Optimizing antithrombotic therapy in patients with coexisting cardiovascular and gastrointestinal disease.

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases.

Analysis of Gender and Race in Pharmacy Faculty and Administrators.

OBJECTIVE: The objective of this report is to identify and characterize the relative likelihood of women and racially minoritized pharmacy faculty being promoted, advancing within leadership roles, and earning comparable salaries. METHODS: Data from the 2010-2021 American Association of Colleges of Pharmacy Profile of Pharmacy Faculty surveys were analyzed to compare odds ratios for promotion, leadership roles, and salary gaps of pharmacy faculty according to race and gender. Changes in the odds ratios over time were characterized by linear regression and predictions about when and if equality would be achieved according to current trends were calculated. RESULTS: Compared to White male counterparts, faculty identifying as women, Black, Hispanic, or Asian had a significantly lower odds ratio of promotion to associate or full professor. Women and Asian faculty also had a lower likelihood of promotion from assistant to associate or Chief Executive Officer (CEO) dean. No demographics studied were more likely than White men to advance in rank or attain associate or CEO dean leadership positions. Furthermore, negative salary gaps for women emerge after promotion from assistant professor, becoming significant and continuing to widen at the associate (-$20,419) and CEO dean (-$37,495) level. CONCLUSION: Despite attention to matters of diversity, equity, and inclusion, female and racially minoritized faculty continue to experience lower rates of promotion, leadership advancement, and wages compared to White male colleagues. These results have negative consequences for recruiting and retaining talented faculty and students, and compromise the benefits that a diverse faculty is known to provide on student learning outcomes.

A Real-World Analysis of New-Onset Heart Failure After Anterior Wall ST-Elevation Acute Myocardial Infarction in the United States.

The 1-year incidence of heart failure (HF) after anterior wall ST-elevation acute myocardial infarction (STEMI) remains difficult to determine because of inconsistencies in reporting, definitions, and adjudication. The objective of this study was to evaluate the 1-year incidence of HF after anterior wall STEMI in a real-world data set using a variety of potential criteria and composite definitions. In a retrospective cohort study, anonymized patient data was accessed through a federated health research network (TriNetX Limited Liability Company (LLC)) of 56 US healthcare organizations (US Collaborative Network). Patients were identified based on the International Classification of Diseases, Tenth Revision criteria for anterior wall STEMI during the 10-year period from 2013 to 2022 and the absence of prespecified signs or symptoms of HF. Values for 1-year incidence were calculated as 1 minus Kaplan-Meier survival at 12 months after anterior wall STEMI. Univariate Cox proportional hazard ratio was calculated to compare risk associated with potential risk factors. The analysis utilized 5 different types of definition criteria for HF: Diagnosis codes, Signs and symptoms, Laboratory/imaging, Medications, and Composites. A total of 34,395 patients from the US Collaborative Network met eligibility criteria and were included in the analysis. The 1-year incidence of HF varied from 2% to 30% depending upon the definition criteria. Although no single criteria exceeded a 1-year incidence of 20%, a simple composite of HF diagnosis (International Classification of Diseases, Tenth Revision-I50) or use of loop diuretic produced a 1-year incidence 26.1% that was used as the benchmark outcome for evaluation of risk factors. Age ≥65 years, Black race, low-density lipoprotein ≥100 mg/100 ml, elevated hemoglobin A1c (7% to 9% and >9%), and body mass index≥35 kg/m2 were also associated with increased risk of HF. In conclusion, patients with anterior wall STEMI continue to be at high risk for new-onset HF. In the absence of structured, prospective, systematically adjudicated diagnostic criteria, composite definitions are more likely to yield accurate estimates of HF incidence.

