of the 2-arm multicenter Systolic Blood Pressure Intervention Trial (SPRINT), which recruited participants from 102 sites in the US and Puerto Rico and was conducted from November 2010 until August 2015. Adults 50 years and older with hypertension and at least 1 other cardiovascular risk factor were included. Participants with baseline left ventricular conduction disease, ventricular pacing, or ventricular pre-excitation were excluded for the current analysis. Data were analyzed from November 2021 to November 2022. Intervention: Participants were randomly assigned to a systolic BP target of less than 140 mm Hg (standard treatment group) or less than 120 mm Hg (intensive treatment group). Main Outcome: The primary outcome was incident left ventricular conduction disease, including any fascicular or left bundle-branch block, assessed by serial electrocardiography. Incident right bundle-branch block was examined as a negative control. Results: Among 3918 participants randomized to standard treatment and 3956 to intensive treatment (mean [SD] age, 67.6 [9.2] years; 2815 [36%] female) monitored for a median [IQR] 3.5 (0.02-5.2) years, 203 developed left ventricular conduction disease. Older age (hazard ratio per 10-year increase [HR], 1.42; 95% CI, 1.21-1.67; P < .001), male sex (HR, 2.31; 95% CI, 1.63-3.32; P < .001), and cardiovascular disease (HR, 1.46; 95% CI, 1.06-2.00; P = .02) were associated with a higher risk of left ventricular conduction disease. Assignment to intensive treatment was associated with a 26% lower risk of left ventricular conduction disease (HR, 0.74; 95% CI, 0.56-0.98; P = .04). These results persisted when incident ventricular pacing was included in the outcome and when considering all-cause death as a competing risk. In contrast, no association between randomization assignment and right bundle-branch block was observed (HR, 0.95; 95% CI, 0.71-1.27; P = .75). Conclusions and Relevance: In this study, targeting intensive BP control was associated with lower risk of left ventricular conduction disease in a randomized clinical trial, suggesting that clinically relevant conduction disease may be preventable. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.