Increasing glycaemia is associated with a significant decline in HDL cholesterol in women with prediabetes in two national populations.

Internationally, studies have shown associations between lipids and glycemia; however, whether the link varies by gender and population has been rarely examined. We investigated relationships between glycemia and HDL- and Non-HDL-cholesterol and their modification by gender. We undertook a cross-sectional analysis from the National Health Examination Survey for Thailand (NHES-Thailand) and the Health Survey for England (HS-England) in adults aged 18-75 year. Glycaemia was assessed by FPG in Thailand and by HbA1c in the UK. In population- and gender-stratified analyses, the relationships between glycemia and lipids were explored. A total of 15,145 Thai and 3484 UK adults with blood measurement were included. The prevalences of prediabetes were: in NHES-Thailand, 16% (SE = 0.004), based on FPG (5.6 to < 7.0 mmol/L) and in HS-England, 19% (0.007) based on HbA1c (39 to < 48 mmol/mol). Increasingly abnormal glucose homeostasis was associated with increasing age, adiposity, SBP, proportion of antihypertensive and lipid-lowering agent use and with decreasing HDL-cholesterol. Independent of age, adiposity, smoking, alcohol, physical activity, and lipid and BP lowering drug use, increasing glycemia was associated with decreasing HDL-cholesterol specifically in women with prediabetes (NHES-Thailand, beta-coefficient - 0.07 (95% CI - 0.15, - 0.001) p = 0.04 and HS-England, - 0.03 (- 0.04, - 0.006) p = 0.01). In both populations, among those with prediabetes, increasing glycaemia is associated with an adverse, significant decline in HDL cholesterol, specifically in women. These adverse effects are apparent in widely-differing international populations.

The Effect of High Carbohydrate-to-fat Intake Ratios on Hypo-HDL-cholesterolemia Risk and HDL-cholesterol Levels over a 12-year Follow-up.

Considering the strong correlation between carbohydrate and fat intake, we defined and assessed the association of the carbohydrate-to-fat ratio with the high-density lipoprotein cholesterol (HDL-c) level using 12-year follow-up data from the community-based cohort of the Korean Genome Epidemiology Study. We evaluated the long-term changes in HDL-c levels according to quartiles of carbohydrate-to-fat ratio using a mixed model. We also assessed the effect of the carbohydrate-to-fat ratio on the prevalence and incidence of hypo-HDL-cholesterolemia. Of 6,627 subjects, the prevalence of undiagnosed hypo-HDL-cholesterolemia at baseline was 35.3% (n = 2,339). Among the disease-free subjects, 56.8% developed hypo-HDL-cholesterolemia (incidence = 92/1,000 person-years). The prevalence and incidence of hypo-HDL-cholesterolemia were higher in females than in males. The highest carbohydrate-to-fat ratio quartile, which was characterized by high and low intake of carbohydrate and fat, was consistently associated with a lower HDL-c level during the 12-year follow up. Moreover, those in the highest quartile had a 1.14-fold greater risk of incident hypo-HDL-cholesterolemia than those in the lowest quartile, with a significant dose-response relationship. We found that high and low intake of carbohydrate and fat, respectively, was consistently associated with a low HDL-c level over a prolonged period. More research is needed to promote appropriate intake of macronutrients.

Assessment of HDL Cholesterol Removal Capacity: Toward Clinical Application.

While there is a controversy regarding the causal relationship between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD), recent studies have demonstrated that the cholesterol efflux capacity (CEC) of HDL is associated with the incidence of CVD. However, there are several limitations to current assays of CEC. First, CEC measurements are not instantly applicable in clinical settings, because CEC assay methods require radiolabeled cholesterol and cultured cells, and these procedures are time consuming. Second, techniques to measure CEC are not standardized. Third, the condition of endogenous cholesterol donors would not be accounted for in the CEC assays. Recently, we established a simple, high-throughput, cell-free assay system to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as "cholesterol uptake capacity (CUC)". We demonstrated that CUC represents a residual cardiovascular risk in patients with optimal low-density lipoprotein cholesterol control independently of traditional risk factors, including HDL-C. Establishing reproducible approaches for the cholesterol removal capacity of HDL is required to validate the impact of dysfunctional HDL on cardiovascular risk stratification in the "real world".

