Cardiotoxicity and cancer therapy

A fundamental concept of treatment is to do no harm. However, with cancer treatment this is not always possible. Chemotherapy is associated with cardiovascular (CV) complications.1,2 This risk is even greater in the elderly patients and patients with established CV disease. More specifically, tachyarrhythmias (eg, cisplatin), bradyarrythmias (eg, paclitaxel), or QT prolongation (eg, dasatinib) have been reported. Furthermore, myocardial necrosis, coronary vaso-occlusion or vasospasm, pericardial disease (eg, cytarabine), endocardial fibrosis (eg, busulfan), and heart failure can occur. Hypotension (eg, fludarabine) or hypertension (eg, vinca alkaloids) has also been reported.1,2 Cardiotoxicity, endothelial injury, and Takotsubo syndrome have been reported in patients treated with 5-fluorouracil (5-FU).3⇓–5 Cardiotoxicity to 5-FU was reported 35 years ago.3⇓–5 Cardiotoxicity of chemotherapy has been reported in patients ranging from children through adults (eg, with anthracyclines or cisplatin).6 Adriamycin-induced myocyte damage has been attributed to the production of toxic oxygen free radicals.7 This can cause lipid peroxidation of membranes resulting in vacuolation, irreversible damage, and myocyte replacement by fibrous tissue.7 The use of angiogenesis inhibitors in cancer therapy is expanding as are the associated adverse CV effects (eg, hypertension, thromboembolism, left ventricular dysfunction, and QTc prolongation).2,8 Vascular endothelial growth factor (VEGF) plays a role in maintaining vascular homeostasis via the production of the vasodilator nitric oxide (NO) and decreased vascular resistance through the generation of new blood vessels.2,8 Therefore, it is not surprising that inhibition of VEGF signaling (eg, … [Full Text of this Article

The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

We investigated the independent and interactive impact of the common APOE genotype and marine n-3 polyunsaturated fatty acids (PUFA) on the development of obesity and associated cardiometabolic dysfunction in a murine model. Human APOE3 and APOE4 targeted replacement mice were fed either a high-fat control diet (HFD) or a HFD supplemented with 3% n-3 PUFA from fish oil (HFD + FO) for 8 wk. We established the impact of intervention on food intake, bodyweight, and visceral adipose tissue (VAT) mass; plasma, lipids (cholesterol and triglycerides), liver enzymes, and adipokines; glucose and insulin during an intraperitoneal glucose tolerance test; and Glut4 and ApoE expression in VAT. HFD feeding induced more weight gain and higher plasma lipids in APOE3 compared to APOE4 mice (P < 0.05), along with a 2-fold higher insulin and impaired glucose tolerance. Supplementing APOE3, but not APOE4, animals with dietary n-3 PUFA decreased bodyweight gain, plasma lipids, and insulin (P < 0.05) and improved glucose tolerance, which was associated with increased VAT Glut4 mRNA levels (P < 0.05). Our findings demonstrate that an APOE3 genotype predisposes mice to develop obesity and its metabolic complications, which was attenuated by n-3 PUFA supplementation.—Slim, K. E., Vauzour, D., Tejera, N., Voshol, P. J., Cassidy, A., Minihane, A. M. The effect of dietary fish oil on weight gain and insulin sensitivity is dependent on APOE genotype in humanized targeted replacement mice

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

Abstract Objective: Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia. Methods: Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t=0 min) and lunch (t=330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples. Results: MetS subjects with 3 or 4 components were subdivided into those without (n=34) and with (n=23) fasting hyperglycaemia (≥ 5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P<0.001). Following the test meals, there was a higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P≤0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P<0.001) and insulin maxC (P=0.010) was also observed in these individuals after the test meals. Multivariate regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response. Conclusion: Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia

Quantifying atherogenic lipoproteins for lipid-lowering strategies : Consensus-based recommendations from EAS and EFLM

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (= total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.Peer reviewe

Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women

Low HDL Cholesterol, Smoking and IL-13 R130Q Polymorphism are Associated with Myocardial Infarction in Greek Cypriot Males. A Pilot Study

This study was carried out in Greek Cypriot males to identify risk factors that predispose to myocardial infarction (MI). Genetic and lipid risk factors were investigated for the first time in a Greek Cypriot male case-control study.Contrary to other studies, mean low density lipoprotein cholesterol did not differ between cases and controls. High density lipoprotein cholesterol on the other hand, although within normal range in cases and controls, was significantly higher in the control population. In agreement with many other studies, smoking was significantly more prevalent in cases compared with controls. In pooled cases and controls, smokers had a significantly lower HDL-C level compared with non-smokers. The frequency of the IL-13 R130Q homozygotes for the mutation (QQ), as well as the mutant allele were significantly higher in cases compared with controls. The IL-13 R130Q variant, or another locus, linked to it, may increase the risk of MI