Derivation and Validation of ICD-10 Codes for Identifying Incident Stroke.

Importance: Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population. Objective: To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data. Design, Setting, and Participants: This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023. Exposures: Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies. Main Outcomes and Measures: The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes. Results: In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%). Conclusions and Relevance: These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

Predicted Cardiovascular Risk by the PREVENT Equations in US Adults With Stage 1 Hypertension.

BACKGROUND: The 2017 American College of Cardiology/American Heart Association blood pressure guideline recommends initiation of antihypertensive medication for adults with stage 1 hypertension (systolic blood pressure, 130-139 mm Hg, or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10% estimated by the pooled cohort equations (PCEs). In 2023, the American Heart Association published the predicting risk of cardiovascular disease events (PREVENT) equations to estimate ASCVD and total cardiovascular disease risk. METHODS: We analyzed US National Health and Nutrition Examination Survey data from 2013 to 2020 for 1703 adults aged 30 to 79 years without self-reported cardiovascular disease with stage 1 hypertension. We estimated 10-year ASCVD risk by the PCEs and 10-year ASCVD and total cardiovascular disease risk by the base PREVENT equations. Analyses were weighted to represent noninstitutionalized US adults with stage 1 hypertension. RESULTS: Mean 10-year ASCVD risk was 5.4% (95% CI, 5.0%-5.9%) and 2.9% (95% CI, 2.7%-3.1%) using the PCEs and PREVENT equations, respectively. The proportion with 10-year ASCVD risk of 10% to <15% and ≥15% was 8.1% and 7.8% estimated by the PCEs, respectively, and 3.0% and 0.3% estimated by the PREVENT equations, respectively. No participants had a 10-year ASCVD risk ≥10% on the PREVENT equations and <10% on the PCEs, while 12.5% had a 10-year ASCVD risk ≥10% on the PCEs and <10% on the PREVENT equations. The mean 10-year total cardiovascular disease risk estimated by the PREVENT equations was lower than the mean 10-year ASCVD risk on the PCEs. CONCLUSIONS: Among US adults with stage 1 hypertension, the 10-year predicted ASCVD risk estimated by the PREVENT equations was approximately half the risk estimated by the PCEs.

Low-Density Lipoprotein Cholesterol Testing Following Myocardial Infarction Hospitalization Among Medicare Beneficiaries.

Background: Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed opportunity for optimizing therapy and reducing cardiovascular risk. Objectives: The purpose of this study was to estimate the proportion of Medicare beneficiaries who had their LDL-C measured within 90 days following MI hospital discharge. Methods: We conducted a retrospective cohort study of Medicare beneficiaries ≥66 years of age with an MI hospitalization between 2016 and 2020. The primary analysis used data from all beneficiaries with fee-for-service coverage and pharmacy benefits (532,767 MI hospitalizations). In secondary analyses, we used data from a 5% random sample of beneficiaries with fee-for-service coverage without pharmacy benefits (10,394 MI hospitalizations), and from beneficiaries with Medicare Advantage (176,268 MI hospitalizations). The proportion of beneficiaries who had their LDL-C measured following MI hospital discharge was estimated accounting for the competing risk of death. Results: In the primary analysis (mean age 76.9 years, 84.4% non-Hispanic White), 29.9% of beneficiaries had their LDL-C measured within 90 days following MI hospital discharge. Among Hispanic, Asian, non-Hispanic White, and non-Hispanic Black beneficiaries, the 90-day postdischarge LDL-C testing was 33.8%, 32.5%, 30.0%, and 26.0%, respectively. Postdischarge LDL-C testing within 90 days was highest in the Middle Atlantic (36.4%) and lowest in the West North Central (23.4%) U.S. regions. In secondary analyses, the 90-day postdischarge LDL-C testing was 26.9% among beneficiaries with fee-for-service coverage without pharmacy benefits, and 28.6% among beneficiaries with Medicare Advantage coverage. Conclusions: LDL-C testing following MI hospital discharge among Medicare beneficiaries was low.

Plasma Proteomics of Exercise Blood Pressure and Incident Hypertension.

