Pre-existing Cardiovascular Disease Risk Factors Research Articles

Impact of Hypomethylating Agents on Cardiovascular Disease Risk Among Patients with Myelodysplastic Syndromes

Introduction: The association between clonal hematopoiesis (CH) and cardiovascular disease (CVD) risk has drawn attention to cardiovascular outcomes in myelodysplastic syndromes (MDS). CVD accounts for 25% of deaths in MDS, potentially via CH-mediated accelerated atherosclerosis from inflammatory vascular responses. We previously demonstrated that MDS was independently associated with increased risk of CVD in older adults from SEER-Medicare. We subsequently hypothesized that treatment with hypomethylating agents (HMA) could reduce CVD risk by ameliorating CH clones and reducing the inflammation. In this study, we aimed to define the impact of HMA on incident cardiovascular events among older adults with MDS. Methods: We identified subjects ≥66 years diagnosed with MDS from 2007 to 2017 in SEER-Medicare. Exclusion criteria including lacking continuous Medicare parts A, B, and D, enrolled in HMO, or incomplete follow-up. Demographics included age, sex, race, rurality, socioeconomic quintile, marital status, and geographic region. Baseline CVD risk factors, defined from ICD-9/10 codes, included hypertension, hyperlipidemia, diabetes, atrial fibrillation, pre-existing cardiac disease, obesity, and smoking. MDS factors, defined using HCPCS codes, ICD-O-3 codes and prescription records, included MDS subtype and histologic risk stratification, transfusion dependence and treatment with hypomethylating agents (HMA), lenalidomide, or erythropoietin-stimulating agents (ESA) as time-varying variables. Incident CVD was defined as new myocardial infarction (MI) and/or ischemic stroke occurring after MDS diagnosis, using published ICD-9/10 algorithms. We controlled for confounding using 2 complementary analytic approaches. First, we assessed the association between HMA use and CVD using propensity score adjusted cause-specific competing risk Cox hazard models with death as competing risk, Second, we used a case-crossover design with conditional logistic regression, in which subjects with CVD served as their own controls, using a 3-month HMA treatment window and a control period 6 months prior to the incident event. Results: We identified a cohort of 15,227 eligible patients with MDS. Of these, 1,125 patients had an MI and/or ischemic stroke within 1 year before MDS diagnoses and were excluded. We analyzed 14,102 MDS patients, with median age 82 years (IQR 77 - 86), who were predominantly male (53.8%), non-Hispanic white (88.6%), and from urban/suburban areas (86.2%). MDS was of low, intermediate, and high histologic risk in 14.7%, 72.8%, and 12.5%, respectively, and 28.6% were transfusion dependent. Pre-existing CVD risk factors at time of MDS diagnosis were present in 12,538 patients, with baseline cardiovascular risk defined as low, intermediate, and high in 11.1%, 32.3%, and 56.6% of the cohort. The cumulative incidences of MI, ischemic stroke and composite CVD events were 11.3%, 10.6% and 20.4%, respectively. The propensity score (PS) conditional probability for being treated with HMA included demographic variables, CVD risk factors, MDS histology and transfusion dependence. Our PS model adequately predicted HMA treatment propensity (AUC 0.76). Cause-specific regression with death as competing risk, adjusted for PS and other MDS-specific treatments (ESA and lenalidomide), showed no significant effect of HMA on the risk of composite CVD events, MI, or ischemic stroke (Table 1). Conditional logistic regression in the case-crossover analysis of 1,907 patients with composite CVD events showed no significant effect of HMA. Results were similar for analysis of patients with MI and ischemic stroke (Table 2). Conclusions: No study has previously investigated the effect of HMA therapy on cardiovascular outcomes in patients with MDS. We demonstrate that HMA therapy is not associated with a significant risk reduction in cardiovascular events among patients with MDS patients from the SEER-Medicare database. These results show that HMA therapy is unlikely to reduce cardiovascular mortality and underscore the need for alternative therapeutic strategies targeting cardiovascular health patients with MDS.

Prepregnancy Cardiovascular Disease Risk Factors and Adverse Pregnancy Outcomes in a Safety-Net Hospital.

