Cardiovascular Disease Medication 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.

Statin use for cardiovascular disease prevention: perceptions among people living with HIV in the United States

BackgroundPeople living with HIV (PLWH) may be at heightened risk for cardiovascular disease (CVD). Statin use and lifestyle changes reduce the risk of CVD but remain under-prescribed among PLWH. The objective of this study was to characterize knowledge of CVD and statin use, current usage, barriers to taking statins, and information desired by PLWH to improve statin uptake among PLWH in Los Angeles, CA.MethodsBetween April 2019 and April 2020, we conducted four focus group discussions (n = 37) with patients across three public community health clinics that serve PLWH in Los Angeles County, California. All clinics participated in a larger study to improve statin prescribing for PLWH. We asked about knowledge of statins, willingness to take a statin, possible barriers to statin usage, preferred information sources for health information, and desired information about statins. We utilized standard qualitative content analysis methods to identify themes.ResultsWe found a range in the awareness of statins, with some participants reporting never having heard of statins while others had a history of statin use. There were concerns about the potential long-term effect of statin use, but participants expressed willingness to use CVD medications generally and statins specifically, especially if recommended by their healthcare provider. Participants also expressed interest in potential alternatives to statin usage such as exercising regularly and nutritious eating.ConclusionsMore interventions are needed to increase statin use among PLWH to improve CVD outcomes, which also has implications for HIV progression. Clinics should aim to increase patient and provider knowledge about CVD risk and statin use for PLWH and provide shared decision-making tools that are easy to use and culturally appropriate.

The Heart of the World.

Cardiovascular diseases (CVDs) are the leading cause of mortality globally. Of the 20.5 million CVD-related deaths in 2021, approximately 80% occurred in low- and middle-income countries. Using data from the Global Burden of Disease Study, NCD Risk Factor Collaboration, NCD Countdown initiative, WHO Global Health Observatory, and WHO Global Health Expenditure database, we present the burden of CVDs, associated risk factors, their association with national health expenditures, and an index of critical policy implementation. The Central Europe, Eastern Europe, and Central Asia region face the highest levels of CVD mortality globally. Although CVD mortality levels are generally lower in women than men, this is not true in almost 30% of countries in the North Africa and Middle East and Sub-Saharan regions. Raised blood pressure remains the leading global CVD risk factor, contributing to 10.8 million deaths in 2019. The regions with the highest proportion of countries achieving the maximum score for the WHF Policy Index were South Asia, Central Europe, Eastern Europe, and Central Asia, and the High-Income regions. The Sub-Saharan Africa region had the highest proportion of countries scoring two or less. Policymakers must assess their country's risk factor profile to craft effective strategies for CVD prevention and management. Fundamental strategies such as the implementation of National Tobacco Control Programmes, ensuring the availability of CVD medications, and establishing specialised units within health ministries to tackle non-communicable diseases should be embraced in all countries. Adequate healthcare system funding is equally vital, ensuring reasonable access to care for all communities.

Comparing knowledge, attitudes, and practices in cardiovascular disease prevention and health promotion between community and hospital pharmacists in Saudi Arabia: A cross-sectional study

PurposeSaudi Arabia is one of the leading nations in the world in terms of the high frequency of chronic diseases and their associated risk factors. Knowledge and awareness are crucial for pharmacists to play an active role in the prevention of cardiovascular diseases (CVD). The current study assessed the pharmacists' knowledge, attitude, and practice to determine the potential differences with respect to their respective practice settings toward CVD prevention and related health promotions. MethodsIt is a cross-sectional study targeted the registered pharmacists in the Kingdom of Saudi Arabia. An online questionnaire was prepared, and the link was circulated through various social media platforms. Descriptive statistics, multivariate linear regression analysis and chi square test were used to analyze the data accordingly. ResultsA total of 324 pharmacists were included in the study. Among these, 157 (48.4 %) were community pharmacists, and the remaining were hospital pharmacists (51.6 %). No significant differences in knowledge scores were observed between community and hospital pharmacists. The mean attitude score among community and hospital pharmacists was found to be 26.40 ± 5.125 and 25.09 ± 5.393 respectively, which was statistically significant (p = 0.026). Similarly, the total practice scores across the settings were statistically significant (p = 0.02). Gender plays a significant role in terms of knowledge scores among both community and hospital pharmacists (p = 0.016 & 0.029). Gender, professional practice experience, and number of prescriptions handled and prescriptions with CVD medications showed significant differences in the distribution of positive attitudes and good practice frequency between community and hospital pharmacists. ConclusionIt is evident that there is a deficiency in knowledge among hospital pharmacists compared to community pharmacists. Which indicates that there is a need for a rigorous continuous pharmacy education covering the fundamental aspects of CVD primary prevention and health promotion among pharmacists, given more focus on hospital pharmacists.