Genetic associations in community context: a mixed model approach identifies a functional variant in the RBP4 gene associated with HDL-C dyslipidemia.

BACKGROUND: The objective of this study was to examine individual and community factors that influence high-density lipoprotein cholesterol (HDL-C) dyslipidemia in Newfoundland and Labrador (NL), a genetically isolated population in Canada with a high prevalence of HDL-C dyslipidemia. METHODS: First, a group of single nucleotide polymorphisms from 10 metabolic trait candidate genes was tested using a multivariate logistic regression model. The significant SNPs were entered into the second phase, where a mixed logistic model incorporated the community disease risk factors together with the individual factors as the fixed part of the model and the geographic region as a random effect. RESULTS: Analysis of 1489 subjects (26.9% HDL-C dyslipidemia) identified rs3758539, a non-coding variant in the 5'UTR of RBP4, to be associated with HDL-C dyslipidemia (odds ratio = 1.45, 95% confidence interval = 1.08-1.97, p = 0.01). The association remained significant, and the effect size did not change after the incorporation of individual and community risk factors from 17 geographic regions (odds ratio: 1.41, 95% confidence interval = 1.03-1.93, p = 0.03) in NL. Besides this variant, sex, BMI, and smoking also showed significant associations with HDL-C dyslipidemia, whereas no role was identified for the community factors. CONCLUSIONS: This study demonstrates the use of community-level data in a genetic association testing. It reports a functional variant in the promoter of RBP4, a gene directly involved in lipoprotein metabolism, to be associated with HDL-C dyslipidemia. These findings indicate that individual factors are the main reason for a higher prevalence of HDL-C dyslipidemia in the NL population.

Low serum levels of High-Density Lipoprotein cholesterol (HDL-c) as an indicator for the development of severe postpartum depressive symptoms.

Postpartum depression (PPD) is a psychiatric complication of childbirth affecting 10-20% of new mothers and has negative impact on both mother and infant. Serum lipid levels have been related to depressive disorders, but very limited literatures are available regarding the lipid levels in women with postpartum depression. The present study is aimed to examine the association of serum lipids with the development of postpartum depressive symptoms. This is a cross sectional study conducted at a tertiary care hospital in South India. Women who came for postpartum check-up at 6th week post-delivery were screened for PPD (September 2014-October 2015). Women with depressive symptoms were assessed using EPDS (Edinburgh Postnatal Depression Scale). The study involved 186 cases and 250 controls matched for age and BMI. Serum levels of lipid parameters were estimated through spectrophotometry and the atherogenic indices were calculated in all the subjects. Low serum levels of Total Cholesterol (TC) and High Density Lipoprotein cholesterol (HDL-c) were significantly low in PPD women with severe depressive symptoms. The study recorded a significant negative correlation between HDL-c and the EPDS score in PPD women (r = -0.140, p = 0.05). Interestingly, the study also observed a significant negative correlation between Body Mass Index (BMI) and EPDS scores in case group (r = -0.146, p = 0.047), whereas a positive correlation between the same in controls (r = 0.187, p = 0.004). Our study demonstrated that low levels of serum HDL-c is correlated with the development of severe depressive symptoms in postpartum women. Study highlights the role of lipids in the development of postpartum depressive symptoms.

Two-year follow-up of patients with septic shock presenting with low HDL: the effect upon acute kidney injury, death and estimated glomerular filtration rate.

