New Users of Angiotensin II Receptor Blocker-Versus Angiotensin-Converting Enzyme Inhibitor-Based Antihypertensive Medication Regimens and Cardiovascular Disease Events: A Secondary Analysis of ACCORD-BP and SPRINT.

BACKGROUND Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) block distinct components of the renin-angiotensin system. Whether this translates into differential effects on cardiovascular disease events remains unclear. METHODS AND RESULTS We used the ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes-Blood Pressure) trial and the SPRINT (Systolic Blood Pressure Intervention Trial) to emulate target trials of new users of ARBs versus ACEIs on cardiovascular disease events (primary outcome) and death (secondary outcome). We estimated marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions with inverse probability of treatment weights. We identified 3298 new users of ARBs or ACEIs (ACCORD-BP: 374 ARB versus 884 ACEI; SPRINT: 727 ARB versus 1313 ACEI). For participants initiating ARBs versus ACEIs, the inverse probability of treatment weight rate of the primary outcome was 3.2 versus 3.5 per 100 person-years in ACCORD-BP (HR, 0.91 [95% CI, 0.63-1.31]) and 1.8 versus 2.2 per 100 person-years in SPRINT (HR, 0.81 [95% CI, 0.56-1.18]). There were no appreciable differences in pooled analyses, except that ARBs versus ACEIs were associated with a lower death rate (HR, 0.56 [95% CI, 0.37-0.85]). ARBs were associated with a lower rate of the primary outcome among subgroups of male versus female participants, non-Hispanic Black versus non-Hispanic White participants, and those randomly assigned to standard versus intensive blood pressure (Pinteraction: <0.01, 0.05, and <0.01, respectively). CONCLUSIONS In this secondary analysis of ACCORD-BP and SPRINT, new users of ARB- versus ACEI-based antihypertensive medication regimens experienced similar cardiovascular disease events rates, with important subgroup differences and lower rates of death overall. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01206062, NCT00000620.

Sex Differences in Bladder Management, Symptoms, and Satisfaction After Spinal Cord Injury.

PURPOSE: We sought to characterize sex-stratified differences in bladder management and bladder symptoms and satisfaction after spinal cord injury. MATERIALS AND METHODS: This study was a prospective, cross-sectional, observational study; eligibility included: age ≥18 years and acquired spinal cord injury. Bladder management was grouped as (1) clean intermittent catheterization, (2) indwelling catheter, (3) surgery, and (4) voiding. Primary outcome was Neurogenic Bladder Symptom Score. Secondary outcomes were subdomains of the Neurogenic Bladder Symptom Score and bladder-related satisfaction. Multivariable regression was used in sex-stratified models to establish associations between participant characteristics and outcomes. RESULTS: A total of 1,479 participants enrolled in the study. Of the patients 843 (57%) were paraplegic and 585 (40%) were women. Median age and time from injury were 44.9 (IQR 34.3, 54.1) and 11 (IQR 5.1, 22.4) years. Women utilized clean intermittent catheterization at a lower rate (42.6% vs 56.5%) and surgery at a higher rate (22.6% vs 7.0%), especially catheterizable channel creation with or without augmentation cystoplasty (11.0% vs 1.9%). Women had worse measures of bladder symptoms and satisfaction across all outcomes. In adjusted analyses, women and men utilizing indwelling catheters had fewer associated overall symptoms (Neurogenic Bladder Symptom Score), less incontinence, and fewer storage and voiding symptoms. Surgery was associated with fewer bladder symptoms (Neurogenic Bladder Symptom Score) and less incontinence in women, and was also associated with better satisfaction in both sexes. CONCLUSIONS: There are significant sex-stratified differences in bladder management after spinal cord injury, which included a much higher use of surgery. Bladder symptoms and satisfaction are worse across all measurements in women. Women have a substantial associated benefit with surgery, while both sexes have fewer bladder symptoms with indwelling catheters compared to clean intermittent catheterization.

