Concurrent Cardiovascular Disease Research Articles

Abstract PO2-11-01: Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors

Abstract Background: Cardiovascular disease (CVD) and cancer are the two leading causes of death in the U.S, and breast cancer (BC) is the most common cancer among women. Most survivors of early-stage BC are prescribed adjuvant endocrine therapy (ET) to decrease their BC recurrence risk; many of them are also on statins and/or antihypertensives to manage concurrent CVD risk factors. Nonadherence to ET or CVD medications is associated with decreased survival and other poor outcomes, yet little is known about how best to identify nonadherence to multiple classes of medications in BC survivors. Methods: We reviewed pharmacy fill data from our electronic health record (EHR) for a diverse cohort of patients seen in our breast oncology clinic with prescriptions for ET and CVD medications (statin and/or antihypertensive(s)). Patients were excluded if their pharmacy data did not show both an active ET order and an active CVD order or fill. Nonadherence to any medication was defined as proportion of days covered (PDC) < 80% over the previous 180 days. A subset of patients also responded to a patient-reported nonadherence screener administered through our EHR at appointment registration starting in 2/2022. Descriptive statistics were used to determine the prevalence of nonadherence to all medications (defined as PDC< 80% for either ET and/or CVD medications) and for each class of medication separately. We also compared the PDC-based combined nonadherence to the self-reported nonadherence. Results: We identified a total of 1,015 BC survivors on ET and CVD medications last seen in clinic between 2/1/2020 and 6/6/2023 (mean age 69 yo; 23.6% non-Hispanic White, 11.3% non-Hispanic Black, and 38.9% Hispanic). Of these, 567 (55.9%) were prescribed ET and statins, and 745 (73.4%) were prescribed ET and antihypertensives. With nonadherence defined as PDC< 80% for any medication (ET and/or CVD medications), the nonadherence prevalence was 38.4%. The nonadherence prevalence by medication class was slightly lower for ET (20.7%) than for statins (25.9%) and antihypertensives (25.0%). Among patients on ET and statins, 10.1% were nonadherent to both medications and 24.3% were nonadherent to only 1 class of medications; the proportion of patients nonadherent to ET only was almost half that of patients nonadherent to statins only (8.5% vs 15.9%). A similar trend was observed among patients on ET and antihypertensives: 10.3% were nonadherent to both classes of medications and 26.2% were nonadherent to only 1 class of medications, with 11.5% of patients nonadherent to ET only and 14.6% nonadherent to antihypertensives only. Of the 1,015 patients, 390 (38.4%) responded to the nonadherence screener between 2/16/2022 and 6/6/2023, of which 93 (23.8%) reported any level of medication nonadherence. Among these, 57 (61.3%) had PDC≥ 80% and thus were categorized as adherent under our PDC-based adherence determination. Of the 297 patients who self-reported adherence to all medications on the screener, 32.3% had PDC< 80% for any medication. When combining nonadherence by PDC and self-report, the overall nonadherence rate for the 390 patients who responded to the screener was considerably higher at 48.5% (vs 33.8% by PDC only and 23.8% by self-report only). Conclusions: EHR-based screening can identify patients with or at risk for medication nonadherence for targeted interventions. Using a combined approach of pharmacy fill data and patient reports, close to 50% of patients were identified as having nonadherence to at least 1 medication. Nonadherence to statins and antihypertensives was more common than nonadherence to ET, which is concerning as early-stage BC survivors are more likely to die from CVD than BC. Interventions to improve adherence to multiple classes of medications are warranted in this population. Citation Format: Claire Sathe, David DeStephano, Shing Lee, Melissa Beauchemin, Nadia Liyanage-Don, Melissa Accordino, Katherine Crew, Ian Kronish, Dawn Hershman. Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-01.

Systemic Impact of Subgingival Infection Control in Periodontitis Patients with Cardiovascular Disease: A Narrative Review.

Periodontitis, an infectious inflammatory condition, is a key contributor to sustained systemic inflammation, intricately linked to atherosclerotic cardiovascular disease (CVD), the leading cause of death in developed nations. Treating periodontitis with subgingival mechanical instrumentation with or without adjunctive antimicrobials reduces the microbial burden and local inflammation, while also potentially bringing systemic benefits for patients with both periodontitis and CVD. This review examines systemic effects of subgingival instrumentation with or without antimicrobial products in individuals with periodontitis and CVD, and explores intricate pathogenetic interactions between periodontitis and CVD. English-language databases (PubMed MEDLINE and Cochrane Library) were searched for studies assessing the effects of nonsurgical periodontal therapies in periodontitis patients with or without CVD. While the ability of periodontal therapy to reduce mortality- and morbidity-related outcomes in CVD patients with periodontitis remains uncertain, some studies indicate a decrease in inflammatory markers and blood cell counts. Subgingival mechanical instrumentation delivered over multiple short sessions carries lower risks of adverse effects, particularly systemic inflammation, compared to the full-mouth delivery, making it a preferable option for CVD patients. Subgingival mechanical instrumentation, ideally conducted in a quadrant-based therapeutic approach, to decontaminate periodontal pockets has the potential to reduce both local and systemic inflammation with minimal adverse effects in patients suffering from periodontitis and concurrent CVD.

Can blood eosinophil count be used as a predictive marker for the severity of COPD and concomitant cardiovascular disease? The relationship with the 2023 Version of the Global Initiative for Chronic Obstructive Lung Disease Staging.

This study was designed to investigate the relationship between eosinophil count and cardiovascular disease (CVD) in subjects with chronic obstructive pulmonary disease (COPD) and the correlation between eosinophil count and the risk of exacerbations in COPD. The study included 405 patients who met the study inclusion criteria. Of the participants, 100 (25%) were classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) A, 105 (26%) as GOLD B, and 200 (49%) as GOLD E. Routine blood tests (including leukocyte count and differential leukocyte count, hemoglobin, and platelet count) were carried out using an automated hematology analyzer. The eosinophil count and eosinophil percentage were significantly higher in 158 patients with COPD and concurrent CVD than in the COPD patients without concurrent CVD [2.95 (2.4), p=2.309e-11, 1.9 (2), p=5.02e-08, respectively). The prevalence of CVD was higher in the GOLD E group that experienced prominent exacerbations, and while the eosinophil count was also higher (p=.03) in this group, the eosinophil percentage did not differ significantly in this group of patients. The results of our study indicate a strong relationship between eosinophils and cardiovascular events in COPD subjects, particularly in subjects at high risk of exacerbations and cardiovascular complications.

Impact of Pre-existing Type 2 Diabetes Mellitus and Cardiovascular Disease on Healthcare Resource Utilization and Costs in Patients With COVID-19.

Background: The economic burden associated with type 2 diabetes mellitus (T2DM) and concurrent cardiovascular disease (CVD) among patients with COVID-19 is unclear. Objective: We compared healthcare resource utilization (HCRU) and costs in patients with COVID-19 and T2DM and CVD (T2DM + CVD), T2DM only, or neither T2DM nor CVD (T2DM/CVD). Methods: A retrospective observational study in COVID-19 patients using data from the Healthcare Integrated Research Database (HIRD®) was conducted. Patients with COVID-19 were identified between March 1, 2020, and May 31, 2021, and followed from first diagnosis or positive lab test to the end of health plan enrollment, end of study period, or death. Patients were assigned one of 3 cohorts: pre-existing T2DM+CVD, T2DM only, or neither T2DM/CVD. Propensity score matching and multivariable analyses were performed to control for differences in baseline characteristics. Study outcomes included all-cause and COVID-19-related HCRU and costs. Results: In all, 321 232 COVID-19 patients were identified (21 651 with T2DM + CVD, 28 184 with T2DM only, and 271 397 with neither T2DM/CVD). After matching, 6967 patients were in each group. Before matching, 46.0% of patients in the T2DM + CVD cohort were hospitalized for any cause, compared with 18.0% in the T2DM-only cohort and 6.3% in the neither T2DM/CVD cohort; the corresponding values after matching were 34.2%, 26.0%, and 21.2%. The proportion of patients with emergency department visits, telehealth visits, or use of skilled nursing facilities was higher in patients with COVID-19 and T2DM + CVD compared with the other cohorts. Average all-cause costs during follow-up were 7882, and $7277 per-patient-per-month after matching for patients with T2DM + CVD, T2DM-only, and neither T2DM/CVD, respectively. COVID-19-related costs contributed to 78%, 75%, and 64% of the overall costs, respectively. The multivariable model showed that per-patient-per-month all-cause costs for T2DM + CVD and T2DM-only were 54% and 21% higher, respectively, than those with neither T2DM/CVD after adjusting for residual confounding. Conclusion: HCRU and costs in patients were incrementally higher with COVID-19 and pre-existing T2DM + CVD compared with those with T2DM-only and neither T2DM/CVD, even after accounting for baseline differences between groups, confirming that pre-existing T2DM + CVD is associated with increased HCRU and costs in COVID-19 patients, highlighting the importance of proactive management.