BACKGROUND: Sepsis is associated with decreased levels of high-density lipoprotein (HDL) cholesterol. HDL has anti-inflammatory properties, and the use of Apo A-I mimetic peptides is associated with renal function improvement in animal models of sepsis. However, it is not known whether decreased HDL level results in impaired renal function in human sepsis. We investigated whether low levels of HDL conferred an increased risk of sepsis-associated acute kidney injury (AKI) or long-term decreased estimated glomerular filtration rate (eGFR) after sepsis. METHODS: HDL concentration (mg dL-1 ) was measured in plasma samples from 180 patients with septic shock at admission to the Emergency Department (ED). We divided the patients using median HDL as a cut-off value and assessed the frequency of sepsis-associated AKI and long-term decreased eGFR after sepsis. Univariate and multivariate analyses were performed. RESULTS: Patients with low HDL had a significantly greater frequency of KDIGO 2 or 3 sepsis-associated AKI [39/90 (43.3%) vs. 12/90 (13.3%), P < 0.001] and decreased long-term eGFR [24/58 (41.4%) vs. 11/57 (19.3%), P = 0.018] compared to those with high HDL. The adjusted OR for sepsis-associated AKI and decreased eGFR after sepsis in the lower HDL group was 2.80 (95% CI 1.08-7.25, P = 0.033) and 5.45 (95% CI 1.57-18.93, P = 0.008), respectively. CONCLUSION: Low HDL levels during sepsis are associated with increased risk of sepsis-associated AKI, and/or subsequent decreased eGFR. These results suggest that HDL may be involved and/or may be a marker of kidney injury during and after sepsis.

Vascular risk factors and progression of white matter hyperintensities in the Lothian Birth Cohort 1936.

We aimed to determine associations between multiple vascular risk factors (VRF) at ∼73 years and progression of white matter hyperintensities (WMH) from ∼73 years to ∼76 years. We calculated correlations and generalized estimating equation models of a comprehensive range of VRF at 73 years and change in WMH volume from 73 years to 76 years. Higher systolic (rho = 0.126, p = 0.009) and diastolic (rho = 0.120, p = 0.013) blood pressure at 73 years were significant predictors for greater WMH volume at 76 years in a simple correlation model. However, neither measured blood pressure nor self-reported hypertension at 73 years was significant predictors of WMH volume change in a fully adjusted model which accounted for initial WMH volume at 73 years. Lower high-density lipoprotein cholesterol (beta = -0.15 % intracranial, -1.80 mL; p < 0.05) and current smoking (beta = 0.43 % intracranial, 5.49 mL; p < 0.05) were the only significant VRF predictors of WMH volume change from 73 years to 76 years. A focus on smoking cessation and lipid lowering, not just antihypertensives, may lead to a reduction in WMH growth in the eighth decade of life.

Interactions of Six SNPs in ABCA1gene and Obesity in Low HDL-C Disease in Kazakh of China.

OBJECTIVE: To detect the interactions between six functional polymorphisms in ABCA1 and obesity in Kazakhs with low HDL-C levels. METHODS: A total of 204 patients with low HDL-C and 207 health control subjects, which were randomly selected from among 5692 adult Kazakhs, were matched for age and sex. We genotyped ABCA1 single nucleotide polymorphisms of rs2515602, rs3890182, rs2275542, rs2230806, rs1800976, and rs4149313. RESULTS: (1) The genotypic and allelic frequencies of rs2515602, rs2230806 and rs4149313 were different between normal HDL-C and low HDL-C subjects, the genotypic frequency of rs2275542 was also different between normal HDL-C and low HDL-C subjects (p < 0.05); (2) the level of HDL-C (rs2515602 and rs2275542) in normal HDL-C subjects were different among the genotypes (p < 0.05); the levels of TC, LDL-C (rs2515602, rs4149313); TG (rs2515602, rs1800976, rs4149313) in low HDL-C patients were different among the genotypes (p < 0.05); (3) interactions between the rs3890182, rs2275542, rs180096, and rs4149313 polymorphisms in ABCA1 gene and obesity may be associated with low HDL-C disease; (4) the C-C-C-A-A-G, T-C-C-A-A-A, T-C-C-A-A-G, C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes were significant between the subjects with normal HDL-C and low HDL-C level (p < 0.05). CONCLUSIONS: The differences in serum lipid levels between normal HDL-C and low HDL-C subjects among Kazakhs might partly result from ABCA1 gene polymorphisms; ABCA1 gene polymorphisms may be associated with low HDL-C disease; the low HDL-C disease might partly result from interactions between ABCA1 gene polymorphisms and obesity; the C-C-C-A-A-G, T-C-C-A-A-A, and T-C-C-A-A-G haplotypes may serve as risk factors of low HDL-C disease among Kazakhs, the C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes may serve as protective factor of low HDL-C disease among Kazakhs.