Impact of Cancer Diagnosis on Appropriate Use of Antithrombotic Medications in Individuals with Cardiovascular Diseases

Introduction: Cancer and Cardiovascular disease (CVD) often coexist and CVD is the leading cause of non-cancer mortality in people with cancer. Antithrombotic medications used to manage CVD are associated with increased bleeding risk, particularly in people with cancer. Appropriate management of CVD is therefore essential in individuals with cancer, both to decrease recurrent CVD as well as to prevent bleeding. In this study, we assessed utilization patterns of antithrombotic medications for CVD following a new diagnosis of cancer. Methods: Among people receiving primary care at the University of Vermont Medical Center from 2010 to 2019, we identified a cohort of 4,010 subjects with baseline CVD, identified from problem lists or billing codes within the first year of follow-up. Exclusion criteria included baseline cancer diagnosis (cancer known at the time of inclusion in the cohort or within the first year of follow-up) or a known history of venous thrombosis. Incident cancer was defined as new diagnosis of cancer after the first year of follow-up and did not include people with non-melanomatous skin cancers. We used the National Cancer Institute list of ICD-9 and ICD-10 codes for different cancer diagnoses. Patient's use of antithrombotics, prescribed or non-prescribed, were captured using computable phenotypes developed from the electronic outpatient medication reconciliation record and validated using chart review. People with baseline CVD who were diagnosed with cancer after the first year of follow up were matched 1:1 by sex and age with people with CVD and no cancer. We used logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (95% CI) of persistent guideline-directed use of antithrombotic medications for 6 months after a new cancer diagnosis versus a matched time-period in those without incident cancer (use of antiplatelets in those with a history of atherosclerotic CVD and use of anticoagulation in those with a history of atrial fibrillation). Results: We identified 4,010 individuals with baseline CVD, 841 of whom (20%) developed incident cancer during follow-up. Distribution of CVD and antithrombotic use in the age- and sex-matched population are presented in Table 1. 2/3 of the population had coronary artery disease and about 30% had atrial fibrillation or flutter. About 65% of individuals were on any antiplatelet therapy and 18% were on anticoagulation for CVD. 41% of people with baseline CVD, and incident cancer diagnosis were still on antiplatelet therapy 6 months after their cancer diagnosis as opposed to 38 % in the matched population without a cancer diagnosis. 33% of individuals with incident cancer were still on anticoagulation for atrial fibrillation or flutter as opposed to 28% of the matched population without cancer. Both of these differences were statistically significant with OR=1.55 (95% CI, 1.15-2.1) for antiplatelets, and OR=1.56 (95% CI, 1.05,2.31) for anticoagulants, compared to those with no cancer diagnosis (Table 2). Conclusion: Surprisingly, our study found that incident cancer in individuals with baseline CVD was associated with increased adherence to antithrombotic therapy. We had hypothesized that incident cancer would be associated with lower use of antithrombotic therapy. This result could be related to increased interaction with medical specialists following a cancer diagnosis. The impact of increased adherence to antithrombotics on bleeding however, will need to be further investigated.

Cardiorespiratory fitness is associated with estimates of myocardial perfusion: influence of age and sex.