Estimated Population Health Benefits of Intensive Systolic Blood Pressure Treatment Among SPRINT-Eligible US Adults.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated an intensive (<120 mm Hg) vs. standard (<140 mm Hg) systolic blood pressure (SBP) goal lowered cardiovascular disease (CVD) risk. Estimating the effect of intensive SBP lowering among SPRINT-eligible adults most likely to benefit can guide implementation efforts. METHODS: We studied SPRINT participants and SPRINT-eligible participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study and National Health and Nutrition Examination Surveys (NHANES). A published algorithm of predicted CVD benefit with intensive SBP treatment was used to categorize participants into low, medium, or high predicted benefit. CVD event rates were estimated with intensive and standard treatment. RESULTS: Median age was 67.0, 72.0, and 64.0 years in SPRINT, SPRINT-eligible REGARDS, and SPRINT-eligible NHANES participants, respectively. The proportion with high predicted benefit was 33.0% in SPRINT, 39.0% in SPRINT-eligible REGARDS, and 23.5% in SPRINT-eligible NHANES. The estimated difference in CVD event rate (standard minus intensive) was 7.0 (95% confidence interval [CI] 3.4-10.7), 8.4 (95% CI 8.2-8.5), and 6.1 (95% CI 5.9-6.3) per 1,000 person-years in SPRINT, SPRINT-eligible REGARDS participants, and SPRINT-eligible NHANES participants, respectively (median 3.2-year follow-up). Intensive SBP treatment could prevent 84,300 (95% CI 80,800-87,920) CVD events per year in 14.1 million SPRINT-eligible US adults; 29,400 and 28,600 would be in 7.0 million individuals with medium or high predicted benefit, respectively. CONCLUSIONS: Most of the population health benefit from intensive SBP goals could be achieved by treating those characterized by a previously published algorithm as having medium or high predicted benefit.

Single-Pill Combination Product Availability of the Antihypertensive Regimens Used for Intensive Systolic Blood Pressure Treatment in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Single-pill combination (SPC) antihypertensive products improve blood pressure control and medication adherence among patients with hypertension. It is unknown to what degree commercially available SPC products could be used to target an intensive systolic blood pressure goal of <120 mm Hg. METHODS: This cross-sectional analysis included participants randomized to the intensive treatment arm (goal systolic blood pressure <120 mm Hg) of the Systolic Blood Pressure Intervention Trial (SPRINT) using ≥2 antihypertensive medication classes at the 12-month postrandomization visit. Antihypertensive medication data were collected using pill bottle review by research coordinators, and regimens were categorized by the unique combinations of antihypertensive classes. We calculated the proportion of regimens used, which are commercially available as one of the 7 SPC class combinations in the United States as of January 2023. RESULTS: Among the 3833 SPRINT intensive arm participants included (median age, 67.0 years; 35.5% female), participants were using 219 unique antihypertensive regimens. The 7 regimens for which there are class-equivalent SPC products were used by 40.3% of participants. Only 3.2% of all medication class regimens used are available as a class-equivalent SPC product (7/219). There are no SPC products available with 4 or more medication classes, which were used by 1060 participants (27.7%). CONCLUSIONS: Most SPRINT participants in the intensive arm used an antihypertensive medication regimen, which is not commercially available as a class equivalent SPC product. To achieve the SPRINT results in real-world settings, maximize the potential benefit of SPCs, and reduce pill burden, improvements in the product landscape are needed. REGISTRATION: URL: https://www. CLINICALTRIALS: gov/ct2/show/NCT01206062; Unique identifier: NCT01206062.

Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit: A Secondary Analysis of the SPRINT Randomized Clinical Trial.

Importance: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients. Objective: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment. Design, Setting, and Participants: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022. Intervention: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target. Main Outcomes and Measures: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI. Results: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk. Conclusions and Relevance: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Evidence for Age Bias Contributing to Therapeutic Inertia in Blood Pressure Management: A Secondary Analysis of SPRINT.

BACKGROUND: Despite evidence supporting the cardiovascular and cognitive benefits of intensive blood pressure management, older adults have the lowest rates of blood pressure control. We determined the association between age and therapeutic inertia (TI) in SPRINT (Systolic Blood Pressure Intervention Trial), and whether frailty, cognitive function, or gait speed moderate or mediate these associations. METHODS: We performed a secondary analysis of SPRINT of participant visits with blood pressure above randomized treatment goal. We categorized baseline age as <60, 60 to <70, 70 to <80, and ≥80 years and TI as no antihypertensive medication intensification per participant visit. Generalized estimating equations generated odds ratios for TI associated with age, stratified by treatment group based on nested models adjusted for baseline frailty index score (fit [frailty index, ≤0.10], less fit [0.100.10). CONCLUSIONS: Older age is associated with greater TI independent of physical or cognitive function, implying age bias in hypertension management.

Antihypertensive Medication Regimens Used by US Adults With Hypertension and the Potential for Fixed-Dose Combination Products: The National Health and Nutrition Examination Surveys 2015 to 2020.