Impact of low level of high-density lipoprotein-cholesterol sampled in overnight fasting state on the clinical outcomes in patients with acute myocardial infarction (difference between ST-segment and non-ST-segment-elevation myocardial infarction).

BACKGROUND: Despite good treatment, there are residual risks in acute myocardial infarction (AMI) patients, and low level of high-density lipoprotein-cholesterol (HDL) has drawn attention as a possible cause. However, the impact of low HDL on ST-segment-elevation myocardial infarction (STEMI) compared with non-ST-segment-elevation myocardial infarction (NSTEMI) is not clear. Our aim was to evaluate the impact of low HDL on clinical outcomes in patients with STEMI or NSTEMI. METHODS: We included 9270 AMI patients undergoing successful percutaneous coronary intervention. They were grouped into STEMI and NSTEMI, and subdivided into two groups according to HDL level sampled in overnight fasting state. Primary end point was in-hospital death. Secondary end point was a composite of major adverse cardiac events (MACE) in hospital survivors during one-year follow-up. RESULTS: In the STEMI population, low HDL group showed significantly higher in-hospital death rate [4.6% vs. 1.4%, hazard ratio (HR): 2.380, 95% confidence interval (CI): 1.143-4.956, p=0.020] than normal HDL group. In NSTEMI population, there was no significant difference between two groups (1.8% vs. 0.9%, HR: 1.231, 95% CI: 0.649-2.335, p=0.525), but in subgroup analysis, very low HDL subgroup showed higher in-hospital mortality rate compared with normal HDL group (4.0% vs. 0.9%, respectively, p=0.009). In 12-month MACE rates, there was no significant difference between two groups in both populations. CONCLUSIONS: Low HDL was associated with significantly higher risk of in-hospital mortality in STEMI patients, but not in NSTEMI patients. Thus, more aggressive treatment should be considered in STEMI patients with low HDL.

Risk of the development of Type 2 diabetes in relation to overall obesity, abdominal obesity and the clustering of metabolic abnormalities in Japanese individuals: does metabolically healthy overweight really exist? The Niigata Wellness Study.

AIMS: We investigated the risk of developing diabetes across various metabolic phenotypes by considering the presence of overall adiposity or abdominal adiposity and the number of metabolic abnormalities and aimed to clarify whether a 'healthy overweight' phenotype, that is, overweight with no metabolic abnormalities, was protective of the development of diabetes. METHODS: We studied 29 564 Japanese individuals without diabetes. The 5-year incidence of diabetes was assessed according to a combination of either overweight (BMI ≥ 25.0 kg/m(2) ) or abdominal obesity (waist circumference ≥ 90 cm in men and ≥ 80 cm in women) and the number of metabolic factors present (hypertension, elevated triglyceride concentration, low HDL cholesterol concentration and impaired fasting glucose). RESULTS: A total of 1188 individuals developed diabetes. Compared with normal weight individuals with none of the four metabolic abnormalities, in overweight individuals with none of the four abnormalities there was an odds ratio (OR) of 2.32 [95% confidence interval (CI) 1.50, 3.59] for diabetes; having any one metabolic abnormality increased the risk of developing diabetes among normal weight individuals [OR 3.23 (2.55, 4.10)] and overweight individuals [OR 5.00 (3.77, 6.63)]. Among overweight individuals, the presence of impaired fasting glucose alone substantially elevated the risk of diabetes by 8.98-fold (5.52, 14.6) in comparison with the absence of the four metabolic factors. CONCLUSIONS: Being 'healthy overweight' was associated with a higher OR of developing future diabetes among Japanese individuals than normal weight individuals with no metabolic abnormalities, and being overweight with one or more abnormalities had a further elevated OR compared with 'healthy overweight' people.

