Sex Differences in Carotid Plaque and Stenosis

Background and Purpose-Women are relatively protected from cardiovascular events; they are 3 times as likely as men to survive to age 90 years. Although clinical trials show an excess of thrombotic events with estrogen/progestin hormone replacement therapy, much experimental and epidemiological evidence suggests that estrogen may have beneficial effects on endothelial function and atherosclerosis, raising the possibility of sex differences in arterial remodeling. We studied sex differences in carotid plaque and stenosis in relation to survival free of stroke, death, and myocardial infarction. Methods-A total of 1686 patients from an atherosclerosis prevention clinic were followed annually for up to 5 years (mean, 2.5 ± 1.3 years) with baseline and follow-up measurements; there were 45 strokes, 94 myocardial infarctions, and 41 deaths. Results-Carotid stenosis and plaque increased with age. Women had greater stenosis compared with men (P=0.001), whereas men had greater plaque area than did women at all ages (P\u3c0.0001). Stroke, myocardial infarction, and death combined were predicted significantly by plaque area (P=0.004) but not by stenosis (P=0.042). Conclusions-Women have more stenosis but less plaque than men, suggesting that differences in sex hormones may affect remodeling of atherosclerosis. Plaque area was a stronger predictor of outcomes than was stenosis

Pathophysiology of vascular dementia

The concept of Vascular Dementia (VaD) has been recognized for over a century, but its definition and diagnostic criteria remain unclear

Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products

Background: Carotid plaque area is a strong predictor of cardiovascular events. High homocysteine levels, which are associated with plaque formation, can result from inadequate intake of folate and vitamin B12. Now that folic acid fortification is widespread in North America, vitamin B12 has become an important determinant of homocysteine levels. We sought to determine the prevalence of low serum levels of vitamin B12, and their relation to homocysteine levels and carotid plaque area among patients referred for treatment of vascular disease since folic acid fortification of enriched grain products. Methods: We evaluated 421 consecutive new patients with complete data whom we saw in our vascular disease prevention clinics between January 1998 and January 2002. We measured total carotid plaque area by ultrasound and determined homocysteine and serum vitamin B12 levels in all patients. Results: The patients, 215 men and 206 women, ranged in age from 37 to 90 years (mean 66 years). Most were taking medications for hypertension (67%) and dyslipidemia (62%). Seventy-three patients (17%) had vitamin B12 deficiency (vitamin B12 level \u3c 258 pmol/L with homocysteine level \u3e 14 μmol/L or methylmalonic acid level \u3e 271 nmol/L). The mean area of carotid plaque was significantly larger among the group of patients whose vitamin B12 level was below the median of 253 pmol/L than among those whose vitamin B12 level was above the median: 1.36 (standard deviation [SD] 1.27) cm2 v. 1.09 (SD 1.0) cm2; p = 0.016. Conclusions: Vitamin B12 deficiency is surprisingly common among patients with vascular disease, and, in the setting of folic acid fortification, low serum vitamin B12 levels are a major determinant of elevated homocysteine levels and increased carotid plaque area. © 2005 CMA Media Inc. or its licensors

Genetic screening of Fabry patients with EcoTILLING and HRM technology

<p>Abstract</p> <p>Background</p> <p>Anderson-Fabry disease (FD) is caused by a deficit of the α-galactosidase A enzyme which leads to the accumulation of complex sphingolipids, especially globotriaosylceramide (Gb3), in all the cells of the body, causing the onset of a multi-systemic disease with poor prognosis in adulthood. In this article, we describe two alternative methods for screening the <it>GLA </it>gene which codes for the α-galactosidase A enzyme in subjects with probable FD in order to test analysis strategies which include or rely on initial pre-screening.</p> <p>Findings</p> <p>We analyzed 740 samples using EcoTILLING, comparing two mismatch-specific<ul/>endonucleases, CEL I and ENDO-1, while conducting a parallel screening of the same samples using HRM (High Resolution Melting). Afterwards, all samples were subjected to direct sequencing. Overall, we identified 12 different genetic variations: -10C>T, -12G>A, -30G>A, IVS2-76_80del5, D165H, C172Y, IVS4+16A>G, IVS4 +68 A>G, c.718_719delAA, D313Y, IVS6-22C>T, G395A. This was consistent with the high genetic heterogeneity found in FD patients and carriers. All of the mutations were detected by HRM, whereas 17% of the mutations were not found by EcoTILLING. The results obtained by EcoTILLING comparing the CEL I and ENDO-1 endonucleases were perfectly overlapping.</p> <p>Conclusion</p> <p>On the basis of its simplicity, flexibility, repeatability, and sensitivity, we believe that<ul/>HRM analysis of the <it>GLA </it>gene is a reliable presequencing screening tool. This method can be applied to any genomic feature to identify known and unknown genetic alterations, and it is ideal for conducting screening and population studies.</p