Background Fixed-dose combination (FDC) antihypertensive products improve blood pressure control and adherence among patients with hypertension. It is unknown to what degree commercially available FDC products meet the current hypertension management prescription patterns in the United States. Methods and Results This cross-sectional analysis of the National Health and Nutrition Examination Surveys 2015 to March 2020 included participants with hypertension taking ≥2 antihypertensive medications (N=2451). After constructing each participant's regimen according to antihypertensive classes used, we estimated the extent to which the 7 class-level FDC regimens available in the United States as of January 2023 would match the regimens used. Among a weighted population of 34.1 million US adults (mean age, 66.0 years; 52.8% women; 69.1% non-Hispanic White race and ethnicity), the proportions using 2, 3, 4, and ≥5 antihypertensive classes were 60.6%, 28.2%, 9.1%, and 1.6%, respectively. The 7 FDC regimens were among 189 total regimens used (3.7%), and 39.2% of the population used one of the FDC regimens (95% CI, 35.5%-43.0%; 13.4 million US adults); 60.8% of the population (95% CI, 57.0%-64.5%; 20.7 million US adults) were using a regimen not available as a class-equivalent FDC product. Conclusions Three in 5 US adults with hypertension taking ≥2 antihypertensive classes are using a regimen that is not commercially available as a class-equivalent FDC product as of January 2023. To maximize the potential benefit of FDCs to improve medication adherence (and thus blood pressure control) among patients taking multiple antihypertensive medications, use of FDC-compatible regimens and improvements in the product landscape are needed.

Hypertension Statistics for US Adults: An Open-Source Web Application for Analysis and Visualization of National Health and Nutrition Examination Survey Data.

BACKGROUND: Data from the US National Health and Nutrition Examination Survey are freely available and can be analyzed to produce hypertension statistics for the noninstitutionalized US population. The analysis of these data requires statistical programming expertise and knowledge of National Health and Nutrition Examination Survey methodology. METHODS: We developed a web-based application that provides hypertension statistics for US adults using 10 cycles of National Health and Nutrition Examination Survey data, 1999 to 2000 through 2017 to 2020. We validated the application by reproducing results from prior publications. The application's interface allows users to estimate crude and age-adjusted means, quantiles, and proportions. Population counts can also be estimated. To demonstrate the application's capabilities, we estimated hypertension statistics for noninstitutionalized US adults. RESULTS: The estimated mean systolic blood pressure (BP) declined from 123 mm Hg in 1999 to 2000 to 120 mm Hg in 2009 to 2010 and increased to 123 mm Hg in 2017 to 2020. The age-adjusted prevalence of hypertension (ie, systolic BP≥130 mm Hg, diastolic BP≥80 mm Hg or self-reported antihypertensive medication use) was 47.9% in 1999 to 2000, 43.0% in 2009 to 2010, and 44.7% in 2017 to 2020. In 2017 to 2020, an estimated 115.3 million US adults had hypertension. The age-adjusted prevalence of controlled BP, defined by the 2017 American College of Cardiology/American Heart Association BP guideline, among nonpregnant US adults with hypertension was 9.7% in 1999 to 2000, 25.0% in 2013 to 2014, and 21.9% in 2017 to 2020. After age adjustment and among nonpregnant US adults who self-reported taking antihypertensive medication, 27.5%, 48.5%, and 43.0% had controlled BP in 1999 to 2000, 2013 to 2014, and 2017 to 2020, respectively. CONCLUSIONS: The application developed in the current study is publicly available at https://bcjaeger.shinyapps.io/nhanesShinyBP/ and produced valid, transparent and reproducible results.

Prevalence of Statin Use for Primary Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and 10-Year Disease Risk in the US: National Health and Nutrition Examination Surveys, 2013 to March 2020.