Cumulative Review of Hypertension in Patients with Chronic Lymphocytic Leukemia (CLL) and Other Hematologic Malignancies Treated with Acalabrutinib

Background: Patients (pts) with CLL have a high rate of comorbidities, including cardiovascular disease (CVD). Comorbid CVD is correlated with higher mortality in this pt population. Hypertension (HTN) is the most common concurrent CVD in pts with CLL and is associated with development of complications such as stroke and heart failure. The incidence of new or worsening HTN in treatment-naive CLL pts receiving placebo within the CLL12 trial was 8.3% over a 69.3-month observation period (Langerbeins et al. Hematol Oncol. 2023). New and/or worsening HTN has been observed in pts with CLL treated with Bruton tyrosine kinase inhibitor (BTKi) therapy. Studies have shown new or worsening HTN with ibrutinib (7−30%) and zanubrutinib (11−20%) (Christensen et al. Expert Rev Hematol. 2022). Acalabrutinib (acala), a selective, second-generation BTKi, demonstrated a lower rate of HTN (8.6%) vs ibrutinib (22.8%) in the head-to-head ELEVATE-RR study at a median follow-up of 40.9 months (Byrd et al. J Clin Oncol. 2021). Here, we performed a cumulative analysis of new or worsening HTN from the acala global development program and compared these data against real-world prevalence and incidence of HTN for pts with CLL prior to treatment initiation using claims data. Methods: Safety reports of new or worsening HTN were obtained from 11 clinical trials with acala (the safety database analysis comprised 2034 pts from studies in CLL [86.3%] and mantle cell lymphoma [6.1%], with the remainder from other B-cell malignancies). The clinical trials analyzed included therapy with acala (monotherapy or in combination with obinutuzumab) and active comparator groups (described in Table 1). Using the narrow Standardized MedDRA Query and the related MedDRA preferred terms for “HTN,” exposure-adjusted incidence rates in events/100 person-years were determined, and as a comparison, HTN prevalence was assessed at median treatment exposure for acala monotherapy. HTN prevalence (proportion of pts with HTN 6 months before treatment initiation) and incidence rates (number of new cases of HTN per 100 person-years during the 5 years before any treatment initiation) were also assessed based on ICD-10 codes from 3 adjudicated closed claims databases (Optum, MarketScan, and IQVIA). Results: In the claims database analysis, prevalence of HTN ranged from 47.3% to 66.1% in pts with TN CLL prior to treatment initiation. HTN prevalence with acala monotherapy at median treatment exposure (45.5 months) was 55.7%. Exposure-adjusted incidence rates of HTN were analyzed from 11 clinical trials; 1225 pts received acala monotherapy (947 pts with CLL), 223 pts received acala + obinutuzumab (all pts with CLL), 264 pts received ibrutinib as a comparator (all pts with CLL), and 322 pts received other comparators (all pts with CLL). Among the 1225 pts treated with acala monotherapy, 165 pts (147 with CLL) experienced a treatment-emergent adverse event of HTN (median age 66 years; 66.1% [n=109] male; 59.4% [n=98] with history of HTN at baseline). The exposure-adjusted incidence rates of HTN with acala monotherapy (3.844) and acala + obinutuzumab (3.926) were similar to that of other comparators (4.788 [excluding ibrutinib]) ( Table 1). In the ELEVATE-RR study specifically (subgroup of the current analysis), the exposure-adjusted incidence rate of HTN with acala (3.053) was approximately one-third that of ibrutinib (8.590). The exposure-adjusted incidence rate of HTN in pts treated with acala monotherapy without history of HTN was 3.239. Conclusions: Our data showed that HTN is a common comorbidity in pts with CLL as demonstrated in the claims database and clinical trial database analyses where 59.4% of pts who experienced HTN with acala monotherapy had history of HTN at baseline. The incidence rates of new or worsening HTN with acala monotherapy and acala + obinutuzumab were low (3.844 and 3.926, respectively). This is supported by similar incidence proportion of new or worsening HTN in pts receiving placebo (8.3%) from CLL12 (median follow-up 69.3 months) and acala monotherapy (8.9%) from ELEVATE-TN (median follow-up 58.2 months; Sharman et al. EHA. 2022), and similar HTN prevalence at median treatment exposure vs before treatment initiation in claims databases. Our analysis, conducted predominantly in patients with CLL, suggests that acala monotherapy did not worsen pre-existing HTN or increase the risk of new-onset HTN.

Effects of SGLT2 inhibitors and GLP1-receptor agonists on cardiovascular and limb events in peripheral artery disease: A review.

Peripheral artery disease (PAD) and diabetes mellitus are two overwhelming health problems associated with major cardiovascular (CV) and limb events, in addition to increased mortality, despite advances in medical therapies including statins and renin-angiotensin system inhibitors. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1-receptor agonists (GLP1-RA) are two new antihyperglycemic drug classes that have been associated with a significant reduction of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) and CV risk. Whereas most studies had enrolled patients with T2D and concurrent CV disease (CVD), patients with PAD were obviously underrepresented. Furthermore, there was a signal of increased risk of amputation in one of the main trials with canagliflozin. We aim to provide a general review of the current literature and summarize societal guideline recommendations addressing the role of SGLT2i and GLP1-RA drugs in patients with CVD focusing on the PAD population when data are available. Endpoints of interest were MACE and, when available, major adverse limb events (MALE).

