Coronary Artery Calcification and Family History of Myocardial Infarction in the Dallas Heart Study

ObjectivesThis study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD).BackgroundFH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for.MethodsAmong 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC.ResultsThe mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile.ConclusionsFH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile.     

Interaction of Shiga toxin 2 with complement regulators of the factor H protein family

Shiga toxin 2 (Stx2) is believed to be a major virulence factor of enterohemorrhagic Escherichia coli (EHEC) contributing to hemolytic uremic syndrome (HUS). The complement system has recently been found to be involved in the pathogenesis of EHEC-associated HUS. Stx2 was shown to activate complement via the alternative pathway, to bind factor H (FH) at short consensus repeats (SCRs) 6–8 and 18–20 and to delay and reduce FH cofactor activity on the cell surface.     

Smoking and FGFR2 rs2981582 variant independently modulate male breast cancer survival: A population-based study in Tuscany,Italy

AimMale breast cancer (MBC) is a rare disease and recommendations for its clinical management are often extrapolated from those for female breast cancer, even if breast cancer (BC) has different characteristics in the two sexes. The purpose of this study was to assess the influence of several individual characteristics including clinico-pathological, lifestyle and genetic factors on overall survival (OS) of a relatively large and well characterized population-based series of 166 MBCs enrolled in Tuscany.MethodsWe genotyped MBC cases at BRCA1/2 genes and at 9 candidate BC susceptibility SNPs. Kaplan-Meier method and multivariate Cox regression, adjusted for several individual characteristics were used. To reduce a possible selection bias related to the interval between diagnosis and enrolment of MBC cases into the study, we used the date of blood donation as the date of the start of observation for survival analysis.ResultsOnly smoking habits had a significant effect on OS at 10 years (for current smokers, HR: 3.34; 95% CI 1.45–7.68; p = 0.004), while lymph node status fell short of reaching statistical significance (for pN positive, HR: 2.07; 95% CI 0.93–4.55; p = 0.07). In the same multivariate analysis we found a significantly higher OS in cases with FGFR2 rs2981582 variant in the dominant transmission model (HR: 0.29; 95% CI: 0.13–0.62; p = 0.028). A sensitivity analysis with left truncation showed similar results.ConclusionsOur results may contribute to shed light on factors influencing MBC survival suggesting an important role for cigarette smoking and FGFR2 rs2981582 variant, and provide clues for better patient management.     

Clinical applications of long-term LDL-apheresis on and beyond refractory hypercholesterolemia

Premature coronary heart disease (CHD) can result from high LDL cholesterol levels even in the absence of any other risk factors. A striking example is found in children who have the homozygous form of familial hypercholesterolemia (FH) with extremely high levels of LDL-cholesterol, and severe atherosclerosis and CHD often develop during the first decades of life. LDL-apheresis was developed for the treatment of severe type of FH patients who are resistant to lipid-lowering drug therapy. Clinical efficacy and safety of the therapeutic tool which directly removes LDL from circulation have already been established in the treatment for refractory hypercholesterolemia in FH patients. The most recently developed method enables lipoproteins to be adsorbed directly from whole blood, using polyacrylate column. In addition to benefits derived from the stabilization or regression of arterial lesions, we highlight other possible clinical applications of LDL-apheresis. However, most of these clinical benefits came from case reports or retrospective studies. Mechanisms related these clinical improvement remain unclear, and prospective randomized controlled trials should be performed for the new clinical indications of LDL-apheresis.     

Tamm－Horsfall蛋白糖基组分的致肾炎作用

我们在体外试验中证实：Ｔａｍｍ－Ｈｏｒｓｆａｌｌ蛋白（ＴＨＰ）刺激人单核细胞产生肿瘤坏死因子和ＩＬ－１的作用依赖其糖基组分的完整。为了探讨糖基组分在ＴＨｐ所致肾小管间质肾炎（ＴＩＮ）发病机制中的作用。我们给Ｗｉｓｔａｒ大鼠肾内直接注射ＴＨＰ制成ＴＩＮ模型。该模型在发病第４ｄ即有明显的肾间质巨噬细胞（ＭΦ）浸润。用高碘酸氢化去除ＴＨＰ的糖基组分明显破坏了ＴＨＰ诱发ＴＩＮ的能力。注射去糖基ＴＨＰ的动物只有轻微的组织学和超微结构改变。肾间质浸润的ＭΦ数量明显减少，亦无肾小管功能障碍。由此表明：ＴＨＰ的糖基组分在其导致ＴＩＮ的发生、发展中具有关键作用。     

Transfer of lipids to high-density lipoprotein (HDL) is altered in patients with familial hypercholesterolemia

Objective

In familial hypercholesterolemia (FH), the metabolism and anti-atherogenic functions of HDL can be affected by the continuous interactions with excess LDL amounts. Here, lipid transfers to HDL, an important step for HDL intravascular metabolism and for HDL role in reverse cholesterol transport (RCT) were investigated in FH patients.

Methods

Seventy-one FH patients (39 ± 15 years, LDL-cholesterol = 274 ± 101; HDL-cholesterol = 50 ± 14 mg/dl) and 66 normolipidemic subjects (NL) (38 ± 11 years, LDL-cholesterol = 105 ± 27; HDL-cholesterol = 52 ± 12 mg/dl) were studied. In vitro, lipid transfers were evaluated by incubation of plasma samples (37 °C, 1 h) with a donor lipid nanoemulsion labeled with 3H-triglycerides (TG) and 14C-unesterified cholesterol (UC) or with 3H-cholesteryl ester (EC) and 14C-phospholipids (PL). Radioactivity was counted at the HDL fraction after chemical precipitation of apolipoprotein (apo) B-containing lipoproteins and the nanoemulsion. Data are % of total radioactivity measured in the HDL fraction.

Results

Transfer of UC to HDL was lower in FH than in NL (5.6 ± 2.1 vs 6.7 ± 2.0%, p = 0.0005) whereas TG (5.5 ± 3.1 vs 3.7 ± 0.9%, p = 0.018) and PL (20.9 ± 4.6 vs 18.2 ± 3.7 %, p = 0.023) transfers were higher in FH. EC transfer was equal. By multivariate analysis, transfers of all four lipids correlated with HDL-cholesterol and with apo A-I.

Conclusion

FH elicited marked changes in three of the four tested lipid transfers to HDL. The entry of UC into HDL for subsequent esterification is an important driving force for RCT and reduction of UC transfer to HDL was previously associated to precocious coronary heart disease. Therefore, in FH, HDL functions can be lessened, which can also contribute to atherogenesis.     

胎心监护在围产保健中的应用研究

目的探讨产前胎心监护对围产儿预后的临床意义。方法选择本院2005年5月-2009年10月1 400例孕妇,从妊娠36周起每周行无应激试验检查,根据有无反应,把有反应1320例为对照组,无反应80例为观察组,观察两组的新生儿窒息率。结果本组1 400例次孕妇无应激试验检查中,反应型1 320例次(94.3%);无反应型80例次(5.7%)观察组80例中共有36例发生新生儿窒息,其发生率为45%,有2例为重度窒息,2例死产;而对照组1 320例中仅有18例发生新生儿窒息,且都为轻度窒息,两组比较有显著差异(P<0.01)。结论孕36周起每周进行产前胎监,发现胎心监护评分异常者及时处理,对降低围产儿死亡率有重要意义。