Late Cardiovascular Disease Research Articles

Etiology and Management of Dyslipidemia in Patients With Cancer.

Patients with cancer are now living longer than ever before due to the growth and expansion of highly effective antineoplastic therapies. Many of these patients face additional health challenges, of which cardiovascular disease (CVD) is the leading contributor to morbidity and mortality. CVD and cancer share common biological mechanisms and risk factors, including lipid abnormalities. A better understanding of the relationship between lipid metabolism and cancer can reveal strategies for cancer prevention and CVD risk reduction. Several anticancer treatments adversely affect lipid levels, increasing triglycerides and/or LDL-cholesterol. The traditional CVD risk assessment tools do not include cancer-specific parameters and may underestimate the true long-term CVD risk in this patient population. Statins are the mainstay of therapy in both primary and secondary CVD prevention. The role of non-statin therapies, including ezetimibe, PCSK9 inhibitors, bempedoic acid and icosapent ethyl in the management of lipid disorders in patients with cancer remains largely unknown. A contemporary cancer patient needs a personalized comprehensive cardiovascular assessment, management of lipid abnormalities, and prevention of late CVD to achieve optimal overall outcomes.

Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi

Simple SummaryThe multidisciplinary team of Fondazione Italiana Linfomi researchers conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) regarding incidence, comparison between systemic therapies and radiotherapy (RT) (old versus modern techniques), and the better monitoring of long-term classical Hodgkin lymphoma and diffuse large B-cell lymphoma survivors on late cardiological sequelae. The research focused on patients treated in adulthood and with first- or second-line antineoplastic therapies, including autologous stem cell transplant. Our purpose was to provide an overall and updated picture of the incidence of the phenomenon, the risk factors, and the updated early detection and follow-up strategies.Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche “Mario Negri”, conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.

Age-associated vulnerability to treatment-related late cardiotoxicity: A report from the Childhood Cancer Survivor Study (CCSS).

10501 Background: Cardiovascular disease (CVD) is the most common non-cancer cause of death in long-term survivors of pediatric cancer. We investigated the role of age at diagnosis in modifying treatment-related late CVD risk in the CCSS population. Methods: We evaluated CTCAE grade 3 – 5 CVD events occurring ≥5 years after diagnosis in 23,465 5-year survivors of pediatric cancer diagnosed 1970-1999. We estimated the rates of developing any CVD, including coronary artery disease (CAD) or heart failure (HF). Modifications of treatment effects by age at diagnosis were analyzed using piecewise exponential models adjusting for current age, race, and smoking. Results: At a median age of 28.4 years (range 5.6 –58.3) and follow up of 20.2 years (5 – 39.3), 239 CAD and 359 HF events occurred. The cumulative incidence of CVD, CAD, and HF were 4.8% (95% CI: 4.3-5.3), 2.4% (95% CI: 2.2-2.9), and 2.5% (95% CI: 2.2-2.9) by 30 years from diagnosis. Mean cardiac radiotherapy (CRT) doses of ≥10 Gy were associated with a progressively increasing risk of CVD (10 - &lt; 20 Gy: RR 3.6, 95% CI 2.1 – 6.2, p &lt; 0.01; 20 - &lt; 30 Gy: RR 4.4, 95% CI 2.7 – 7.2, p &lt; 0.01; ≥30 Gy: RR 7.5, 95% CI 4.9 – 11.5, p &lt; 0.01) relative to those receiving no CRT. In those receiving a low mean CRT dose (0.1 - &lt; 10 Gy), younger children had higher rates of CVD (0 – 4 years: RR = 2.2, 95% CI = 1.0 – 4.6, p = 0.04; &gt; 4 - ≤13 years: RR = 2.1, 95% CI = 1.1 – 4.1, p = 0.03) compared to those &gt; 13 years, an effect not seen at higher doses. Among survivors exposed to anthracycline doses ≥250 mg/m2, those age 0 – 4 at diagnosis had increased risk of both CAD (RR = 4.9, 95% CI 1.5 – 16.3, p = 0.01) and HF (RR = 3.0, 95% CI 1.6 – 5.0, p &lt; 0.01). Cisplatin exposure ≥300 mg/m2 was associated with increased risk of any CVD (RR = 1.8, CI = 1.2 – 2.6, p &lt; 0.01), primarily attributable to increased risk of HF (RR = 2.3, 95% CI = 1.5 - 3.5, p &lt; 0.01). Conclusions: Among long-term survivors of pediatric cancer, increasing CRT dose is associated with increased risk for CVD in a dose-response relationship. Young children are at higher risk for CVD after low-dose CRT or high-dose anthracycline exposure. Cisplatin exposure significantly increases risk for CVD. These findings should inform future treatment and surveillance protocols.

