Home About us Contact
|
Home About us Contact | ||
|
|
||
Premature Cardiovascular Disease (premature + cardiovascular_disease)
Selected AbstractsHomocysteine, the MTHFR 677 C,T polymorphism and family history of premature cardiovascular diseaseJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2009A. Carey Background:, Cardiovascular disease (CVD) is the main cause of premature death in the UK and accounts for 36% of all premature male deaths and 27% of female deaths every year (British Heart Foundation, 2006). Although many risk factors for CVD are known, family history has been identified as being of particular importance in premature CVD (Lloyd-Jones et al., 2004). Recently, it was suggested that an elevated homocysteine (tHcy) may be associated with premature CVD (Homocystiene Studies Collaboration, 2002). The main genetic determinant of tHcy is the common 677 C,T polymorphism, in the enzyme methylenetetrahydrofolate reductase (MTHFR), which is prevalent in approximately 10% of the UK population. Relatively few studies have examined the association between tHcy and premature CVD and hardly any have considered the role of this polymorphism. The aim of this study therefore was to examine the relationships between the MTHFR 677 C,T polymorphism, tHcy and a family history of CVD in patients with established premature CVD. Methods:, An analysis was conducted on medical, lifestyle and family history data collected from patients and age-sex matched controls, recruited through the GENOVIT study in 2003. This case,control study involved n = 404 premature CVD patients and a similar number of age-sex matched controls, all of whom were screened for the TT genotype. A subset of patients (n = 196) and controls (n = 167) provided a blood sample, from which the tHcy concentration was established. Independent sample t -tests were used to determine differences between patients and controls and differences among genotype groups were examined using a one-way analysis of variance, followed by a Tukey's post hoc test. Results:, Plasma tHcy was significantly elevated in patients with a family history of CVD (compared to those without) (P = 0.013). A nonsignificant trend towards higher tHcy (compared to those without) was observed in patients with the TT genotype (P = 0.419). Furthermore, specifically in those with the TT genotype, those with a family history of CVD (compared to those without) showed significantly higher tHcy concentrations (P < 0.005). Those with the TT genotype who smoked had significantly higher tHcy (P < 0.05) than the CC and CT genotypes. Discussion:, The findings presented provide evidence to support an association between the MTHFR 677C,T polymorphism, elevated homocysteine and family history of premature CVD. Given that dietary levels of riboflavin have been shown to lower homocysteine specifically in individuals with the TT genotype (McNulty et al., 2006), these results have implications for the dietary management of premature CVD in those individuals with a genetic predisposition for elevated tHcy. In conclusion, further research in larger cohort numbers, regarding the correlation between family history, tHcy and the MTHFR polymorphism, would be beneficial for establishing their cause and effect relationship. References British Heart Foundation (2006) All Deaths and Deaths Under 75 by Cause and Sex, 2005, England, Wales, Scotland, N Ireland and United Kingdom. Available at http://www.bhf.org.uk/research_health_professionals/resources/heart_statistics.aspx. Homocystine Studies Collaboration (2002) Homocysteine and the risk of ishaemic heart disease and stroke. JAMA288, 2015,2022. Llyod-Jones, D.M., Nam, B.H., D'Agostino, R.B., Levy, D., Murabito, J.M., Wang, T.J., Wilson, P.W. & O'Donnell, C.J. (2004) Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults, a prospective study of parents and offspring. JAMA291, 2204,2211. McNulty, H., Dowey le, R.C., Strain, J.J., Dunne, A., Ward, M., Molloy, A.M., McAnena. L.B., Hughes, J.P., Hannon-Fletcher, M. & Scott, J.M. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation113, 74,80. [source] Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: A randomized placebo-controlled study,ARTHRITIS & RHEUMATISM, Issue 4 2009Gudrun E. Norby Objective Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. Methods Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40,80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5,6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7,8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. Results Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3,40%), from a mean ± SD of 4.0 ± 0.9 mmoles/liter to 2.8 ± 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7,27.5%), from 6.4 ± 0.9 mmoles/liter to 5.1 ± 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9,119.4], P = 0.064). Conclusion Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole. [source] Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2006D. J. Parry Background: Raised fibrinolytic factors predict cardiovascular risk in healthy subjects. The aim of this study was to measure fibrinolytic factors and insulin resistance in healthy male first-degree relatives of men with intermittent claudication younger than 65 years. Methods: The study compared 165 healthy first-degree relatives with 165 age-, sex- and race-matched control subjects free from a personal or family history of premature cardiovascular disease. Primary outcome measures were plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and D-dimer levels. Insulin resistance was estimated by Homeostasis Model Assessment. Clinical and biochemical risk factors were measured and subjects genotyped for the PAI-1 4G/5G polymorphism. Results: First-degree relatives had significantly higher mean PAI-1 (10·23 versus 7·85 ng/ml; P = 0·024), tPA (9·98 versus 8·29 ng/ml; P < 0·001) and D-dimer levels (56·6 versus 46·1 ng/ml; P = 0·004). They also had significantly higher insulin resistance (1·85 versus 1·53; P < 0·001) and clustered multiple atherogenic risk factors. On multivariate analysis the association between both tPA and D-dimer levels and relative status was independent of other variables. Conclusion: Raised levels of PAI-1, tPA, D-dimer and estimated insulin resistance were present in the healthy male first-degree relatives of men with intermittent claudication. These data support the hypothesis of fibrinolytic risk factor clustering in this high-risk population. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Calcineurin inhibitor effects on glucose metabolism and endothelial function following renal transplantationCLINICAL TRANSPLANTATION, Issue 4 2009Anders Åsberg Abstract:,Background:, Calcineurin inhibitors (CNI) are involved in the development of post-transplant diabetes mellitus (PTDM). Changes in insulin secretion and sensitivity contribute to the development of PTDM and are associated with endothelial function. Methods:, In a pre-defined substudy of a previously published randomized trial in renal transplant recipients we compared the effect of CNI treatment (n = 23) with complete CNI-avoidance (n = 21) on insulin secretion and sensitivity (oral glucose tolerance test) as well as endothelial function (laser Doppler flowmetry), 10 wk and 12 months following transplantation. Results:, Insulin sensitivity differed 10 wk post-transplant and was significantly better after 12 months in patients never treated with CNI drugs [0.091 (0.050) vs. 0.083 (0.036) ,mol/kg/min/pmol/L, p = 0.043]. Insulin secretion tended to be higher in CNI treated patients at both time points (p = 0.068). Endothelial function was not significantly different at week 10 [540 (205) vs. 227 (565) arbitary units × minutes, p = 0.35] or month 12 [510 (620) vs. 243 (242), p = 0.33]. Conclusions:, Findings in the present study indicate that long-term CNI treatment negatively affects glucose metabolism and this may contribute to the increased risk for premature cardiovascular disease in CNI treated renal transplant recipients. Further studies to elucidate this hypothesis are, however, needed. [source] | ||||||||||