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BACKGROUND: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear. OBJECTIVES: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years. METHODS: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years. RESULTS: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile. CONCLUSIONS: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events.

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Lipoprotein(a) has been shown to be disruptive to local endothelial cells, whose integrity is critical to blood pressure (BP) regulation. Cross-sectional analysis has shown an association between lipoprotein(a) and prevalent hypertension, though it is unclear if lipoprotein(a) increases risk of incident hypertension. To assess this, the authors measured baseline lipoprotein(a) among 5307 normotensive patients (median age 26 years (interquartile range [IQR] 12-50) and used Cox proportional hazard models to generate hazard rations (HR) with 95% confidence intervals (CI; median follow-up 10-years). The authors categorized lipoprotein(a) as <15 mg/dL, 15-<30 mg/dL, 30-50 mg/dL, >50 mg/dL, and performed subgroup analysis of adults >50 years at baseline. Incident hypertension was defined as a measured BP ≥140/90 mm Hg or a new ICD-9/10 code. After adjustment, hypertension for patients with baseline lipoprotein(a) 15-<30 mg/dL, 30-50 mg/dL, and >50 mg/dL was 0.91 (0.72-1.16), 1.05 (0.79-1.38), and 1.02 (0.83-1.26; vs. <15 mg/dL). However, among adults >50 years, lipoprotein(a) >50 mg/dL was associated with increased incident hypertension (1.62 [1.17-2.26]).

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BACKGROUND: Young adults with elevated LDL-C may experience increased burden of additional cardiovascular disease (CVD) risk factors. It is unclear how much LDL-C levels, a modifiable factor, correlate with non-LDL-C CVD risk factors among young adults or how strongly these CVD risk factors are associated with long-term predicted CVD risk. We quantified clustering of non-LDL-C CVD risk factors by LDL-C among young adults to assess the association between non-LDL-C and LDL-C risk factors with predicted CVD risk in young adults. METHODS: The current analysis is a cross-sectional study of adults < 40 years with an LDL-C< 190 mg/dL participating in the National Health and Nutrition Examination Survey (NHANES) between January 2015 and March 2020. We measured the prevalence of non-LDL-C risk factors by LDL-C and association between LDL-C and non-LDL-C risk factors with predicted risk of CVD by the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations. RESULTS: Among 2108 young adults, the prevalence of LDL-C ≥ 130 mg/dL was 15.5%. Compared with young adults with LDL-C < 100 mg/dL, those with LDL-C 100-< 130, 130-< 160, and 160-< 190 mg/dL had greater non-LDL-C risk factors. Both LDL-C and non-LDL-C risk factors were independently associated with a 30-year risk of CVD (OR 1.05, 95% CI 1.03-1.07 and OR 1.17, 95% CI 1.12-1.23, respectively). The association of LDL-C and 30-year risk did not vary by non-LDL-C risk factor burden (pinteraction = 0.43). CONCLUSION: Non-LDL-C risk factors cluster among increasing levels of LDL-C in young adults. Greater guidance on how to manage cardiovascular risk factors in young adults is needed.

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BACKGROUND: Antihypertensive medication use patterns have likely been influenced by changing costs and accessibility over the past 3 decades. This study examines the relationships between patent exclusivity loss, medication costs, and national health policies on antihypertensive medication use. METHODS: Using 1996 to 2021 Medical Expenditure Panel Survey data of US adults with hypertension taking at least 1 antihypertensive medication, we conducted a cross-sectional analysis. We explored the associations between patent exclusivity loss, per-pill costs, and Medicare Part D enactment on medication use over time, focusing on the most commonly used medications (lisinopril, amlodipine, losartan, hydrochlorothiazide, and metoprolol). RESULTS: The unweighted sample comprised 50 095 US adults (mean age, 62 years; 53% female). The survey-weighted number of adults taking antihypertensive medications increased from 22 million (95% CIs, 20-23 million) to 55 million (95% CI, 51-60 million) between 1996 and 2021. Loss of patent exclusivity led to increased medication fills, notably for lisinopril, amlodipine, and losartan, which all exhibited within-class dominance. However, per-pill cost decreases coinciding with Medicare Part D did not increase the number of individuals treated or the use of specific antihypertensive medications or classes. CONCLUSIONS: The increase in antihypertensive medication use over the past decades highlights the significant impact of loss of patent exclusivity on the uptake in the use of specific medications. These findings underscore the complexity of factors influencing medication use, beyond cost reductions alone, and suggest that policies need to consider multiple facets to effectively improve antihypertensive medication accessibility and utilization.