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. METHODS: We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. RESULTS: We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). CONCLUSIONS: Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed. METHODS: We analyzed 139 patients from three Virginia Commonwealth University Anakinra Response Trial randomized clinical trials to assess whether CRP levels predicted HF hospitalization or death in patients with STEMI, and if CRP levels influenced the effects of treatment with anakinra. RESULTS: CRP cut-off levels for prediction of the composite of death or HF hospitalization for CRP at admission, 3 and 14 days were, respectively 6.45 mg/L (100% of sensitivity and 66.1% specificity), 26 mg/L (100% of sensitivity and 78% specificity) and 9.56 mg/L (100% of sensitivity and 80% specificity). More patients with elevated CRP levels died or had a HF hospitalization (5/47 [11%] vs 0/82 [0%], p = 0.004 for CRP at admission; 5/32 [15.6%] vs 0/92 [0%], p < 0.001 for day 3 and 5/26 [19%] vs 0/89 [0%], p < 0.001 for day 14). A greater number of patients treated with anakinra had low CRP levels at 3 and 14 days compared to placebo (Odds Ratio 0.11 [95% IC 0.04-0.28], p < 0.0001 and OR 0.35 [95% CI 0.14-0.86], p = 0.02, respectively). Anakinra significantly prevented death or HF hospitalization in patients with high inflammatory burden (p = 0.04 for admission, p = 0.24 for day 3, and p = 0.05 for day 14). CONCLUSION: Patients with elevated CRP had higher incidence of HF hospitalization or death. Anakinra reduced the number of patients with elevated CRP levels and prevented death or HF hospitalization in patients with elevated CRP levels.

Interleukin-1 Inhibition for the Prevention and Treatment of Heart Failure.

ABSTRACT: Heart failure (HF) is a complex syndrome that remains a leading cause of morbidity and mortality worldwide. Abundant evidence suggests inflammation plays a key role in the development and perpetuation of HF, but there are currently no anti-inflammatory treatments approved for use in HF. Interleukin-1 (IL-1), the prototypical pro-inflammatory cytokine, has been implicated in adverse cardiac remodeling and left ventricular dysfunction. Multiple early phase clinical trials using IL-1 blockade in patients at risk for or diagnosed with HF have suggested favorable safety and efficacy in reducing inflammatory biomarkers, as well as positive signals in surrogate and clinical endpoints. Additional large scale clinical trials are urgently needed to confirm the safety and efficacy of this therapeutic approach specifically in HF. In this narrative review, we discuss current evidence regarding IL-1 blockade in the prevention and treatment of HF.

ACE-Inhibitors in Hypertension: A Historical Perspective and Current Insights.

PURPOSE OF REVIEW: This review describes the discovery and development of ACE inhibitors as antihypertensive agents, compares their efficacy, tolerability, and safety to ARBs, and highlights the contemporary issues surrounding ACE inhibitor use for HTN. RECENT FINDINGS: Angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed medications for the management of hypertension (HTN) and other chronic conditions including heart failure and chronic kidney disease. These agents inhibit ACE, the enzyme that is responsible for converting angiotensin (AT) I to AT II. Inhibiting the synthesis of AT II causes arterial and venous vasodilation, natriuresis, and a decrease in sympathetic activity, resulting in the reduction of blood pressure. ACE inhibitors are first-line therapy in HTN management along with thiazide diuretics, calcium channel blockers, and angiotensin receptor blockers (ARB). Along with inhibiting AT II synthesis, inhibition of ACE causes accumulation of bradykinin, increasing the risk of bradykinin-mediated side effects like angioedema and cough. Since ARBs do not work on ACE in the renin-angiotensin system, the risk of angioedema and cough are lower with ARBs. Recent evidence has also suggested ARBs may have neuroprotective effects compared to other antihypertensives, including ACE inhibitors; however, this warrants further study. Currently, ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment for the management of HTN. Recent evidence has shown ARBs to be just as effective as ACE inhibitors for HTN but with improved tolerability.

Curriculum mapping of accredited pharmacy programs in the United States.

INTRODUCTION: No current guidance exists to inform the content area credit hours for doctor of pharmacy (PharmD) programs in the United States (US). METHODS: Public websites were accessed for all Accreditation Council for Pharmacy Education (ACPE) accredited PharmD programs in the US to record the credit hours devoted to drug therapy, clinical skills, experiential learning, scholarship, social and administrative sciences, physiology/pathophysiology, pharmacogenomics, medicinal chemistry, pharmacology, pharmaceutics, and pharmacokinetics/pharmacodynamics in the didactic curricula. Due to the high prevalence of programs that integrate drug therapy, pharmacology, and medicinal chemistry into a single course, we subdivided programs based upon whether drug therapy courses were "integrated" or "non-integrated." A regression analyses was conducted to explore the relationship between each content area and North American Pharmacist Licensure Examination (NAPLEX) pass rates and residency match rates. RESULTS: Data were available for 140 accredited PharmD programs. Drug therapy had the highest credit hours in programs with both integrated and non-integrated drug therapy courses. Programs with integrated drug therapy courses had significantly more credit hours in experiential and scholarship and fewer credit hours in stand-alone courses for pathophysiology, medicinal chemistry, and pharmacology. Credit hours in content areas did not predict NAPLEX pass rate nor residency match success rate. CONCLUSIONS: This is the first comprehensive description of all ACPE accredited pharmacy schools with credit hours broken down by content areas. While content areas did not directly predict success criteria, these results may still be useful to describe curricular norms or inform the design of future pharmacy curricula.

A Four-day Pharmacy Course Schedule.

OBJECTIVE: To discuss the results of implementing a 4-day student didactic course schedule. METHODS: The change from a 5-day to a 4-day course schedule was implemented in spring 2021. Students in the classes of 2023 and 2024 and faculty course coordinators were surveyed in fall 2021 regarding their experience with the new schedule format. Baseline data from fall 2020 were also collected for comparison. Quantitative data was described using frequencies, percentages, odds ratios, and 95% confidence intervals. Open-ended questions were evaluated using qualitative thematic analysis. RESULTS: Almost all students (n = 193, 97%) who responded to the course planning survey in fall 2021 wanted to continue the 4-day course schedule. Students perceived the benefits of the 4-day schedule, to include more time for studying/preparing for classes (69%), and for self-care and wellness activities (20%). Student survey responses showed increased odds of engagement outside of the class. Qualitative analysis found that students reported increased engagement and liked the improved course structure. Students disliked the longer time spent in class. Academic performance was reported as somewhat or significantly improved by 85% of respondents. Faculty (n = 31; response rate 80%) reported that the 4-day course schedule positively impacted (48%) or had no impact (42%) on their job responsibilities. Work-life balance (87%) was noted as the most positive effect from faculty respondents. CONCLUSION: A 4-day course schedule was well received by both students and faculty. Institutions may consider a similar approach to allow students the flexibility of this novel schedule so as to have more time to prepare for class and wellness activities.

Interleukin-1 blockers for the treatment of recurrent pericarditis: pathophysiology, patient reported outcomes and perspectives.

ABSTRACT: Recurrent pericarditis (RP) is the most troublesome complication of acute pericarditis reflecting an unresolving inflammation of the pericardial sac around the heart and associated with significant morbidity. Recent studies have shown interleukin-1 (IL-1) signaling to be central to the pathophysiology of cases of RP with evidence of activation of systemic inflammation. We herein review the literature and clinical trials discussing the utility of IL-1 blockade for RP. The early experience of IL-1 blockade with anakinra (Kineret) and its favorable safety profile paved the way for the clinical development of rilonacept (Arcalyst) and subsequent approval by the US FDA for RP. In patients with RP who have become colchicine-resistant and glucocorticoid-dependent, IL-1 blockade with rilonacept or anakinra effectively treats recurrences and prevents future flares, and significantly improves quality of life.

Change in Eosinophil Count in Patients with Heart Failure Treated with Anakinra.