S-52-1: CARDIOVASCULAR OUTCOMES IN HYPERTENSIVE PATIENTS WHO DISCONTINUE STUDY MEDICATION IN A LARGE OUTCOME TRIAL. THE LIFE STUDY.

Objective: Patient discontinuation of study medication during an outcome trial has significant implications for study power. However, patients who discontinue cardiovascular outcome trials are not well described. We aimed to assess readily available patient characteristics and outcomes in patients with hypertension and left ventricular hypertrophy (LVH) who discontinued the study drug but otherwise remained in the study until the end of follow-up. Methods: In patients who discontinued vs. those continuing, Cox proportional hazards models identified baseline variables that had a significant impact on the occurrence of the primary composite endpoint (cardiovascular death, stroke, and myocardial infarction) in 9,193 hypertensive patients and LVH in the LIFE study. Results: During a mean follow-up of 4.8 years, 3,281 patients (35.7%) discontinued one or more days during the trial, not counting death as a reason for discontinuation. The distribution of days to discontinuation was highly skewed towards the first part of the study; the 25th percentile was at day 161, and the median was at day 669. Reasons for discontinuation were a clinical adverse event (50%), a secondary study endpoint (19%), required study therapy (11%), withdrawal (2%), administrative (18%), and lost to follow-up (0.2%). Those who discontinued were older, more often male, had slightly lower body mass index, higher systolic and lower diastolic pressure, higher Framingham Risk Score (FRS), and more ECG LVH determined by either Cornell voltage-duration product or Sokolow-Lyon criteria compared to those who continued in the study. Of particular note, the discontinuation rate between the two study drugs was not equal. Patients randomized to losartan discontinued less than those randomized to atenolol. Multivariate analyses showed that older age, male gender, FRS, Sokolow-Lyon criteria, atenolol treatment as well as a history of pre-study myocardial infarction, cerebral vascular disease, peripheral vascular disease, and atrial fibrillation as well as lower levels of hemoglobin, higher serum creatinine and lower cholesterol all independently predicted discontinuation from the study drug. Conclusions: Patients discontinued during the first part of the study mainly due to experience of a clinical adverse event. Patients who discontinued the study drug had, on average, more previous and concurrent cardiovascular disease than those who continued until the study ended. There is no risk reduction and futility if an outcome study recruits patients with too little risk. However, too high risk implies early drug discontinuation and thus reduction in the study power.

Intensive systolic blood pressure treatment remodels brain perivascular spaces: A secondary analysis of the Systolic Pressure Intervention Trial (SPRINT)

BackgroundBrain perivascular spaces (PVS) are part of the glymphatic system and facilitate clearance of metabolic byproducts. Since enlarged PVS are associated with vascular health, we tested whether intensive systolic blood pressure (SBP) treatment affects PVS structure. MethodsThis is a secondary analysis of the Systolic PRessure INtervention Trial (SPRINT) MRI Substudy: a randomized trial of intensive SBP treatment to goal < 120 mm Hg vs < 140 mm Hg. Participants had increased cardiovascular risk, pre-treatment SBP 130–180, and no clinical stroke, dementia, or diabetes. Brain MRIs acquired at baseline and follow-up were used to automatically segment PVS in the supratentorial white matter and basal ganglia using a Frangi filtering method. PVS volumes were quantified as a fraction of the total tissue volume. The effects of SBP treatment group and major antihypertensive classes on PVS volume fraction were separately tested using linear mixed-effects models while covarying for MRI site, age, sex, Black race, baseline SBP, history of cardiovascular disease (CVD), chronic kidney disease, and white matter hyperintensities (WMH). ResultsFor 610 participants with sufficient quality MRI at baseline (mean age 67 ± 8, 40 % female, 32 % Black), greater PVS volume fraction was associated with older age, male sex, non-Black race, concurrent CVD, WMH, and brain atrophy. For 381 participants with MRI at baseline and at follow-up (median ± IQR = 3.9 ± 0.4 years), intensive treatment was associated with decreased PVS volume fraction relative to standard treatment (interaction coefficient: −0.029 [−0.055 to −0.0029] p = 0.029). Reduced PVS volume fraction was also associated with exposure to calcium channel blockers (CCB). ConclusionsPVS enlargement was partially reversed in the intensive SBP treatment group. The association with CCB use suggests that improved vascular compliance may be partly responsible. Improved vascular health may facilitate glymphatic clearance.Clincaltrials.gov: NCT01206062.

Abstract 11750: Disparities Among Covid-19 Mortality in Patients With Concurrent Cancer and Cardiovascular Disease in 2020: A Nationwide Analysis

Introduction: The COVID-19 pandemic has highlighted important socioeconomic health disparities in the United States. Both cardiovascular disease (CVD) and cancer are associated with worse COVID-19 outcomes. We describe racial or ethnic, sex, and rural disparities in mortality rates from COVID-19 in the US cardio-oncology (C-O) population with concurrent cancer and CVD. Methods: Using the multiple causes of death data files within CDC WONDER, we assessed survival outcomes from March to December 2020 (most intense for COVID-19 deaths) by race or ethnicity, sex, and rural status. C-O populations were defined as having ICD 10 codes C00-C97 for “malignant neoplasms” and ICD 10 codes I10-I15 for “hypertensive heart disease”, I20-I25 for “ischemic heart disease” I30-I51 for “other forms of heart disease” encompassing valvular disorders, cardiac arrythmias, myocarditis, and heart failure &amp; cardiomyopathies, or I70 for peripheral atherosclerosis listed as contributing causes of death. In this population, those with ICD 10 code U07.1 for “COVID-19” listed as an underlying cause of death were included. Age-adjusted mortality rates (AAMR) were calculated based on contemporary US population standards. Results: Overall, there were 6,311 deaths from COVID-19 among 16,282 all-cause deaths in the C-O population (AAMR 5.17 deaths/1,000,000 person-years; 95% CI 5.04-5.29). These deaths comprised 1.80% of all COVID-19 deaths (total 350,831) in the study period. Mortality rates were higher in men than women (AAMR 7.35 vs 3.44 deaths/1,000,000; HR 2.13, p&lt;0.0001). Among racial or ethnic groups, mortality rates were highest among African Americans (AAMR 9.31 deaths/1,000,000; 95% CI 8.75-9.88), and higher among Hispanic than non-Hispanic Americans (AAMR 7.10 vs 4.86 deaths/1,000,000; HR 1.46, p&lt;0.0001). Mortality rates were higher in rural areas than metropolitan areas (crude mortality rate 9.15 vs 6.20 deaths/1,000,000; HR 1.48, p &lt;0.001). Conclusion: Among cancer patients with concurrent CVD, COVID-19 deaths were disproportionately higher in male, African American, Hispanic, and rural patients. Further research is needed to understand socioeconomic factors underpinning these disparities and design interventions to improve patient outcomes.

Abstract P221: Cardiovascular Outcomes In Hypertensive Patients Who Discontinue Study Medication In A Large Outcome Trial. The Life Study.

Objective: Patient discontinuation of study medication during a hypertension outcome trial has implications for study power. We aimed to assess patient characteristics and outcomes in patients with hypertension and left ventricular hypertrophy (LVH) who discontinued the study drug but otherwise remained in the study until the end of follow-up. Methods: In patients who discontinued vs. those continuing, Cox proportional hazards models identified baseline variables that had a significant impact on the occurrence of the primary composite endpoint (cardiovascular death, stroke, and myocardial infarction) in 9,193 hypertensive patients and LVH in the LIFE study. Results: During a mean follow-up of 4.8 years, 3,281 patients (35.7%) discontinued one or more days, not counting death as a reason for discontinuation. The distribution of days to discontinuation was highly skewed towards the first part of the study; the 25 th percentile was at day 161, and the median was at day 669. Reasons for discontinuation were a clinical adverse event (50%), a secondary study endpoint (19%), required study therapy (11%), withdrawal (2%), administrative (18%), and lost to follow-up (0.2%). Those who discontinued were older, more often male, had slightly lower body mass index, higher systolic and lower diastolic pressure, higher Framingham Risk Score (FRS), and more ECG LVH determined by either Cornell product or Sokolow-Lyon criteria. Patients randomized to losartan discontinued less than those randomized to atenolol. Multivariate analyses showed that older age, male gender, FRS, Sokolow-Lyon criteria, atenolol treatment as well as a history of pre-study myocardial infarction, cerebral vascular disease, peripheral vascular disease, and atrial fibrillation as well as lower levels of hemoglobin, higher serum creatinine and lower cholesterol independently predicted discontinuation. Conclusions: Patients discontinued during the first part of the study mainly due to a clinical adverse event. Patients who discontinued the study drug had, on average, more previous and concurrent cardiovascular disease than those who continued until the study ended. Thus, too high risk in an outcome study implies early drug discontinuation and thus reduction in the study power.

Interventional Cardiac Procedures and Pregnancy

<h2>Abstract</h2> As the average maternal age advances with increasing concurrent cardiovascular disease risk factors, more women are entering pregnancy with or at risk for various cardiovascular conditions. Although rare, pregnant patients may require various cardiac interventions in the catheterization laboratory. An understanding of indications for intervention in pregnant patients with conditions such as myocardial infarction, severe valvular disease, and cardiogenic shock is critical to optimizing both fetal and maternal outcomes. This document highlights the most common cardiovascular conditions that may be encountered during pregnancy that may require intervention and highlights indications for intervention and periprocedural considerations to facilitate favorable maternal and fetal outcomes.

Abstract P318: Blood Pressure And Cardiovascular Disease Mortality Among US Adults, 1999-2019

Introduction: Elevated blood pressure (BP) is recognized as the leading risk factor for cardiovascular disease (CVD). Low BP values are also markers of concurrent CVD. Our objective was to determine the association between systolic BP (SBP) and diastolic BP (DBP) with CVD mortality, comparing different BP ranges in a contemporaneous population. Methods: The National Health and Nutrition Examination Survey is a nationally representative survey of the US population. Our sample included data from 53,561 adult participants of the 1999-2018 cycles, with measured BP and mortality data available through 2019 linked from the National Death Index. BP was measured three times with a standardized sphygmomanometer and averaged. CVD mortality was defined through ICD-10 codes as diseases of the heart or cerebrovascular disease. We used age adjusted Poisson regression models to estimate incidence densities ratios (IDRs) for CVD mortality. All analyses accounted for the complex survey design. Results: The population was comprised of 51% women with a mean age of 46 years. After an average follow-up of 9.9 years, 7,825 (10.5%) died of any cause and 2,451 (3.1%) died of CVD. Compared with SBP 110 - &lt; 120mmHg, CVD mortality did not differ at SBP 100-&lt;100mmHg or 120-&lt;130 mmHg, but was significantly higher by: 56% with SBP &lt;100mmHg (IDR: 1.56, 95% CI: 1.15, 2.10), 21% with SBP 130 – &lt; 140mmHg (IDR: 1.21, 95% CI: 1.04, 1.42), 36% with SBP 140 – &lt; 160mmHg (IDR: 1.36, 95% CI: 1.14, 1.64), and 77% with SBP ≥160mmHg (IDR: 1.77, 95% CI: 1.47, 2.14). Compared with DBP 70 - &lt; 80mmHg, CVD mortality was significantly higher by 64% with DBP &lt; 50mmHg (IDR: 1.64, 95% CI: 1.38, 1.94), 46% with DBP 50 - &lt; 60mmHg (IDR: 1.46, 95% CI: 1.26, 1.670), 24% with DBP 60 – &lt; 70 mmHg (IDR: 1.24, 95% CI: 1.09, 1.41), 36% with DBP 80 – &lt; 90mmHg (IDR: 1.36, 95% CI: 1.15, 1.61), 54% with DBP 90 – &lt; 100mmHg (IDR: 1.54, 95% CI: 1.20, 1.97), and 182% with DBP ≥100mmHg (IDR: 2.82, 95% CI: 1.90, 4.19). Conclusion: Among US adults, we found a J shaped association between both SBP and DBP with CVD mortality. Lowest risk of CVD mortality was found at SBP 110 - &lt; 120mmHg, with higher risk at levels below 100mmHg or at or above 130mmHg. For DBP, lowest risk of CVD mortality was found at DBP 70 - &lt; 80mmHg, with higher risk at levels below 70mmHg or at or above 80mmHg.

Beta Blockers and Chronic Obstructive Pulmonary Disease (COPD): Sum of Evidence.

Approximately half a century has passed since the discovery of beta-blockers. Then, their prime therapeutic purpose was to treat angina and cardiac arrhythmias; nowadays, beta-blockers' usage and effectiveness are extended to treat other cardiovascular diseases, such as hypertension, congestive heart failure, and coronary artery disease. Safety concerns were raised about beta- blockers and their use for chronic obstructive pulmonary disease (COPD) patients with concurrent cardiovascular disease. After thorough research of the literature, this review summarizes the evidence proving that beta-blockers not only might be well tolerated in COPD patients, but they might also have a beneficial effect in this group of patients.

A safety and clinical efficacy analysis of PCSK9 monoclonal antibodies in patients with markedly elevated creatine phosphokinase levels

Abstract Introduction PCSK9 inhibitors have been used in statin intolerant patients to reduce low-density lipoprotein cholesterol (LDL-C) safely and effectively. However, evidence is lacking regarding the safety and clinical utility of PCSK9 inhibition in patients with markedly elevated creatine phosphokinase (CPK) levels. Methods We searched a large HMO database for patients with CPK levels above 1000 U/L, who were initiating PCSK9 inhibition therapy (Jan 2016–Dec 2019). The patients' treatment plans, adherence, CPK and LDL-C levels were analyzed. Results Of the1600 patients initiating PCSK9 inhibitors, 26 met study criteria, and all were previously treated by statins (in 18 patients ≥3 different statin types were prescribed). Myalgia was evident in most patients (n=24), and 5 were clinically diagnosed with rhabdomyolysis. Abnormal liver function tests were noted in 8 of the 26 patients. Most were very-high cardiovascular risk patients, with concurrent atherosclerotic cardiovascular disease (n=17) and baseline LDL-C levels &amp;gt;190 mg/dL (n=19). Peak CPK levels ranged from 1050–53540 U/L [median (IQR), 3687 (1876–8344)]. Concomitant secondary factors for CPK elevation included renal failure (n=5), inflammatory rheumatoid disorders (n=3), severe hypothyroidism (n=3), intensive exercise (n=2), nephrotic range proteinuria (n=1) and genetic muscular disease (n=1). The monoclonal antibodies, Alirocumab and Evolocumab, were initiated in 12 and 14 patients respectively. In 24 patients (92%) CPK reduction of &amp;gt;50% was noted and in 12 patients (46%) CPK levels returned to normal range (Figure). Under PCSK9 inhibition, 17 patients (65%) achieved LDL-C levels &amp;lt;70 mg/dL and in 12 patients (46%) LDL-C was &amp;lt;55 mg/dL. Only 2 patients discontinued PCSK9 inhibitors. Conclusions High-risk patients with markedly elevated CPK levels, can safely reduce LDL-C levels with PCSK9 inhibitors, and although statin intolerance is a major cause of elevated CPK, other predisposing and precipitating factors are common. Funding Acknowledgement Type of funding sources: None.

Leadless cardiac pacemaker implantations after infected pacemaker system removals in octogenarians.

BackgroundManagement of pacemaker (PM) infections among advanced aged patients possesses particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities. Novel leadless cardiac pacemakers (LCPs) may provide new opportunities for better management options in this population, however, there is limited data especially in Asian populations to guide the decision making.MethodsWe reviewed 11 octogenarians (median age: 86 [minimum 82–maximum 90] years; male: 73%; median body mass index (BMI): 20.1 kg/m2) who received Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) implantations following transvenous lead extractions (TLEs) for PM infections. ResultsAll patients had more than two medical comorbidities (average 3.7 comorbidities). The indications for LCP implantations were atrioventricular block in four patients, atrial fibrillation bradycardia in five, and sinus node dysfunction in two. Eight patients (73%) were bridged with temporary pacing using active fixation leads (median interval of 14.0 days), while one with severe dementia underwent a concomitant LCP implantation and TLE during the same procedure. Successful TLEs and LCP implantations were successfully accomplished in all without any complications. The median time from the TLE procedure to discharge was 22 days (minimum 7–maximum 136). All patients remained free of infections during a mean follow-up period of 17.2 ± 6.5 months.ConclusionsLCP implantations were safe and effective after removing the entire infectious PM system in all octogenarians. The novel LCP technology may offer an alternative option for considering a re-implantation strategy after transvenous PM infections in elderly patients, particularly those with severe frailty and PM dependency.

Abstract P025: Atrial Fibrillation Associated With Worsened Postoperative Outcomes In Patients Undergoing Orthotropic Liver Transplantation.

Introduction: Pre-orthotropic liver transplant (OLT) cardiac risk assessment commonly focuses on evaluation of coronary artery disease (CAD). However, the effect of atrial fibrillation (AF) on post-OLT outcomes is less well known. In this study, we sought to evaluate the prevalence and effect of pre-transplant AF on 30-day post-operative outcomes in patients undergoing OLT. Methods: The National Inpatient Sample Database was queried from 2011 to 2017 for relevant ICD-9 and -10 procedural and diagnostic codes. Baseline characteristics and in-hospital outcomes were compared in patients who underwent OLT with AF and those without. Results: Among 45,357 patients who underwent OLT, 35.8 % were women. The prevalence of AF prior to transplant was 2,932 (6.5%) with a trend towards increasing prevalence between 2011 and 2017 with an annual change rate of 4.19%, see Figure 1. Compared to the non-AF cohort, the AF group was older (59.9±7.9 vs 51.2±16.9 years old, p&lt;0.001), with a higher prevalence of diabetes mellitus (DM), CAD, chronic kidney disease, heart failure (HF), anemia, and thrombocytopenia (p&lt;0.001 for all). In-hospital 30-day mortality (5.8% vs. 3.6%, p&lt;0.001), intra-operative cardiac arrest (8.1% vs. 1.7%, p&lt;0.001), post-operative ventricular tachycardia (7.5% vs. 2.6%, p&lt;0.001) and acute kidney injury (64.2% vs. 49.3%, p&lt;0.001) were higher in the AF group when compared to those without. Using a multivariate logistic regression model to adjust for confounding factors, AF was still predictive of an increased odds of in-hospital 30-day mortality (OR: 1.92; 95% CI [1.61-2.30], p&lt;0.001). Conclusion: In patients undergoing OLT, pre-transplant AF is increasing in prevalence and appears to be associated with worse in-hospital outcomes and 30-day mortality. This effect may be driven in part by a higher prevalence of concurrent cardiovascular disease and associated risk factors in patients with AF. Greater emphasis should be placed on AF in the preoperative cardiovascular risk stratification of patients undergoing OLT.

Update on management of hypokalaemia and goals for the lower potassium level in patients with cardiovascular disease: a review in collaboration with the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy.

Hypokalaemia is common in patients with cardiovascular disease. In this review, we emphasize the importance of tight potassium regulation in patients with cardiovascular disease based on findings from observational studies. To enhance the understanding, we also describe the mechanisms of potassium homeostasis maintenance, the most common causes of hypokalaemia and present strategies for monitoring and management of low potassium levels. We propose elevation of potassium in asymptomatic patients with lower normal concentrations and concurrent cardiovascular disease. These proposals are intended to assist clinicians until more evidence is available.

Retrospective cohort analysis of real-world clinical outcomes in nonmetastatic (M0) castration-resistant prostate cancer (CRPC) treated with novel androgen receptor pathway inhibitors (ARPI).

51 Background: The landscape of M0 CRPC has changed with the recent demonstration of metastasis-free survival (MFS) and overall survival (OS) improvements with the use of ARPIs in clinical trial settings. However, the extrapolation of this data to clinical practice is limited by strict exclusion criteria in these trials, including prior or concurrent malignancy, cardiovascular disease, or hypertension. The purpose of this study was to assess real-world outcomes in patients with M0 CRPC treated with ARPIs compared to historical controls. Methods: We designed a retrospective cohort study with the inclusion of patients in Alberta, Canada diagnosed with M0 CRPC between 2001-2020. Via chart review, we identified baseline characteristics, potential confounders, treatment details, and clinical outcomes. The primary outcome of interest was MFS. Secondary outcomes included: second progression-free survival (PFS2) and OS. Median survival times were measured using the Kaplan-Meier method and the log-rank test was used for comparison of outcomes based on ARPI exposure. Cox proportional hazard regression models were used to calculate hazard ratios (HR) accounting for impact of PSA doubling time (PSADT), use of osteoclast inhibiting agents, and presence of pelvic lymphadenopathy. Results: We identified 211 patients across multiple centres in Alberta with M0 CRPC, with 54 having received apalutamide (40/54), enzalutamide (7/54), or darolutamide (7/54). Median age at M0 CRPC diagnosis was 74 years; median PSADT was 4.4 months; and 19% of patients (40/211) had pelvic lymphadenopathy at diagnosis. Median MFS in patients treated with ARPIs was 47.5 months compared to 20.6 months in those not treated with ARPIs (HR, 0.23; 95% confidence interval [CI], 0.11-0.49; p &lt; 0.001). Median PFS2 in ARPI treated patients was 66.3 months compared with 35.6 months (HR, 0.40; 95% CI, 0.18-0.87; p = 0.022). Median OS for patients treated with ARPI was not reached. Conclusions: Given the older age of men with advanced prostate cancer, real-world outcomes that include patients with comorbidities are important adjuncts to the interpretation of clinical trials exploring the benefit of novel therapeutics. Here, we demonstrate that in a real-world, unselected population of men with M0 CRPC, apalutamide, enzalutamide, and darolutamide seem to confer similar MFS and PFS2 benefits to those demonstrated in the SPARTAN, PROSPER, and ARAMIS studies. Real-world OS data remain immature and will be an important addition to these findings.

Association of Diabetes Subgroups With Race/Ethnicity, Risk Factor Burden and Complications: The MASALA and MESA Studies.

There are known disparities in diabetes complications by race and ethnicity. Although diabetes subgroups may contribute to differential risk, little is known about how subgroups vary by race/ethnicity. Data were pooled from 1293 (46% female) participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) who had diabetes (determined by diabetes medication use, fasting glucose, and glycated hemoglobin [HbA1c]), including 217 South Asian, 240 non-Hispanic white, 125 Chinese, 387 African American, and 324 Hispanic patients. We applied k-means clustering using data for age at diabetes diagnosis, body mass index, HbA1c, and homeostatic model assessment measures of insulin resistance and beta cell function. We assessed whether diabetes subgroups were associated with race/ethnicity, concurrent cardiovascular disease risk factors, and incident diabetes complications. Five diabetes subgroups were characterized by older age at diabetes onset (43%), severe hyperglycemia (26%), severe obesity (20%), younger age at onset (1%), and requiring insulin medication use (9%). The most common subgroup assignment was older onset for all race/ethnicities with the exception of South Asians where the severe hyperglycemia subgroup was most likely. Risk for renal complications and subclinical coronary disease differed by diabetes subgroup and, separately, race/ethnicity. Racial/ethnic differences were present across diabetes subgroups, and diabetes subgroups differed in risk for complications. Strategies to eliminate racial/ethnic disparities in complications may need to consider approaches targeted to diabetes subgroup.

Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study.

Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD. We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013-2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose-response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies. In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.