Background: Many adverse pregnancy outcomes (APOs) are associated with elevated cardiovascular disease (CVD) risk. However, APO data in the context of pre-existing CVD risk factors, and from diverse populations, are limited. We assessed the occurrence of APOs among individuals with and without prepregnancy CVD risk factors, overall and by race/ethnicity. Methods: We conducted a retrospective study using electronic medical record data from a large urban safety-net hospital. Individuals with prenatal care and delivery between 2016 and 2018 at the hospital were included, and data from prenatal intake through the delivery hospitalization were captured. The exposure, prepregnancy CVD risk factors (hypertension, diabetes, tobacco use, and obesity), and the outcome, APOs (hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, low birth weight, and stillbirth), were identified from electronic medical records. Results: We identified 3760 unique delivering individuals, of whom 55.1% self-identified as Black non-Hispanic and 17% as Hispanic. Prepregnancy CVD risk factor prevalence was 45.6%, most commonly obesity (26.6%). APO prevalence was 35.6%, most commonly a hypertensive disorder of pregnancy (20.1%). Overall, 45.7% of APOs occurred in the absence of recognized prepregnancy CVD risk factors, representing 16.3% of the total sample. Among individuals without prepregnancy CVD risk factors, APO prevalence was 30.0% and did not vary by race/ethnicity. Conclusions: In this racially and ethnically diverse hospital-based sample, APOs were present in one in three parous individuals without prepregnancy CVD risk factors-a group with potentially elevated CVD risk who might otherwise be missed by traditional CVD risk factor screening.

COVID-19 and Cardiovascular Diseases: From Cellular Mechanisms to Clinical Manifestations.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), quickly spread worldwide and led to over 581 million confirmed cases and over 6 million deaths as 1 August 2022. The binding of the viral surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor is the primary mechanism of SARS-CoV-2 infection. Not only highly expressed in the lung, ACE2 is also widely distributed in the heart, mainly in cardiomyocytes and pericytes. The strong association between COVID-19 and cardiovascular disease (CVD) has been demonstrated by increased clinical evidence. Preexisting CVD risk factors, including obesity, hypertension, and diabetes etc., increase susceptibility to COVID-19. In turn, COVID-19 exacerbates the progression of CVD, including myocardial damage, arrhythmia, acute myocarditis, heart failure, and thromboembolism. Moreover, cardiovascular risks post recovery and the vaccination-associated cardiovascular problems have become increasingly evident. To demonstrate the association between COVID-19 and CVD, this review detailly illustrated the impact of COVID-19 on different cells (cardiomyocytes, pericytes, endothelial cells, and fibroblasts) in myocardial tissue and provides an overview of the clinical manifestations of cardiovascular involvements in the pandemic. Finally, the issues related to myocardial injury post recovery, as well as vaccination-induced CVD, has also been emphasized.

The importance of cardiovascular disease in breast cancer survivors. mini review

Objective: Breast cancer (BC) is the most frequent neoplastic disease in women. Recently, cardiovascular disease (CVD) has arisen as a non-cancer related mortality cause between breast cancer survivors. The aim of this paper is to establish the importance of CVD in BC survivors in order to draw attention to this public health problem so new strategies can be implemented in the future. Methods: A PubMed research of the Mesh terms “Breast Neoplasms” and “Heart Disease Risk Factors” was made. Journals available to the Universidad Nacional Autónoma de México – U.N.A.M. (National Autonomous University of México) were revised. Of 130 articles, 52 were selected and were cited for this review. Conclusion: Earlier detection rates and advances in breast cancer therapies have improved overall survival in BC patients. CVD is now an important cause of mortality in BC survivors. This might be explained by the conjunction of pre-existing CVD risk factors and cardiovascular injury secondary to cancer therapy.

Coronary artery calcifications on breast cancer radiotherapy planning CT scans and cardiovascular risk: What do patients want to know?

BackgroundCoronary artery calcifications (CAC) is a strong predictor of cardiovascular disease (CVD), which can be automatically quantified on routine breast radiotherapy planning computed tomography (CT) scans. Around 8% of patients have (very) high CAC scores and corresponding increased risks of CVD. AimThis study explores whether, how, and under what conditions women with breast cancer want to be informed about their CAC-based CVD risk. MethodsA cross-sectional survey study was conducted in a random sample of UMBRELLA, a prospective breast cancer cohort. Participants (n = 79) filled out a questionnaire about their knowledge on the CVD risk following breast cancer, their interest in being informed about their CVD risk based on CAC score, and preferences on how they would want to receive this information. ResultsMost participants (66%) were not aware that the presence of CAC indicates an increased CVD risk. Participants indicated that they were not or only slightly aware of the risk of treatment-induced cardiotoxicity (48%), and that the risk of cardiotoxicity was higher in patients with pre-existing CVD risk factors (82%). The vast majority (90%) indicated that they want to be informed about in increased CAC-based CVD risk. ConclusionsThe majority of patients with breast cancer wants to be informed about their CAC-based CVD risk. With the majority of patients with breast cancer undergoing radiotherapy, and with low cost and automated options for accurate CAC measurement in planning CT scans, it is important to develop strategies to manage patients with an increased CAC-based risk of CVD.

Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer

Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. In this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Of the 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. ClinicalTrials.gov Identifier: NCT03206333.

