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 association between serum uric acid levels and 10-year cardiovascular disease incidence: results from the ATTICA prospective study.

Limited data suggests possible gender-specific association between serum uric acid (SUA) and cardiovascular disease (CVD) incidence. The aim of the present analysis was to evaluate the association between SUA levels and 10-year CVD incidence (2002-2012) in the ATTICA study participants. Overall, 1687 apparently healthy volunteers, with SUA measurements, residing in the greater metropolitan Athens area (Greece), were included. Multivariable Cox-regression models were used to estimate the hazard ratios for SUA in relation to 10-year CVD incidence. Receiver operating curve analysis was conducted to detect optimal SUA cut-off values. Participants in the 2nd and 3rd SUA tertile had 29 and 73% higher 10-year CVD incidence compared with those in the 1st tertile (p < 0.001). In gender-specific analysis, only in women SUA was independently associated with CVD incidence; women in the 3rd SUA tertile had 79% greater 10-year CVD event risk compared to their 1st tertile counterparts. Obese in the 3rd SUA tertile had 2-times higher CVD incidence compared to those in the 1st tertile. Similar findings were observed in metabolically healthy (vs. unhealthy) and metabolically healthy obese. SUA thresholds best predicting 10-year CVD incidence was 5.05 and 4.15 mg/dL (0.30 and 0.25 mmol/L) in men and women, respectively. In conclusion, increased SUA levels were independently related to 10-year CVD event rate in women, obese and metabolically healthy individuals. SUA could predict 10-year CVD incidence even at low levels. Further studies are warranted to identify SUA cut-off values that may improve the detection of individuals at higher CVD risk in clinical practice

Assessment of non-alcoholic fatty liver disease (NAFLD) severity with novel serum-based markers: A pilot study

BACKGROUND/AIMS: Non-alcoholic fatty liver disease (NAFLD) represents a significant public health issue. Identifying patients with simple steatosis from those with non-alcoholic steatohepatitis (NASH) is crucial since NASH is correlated with increased morbidity and mortality. Serum-based markers, including adipokines and cytokines, are important in the pathogenesis and progression of NAFLD. Here we assessed the usefulness of such markers in patients with NAFLD. METHODS: This prospective, cross-sectional study included 105 adult patients with varying severity of NAFLD. Twelve serum-based markers were measured by 3 biochip platforms and 2 enzyme-linked immunosorbent assay (ELISA) methods. We also developed a NAFLD individual fibrosis index (NIFI) using the serum-based markers mostly correlated with fibrosis severity. RESULTS: Sixty-one out of 105 patients were male (58.1%) with mean age was 53.5 years. Higher Interleukin-6 (IL-6) increased (p = 0.0321) and lower Matrix Metalloproteinase-9 (MMP-9) serum levels (p = 0.0031) were associated with higher fibrosis as measured by Fibroscan® in multivariable regression analysis. Using receiver-operating characteristic (ROC) curve analysis for the NIFI, area under the curve for predicting Fibroscan values ≥ 7.2 kPa was 0.77 (95%CI: 0.67, 0.88, p<0.001), with sensitivity of 89.3%, specificity of 57.9% and a positive likelihood ratio of 2.8. CONCLUSIONS: Increasing fibrosis severity in NAFLD is associated with differential expression of IL-6 and MMP-9. NIFI could be valuable for the prediction of advanced NAFLD fibrosis and potentially help avoid unnecessary interventions such as liver biopsy in low-risk patients

All-cause mortality and estimated renal function in type 2 diabetes mellitus outpatients: is there a relationship with the equation used?

BACKGROUND: We investigated the relationship between serum creatinine (SCr) and estimated glomerular filtration rate (eGFR), evaluated by different formulae, and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) outpatients. METHODS: This observational cohort study considered 1365 T2DM outpatients, who had been followed up for a period of up to 11 years. eGFR was estimated using several equations. RESULTS: Seventy subjects (5.1%) died after a follow-up of 9.8 ± 3 years. Univariate analysis showed that diagnosis of nephropathy (odds ratio (OR): 2.554, 95% confidence interval (CI): 1.616-4.038, p < 0.001) and microvascular complications (OR: 2.281, 95% CI: 1.449-3.593, p < 0.001) were associated with ACM. Receiving operating characteristic (ROC) curves showed that the areas under the curve for ACM were similar using the different eGFR equations. eGFR values were predictors of ACM, and the hazard ratios (HRs) of the different equations for eGFR estimation were similar. CONCLUSION: In our cohort of T2DM outpatients, different eGFR equations perform similarly in predicting ACM, whereas SCr did not

