Effects of Chemotherapy on Aortic 18-Fluorodeoxyglucose Uptake in Patients With Hodgkin and Non-Hodgkin Lymphoma.

Background: Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity. Inflammatory activation that has been linked to cardiovascular disease is crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives: The purpose of this study was to assess the vascular effects of chemotherapy in patients with HL and NHL by positron emission tomography/computed tomography with 18-fluorodeoxyglucose (18-FDG PET/CT) and to investigate interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods: Between July 2015 and July 2019, 65 consecutive patients (mean age 56 ± 17.78 years) with confirmed diagnosis of either HL (n = 33) or NHL (n = 32) were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase, and after first-line treatment. Aortic FDG uptake was assessed by measuring global aortic target-to-background ratio (GLA-TBR). Serum biomarkers interleukin (IL)-6 and IL-1b were measured at each phase. Results: Patients with HL demonstrated significant reduction in aortic TBR after first-line treatment (median GLA-TBR baseline: 1.98, median GLA-TBR third scan: 1.75, median difference = -0.20, 95% CI: -0.07 to -0.33, P = 0.006), which remained significant after adjustment for confounders (adj. R2 of model = 0.53). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (P = 0.306). Furthermore, patients with HL demonstrated a significant reduction in IL-6 (P = 0.048) and IL-1b (P = 0.045), whereas patients with NHL did not demonstrate significant reduction in IL-6 (P = 0.085) and IL-1b levels (P = 0.476). Conclusions: Aortic inflammation, as assessed by 18-FDG PET/CT, is reduced in HL patients after first-line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways for patients with lymphoma.

Sleep Apnea and Cardiovascular Risk in Patients with Prediabetes and Type 2 Diabetes.

Obstructive sleep apnea (OSA) is a common but largely undiagnosed clinical condition, which is turning into a serious public health issue. Of note is that its prevalence is gradually increasing in parallel with the obesity and type 2 diabetes mellitus (T2DM) epidemics. The aim of this article is to comprehensively review the literature in order to evaluate the cardiovascular (CV) risk among patients with OSA and prediabetes or T2DM. OSA seems to be an independent risk factor for the development as well as the progression of T2DM, whereas it is associated with T2DM-related macrovascular and microvascular complications. OSA may also act as a potential risk factor for the presentation and development of CV disease, such as hypertension, coronary artery disease, heart failure, pulmonary hypertension, atrial fibrillation and other cardiac arrythmias, as well as stroke. OSA and T2DM also share common pathophysiological mechanisms leading to atherosclerosis. Considering that the coexistence of OSA and T2DM is an independent and cumulative risk factor for CV mortality, more so than the two diseases separately, clinicians and healthcare professionals should be aware of and screen for OSA in patients with T2DM. Notably, targeted therapy for both conditions seems to substantially improve CV prognosis.

Lymphoma Severity and Type Are Associated With Aortic FDG Uptake by 18F-FDG PET/CT Imaging.

BACKGROUND: There is evidence that metabolic disease burden in lymphoma influences patient outcome. However, the impact of disease severity on the cardiovascular system is unknown. OBJECTIVES: The aim of this study was to examine whether lymphoma is associated with arterial inflammation by investigating the relationship between disease metabolic burden and arterial fluorodeoxyglucose (FDG) uptake. METHODS: Sixty-two chemotherapy-naïve patients with active Hodgkin's or non-Hodgkin's lymphoma were matched (2:1) to individual control groups of lymphoma patients previously treated and free of active disease. All groups underwent 18F-FDG position emission tomography-computed tomography imaging. Disease severity was quantified by metabolic tumor volume (MTV) and total lesion glycolysis corresponding to standardized uptake values (SUVs) ≥41% or ≥2.5 of the maximum SUV within lymphoma regions, and aortic FDG uptake was quantified through the target-to-background ratio (TBR). Inflammatory and disease severity biomarkers were also measured. RESULTS: MTV and total lesion glycolysis measurements were significantly correlated with inflammatory and disease biomarkers. Aortic TBR was higher in patients with active non-Hodgkin's lymphoma compared with control subjects (median difference 0.51; 95% confidence interval [CI]: 0.28 to 0.78; p < 0.001). Similarly, patients with active Hodgkin's lymphoma had higher values of aortic TBR compared with control subjects (median difference 0.31; 95% CI: 0.15 to 0.49; p < 0.001). In addition, aortic TBR was modestly increased in patients with stage III to IV disease compared with those with stage I to II disease (median aortic TBR: 2.23 [interquartile range: 2.01 to 2.54] vs. 2.06 [interquartile range: 1.83 to 2.27; p = 0.050). In multivariable analysis, aortic FDG uptake and MTV≥2.5 values were independently associated (ß = 0.425; 95% CI: 0.189 to 0.662; p = 0.001; R2 = 0.208), as were aortic FDG uptake and MTV≥41% (ß = 0.407; 95% CI: 0.167 to 0.649, p = 0.001; R2 = 0.191). CONCLUSIONS: Aortic wall FDG uptake is related with disease severity indicative of a possible vascular effect of lymphoma. This work highlights a new potential role of molecular imaging in cardio-oncology for evaluating disease severity and its consequences on the vasculature.