Cardiorespiratory fitness (CRF) and the subendocardial viability ratio (SEVR) decline with age and predict future cardiovascular disease (CVD) events in a sex-dependent manner. However, the relation between CRF and SEVR in apparently healthy males and females across the age span is largely unknown. We hypothesized higher CRF is associated with greater SEVR in older females but not in males. Two-hundred sixty-two (126 M/136 F, age range 20-84 yr) participants underwent measures of CRF (maximal O2 consumption, V̇o2max) and SEVR (pulse wave analysis, PWA). A two-way analysis of variance (ANOVA) was used to examine differences in baseline characteristics between younger (<45 yr) and middle-aged and older (MA/O, ≥45 yr) males and females. Bivariate correlations assessed the relation between CRF, SEVR, and age in males and females. Partial correlations adjusted for CVD risk factors and medications. MA/O females had the lowest CRF and SEVR compared with all other groups (P < 0.05, both). SEVR was negatively correlated with age (r = -0.29) and positively correlated with CRF (r = 0.53) in females (P < 0.05, both) that persisted after controlling for CVD risk factors and medications (P < 0.05, all). SEVR was correlated with CRF in males only after adjusting for CVD risk factors and medications (r = 0.26, P < 0.05). These findings collectively demonstrate higher CRF is associated with greater SEVR in males and females after adjusting for CVD risk factors and medications, therefore highlighting subtle sex-specific nuances that warrant further investigation.NEW & NOTEWORTHY Cardiorespiratory fitness (CRF) and the subendocardial viability ratio (SEVR) are independent predictors of mortality and decline with age. However, the sex-specific relationship between CRF and SEVR with aging in adult males and females is unknown. Our findings demonstrate higher CRF is associated with greater age-related SEVR in males and females, after adjusting for traditional cardiovascular disease (CVD) risk factors and medications. However, subtle sex-related nuances exist in the relationship between SEVR and CRF that require further investigation.

Abstract 14482: Low Utilization of Guideline-Recommended Genetic and Pharmacogenetic Testing Among Patients With Cardiovascular Conditions in the United States (US)

Introduction: Cardiovascular disease (CVD) continues to be the leading cause of death in the US and globally. Clinical practice guidelines recommend genetic testing for the diagnosis of select CVDs to improve disease management, reduce incidence of cardiac events, and positively impact major cardiac adverse events. Professional guidelines also recommend pharmacogenomic (PGx) testing for patients being prescribed certain medications. Research Question: What is the utilization of genetic diagnosis and PGx testing in patients with CVD in the US? Methods: This study used data from the Optum Labs Data Warehouse, composed of de-identified administrative claims data for both commercially insured and Medicare Advantage enrollees to assess rates of genetic testing among adult patients diagnosed with 4 major types of CVD conditions (arrhythmias (N=518,316), familial hypercholesterolemia (FH) (N=38,068), cardiomyopathies (CM) (N=74,597), and aortopathies (N=58,316)) and PGx testing rates in patients prescribed CVD medications with PGx test recommendations (per CPIC guidelines) between January 1, 2017 to December 31, 2021. Patients were required to have ≥12 months of continuous enrollment prior (baseline) to diagnosis (index date) and ≥12 months post-index period unless they died (follow-up). Genetic and PGx testing was captured using Current Procedural Terminology (CPT®) codes in both baseline and follow-up periods. Results: Low genetic testing utilization was found across the 4 major types of CVD conditions. Genetic testing rates were 1.3% in the arrythmia cohort, 1.9% in the CM cohort, 2.0% in the aortopathy cohort and 1.9% in the FH cohort. PGx testing rates in patients prescribed with CVD relevant medications were 0.6% (N=2,094/377,111) in the arrhythmia cohort, 0.8% (N=501/60,632) in the CM cohort, 0.7% (N=247/37,344) in the aortopathy cohort, and 1.3% (N=329/25,835) in FH cohort. Conclusions: Despite clinical practice guidelines, genetic and PGx testing in patients with CVD conditions remains underutilized. Future work will help us understand the barriers to guideline adherence both for genetic diagnosis and PGx testing that could impact clinical management and patient outcomes.

