Comorbid Cardiovascular Disease Research Articles

Prognostic significance of chronic kidney disease and impaired renal function in Japanese patients with COVID-19

BackgroundRenal impairment is a predictor of coronavirus disease (COVID-19) severity. No studies have compared COVID-19 outcomes in patients with chronic kidney disease (CKD) and patients with impaired renal function without a prior diagnosis of CKD. This study aimed to identify the impact of pre-existing impaired renal function without CKD on COVID-19 outcomes.MethodsThis retrospective study included 3,637 patients with COVID-19 classified into three groups by CKD history and estimated glomerular filtration rate (eGFR) on referral: Group 1 (n = 2,460), normal renal function without a CKD history; Group 2 (n = 905), impaired renal function without a CKD history; and Group 3 (n = 272), history of CKD. We compared the clinical characteristics of these groups and assessed the effect of CKD and impaired renal function on critical outcomes (requirement for respiratory support with high-flow oxygen devices, invasive mechanical ventilation, or extracorporeal membrane oxygen, and death during hospitalization) using multivariable logistic regression.ResultsThe prevalence of comorbidities (hypertension, diabetes, and cardiovascular disease) and incidence of inflammatory responses (white blood counts, and C-reactive protein, procalcitonin, and D-dimer levels) and complications (bacterial infection and heart failure) were higher in Groups 2 and 3 than that in Group 1. The incidence of critical outcomes was 10.8%, 17.7%, and 26.8% in Groups 1, 2, and 3, respectively. The mortality rate and the rate of requiring IMV support was lowest in Group 1 and highest in Group 3. Compared with Group 1, the risk of critical outcomes was higher in Group 2 (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.03–1.70, P = 0.030) and Group 3 (aOR: 1.94, 95% CI: 1.36–2.78, P < 0.001). Additionally, the eGFR was significantly associated with critical outcomes in Groups 2 (odds ratio [OR]: 2.89, 95% CI: 1.64–4.98, P < 0.001) and 3 (OR: 1.87, 95% CI: 1.08–3.23, P = 0.025) only.ConclusionsClinicians should consider pre-existing CKD and impaired renal function at the time of COVID-19 diagnosis for the management of COVID-19.

#2609 Comparison of baseline patient characteristics of the CONVINCE randomized controlled trial with existing trial and registry populations

Abstract Background and Aims The generalizability of randomized controlled trials (RCTs) results is based on representativeness of the population involved. Trial populations may have different baseline characteristics compared to the general population that could benefit from the intervention. We compare the baseline characteristics of patients involved in the CONVINCE trial with those involved in all previous RCTs and representative registries of patients receiving hemodialysis as renal replacement therapy. Method Based on world class methods for systematic reviews, we identified all RCTs comparing hemodiafiltration (HDF) with hemodialysis (HD) published up to January 2024 and extracted data on baseline patient characteristics. Where data were missing, authors have been contacted and data so far obtained were included in this analysis (Fig. 1). Additional contact attempts are being performed. In addition, a comprehensive search was conducted to identify renal registries from all geographic regions. Those without information in English, without information on HDF and registries focusing on special patient groups (e.g. transplantation only) were excluded. This registry data will not be analyzed in this abstract as we are in progress of extracting the patient data from the latest registry annual reports available up to January 2024 for further analysis. Results We have selected 11 RCTs for further analysis, with the selection criteria and outcomes presented in Fig. 1. Key patient characteristics from RCTs were compared with those of patients in the CONVINCE trial using descriptive statistics and forest plots (Fig. 1). Comparison of differences was analyzed with the Kruskal-Wallis-Test. Interpretation of the results are as follows: • Age: Mean age of 76.5 years noted in Morena et al. (2017) because study inclusion criterion was ≥65 years. Other RCTs ranged from 54.1 to 68 years, which is consistent with 62.4 years in the CONVINCE trial (χ2 = 10, df = 10, p = 0.44). • Sex: 16.7% and 50% female noted in Selby et al. (2006) and Meert et al. (2009) respectively probably due to limited sample size (12 patients and 14 patients respectively). Other RCTs ranges from 30.4% to 42.5%, which is consistent with 36.0% in the CONVINCE trial (χ2 = 11, df = 11, p = 0.44). • Diabetes comorbidities: Ranges from 17.8% to 45%. CONVINCE trial is 35.0% (χ2 = 6, df = 6, p = 0.42). • Cardiovascular diseases comorbidities: Range from 26.4% to 45%. CONVINCE trial is 45% (χ2 = 3, df = 3, p = 0.39). • AVF as vascular access: value of 100% in Pedrini et al. (2011) because it was an inclusion criterion. Other RCTs ranged from 79.4% to 90%, which is consistent with 82% in the CONVINCE trial (χ2 = 7, df = 7, p = 0.43). There were no significant differences between CONVINCE and other RCTs data regarding all 5 patient baseline characteristics. Conclusion Our analysis showed the CONVINCE trial has no significant differences in patient baseline characteristics compared to previous RCTs. For a more comprehensive evaluation of representativeness of the trial's population, we are currently retrieving missing data from the trial authors and analyzing data from hemodialysis registries.

Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease.

Epidemiological evidence suggests existing comorbidity between postmenopausal osteoporosis (OP) and cardiovascular disease (CVD), but identification of possible shared genes is lacking. The skeletal global transcriptomes were analyzed in trans-iliac bone biopsies (n = 84) from clinically well-characterized postmenopausal women (50 to 86 years) without clinical CVD using microchips and RNA sequencing. One thousand transcripts highly correlated with areal bone mineral density (aBMD) were further analyzed using bioinformatics, and common genes overlapping with CVD and associated biological mechanisms, pathways and functions were identified. Fifty genes (45 mRNAs, 5 miRNAs) were discovered with established roles in oxidative stress, inflammatory response, endothelial function, fibrosis, dyslipidemia and osteoblastogenesis/calcification. These pleiotropic genes with possible CVD comorbidity functions were also present in transcriptomes of microvascular endothelial cells and cardiomyocytes and were differentially expressed between healthy and osteoporotic women with fragility fractures. The results were supported by a genetic pleiotropy-informed conditional False Discovery Rate approach identifying any overlap in single nucleotide polymorphisms (SNPs) within several genes encoding aBMD- and CVD-associated transcripts. The study provides transcriptional and genomic evidence for genes of importance for both BMD regulation and CVD risk in a large collection of postmenopausal bone biopsies. Most of the transcripts identified in the CVD risk categories have no previously recognized roles in OP pathogenesis and provide novel avenues for exploring the mechanistic basis for the biological association between CVD and OP.

Young Trauma-Exposed Women with Low Sleep Effciency have Blunted Sympathetic Baroreflex Sensitivity and Higher Muscle Sympathetic Nerve Activity

Introduction: Poor sleep, a known risk factor for cardiovascular disease (CVD) and one of the American Heart Association’s essential 8th, is common after trauma-exposure. Although premenopausal women are thought to be protected from CVD, trauma exposure might increase their CVD risk. In a recent large epidemiological study examining sleep-related CVD comorbidities, the empirical cut off point for optimal sleep effciency (SE) was set at 83%, distinguishing between good and poor sleep effciency. Studies have suggested an overactive sympathetic nervous system and an impaired baroreflex sensitivity (BRS) as potential mechanisms of increased CVD risk. However, the impact of poor sleep effciency on muscle sympathetic nerve activity (MSNA) and BRS in young trauma-exposed women is unknown. We hypothesized that young trauma-exposed women with poor sleep effciency will present with impaired BRS and increased MSNA at rest. Methods: We collected data on 30 women (18 – 40 years) from diverse backgrounds who had been exposed to trauma. Sleep data was acquired via ActiWatch for 7 days and used to categorize our participants into two groups: good effciency (SE &gt; 83%, n=17) and poor effciency (SE &lt; 83%, n=13), with SE calculated as the percentage of time spent asleep while in bed. Additionally, we collected continuous noninvasive blood pressure (BP), heart rate (HR), and MSNA (burst frequency, incidence, and total activity) during 10 minutes of quiet rest. Sympathetic BRS was determined as the slope of the regression between individual sympathetic bursts and diastolic BP bins (3 mmHg), weighted against the number of cardiac cycles, utilizing an automated program (Ensemble, NZ). Results: There were no significant differences in trauma symptom severity, resting BP and HR between the two groups (p&gt;0.05 for all). However, resting sympathetic BRS was blunted in the poor SE (-0.10±0.88 bursts/100hb/mmHg) compared to the good SE (-1.44±1.58 bursts/100hb/mmHg, p=0.006) group, even after adjusting for age (p=0.009). Likewise, resting total MSNA was higher in the poor SE compared to the good SE after adjusting for age (p=0.028). MSNA burst frequency and burst incidence were comparable between the groups (p&gt;0.05). Conclusion: Our analyses revealed that poor sleep effciency is associated with decreased sympathetic baroreflex sensitivity and higher total muscle sympathetic activity at rest, regardless of age. Blunted sympathetic BRS may contribute to increased sympathetic activity in young women with poor sleep effciency. Future studies testing strategies to improve sleep effciency in this population could provide potential long-term cardiovascular benefits. UL1TR002494 and NIH K01HL161027 No disclosure. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Central retinal artery occlusion after intravitreal brolucizumab injection for treatment-naïve neovascular age-related macular degeneration; a case report

BackgroundTo report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history.Case presentationA 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication.ConclusionsIn rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history.

Common Risk Factors and Comorbidity of Cardiovascular Diseases and Cancer

Common Risk Factors and Comorbidity of Cardiovascular Diseases and Cancer

Abstract 2238: Reducing cardiovascular disease risk in cancer survivors: Impact of a 16-week circuit-based interval exercise intervention

Abstract Introduction: Obesity and physical inactivity pose a significant health concern for cancer survivors in developing comorbid conditions such as type 2 diabetes, hypertension, and metabolic syndrome that lead to a heightened risk of cardiovascular disease (CVD). Therefore, regular physical activity plays a central role in reducing the risk of CVD. The Framingham risk score (FRS) is an established assessment of CVD risk that combines six risk factors including age, gender, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, diabetes, and smoking status. The objective of the study was to investigate the effects of a 16-week circuit, interval-based exercise training intervention on FRS and the 10-year FRS-predicted risk of developing CVD among breast, prostate, and colorectal cancer survivors. Methods: This single center, pilot randomized controlled trial consisted of 90 sedentary, overweight or obese (BMI &amp;gt; 25.0 kg/m2) survivors of breast, prostate or colorectal cancers, randomized to exercise (n=60) or usual care (n=30). The 16-week intervention comprised supervised moderate to vigorous intensity aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) exercise sessions conducted in a circuit-based interval fashion, occurring three times per week. Blood samples were obtained at baseline and post-intervention time points to measure fasting plasma levels of HDL-C and LDL-C, along with resting systolic blood pressure and diagnosis of diabetes. Paired t-test and repeated measure ANOVA were used to determine between-group differences. Results: Participants (age 63.2 ± 10.8 years) were diagnosed with breast (35%), prostate (30%), and colorectal (35%) cancers and consisted of 55% female participants, participants had a mean BMI of 34.7±5.9, and 85% were obese. Chemotherapy and/or radiation therapy was completed by 75% of participants. Retention and adherence rates to exercise were high (100% and 92%, respectively). Compared to usual care, circuit, interval-based exercise significantly reduced total FRS (between group mean difference, -12.0 points p&amp;lt;0.001) and 10-year CVD risk (-10.0%; p&amp;lt;0.001). Conclusions: This study underscores the critical role of circuit-based, interval exercise interventions in mitigating the elevated cardiovascular risk faced by sedentary, overweight, or obese cancer survivors. The significant reduction in FRS components highlights the potential of structured exercise programs to enhance cardiovascular health, thereby reducing the burden of comorbid conditions and CVD risk in cancer survivors. Citation Format: Amber J. Normann, Rebekah L. Wilson, Cami N. Christopher, Mary K. Norris, Simone Cuomo, Christina M. Dieli-Conwright. Reducing cardiovascular disease risk in cancer survivors: Impact of a 16-week circuit-based interval exercise intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2238.

Abstract 6290: Effects of a circuit, interval-based exercise program on vascular function among cancer survivors

Abstract Background: Cancer survivors are at an increased risk of cardiovascular comorbidity, including atherosclerosis, hypertension, and heart failure, due to negative impacts of cancer treatments on vascular function. Exercise is recommended in recent cardio-oncology rehabilitation guidelines and has been shown to improve vascular function in clinical populations; however, its effects on vascular function are understudied in clinical oncology settings. Purpose: This pilot study examined whether a circuit, interval-based exercise intervention can improve vascular function, assessed by brachial artery flow-mediated dilation (baFMD) and carotid intima media thickness (cIMT) in breast, prostate, and colorectal cancer survivors. Methods: Overweight or obese (BMI&amp;gt;25.0 kg/m2), sedentary breast, prostate or colorectal cancer survivors were randomized to exercise (n=60) or usual care (n=30). Survivors in the 4-month exercise intervention trained three times/week, in a circuit, interval-based supervised moderate-vigorous aerobic (65-85% of VO2max) and resistance (65-85% of 1-repetition maximum) program. cIMT and baFMD were measured at baseline and post-intervention via an ultrasound. Paired t-tests and repeated-measures analysis of variance were run to assess within- and between-group differences. Results: The study sample included breast (n=38), prostate (n=24), colorectal (n=28) cancer survivors who were 63.2 ± 10.8 years old, completed chemotherapy and/or radiation (75%) and were obese (87%). Post-intervention, baFMD significantly increased in the exercise group compared to the control group (between-group mean difference: 6.3%; 95% CI: [1.9 to 9.3], p=0.001). There was also a significant reduction in cIMT in the exercise group compared to the control group (between-group mean difference: -0.039mm, 95% CI: [-0.080 to -0.009], p=0.002). Conclusions: Our findings in this pilot study support that a circuit, interval-based aerobic and resistance exercise intervention may improve vascular function in breast, prostate, and colorectal cancer survivors. Future studies are recommended to understand how exercise interventions can be utilized clinically to improve cardiovascular disease risk and co-morbidity among cancer survivors. Citation Format: Cami N. Christopher, Dong-Woo Kang, Paola Gonzalo-Encabo, Rebekah L. Wilson, Amber J. Normann, Mary K. Norris, Christina M. Dieli-Conwright. Effects of a circuit, interval-based exercise program on vascular function among cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6290.

