Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. METHODS AND RESULTS: In 1814 individuals with a median (interquartile range) age of 53 (44–60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57–0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. CONCLUSIONS: Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high-and very high-risk patients for cardiovascular disease is recommended.</p

Echocardiography protocol for early detection of cardiac dysfunction in childhood cancer survivors in the multicenter DCCSS LATER 2 CARD study:Design, feasibility, and reproducibility

Background Cardiotoxicity is a well-known side effect after anthracyclines and chest radiotherapy in childhood cancer survivors (CCS). The DCCSS LATER 2 CARD (cardiology) study includes evaluation of echocardiographic measurements for early identification of CCS at highest risk of developing heart failure. This paper describes the design, feasibility, and reproducibility of the echocardiography protocol. Methods Echocardiograms from CCS and sibling controls were prospectively obtained at the participating centers and centrally analyzed. We describe the image acquisition, measurement protocol, and software-specific considerations for myocardial strain analyses. We report the feasibility of the primary outcomes of systolic and diastolic function, as well as reproducibility analyses in 30 subjects. Results We obtained 1,679 echocardiograms. Biplane ejection fraction (LVEF) measurement was feasible in 91% and 96% of CCS and siblings, respectively, global longitudinal strain (GLS) in 80% and 91%, global circumferential strain (GCS) in 86% and 89%, and >= 2 diastolic function parameters in 99% and 100%, right ventricle free wall strain (RVFWS) in 57% and 65%, and left atrial reservoir strain (LASr) in 72% and 79%. Intra-class correlation coefficients for inter-observer variability were 0.85 for LVEF, 0.76 for GLS, 0.70 for GCS, 0.89 for RVFWS and 0.89 for LASr. Intra-class correlation coefficients for intra-observer variability were 0.87 for LVEF, 0.82 for GLS, 0.82 for GCS, 0.85 for RVFWS and 0.79 for LASr. Conclusion The DCCSS LATER 2 CARD study includes a protocolized echocardiogram, with feasible and reproducible primary outcome measurements. This ensures high-quality outcome data for prevalence estimates and for reliable comparison of cardiac function parameters

Extensive Cardiac Function Analyses Using Contemporary Echocardiography in Childhood Cancer Survivors:A DCCSS LATER Study

Background: Childhood cancer survivors (CCS) are at risk for cardiotoxicity.Objectives: We sought to assess how cardiac dysfunction measurements in CCS overlap and are differentially influenced by risk factors.Methods: This cross-sectional Dutch Childhood Cancer Survivor Study evaluated echocardiograms of 1,397 ≥5-year CCS and 277 siblings. Of CCS, n = 1,254 received cardiotoxic (anthracyclines/mitoxantrone/radiotherapy involving the heart region [RTheart]) and n = 143 received potentially cardiotoxic (cyclophosphamide, ifosfamide, or vincristine) therapy. We assessed demographic, treatment-related, and traditional cardiovascular risk factors for cardiac dysfunction using multivariable logistic regression.Results: CCS were a median of 26.7 years after diagnosis; 49% were women. Abnormal left ventricular ejection fraction (LVEF) (defined as &lt;52% in men, &lt;54% in women) occurred most commonly in CCS treated with anthracyclines and RTheart combined (38%). Age/sex-specific abnormal global longitudinal strain (GLS) occurred most commonly in CCS treated with RTheart, either with (41%) or without (38%) anthracyclines. Of CCS with normal LVEF, 20.2% showed abnormal GLS. Diastolic dysfunction grade ≥II was rare. Abnormal LVEF was mainly associated with female sex, anthracycline dose, and only in women, RTheart dose. Abnormal GLS was associated with female sex, RTheart dose, diastolic blood pressure, and only in women, anthracycline dose. Cyclophosphamide, ifosfamide, and vincristine were not associated with LVEF or GLS. Compared with siblings, CCS showed higher risk of abnormal LVEF (OR: 2.9; 95% CI: 1.4-6.6) and GLS (OR: 2.1; 95% CI: 1.2-3.7), independent of (potentially) cardiotoxic treatment-related and cardiovascular risk factors.Conclusions: Abnormal LVEF and GLS constitute complementary measures of systolic dysfunction among long-term CCS. Their diagnostic value may differ according to cardiotoxic exposures. Also, CCS have residual, unexplained risk of cardiac dysfunction.</p

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors:Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart failure. The results of the study will enable us to improve long-term follow-up surveillance guidelines for CCS at risk for heart failure