Genetic association of cardiovascular disease related biomarkers with the overall survival of hepatocellular carcinoma: a Mendelian randomization analysis.

Observational studies have reported associations between circulating biomarkers related to cardiovascular disease and the survival of patients with hepatocellular carcinoma. However, the relationship between these biomarkers and survival remains controversial. We conducted a two-sample Mendelian randomization analysis to investigate possible causal associations between cardiovascular disease biomarkers and hepatocellular carcinoma survival. Genetic risk scores, calculated using individual-level data from 866 cases of hepatitis B virus-related hepatocellular carcinoma in Guangxi, were utilized as proxies for four cardiovascular disease biomarkers: C-reactive protein, Apolipoprotein A-1, Cystatin C, and Lipoprotein(a). Associations between the genetic scores and survival were analyzed using Cox regression. The inverse-variance weighted method was used to estimate the summary statistics for the biomarkers and survival. Considering the multiple comparisons, the statistical significance was set at P < 0.0125. We observed a significant risk signal between genetically increased Cystatin C levels and poorer survival in hepatocellular carcinoma (HR for genetic scores = 1.29, 95% CI = 1.02-1.64; HR for inverse-variance weighted = 2.60, 95% CI = 1.45-4.65). Furthermore, we found a causal relationship of genetically determined Cystatin C and Lipoprotein(a) level with the survival of hepatocellular carcinoma patients with embolus. Our findings indicated the causal effects of increased levels of Cystatin C and Lipoprotein(a) on poorer survival in hepatocellular carcinoma.

Advanced Glycations End Products in the Skin as Biomarkers of Cardiovascular Risk in Type 2 Diabetes.

The incidence and prevalence of diabetes are increasing worldwide, and cardiovascular disease (CVD) is the leading cause of death among subjects with type 2 diabetes (T2D). The assessment and stratification of cardiovascular risk in subjects with T2D is a challenge. Advanced glycation end products are heterogeneous molecules produced by non-enzymatic glycation of proteins, lipids, or nucleic acids. Accumulation of advanced glycation end products is increased in subjects with T2D and is considered to be one of the major pathogenic mechanism in developing complications in diabetes. Skin AGEs could be assessed by skin autofluorescence. This method has been validated and related to the presence of micro and macroangiopathy in individuals with type 2 diabetes. In this context, the aim of this review is to critically summarize current knowledge and scientific evidence on the relationship between skin AGEs and CVD in subjects with type 2 diabetes, with a brief reference to other diabetes-related complications.

Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Cardiovascular Events in Type 2 Diabetic Patients.

Risk of cardiovascular events is not homogeneous in subjects with type 2 diabetes; therefore, its early identification remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy and accumulation of advanced glycation end-products in subcutaneous tissue can help identify patients at high risk of cardiovascular events. For this purpose, we conducted a prospective study (mean follow-up: 4.35 years) comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls matched by age and sex. The primary outcome was defined as the composite of myocardial infarction, coronary revascularization, stroke, lower limb amputation or cardiovascular death. The Cox proportional hazard multiple regression analysis was used to determine the independent predictors of cardiovascular events. The patients with type 2 diabetes had significantly more cardiovascular events than the non-diabetic subjects. Apart from the classic factors such as age, sex and coronary artery calcium score, we observed that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue were independent predictors of cardiovascular events. We conclude that the diabetic retinopathy and advanced glycation end-products in subcutaneous tissue could be useful biomarkers for selecting type 2 diabetic patients in whom the screening for cardiovascular disease should be prioritized, thereby creating more personalized and cost-effective medicine.

Growth differentiation factor 15 (GDF-15) as potential cardiovascular risk biomarker in antiphospholipid syndrome.

OBJECTIVE: An interplay between thrombo-inflammatory and atherogenic mechanisms is recognized in cardiovascular disease (CVD) pathogenesis in APS. Herein, we examine associations of growth differentiation factor-15 (GDF-15), a pro-inflammatory cytokine identified as a potent CVD risk biomarker in the general population, with subclinical atherosclerosis in APS. METHODS: We measured plasma GDF-15 levels by an electrochemiluminescence immunoassay (cut-off 1200 pg/ml) and we examined carotid intima-media thickness (IMT) and the presence of carotid and femoral plaques using vascular ultrasound in 80 patients with APS (44 primary, 36 SLE/APS) and 40 healthy controls. We calculated the adjusted Global APS Score for cardiovascular disease (aGAPSSCVD), a revised adjusted Global APS Score (aGAPSS) for predicting CVD, including lupus anticoagulant, anticardiolipin and anti-beta2glycoprotein-I antibodies, and hypertension, dyslipidaemia, obesity, diabetes and smoking. RESULTS: GDF-15 levels were higher in APS patients vs controls, after adjusting for age and gender [absolute difference: 281 (95% CI: 141, 421) pg/ml, P < 0.001]. GDF-15 levels ≥1200 pg/ml were associated with higher mean IMT of the right and left carotid arteries [beta coefficient 0.068 (95% CI: 0.020, 0.116), P = 0.006] compared with GDF-15 levels <1200 pg/ml. GDF-15 was independently associated with mean IMT, after adjusting for gender and aGAPSSCVD [beta coefficient 0.059 (95% CI: 0.008, 0.110), P = 0.024], and additionally for statin (P = 0.025) and HCQ use (P = 0.011). GDF-15 levels ≥1200 pg/ml were associated with 2.4 times higher odds for atherosclerotic plaques (odds ratios = 2.438, 95% CI: 0.906, 6.556, P = 0.078), while this effect was reduced by including more covariates in the model. CONCLUSION: GDF-15 is independently associated with subclinical atherosclerosis in APS patients, suggesting its potential role in CVD risk stratification in APS.

Increased levels of the cardiovascular disease risk biomarkers GDF15 and myostatin in patients with chronic lymphocytic leukemia.

Individuals suffering from cancer, including hematological malignancies, are at increased risk of cardiovascular disease (CVD). Elevated levels of several biomarkers in blood are associated with an increased risk of CVD. The aim of this study was to investigate whether a subset of such CVD risk biomarkers was elevated in patients with untreated chronic lymphocytic leukemia (CLL). Blood plasma and serum from 139 CLL patients and 71 healthy age-matched controls were analyzed for 11 proposed CVD risk biomarkers. The CLL cohort displayed a more heterogeneous pattern of biomarker expression compared to controls. The majority, eight out of 11, analyzed CVD risk biomarkers differed significantly in concentrations between CLL patients and controls. Increased levels of the biomarkers GDF15 and myostatin have not previously been reported in CLL. Further prospective studies are warranted to investigate whether these biomarkers predict future cardiovascular events in patients with CLL.

The relationship between physical activity level and cardiovascular disease biomarkers in healthy, normal-weight 3- to 6-year-old children and their parents.

To determine if physical activity is linked to cardiovascular biomarkers in preschool children at risk, we need information on these biomarkers in healthy normal-weight children. In this population, multi-level modelling analyses found no correlation between accelerometer recorded physical activity and fasting lipids, adiponectin, or insulin sensitivity. Exploratory analyses found positive correlations between adiponectin and time spent in light physical activity, and between triglyceride and time spent in sedentary behaviour; these findings need to be confirmed in longitudinal prospective studies.

Switch to etravirine for HIV-positive patients receiving statin treatment: a prospective study.

BACKGROUND: Lifestyle changes and statins are the cornerstones in management of dyslipidaemia in patients with HIV infection. Replacement of an antiretroviral therapy (ART) component is a proposed therapeutic strategy to reduce cardiovascular risk. In dyslipidaemic patients with HIV infection, we assessed the efficacy of replacing boosted protease inhibitor (bPI) or efavirenz (EFV) by etravirine (ETR) as an alternative to statin therapy. MATERIALS AND METHODS: A prospective, open-label, multicentre, 12-week study of patients with HIV infection on ART including bPI or EFV, and statin treatment. Four weeks after statin interruption, bPI or EFV was switched to ETR (400 mg, 8 weeks) if serum low-density lipoprotein cholesterol (LDL-C) was ≥ 3 mM. The primary endpoint was the proportion of patients on ETR with no indication for statin treatment at study completion. Serum levels of HIV RNA, lipids and biomarkers of cardiovascular disease were also measured. (ClinicalTrials.gov: NCT01543035). RESULTS: The 31 included patients had a HIV-1 RNA < 50 copies/mL (median age, 52 years; median CD4, 709 cell/mL; median LDL-C, 2·89 mM), 68% were on EFV, and 32% were on bPI. At week 4, 27 patients switched to ETR. At study completion, 15 patients (56%) on ETR did not qualify for statin treatment. After the ETR switch, serum levels of the cardiovascular biomarkers sICAM and MCP1/CCL2 decreased by 11·2% and 18·9%, respectively, and those of CCL5/RANTES and tissue inhibitor of metalloproteinase-1 increased by 14·3% and 13·4%, respectively, indicating reduced cardiovascular risk. There were no notable treatment-related adverse events. CONCLUSIONS: Replacing bPI or EFV by ETR is a viable strategy to obviate primary prevention statin treatment.

Modificaciones de las lipoproteínas del plasma en voluntarios sometidos a dietas preparadas con aceite de girasol solo o mezclado con oleína de palma / Changes in the content of plasma lipoproteins in persons subjected to diets prepared with sunflower oil alone or mixed with palm olein

En 31 comensales regulares del Comedor Universitario de la Universidad Central de Venezuela (CUUCV), en Caracas. Se observó el efecto de la sustitución del aceite de girasol que se utiliza corrientemente en la preparación de las comidas en ese comedor, por un aceite obtenido de la mezcla de aceite de girasol y oleína de palma, en la proporción 70/30 (v/v) respectivamente. Después de 40 días continuos de la sustitución no hubo cambios significativos en las concentraciones de colesterol total (CT), ni del colesterol de las lipoproteínas de baja densidad (LDL) y muy baja densidad (VLDL). La concentración del colesterol de las lipoproteínas de alta densidad (HDL) aumentó significativamente (p<0,05). Los triglicéridos (TG) del plasma aumentaron en un 30%. La resistencia a la oxidación de las LDL aumentó considerablemente (p< 0,01). Hoy se considera a esta resistencia como un factor protector de gran importancia en la prevención del inicio del proceso aterogénico. Tomando en cuenta las modificaciones favorables como el aumento de colesterol de HDL sin modificación de la LDL y el claro aumento de la resistencia a la oxidación de la LDL, se considera que la oleína de palma es un aceite vegetal que puede ser utilizado sin mayores riesgos en mezcla con otros aceites que tengan una relación linoleico/palmítico más elevada como los aceites de girasol, maíz, soja y otros.

We analyzed in 31 subjects, regular guests of the University food service of the Central University of Venezuela (UCVFS), in Caracas, the effects of replacing sunflower oil, commonly used in the preparation of meals, by a mix of sunflower oil and palm olein 70/30 (v/v) respectively. Plasma concentrations of total cholesterol, low and very low density lipoproteins were not changed after 40 days of the substitution. On the contrary, concentrations of high density lipoprotein and total triglycerides increased. The resistance to the oxidation of low-density lipoproteins increased considerably (p<0, 01). Today this resistance is considered as a protective factor of great importance in the prevention of the initiation of the atherogenic process. Taking into account the favorable modifications of HDL cholesterol and the clear increased resistance to the oxidation of LDL, we think that palm olein, mixed with other oils with a high ratio linoleic/palmític (sunflower, corn, soya an the likes), can be used as a healthy alternative in human nutrition.