BACKGROUND: Interleukin-1 blockade with anakinra leads to a transient increase in eosinophil blood count (eosinophils) in patients with acute myocardial infarction. We aimed to investigate the effect of anakinra on changes in eosinophils in patients with heart failure (HF) and their correlation with cardiorespiratory fitness (CRF). METHODS: We measured eosinophils in 64 patients with HF (50% females), 55 (51-63) years of age, before and after treatment, and, in a subset of 41 patients, also after treatment cessation. We also evaluated CRF, measuring peak oxygen consumption (VO2) with a treadmill test. RESULTS: Treatment with anakinra significantly and transiently increased eosinophils, from 0.2 [0.1-0.3] to 0.3 [0.1-0.4] × 103 cells/µL (p < 0.001) and from 0.3 [0.2-0.5] to 0.2 [0.1-0.3] × 103 cells/µL, with suspension (p < 0.001). Changes in eosinophils correlated with the changes in peak VO2 (Spearman's Rho = +0.228, p = 0.020). Eosinophils were higher in patients with injection site reactions (ISR) (n = 8, 13%; 0.5 [0.4-0.6] vs. 0.2 [0.1-0.4] × 103 cells/µL, p = 0.023), who also showed a greater increase in peak VO2 (3.0 [0.9-4.3] vs. 0.3 [-0.6-1.8] mLO2·kg-1·min-1, p = 0.015). CONCLUSION: Patients with HF treated with anakinra experience a transient increase in eosinophils, which is associated with ISR and a greater improvement in peak VO2.

Clinical and Pharmacological Implications of Time to Treatment with Interleukin-1 Blockade in ST-Segment Elevation Myocardial Infarction.

Interleukin-1 (IL-1) blockade with anakinra given within 12 hours from reperfusion has been shown to reduce the inflammatory response as well as prevent heart failure (HF) events in patients with STEMI. We sought to determine whether time-to-treatment influences the efficacy of anakinra on systemic inflammation and incidence of HF events in patients with STEMI. We divided the cohort in two groups base6d on the median time from percutaneous coronary intervention (PCI) to investigational drug, and analyzed the effects of anakinra on the area-under-the-curve for C reactive protein (AUC-CRP) and on incidence of the composite endpoint of death or new onset HF. We analyzed data from 139 patients: 84 (60%) treated with anakinra and 55 (40%) with placebo. The median time from PCI to investigational treatment was 271 (182-391) minutes. The AUC-CRP was significantly higher in patients receiving placebo versus anakinra both in those with time from PCI to treatment <271 minutes (222.6 [103.9-325.2] vs. 78.4 [44.3-131.2], P < 0.001) and those with time from PCI to treatment ≥271 minute (235.2 [131.4-603.4] vs. 75.5 [38.9-171.9], P < 0.001) (P > 0.05 for interaction). Anakinra significantly reduced the combined endpoint of death or new onset HF in patients with time from PCI to treatment <271 minutes (5 [11%] vs. 9n[36%], log-rank χ 2 5.985, P = 0.014) as well as in patients with time from PCI to drug ≥271 minutes (2n[5%] vs. 7 [23%], log-rank χ 2 3.995, P = 0.046) (P > 0.05 for interaction). IL-1 blockade with anakinra blunts the acute systemic inflammatory response and prevents HF events independent of time-to-treatment. SIGNIFICANCE STATEMENT: In patients with ST segment elevation presenting within 12 hours of pain onset and treated within 12 hours of reperfusion, interleukin-1 blockade with anakinra blunts the acute systemic inflammatory response, a surrogate of interleukin-1 activity, and prevents heart failure events independent of time-to-treatment.

Comparison of Safety and Biological Efficacy of Anakinra (Kineret) Dispensed in Polycarbonate Plastic versus Borosilicate Glass Syringes: A Patient-Level Analysis of VCUART2 and VCUART3 Clinical Trials.

Anakinra is a recombinant human interleukin-1 receptor antagonist approved for the treatment of inflammatory diseases. Kineret is available as a solution prepared in a borosilicate glass syringe. For implementing a placebo-controlled double-blind randomized clinical trial, anakinra is commonly transferred into plastic syringes. However, there is limited data on anakinra's stability in polycarbonate syringes. We described the results of our previous studies on the use of anakinra in glass (VCUART3) versus plastic syringes (VCUART2) compared with placebo. These studies were conducted in patients with ST-segment elevation myocardial infarction (STEMI), and we assessed the anti-inflammatory effects of anakinra versus placebo by comparing the area under the curve for high-sensitivity cardiac reactive protein (AUC-CRP) levels during the first 14 days of STEMI, its clinical effects on heart failure (HF) hospitalization, cardiovascular death, or new diagnosis of HF as well as adverse events profile between groups. The levels of AUC-CRP were 75 (50-255 mg·day/l) for anakinra in plastic syringes versus 255 (116-592 mg·day/l) in placebo and 60 (24-139 mg·day/l) and 86 (43-123 mg·day/l) for anakinra once and twice daily in glass syringes, respectively, compared with placebo 214 (131-394 mg·day/l). The rate of adverse events was also comparable between groups. There were no differences in the rate of HF hospitalization or cardiovascular death in patients who received anakinra in plastic or glass syringes. Fewer cases of new-onset heart failure occurred in patients receiving anakinra in plastic or glass syringes compared with placebo. Anakinra stored in plastic (polycarbonate) syringes provides comparable biologic and clinical effect to glass (borosilicate) syringes. SIGNIFICANCE STATEMENT: Anakinra (Kineret) 100 mg administered subcutaneously in patients with ST-segment elevation myocardial infarction (STEMI) for a duration of up to 14 days appears to have comparable safety and biological efficacy signals when delivered in prefilled glass or transferred into plastic polycarbonate syringes. This may have important implications for the feasibility of designing clinical trials in STEMI and other clinical conditions.

Effects of Intensive Systolic Blood Pressure Lowering on End-Stage Kidney Disease and Kidney Function Decline in Adults With Type 2 Diabetes Mellitus and Cardiovascular Risk Factors: A Post Hoc Analysis of ACCORD-BP and SPRINT.

OBJECTIVE: To determine the effects of intensive systolic blood pressure (SBP) lowering on the risk of major adverse kidney outcomes in people with type 2 diabetes mellitus (T2DM) and/or prediabetes and cardiovascular risk factors. RESEARCH DESIGN AND METHODS: This post hoc ACCORD-BP subgroup analysis included participants in the standard glucose-lowering arm with cardiovascular risk factors required for SPRINT eligibility. Cox proportional hazards regression models compared the hazard for the composite of dialysis, kidney transplant, sustained estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2, serum creatinine >3.3 mg/dL, or a sustained eGFR decline ≥57% between the intensive (<120 mmHg) and standard (<140 mmHg) SBP-lowering arms. RESULTS: The study cohort included 1,966 SPRINT-eligible ACCORD-BP participants (40% women) with a mean age of 63 years. The mean SBP achieved after randomization was 120 ± 14 and 134 ± 15 mmHg in the intensive and standard arms, respectively. The kidney composite outcome occurred at a rate of 9.5 and 7.2 events per 1,000 person-years in the intensive and standard BP arms (hazard ratio [HR] 1.35 [95% CI 0.85-2.14]; P = 0.20). Intensive SBP lowering did not affect the risk of moderately (HR 0.96 [95% CI 0.76-1.20]) or severely (HR 0.92 [95% CI 0.66-1.28]) increased albuminuria. Including SPRINT participants with prediabetes in the cohort did not change the overall results. CONCLUSIONS: This post hoc subgroup analysis suggests that intensive SBP lowering does not increase the risk of major adverse kidney events in individuals with T2DM and cardiovascular risk factors.

Abnormal left ventricular subendocardial perfusion and diastolic function in women with obesity and heart failure and preserved ejection fraction.

