Cumulative Cardiovascular Risk Research Articles

ASSOCIATION OF CIRCULATING ENDOTHELIAL CELLS AND ENDOTHELIAL PROGENITOR CELLS IN DYSLIPIDEMIC CHILDREN AND ADOLESCENTS

Circulating endothelial progenitor cells (CEPCs) and endothelial cells (CECs) have been hypothesized to be an important etiologic and surrogate biologic marker for vascular dysfunction/damage and cumulative cardiovascular risk, but the direction of association may differ for children versus adults. For adults, lower CEPCs is felt to be a biomarker of increased CV risk and higher CECs a biomarker of vascular damage. n=134 children (52% males; mean age 11.7+3.3 years; mean LDL-C 4.29+1.79 mmol/L) were enrolled from a pediatric lipid disorders clinic, and had medical, lifestyle behavior (food records, accelerometry) and family history review, anthropometry, and assessment of blood pressure and fasting blood work. Flow cytometry separately identified and enumerated CD45 negative/CD31 positive/CD146 positive/VEGFR2 positive cells that were CD133 positive (CECs) and negative (CEPCs). Factors associated with CECs and with CEPCs were sought in linear regression models. Higher CECs was significantly associated with higher systolic blood pressure z-score (p=0.03), paternal hypertension (p=0.01), older age (p=0.02), higher weight (p=0.03), higher total (p=0.05), non-HDL (p=0.05) and LDL cholesterol (p=0.04), as well as higher hepatic transaminases (AST, p=0.04; ALT, p<0.001). Higher CEPCs was significantly associated with better nutritional score (p<0.001), higher waist circumference percentile (p=0.04) and systolic hypertension (p=0.03). n=23 patients were treated with rosuvastatin. The proportion of patients with CECs >0.10 cells/uL was 65% at baseline, and 91% after 12 and 89% after 24 months of statin (p=0.04). The proportion of patients with CEPCs >0 cells/uL was 35% at baseline, and 35% after 12 and 37% after 24 months of statin (p=NS). For children with dyslipidemia, higher CECs more so than CEPCs was associated with increased CV risk, and were paradoxically increased with treatment with statin. The relationship between CECs and CEPCs and CV risk may be more complex in pediatric patients.

The non-alcoholic fraction of beer increases stromal cell derived factor 1 and the number of circulating endothelial progenitor cells in high cardiovascular risk subjects: A randomized clinical trial

RationaleModerate alcohol consumption is associated with a decrease in cardiovascular risk, but fermented beverages seem to confer greater cardiovascular protection due to their polyphenolic content. Circulating endothelial progenitor cells (EPC) are bone-marrow-derived stem cells with the ability to repair and maintain endothelial integrity and function and are considered as a surrogate marker of vascular function and cumulative cardiovascular risk. Nevertheless, no study has been carried out on the effects of moderate beer consumption on the number of circulating EPC in high cardiovascular risk patients. ObjectiveTo compare the effects of moderate consumption of beer, non-alcoholic beer and gin on the number of circulating EPC and EPC-mobilizing factors. MethodsIn this crossover trial, 33 men at high cardiovascular risk were randomized to receive beer (30g alcohol/d), the equivalent amount of polyphenols in the form of non-alcoholic beer, or gin (30g alcohol/d) for 4 weeks. Diet and physical exercise were carefully monitored. ResultsThe number of circulating EPC and EPC-mobilizing factors were determined at baseline and after each intervention. After the beer and non-alcoholic beer interventions, the number of circulating EPC significantly increased by 8 and 5 units, respectively, while no significant differences were observed after the gin period. In correlation, stromal cell derived factor 1 increased significantly after the non-alcoholic and the beer interventions. ConclusionsThe non-alcoholic fraction of beer increases the number of circulating EPC in peripheral blood from high cardiovascular risk subjects. Clinical trial registrationhttp://www.controlled-trials.com/ISRCTN95345245 ISRCTN95345245

Intima-Media Thickness of Brachial Artery, Vascular Function, and Cardiovascular Risk Factors

Cardiovascular diseases are associated with impaired flow-mediated vasodilation (FMD) and increase in carotid intima-media thickness (IMT). Both FMD and IMT are independent predictors for cardiovascular outcomes. When measuring FMD and nitroglycerine-induced vasodilation in the brachial artery, IMT can also be simultaneously assessed in the same brachial artery. The purpose of this study was to determine the relationships between IMT of the brachial artery, vascular function, and cardiovascular risk factors. We measured brachial IMT, FMD, and nitroglycerine-induced vasodilation by ultrasound in 388 subjects who underwent health examination (mean age, 45±22 years; age range, 19-86), including patients with cardiovascular diseases. Univariate regression analysis revealed that brachial IMT significantly correlated with age (r=0.71; P<0.001), body mass index (r=0.27; P<0.001), systolic blood pressure (r=0.40; P<0.001), diastolic blood pressure (r=0.31; P<0.001), heart rate (r=0.15; P=0.002), glucose level (r=0.18; P=0.01), and smoking pack-years (r=0.42; P<0.001), as well as Framingham risk score, a cumulative cardiovascular risk index for heart attack (r=0.49; P<0.001). FMD and nitroglycerine-induced vasodilation were inversely associated with brachial IMT (r=-0.39, P<0.001; r=-0.32, P<0.001, respectively). In addition, there was a significant relationship between brachial IMT and carotid IMT (r=0.58; P<0.001). Multivariate analysis revealed that age, sex, hypertension, and brachial artery diameter were independent predictors of brachial IMT. These findings suggest that brachial IMT may be a marker of the grade of atherosclerosis and may be used as a marker of vascular function, providing additive information for stratifying subjects with cardiovascular risk factors.

Rho-Associated Kinase Activity, Endothelial Function, and Cardiovascular Risk Factors

Cardiovascular diseases are associated with chronic activation of Rho-associated kinases (ROCKs) and endothelial dysfunction. Both increased ROCK activity and endothelial dysfunction are thought to be closely associated with conventional cardiovascular risk factors. The purpose of this study was to determine the relationships between ROCK activity, endothelial function, and cardiovascular risk factors. We evaluated ROCK activity in peripheral leukocytes by Western blot analysis and flow-mediated vasodilation by ultrasonography in 242 men who had no cardiovascular or cerebrovascular diseases (mean age, 40±10 years; range, 20 to 73 years). ROCK activity was defined as the ratio of phospho myosin-binding subunit on myosin light chain phosphatase to total myosin-binding subunit. Univariate regression analysis revealed that leukocyte ROCK activity significantly correlated with body mass index (r=0.29, P=0.003); systolic blood pressure (r=0.25, P=0.01); low-density lipoprotein cholesterol level (r=0.21, P=0.04); and Framingham risk factor score, a cumulative cardiovascular risk index for heart attack (r=0.31, P<0.001), and that flow-mediated vasodilation significantly correlated with age (r=-0.23, P=0.02), body mass index (r=0.19, P=0.05), systolic blood pressure (r=-0.22, P=0.03), total cholesterol level (r=-0.21, P=0.04), low-density lipoprotein cholesterol level (r=-0.22, P=0.04), glucose level (r=-0.20, P=0.04), and Framingham risk factor score (r=-0.37, P<0.001). There was a significant correlation between leukocyte ROCK activity and flow-mediated vasodilation (r=-0.41, P<0.001). Multivariate analysis revealed that flow-mediated vasodilation was an independent predictor of leukocyte ROCK activity. These findings suggest that cumulative cardiovascular risk may enhance ROCK activity and endothelial dysfunction, leading to progression of cardiovascular diseases and outcomes.

Midlife aspiration and optimism to improve status at work is associated with lower risk for late life dementia

Background:Vascular risk is consistently associated to the onset of dementia. Schooling and cardiovascular (CV) risk factors might have an impact on the rate of progression of Alzheimer’s disease (AD).Methods: Forty-seven patients with probable AD were recruited and classified in two groups according to their score on the Mini-Mental State Examination (MMSE): patients scoring 20 within 3 years after disease onset. Additionally, twenty-six patients who had already scored 15 were classified in two groups: patients scoring 15 within 4 years after disease onset. Also, forty patients with a score > 1.0 on the Clinical Dementia Rating (CDR) were allocated into one of two groups: patients reaching a score > 1.0 within 1⁄44 years after disease onset. Patients were assessed for gender, schooling ( 4 years), age of estimated disease onset ( 1⁄470 years), number of CV risk factors (>1⁄43, or 1⁄470kgf, or 1⁄430kg/m, or ) and waist circumference (> 1⁄4102cm, orChi-squarewas used for statistics, with the threshold of significance at ? 1.0, there were no significant results for gender (?1⁄40.702), schooling (?1⁄40.507), age at disease onset (?1⁄40.666), BMI (?1⁄40.926), weight (?1⁄40.169) or waist circumference (?1⁄40.787). Cumulative CV risk was non-significant for reaching CDR> 1.0 (?1⁄40.641), MMSE1⁄420 (?1⁄4 0.861) or MMSE1⁄415 (?1⁄40.716).Conclusions:Weight and lower schooling had marginally significant effects for a faster rate of progression of AD, assessed by way of MMSE scores.

CUMULATIVE CARDIO-VASCULAR RISK IN HYPERTENSIVE PATIENTS: EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITORS

Aim. To assess cumulative cardio-vascular (CV) risk and elasticity of big-to-middle size arteries in hypertensive patients depending on age, sex and enalapril (Enap, Dr. Reddy’s) effects on these features. Material and methods. 143 patients with arterial hypertension of 1-2 stages were split in 3 groups: 1st – patients younger than 55 y.o. (17 men, 27 women before menopause); 2nd – patients aged 55-65 y.o. (16 men, 38 women); 3rd – elder than 65 y.o. (11 men, 34 women). Fatal CV risk according to SCORE scale and cumulative risk of acute coronary disease (CAD) events according to PRCAM program was assessed before and after 4 weeks of enalapril therapy (5-30 mg/d). Besides the speed of pulse wave spread (SPWS) was determined by method of volume sphygmography. Results. Normal SPWS in elastic arteries was observed in women under 55 y.o. SPWS disturbances were detected in elderly patients. Lower blood pressure (BP) levels and better plasma lipid profile was found in women of young and middle age in comparison with these in men of the same age. More than 80% of hypertensive patients have high CV risk, especially in elderly ones. Enam improved SPWS in elastic arteries, reduced BP and cumulative CV risk. Conclusion. There are gender and age differences between BP levels, SPWS indices, plasma lipid profiles and cumulative CV risks in hypertensive patients. Enalapril improves these characteristics.

Immune Cells Mimic Endothelial Progenitor Colonies.

Colony-forming units of endothelial progenitor cells (“CFU-EC”) have been introduced as a powerful biological marker for vascular function and cumulative cardiovascular risk. The precise mechanisms underlying the colony formation and their cellular composition are unclear. We hypothesized that “CFU-EC” display an immune cell function distinct from circulating endothelial progenitors.We performed detailed subtractive “CFU-EC” analyses in blood samples from 18 healthy volunteers. The impact of various blood cell types and kinetics of protein and gene expression were studied by cell sorting, flow cytometry, quantitative RT-PCR and full genome microarray analyses. “CFU-EC”-derived soluble factors were determined in multiplex cytokine measurements and tested during endothelial network formation.“CFU-EC” contained more than 99% CD45+ nucleated hematopoietic cells mainly comprising T cells and monocytes admixed with B and NK cells. Interestingly, purified T-cells plus monocytes formed “CFU-EC” clusters. The complete lack of colony formation after depletion of T cells or monocytes was contrasted by effective “CFU-EC” formation after depletion of CD34+ progenitors. Microarray analyses revealed an activation of immune function-related biological processes without changes in pathways assigned to angiogenesis. Soluble factors derived from “CFU-EC” cultures supported vascular regeneration in vitro. Unravelling “CFU-EC” formation as a result of a functional crosstalk between T cells and monocytes shifts expectations on vascular regenerative medicine. The data support a switch from a sole view on circulating endothelial progenitors towards models that favor the contribution of immune cells to vascular regeneration.

Endothelial Progenitor Cells and Vascular Biology in Diabetes Mellitus: Current Knowledge and Future Perspectives

A growing amount of evidence demonstrates that Endothelial Progenitor Cells (EPCs) are involved in adult neovasculogenesis and maintenance of vascular integrity. EPC decrease and dysfunction are related to atherosclerosis and cardiovascular disease (CVD), and it has been proposed that the level of circulating EPCs may be used as a surrogate index of cumulative cardiovascular risk. Moreover, many experimental approaches reveal that exogenous EPC injection stimulates blood flow recovery in critical limb and myocardial ischemia, providing a new therapeutic tool for CVD. Diabetes Mellitus is a clinical condition characterized by a high incidence of CVD and is indeed associated with alterations in EPC physiology. In this review we focus on the relationships between EPCs and vascular biology, with particular regard to Diabetes Mellitus and future therapeutical implications.

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