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Socioeconomic status (SES) is a multi-faceted theoretical construct associated with stroke risk and outcomes. Knowing which SES measures best correlate with population stroke metrics would improve its accounting in observational research and inform interventions. Using the Centers for Disease Control and Prevention's (CDC) Population Level Analysis and Community Estimates (PLACES) and other publicly available databases, we conducted an ecological study comparing correlations of different United States county-level SES, health care access and clinical risk factor measures with age-adjusted stroke prevalence. The prevalence of adults living below 150% of the federal poverty level most strongly correlated with stroke prevalence compared to other SES and non-SES measures (correlation coefficient = 0.908, R2 = 0.825; adjusted partial correlation coefficient: 0.589, R2 = 0.347). ANN NEUROL 2024.

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BACKGROUND: Peripheral intravenous catheters (PIVs) are the most frequently used invasive device in hospitalized patients. These devices are not benign and are associated with complications. However, clinician awareness of them is variable and poorly understood. METHODS: We conducted a prospective, multicenter, observational point prevalence study to assess awareness of PIV presence among clinicians caring for hospitalized patients in 4 hospitals between May 2018 and February 2019 located in Michigan, USA. We first assessed patients for the presence of a PIV then interviewed their providers. Differences in awareness by provider type were assessed via χ² tests; P < .05 was considered statistically significant. Analyses were performed on Stata MP v16. RESULTS: A total of 1,385 patients and 4,003 providers were interviewed. Nurses had the greatest awareness of overall PIV presence, 98.6%, while attendings were correct 88.1% of the time. Nurses were more likely to correctly assess PIV presence and exact location than physicians (67.7% vs <30% for all others). Awareness of PIV presence did not significantly vary in patients on contact precautions or those receiving infusions. CONCLUSIONS: Given the ubiquity of PIVs and known complications, methods to increase awareness to ensure appropriate care and removal are necessary.

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BACKGROUND: Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort. METHODS AND RESULTS: A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses. CONCLUSIONS: Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.

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BACKGROUND: Therapeutic inertia (TI), failure to intensify antihypertensive medication when blood pressure (BP) is above goal, remains prevalent in hypertension management. The degree to which self-reported antihypertensive adherence is associated with TI with intensive BP goals remains unclear. METHODS AND RESULTS: Cross-sectional analysis was performed of the 12-month visit of participants in the intensive arm of SPRINT (Systolic Blood Pressure Intervention Trial), which randomized adults to intensive (<120 mm Hg) versus standard (<140 mm Hg) systolic BP goals. TI was defined as no increase in antihypertensive regimen intensity score, which incorporates medication number and dose, when systolic BP is ≥120 mm Hg. Self-reported adherence was assessed using the 8-Item Morisky Medication Adherence Scale (MMAS-8) and categorized as low (MMAS-8 score <6), medium (MMAS-8 score 6 to <8), and high (MMAS-8 score 8). Poisson regressions estimated prevalence ratios (PRs) and 95% CIs for TI associated with MMAS-8. Among 1009 intensive arm participants with systolic BP >120 mm Hg at the 12-month visit (mean age, 69.6 years; 35.2% female, 28.8% non-Hispanic Black), TI occurred in 50.8% of participants. Participants with low adherence (versus high) were younger and more likely to be non-Hispanic Black or smokers. The prevalence of TI among patients with low, medium, and high adherence was 45.0%, 53.5%, and 50.4%, respectively. After adjustment, neither low nor medium adherence (versus high) were associated with TI (PR, 1.11 [95% CI, 0.87-1.42]; PR, 1.08 [95% CI, 0.84-1.38], respectively). CONCLUSIONS: Although clinician uncertainty about adherence is often cited as a reason for why antihypertensive intensification is withheld when above BP goals, we observed no evidence of an association between self-reported adherence and TI.

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BACKGROUND: Considering that mail-order pharmacy use remains low in the United States, geographic accessibility of community pharmacies (pharmacy access) can have an outsized impact on a community's access to services and care, especially among rural residents. However, previous measurements of pharmacy access rely on methods that do not capture all aspects of geographic access. OBJECTIVES: This study aimed to measure pharmacy access across the contiguous United States and by rural, suburban, and urban areas using drive-time analysis and an improved methodological approach. METHODS: The 2-step floating catchment area method was used to measure pharmacy access by considering the supply capacity of pharmacies, population demand for pharmacies, and the interaction between them within a reasonable travel time range. This method is a methodologically improved approach compared with previous methods for measuring geographic access. Network analysis was used to measure drive time from the population-weighted centroids of census tracts to the geocoded location of community pharmacies. Census tract-level pharmacy access was measured using a 10- and 20-minute drive time. Census tracts were also categorized based on population per square mile as rural (< 1000), suburban (1000-3000), and urban (> 3000). RESULTS: Across the contiguous United States, 79.9% and 91.1% of census tracts had access to at least 1 pharmacy per 10,000 people within a 10- and 20-minute drive time, respectively. Rural census tracts had the lowest share of access to at least 1 pharmacy per 10,000 people compared with suburban and urban tracts and for both drive times. CONCLUSION: Community pharmacies are highly accessible health care access points, specifically in urban and suburban areas. Pharmacies should be considered to expand access to services with limited geographic accessibility such as treatment programs for opioid use disorders, primary care, and healthy foods.

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Objective: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2Is) lower adverse cardiac and kidney events among high-risk patients with diabetes mellitus (DM) and are now guideline-recommended as first-line therapy alongside metformin. However, the adoption of these new treatments from 2015 to 2020 among the highest-risk adults with DM remains unclear. Methods: We performed a cross-sectional analysis of the National Health and Nutrition Examination Surveys (NHANES) 2015-2020 to estimate the use of GLP1-RAs and SGLT2Is among adults with DM overall and by level of cardiovascular and kidney risk (CKR). We defined high CKR by history of atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), heart failure, or age ≥55 years with at least 2 ASCVD risk factors (i.e., obesity, hypertension, hyperlipidemia, or current smoker). Results: Overall, 2,432 participants with DM (mean age 60.6 years, 46.8 % female, 58.8 % Non-Hispanic White) were included, of which 1,869 and 563 were with and without high CKR, respectively. Participants with vs. without high CKR were more likely to be older, have higher systolic blood pressure, lower estimated glomerular filtration rate, use oral antidiabetic agents, and have health insurance. Overall, the weighted prevalence of GLP1-RA or SGLT2I was 9.0 % (95 % confidence interval [CI] 6.9-11.0): 4.8 % (95 % CI 3.6-6.1) took GLP1-RAs, and 5.1 % (95 % CI 3.3-7.0) took SGLT2Is. Use of GLP1-RAs or SGLT2Is did not differ between participants with vs. without high CKR (adjusted prevalence ratio [aPR] 1.00; 95 % CI 0.98-1.02). Participants with ASCVD were more likely to be on a GLP1-RA or SGLT2I (aPR 1.28; 95 % CI 1.25-1.31), while adults with CKD were less likely (aPR 0.84; 95 % CI 0.82-0.86). Conclusion: Among US adults with DM, GLP1-RA and SGLT2I use was low regardless of CKR. Data since 2020 analyzing the utilization of GLP1-RAs and SGLT2Is among high-CKR patients with DM is needed to identify implementation strategies for increased utilization.

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Associations of anticoagulation with primary endpoints in longitudinal studies are impacted by selection bias and time-varying covariates (e.g. comorbidities). We demonstrate how time-varying covariates and selection bias influence association estimates between anticoagulation and health-related quality of life (HRQoL) in patients with atrial fibrillation. We performed a secondary analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial quality of life substudy. Dichotomized warfarin use was ascertained at the study baseline, 2 months later, and annually for up to 6 years. HRQoL was measured at every time point using a self-reported ordinal 5-point Likert-scale (lower score and lower odds ratio represents better health-related quality of life). Static and time-varying covariates were ascertained throughout the study period. Confounder-adjusted generalized mixed model and generalized estimating equation regressions were used to demonstrate traditional association estimates between anticoagulation and HRQoL. Inverse probability of treatment and censorship weights were used to ascertain the influence of time-varying confounding and selection bias. Age-stratified analysis (age ≥ 70 years) evaluated for effect modification. 656 individuals were included in the analysis, 601 on warfarin at baseline. The association of warfarin use with better HRQoL over time strengthened when accounting for time-varying confounding and selection bias (OR 0.30, 95% CI 0.14-0.55) compared to traditional analyses (OR 0.61, 95% CI 0.38-0.97), and was most pronounced in those ≥ 70 years upon stratified analysis. Anticoagulation is associated with higher HRQoL in patients with atrial fibrillation, with time-varying confounding and selection bias likely influencing longitudinal estimates in anticoagulation-HRQoL research.