Importance: The burden of atherosclerotic cardiovascular disease (ASCVD) in the US is higher among Black and Hispanic vs White adults. Inclusion of race in guidance for statin indication may lead to decreased disparities in statin use. Objective: To evaluate prevalence of primary prevention statin use by race and ethnicity according to 10-year ASCVD risk. Design, Setting, and Participants: This serial, cross-sectional analysis performed in May 2022 used data from the National Health and Nutrition Examination Survey, a nationally representative sample of health status in the US, from 2013 to March 2020 (limited cycle due to the COVID-19 pandemic), to evaluate statin use for primary prevention of ASCVD and to estimate 10-year ASCVD risk. Participants aged 40 to 75 years without ASCVD, diabetes, low-density lipoprotein cholesterol levels 190 mg/dL or greater, and with data on medication use were included. Exposures: Self-identified race and ethnicity (Asian, Black, Hispanic, and White) and 10-year ASCVD risk category (5%-<7.5%, 7.5%-<20%, ≥20%). Main Outcomes and Measures: Prevalence of statin use, defined as identification of statin use on pill bottle review. Results: A total of 3417 participants representing 39.4 million US adults after applying sampling weights (mean [SD] age, 61.8 [8.0] years; 1289 women [weighted percentage, 37.8%] and 2128 men [weighted percentage, 62.2%]; 329 Asian [weighted percentage, 4.2%], 1032 Black [weighted percentage, 12.7%], 786 Hispanic [weighted percentage, 10.1%], and 1270 White [weighted percentage, 73.0%]) were included. Compared with White participants, statin use was lower in Black and Hispanic participants and comparable among Asian participants in the overall cohort (Asian, 25.5%; Black, 20.0%; Hispanic, 15.4%; White, 27.9%) and within ASCVD risk strata. Within each race and ethnicity group, a graded increase in statin use was observed across increasing ASCVD risk strata. Statin use was low in the highest risk stratum overall with significantly lower rates of use among Black (23.8%; prevalence ratio [PR], 0.90; 95% CI, 0.82-0.98 vs White) and Hispanic participants (23.9%; PR, 0.90; 95% CI, 0.81-0.99 vs White). Among other factors, routine health care access and health insurance were significantly associated with higher statin use in Black, Hispanic, and White adults. Prevalence of statin use did not meaningfully change over time by race and ethnicity or by ASCVD risk stratum. Conclusions and Relevance: In this study, statin use for primary prevention of ASCVD was low among all race and ethnicity groups regardless of ASCVD risk, with the lowest use occurring among Black and Hispanic adults. Improvements in access to care may promote equitable use of primary prevention statins in Black and Hispanic adults.

Abdominal aortic aneurysm and exfoliation syndrome in Utah.

PURPOSE: A pilot study of electronic medical records (EMR) in Utah was undertaken to investigate exfoliation syndrome and exfoliation glaucoma (XFS/XFG) in abdominal aortic aneurysm (AAA) patients. In a subsequent retrospective cohort study of Utah XFS/XFG patients and population controls, the risk of AAA was examined. METHODS: EMR of a statewide healthcare population were obtained from the Utah Population Database (UPDB) which links decades of medical records with Utah demographic and vital records data. In a pilot study, 7167 patients ages ≥40 years identified with AAA diagnosed from 1996 to 2015, based on International Classification of Diseases (ICD) version 9/10 codes, were included. A univariable hazards model was used to determine the risk of XFS/XFG in AAA patients. An XFS/XFG outcome based on ICD 9/10 codes in AAA patients and in 5:1 sex- and age-matched non-AAA controls was determined. A retrospective cohort of 3412 XFS/XFG patients ages ≥50 years diagnosed from 1996 to 2020 and 10 227 3:1 sex- and age-matched controls who underwent ≥1 dilated eye examination(s) were recently identified and updated diagnoses of AAA were obtained. Multivariable logistic regression was used to estimate AAA risk in XFS/XFG patients compared with controls. In a subset of XFS/XFG patients, chart reviews were conducted to confirm clinically diagnosed AAA. RESULTS: In the AAA pilot, 20 patients (0.3%) and 118 controls (0.3%) developed XFS/XFG, respectively. We observed no increased risk of XFS/XFG in AAA patients compared with non-AAA-matched controls (HR = 0.99, 95% CI 0.6-1.6). Among XFS/XFG study patients and controls, 122 patients (3.6%) and 376 controls (3.7%) had an AAA diagnosis. We likewise observed no increased risk of AAA in XFS/XFG patients (OR = 0.97, 95% CI 0.8-1.2). In 14 XFS/XFG patients with an ICD 9/10 diagnosis of AAA who underwent chart review, a clinical diagnosis of AAA was confirmed in 9 patients (64.3%). CONCLUSION: Our findings do not support an association between AAA and XFS/XFG.