Association between pneumococcal vaccination and cardiovascular outcomes: a systematic review and meta-analysis of cohort studies.

AIMS: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP) and CAP-related mortality in adults. Pneumococcal vaccination (PV) could protect subjects from cardiovascular events by reducing pneumonia severity or even preventing it. We sought to determine the ability of PV to protect from the risk of cardiovascular events. METHODS AND RESULTS: A comprehensive search of electronic databases was conducted up to March 2014. Cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CI) were included. Eleven studies were included (332,267 participants, mean follow-up 20.1 months). The pooled RRs for cardiovascular events and cardiovascular mortality were 0.86 (95% CI: 0.76-0.97) and 0.92 (95% CI: 0.86-0.98; fixed-effects), respectively, for subjects with PV versus without PV. Protective ability was more prominent in high cardiovascular risk populations and with older age. The protective role of PV was attenuated after 1 year (RR: 0.72; 95% CI: 0.59-0.88 vs RR: 1.03; 95% CI: 0.93-1.14; p = 0.002, for follow-up >1 year vs ≤1 year, respectively). It also increased as the presence of cardiovascular and pulmonary disease increased. Regarding myocardial infarction (MI) and cerebrovascular events, the protective role of PV was statistically significant only in the elderly (RR: 0.90; 95% CI: 0.817-0.999; fixed-effects and RR: 0.86; 95% CI: 0.75-0.99, respectively). CONCLUSION: PV is associated with decreased risk of cardiovascular events and mortality. This protective effect increases at older age and in high cardiovascular risk subjects and decreases as the time elapses from PV. PV decreases the risk of MI and cerebrovascular events in the elderly.

Prediction of cardiovascular events and all-cause mortality with erectile dysfunction: a systematic review and meta-analysis of cohort studies.

BACKGROUND: Erectile dysfunction (ED) carries an independent risk for cardiovascular (CV) events. We conducted a meta-analysis of all longitudinal studies for determining the ability of ED to predict risk of clinical events and to dissect factors influencing this ability. METHODS AND RESULTS: We conducted a comprehensive search of electronic databases through July 2012. Longitudinal studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) were included. Of the 14 studies included (92 757 participants; mean follow-up, 6.1 years; 16 articles), 13 (14 articles) reported results on total CV events (91 831 individuals), 4 on CV mortality (34 761 individuals), 4 on myocardial infarction (35 523 individuals), 6 on cerebrovascular events (27 689 individuals), and 5 on all-cause mortality (17 869 individuals). The pooled RRs for the above-mentioned end points were 1.44 (95% CI, 1.27-1.63), 1.19 (95% CI, 0.97-1.46), 1.62 (95% CI, 1.34-1.96), 1.39 (95% CI, 1.23-1.57), and 1.25 (95% CI, 1.12-1.39), respectively, for men with versus without ED. The RR was higher in intermediate- compared with high- or low-CV-risk populations and with younger age. The RR for studies that diagnosed ED with the use of a questionnaire compared with a single question was higher (RR, 1.61; 95% CI, 1.38-1.86 versus RR, 1.27; 95% CI, 1.18-1.37, respectively; P=0.006). CONCLUSIONS: ED is associated with increased risk of CV events and all-cause mortality. RR is higher at younger ages, in intermediate-risk groups, and when a questionnaire is used instead of a single question.