Evaluación de lípidos y lipoproteínas en escolares residentes de gran altitud / Evaluation of lipids and lipoproteins in school children high altitude residents

PREGUNTA DE INVESTIGACIÓN: ¿Cuáles serán los valores de lípidos y lipoproteínas en niños y niñas en edad escolar, de zona periférica de La Paz, Bolivia, residentes de altitud, en la gestión 2011? OBJETIVO: establecer los valores de lípidos y lipoproteínas en niños y niñas en edad escolar de zona periférica de La Paz, Bolivia, residentes de altitud, en la gestión 2011. MATERIAL Y MÉTODOS: estudio descriptivo transversal, en 84 escolares de 6 a 13 años de edad. Realizado en zona periurbana y otra no periurbana, ciudad de La Paz, a 3700 metros de altitud. Se realizaron, examen clínico pediátrico; peso, talla, índice de masa corporal (IMC) (kg/talla2), pliegues tricipital, subescapular, suprailíaco; perímetro de cintura, y dosificación de triglicéridos, colesterol total, lipoproteína de alta densidad, HDL-c y de baja densidad, LDL-c. RESULTADOS: la obesidad era de 8% (IMC-Z > 2), la circunferencia de cintura, estaba incrementada en 24 escolares (28%), a predominio de varones. Los varones tenían valores promedio más elevados de colesterol total, LDL-c y HDL-c que las mujeres, diferencia estadísticamente significativa. Acorde a referencias de poblaciones de nivel del mar, se encontró triglicéridos, en < 10 años, elevados en 13 escolares (31 %). HDL-c baja en 28 escolares (33%). Nivel socio económico (NSE) bajo, en < 10 años, triglicéridos elevados, 11 escolares (34%); HDL-c baja, 23 escolares (38 %). NSE medio, HDL-c baja, 5 escolares (21 %). En mujeres, en < 10 años, triglicéridos elevados en 6 escolares (24%). HDL-c baja en 19 escolares (40%). En varones, en < 10 años, triglicéridos elevados en 7 escolares (41%), y HDL-c baja en 9 escolares (24%). CONCLUSIONES: escolares de gran altitud presentaron valores elevados de triglicéridos, a predominio de los menores de 10 años, de un NSE bajo; las lipoproteínas HDL-c estaban disminuidas en estos mismos grupos. La prevención primaria de los factores de riesgo, debe ser uno de los principales propósitos, de alta prioridad, de las estrategias de salud escolar en nuestro contexto de altitud.

RESEARCH QUESTION: which are the values of lipids and lipoproteins values of school children high altitude residents in peripheral areas of La Paz city, Bolivia, 2011? OBJECTIVE: To determine lipids and lipoproteins values of schoolchildren high altitude residents in peripheral areas of La Paz city, Bolivia, 2011 METHODS: a descriptive, transversal study was conducted in urban and periurban areas of La Paz city at 3700 meters above sea level. The study included 84 schoolchildren between 6 to 13 years old. A pediatric clinic examination and anthropometric measurements such as weight, height, skin folds and circumferences were performed. Cholesterol, triglycerides, high and low density lipoproteins (HDL-c and LDL-c) were determinate by conventional methods. RESULTS: We found obesity in 8% of school children defined by BMI-age Z score > 2 SD, waist circumference was increased in 24 subjects (28%), with male predomination. Total cholesterol, HDL-c and LDL-c were higher in males than females, difference statistic significant (p=0.05). According to references values at sea level populations, the triglycerides were higher in 13 subjects younger than 10 years (31%), HDL-c was low in 28 subjects (33%). By socioeconomic level we found in the low group high values of triglycerides in 11 subjects younger than 10 years and HDL-c low in 23 subjects (38%), in the medium group we found HDL-c low in 5 subjects (21%). By sex in females we found triglycerides high in 6 subjects younger than 10 years and HDL-c low in 19 subjects (40%), in males younger than 10 years we found triglycerides high in 7 subjects (41%) and HDL-c low in 9 subjects (24%). CONCLUSIONS: school children living at high altitude present high values of triglycerides, in subjects under 10 years old with a low socioeconomic level and HDLc were low in this same groups. The primary prevention of risk factors against cardiovascular diseases must to be a priority in health scholar strategies in our context.