Predictors of Late Cardiovascular Complications in Survivors of Hematopoietic Cell Transplantation

Long-term survival after hematopoietic cell transplantation (HCT) is now an expected outcome. The growing population of survivors is at risk of developing treatment-related complications, including cardiovascular disease (CVD). A nested case-controlled design was used to identify clinical and treatment-related risk factors for development of late (1+ years after HCT) CVD. Cases were identified from a cohort of 1+-year survivors who underwent transplantation at City of Hope between 1977 and 2006. Controls (HCT survivors without CVD) were matched on age, year of HCT, type of HCT, and duration of follow-up. Sixty-three patients with late CVD were identified, 44 (69.8%) with a coronary artery event and 19 (30.2%) with a cerebrovascular event. Median age at HCT was 49.0 years. Median age at onset of late CVD was 54.0 years; 66.7% of the affected patients had undergone autologous HCT. Multivariate logistic regression analysis showed that the presence of multiple cardiovascular risk factors (2 or more of the following: obesity, dyslipidemia, hypertension, and diabetes) after HCT was associated with a 5.2-fold increased risk of late CVD (P < .01), and that pre-HCT chest radiation exposure was associated with a 9.5-fold greater risk of coronary artery disease (P = .03). Pre-HCT exposure to chest radiation and the presence of comorbidities were primarily responsible for the risk associated with late CVD after HCT. These data form the basis for developing predictive models for identifying high-risk individuals for targeted surveillance and aggressive management of comorbidities.

Late Cardiovascular Events in Survivors of Hematopoietic Cell Transplantation (HCT).

Abstract 2252Poster Board II-229 Introduction:HCT is increasingly offered as a therapeutic option for hematological malignancies. Improvement in therapeutic and supportive care strategies has resulted in a growing population of long-term survivors. These survivors are at a substantial risk of morbidity, contributed to by therapeutic exposures, and development of comorbidities. For example, HCT survivors are potentially at increased risk of atherosclerotic disease of large and small vessels, due to the higher risk of dyslipidemia, diabetes, and hypertension in HCT survivors (Blood2007;109:1765-72) as well as prior exposures to atherogenic therapeutic exposures (pre-HCT, during conditioning and post-HCT). However, cardiovascular disease (CVD) has not been well-characterized in HCT survivors, in part because of the long latency of clinically overt disease, requiring extended follow-up of large cohorts. The current report addresses this gap in literature by comprehensively evaluating the role of pre- and post-HCT therapeutic exposures (chemotherapy, radiation), transplant-related conditioning regimens, and comorbidities (pre- and post-HCT) in the development of late CVD after HCT. Methods:Utilizing a nested case-control design, individuals with late CVD (diagnosed ≥1 year after HCT) were identified from a cohort of 3,287 1+ year survivors who underwent HCT at a single institution. This cohort formed the sampling frame for selecting controls (without CVD) matched for age and year of HCT, donor source (allogeneic vs. autologous), and length of follow-up. All episodes of CVD (cases) were clinically validated, and included coronary artery disease (CAD) or cerebrovascular events (stroke). Results:Sixty-three patients with late CVD were identified; 44 (69.8%) had CAD and 19 (30.2%) had stroke. Median age at HCT was 49.0 years (range, 18.6 to 78.9 years); median time to CVD was 4.1 years (range, 1.15 to 19.45 years); 66.7% received autologous HCT. Compared to matched controls (N=183), patients with late CVD were more likely to be male (68.3% vs. 51.6%; p=0.02), had greater body mass index at HCT (28.5 vs. 26.6 kg/m2; p=0.03), and were more likely to have multiple comorbidities after HCT (47.6% vs. 13.4%; p<0.01). Conditioning with total body irradiation (TBI), cyclophosphamide, and TBI + cyclophosphamide were associated with incremental increased risk (Odds Ratio [OR]=1.2, 2.5, 2.9, respectively; p for trend=0.04). Multivariate logistic regression revealed that having 2 of 4 cardiovascular risk factors (obesity, dyslipidemia, hypertension, and diabetes) was independently associated with a 5-fold risk of developing late CVD (OR=5.2; p<0.01). Multivariate analyses restricted to CAD cases and their matched controls revealed the following risk factors: pre-HCT exposure to mediastinal radiation (OR=9.3; p=0.04), and presence of 2 of 4 cardiovascular risk factors (OR=4.6, p=<0.01). No interactions were observed between therapeutic exposures and presence of comorbidities. Conclusions:The current study represents the most comprehensive experience to date describing risk factors for late CVD following HCT, and demonstrates that mediastinal radiation and presence of comorbidities are primarily responsible for the risk of late CVD. These data form the basis for identifying high-risk individuals for targeted surveillance, as well as developing preventive strategies in the form of aggressive management of comorbidities. Disclosures:No relevant conflicts of interest to declare.

Cardiovascular risk factors (CVRF) and late cardiovascular disease (LCD) in orthotopic liver transplantation (OLT)

Cardiovascular risk factors (CVRF) and late cardiovascular disease (LCD) in orthotopic liver transplantation (OLT)