Adipose Tissue Distribution and Cardiovascular Disease Risk Among Breast Cancer Survivors.

Cardiovascular disease (CVD) is a major source of morbidity and mortality among breast cancer survivors. Although body mass index (BMI) is associated with CVD risk, adipose tissue distribution may better identify patients with a high risk of CVD after breast cancer. Among 2,943 patients with nonmetastatic breast cancer without prior CVD, we used International Classification of Diseases (9th and 10th revisions) codes to identify incidence of nonfatal stroke, myocardial infarction, heart failure, or CVD death. From clinically acquired computed tomography scans obtained near diagnosis, we measured visceral adiposity (centimeters squared), subcutaneous adiposity (centimeters squared), and intramuscular adiposity (fatty infiltration into muscle [Hounsfield Units, scored inversely]). We estimated hazard ratios (HRs) and 95% CIs per SD increase in adiposity accounting for competing risks and adjusting for demographics, smoking, cancer treatment, and pre-existing CVD risk factors. Mean (SD) age was 56 (12) years. Over a median follow-up of 6 years, 328 CVD events occurred. Each SD increase in visceral or intramuscular adiposity was associated with an increase in CVD risk (HR, 1.15 [95% CI, 1.03 to 1.29] and HR, 1.21 [95% CI, 1.06 to 1.37]), respectively). Excess visceral and intramuscular adiposity occurred across all BMI categories. Among normal-weight patients, each SD greater visceral adiposity increased CVD risk by 70% (HR, 1.70 [95% CI, 1.10 to 2.62]). Visceral and intramuscular adiposity were associated with increased CVD incidence after breast cancer diagnosis, independent of pre-existing CVD risk factors and cancer treatments. The increased CVD incidence among normal-weight patients with greater visceral adiposity would go undetected with BMI alone. Measures of adipose tissue distribution may help identify high-risk patients and tailor CVD prevention strategies.

Adiposity, post-diagnosis weight change, and risk of cardiovascular events among early-stage breast cancer survivors

Little research examines whether adiposity or post-diagnosis weight changes influence Cardiovascular disease (CVD) among breast cancer patients for whom effects may differ due to treatment and recovery. We studied Stage I-III breast cancer survivors 18 to <80years, without pre-existing CVD, diagnosed from 1997 to 2013 at Kaiser Permanente. Women reported weight at diagnosis and weight and waist circumference (WC) around 24months post diagnosis. Using Cox models for time to incident coronary artery disease, heart failure, valve abnormality, arrhythmia, stroke, or CVD death, we examined at-diagnosis body mass index (BMI, n=3109) and post-diagnosis WC (n=1898) and weight change (n=1903, stable,±5 to <10-lbs or±≥10-lbs). Mean (SD) age was 57 (11) years, and BMI was 28 (6) kg-m2. Post diagnosis, 25% of women gained and 14% lost≥10-lbs; mean (SD) WC was 90 (15) cm. Over a median of 8.28years, 915 women developed CVD. BMI 25-30-kg/m2 (vs. BMI<25-kg/m2) was not associated with CVD, while BMI≥35-kg/m2 increased risk by 33% (HR: 1.33; 95%CI 1.08-1.65), independent of lifestyle and tumor/treatment factors. The increased risk at BMI≥35-kg/m2 attenuated with adjustment for pre-existing CVD risk factors to HR: 1.20; 95%CI 0.97-1.50. By contrast, even moderate elevations in WC increased risk of CVD, independent of pre-existing risk factors (HR: 1.93; 95%CI 1.31-2.84 comparing≥100-cm vs.≤80-cm). Post-diagnosis weight change had no association with CVD. Extreme adiposity and any elevation in WC increased risk of CVD among breast cancer survivors; however, changes in weight in the early post-diagnosis period were not associated with CVD. Survivors with high WC and existing CVD risk factors should be monitored.

Abstract 16746: Cardiovascular Disease Outcomes After Breast Cancer in Postmenopausal Women: Results From the Women’s Health Initiative

Introduction: A growing population of older breast cancer (BC) survivors may be at risk of cardiovascular disease (CVD). Pre-existing CVD risk factors may impact on subsequent development of CVD after BC among postmenopausal women. Objectives: (1) To describe baseline CVD risk factors among postmenopausal women with and without BC prior to diagnosis of BC; and (2) To examine independent associations of BC with individual and composite CVD events (i.e., the first occurrence of coronary heart disease [CHD], angina, coronary revascularization, congestive heart failure, peripheral arterial disease, and stroke) and mortality outcomes (i.e., all-cause, CVD, and CHD death) after BC adjusting for baseline characteristics and CVD risk factors. Methods: This prospective cohort study included 101,916 women in the Women’s Health Initiative (WHI) (including 4,340 women with invasive BC) aged 50-79 years without CVD at baseline (1993-1998) through December 2010. Over a period of 10 years after BC, CVD morbidity and mortality outcomes were identified and age-adjusted rates per 1,000 person-years and hazard ratios (HRs) with 95% confidence intervals (CIs) from Cox models were determined for women who did and did not develop BC. Results: Regardless of BC status, baseline CVD risk factors prior to BC, such as smoking, hypertension, diabetes and hypercholesterolemia, were strong predictors of CVD outcomes in postmenopausal women. Multivariable Cox models revealed that women who developed BC (n = 4,340) had a similar risk of composite CVD (HR = 0.91, 95% CI, 0.82-1.02), but a higher risk of CHD (HR=1.33, 95% CI, 1.12-1.58), compared with women without BC (n = 97,576). Women aged 70-79 and on hormonal therapy at the WHI entry with localized BC during follow-up period had the highest CHD death rate. The results were similar after excluding women with baseline cancer at the WHI study entry. Conclusions: These results emphasize the great need for identification and timely management of pre-existing CVD risk factors for postmenopausal women with BC. CVD accounts for almost as many deaths as BC among women with localized disease, indicating that improved effort to prevent and treat CVD risk factors could improve survival of postmenopausal BC survivors.

Exposure to experimental preeclampsia in mice enhances the vascular response to future injury.

Cardiovascular disease (CVD) remains the leading killer of women in developed nations. One sex-specific risk factor is preeclampsia, a syndrome of hypertension and proteinuria that complicates 5% of pregnancies. Although preeclampsia resolves after delivery, exposed women are at increased long-term risk of premature CVD and mortality. Pre-existing CVD risk factors are associated with increased risk of developing preeclampsia but whether preeclampsia merely uncovers risk or contributes directly to future CVD remains a critical unanswered question. A mouse preeclampsia model was used to test the hypothesis that preeclampsia causes an enhanced vascular response to future vessel injury. A preeclampsia-like state was induced in pregnant CD1 mice by overexpressing soluble fms-like tyrosine kinase-1, a circulating antiangiogenic protein that induces hypertension and glomerular disease resembling human preeclampsia. Two months postpartum, soluble fms-like tyrosine kinase-1 levels and blood pressure normalized and cardiac size and function by echocardiography and renal histology were indistinguishable in preeclampsia-exposed compared with control mice. Mice were then challenged with unilateral carotid injury. Preeclampsia-exposed mice had significantly enhanced vascular remodeling with increased vascular smooth muscle cell proliferation (180% increase; P<0.01) and vessel fibrosis (216% increase; P<0.001) compared with control pregnancy. In the contralateral uninjured vessel, there was no difference in remodeling after exposure to preeclampsia. These data support a new model in which vessels exposed to preeclampsia retain a persistently enhanced vascular response to injury despite resolution of preeclampsia after delivery. This new paradigm may contribute to the substantially increased risk of CVD in woman exposed to preeclampsia.

The CD14 C-260T single nucleotide polymorphism (SNP) modulates monocyte/macrophage activation in treated HIV-infected individuals.

BackgroundHIV-infected individuals have an increased risk of cardiovascular disease (CVD). T-allele carriers of the CD14 C-260T single-nucleotide polymorphism (SNP) have reported increased expression of the LPS-binding receptor, CD14 and inflammation in the general population. Our aim was to explore the relationship of this SNP with monocyte/macrophage activation and inflammation and its association with sub-clinical atherosclerosis in HIV-infected individuals.MethodsPatients with no pre-existing CVD risk factors on suppressive antiretroviral therapy were recruited from University Malaya Medical Centre, Malaysia (n = 84). The CD14 C-260T and TLR4 SNPs, Asp299Gly and Thr399Ile were genotyped and soluble(s) CD14 and sCD163 and high-sensitivity C-reactive protein, hsCRP were measured in plasma. Subclinical atherosclerosis was assessed by measuring carotid intima media thickness (cIMT). The association between CD14 C-260T SNP carriage and cIMT was assessed in a multivariable quantile regression model where a p-value of <0.05 was considered significant.ResultsWe found the CD14 C-260T T-allele in 56% of the cohort and evidence of subclinical atherosclerosis in 27%. TT genotype was associated with higher sCD163 (p = 0.009) but only marginally higher sCD14 (p = 0.209) and no difference in hsCRP (p = 0.296) compared to CC/CT. In multivariable analysis, only Framingham risk score was independently associated with higher cIMT while lower sCD163 was trending towards significance. No association was found in TT-genotype carriers and cIMT measurements.ConclusionThe CD14 C-260T SNP was associated with increased monocyte activation but not systemic inflammation or cIMT in this HIV-infected cohort with low CVD risk profile.