Importance: Blood pressure response during acute exercise (exercise blood pressure [EBP]) is associated with the future risk of hypertension and cardiovascular disease (CVD). Biochemical characterization of EBP could inform disease biology and identify novel biomarkers of future hypertension. Objective: To identify protein markers associated with EBP and test their association with incident hypertension. Design, Setting, and Participants: This study assayed 4977 plasma proteins in 681 healthy participants (from 763 assessed) of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE; data collection from January 1993 to December 1997 and plasma proteomics from January 2019 to January 2020) Family Study at rest who underwent 2 cardiopulmonary exercise tests. Individuals were free of CVD at the time of recruitment. Individuals with resting SBP ≥160 mm Hg or DBP ≥100 mm Hg or taking antihypertensive drug therapy were excluded from the study. The association between resting plasma protein levels to both resting BP and EBP was evaluated. Proteins associated with EBP were analyzed for their association with incident hypertension in the Framingham Heart Study (FHS; n = 1177) and validated in the Jackson Heart Study (JHS; n = 772) and Multi-Ethnic Study of Atherosclerosis (MESA; n = 1367). Proteins associated with incident hypertension were tested for putative causal links in approximately 700 000 individuals using cis-protein quantitative loci mendelian randomization (cis-MR). Data were analyzed from January 2023 to January 2024. Exposures: Plasma proteins. Main Outcomes and Measures: EBP was defined as the BP response during a fixed workload (50 W) on a cycle ergometer. Hypertension was defined as BP ≥140/90 mm Hg or taking antihypertensive medication. Results: Among the 681 participants in the HERITAGE Family Study, the mean (SD) age was 34 (13) years; 366 participants (54%) were female; 238 (35%) were self-reported Black and 443 (65%) were self-reported White. Proteomic profiling of EBP revealed 34 proteins that would not have otherwise been identified through profiling of resting BP alone. Transforming growth factor ß receptor 3 (TGFBR3) and prostaglandin D2 synthase (PTGDS) had the strongest association with exercise systolic BP (SBP) and diastolic BP (DBP), respectively (TGFBR3: exercise SBP, ß estimate, -3.39; 95% CI, -4.79 to -2.00; P = 2.33 × 10-6; PTGDS: exercise DBP ß estimate, -2.50; 95% CI, -3.29 to -1.70; P = 1.18 × 10-9). In fully adjusted models, TGFBR3 was inversely associated with incident hypertension in FHS, JHS, and MESA (hazard ratio [HR]: FHS, 0.86; 95% CI, 0.75-0.97; P = .01; JHS, 0.87; 95% CI, 0.77-0.97; P = .02; MESA, 0.84; 95% CI, 0.71-0.98; P = .03; pooled cohort, 0.86; 95% CI, 0.79-0.92; P = 6 × 10-5). Using cis-MR, genetically predicted levels of TGFBR3 were associated with SBP, hypertension, and CVD events (SBP: ß, -0.38; 95% CI, -0.64 to -0.11; P = .006; hypertension: odds ratio [OR], 0.99; 95% CI, 0.98-0.99; P < .001; heart failure with hypertension: OR, 0.86; 95% CI, 0.77-0.97; P = .01; CVD: OR, 0.84; 95% CI, 0.77-0.92; P = 8 × 10-5; cerebrovascular events: OR, 0.77; 95% CI, 0.70-0.85; P = 5 × 10-7). Conclusions and Relevance: Plasma proteomic profiling of EBP identified a novel protein, TGFBR3, which may protect against elevated BP and long-term CVD outcomes.

Awareness, treatment, and control of hypertension among women at risk or living with HIV in the US South: a prospective study.

OBJECTIVES: Timely control of hypertension is vital to prevent comorbidities. We evaluated the association of race/ethnicity and HIV infection with incident hypertension outcomes, including awareness, treatment, and control. DESIGN: We evaluated cisgender women living with HIV and sociodemographically matched women living without HIV recruited into four Southern sites of the Women's Interagency HIV Study (2013-2019). METHODS: We calculated measurements of the time to four events or censoring: incident hypertension, hypertension awareness, hypertension treatment, and hypertension control. Hazard ratios for race/ethnicity and HIV status were calculated for each outcome using Cox proportional-hazards models adjusted for sociodemographic, behavioral, and clinical risk factors. RESULTS: Among 712 women, 56% were hypertensive at baseline. Forty-five percent of the remaining women who were normotensive at baseline developed incident hypertension during follow-up. Non-Hispanic White and Hispanic women had faster time to hypertension control compared to non-Hispanic Black women (p = 0.01). In fully adjusted models, women living with HIV who were normotensive at baseline had faster time to treatment compared to normotensive women living without HIV (p = 0.04). CONCLUSIONS: In our study of women in the US South, non-Hispanic Black women became aware of their hypertension diagnosis more quickly than non-Hispanic White and Hispanic women but were slower to control their hypertension. Additionally, women living with HIV more quickly treated and controlled their hypertension compared to women living without HIV.