An unexpected interaction between diabetes and cardiovascular diseases on cognitive function: A cross-sectional study

ObjectiveImpaired cognitive function in older individuals significantly affects quality of life. The interaction between comorbid diabetes and cardiovascular disease (CVD) and its impact on cognitive impairment remains unclear. MethodsThis study analyzed 2564 subjects from the National Health and Nutrition Examination Survey dataset. Cognitive function was measured using various scores, including CERAD Total Score, CERAD Delayed Recall Score (CDRS), Animal Fluency Total Score, and Digit Symbol Score. Multiple regression models were constructed to explore the relationship between different diseases and cognitive function, considering covariates such as age, sex, education, body mass index, alcohol intake, smoking, physical activity, kidney function, and hypertension. ResultsAfter adjusting for multiple factors, the presence of CVD, diabetes, or both showed a significant negative association with the total cognitive score. The CDRS was associated with both CVD and diabetes. The Digit Symbol score was associated with the presence of CVD, diabetes, or both. No significant differences were found between patients with diabetes and CVD in cognitive test results. An interaction between CVD and diabetes was observed in relation to the CDRS but not in other test scores or the total score. ConclusionThe individual impact of each disease on cognitive function was not significant. However, an interaction between CVD and diabetes was found when both diseases coexisted, specifically in relation to delayed learning ability.

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.

Abstract P256: Rationale, Development, and Implementation of a Multidisciplinary Digital Lifestyle Health Education Program for Older Adults With Cardiovascular Disease and Osteoarthritis

Introduction: Cardiovascular disease (CVD) is the leading cause of death worldwide. Globally, osteoarthritis (OA) affects 654 million. In 2018, of the 1.2 million Australians who had CVD, half also had arthritis, with the most common form in Australia being OA. Ongoing pain and physical limitations from OA can affect lifestyle choices, contributing to the shared risk factor profile of CVD and OA (physical inactivity, overweight/obesity, poor diet, high medication use). This contributes further to the burden of both diseases including reduced 6-minute walk (6MW) performance, which is directly related to increased CVD mortality. This project outlines the rationale for and development of a multidisciplinary digital lifestyle health education program for the treatment and secondary prevention of CVD and its common comorbidity of OA. Methods: This study is a cross-sectional analysis of older adults in Sydney. Class was classified based on the Australian socioeconomic index for areas. Conditions were defined according to Australian national guidelines. Medical history, body mass index (BMI), waist measurement, muscle strength, and 6MW measurements were assessed. Differences between those with and without OA were determined via one-way analysis of variance. Simple linear regressions assessed potential relationships. Results: In a cohort of 532 adults; n=341 (64.1%) had diagnosed CVD; 48.4% of which had OA (mean age 66±12 years; 73.3% female). Socioeconomic index was deemed high. In the OA cohort mean BMI and waist were above healthy heart recommendations according to the World Health Organisation. There were no significant differences between those with OA and those without for cardiovascular risk factors of body weight, BMI, waist measurement, blood pressure, 6MW, or muscle strength. However, in those with CVD and OA, the relationship between age and 6MW was stronger and age accounted for more of the variance in performance (r=-0.44; r 2 =0.19; p&lt;0.001) than those without OA (r=-0.37; r 2 =0.17; p&lt;0.001), indicating a greater reduction in walking ability in those with OA as they get older. Conclusion: With 6MW performance being related to CVD mortality, interventions are needed to improve health and fitness in this cohort. International guidelines for CVD and OA recommend treatment should prioritise lifestyle changes, including a healthy diet, regular physical activity, and interventions that address all risk factors. Lifestyle LIFEMAP will assess the efficacy of a widely translatable multidisciplinary digital evidence-based 10-module lifestyle, food, exercise, medication, and park prescription education program for adults with the comorbidity of CVD and OA. We expect this program to improve knowledge, and healthy lifestyle choices, thereby improving physical activity and health outcomes in this highly vulnerable population.

Abstract P304: Sex Differences for the Progression of Cardiovascular Multimorbidity in Older Adults in the United States

Introduction: Understanding the progression of cardiovascular multimorbidity and recognizing differences are needed to develop effective strategies to improve health outcomes. There is a knowledge gap in the potential unequal burden and progression of cardiovascular multimorbidity. Our objective is to investigate sex differences in the progression of cardiovascular multimorbidity among older adults in the US and estimate relative life expectancies among patients with severe multimorbidity. Hypothesis: We hypothesized that life expectancy among older adults with severe cardiovascular multimorbidity is inversely related to the number of comorbid conditions and progresses more acutely in males. Methods: Repeated cross-sectional cohort study of inpatient, outpatient, and carrier claims for a 5% nationwide Medicare sample. We included Medicare beneficiaries aged 65 or older enrolled in Medicare Fee-For-Service program from 2010 to 2020 and living in the continental US. Multistate life table models were employed to estimate cardiovascular disease (CVD) progression and total life expectancies from ages 65 to 85 years. Progression probabilities and life expectancies were adjusted for age, non-cardiovascular comorbidities, and Medicaid dual eligibility. A microsimulation approach was utilized to derive life tables, and bootstrapping was used to estimate variability. The primary outcome was the development and progression of cardiovascular multimorbidity, defined by the number of major cardiovascular conditions (atrial fibrillation, acute myocardial infarction, heart failure, stroke, and chronic ischemic heart disease). Comorbidities were assessed using validated algorithms based on diagnostic codes billed over a 1-year lookback period, and beneficiaries were followed forward from their index date. Results: Of 2,189,633 beneficiaries, the median age was 69, median follow-up was 5 years, and 55.9% were female. For male beneficiaries, odds of developing cardiovascular comorbidities were significantly higher than for females, with odds ratios ranging from 1.20 (95% CI 1.19-1.21) for one CVD to 1.97 (95% CI 1.88-2.06) for 1 or more of the 4 CVD comorbidities. Men with 1 CVD at baseline had significant odds of developing 2 (OR: 1.10, 95% CI 1.09-1.11) and four CVDs (OR: 1.29, 95% CI 1.24-1.34), as well as a significant mortality risk (OR: 1.19, 95% CI 1.18-1.21). However, for men with 4 CVDs, the odds of progressing to 5 were not significant (OR: 1.00, 95% CI 0.97-1.04). Across levels of baseline multimorbidity, male beneficiaries had significantly elevated mortality risks compared to females, with the highest risk for those with no baseline CVD (OR: 1.50, 95% CI 1.48-1.52). Conclusions: These findings suggest persistent sex differences in cardiovascular multimorbidity progression, identifying a potentially important target for the improvement of health outcomes.

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response.

Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had≥ 12months of continuous enrollment prior to initiation (preindex period) and ≥ 6months of data following initiation (postindex period; variable follow-up after 6months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6months postindex. Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article.

Changes in Healthcare Spending Attributable to High Deductible Health Plan Offer Among Enrollees with Comorbid Substance Use Disorder and Cardiovascular Disease.

The rise in prevalence of high deductible health plans (HDHPs) in the United States may raise concerns for high-need, high-utilization populations such as those with comorbid chronic conditions. In this study, we examine changes in total and out-of-pocket (OOP) spending attributable to HDHPs for enrollees with comorbid substance use disorder (SUD) and cardiovascular disease (CVD). We used de-identified administrative claims data from 2007 to 2017. SUD and CVD were defined using algorithms of ICD 9 and 10 codes and HEDIS guidelines. The main outcome measures of interest were spending measure for all non-SUD/CVD-related services, SUD-specific services, and CVD-specific services, for all services and medications specifically. We assessed both total and OOP spending. We used an intent-to-treat two-part model approach to model spending and computed the marginal effect of HDHP offer as both the dollar change and percent change in spending attributable to HDHP offer. Our sample included 33,684 enrollee-years and was predominantly white and male with a mean age of 53 years. The sample had high demonstrated substantial healthcare utilization with 94% using any non-SUD/CVD services, and 84% and 78% using SUD and CVD services, respectively. HDHP offer was associated with a 17.0% (95% CI = [0.07, 0.27] increase in OOP spending for all non-SUD/CVD services, a 21.1% (95% CI = [0.11, 0.31]) increase in OOP spending for all SUD-specific services, and a 13.1% (95% CI = [0.04, 0.23]) increase in OOP spending for all CVD-specific services. HDHP offer was also associated with a significant increase in OOP spending on non-SUD/CVD-specific medications and SUD-specific medications, but not CVD-specific medications. This study suggests that while HDHPs do not change overall levels of annual spending among enrollees with comorbid CVD and SUD, they may increase the financial burden of healthcare services by raising OOP costs, which could negatively impact this high-need and high-utilization population.

Cardiac interventions on total knee arthroplasty: a national inpatient sample-based analysis.