Association of Types of Dietary Fats and All-Cause and Cause-Specific Mortality: A Prospective Cohort Study and Meta-Analysis of Prospective Studies with 1,148,117 Participants

Background: Associations between dietary fats and mortality are unclear. Methods: We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999-2010. We added our results to a meta-analysis based on searches until November 2018. Results: In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78-0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04-1.11). In the meta-analysis of 29 prospective cohorts (n=1,148,117) we found a significant inverse association between total fat (0.89, 0.82-0.97), MUFA (0.93, 0.87-0.99) and PUFA (0.86, 0.80-0.93) consumption and all-cause mortality. No association was observed between total fat and CVD (0.92, 0.79-1.08) or CHD mortality (1.03 0.99-1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01-1.20) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67-0.96) and PUFA (0.84, 0.80-0.90) intakes and stroke mortality. Conclusions: We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes

Nutraceutical approaches to non-alcoholic fatty liver disease (NAFLD): A position paper from the International Lipid Expert Panel (ILEP)

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10-25% of the general adult population, 15% of children, and even &gt; 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease. The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety

The Differences in the Prevalence of Cardiovascular Disease, Its Risk Factors, and Achievement of Therapeutic Goals among Urban and Rural Primary Care Patients in Poland: Results from the LIPIDOGRAM 2015 Study

A nationwide cross-sectional study, LIPIDOGRAM2015, was carried out in Poland in the years 2015 and 2016. A total of 438 primary care physicians enrolled 13,724 adult patients that sought medical care in primary health care practices. The prevalence of hypertension, diabetes mellitus, dyslipidaemia, and CVD were similar in urban and rural areas (49.5 vs. 49.4%; 13.7 vs. 13.1%; 84.2 vs. 85.2%; 14.4 vs. 14.2%, respectively). The prevalence of obesity (32.3 vs. 37.5%, p < 0.01) and excessive waist circumference (77.5 vs. 80.7%, p < 0.01), as well as abdominal obesity (43.2 vs. 46.4%, p < 0.01), were higher in rural areas in both genders. Mean levels of LDL-C (128 vs. 130 mg/dL, p = 0.04) and non-HDL-C (147 vs. 148 mg/dL, p = 0.03) were slightly higher in rural populations. Altogether, 14.3% of patients with CVD from urban areas and 11.3% from rural areas reached LDL <70 mg/dL (p = 0.04). There were no important differences in the prevalence of hypertension, diabetes, dyslipidaemia, and CVD, or in mean levels of blood pressure, cholesterol fractions, glucose, and HbA1c between Polish urban and rural primary care patient populations. A high proportion of patients in cities and an even-higher proportion in rural areas did not reach the recommended targets for blood pressure, LDL-C, and HbA1c, indicating the need for novel CVD-prevention programs

Analysis of the impact of sex and age on the variation in the prevalence of antinuclear autoantibodies in Polish population: a nationwide observational, cross-sectional study

The detection of antinuclear autoantibody (ANA) is dependent on many factors and varies between the populations. The aim of the study was first to assess the prevalence of ANA in the Polish adult population depending on age, sex and the cutoff threshold used for the results obtained. Second, we estimated the occurrence of individual types of ANA-staining patterns. We tested 1731 patient samples using commercially available IIFA using two cutoff thresholds of 1:100 and 1:160. We found ANA in 260 participants (15.0%), but the percentage of positive results strongly depended on the cutoff level. For a cutoff threshold 1:100, the positive population was 19.5% and for the 1:160 cutoff threshold, it was 11.7%. The most prevalent ANA-staining pattern was AC-2 Dense Fine speckled (50%), followed by AC-21 Reticular/AMA (14.38%) ANA more common in women (72%); 64% of ANA-positive patients were over 50 years of age. ANA prevalence in the Polish population is at a level observed in other highly developed countries and is more prevalent in women and elderly individuals. To reduce the number of positive results released, we suggest that Polish laboratories should set 1:160 as the cutoff threshold

The role of nutraceuticals in heart failure muscle wasting as a result of inflammatory activity. The International Lipid Expert Panel (ILEP) Position Paper.

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated, as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting