Cooper‐DeHoff, Rhonda M.

Background Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID‐19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. Methods Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient‐Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12‐month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). Results Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65–85 years, 52.9% men, 66.2% non‐Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65–85 years, 47.1% men, 62.7% non‐Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, −2.6 percentage points [95% CI, −5.0 to −0.2]). Non‐Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. Conclusions BP control was disrupted during the COVID‐19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.

Background: The COVID-19 pandemic resulted in reduced in-person clinic visits and declines in blood pressure (BP) control among patients with hypertension. The purpose of this study was to report on pre- to post-pandemic trends in BP control and related BP metrics through 2022. Methods: We utilized data from 17 US health systems with electronic health record data standardized to the PCORnet ® Common Data Model. Multiple BP control metrics were calculated as a series of quarterly, 12-month rolling measurement periods from 2017 to 2022 (i.e., 1/1/2017-12/31/2017, 4/1/2017-3/31/2018, …, 1/1/2022-12/31/2022). BP control was defined as the percentage of patients with hypertension whose most recent BP measurement at an ambulatory visit was <140/<90 mmHg. Improvement in BP was defined as the percentage of patients with a reduction of 10 mmHg in systolic BP or achievement of systolic BP <140 mmHg during the last 3 months of the measurement period in patients with previously uncontrolled hypertension. Results: In 2022, 1,499,418 persons with hypertension were included (50% 65-85 years old; 47% men; 11% Hispanic, 3% non-Hispanic Asian, 20% non-Hispanic Black, 63% non-Hispanic White). BP control was relatively stable within health systems prior to the COVID-19 pandemic. Worsening of BP control was seen for most health systems in the second quarter of 2020 coinciding with onset of the COVID-19 pandemic (Figure, left panel). The weighted average BP control was 65.3% in 2019, dropped to 61.8% in 2020, and increased to 62.9% in 2021 and 62.6% in 2022. Similar patterns were observed for the improvement in BP metric (Figure, right panel): weighted average 31.4% in 2019, 25.7% in 2020, 29.1% in 2021 and 28.6% in 2022. Conclusion: BP control and improvement in BP decreased substantially during the COVID-19 pandemic. While both metrics improved after 2020, they were still below pre-pandemic levels through 2022. These findings underscore the importance of continued surveillance of BP control and other health impacts of the COVID-19 pandemic.

Introduction: Hydrochlorothiazide (HCTZ) is among the most commonly prescribed antihypertensives in the US, yet <50% of HCTZ treated patients achieve blood pressure (BP) control. Hypothesis: Integrating metabolomic and genomic profiles of HCTZ treated patients could identify novel pathways/biomarkers for optimizing the use of HCTZ. Methods: Primary analysis included 228 white hypertensives treated with HCTZ from the Pharmacogenomic Evaluation of Antihypertensive Response (PEAR) study. Genotyping was determined via Illumina Omni 1M-Quad Chip and untargeted metabolomics was performed on baseline fasting plasma samples using a GC-TOF MS platform. Pathway analysis was used to integrate metabolites significantly associated with HCTZ BP response (FDR<.05) and genetic signals at p<5x10-5 from HCTZ BP genome-wide analysis. Replication was conducted in another 212 white HCTZ treated patients. Replicated genetic signals were used to create a BP response score by summing their BP lowering alleles. We validated this score by testing it in 196 white HCTZ treated patients in the Genetic Epidemiology of Responses to Antihypertensives (GERA) study. Results: Thirteen metabolites were significantly associated with HCTZ systolic BP (SBP) and diastolic BP (DBP) responses (FDR<.05). Metabolomics-genomics integration revealed significant metabolites along with rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2, in the netrin signalling pathway (p=1x10-5), as potential markers significantly influencing HCTZ BP response. We successfully replicated those 3 genetic signals and added their alleles to create a response score which explained 11.3% and 11.9% of the variability to HCTZ SBP and DBP responses, respectively. We found that patients carrying one “response” allele had a significantly worse response than carriers of six alleles (ΔSBP/ΔDBP: -1.5/1.2 vs -16.3/-10.4 mmHg, respectively, SBP score p=1x10-8 and DBP score p=3x10-9). We further validated this response score by testing it in the GERA (DBP score p=0.03, SBP score p=0.07). Conclusion: This study highlights the power of using different omics to identify novel pathways/biomarkers of drug response, and suggests that PRKAG2, DCC and EPHX2 might be important determinants of HCTZ BP response.

Abstract Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double‐blind, placebo‐controlled randomized pragmatic clinical trial, will compare high‐intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community‐dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site‐reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co‐secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.

Objective: We aimed to characterize seasonal variation in US population-based blood pressure (BP) control and BP-related metrics and evaluate the association between outdoor temperature and BP control variation. Methods: We queried electronic health records (EHRs) from 26 health systems, representing 21 states, to summarize BP metrics by quarters of 12-month periods from January 2017 to March 2020. Patients with at least one ambulatory visit during the measurement period and a hypertension diagnosis during the first 6 months or prior to the measurement period were included. Changes in BP control, BP improvement, medication intensification, average SBP reduction after medication intensification across quarters and association with outdoor temperature were analyzed using weighted generalized linear models with repeated measures. Results: Among 1 818 041 people with hypertension, the majority were more than 65 years of age (52.2%), female (52.1%), white non-Hispanic (69.8%) and had stage 1/2 hypertension (64.8%). Overall, BP control and process metrics were highest in quarters 2 and 3, and lowest in quarters 1 and 4. Quarter 2 had the highest percentage of improved BP (31.95 ± 0.90%) and average SBP reduction after medication intensification (16 ± 0.23 mmHg). Quarter 3 had the highest percentage of BP controlled (62.25 ± 2.55%) and lowest with medication intensification (9.73 ± 0.60%). Results were largely consistent in adjusted models. Average temperature was associated with BP control metrics in unadjusted models, but associations were attenuated following adjustment. Conclusion: In this large, national, EHR-based study, BP control and BP-related process metrics improved during spring/summer months, but outdoor temperature was not associated with performance following adjustment for potential confounders.

Background Uncontrolled blood pressure (BP) remains a leading cause of death in the United States. The American Medical Association developed a quality improvement program to improve BP control, but it is unclear how to efficiently implement this program at scale across multiple health systems. Methods and Results We conducted BP MAP (Blood Pressure Measure Accurately, Act Rapidly, and Partner With Patients), a comparative effectiveness trial with clinic‐level randomization to compare 2 scalable versions of the quality improvement program: Full Support (with support from quality improvement expert) and Self‐Guided (using only online materials). Outcomes were clinic‐level BP control (<140/90 mm Hg) and other BP‐related process metrics calculated using electronic health record data. Difference‐in‐differences were used to compare changes in outcomes from baseline to 6 months, between intervention arms, and to a nonrandomized Usual Care arm composed of 18 health systems. A total of 24 safety‐net clinics in 9 different health systems underwent randomization and then simultaneous implementation. BP control increased from 56.7% to 59.1% in the Full Support arm, and 62.0% to 63.1% in the Self‐Guided arm, whereas BP control dropped slightly from 61.3% to 60.9% in the Usual Care arm. The between‐group differences‐in‐differences were not statistically significant (Full Support versus Self‐Guided=+1.2% [95% CI, −3.2% to 5.6%], P =0.59; Full Support versus Usual Care=+3.2% [−0.5% to 6.9%], P =0.09; Self‐Guided versus Usual Care=+2.0% [−0.4% to 4.5%], P =0.10). Conclusions In this randomized trial, 2 methods of implementing a quality improvement intervention in 24 safety net clinics led to modest improvements in BP control that were not statistically significant. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03818659.

ImportanceSelf-measured blood pressure (SMBP) with commercially available connected smartphone applications may help patients effectively use SMBP measurements.ObjectiveTo determine if enhanced SMBP paired with a connected smartphone application was superior to standard SMBP for blood pressure (BP) reduction or patient satisfaction.Design, Setting, and ParticipantsThis randomized clinical trial was conducted among 23 health systems participating in PCORnet, the National Patient-Centered Clinical Research Network, and included patients who reported having uncontrolled BP at their last clinic visit, a desire to lower their BP, and a smartphone. Enrollment and randomization occurred from August 3, 2019, to December 31, 2020, which was followed by 6 months of follow-up for each patient. Analysis commenced shortly thereafter.InterventionsEligible participants were randomly assigned to enhanced SMBP using a device that paired with a connected smartphone application (enhanced) or a standard device (standard). Participants received their device in the mail, along with web-based educational materials and phone-based support as needed. No clinician engagement was undertaken, and the study provided no special mechanisms for delivering measurements to clinicians for use in BP management.Main Outcomes and MeasuresReduction in systolic BP, defined as the difference between clinic BP at baseline and the most recent clinic BP extracted from electronic health records at 6 months.ResultsEnrolled participants (1051 enhanced [50.0%] vs 1050 standard [50.0%]; 1191 women [56.7%]) were mostly middle-aged or older (mean [SD] age, 58 [13] years), nearly a third were Black or Hispanic (645 [31%]), and most were relatively comfortable using technology (mean [SD], 4.1 [1.1] of 5). The mean (SD) change in systolic BP from baseline to 6 months was −10.8 (18) mm Hg vs −10.6 (18) mm Hg (enhanced vs standard: adjusted difference, −0.19 mm Hg; 95% CI, −1.83 to 1.44;P = .81). Secondary outcomes were mostly null, except for documented attainment of BP control to lower than 140/&amp;lt;90 mm Hg, which occurred in 32% enhanced vs 29% standard groups (odds ratio, 1.15; 95% CI, 1.01-1.34). Most participants were very likely to recommend their SMBP device to a friend (70% vs 69%).Conclusions and RelevanceThis randomized clinical trial found that enhanced SMBP paired with a smartphone application is not superior to standard SMBP for BP reduction or patient satisfaction.Trial RegistrationClinicalTrials.gov Identifier:NCT03796689