Comorbid cardiovascular diseases have been associated with poor outcomes in total knee arthroplasty (TKA); however, our understanding of TKA with prior cardiac treatment procedures has largely been undocumented. In this study, we examined TKA patients who had undergone different cardiac interventions that addressed their condition. The purpose was to characterize and compare outcomes for a growing patient population not yet analyzed. The 2016-2019 Nationwide Inpatient Sample database was queried for 558,256 patients who had TKA (ICD-10CM). Backgrounds significant for pacemaker [PM] (n = 8025), coronary artery bypass [CABG] (n = 12,683), heart valve surgery [HV] (n = 4125), or coronary stent [CS] (n = 19,483) were compared against those without, across demographics, admission information, and various complications. Cardiac interventions were associated with increased age, male gender, length of stay, and cost of care. CABG, and Stent groups had more diabetics, but HV had significantly fewer (p = 0.008). PM and HV had significantly less tobacco use and, in addition to CABG, less obesity. Postoperatively, mortality was elevated in the PM [Odds ratio (OR) 2.89, p = 0.008], CABG (OR 2.53, p = 0.006) and CS group (OR 1.94, p = 0.018), but not HV. Myocardial infarctions were elevated in the CABG (OR 3.874) and CS group (OR 5.11) (p < 0.001). PM, HV, and CS had increased odds of periprosthetic fracture by 2.15-fold (p < 0.001), 2.09-fold (p < 0.001), 1.29-fold (p = 0.011) respectively. HV saw increased periprosthetic mechanical complications (OR 1.48, p = 0.006). CABG increased the odds of deep surgical site infection 14.23-fold and CS 9.22-fold (p < 0.001). Postoperative pneumonia was increased in PM, CABG, and CS groups (OR 2.15,), (OR 2.21,), (OR 1.64,) (p < 0.001). Patients who have undergone cardiac intervention are generally at risk for adverse stays. Furthermore, risk factors and complications vary between the groups. Our analysis emphasizes the importance of individualized medical care and as a basis for electing and informing patients for TKA.

Metabolic Abnormalities Following Tirzepatide Monotherapy in Japanese Patients with Type 2 Diabetes: A Phase 3 SURPASS J-mono Post Hoc Analysis.

The presence of metabolic abnormalities in patients with type 2 diabetes (T2D) increases the risk of cardiovascular disease and other comorbidities. This analysis compared the effects of tirzepatide (5, 10, and 15mg) and dulaglutide 0.75mg on the prevalence of metabolic abnormalities in Japanese patients with T2D. This was a post hoc analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled, parallel-group, phase 3 trial that compared the efficacy and safety of tirzepatide monotherapy (5, 10, and 15mg) to dulaglutide 0.75mg in Japanese patients with T2D. Thresholds for abnormalities were based on the Japanese criteria for metabolic syndrome. Proportions of participants meeting a composite endpoint (visceral fat accumulation measured by waist circumference plus two or more of dyslipidemia, hypertension, or hyperglycemia) or individual component thresholds were calculated at baseline and week 52 for the overall population and for baseline body mass index (BMI) subgroups (< 25, 25 to < 30, and ≥ 30kg/m2). Of 636 randomized participants, 431 (67.8%) met the composite endpoint at baseline, with similar findings observed across treatment arms. At week 52, the proportion of participants on treatment that met the composite endpoint was 31.7%, 23.0%, and 14.2% in the tirzepatide 5-, 10-, and 15-mg arms, respectively, and 56.5% in the dulaglutide arm (p < 0.001). A higher proportion met the composite endpoint at baseline in the BMI 25 to < 30 and ≥ 30kg/m2 subgroups (73.2-79.3%) compared with the < 25kg/m2 subgroup (45.3%), with reductions observed across all BMI subgroups treated with tirzepatide. The proportion of participants with individual metabolic abnormalities showed similar trends to those observed for the composite endpoint. Tirzepatide was consistently superior to dulaglutide across all assessments. Tirzepatide reduced the prevalence of multiple metabolic abnormalities, indicating tirzepatide may have metabolic benefit in Japanese patients with T2D. ClinicalTrials.gov, NCT03861052.

ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ ЭНДОТЕЛИЯ У БОЛЬНЫХ ПСОРИАЗОМ

Abstract. Introduction. Psoriasis is an independent risk factor for cardiovascular diseases, accompanied by an increased risk of mortality from cardiovascular diseases, as compared with the population, which is mainly associated with chronic systemic inflammation (increased levels of C-reactive protein, fibrinogen, and homocysteine) and with the accumulation of conventional cardiovascular risk factors, such as dyslipidemia, obesity, decreased physical activity, and arterial hypertension. There are only few studies evaluating the link between psoriasis, inflammation, and cardiovascular disease. Our aim was to study the relationship between pro-inflammatory mediators and the endothelium functional state indicators of the in patients with psoriasis. Materials and Methods. We examined 116 patients with verified psoriasis, aged 19-62 years. The control group consisted of 25 comparably aged and practically healthy individuals. The diagnosis was made considering the psoriasis clinical form, stage, seasonality, type, and severity. All patients underwent a standard laboratory and instrumental examination. The levels of pro-inflammatory markers (IL-6, VEGF,CRPvh) were determined by enzyme-linked immunosorbent assay using commercial ELISA-BEST kits manufactured by OOO Vector-Best, Novosibirsk, Russia. The endothelial function was assessed by using the Biomedical ENDOTELIN test system by BioKhimMak JSC to measure the quantitative content of endothelin-1, a characteristic of the vasomotor function of endothelium, determined by ultrasound according to the method proposed by Celermajer D. et al. Results and Discussion. The study revealed a high incidence of the disease in people of working age and a slight predominance among male patients. In 55.2% of patients, classic atherosclerosis risk factors were identified: Arterial hypertension, smoking, low physical activity, alcohol abuse, and improper nutrition. 33.6% of patients were overweight; 24.1% had obesity I-II degree, and 39.7% with abdominal obesity. According to the findings of the study of pro-inflammatory markers in the blood serum, there is a significant increase in their levels as compared with the control group indicators, which correlates with the severity of psoriasis and a decrease in the ratio of IL-6/CRPvh. Endothelial dysfunction was characterized by a statistically significant increase in endothelin-1 and a significant increase in the content of vascular endothelial growth factor (VEGF) in the blood serum of psoriasis patients. Percentage increase in the brachial artery diameter on the endothelium-dependent stimulus was reduced and averaged 9.14% in the group of patients with psoriasis. Conclusion. A high comorbidity of psoriasis and cardiovascular diseases has been established. A significant increase in the levels of systemic immune inflammation mediators IL-6 and C-RBhv and a decrease in the ratio of IL-6/C-RPhvh were identified, which correlates with the severity of the disease and the presence of cardiovascular diseases. Vascular endothelium dysfunction is characterized by an increase in the content of ET-1 and VEGF in the blood serum and a decrease in the flow-mediated dilatation of the brachial artery.

Weight variation during androgen deprivation therapy in patients with localized prostate cancer: Data from two prospective randomized trials.

296 Background: In prostate cancer (PCa) treated with androgen deprivation therapy (ADT) and radiotherapy (RT), limited prospective data exist regarding weight variation during ADT. Using our prospective data from two phase III trials we compare the magnitude of weight variation during different duration of ADT. Methods: 400 patients (pts) with intermediate risk PCa received 6 months of ADT (Bicalutamide 1 month (m) and Goserelin 10,8 mg x 2), and 630 pts with high-risk PCa were treated with 18 or 36m of ADT (Bicalutamide 1m and Goserelin 10,8 mg x 6 or 12). Pts’ weights were measured at baseline then at each Goserelin dose. 463/1030 pts were excluded from the analysis: 90 no or incomplete ADT, 127 no initial weight and 246 no weight at the end of ADT. Regular patient weighing was available in 567/1030 pts (55%) from whom 250, 191 and 124 received, respectively, 6, 18 or 36m of ADT. Pt’s characteristics and weights were compared with Kruskal-Wallis and Chi squared test between groups of ADT. Multivariable logistic regression was performed to assess predictors of weight gain over 2 kg. Variables included were duration of ADT, age ≥65 vs. &lt; 65 and baseline comorbidities (cardiovascular disease, diabetes, chronic obstructive pulmonary disease, hypertension). Results: Comparing weights between the beginning and the end of ADT, 375/567 (66.1%) pts gained and 192/567 (33.9%) lost weight. The mean ± SD weight gain at the end of ADT was significantly higher in pts receiving 18m of ADT (1.98 ± 4.05) or 36m (2.38 ± 5.15) compared to pts receiving only 6m (0.98 ± 3.10, p=0.003). As ADT duration increased (6, 18 or 36m), weight gain over 2 kg (34.1% vs. 48.2% vs. 53.2%, p&lt;0.001) and over 4 kg (12.7% vs. 26.2% vs. 36.3%, p&lt;0.001) significantly increased. In multivariable logistic regression, predictors of weight gain over 2 kg were 18m ADT [OR=1.85 (1.25-2.74), p=0.002] and 36m ADT [OR=2.23 (1.43-3.48), p&lt;0.001] compared to 6m ADT and non-diabetic pts (OR=2.13 (1.28-3.54), p=0.003). Age was not a factor. In the 375 pts who gained weight, the rate of patients that gained 0.1 to 2 kg, 2.1 to 4 kg and more than 4 kg were respectively (47.2%, 33.1% and 19.6%) in the 163 receiving 6m ADT, (30.3%, 32.6% and 37.1%) in 132 pts receiving 18m ADT, and (17.6%, 26.3% and 56.4%) in the 80 pts receiving 36m ADT. In the 192 pts who lost weight, the rate of patients that lost 0.1 to 2 kg, 2.1 to 4 kg and more than 4 kg were respectively (62.9%, 21.3% and 15.6%) in 89 receiving 6m ADT, (50.8%, 27.1% and 22.1%) in 59 pts receiving 18m ADT and (59.1%, 15.9% and 25%) in 44 pts receiving 36m ADT. Conclusions: ADT is not associated with weight gain in all pts. Based on our prospective data, one third of pts lose weight at the end of ADT. However, weight gain above 2 kg or 4 kg increases with ADT duration and non-diabetics pts, regardless of age. Weight monitoring in pts receiving ADT should be done regularly and pts counseled accordingly.