Evidence-Based Cardiovascular Disease Medicines' Availability in Low-Cost Generic Drug Programs in the United States : A Cross-Sectional Study.

Low-cost generic programs (LCGPs) that expand access to affordable cardiovascular disease (CVD) medicines can assist patients in achieving desired cardiovascular outcomes. It is important that LCGPs offer CVD medicines that promote evidence-based prescribing. To evaluate LCGPs' coverage of evidence-based CVD medications using a clinical framework that examines coverage of core treatments, coverage of options with the highest-quality evidence, and the variety of medication options and strengths that create choices and allow dosing titration. Cross-sectional study. Publicly available LCGPs in March and April 2023 in the United States. 19 LCGPs. Proportion of LCGPs that offered evidence-based CVD medicines within a clinical framework for 6 CVDs (atrial fibrillation, heart failure, hyperlipidemia, hypertension, post-acute coronary syndrome secondary prevention, and stable angina) according to 4 availability metrics (breadth, choice, high-quality evidence, and titratability). The availability of CVD medication varied by program, drug, and CVD condition. Some programs had more breadth and choice of coverage for most CVDs (H-E-B, Kroger, Mark Cuban Cost Plus Drug Company, and Walmart), whereas many had more focused coverage and others markedly limited offerings. Nearly all LCGPs offered angiotensin-converting enzyme inhibitors, β-blockers, thiazides, and moderate-intensity statins, but availability was low for higher-cost or lower-use generics (antiplatelets and antiarrhythmics). Core pharmacotherapy coverage and choices were limited for atrial fibrillation and heart failure but widely available for hypertension and hyperlipidemia. In-depth cost analysis was not investigated. Coverage of evidence-based medications for the 6 CVDs investigated varied by LCGP and condition. Because high availability of core CVD pharmacotherapy can enhance optimal disease state management, LCGPs should identify existing limitations in their coverage and continuously revise their formularies to improve the comprehensiveness of CVD medication coverage. None.

Association of anxiety and depressive symptoms with C-reactive protein in diverse Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; ≥ 3mg/L, high). Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(β) = 1.12; p<0.01) and anxiety symptoms (exp(β) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

Danish men's experiences of cardiovascular screening and their views on preventive cardiovascular medication: A qualitative explorative nurse study

ObjectivesThis study explored Danish men's experience of participating in a screening program for cardiovascular disease (CVD) and their perceptions of preventive medication for CVD before and after participation in the screening program. MethodsAn exploratory phenomenological-hermeneutical study. Fifteen men from a cardiovascular screening program for men aged 65–74 years participated. Semi-structured interviews were conducted before screening and one year later (2015–2017). The interviews were transcribed verbatim and analysed using Kvale and Brinkmann's approach to data analysis. ResultsTwo main themes were identified: (i) seeking confirmation and control of health: familiarity with CVD; understanding the screening program; confirmation of health; perception of preventive medication, and (ii) sense of own health and prevention: experiences with the screening program; accept or denial of diagnosis and preventive medication. ConclusionA minority of the men understood the nature of the diseases for which they were being examined. The invitation for screening and the outcome of the examinations must be communicated more skilfully. The health providers need to engage early in treatment after the screening and provide an individualised plan that addresses patients concerns and knowledge based on their needs.

Are doctors using more preventive medication for cardiovascular disease? A Swedish cross-sectional study

Background Despite decreasing mortality from cardiovascular disease (CVD), there are persistent inequities in mortality between socioeconomic groups. Primary preventative medications reduce mortality in CVD; thus, inequitable treatments will contribute to unequal outcomes. Physicians might contribute to inequality by prescribing preventative medication for CVD to themselves in a biased manner. Aim To determine whether primary medications for preventing CVD were prescribed inequitably between physicians and non-physicians. Design and setting This retrospective study retrieved registry data on prescribed medications for all physicians in Sweden aged 45–74 years, during 2013, and for reference non-physician individuals, matched by sex, age, residence, and level of education. The outcome was any medication for preventing CVD, received at least once during 2013. Method Age and the sex-specific prevalence of myocardial infarction (MI) among physicians and non-physicians were used as a proxy for the need for medication. Thereafter, to limit the analysis to preventative medication, we excluded individuals that were diagnosed with CVD or diabetes. To analyse differences in medication usage between physicians and matched non-physicians, we estimated odds ratios (ORs) with conditional logistic regression and adjusted for need and household income. Results MI prevalences were 5.7% for men and 2.3% for women, among physicians, and 5.4% for men and 1.8% for women, among non-physicians. We included 25,105 physicians and 44,366 non-physicians. The OR for physicians receiving any CVD preventative medication, compared to non-physicians, was 1.65 (95% confidence interval 1.59–1.72). Conclusion We found an inequity in prescribed preventative CVD medications, which favoured physicians over non-physicians.

Identification and management of clonal hematopoiesis of indeterminate potential (CHIP) in cancer survivors: The Cleveland Clinic experience.

7010 Background: Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is found in healthy populations as well as cancer patients (pts) and is associated with (w/) cardiovascular disease (CVD), risk of hematologic neoplasms (HN), and all-cause mortality. Germline variants (var) predispose to CHIP. However, described var are nonspecific to solid tumor pts. Identifying CHIP risk factors and mitigation strategies is paramount for improving outcomes. Methods: Pts in breast (BC) and head &amp; neck cancer (HNC) survivorship (2020-2023) following curative treatment (tx) were eligible for our 10 year (yr) prospective study of annual next generation sequencing (NGS) and complete blood count (CBC) to identify CHIP. Mutations (mt) were classified as clinically significant (CS) or var of unknown significance (VUS), and as CH (med. VAF 4.7%) or potentially germline (PG; med. VAF 50%). Pts w/ CHIP were managed in both CHIP Clinic (CC) and Preventive Cardiology (PC) for monitoring and CVD reduction. Fisher’s exact and ANOVA tests were used for analyses. Results: Of 168 pts enrolled (117 BC, 51 HNC), 158 had NGS: 73 yr 1, 85 through yr 2 or 3; 22 pts received chemotherapy (CT), 49 radiation therapy (RT), 72 CT &amp; RT (CRT). Sixty-eight pts (43%) had a mt; 21 (13%) had CHIP (6 w/ PG VUS). CHIP was found to be associated w/ older age (69 vs. 58, p= 0.0002). The most common CHIP mt were DNMT3A (n = 11), PPM1D (6), TET2 (6), JAK2 a nd TP53 (2). Two pts without yr 1 mt developed CHIP in yr 2. For PPM1D, 2 PG VUS were point mt from DNA transitions while 6 CHIP were truncating from transversions and deletions. All pts w/ PPM1D had RT (7/8 CRT), suggesting a molecular signature which varies from transition-driven aging. Six pts had thrombocytopenia (TP), 3 w/ PPM1D CHIP. TP was more common in CHIP (OR 11, p= 0.0356) and PPM1D (OR 29, p= 0.0016). In this cohort, anemia was not seen in pts w/ CHIP ( p= 0.048). Normal CBC was 6x less common in pts w/ CRT ( p= 2.3x10-7). Seven CHIP pts were seen by PC; 4 had yr 2 NGS following PC visit. All pts had addition of new/dose escalation of current CVD medication. Two CHIP pts had stable NGS; 2 CHIP &amp; PG VUS pts had clonal changes including mt disappearance and acquisition. Of note, the PG VUS’s were assessed for institutional incidence in 3,918 HN pts w/ NGS data and in Mastermind (MM) for frequency of occurrence in published literature. Sixteen PG VUS (40%) occurred at our institution (13 found in MM, 7 classified as rare (avg gnomAD MAF 6x10-4)) and associated w/ HN, notably TET2 (n = 3). Conclusions: This ongoing prospective study is one of the largest to report characteristics and outcomes of CHIP pts in CC/PC and is expected to accrue more in expansion. We anticipate highlighting risk factors for CHIP progression and report novel PG VUS, which may portend health risks based on their prevalence in HN. Furthermore, it appears that a strategy for CVD prevention may promote clonal stability in survivorship pts.