Differential impact of metabolic syndrome on arterial stiffness and wave reflections: focus on distinct definitions.

BACKGROUND: Arterial stiffness and wave reflections are independent predictors of cardiovascular disease. Metabolic syndrome (MS) is related to increased aortic stiffness in several populations. However, it is unclear whether the association of MS with aortic stiffness differs according to the considered definition. Moreover, data regarding the association of wave reflections with MS are limited. For this purpose, we examined the relationship of arterial stiffness and wave reflections with MS by using four current definitions and a score. METHODS: We studied 732 never treated, non-diabetic hypertensive patients. Metabolic syndrome was defined by Adult Treatment Panel III, American Heart Association, World Health Organization (WHO), International Diabetes Federation criteria and MS (GISSI) score. Arterial stiffness was assessed by measuring carotid-femoral pulse wave velocity (PWVc-f). Heart rate-corrected augmentation index (AIx(75)) was estimated as a measure of wave reflections. RESULTS: By all definitions, hypertensive patients with MS had higher PWVc-f compared to hypertensives without MS. On the contrary, no significant difference was observed in AIx(75) between patients with and those without MS except when MS was defined by WHO criteria. An independent association emerged between PWVc-f and GISSI score and MS components (p=0.038 and 0.033 respectively) in patients with MS, after adjustment for age, gender, LDL cholesterol and smoking. Nevertheless, after further adjustment for systolic blood pressure or body mass index, the strength of this association was reduced to a non-significant level. CONCLUSION: Arterial stiffness is increased in patients with metabolic syndrome irrespective of the definition criteria. On the contrary, metabolic syndrome has no effect on wave reflections, except when this is defined by WHO criteria. Regarding the high prognostic significance of both arterial stiffness and wave reflections, these findings might have important clinical implications.

The effect of heart rate on wave reflections may be determined by the level of aortic stiffness: clinical and technical implications.

BACKGROUND: Augmentation Index (AIx) is related to cardiovascular diseases, risk, and mortality. AIx is associated with heart rate but the effect of aortic stiffness on this relationship has not been studied. The purpose of our study was to investigate the relationship between AIx and heart rate at different aortic stiffness levels. METHODS: The study consisted of 425 normotensive and untreated hypertensive subjects. Wave reflections and pulse-wave velocity (PWV) were determined by the Sphygmocor and the Complior systems, respectively. RESULTS: AIx was independently associated with heart rate, age, gender, height, mean blood pressure (BP) and the effective reflection site distance (ERD). The population was divided into three groups of those with different PWV levels (tertiles). The regression lines for AIx with heart rate differed significantly between the 3rd and the other two tertiles of PWV (P = 0.039 for slopes and P = 0.002 for intercepts). This difference remained significant even after adjustment for age, gender, height, mean BP, and distance of wave reflections. CONCLUSIONS: A significantly stronger correlation of AIx with heart rate was observed in subjects with higher levels of aortic stiffness as compared to those with lower levels; namely, the same increase in the heart rate between subjects, induced a greater decrease in the AIx at higher compared to lower PWV levels. The correction of AIx for heart rate should be reconsidered based on the aortic stiffness level. This finding has implications for interventional studies that aim to improve central hemodynamics but simultaneously affect heart rate. Further studies that show acute modifications of heart rate at different arterial stiffness levels are required to support these findings.

Relation of habitual cocoa consumption to aortic stiffness and wave reflections, and to central hemodynamics in healthy individuals.

The effect of habitual cocoa consumption on arterial stiffness and wave reflection indexes, as well as on peripheral and central blood pressure, was assessed in 198 healthy subjects. In conclusion, higher cocoa intake was an independent determinant of low arterial stiffness and wave reflection indexes and was also independently associated with significantly lower central (aortic) pulse pressure.