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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.

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Statin use among younger adults at high atherosclerotic cardiovascular disease (ASCVD) risk compared with older adults at the same risk is unclear. We determined prevalent statin use by 10-year ASCVD risk and age among US participants aged 40-75 eligible for risk-indicated primary prevention statins from the 2013-2020 National Health and Nutrition Examination Survey cycles. Among 3,503 participants, statin use by ASCVD risk (5-<7.5%, 7.5-<20%, and ≥20%) was 9.4%, 9.0%, and 12.2% among those age 40-54 compared to 22.0%, 23.9%, and 14.3% among adults 55-64 years and 39.3%, 33.6%, and 38.1% age 65-75 years. After adjusting for sociodemographic and healthcare access, the prevalence ratio (vs. 65-75 years) for statin use among adults with an ASCVD risk of 7.5-<20% age 40-54 years was 0.40 (95% confidence interval [CI] 0.39,0.41) and 0.87 (95% CI 0.87,0.88) for adults 55-64 years. Among high ASCVD-risk adults aged 40-75 years, primary prevention statin use was lower among adults <65 years despite similar ASCVD risk as older adults.

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BACKGROUND AND OBJECTIVES: It is unclear whether blood pressure variability's (BPV) association with worse outcomes is unique to patients with stroke or a risk factor among all critically ill patients. We (1) determined whether BPV differed between patients with stroke and nonstroke patients, (2) examined BPV's associations with in-hospital death and favorable discharge destination in patients with stroke and nonstroke patients, and (3) assessed how minimum mean arterial pressure (MAP)-a correlate of illness severity and cerebral perfusion-affects these associations. METHODS: This is a retrospective analysis of adult intensive care unit patients hospitalized between 2001 and 2012 from the Medical Information Mart for Intensive Care III database. Confounder-adjusted logistic regressions determined associations between BPV, measured as SD and average real variability (ARV), and (1) in-hospital death and (2) favorable discharge, with testing of minimum MAP for effect modification. RESULTS: BPV was higher in patients with stroke (N = 2,248) compared with nonstroke patients (N = 9,085) (SD mean difference 2.3, 95% CI 2.1-2.6, p < 0.01). After adjusting for minimum tertile of MAP and other confounders, higher SD remained significantly associated (p < 0.05) with higher odds of in-hospital death for patients with acute ischemic strokes (AISs, odds ratio [OR] 2.7, 95% CI 1.5-4.8), intracerebral hemorrhage (ICH, OR 2.6, 95% CI 1.6-4.3), subarachnoid hemorrhage (SAH, OR 3.4, 95% CI 1.2-9.3), and pneumonia (OR 1.9, 95% CI 1.1-3.3) and lower odds of favorable discharge destination in patients with ischemic stroke (OR 0.3, 95% CI 0.2-0.6) and ICH (OR 0.4, 95% CI 0.3-0.6). No interaction was found between minimum MAP tertile with SD (p > 0.05). Higher ARV was not significantly associated with increased risk of death in any condition when adjusting for illness severity but portended worse discharge destination in those with AIS (OR favorable discharge 0.4, 95% CI 0.3-0.7), ICH (OR favorable discharge 0.5, 95% CI 0.3-0.7), sepsis (OR favorable discharge 0.8, 95% CI 0.6-1.0), and pneumonia (OR favorable discharge 0.5, 95% CI 0.4-0.8). DISCUSSION: BPV is higher and generally associated with worse outcomes among patients with stroke compared with nonstroke patients. BPV in patients with AIS and patients with ICH may be a marker of central autonomic network injury, although clinician-driven blood pressure goals likely contribute to the association between BPV and outcomes.

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