Betulinaldehyde inhibits vascular remodeling by regulating the microenvironment through the PLCγ1/Ca2+/MMP9 pathway

BackgroundVascular remodeling plays a crucial role in the pathogenesis of several cardiovascular diseases (CVDs). Unfortunately, current drug therapies offer limited relief for vascular remodeling. Therefore, the development of innovative therapeutic strategies or drugs that target vascular remodeling is imperative. Betulinaldehyde (BA) is a triterpenoid with diverse biological activities, but its effects on vascular remodeling remain unclear. ObjectiveThis study aimed to investigate the role of BA in vascular remodeling and its mechanism of action, providing valuable information for future applications of BA in the treatment of CVDs. MethodsNetwork pharmacology was used to predict the key targets of BA in vascular remodeling. The effect of BA on vascular remodeling was assessed in a rat model of balloon injury using hematoxylin and eosin staining, Masson staining, immunohistochemistry staining, and Western blotting. A phenotypic transformation model of vascular smooth muscle cells (VSMCs) was induced by platelet-derived growth factor-BB, and the functional impacts of BA on VSMCs were assessed via CCK-8, EdU, Wound healing, Transwell, and Western blotting. Finally, after manipulation of phospholipase C gamma1 (PLCγ1) expression, Western blotting and Ca2+ levels determination were performed to investigate the potential mechanism of action of BA. ResultsThe most key target of BA in vascular remodeling, matrix metalloproteinase 9 (MMP9), was identified through network pharmacology screening. Vascular remodeling was alleviated by BA in vivo and its effects were associated with decreased MMP9 expression. In vitro studies indicated that BA inhibited VSMC proliferation, migration, phenotypic transformation, and downregulated MMP9 expression. Additionally, BA decreased PLCγ1 expression and Ca2+ levels in VSMCs. However, after pretreatment with a phospholipase C agonist, BA's effects on down-regulating the expression of PLCγ1 and Ca2+ levels were inhibited, while the expression of MMP9 increased compared to that in the BA treatment group. ConclusionThis study demonstrated the critical role of BA in vascular remodeling. These findings revealed a novel mechanism whereby BA mediates its protective effects through MMP9 regulation by inhibiting the PLCγ1/Ca2+/MMP9 signaling pathway. Overall, BA may potentially be developed into a novel medication for CVDs and may serve as a promising therapeutic strategy for improving recovery from CVDs by targeting MMP9.

B-vitamin Treatment Modifies the Mortality Risk Associated with Calcium Channel Blockers in Patients with Suspected Stable Angina Pectoris: A Prospective Cohort Study

BackgroundCalcium channel blockers (CCBs) are used for the treatment of cardiovascular disease (CVD), including angina pectoris, and hypertension; however, the effect on survival remains uncertain. CCBs impair fibrinolysis and have been linked to elevated plasma homocysteine (Hcy), a CVD risk marker. ObjectiveWe explored the association between CCB use and mortality in a large prospective cohort of patients with suspected stable angina pectoris (SAP), and potential effect modifications by Hcy-lowering B-vitamin treatment (folic acid, B12, and/or B6) as 61.8% of the patients participated in a randomized placebo-controlled B-vitamin intervention trial. MethodsPatient baseline continuous characteristics according to CCB treatment were tested by linear regression. Hazard ratios (HRs) for mortality associated with CCB treatment, also according to B-vitamin intervention, were examined using Cox regression analysis. The multivariable model included CVD risk factors, medical histories, and the use of CVD medications. ResultsA total of 3991 patients (71.5 % men) were included, of whom 907 were prescribed CCBs at discharge. During 10.3 years of median follow-up, 20.6% died and 8.9% from cardiovascular- and 11.7% from non-cardiovascular causes. Patients treated with CCBs had higher plasma Hcy, fibrinogen levels, and erythrocyte sedimentation rate (all P<0.001). Furthermore, CCB use was positively associated with mortality, also after multivariable adjustments (HRs [95% CIs]: 1.34 [1.15,1.57], 1.35 [1.08,1.70], and 1.33 [1.09,1.64] for total, CVD, and non-CVD death, respectively). Numerically stronger associations were observed among patients not treated with B-vitamins (HR [95% CI]: 1.54 [1.25, 1.88], 1.69 [1.25, 2.30], and 1.41 [1.06, 1.86] for total, CVD deaths, and non-CVD deaths, respectively), whereas no association was seen in patients treated with B-vitamins (HR [95% CI]: 1.15 [0.91, 1.46], 1.09 [0.76, 1.57], and 1.20 [0.88, 1.65]). ConclusionsIn patients with suspected SAP, CCB treatment was associated with increased mortality risk primarily among patients not treated with B-vitamins.