Antihypertensive Medication Regimens Used in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Describing the antihypertensive medication regimens used in the SPRINT (Systolic Blood Pressure Intervention Trial) would contextualize the standard and intensive systolic blood pressure (SBP) interventions and may inform future implementation efforts to achieve population-wide intensive SBP goals. METHODS: We included SPRINT participants with complete medication data at the prerandomization and 12-month visits. Regimens were categorized by antihypertensive medication class. Analyses were stratified by treatment group (standard goal SBP <140 mm Hg versus intensive goal SBP <120 mm Hg). RESULTS: Among 7860 participants (83.7% of 9361 randomized), the median number of classes used at the prerandomization visit was 2.0 and 2.0 in the standard and intensive groups (P=0.559). At 12-months, the median number of classes used was 3.0 and 2.0 in the intensive and standard groups (P<0.001). Prerandomization, angiotensin-converting enzyme inhibitor (ACE), or angiotensin-II receptor blocker (ARB) monotherapy was the most common regimen in the intensive and standard groups (12.6% versus 12.2%). At 12-months, ACE/ARB monotherapy was still the most common regimen among standard group participants (14.7%) and was used by 5.3% of intensive group participants. Multidrug regimens used by the intensive and standard participants at 12 months were as follows: an ACE/ARB with thiazide (12.2% and 7.9%); an ACE/ARB with calcium channel blocker (6.2% and 6.8%); an ACE/ARB, thiazide, and calcium channel blocker (11.4% and 4.3%); and an ACE/ARB, thiazide, calcium channel blocker, and beta-blocker (6.5% and 1.2%). CONCLUSIONS: SPRINT investigators favored combining ACEs or ARBs, thiazide diuretics, and calcium channel blockers to target SBP <120 mm Hg, compared to ACE/ARB monotherapy to target SBP <140 mm Hg. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT01206062.

Lipid-Lowering Therapy Use and Intensification Among United States Veterans Following Myocardial Infarction or Coronary Revascularization Between 2015 and 2019.

BACKGROUND: Understanding how statins, ezetimibe, and PCSK9i (proprotein convertase subtilisin/kexin type 9 serine protease inhibitors) are prescribed after a myocardial infarction (MI) or elective coronary revascularization may improve lipid-lowering therapy (LLT) intensification and reduce recurrent atherosclerotic cardiovascular disease events. We described the use and intensification of LLT among US veterans who had a MI or elective coronary revascularization between July 24, 2015, and December 9, 2019, within 12 months of hospital discharge. METHODS: LLT intensification was defined as increasing statin dose, or initiating a statin, ezetimibe, or a PCSK9i, overall and among those with an LDL-C (low-density lipoprotein cholesterol) ≥70 or 100 mg/dL. Poisson regression was used to determine patient characteristics associated with a greater likelihood of LLT intensification following hospitalization for MI or elective coronary revascularization. RESULTS: Among 81 372 index events (mean age, 69.0 years, 2.3% female, mean LDL-C 89.6 mg/dL, 33.8% with LDL-C <70 mg/dL), 39.7% were not taking any LLT, and 22.0%, 37.2%, and 0.6% were taking a low-moderate intensity statin, a high-intensity statin, and ezetimibe, respectively, before MI/coronary revascularization during the study period. Within 14 days, 3 months, and 12 months posthospitalization, 33.3%, 41.9%, and 47.3%, respectively, of veterans received LLT intensification. LLT intensification was most common among veterans taking no LLT (82.5%, n=26 637) before MI/coronary revascularization. Higher baseline LDL-C, having a lipid test, and attending a cardiology visit were each associated with a greater likelihood of LLT intensification, while age ≥75 versus <65 years was associated with a lower likelihood of LLT intensification within 12 months posthospitalization. CONCLUSIONS: Less than half of veterans received LLT intensification in the year after MI or coronary revascularization suggesting a missed opportunity to reduce atherosclerotic cardiovascular disease risk.

Risk of Mild Cognitive Impairment or Probable Dementia in New Users of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors: A Secondary Analysis of Data From the Systolic Blood Pressure Intervention Trial (SPRINT).

