Oxidação, diabetes, doença coronariana

Oxidation, Type 2 Diabetes, and Coronary Heart Disease: A Complex Interaction
Findings from a population-based study.

Saverio Stranges, MD, PHD1,2, Joan M. Dorn, PHD2, Richard P. Donahue, PHD2, Richard W. Browne, PHD3, Jo L. Freudenheim, PHD2, Kathleen M. Hovey, MSC2 and Maurizio Trevisan, MD, MSC2
OBJECTIVE—The purpose of this study was to analyze the interrelationship among oxidation, myocardial infarction (MI), and type 2 diabetes in a population-based case-control study of MI.
RESEARCH DESIGN AND METHODS—Participants were 1,709 individuals from western New York: 257 women and men with incident MI and 1,452 healthy control subjects (aged 35–70 years). Lipid peroxidation was measured by plasma levels of thiobarbituric acid reactive substances (TBARS). History of type 2 diabetes was determined by self-reported history of medical diagnosis.
RESULTS—In multivariate analyses, there was no significant difference in TBARS levels between case and control subjects in both sexes. In subgroup analyses by diabetes status, diabetic subjects, regardless of MI status, exhibited significantly higher TBARS values than nondiabetic subjects. For diabetic women, TBARS values were 1.84 and 1.83 nmol/ml for case and control subjects, respectively. Values for nondiabetic women were 1.29 and 1.31 nmol/ml, respectively. In diabetic men, values were 1.65 and 1.97 nmol/ml for case and control subjects, respectively. Values for nondiabetic men were 1.36 and 1.36 nmol/ml, respectively.
CONCLUSIONS—Whereas type 2 diabetes may be an important correlate of lipid peroxidation, clinical coronary heart disease may not.

Genética do fibrinogênio

Linkage Study of Fibrinogen Levels: The Strong Heart Family Study
Lyle G. Best , Kari E. North , Xia Li , Vittorio Palmieri , Jason G. Umans , Jean MacCluer , Sandra Laston , Karin Haack , Harald Goring , Laura Almasy , Elisa T. Lee , Russell P. Tracy and Shelley A. Cole
BMC Medical Genetics 2008, 9:77doi:10.1186/1471-2350-9-77
Published: 12 August 2008
Abstract (provisional)
Background
The pathogenesis of atherosclerosis involves both hemostatic and inflammatory mechanisms. Fibrinogen is associated with both risk of thrombosis and inflammation. A recent meta-analysis showed that risk of coronary heart disease may increase 1.85 fold for each 1g/L of increased fibrinogen, independent of traditional risk factors. It is known that fibrinogen levels may be influenced by demographic, environmental and genetic factors. Epidemiologic and candidate gene studies are available; but few genome-wide linkage studies have been conducted, particularly in minority populations. The Strong Heart Study has demonstrated an increased incidence of cardiovascular disease in the American Indian population, and therefore represents an important source for genetic-epidemiological investigations.
Methods
The Strong Heart Family Study enrolled over 3,600 American Indian participants in large, multi-generational families, ascertained from an ongoing population-based study in the same communities. Fibrinogen was determined using standard technique in a central laboratory and extensive additional phenotypic measures were obtained. Participants were genotyped for 382 short tandem repeat markers distributed throughout the genome; and results were analyzed using a variance decomposition method, as implemented in the SOLAR 2.0 program.
Results
Data from 3535 participants were included and after step-wise, linear regression analysis, two models were selected for investigation. Basic demographic adjustments constituted model 1, while model 2 considered waist circumference, diabetes mellitus and postmenopausal status as additional covariates. Five LOD scores between 1.82 and 3.02 were identified, with the maximally adjusted model showing the highest score on chromosome 7 at 28cM. Genes for two key components of the inflammatory response, i.e. interleukin-6 and "signal transducer and activator of transcription 3" (STAT3), were identified within 2 and 8 Mb of this 1 LOD drop interval respectively. A LOD score of 1.82 on chromosome 17 between 68 and 93cM is supported by reports from two other populations with LOD scores of 1.4 and 1.95.
Conclusion
In a minority population with a high prevalence of cardiovascular disease, strong evidence for a novel genetic determinant of fibrinogen levels is found on chromosome 7 at 28cM. Four other loci, some of which have been suggested by previous studies, were also identified

Androgenicidade e risco cardiovascular na pós menopausa

Metabolism. 2008 Jul;57(7):961-5.

Relationship between endogenous testosterone and cardiovascular risk in early postmenopausal women.
Maturana MA, Breda V, Lhullier F, Spritzer PM.
Gynecological Endocrinology Unit, Division of Endocrinology, Hospital de Clínicas de Porto Alegre, 90050-170 Porto Alegre, RS, Brazil.
Cardiovascular disease (CVD) is the leading cause of death among postmenopausal women. Changes in endothelial function play an important role in the pathophysiology of atherosclerosis, and evidence suggests that interventions to improve endothelial function could modify the rates of progression and the risk of cardiovascular events. In addition, a positive association between markers of endothelial dysfunction and androgenicity has been described in women with polycystic ovary syndrome, suggesting a correlation with the early-onset endothelial dysfunction found in these patients. We performed a cross-sectional study to verify whether endogenous testosterone levels are correlated with markers of inflammation and endothelial function and with anthropometric and metabolic profile in 53 postmenopausal women. Serum testosterone, sex hormone-binding globulin, C-reactive protein (CRP), fibrinogen, and plasma endothelin-1 (ET-1) were determined. Patients were stratified into 2 groups (higher or lower than the mean testosterone levels of the studied sample). Mean age was 55 years (+/-5), and median time since menopause was 5.5 years (interquartile range, 3-8 years). Body mass index and waist circumference were significantly higher in the group with testosterone levels >or=0.49 ng/mL. Median CRP levels were greater in the group with higher testosterone levels (1.17 [0.17-2.36] vs 0.17 [0.17-0.61] mg/L, P = .039). Median ET-1 levels were also higher in women with greater testosterone levels (0.84 [0.81-0.97] vs 0.81 [0.74-0.84] pg/mL, P = .023). An association of testosterone with CRP (r = 0.416, P = .004) and ET-1 (r = 0.323, P = .031) was observed. This association was dependent on homeostasis model assessment index for ET-1 but not CRP. Testosterone was also associated with waist circumference and blood pressure (P = .001). These data suggest that endogenous testosterone levels in recently postmenopausal women may be part of a proatherogenic profile. Longitudinal studies are needed to assess if androgenicity represents a risk factor for cardiovascular disease and the clinical relevance of its association with ET-1 and CRP in this population.