Association of Integrase Strand Transfer Inhibitor-Based Antiretroviral Therapy with Blood Pressure and Sustained Hypertension in People with HIV.

BACKGROUND: Integrase strand transfer inhibitors (INSTI) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP). METHODS: We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic. Office BP was measured unattended using an automated (AOBP) device. Awake, asleep and 24-hour BP were measured through ambulatory BP monitoring. Among participants with SBP ≥130 mmHg or DBP≥80 mmHg on AOBP, sustained hypertension was defined as awake SBP≥130 mmHg or DBP≥80 mmHg. RESULTS: Mean SBP and DBP was higher among participants taking INSTI-based versus non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 versus 135.3/79.3 mmHg; awake-SBP/DBP: 143.2/80.9 versus 133.4/76.3 mmHg; asleep-SBP/DBP: 133.3/72.9 versus 120.3/65.4 mmHg; 24-hour-SBP/DBP: 140.4/78.7 versus 130.0/73.7 mmHg). After multivariable adjustment, AOBP, awake, asleep and 24-hour SBP was 12.5 (95%CI 5.0-20.1), 9.8 (95%CI 3.6-16.0), 10.4 (95%CI 2.0-18.9), and 9.8 (95%CI 4.2-15.4) mmHg higher among those taking INSTI-based versus non-INSTI-based ART, respectively. AOBP, awake, asleep and 24-hour DBP was 7.5 (95%CI 0.3-14.6), 6.1 (95%CI 0.3-11.8), 7.5 (95%CI 1.4-13.6), and 6.1 (95%CI 0.9-11.3) mmHg higher among those taking INSTI-based versus non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mmHg or DBP≥80 mmHg on AOBP and 97.9% and 65.7% of participants taking INSTI-based and non-INSTI-based ART had sustained hypertension, respectively. CONCLUSION: INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART.

Persistence and Adherence to PCSK9 Inhibitor Monoclonal Antibodies Versus Ezetimibe in Real-World Settings.

INTRODUCTION: The cardiovascular disease risk reduction benefits of proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibodies (PCSK9i mAb) and ezetimibe are dependent on remaining on treatment and being persistent and adherent. We estimated the percentage of patients on therapy, persistent and adherent at 182 and 365 days among US adults with health insurance who initiated a PCSK9i mAb (n = 16,588) or ezetimibe (n = 83,086) between July 2015 and December 2019. METHODS: Using pharmacy fill claims, being on therapy was defined as having a day of medication supply in the last 60 of 182 and 365 days following treatment initiation, being persistent was defined as not having a gap of 60 days or more between the last day of supply from one prescription fill and the next fill, and being adherent was defined by having medication available to take on ≥ 80% of the 182 and 365 days following treatment initiation. We estimated multivariable-adjusted risk ratios for being persistent and adherent comparing patients initiating PCSK9i mAb versus ezetimibe using Poisson regression. RESULTS: At 182 days following initiation, 80% and 68% were on therapy and 76% and 64% were persistent among patients who initiated a PCSK9i mAb and ezetimibe, respectively. Among patients who were on therapy and persistent at 182 days following initiation, 88% and 81% of those who initiated a PCSK9i mAb and ezetimibe, respectively, were on therapy at 365 days. Among those on therapy and persistent at 182 days following initiation, being persistent and being adherent at 365 days were each more common among PCSK9i mAb versus ezetimibe initiators (persistent: 82% versus 76%, multivariable-adjusted risk ratio 1.07; 95% confidence interval [CI] 1.06-1.08; adherent: 74% versus 71%, multivariable-adjusted risk ratio 1.02; 95% CI 1.01-1.03). CONCLUSIONS: These data suggest approaches to increase persistence and adherence to PCSK9i mAb and ezetimibe should be implemented prior to or within 182 days following treatment initiation.

Social Determinants of Health and Incident Apparent Treatment-Resistant Hypertension Among White and Black US Adults: The REGARDS Study.

BACKGROUND: We examined the association of multilevel social determinants of health with incident apparent treatment-resistant hypertension (aTRH). METHODS AND RESULTS: We analyzed data from 2774 White and 2257 Black US adults from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study taking antihypertensive medication without aTRH at baseline to estimate the association of social determinants of health with incident aTRH. Selection of social determinants of health was guided by the Healthy People 2030 domains of education, economic stability, social context, neighborhood environment, and health care access. Blood pressure (BP) was measured during study visits, and antihypertensive medication classes were identified through a pill bottle review. Incident aTRH was defined as (1) systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg, or systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg for those with diabetes or chronic kidney disease while taking ≥3 classes of antihypertensive medication or (2) taking ≥4 classes of antihypertensive medication regardless of BP level, at the follow-up visit. Over a median 9.5 years of follow-up, 15.9% of White and 24.0% of Black adults developed aTRH. A percent of the excess aTRH risk among Black versus White adults was mediated by low education (14.2%), low income (16.0%), not seeing a friend or relative in the past month (8.1%), not having someone to care for them if ill or disabled (7.6%), lack of health insurance (10.6%), living in a disadvantaged neighborhood (18.0%), and living in states with poor public health infrastructure (6.0%). CONCLUSIONS: Part of the association between race and incident aTRH risk was mediated by social determinants of health.

Association Between Young Adult Characteristics and Blood Pressure Trajectories.

BACKGROUND: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample. METHODS AND RESULTS: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m2, 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m2, 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2). CONCLUSIONS: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Maintenance of Normal Blood Pressure From Middle to Older Age: Results From the Atherosclerosis Risk in Communities Study.

BACKGROUND: It is unknown whether maintaining normal blood pressure (BP) from middle to older age is associated with improved health outcomes. METHODS: We estimated the proportion of Atherosclerosis Risk in Communities study participants who maintained normal BP from 1987 to 1989 (visit 1) through 1996 to 1998 and 2011 to 2013 (over 4 and 5 visits, respectively). Normal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg, without antihypertensive medication. We estimated the risk of cardiovascular disease, dementia, and poor physical functioning after visit 5. In exploratory analyses, we examined participant characteristics associated with maintaining normal BP. RESULTS: Among 2699 participants with normal BP at baseline (mean age 51.3 years), 47.1% and 15.0% maintained normal BP through visits 4 and 5, respectively. The hazard ratios comparing participants who maintained normal BP through visit 4 but not visit 5 and through visit 5 versus those who did not maintain normal BP through visit 4 were 0.80 (95% CI, 0.63-1.03) and 0.60 (95% CI, 0.42-0.86), respectively, for cardiovascular disease, and 0.85 (95% CI, 0.71-1.01) and 0.69 (95% CI, 0.54-0.90), respectively, for poor physical functioning. Maintaining normal BP through visit 5 was more common among participants with normal body mass index versus obesity at visit 1, those with normal body mass index at visits 1 and 5, and those with overweight at visit 1 and overweight or normal body mass index at visit 5, compared with those with obesity at visits 1 and 5. CONCLUSIONS: Maintaining normal BP was associated with a lower risk of cardiovascular disease and poor physical functioning.

Trends in the Prevalence of Multiple Chronic Conditions Among US Adults With Hypertension From 1999-2000 Through 2017-2020.

BACKGROUND: The prevalence of many chronic conditions has increased among US adults. Many adults with hypertension have other chronic conditions. METHODS: We estimated changes in the age-adjusted prevalence of multiple (≥3) chronic conditions, not including hypertension, using data from the National Health and Nutrition Examination Survey, from 1999-2000 to 2017-2020, among US adults with (n = 24,851) and without (n = 24,337 hypertension. Hypertension included systolic blood pressure (BP) ≥130 mm Hg, diastolic BP ≥80 mm Hg, or antihypertensive medication use. We studied 14 chronic conditions: arthritis, asthma, cancer, coronary heart disease, chronic kidney disease, depression, diabetes, dyslipidemia, hepatitis B, hepatitis C, heart failure, lung disease, obesity, and stroke. RESULTS: From 1999-2000 to 2017-2020, the age-adjusted mean number of chronic conditions increased more among US adults with vs. without hypertension (2.2 to 2.8 vs. 1.7 to 2.0; P-interaction <0.001). Also, the age-adjusted prevalence of multiple chronic conditions increased from 39.0% to 52.0% among US adults with hypertension and from 26.0% to 30.0% among US adults without hypertension (P-interaction = 0.022). In 2017-2020, after age, gender, and race/ethnicity adjustment, US adults with hypertension were 1.94 (95% confidence interval: 1.72-2.18) times as likely to have multiple chronic conditions compared to those without hypertension. In 2017-2020, dyslipidemia, obesity, and arthritis were the most common 3 co-occurring chronic conditions among US adults with and without hypertension (age-adjusted prevalence 16.5% and 3.1%, respectively). CONCLUSIONS: In 2017-2020, more than half of US adults with hypertension had ≥3 additional chronic conditions, a substantial increase from 20 years ago.

Comparing PCSK9 Monoclonal Antibody Treatment Strategies Following Myocardial Infarction Using Negative Control Outcomes: A Target Trial Emulation Study.

BACKGROUND: Initiation of proprotein convertase subtilisin/kexin type 9 monoclonal antibody (PCSK9 mAb) for lipid-lowering following myocardial infarction (MI) is likely affected by patients' prognostic factors, potentially leading to bias when comparing real-world treatment effects. METHODS: Using target-trial emulation, we assessed potential confounding when comparing two treatment strategies post-MI: initiation of PCSK9 mAb within 1 year and no initiation of PCSK9 mAb. We identified MI hospitalizations during July 2015-June 2020 for patients aged ≥18 years in Optum's de-identified Clinformatics Data Mart (CDM) and MarketScan, and those aged ≥66 in the US Medicare claims database. We estimated a 3-year counterfactual cumulative risk and risk difference (RD) for 10 negative control outcomes using the clone-censor-weight approach to address time-varying confounding and immortal person-time. RESULTS: PCSK9 mAb initiation within 1-year post-MI was low (0.7% in MarketScan and 0.4% in both CDM and Medicare databases). In CDM, there was a lower risk for cancer (RD = -3.6% [95% CI: -4.3%, -2.9%]), decubitus ulcer (RD = -7.7% [95% CI: -11.8%, -3.7%]), fracture (RD = -8.1% [95% CI: -9.6%, -6.6%]), influenza vaccine (RD = -9.3% [95% CI: -17.5%, -1.1%]), and visual test (RD = -0.6% [95% CI: -0.7%, -0.6%]) under the PCSK9 mAb initiation versus no initiation strategy. Similar differences persisted in the MarketScan and Medicare databases. In each database, ezetimibe and low-density lipoprotein testing were unbalanced between treatment strategies. CONCLUSION: A comparative effectiveness study of these treatments using the current approach would likely bias results due to the low number of PCSK9 mAb initiators.

Antihypertensive medication persistence and adherence among non-Hispanic Asian US patients with hypertension and fee-for-service Medicare health insurance.

BACKGROUND: Less than 50% of non-Hispanic Asian adults taking antihypertensive medication have controlled blood pressure. METHODS: We compared non-persistence and low adherence to antihypertensive medication between non-Hispanic Asian and other race/ethnicity groups among US adults ≥66 years who initiated antihypertensive medication between 2011 and 2018 using a 5% random sample of Medicare beneficiaries (non-Hispanic Asian, n = 2,260; non-Hispanic White, n = 56,000; non-Hispanic Black, n = 5,792; Hispanic, n = 4,212; and Other, n = 1,423). Non-persistence was defined as not having antihypertensive medication available to take in the last 90 of 365 days following treatment initiation. Low adherence was defined as having antihypertensive medication available to take on <80% of the 365 days following initiation. RESULTS: In 2011-2012, 2013-2014, 2015-2016 and 2017-2018, the proportion of non-Hispanic Asian Medicare beneficiaries with non-persistence was 29.1%, 25.6%, 25.4% and 26.7% (p-trend = 0.381), respectively, and the proportion with low adherence was 58.1%, 54.2%, 53.4% and 51.6%, respectively (p-trend = 0.020). In 2017-2018, compared with non-Hispanic Asian beneficiaries, non-persistence was less common among non-Hispanic White beneficiaries (risk ratio 0.74 [95%CI, 0.64-0.85]), non-Hispanic Black beneficiaries (0.80 [95%CI 0.68-0.94]) and those reporting Other race/ethnicity (0.68 [95%CI, 0.54-0.85]) but not among Hispanic beneficiaries (1.04 [95%CI, 0.88-1.23]). Compared to non-Hispanic Asian beneficiaries, non-Hispanic White beneficiaries and beneficiaries reporting Other race/ethnicity were less likely to have low adherence to antihypertensive medication (relative risk 0.78 [95%CI 0.72-0.84] and 0.84 [95%CI 0.74-0.95], respectively); there was no association for non-Hispanic Black or Hispanic beneficiaries. CONCLUSIONS: Non-persistence and low adherence to antihypertensive medication were more common among older non-Hispanic Asian than non-Hispanic White adults.

Staging and clean room: Constructs designed to facilitate transparency and reduce bias in comparative analyses of real-world data.

PURPOSE: We describe constructs designed to protect the integrity of the results from comparative analyses using real-world data (RWD): staging and clean room. METHODS: Staging involves performing sequential preliminary analyses and evaluating the population size available and potential bias before conducting comparative analyses. A clean room involves restricted access to data and preliminary results, policies governing exploratory analyses and protocol deviations, and audit trail. These constructs are intended to allow decisions about protocol deviations, such as changes to design or model specification, to be made without knowledge of how they might affect subsequent analyses. We describe an example for implementing staging with a clean room. RESULTS: Stage 1 may involve selecting a data source, developing and registering a protocol, establishing a clean room, and applying inclusion/exclusion criteria. Stage 2 may involve attempting to achieve covariate balance, often through propensity score models. Stage 3 may involve evaluating the presence of residual confounding using negative control outcomes. After each stage, check points may be implemented when a team of statisticians, epidemiologists and clinicians masked to how their decisions may affect study outcomes, reviews the results. This review team may be tasked with making recommendations for protocol deviations to address study precision or bias. They may recommend proceeding to the next stage, conducting additional analyses to address bias, or terminating the study. Stage 4 may involve conducting the comparative analyses. CONCLUSIONS: The staging and clean room constructs are intended to protect the integrity and enhance confidence in the results of analyses of RWD.

Trends in All-Cause, Cardiovascular, and Noncardiovascular Mortality Among US Adults With Hypertension.

BACKGROUND: Death certificate data indicate that hypertension may have increased as a contributing cause of death among US adults. Hypertension is not commonly recorded on death certificates although it contributes to a substantial proportion of cardiovascular disease (CVD) deaths. METHODS: We estimated changes in all-cause, CVD, and non-CVD mortality over 5 years of follow-up among 4 cohorts of US adults with hypertension using mortality follow-up data from National Health and Nutrition Examination Survey III in 1988 to 1994, and National Health and Nutrition Examination Survey cycles from 1999 to 2000 through 2015 to 2016 (n=20 927). Hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or antihypertensive medication use. Participants were grouped according to the date of their National Health and Nutrition Examination Survey study visit (1988-1994, 1999-2004, 2005-2010, 2011-2016). RESULTS: There were 2646, 1048, and 1598 all-cause, CVD, and non-CVD deaths, respectively. After age, gender, and race/ethnicity adjustment and compared with the 1988 to 1994 cohort, the hazard ratio of all-cause mortality was 0.88 (95% CI, 0.76-1.01) for the 1999 to 2004 cohort, 0.82 (95% CI, 0.70-0.95) for the 2005 to 2010 cohort, and 0.89 (95% CI, 0.75-1.05) for the 2011 to 2016 cohort (P trend=0.123). The age, gender, and race/ethnicity-adjusted hazard ratios for CVD mortality compared with the 1988 to 1994 cohort were 0.74 (95% CI, 0.60-0.90) for the 1999 to 2004 cohort, 0.61 (95% CI, 0.50-0.74) for the 2005 to 2010 cohort, and 0.57 (95% CI, 0.44-0.74) for the 2011 to 2016 cohort (P trend <0.001). There was no evidence of a change in CVD mortality between the 2005 to 2010 and 2011 to 2016 cohorts (P=0.661). Noncardiovascular mortality did not decline over the study period (P trend=0.145). CONCLUSIONS: The decline in CVD mortality among US adults with hypertension stalled after 2005 to 2010.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium >1,000.

BACKGROUND: Although a coronary artery calcium (CAC) of ≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. OBJECTIVES: Among persons with a CAC of ≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. METHODS: The authors studied 2,246 asymptomatic patients with a CAC of ≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by ≥2 major ASCVD events or 1 major event and ≥2 high-risk conditions (1.4 per 100 person-years). RESULTS: The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC ≥300). Diabetes (HR: 2.04 [95% CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95% CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95% CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95% CI: 0.8-1.9]), severe LM CAC (1.3 [95% CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95% CI: 3.4-10.8]). CONCLUSIONS: Among asymptomatic patients with a CAC of ≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.