Trends of Antidiabetic and Cardiovascular Diseases Medication Prescriptions in Type 2 Diabetes between 2005 and 2017—A German Longitudinal Study Based on Claims Data

With an attempt to understand possible mechanisms behind the severity-dependent development of type 2 diabetes (T2D) comorbidities, this study examines the trends of antidiabetic and cardiovascular diseases (CVD) medication prescriptions in individuals with T2D. The study is based on claims data from a statutory health insurance provider in Lower Saxony, Germany. The period prevalence of antidiabetic and CVD medication prescriptions was examined for the periods 2005-2007, 2010-2012, and 2015-2017 in 240,241, 295,868, and 308,134 individuals with T2D, respectively. (Ordered) logistic regression analyses were applied to examine the effect of time period on the number and prevalence of prescribed medications. Analyses were stratified by gender and three age groups. The number of prescribed medications per person has increased significantly for all examined subgroups. For the two younger age groups, insulin prescriptions decreased but those of non-insulin medications increased, while both increased significantly over time for the age group of 65+ years. Except for glycosides and antiarrhythmic medications, the predicted probabilities for CVD medications increased over the examined periods, with lipid-lowering agents demonstrating the highest increase. Results point towards an increase in medication prescriptions in T2D, which is in line with the evidence of the increase in most comorbidities indicating morbidity expansion. The increase in CVD medication prescriptions, especially lipid-lowering agents, could explain the specific development of severe and less severe T2D comorbidities observed in this population.

Effectiveness of mHealth Interventions in Medication Adherence among Patients with Cardiovascular Diseases: A Systematic Review.

mHealth interventions have been reported to improve adherence to long-term therapies in chronic conditions. Therefore, this study aimed at determining the effectiveness of mHealth interventions in medication adherence among patients with cardiovascular diseases (CVDs), a leading cause of mortality globally. Relying on our inclusion criteria and the PRISMA recommendations, a literature search was carried out in the PubMed, Medline, and ProQuest databases for primary studies that investigated the impact of mHealth on medication adherence for cardiovascular disease (CVD) between 2000-2021. A total of 23 randomized controlled trials with 34,915 participants matched the selection criteria. The mHealth interventions used included text messages, mobile phone applications, and voice calls, which were used either as a single intervention or combined. Additionally, studies on enhancing drug adherence had contradictory findings: most of the studies elaborated positive results; however, six studies were unable to reveal any significant effect. Finally, a risk bias analysis revealed varying outcomes across all studies. This review, as a whole, supported the notion that mHealth interventions can be effective in improving adherence to CVD medication even though they could not improve adherence to all CVD medications when compared with controls. Further trials with more refined designs integrated with comprehensive interventions are needed to produce better health outcomes.

Utilizing quantitative dried blood spot analysis to objectively assess adherence to cardiovascular pharmacotherapy among patients at Kenyatta National Hospital, Nairobi, Kenya.

The burden of cardiovascular disease (CVD) is rising in Kenya and non-adherence to cardiovascular pharmacotherapy is a growing global public health issue that leads to treatment failure, an increased risk of cardiac events and poor clinical outcomes. This study assessed adherence to selected cardiovascular therapy medications among CVD patients attending outpatient clinics at Kenyatta National Hospital, Kenya by determining drug concentration(s) in patient dried blood spot (DBS) samples. Patients who had been taking one or more of the five commonly prescribed CVD medications (amlodipine, atenolol, atorvastatin, losartan, and valsartan) for at least six months were enrolled. Each patient completed a short questionnaire about their medication history and then provided a finger-prick blood spot sample from which drug concentrations were determined by liquid chromatography-high resolution mass spectrometry analysis. Two hundred and thirty-nine patients (62.3% female) participated in the study. The median number of medications used by patients was 2 (IQR 75%-25% is 3-1). Less than half (117; 49.0%) of patients were adherent to their prescribed CVD pharmacotherapy. Binary regression analysis revealed a significant correlation between non-adherence and the number of medications in the treatment regimen (Odds Ratio (OR) 1.583; 95%CI: 0.949-2.639; P-value = 0.039) and that gender was not an independent predictor of medication adherence (OR 1.233; 95%CI: 0.730-2.083; P-value = 0.216). Valuable information about adherence to each medication in the patient's treatment regimen was obtained using quantitative DBS analysis showing that adherence to CVD medications was not uniform. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence to pharmacotherapies objectively, when combined with hyphenated mass spectrometry analytical techniques. This information can provide physicians with an evidence-based novel approach towards personalization and optimization of CVD pharmacotherapy and implementing interventions in the Kenyan population, thereby improving clinical outcomes.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

Age-dependent prevalence of type 2 diabetes, cardiovascular risk profiles and use of diabetes drugs in Germany using health claims data.

This study evaluates type 2 diabetes mellitus (T2DM) prevalence in Germany, focusing on patients at risk for, or with already established, cardiovascular disease (CVD), as well as their antidiabetic and cardiovascular treatments. Using anonymized claims data from the WIG2 database, we calculated 2018 T2DM prevalence, extrapolating rates to the German statutory health insurance population. In the study period, 3 376 228 patients were eligible in the database. Forming antidiabetic medication groups, we evaluated treatment regimens of patients at risk for, or with already established CVD, based on the REWIND study criteria. We also evaluated their CVD medication prescriptions. Statutory health insurance extrapolated T2DM prevalence was estimated at 11.9%, with higher prevalence rates in older patients. When only patients with prescriptions of antidiabetic drugs were included, prevalence was 7.6%. At least 94% of patients with T2DM medication had at least one risk factor (without considering age) according to REWIND criteria, while 67%-80% had at least two risk factors depending on treatment received. Patients taking insulin combined with oral therapy comprised the largest proportion of patients with at least two REWIND risk factors. Approximately 85% of all patients with T2DM in the population were treated with antihypertensive medication. T2DM is widespread and affects older patients particularly. Most patients with T2DM had at least one CV risk factor, and about half already had established CVD. Early prevention of CVD, which disproportionately affects patients with T2DM, is necessary. Furthermore, the treatment of older patients with T2DM with insulin is still common and needs further evaluation.

Chinese expert consensus on the management of cardiovascular comorbidities in patients with chronic obstructive pulmonary disease

Patients with chronic obstructive pulmonary disease(COPD) often have co-existent systemic diseases(comorbidities), among which cardiovascular diseases (CVD) are the most common. The interactions between COPD and CVD are manifested in shared risk factors, disease severity, common symptoms, risks for exacerbations and disease progression, as well as therapeutic interventions. However, there is a knowledge gap in the management of COPD comorbidities. This expert consensus aims to increase the awareness, and to promote early diagnosis and proper management of cardiovascular comorbidities of COPD in medical professionals in China. The experts recommend that differential diagnosis should be performed for exertional dyspnea, a common symptom of COPD and cardiovascular diseases especially heart failure. Screening for cardiovascular diseases is needed in patients with COPD, and should be managed accordingly. COPD and comorbid CVD should be treated according to usual guidelines. Patients with COPD tolerate well to most of the medications for CVD. Selective β1-blockers for cardiovascular diseases are not contraindicated in COPD, but should be initiated from lower doses, and symptoms of airflow limitation be monitored. Likewise, β2-agonists and antimuscarinic drugs for COPD are generally safe for patients with comorbid CVD. Optimization of COPD management can improve heart function and cardiovascular outcomes.