Importance: The cardiovascular and renal outcomes of angiotensin-II receptor blocker (ARB) and angiotensin-converting enzyme inhibitor (ACEI) treatment are well-known; however, few studies have evaluated initiation of these agents and cognitive impairment. Objective: To emulate a target trial to evaluate the cognitive outcomes of initiating an ARB- vs ACEI-based antihypertensive regimen in individuals at risk for mild cognitive impairment (MCI) and probable dementia (PD). Design, Setting, and Participants: Active comparator, new-user observational cohort study design using data from the Systolic Blood Pressure Intervention Trial (SPRINT), conducted November 2010 through July 2018. Marginal cause-specific hazard ratios (HRs) and treatment-specific cumulative incidence functions were estimated with inverse probability (IP) weighting to account for confounding. Participants were using neither an ARB nor ACEI at baseline. Data analysis was conducted from April 7, 2021, to April 26, 2022. Exposures: New users of ARB vs ACEI during the first 12 months of trial follow-up. Main Outcomes and Measures: Composite of adjudicated amnestic MCI or PD. Results: Of 9361 participants, 727 and 1313 new users of an ARB or ACEI, respectively, with well-balanced baseline characteristics between medication exposure groups after inverse probability weighting (mean [SD] age, 67 [9.5] years; 1291 ]63%] male; 240 [33%] Black; 89 [12%] Hispanic; 383 [53%] White; and 15 [2%] other race or ethnicity. In the primary analysis, during a median follow-up of 4.9 years, the inverse probability-weighted rate of amnestic MCI or PD was 4.3 vs 4.6 per 100 person-years among participants initiating ARB vs ACEI (HR, 0.93; 95% CI, 0.76-1.13). In subgroup analyses, new users of an ARB vs ACEI had a lower rate of amnestic MCI or PD among those in the standard systolic blood pressure treatment arm (HR, 0.61; 95% CI, 0.41-0.91) but not in the intensive arm (HR, 1.17; 95% CI, 0.90-1.52) (P = .007 for interaction). Conclusions and Relevance: In this observational cohort study of US adults at high cardiovascular disease risk, there was no difference in the rate of amnestic MCI or PD among new users of an ARB compared with ACEI, although 95% CIs were wide.

The potential population health impact of treating REDUCE-IT eligible US adults with Icosapent Ethyl.

Objective: To explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs. Methods: We derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59. Results: We estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion). Conclusions: Treating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.

Exfoliation Syndrome in Baja Verapaz Guatemala: A Cross-Sectional Study and Review of the Literature.

There are little epidemiologic data on exfoliation syndrome (XFS) or exfoliation glaucoma (XFG) in Guatemala, especially in the underserved Baja Verapaz region. This observational study assessing XFS/XFG and demographic factors of this region aims to better understand unique exogenous and endogenous risk factors associated with XFS/XFG in Guatemala. During Moran Eye Center's global outreach medical eye camps from 2016-2017, 181 patients age 15 years and older presented for complete eye exams. These individuals were screened for eye disease and evaluated for possible surgical interventions that could occur during the camps to improve eyesight. During the dilated exams, XFS was noted as missing or present. Of those 181, 10 had insufficient data and 18 lacked a definitive diagnosis of XFS or XFG, resulting in 153 evaluable patients; 46 XFS and 9 XFG were identified. Age, gender, hometown, ancestry (languages spoken by parents and grandparents), past medical history, family medical history, and occupational data (only 2017 trip) were obtained for each patient. The most common occupations of these individuals were farming and housekeeping. Higher rates of XFS/XFG were noted in individuals of rural compared to urban settings and Mayan speaking people compared with Spanish speakers. Based on this subset of patients, with various ocular pathologies being evaluated during medical eye outreach camps, the prevalence of XFS/XFG appeared to be 36%, a high prevalence compared to other world populations. Location and higher altitude, along with a farming occupation, may contribute to XFS development and subsequent progression to XFG. To our knowledge, this is the largest study looking at the epidemiology of XFS/XFG in the Baja Verapaz region of Guatemala for those over the age of 15 years seeking eye exams and interventions.

Association of Intensive vs Standard Blood Pressure Control With Cerebral Blood Flow: Secondary Analysis of the SPRINT MIND Randomized Clinical Trial.