PURPOSE: - Coronary microvascular dysfunction (CMD) is common in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. Stress cardiovascular magnetic resonance (CMR) has been proposed as a non-invasive tool for detection of CMD. The aim of this study was to determine relationship between CMD and diastolic function in patients with HFpEF using a novel CMR technique. METHODS: - Patients with obesity and HFpEF without epicardial coronary artery disease (CAD) underwent Doppler echocardiography to measure diastolic function, followed by vasodilator stress CMR, using a single bolus, dual sequence, quantitative myocardial perfusion mapping to measure myocardial blood flow (MBF) at rest and at peak hyperemia. With this, myocardial perfusion reserve (MPR), global stress endocardial-to-epicardial (endo:epi) perfusion ratio, and total ischemic burden (IB, defined as myocardial segments with MBF < 1.94 mL/min/g) were calculated. Results are reported as median and interquartile range. RESULTS: - Nineteen subjects were enrolled (100% female, 42% Black). Median age was 64 [56-72] years. Global stress MBF was 2.43 ml/min/g [2.16-2.78] and global myocardial perfusion reserve (MPR) was 2.34 [2.07-2.88]. All had an abnormal subendocardial perfusion with an endo:epi of less than 1 (0.87 [0.81-0.90]). Regional myocardial hypoperfusion was detected in 14 (74%) patients with an IB of 6% [0-34.4]. Endo:epi ratio significantly correlated with IB (R=-0.510, p = 0.026) and measures of diastolic function (R = 0.531, p = 0.019 and R=-0.544, p = 0.014 for e' and E/e' respectively). CONCLUSION: - Using a novel quantitative stress CMR myocardial perfusion mapping technique, women with obesity and HFpEF were found to have patterns of abnormal subendocardial perfusion which significantly correlated with measures of diastolic dysfunction.

Systolic Blood Pressure Time in Target Range and Major Adverse Kidney and Cardiovascular Events.

BACKGROUND: Whether time-in-target range (TTR) for systolic blood pressure (SBP) associates with adverse kidney and cardiovascular events remains incompletely understood. METHODS: This study included participants in 2 clinical trials that compared intensive (<120 mm Hg) and standard (<140 mm Hg) SBP lowering. SBP-TTR for months 0 to 3 was calculated using therapeutic ranges of 110 to 130 mm Hg and 120 to 140 mm Hg for the intensive and standard arms, respectively. Adverse kidney events included the composite of dialysis, kidney transplant, serum creatinine >3.3 mg/dL, sustained eGFR <15 mL/(min·1.73 m2), or sustained eGFR decline >40%. Adverse cardiovascular events included myocardial infarction, stroke, heart failure, and cardiovascular death. Adjusted Cox proportional hazards regression models were used to estimate the association between SBP-TTR and kidney and cardiovascular events. RESULTS: Participants with higher TTR were younger and less likely to have preexisting cardiovascular disease. Compared with participants with TTR of 0%, the risk of adverse kidney events was lower for participants with TTR of >0% to 43% (hazard ratio [95% CI], 0.57 [0.42-0.76]; P<0.001), 43% to <70% (0.57 [0.42-0.78]; P=0.001), 70% to <100% (0.53 [0.38-0.74]; P<0.001), and 100% (0.33 [0.20-0.57]; P<0.001) in fully adjusted models. The risk of major adverse cardiovascular events was lower for participants with TTR of >0% to 43% (0.66 [0.52-0.83]; P=0.001), 43% to <70% (0.70 [0.55-0.90]; P=0.005), 70% to <100% (0.65 [0.50-0.84]; P=0.001), or 100% (0.56 [0.39-0.80]; P=0.001) compared with those with TTR of 0%. CONCLUSIONS: Higher SBP-TTR associates with lower risks of adverse kidney and cardiovascular events in adults with hypertension. SBP-TTR may be a potential therapeutic target and quality metric.