Early senescence in heterozygous ABCA1 mutation skin fibroblasts: a gene dosage effect beyond HDL deficiency?

PURPOSE: Homozygous ABCA1 gene mutation causes Tangier disease (TD). The effects reported in heterozygous state regard plasma HDL, cell cholesterol efflux and coronary artery disease. We investigated whether in vitro replicative skin fibroblast senescence shown in TD proband (Hom), his father (Het), and in a healthy control might be induced in a "gene-dosage way". METHODS: Senescence was evaluated by staining test for ß-Galactosidase and telomere length (TL) on fibroblast DNA at different replicative stages. ABCG1 and LDLR (low density lipoprotein receptor) gene expression was also evaluated. RESULTS: Hom cells showed early senescent morphology and reduced growth at all passages in vitro. The cell positive percentage for ß-Galactosidase test was highly increased in Hom compared to Het cells at late replicative status (66.1% vs 41.3% respectively). TL was significantly shorter at high stage either in Hom (p<0.0001) or in Het (p<0.005). At early replication cycles ABCG1 gene expression was about 3-fold higher in Hom compared to Het cells (0.44 vs 0.14 arbitrary unit). CONCLUSIONS: ABCA1 gene mutation may have "gene-dosage way" effect on in vitro fibroblast senescence. Furthermore, increased ABCG1 and LDLR gene expression could highlight a role of ABCA1 on cytoskeleton regulation associated to cell cholesterol metabolism.

Lipid parameters in a hyperendemic area for malaria.

BACKGROUND: This is a cross-sectional study with the objective to analyze lipid parameters of individuals living in Brazilian Amazon, where malaria is endemic. METHODS: The city chosen was Anajás in the state of Pará, Brazil, in Amazon region. The study analyzed lipid parameters of 46 subjects, 31 male and 15 female, aged between 20-60 years without malaria, and residents for more than five years in this city considered an area hyperendemic for disease. It was established three groups according to the number of previous episodes of malaria: group I (n = 22) one to five episodes, group II (n = 20) six to ten episodes and group III (n = 4) eleven to fifteen episodes. Total cholesterol, high density lipoprotein (HDL cholesterol), and low density lipoprotein (LDL cholesterol) were measured and was confected the thick smear for malaria of all individuals. RESULTS: The hypocholesterolemia, the main characteristic of hyperendemic areas for malaria, was confirmed, but the mean of HDL cholesterol levels were 9.78% higher than the reference of World Health Organization. CONCLUSION: Although other factors might have contributed to lipid profile, the constant exposure to infection by Plasmodium, according to the physiology of the parasite, may have played an important role in defining the lipid parameters observed for this region. Further studies, such as the case-control is needed to confirm this hypothesis.

A sudden onset and the spontaneous remission of severe hypo-high-density lipoprotein cholesterolemia without serious underlying disease: a case report.

BACKGROUND: Severe hypo-high-density lipoprotein (HDL) cholesterolemia is defined by serum values less than 20mg/dl. Few acquired cases, without serious underlying disease, have been reported. CASE: An asymptomatic 75-y-old man was admitted for evaluation of low serum HDL-cholesterol (HDL-C) levels (2-8 mg/dl). The record of periodic medical examinations revealed that a sudden decrease had occurred 5 y ago. Mild anemia and proteinuria were noted but the liver and thyroid function tests were normal. ß-Quantification revealed a relatively low HDL-C (10.8 mg/dl) and the serum lecithin cholesterol acyltransferase (LCAT) activity was low (29.4 nmol/ml/h). Unexpectedly, serum HDL-C levels recovered 2 y after hospital discharge. In addition, the serum LCAT activity, hemoglobin concentrations, and urine protein tests all returned to within the reference interval. Subsequent examinations could not clarify the cause of the sudden onset and spontaneous recovery of the extremely low HDL-C. CONCLUSIONS: We describe an unusual case of acquired HDL-C deficiency in a 75-y-old man that did not have serious pre-existing disease. Recently, extremely low HDL-C levels in patients with the nephrotic syndrome, associated with acquired LCAT deficiency, have been reported. The present case might illustrate a milder form of this disorder, because the clinical findings show many similarities.

