Relationship between Discordance of Low-Density Lipoprotein and Non-High-Density Lipoprotein Cholesterol and Risk Stratification in Acute Myocardial Infarction

Abstract Background: Sizeable proportion of patients have discordant low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein cholesterol (NHDL-C). It has been shown that discordance of LDL-C and NHDL-C either underestimates or overestimates coronary risk. Objectıve: We assessed whether this discordance has an impact on GRACE and TIMI risk scores in patients with acute myocardial infarction (AMI). Methods: We retrospectively evaluated the data of 198 consecutive patients with AMI. Fasting serum lipid profiles were recorded, GRACE and TIMI scores were calculated. Patients were divided into 3 groups according to LDL-C and NHDL-C percentiles: Discordant group: LDL-C<NHDL-C (n=38), concordant group: LDL-C=NHDL-C (n=112) and discordant group LDL-C>NHDL-C (n=48). GRACE and TIMI scores, mortality and cardiovascular events (heart failure, non-fatal myocardial infarction and angina) at sixth month were compared between these three groups. Differences between these groups were analyzed with One-way ANOVA or Kruskal-Wallis rank test, and with chi-square for percentages. Also, post hoc LSD or Conover-Iman's non-parametric multiple comparison test were used. A p value <0.05 was accepted as statistically significant. Results: TIMI risk score didn't differ between discordant or concordant groups. Mean GRACE (death) and GRACE (death and MI) scores were higher in group with LDL-C<NHDL-C than with LDL-C=NHDL-C and LDL-C>NHDL-C (p=0.029 and 0.008, respectively). Cardiovascular events and mortality at sixth month were not different among groups (p=0.473 and p=0.176, respectively). Conclusion: GRACE score was higher in discordant group with LDL-C<NHDL-C, but there is no difference regarding TIMI scores between discordant and concordant groups in AMI patients.

Single-nucleotide polymorphisms of GSK3B, GAB2 and SORL1 in late-onset Alzheimer's disease: interactions with the APOE genotype

In this study, we investigated the associations between single-nucleotide polymorphisms in GAB2 (rs2373115), GSK3B (rs6438552) and SORL1 (rs641120) and Alzheimer's disease (AD), both alone and in combination with the APOE*4 allele.

Efeitos da quimioterapia neoadjuvante sobre os receptores de lipoproteínas no tecido tumoral em pacientes com carcinoma da mama localmente avançado / Effects of neoadjuvant chemotherapy on lipoprotein receptors in tumor tissues of patients with locally advanced breast cancer

Os tumores malignos apresentam um aumento da expressão dos receptores de lipoproteínas, devido ao aceleramento da proliferação celular com consequente aumento da necessidade de lípides para a síntese das membranas celulares. Esse aumento da expressão dos receptores de LDL no câncer pode ser utilizado para concentrar fármacos de ação antineoplásica em tecido tumoral, utilizando lipoproteínas ou nanoemulsões semelhantes a lipoproteínas como veículo. No presente estudo, foram investigados os efeitos da quimioterapia convencional na expressão dos receptores de LDL e LRP-1 em 16 pacientes com carcinoma de mama estádios II ou III, não candidatas à cirurgia conservadora e com indicação de tratamento quimioterápico neoadjuvante. A expressão dos receptores LDLR e LRP-1 foi avaliada por imunoistoquimica em tecido mamário normal e em tecido neoplásico antes e depois da quimioterapia neoadjuvante. Quatro pacientes que apresentaram resposta completa à quimioterapia foram retiradas da análise da expressão de receptores por não existir tumor no fragmento cirúrgico. Em relação ao LDLR, a expressão desse receptor no tecido neoplásico foi maior em comparação ao tecido normal em 8 das 11 pacientes. Após a quimioterapia, a expressão do receptor de LDL diminuiu em 6, aumentou em 4 e não se alterou em 2 pacientes. Do mesmo modo, a expressão do receptor LRP-1 no tecido tumoral estava aumentada em relação ao tecido normal em 4 pacientes das 12 avaliadas. Em comparação com o tecido tumoral antes da quimioterapia, a expressão do receptor LRP-1 diminuiu em 6, aumentou em 4 e permaneceu inalterada em 2 pacientes após a quimioterapia. Esses dados mostram que o efeito da quimioterapia na expressão dos receptores de lipoproteínas foi heterogêneo. A redução da expressão dos receptores não foi o padrão observado, o que indica que o uso de sistemas de carreamento de fármacos via receptores de LDL para o tratamento do câncer pode ser de grande importância...

Proliferative tumor cells present a high expression of LDL receptors due to accelerated mitosis rates which takes to increased need of lipids internalization for building new membranes. Upregulation of LDL receptors may be used as a gate to deliver anticancer drugs to tumor tissues using lipoproteins or artificial nanoemulsions as vehicle. This study investigated the effects of conventional chemotherapy on the expression of LDL and LRP-1 receptors in 16 patients with breast cancer in stage II or III who were not candidates to conservative surgery and with indication of neo-adjuvant chemotherapy. Expression of LDL and LRP-1 receptor was evaluated by immunohistochemistry in normal and neoplastic breast tissue before and after chemotherapy. For absence of tumor in the surgical fragments, 4 patients who presented complete response to chemotherapy were excluded from this analysis. In relation of LDLR, the expression in neoplastic tissue was higher than in normal tissue in 8 of 11 patients. After chemotherapy, LDL receptor expression diminished in 6, increased in 4 and unchanged in 2 patients. Expression of LRP-1 in tumor tissue was higher in 4 of 12 patients when compared to normal tissue. After chemotherapy, the expression of LRP-1 diminished in 6, increased in 4 and showed no difference in 2 patients. These data show that the chemotherapy effects on the tumor expression of LDL receptors were very heterogeneous. The diminution of the receptor expression is not the post-chemotherapy pattern, allowing the use of drug carrier systems that target cancer cells via the LDL receptor pathway. These results may contribute for the design of future clinical assays.

Hipercolesterolemia familiar heterocigota: diagnóstico molecular y terapia combinada. Caso clínico / Molecular diagnosis and combined lipid lowering therapy of heterozygous familial hypercholesterolemia: Report of one case

Heterozygous familial hypercholesterolemia affects one every 400 individuals, is caused by mutations in the LDL receptor gene and is associated with premature coronary artery disease. Nowadays, LDL cholesterol can be efficiently reduced with the new therapies to reduce blood lipids. We report a female patient who consulted in 1975, when she was 46 years old, for severe hypercholesterolemia. In 2003, a sample of leukocyte DNA was obtained and the uncommon 1705 + 1G >A mutation of the LDL receptor gene was detected. No mutations in the apolipoprotein B gene were found. The patient was treated successfully with simvastatin 80 mg/day and ezetimibe 10 mg/day and LDL cholesterol levels were reduced below 200 mg/dl.