Background The National Patient‐Centered Clinical Research Network Blood Pressure Control Laboratory Surveillance System was established to identify opportunities for blood pressure (BP) control improvement and to provide a mechanism for tracking improvement longitudinally. Methods and Results We conducted a serial cross‐sectional study with queries against standardized electronic health record data in the National Patient‐Centered Clinical Research Network (PCORnet) common data model returned by 25 participating US health systems. Queries produced BP control metrics for adults with well‐documented hypertension and a recent encounter at the health system for a series of 1‐year measurement periods for each quarter of available data from January 2017 to March 2020. Aggregate weighted results are presented overall and by race and ethnicity. The most recent measurement period includes data from 1 737 995 patients, and 11 956 509 patient‐years were included in the trend analysis. Overall, 15% were Black, 52% women, and 28% had diabetes. BP control (<140/90 mm Hg) was observed in 62% (range, 44%–74%) but varied by race and ethnicity, with the lowest BP control among Black patients at 57% (odds ratio, 0.79; 95% CI, 0.66–0.94). A new class of antihypertensive medication (medication intensification) was prescribed in just 12% (range, 0.6%–25%) of patient visits where BP was uncontrolled. However, when medication intensification occurred, there was a large decrease in systolic BP (≈15 mm Hg; range, 5–18 mm Hg). Conclusions Major opportunities exist for improving BP control and reducing disparities, especially through consistent medication intensification when BP is uncontrolled. These data demonstrate substantial room for improvement and opportunities to close health equity gaps.

Introduction: β-blockers, including atenolol, are among the most widely prescribed antihypertensive drug classes. However, their use has been associated with hyperglycemia and incident diabetes, which poses concern for prescribers and patients. The Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) study is a multicenter clinical trial with one of its objectives to identify genetic influences on adverse metabolic events in patients treated with atenolol. Here we report a genomics-metabolomics integrative approach to identify biomarkers associated with atenolol-induced glucose change. Methods: PEAR participants were genotyped using the Illumina Omni 1M-Quad Chip. Metabolite profiles were acquired through GC-TOF-MS. Association between baseline levels of metabolites and glucose change was conducted using a multivariate linear regression model adjusted for age, gender and baseline fasting glucose. Genomics-metabolomics integration included selecting SNPs within genes involved in the synthesis and degradation of top metabolites and testing their effect on glucose change in 234 atenolol-treated Caucasians in PEAR, adjusting for age, gender, baseline glucose and principal components 1 and 2. A false discovery rate (FDR) of .05 was used to adjust for multiple comparisons. Replication of significant SNPs was conducted in an additional 228 participants treated with atenolol in PEAR. Results: Metabolomics analysis revealed 3 metabolites associated with glucose change that passed FDR adjustment. The top metabolite signal was beta-alanine. Increasing levels of baseline beta-alanine was significantly correlated with greater glucose increases after atenolol treatment (p=.0003). A total of 79 SNPs in 12 genes in the beta-alanine pathway were explored. SNP rs2669429 in DPYS was significantly associated with glucose change, after FDR adjustment. We found that G allele carriers had significantly greater glucose change compared with non-carriers (p=.0006; β=+2.76 mg/dL). This finding was successfully replicated in the other 228 patients who received atenolol (p=.04; β=+1.86 mg/dL). Conclusions: These results suggest that beta alanine and DPYS rs2669429 SNP might be an important predictor of atenolol-induced dysglycemia.