IMPORTANCE: Antihypertensive treatments benefit cerebrovascular health and cognitive function in patients with hypertension, but it is uncertain whether an intensive blood pressure target leads to potentially harmful cerebral hypoperfusion. OBJECTIVE: To investigate the association of intensive systolic blood pressure (SBP) control vs standard control with whole-brain cerebral blood flow (CBF). DESIGN, SETTING, AND PARTICIPANTS: This substudy of the Systolic Blood Pressure Intervention Trial (SPRINT) randomized clinical trial compared the efficacy of 2 different blood pressure-lowering strategies with longitudinal brain magnetic resonance imaging (MRI) including arterial spin labeled perfusion imaging to quantify CBF. A total of 1267 adults 50 years or older with hypertension and increased cardiovascular risk but free of diabetes or dementia were screened for the SPRINT substudy from 6 sites in the US. Randomization began in November 2010 with final follow-up MRI in July 2016. Analyses were performed from September 2020 through December 2021. INTERVENTIONS: Study participants with baseline CBF measures were randomized to an intensive SBP target less than 120 mm Hg or standard SBP target less than 140 mm Hg. MAIN OUTCOMES AND MEASURES: The primary outcome was change in whole-brain CBF from baseline. Secondary outcomes were change in gray matter, white matter, and periventricular white matter CBF. RESULTS: Among 547 participants with CBF measured at baseline, the mean (SD) age was 67.5 (8.1) years and 219 (40.0%) were women; 315 completed follow-up MRI at a median (IQR) of 4.0 (3.7-4.1) years after randomization. Mean whole-brain CBF increased from 38.90 to 40.36 (difference, 1.46 [95% CI, 0.08-2.83]) mL/100 g/min in the intensive treatment group, with no mean increase in the standard treatment group (37.96 to 37.12; difference, -0.84 [95% CI, -2.30 to 0.61] mL/100 g/min; between-group difference, 2.30 [95% CI, 0.30-4.30; P = .02]). Gray, white, and periventricular white matter CBF showed similar changes. The association of intensive vs standard treatment with CBF was generally similar across subgroups defined by age, sex, race, chronic kidney disease, SBP, orthostatic hypotension, and frailty, with the exception of an indication of larger mean increases in CBF associated with intensive treatment among participants with a history of cardiovascular disease (interaction P = .05). CONCLUSIONS AND RELEVANCE: Intensive vs standard antihypertensive treatment was associated with increased, rather than decreased, cerebral perfusion, most notably in participants with a history of cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062.

Association of Antihypertensives That Stimulate vs Inhibit Types 2 and 4 Angiotensin II Receptors With Cognitive Impairment.

Importance: Use of antihypertensive medications that stimulate type 2 and 4 angiotensin II receptors, compared with those that do not stimulate these receptors, has been associated with a lower risk of dementia. However, this association with cognitive outcomes in hypertension trials, with blood pressure levels in the range of current guidelines, has not been evaluated. Objective: To examine the association between use of exclusively antihypertensive medication regimens that stimulate vs inhibit type 2 and 4 angiotensin II receptors on mild cognitive impairment (MCI) or dementia. Design, Setting, and Participants: This cohort study is a secondary analysis (April 2011 to July 2018) of participants in the randomized Systolic Blood Pressure Intervention Trial (SPRINT), which recruited individuals 50 years or older with hypertension and increased cardiovascular risk but without a history of diabetes, stroke, or dementia. Data analysis was conducted from March 16 to July 6, 2021. Exposures: Prevalent use of angiotensin II receptor type 2 and 4-stimulating or -inhibiting antihypertensive medication regimens at the 6-month study visit. Main Outcomes and Measures: The primary outcome was a composite of adjudicated amnestic MCI or probable dementia. Results: Of the 8685 SPRINT participants who were prevalent users of antihypertensive medication regimens at the 6-month study visit (mean [SD] age, 67.7 [11.2] years; 5586 [64.3%] male; and 935 [10.8%] Hispanic, 2605 [30.0%] non-Hispanic Black, 4983 [57.4%] non-Hispanic White, and 162 [1.9%] who responded as other race or ethnicity), 2644 (30.4%) were users of exclusively stimulating, 1536 (17.7%) inhibiting, and 4505 (51.9%) mixed antihypertensive medication regimens. During a median of 4.8 years of follow-up (95% CI, 4.7-4.8 years), there were 45 vs 59 cases per 1000 person-years of amnestic MCI or probable dementia among prevalent users of regimens that contained exclusively stimulating vs inhibiting antihypertensive medications (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87). When comparing stimulating-only vs inhibiting-only users, amnestic MCI occurred at rates of 40 vs 54 cases per 1000 person-years (HR, 0.74; 95% CI, 0.64-0.87) and probable dementia at rates of 8 vs 10 cases per 1000 person-years (HR, 0.80; 95% CI, 0.57-1.14). Negative control outcome analyses suggested the presence of residual confounding. Conclusions and Relevance: In this secondary analysis of SPRINT, prevalent users of regimens that contain exclusively antihypertensive medications that stimulate vs inhibit type 2 and 4 angiotensin II receptors had lower rates of incident cognitive impairment. Residual confounding cannot be ruled out. If these results are replicated in randomized clinical trials, certain antihypertensive medications could be prioritized to prevent cognitive decline.

Factors associated with antihypertensive monotherapy among US adults with treated hypertension and uncontrolled blood pressure overall and by race/ethnicity, National Health and Nutrition Examination Survey 2013-2018.

BACKGROUND: Treating hypertension with antihypertensive medications combinations, rather than one medication (ie, monotherapy), is underused in the United States, particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations. METHODS: Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥ 140 mmHg or diastolic BP [DBP] ≥ 90 mmHg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression. RESULTS: Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher body mass index, and having heart failure were associated with lower monotherapy use. CONCLUSION: Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.

Positive End-Expiratory Pressure and Respiratory Rate Modify the Association of Mechanical Power and Driving Pressure With Mortality Among Patients With Acute Respiratory Distress Syndrome.

IMPORTANCE: Mechanical power and driving pressure have known associations with survival for patients with acute respiratory distress syndrome. OBJECTIVES: To further understand the relative importance of mechanical power and driving pressure as clinical targets for ventilator management. DESIGN: Secondary observational analysis of randomized clinical trial data. SETTING AND PARTICIPANTS: Patients with the acute respiratory distress syndrome from three Acute Respiratory Distress Syndrome Network trials. MAIN OUTCOMES AND MEASURES: After adjusting for patient severity in a multivariate Cox proportional hazards model, we examined the relative association of driving pressure and mechanical power with hospital mortality. Among 2,410 patients, the relationship between driving pressure and mechanical power with mortality was modified by respiratory rate, positive end-expiratory pressure, and flow. RESULTS: Among patients with low respiratory rate (< 26), only power was significantly associated with mortality (power [hazard ratio, 1.82; 95% CI, 1.41-2.35; p < 0.001] vs driving pressure [hazard ratio, 1.01; 95% CI, 0.84-1.21; p = 0.95]), while among patients with high respiratory rate, neither was associated with mortality. Both power and driving pressure were associated with mortality at high airway flow (power [hazard ratio, 1.28; 95% CI, 1.15-1.43; p < 0.001] vs driving pressure [hazard ratio, 1.15; 95% CI, 1.01-1.30; p = 0.041]) and neither at low flow. At low positive end-expiratory pressure, neither was associated with mortality, whereas at high positive end-expiratory pressure (≥ 10 cm H2O), only power was significantly associated with mortality (power [hazard ratio, 1.22; 95% CI, 1.09-1.37; p < 0.001] vs driving pressure [hazard ratio, 1.16; 95% CI, 0.99-1.35; p = 0.059]). CONCLUSIONS AND RELEVANCE: The relationship between mechanical power and driving pressure with mortality differed within severity subgroups defined by positive end-expiratory pressure, respiratory rate, and airway flow.

Determining the impact of the Zika pandemic on primary care providers' contraceptive counseling of non-pregnant patients in the US: a mixed methods study.

BACKGROUND: Global pandemics like Zika (ZIKV) factor into pregnancy planning and avoidance, yet little is known about how primary care providers (PCPs) incorporate public health guidance into contraceptive counseling. Study objectives include: 1) determining the impact of the ZIKV pandemic on contraceptive counseling changes; and 2) assessing PCP knowledge and practice regarding contraception, ZIKV, and CDC ZIKV guidelines. METHODS: Study components included: (1) a retrospective review of electronic health records of non-pregnant, reproductive age women presenting for preventive health visits between 2014 and 2017 assessed using interrupted time series analyses (ITSA) to identify changes in documentation of ZIKV risk assessment and contraceptive counseling; and (2) a sequential, cross-sectional study with quantitative surveys and qualitative, semi-structured interviews of PCPs providing preventive care to non-pregnant patients at eight federally qualified health centers in Utah. We performed descriptive analyses on survey data and analyzed qualitative data for dominant themes using a modified Health Belief Model. RESULTS: We conducted 6634 chart reviews yielding 9840 visits. The ITSA did not reveal changes in ZIKV risk assessment or contraceptive counseling. Twenty-two out of 40 (55%) eligible providers participated in the provider component. Participants averaged 69 and 81% correct on contraceptive and ZIKV knowledge questions, respectively. Sixty-five percent reported counseling consistent with CDC ZIKV guidelines. Qualitative analysis found providers unlikely to prioritize ZIKV risk assessment in contraceptive counseling for non-pregnant patients. CONCLUSIONS: PCPs who care for non-pregnant women are knowledgeable about contraception and ZIKV; however, there was no change in ZIKV risk assessment or contraceptive counseling. This stresses the importance of developing strategies to improve guideline uptake.