Cardiovascular medications and overall survival in metastatic hormone-sensitive prostate cancer.

75 Background: The assessment of comorbid cardiovascular disease can predict health outcomes and may risk-stratify patients for adverse events and death. Current methods used to estimate patient risk, such as the Charlson Comorbidity Index (CCI), are based on International Classification of Diseases (ICD) codes, which are a poor indicator of severity and complexity of comorbid disease. Alternatively, the number of cardiovascular drugs could be an efficient tool for estimating patient risk. In this study, we examined the relationship between cardiovascular medications and survival in patients being treated for metastatic hormone-sensitive prostate cancer (mHSPC). Methods: A nationwide retrospective observational study of US Veterans with de novo mHSPC in the Veterans Health Administration between 2011-2021 with at least 1 prescription medicine of any class. We determined the number of cardiovascular drugs from Anatomic Therapeutic Chemical (ATC) drug class C prescribed in the year prior up to 14 days before initiation of treatment. Multivariable logistic regression and Cox proportional hazard modeling was used to assess the association between number of drugs with overall survival (OS) while accounting for important covariates including age, body-mass index (BMI), prostate specific antigen (PSA), CCI, race, and weight change. Results: Among 7,875 veterans, a median (IQR) of 2 (1-4) unique cardiovascular medications were filled in the year prior to treatment. The mean age was 74.3 years (SD 10.0) with a median CCI of 3 (3-6). Age was associated with increased number of cardiac medicines with a mean of 1.6 drugs in &lt;60 years, 2.2 drugs in 60-69, 2.5 drugs in 70-80, and 2.5 drugs in 80+ years (p&lt;0.001). Increased number of medications was associated with decreased OS using the Kaplan-Meier method (p&lt;0.001, see table). After adjusting for age, race, BMI, weight change, PSA, and CCI, the number of medications was independently associated with increased mortality with an adjusted hazard ratio (aHR) of 1.05 (1.03-1.06) for each additional cardiac drug. Increased mortality was observed in patients treated with 2 or more cardiac drugs (see table). Conclusions: The number of cardiovascular medications is associated with decreased survival in veterans undergoing treatment for mHSPC, even after accounting for important covariates including age, BMI, PSA, and CCI. The assessment of cardiovascular medications may provide a simple and reliable tool to estimate comorbid disease and survival in patients with cancer. [Table: see text]

The potential interaction between chemosensitivity and the development of cardiovascular disease in obstructive sleep apnea

ObjectivesChemosensitivity is an essential part of the pathophysiological mechanisms of obstructive sleep apnea (OSA). Not only does OSA have a certain relationship with the comorbidity of cardiovascular disease (CVD) but also chemosensitivity plays a crucial role in the development of CVD. This study aims to investigate the potential interaction between chemosensitivity and the development of CVD in OSA. MethodsA total of 169 participants with suspected OSA were included. Data were gathered on the parameters of polysomnography and baseline clinical features. Peripheral chemosensitivity was evaluated by employing the rebreathing test. The lifetime CVD risk was computed using the China-PAR (Prediction for atherosclerotic CVD Risk in China) risk equation. ResultsAfter controlling for covariates, participants with chemosensitivity levels in the second and fifth quantiles tended to hold an increased proportion of high lifetime CVD risk (OR 10.90, 95%CI [2.81–42.28]; OR 6.78, 95%CI [1.70–27.05], respectively). The diagnosis of OSA would significantly increase the 10-year and lifetime CVD risks in participants with low chemosensitivity, while no such differences were found in participants with high chemosensitivity. ConclusionHigher lifetime CVD risk was associated with participants who had greater peripheral chemosensitivity. In terms of the CVD outcomes, adult patients with a relatively low level of chemosensitivity may be primarily related to their diagnosis of OSA, whereas adult patients with a relatively high level of chemosensitivity may be more strongly associated with their elevated levels of chemosensitivity rather than OSA.