Impact of ApoB-100 expression on cognition and brain pathology in wild-type and hAPPsl mice.

During their lifetime, people are commonly exposed to several vascular risk factors that may affect brain ageing and cognitive function. In the last few years, increasing evidence suggests that pathological plasma lipid profiles contribute to the pathogenesis of late-onset Alzheimer's disease. Importantly, hypercholesterolemia, especially elevated low-density lipoprotein cholesterol values, that is, increased apolipoprotein B-100 (ApoB-100) levels, represents an independent risk factor. In this study, the effects of ApoB-100 overexpression, either alone or in combination with cerebral expression of human amyloid precursor protein (hAPP), on cognitive functions and brain pathology were assessed. Our results show that ApoB-100 overexpression induces memory decline and increases cerebral lipid peroxidation and amyloid beta levels compared to those in wild-type animals. Although double-transgenic ApoBxAPP animals did not develop more distinct behavioral deficits than single-transgenic hAPP littermates, hApoB-100 expression caused additional pathophysiological features, such as high LDL and low HDL-cholesterol levels, increased lipid peroxidation, and pronounced ApoB-100 accumulation in cerebral vessels. Thus, our results indicate that ApoBxAPP mice might better reflect the situation of elderly humans than hAPPsl overexpression alone.

The Year in Cardiology 2012: focus on cardiovascular disease prevention.

Current data suggest that advances in cardiovascular (CV) treatment have resulted in significant reduction in CV mortality but also in prolongation of life with disability. Focus on CV prevention is likely to reverse this unfavourable trend. In this review we provide information on the new European guidelines on CV prevention and discuss biomarkers and vascular imaging techniques which can assist in refining CV risk prediction. Finally, we provide new information on lifestyle and pharmacological advances which are likely to result in significant CV risk reduction.

ABCA1 mutation carriers with low high-density lipoprotein cholesterol are characterized by a larger atherosclerotic burden.

AIMS: Low HDL-C is a potent risk factor for cardiovascular disease (CVD). Yet, mutations in ABCA1, a major determinant of circulating HDL-C levels, were previously not associated with CVD risk in cohort studies. To study the consequences of low plasma levels of high-density lipoprotein cholesterol (HDL-C) due to ATP-binding cassette transporter A1 (ABCA1) dysfunction for atherosclerotic vascular disease in the carotid arteries. METHODS AND RESULTS: We performed 3.0 Tesla magnetic resonance imaging (MRI) measurements of the carotid arteries in 36 carriers of high impact functional ABCA1 mutations and 36 normolipidemic controls. Carriers presented with 42% lower HDL-C levels (P < 0.001), a larger mean wall area (18.6 ± 6.0 vs. 15.8 ± 4.3 mm(2); P = 0.02), a larger mean wall thickness (0.82 ± 0.21 vs. 0.70 ± 0.14 mm; P = 0.005), and a higher normalized wall index (0.37 ± 0.06 vs. 0.33 ± 0.04; P = 0.005) compared with controls, retaining significance after adjustment for smoking, alcohol consumption, systolic blood pressure, diabetes, body mass index, history of CVD, LDL-C, and statin use (P = 0.002). CONCLUSION: Carriers of loss of function ABCA1 mutations display a larger atherosclerotic burden compared with age and sex-matched controls, implying a higher risk for CVD. Further studies are needed to elucidate the full function of ABCA1 in the protection against atherosclerosis. These data support the development of strategies to up-regulate ABCA1 in patients with established CVD.

U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments. OBJECTIVES: To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect. METHODS: Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature. RESULTS: The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting. CONCLUSION: Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose.