Higher High-density Lipoprotein Levels Research Articles

STATIN TREATMENT REDUCES PEBETA-1 HDL LEVELS IN DYSLIPIDEMIC PATIENTS

Prebeta-1 HDL is a small molecular species of high-density lipoprotein (HDL) that is the principal acceptor of cholesterol effluxed from macrophages. High prebeta-1 HDL levels are associated with increased risk of structural coronary artery disease (CAD) and myocardial infarction. Prebeta-1 HDL

Macrophage functions in atherosclerosis.

Atherosclerosis is a chronic inflammatory disease of the arterial wall instigated by the excessive accumulation of lipoproteins; monocyte recruitment and their differentiation into macrophages in the subendothelial space. Repeated failure of innate immune responses to clear subintimal low-density lipoprotein (LDL), results in the deposition of lipid-laden macrophages or foam cells. Foam cells secrete proinflammatory mediators that facilitate lipoprotein retention and maintain vascular inflammation.1 Advancement of lesion is characterized by the apoptosis of these macrophages in the lipid core. Macrophage apoptosis plays a dual role in atherosclerosis. In early fatty streaks lesions, efferocytosis removes apoptotic cells and prevents lesion development, whereas in the advanced lesions, efferocytosis is not efficient to clear the apoptotic debri, leading to the formation of necrotic core which further enhances inflammation and atherogenesis.2 Accumulating indirect evidence suggests that the antiatherogenic role of high density lipoprotein (HDL) could at least in part, be due to its ability to stimulate cholesterol efflux from macrophages by ATP-binding cassette transporter A1 and G1 (ABCA1 and ABCG1). Complementing this notion, recent studies by Westerterp et al3 show that macrophage deficiency of ABCA1/G1 enhances lipid accumulation in macrophages, atherosclerosis and lesion inflammation. These authors observed that macrophage foam cells in spleen facilitate monocytosis which is inhibited by ABCA1/G1 and high levels of HDL. Studies by Ramirez et al4 demonstrate that activation of liver X receptor (LXR) augments the transcription of microRNA 144 (miR144) and inhibition of miR144 in macrophages upregulates ABCA1 expression and cholesterol efflux. In vivo, supplementation of mice with miR144 suppresses ABCA1 expression in the liver and reduces plasma HDL levels. Silencing of miR144 …

Ventilatory function and cardiovascular disease risk factors: a cross-sectional study in young adults.

BackgroundThe association between impaired lung function and cardiovascular disease (CVD) risk factors has been shown in adults. However, there is little evidence of such an association in young adults, particularly from South America, where the burden of CVD and chronic obstructive pulmonary disease (COPD) is as high as that observed in more developed countries. We therefore investigated the relation between CVD risk factors including metabolic syndrome (MS), and lung function status in young adults from Chile.Methods970 subjects from a sample of 998 adults born between 1974 and 1978 in Limache, Chile, were studied. A Spanish translation of the European Community Respiratory Health Survey (ECRHS) questionnaire was used. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured. Weight, height, waist circumference (WC), blood pressure, Homeostatic model assessment (HOMA-IR), triglycerides, high density lipoprotein (HDL), glycaemia, and metabolic syndrome (MS) were also assessed.ResultsThe prevalence of MS was 11.8%. A lower FEV1 and lower FVC were associated with having MS (β-coefficient -0.13; 95% Confidence Interval [CI] -0.21 to -0.05, and β-coefficient -0.18; 95% CI -0.27 to -0.09, respectively). Both spirometric measures were also negatively associated with having an elevated HOMA-IR (β-coefficient for FEV1 -0.08; 95% CI -0.13 to -0.03, and β-coefficient for FVC -0.11; 95% CI -0.17 to -0.05). In males only, a lower FEV1 and FVC were associated with having elevated triglycerides (β-coefficient highest vs. lowest tertile -0.13, 95% CI -0.24 to -0.03, and β-coefficient -0.13, 95% CI -0.25 to -0.01, respectively). In women, a higher FEV1 and FVC were statistically significantly related to having higher levels of HDL. Ventilatory function was unrelated to hypertension or WC in this population.ConclusionIn this population-based study of young adults, a poorer ventilatory function was associated with many CVD risk factors. Endeavours to understand better causality issues of such associations are warranted.

Impact of acculturation on cardiovascular risk factors among elderly Mexican Americans

PurposeHigher levels of acculturation among Latinos have been shown to be associated with a higher prevalence of cardiovascular (CV) risk factors in some studies of middle-age persons. The association of acculturation and prevalence of CV risk factors in elderly Latinos is less well established. MethodsAcculturation was measured using the validated bidimensional Acculturation Rating Scale for Mexican Americans-II. We conducted a cross-sectional analysis of the association of acculturation with prevalence of CV risk factors among 1789 elderly men and women from the Sacramento Area Latino Study on Aging using multivariate linear and logistic regression. We tested for the interaction of acculturation with risk factors by nativity status. ResultsMedian age was 69.8 years. Higher acculturation was associated with lower systolic blood pressure, lower low-density lipoprotein, higher high-density lipoprotein, and lower prevalence of CV disease after age and sex adjustment. Higher acculturation remained associated with lower level of low-density lipoprotein and higher level of high-density lipoprotein after full adjustment. Nativity status did not affect these results. ConclusionsContrary to other reports in middle-aged persons, higher levels of acculturation were associated with better lipid profiles and no significant differences in other CV risk factors by acculturation level in elderly Latinos.

Age-Related Macular Degeneration: Prevalence and Risk Factors from Korean National Health and Nutrition Examination Survey, 2008 through 2011

To investigate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. A cross-sectional study using a complex, stratified, multistage, probability-cluster survey, which can produce nationally representative estimates. Using the database of Korean National Health and Nutrition Examination Survey from 2008 through 2011, 14 352 participants 40 years of age or older with gradable fundus photographs were included. Age-related macular degeneration was determined by fundus photograph. Prevalences of AMDs were estimated. Risk factor analyses were conducted using logistic regression analyses (LRAs). Prevalence and risk factors of AMD. The prevalence of AMD was 6.62% (95% confidence interval [CI], 6.15%-7.09%) in the Korean population: 6.02% (95% CI, 5.56%-6.48%) were early AMD and 0.60% (95% CI, 0.45%-0.75%) were late AMD. The prevalence of early AMD in women (6.73%; 95% CI, 6.11%-7.35%) was higher than that in men (5.25%; 95% CI, 4.61%-5.89%; P<0.001), and the prevalence of late AMD in women (0.37%; 95% CI, 0.22%-0.52%) was lower than that in men (0.85%; 95% CI, 0.59%-1.12%; P<0.001). However, in multiple LRAs both early and late AMD had no association with gender, house income, residence, sun exposure, or systemic comorbidities, including hypertension, diabetes mellitus, and cardiovascular diseases. Early AMD had positive associations with older age groups (P<0.001), lower education (P = 0.027), occupation (P<0.001), anemia (P = 0.027), hepatitis B surface antigen carrier status (P<0.001), not being overweight (body mass index [BMI], P = 0.032; waist circumference, P = 0.041, in separate analyses), and higher serum high-density lipoprotein (HDL) level (P = 0.046), but not with smoking status. Late AMD had positive associations with age groups (P<0.001), current smokers (P = 0.022), and lower BMI (P = 0.037). The results suggest that there are 1.21 million individuals with early AMD and 121 000 individuals with late AMD in Korea. Nonoverweight status and higher HDL levels, generally assumed as positive health indicators, as well as anemia and hepatitis B infection had harmful associations with AMD in our study, implying a possible different pathophysiologic process of AMD in Asians compared with that of white persons.

Temporal course of neointimal hyperplasia following drug-eluting stent implantation: a serial follow-up optical coherence tomography analysis.

We sought to evaluate the temporal course of neointimal hyperplasia (NIH) after drug-eluting stent (DES) implantation, using serial optical coherence tomography (OCT). We identified 89 DES (82 patients) that had at least three consecutive cross-sections with a mean NIH thickness >100 µm on first follow-up OCT. Qualitative and quantitative changes in NIH were then assessed at a second follow-up OCT. NIH regression and progression were defined as a decrease or increase in mean NIH cross-sectional area >0.2 mm2, respectively, between the two studies. Between the first and second OCT there was a decrease in NIH in 29 lesions (32.6%), and an increase in NIH in 37 lesions (41.6%). Compared to patients with neointimal progression, those with regression showed lower levels of high sensitivity C-reactive protein (hsCRP) (p = 0.036) and higher levels of high-density lipoprotein (p = 0.012). Between the first and the second OCT, there were no significant changes in NIH morphologic patterns in 67 (75.3%) of 89 DES. In lesions with NIH regression, the evolution of heterogeneous to homogeneous neointima was observed, while the evolution of heterogeneous or homogeneous to layered neointima or the evolution of heterogeneous, homogeneous, or layered neointima to neoatherosclerosis was detected in lesions with NIH progression (p < 0.001). The hsCRP level at index procedure was significantly associated with neointimal regression in multivariate model (odds ratio 0.891, 95% confidence interval 0.796-0.999, p = 0.048). During late follow-up, OCT shows both NIH progression and regression that are paralleled by qualitative changes indicating increasing stability (in regression) and increasing instability (in progression).

Serum lipids, recent suicide attempt and recent suicide status in patients with major depressive disorder

Major depressive disorder (MDD) is associated with suicide. Although several studies have reported its association with low serum lipid, few studies have investigated relationships between current suicidality and lipid profiles, comparing with other blood measures in MDD patients. The study population consisted of 555 subjects with MDD who were ≥ 18 years old, evaluated by the Mini International Neuropsychiatric Interview (MINI) with the suicidality module. At the evaluation visit, we measured serum lipid profiles including total cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL), and blood measures such as fasting glucose, total protein, albumin, blood urea nitrogen, creatinine, thyroid hormones, red and white blood cells, platelet count, hemoglobin, and hematocrit. Recent attempters who had attempted suicide within the past month showed significantly lower TG and higher HDL levels than lifetime and never attempters, using Tukey's post-hoc analysis. Recent attempters exhibited lower TG and higher HDL than those with recent suicide ideation and wish to self-harm and those without previous attempt. Linear regression analysis revealed that TG was negatively associated with current suicidality scores (β = -0.187, p = 0.039), whereas VLDL was positively associated with the recent suicide status (β = 0.198, p = 0.032) after controlling for age and sex. There were no significant differences between the groups in terms of other serum lipid profiles and blood measures. Low serum TG, high HDL and VLDL levels are associated with recent suicide attempt or recent suicide status in patients with MDD.

Serum Osteocalcin Is Significantly Related to Indices of Obesity and Lipid Profile in Malaysian Men

Background and aim: Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men.Methods: A total of 373 men from the Malaysian Aging Male Study were included in the analysis. Data on subjects' demography, body mass index (BMI), body fat (BF) mass, waist circumference (WC), serum osteocalcin and fasting lipid levels were collected. Bioelectrical impendence (BIA) method was used to estimate BF. Multiple linear and binary logistic regression analyses were performed to analyze the association between serum osteocalcin and the aforementioned variables, with adjustment for age, ethnicity and BMI.Results: Multiple regression results indicated that weight, BMI, BF mass, BF %, WC were significantly and negatively associated with serum osteocalcin (p < 0.001). There was a significant positive association between serum osteocalcin and high density lipoprotein (HDL) cholesterol (p = 0.032). Binary logistic results indicated that subjects with low serum osteocalcin level were more likely to be associated with high BMI (obese and overweight), high BF%, high WC and low HDL cholesterol (p < 0.05). Subjects with high osteocalcin level also demonstrated high total cholesterol level (p < 0.05) but this association was probably driven by high HDL level. These variables were not associated with serum C-terminal of telopeptide crosslinks in the subjects (p > 0.05).Conclusion: Serum osteocalcin is associated with indices of obesity and HDL level in men. These relationships should be validated by a longitudinal study, with comprehensive hormone profile testing.

Abstract 9258: LDL Phenotype-B is Strongly Associated With CHD Risk Among Individuals With CKD. The Multi-ethnic Study of Atherosclerosis (MESA)

Introduction: LDL phenotype B, characterized by high triglyceride (TG), small dense LDL (sd-LDL), and very low-density lipoprotein (VLDL) levels, and low high-density lipoprotein (HDL) levels, is the hallmark lipid phenotype of chronic kidney disease (CKD). Whether this phenotype is associated with clinical coronary heart disease (CHD) in individuals with CKD is not known. Methods: CKD was defined as an eGFR of 15-59 ml/min/1.63m2 (stage 3-4). Principal component analyses were used to account for the correlations among lipoproteins defining lipid phenotype B. Nuclear magnetic resonance spectroscopy was used to measure lipoprotein sub-fractions. CHD was defined as a new MI, angina followed by revascularization, resuscitated cardiac arrest or CHD death. Results: A total of 6,814 individuals free of CHD at baseline were followed for a median time of 8.5 years. CHD developed in 303 individuals (5%) with eGFR≥60 and in 72 individuals (12%) with CKD (p for difference&lt;0.001). Principal component 1 captured the lipoprotein abnormalities defining lipid phenotype B: high TG levels (r for correlation with PC1=0.78), VLDL (r=0.73), sd-LDL(r=0.82) and low levels of HDL (r=-0.80). Compared to those without CKD, this phenotype (and its components) was more common (p for difference&lt;0.001), and was more strongly associated with CHD in those with CKD (figure): adjusted hazard ratios and 95% confidence intervals 1.13 (1.00-1.28; p=0.05) and 1.51 (1.17-1.94; p=0.001) in eGFR≥60 and CKD respectively (p for interaction=0.04). Conclusion: LDL phenotype-B is strongly associated with CHD risk in individuals with CKD. Whether a modification of the components of this phenotype leads to a reduction in the cardiovascular disease burden of individuals with CKD should be established in future studies.

APOM and high-density lipoprotein cholesterol are associated with lung function and per cent emphysema.

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.

The Association of Serum Lipids With Colorectal Adenomas

There is suggestive but sparse evidence that dyslipidemia is associated with colorectal neoplasms. We investigated the association of serum lipid and apolipoprotein concentrations with the prevalence of colorectal adenomas. Cross-sectional study of 19,281 consecutive participants aged 40-79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. We identified 5,958 participants with colorectal adenomas (30.9%), including 5,504 (28.5%) with non-advanced adenomas and 454 (2.4%) with advanced adenomas. The adjusted relative prevalence ratios (aRPRs) comparing the fourth with the first quartiles of serum triglycerides were 1.35 (95% confidence interval (CI) 1.20-1.52; P trend<0.001) for non-advanced adenomas and 1.45 (95% CI 1.02-2.06; P trend=0.005) for advanced adenomas. Higher levels of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1 (ApoA-1) were significantly associated with 12% (Q4 vs. Q1 aRPR 1.12; 95% CI 1.00-1.26; P trend=0.049) and 17% (Q4 vs. Q1 aRPR 1.17; 95% CI 1.04-1.31; P trend=0.004) higher prevalence of non-advanced adenoma. There was also a non-significant association between higher levels of low-density lipoprotein (LDL) cholesterol (Q4 vs. Q1 aRPR 1.22; 95% CI 0.91-1.66; P trend= 0.12) and apolipoprotein B (ApoB) (Q4 vs. Q1 aRPR 1.32; 95% CI 0.94-1.83; P trend=0.07) with higher prevalence of advanced adenoma. There was no association between total cholesterol levels with colorectal adenoma. In this large cross-sectional study, higher levels of serum triglycerides were significantly associated with an increasing prevalence of both non-advanced and advanced colorectal adenomas, while higher levels of ApoA-1 and HDL cholesterol were significantly associated with an increasing prevalence of non-advanced adenomas.

Systematic review of Wild Rice: an ancient grain with modern benefits

Wild rice (Zizania sp.) grows in shallow waters of North America and is distinct from white rice (Oryza sp.). The recent trend toward gluten free foods and ancient grains presents an opportunity for increased interest in the health benefits of wild rice. Wild rice is classified as a whole grain and typically contains 74% starch, 6.8% dietary fiber, 14% protein, and 0.7–0.9% of lipids. Wild rice is a good source of dietary fiber and has a good protein efficiency ratio (1.7), which is high for a grain. The lipid content is low; however most of the lipids are Ω‐6 (35–37%) and Ω‐3 (20–31%) fatty acids with a very favorable ratio of (1.1). In addition to macronutrient content, wild rice contains phytosterols levels several times higher than other grains. Furthermore, the antioxidant activity of wild rice is between 10–15 times higher than white rice. A new study of wild rice added to a high fat/cholesterol diet showed significant attenuation of serum free fatty acids, total cholesterol, and triglyceride levels while maintaining higher high density lipoprotein levels compared to control. The exact explanation of the protective mechanism of wild rice is uncertain, but the dietary fiber, phytosterol, or antioxidant capacity of wild rice may be the reason for this. Current interest in ancient grains and gluten‐free diets, as well as antioxidants and phytochemicals, makes wild rice an attractive grain addition to the diet.Grant Funding Source: MN Wild Rice Council

GAMBARAN KADAR HIGH DENSITY LIPOPROTEIN DARAH PADA LAKI-LAKI BERUSIA 40-59 TAHUN DENGAN INDEKS MASSA TUBUH ≥23 kg/m2

Abstract: High density lipoprotein (HDL) is a lipoprotein containing apo A-1, associated with other apolipoproteins. One of the HDL functions is as the reversed transporter of cholesterol in order to reduce cholesterol level in peripheral tissues. Low HDL cholesterol level is often related to obesity. High cholesterol level, obesity, and low HDL level are known as risk factors of coronary heart diseases. Overweight subjects have higher probabality for suffering from heart diseases and stroke. This study aimed to elaborate high density lipoprotein (HDL) levels in males aged 40-59 years with body mass index higher than 23 kg/m2. This study used consecutive sampling method. Total subjects involved in this study were 20 males who lived in Malalayang. The results showed that there were 11 subjects with normal HDL levels and nine subjects (45%) with low HDL levels (&lt;45 mg/dL). No subjects had high HDL level. Nineteen subjects (95%) were classified as obesity and only one subject (5%) as overweight. Conclusion: Most of the males 40-59 aged with body mass index ≥23 kg/m2 who lived in Malalayang Manado has normal HDL level. Keywords: males, high density lipoprotein, body mass index Abstrak: High density lipoprotein (HDL) ialah lipoprotein yang mengandung apoA-I, disamping apolipoprotein lainnya. Salah satu fungsi HDL ialah transpor balik kolesterol untuk menurunkan kadar kolesterol di jaringan perifer. Rendahnya kolesterol HDL sering dikaitkan dengan obesitas. Tingginya kolesterol, obesitas, dan rendahnya kadar HDL merupakan faktor risiko penyakit jantung koroner. Individu dengan berat badan berlebihan berpeluang lebih besar untuk terkena penyakit jantung dan stroke. Penelitian ini bertujuan untuk mengetahui gambaran kadar high density lipoprotein (HDL) pada laki-laki berusia 40-59 tahun dengan indeks massa tubuh ≥23 kg/m2. Metode penelitian yang digunakan ialah consecutive sampling. Subyek penelitian berjumlah 20 orang laki-laki yang berdomisili di Kecamatan Malalayang Manado. Hasil penelitian memperlihatkan 11 subyek (55%) dengan kadar HDL normal, sembilan subyek (45%) dengan kadar HDL rendah (&lt;45 mg/dL); dan tidak ada (0%) yang memiliki kadar HDL tinggi (&gt;60 mg/dL). Terdapat 19 subjek (95%) dengan obesitas dan hanya satu subjek (5%) yang mengalami overweight. Simpulan: Sebagian besar laki-laki berusia 40-59 tahun yang berdomisili di Kecamatan Malalayang Manado dengan indeks massa tubuh ≥23 kg/m2 mempunyai kadar HDL normal. Kata kunci: laki-laki, high density lipoprotein, indeks massa tubuh

Estimation of lipid profile and glucose level in alloxan-induced diabetic rats treated with Cymbopogon citratus (lemongrass)

Objective: Cymbopogon citratus extract has been reported to have hypoglycemic properties but not much is known about its hypolipidemic effects. In this study it was aimed to demonstrate the hypolipidemic and hypoglycemic potentials of Cymbopogon citratus extract on alloxan-induced diabetic rats. Methods: Eighteen male albino rats of weights between 106-118 g were used for the study and divided into three groups of six rats each. The rats of the non-diabetic control group were given 1 ml of distilled water daily. Two other groups induced with diabetes using alloxan by a single dose administration of 120 mg/kg body weight (BW); one of these diabetic rat groups were treated with Cymbopogon citratus extract daily at 1.5 ml/100 g BW for 4 weeks while the other group was left untreated. Blood samples were collected and total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and glucose levels were assayed. Results: After four weeks of treatment, data indicated significant reductions in BW, blood glucose, TG, TC and LDL levels of diabetic rats treated with Cymbopogon citratus extract compared to the non-treated group. The treated diabetic rats also indicated significantly higher HDL levels compared to the non-treated group. Conclusion: Treatment of diabetic rats with the Cymbopogon citratus extract lowered blood glucose, TG, TC and LDL levels and increased the HDL level. This shows that the extract has both hypoglycemic and hypolipidemic effects.

Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome

BackgroundIn observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes.MethodsWe randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation.ResultsAt the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P=0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (P<0.001 for both comparisons).ConclusionsIn patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann–La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)

High-Density Lipoprotein Function, Dysfunction, and Reverse Cholesterol Transport

Although high high-density lipoprotein (HDL)-cholesterol levels are associated with decreased cardiovascular risk in epidemiological studies, recent genetic and pharmacological findings have raised doubts about the beneficial effects of HDL. Raising HDL levels in animal models by infusion or overexpression of apolipoprotein A-I has shown clear vascular improvements, such as delayed atherosclerotic lesion progression and accelerated lesion regression, along with increased reverse cholesterol transport. Inflammation and other factors, such as myeloperoxidase-mediated oxidation, can impair HDL production and HDL function, with regard to its reverse cholesterol transport, antioxidant, and anti-inflammatory activities. Thus, tests of HDL function, which have not yet been developed as routine diagnostic assays, may prove useful and be a better predictor of cardiovascular risk than HDL-cholesterol levels.

Adult‐type hypolactasia and calcium intake in polycystic ovary syndrome

Adult-type hypolactasia (ATH) is related to lower calcium and milk intake, which might be associated with obesity and metabolic disturbances. Women with polycystic ovary syndrome (PCOS) frequently suffer from metabolic disturbances including central obesity. We aimed to examine the association of ATH and calcium intake with anthropometric, metabolic and endocrine parameters in a cohort of PCOS and control women. Metabolic, endocrine and anthropometric measurements and oral glucose tolerance tests were performed in 504 PCOS and 366 control women. Genotyping of ATH, defined by the -13910 variant of the MCM6 gene, was performed. Calcium intake was assessed by questionnaires. Adult-type hypolactasia was more prevalent in PCOS women (29·8%) than in controls (23·5%) (P = 0·040). PCOS women with ATH had higher waist-to-hip ratio (WHR) (0·80 [0·75-0·88] vs 0·78 [0·73-0·85], P = 0·046), glucose 2 h (5·28 [4·57-6·33] mmol/l vs 5·67 [4·68-6·78] mmol/l, P = 0·037), HbA1c (5·2 [5·0-5·4]%vs 5·1 [5·0-5·3]%, P = 0·009), parathyroid hormone (3·72(2·91-4·86] pmol/l vs 3·61 [2·94-4·63] pmol/l, P = 0·030) and Ferriman-Gallwey-Scores (FG Scores) (7 [3-12] vs 4 [1-9], P = 0·002) and lower 25(OH)D levels (54·4 [35·2-80·6] nmol/l vs 68·4 [49·7-89·4] nmol/l, P < 0·001) than PCOS women without ATH. The association of 25(OH)D and FG-Scores with ATH remained significant in age-, BMI- and WHR-adjusted analyses. PCOS women within the highest quartile of calcium intake had significantly lower testosterone (P = 0·023) and androstenedione (P = 0·032) and significantly higher high-density lipoprotein (HDL) levels (P = 0·035) than PCOS women with lower calcium intake. Our results indicate an association of ATH with PCOS susceptibility. Moreover, ATH might influence WHR, HbA1c and FG-Scores as well as 25(OH)D levels. Higher calcium intake was associated with lower androgens and higher HDL levels.

Comprehensive Intensive Therapy for Chinese Gestational Diabetes Benefits Both Newborns and Mothers

This study identified the impact of intensive therapy on neonatal outcomes in women with gestational diabetes mellitus (GDM) and determined the effects on the postpartum metabolic status of the mothers. In total, 127 pregnant women with GDM were randomly selected to receive an intensive treatment regimen, which included one-to-one education, lifestyle intervention, scheduled clinic visits, strict glucose control, and frequent glucose self-monitoring. Meanwhile, 148 age-matched pregnant women with GDM were selected as controls and given the standard treatment regimen. Pregnancy outcomes including parameters related to the GDM mothers and to their neonates were comparatively analyzed between the two treatment groups. GDM patient follow-up (range, 1-3 years after delivery) included an oral glucose tolerance test and measurements of lipid concentration and insulin secretion. The insulinogenic index (ΔInsulin(30 min)/ΔBlood glucose(30 min)) and homeostasis model assessment index of β-cell function and insulin resistance were calculated. The patients' demographic and anthropometric data were also recorded for comparative analysis. Compared with GDM patients receiving standard treatment, GDM patients receiving intensive treatment had lower instances of premature delivery (2.4% vs. 8.3%, P<0.05) and neonatal care unit admission (21.3% vs. 33.3%, P<0.05) and lower neonatal birth weight (3.26±0.53 vs. 3.45±0.55 kg, P<0.0001). At follow-up, GDM patients from the intensive treatment group had a smaller waist circumference (75.83±3.11 vs. 78.34±4.20 cm, P<0.01), lower 30-min glucose levels after a 75-g glucose load (8.26±1.85 vs. 9.46±2.74 mmol/L, P<0.05), and higher high-density lipoprotein levels (1.30±0.24 vs. 1.18±0.23 mmol/L, P<0.05). The intensive GDM treatment regimen led to healthier outcomes for the women, the neonates, and the birth event and was associated with better maternal metabolic situations in the months and years after delivery.

Effect of Two Intensive Statin Regimens on Progression of Coronary Disease

After 104 weeks of therapy, the rosuvastatin group had lower levels of LDL cholesterol than the atorvastatin group (62.6 vs. 70.2 mg per deciliter [1.62 vs. 1.82 mmol per liter], P<0.001), and higher levels of high-density lipoprotein (HDL) cholesterol (50.4 vs. 48.6 mg per deciliter [1.30 vs. 1.26 mmol per liter], P = 0.01). The primary efficacy end point, percent atheroma volume (PAV), decreased by 0.99% (95% confidence interval [CI], −1.19 to −0.63) with atorvastatin and by 1.22% (95% CI, −1.52 to −0.90) with rosuvastatin (P = 0.17). The effect on the secondary efficacy end point, normalized total atheroma volume (TAV), was more favorable with rosuvastatin than with atorvastatin: −6.39 mm 3 (95% CI, −7.52 to −5.12), as compared with −4.42 mm 3 (95% CI, −5.98 to −3.26) (P = 0.01). Both agents induced regression in the majority of patients: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (P = 0.07) and 64.7% and 71.3%, respectively, for TAV (P = 0.02). Both agents had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events. Conclusions Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups. (Funded by AstraZeneca Pharmaceuticals; ClinicalTrials.gov number, NCT000620542.)

Familial Amyloid Polyneuropathy Associated with S50A, S52P and G47A Mutations (P03.185)

Objective: We aim to describe the main characteristics of patients with 3 different TTR mutations. Background Familial amyloid polyneuropathy is a late-onset inherited amyloidosis associated with a mutation on the transthyretin (TTR) gene. Marked diversity exists in clinical characteristics. Design/Methods: 33 patients from 10 different families with proven TTR mutation (27 S50A, 4 S52P, and 2 G47A) underwent prospective neurologic and autonomic examination. All evaluations were performed in a period of 12 months. Results: 19 male and 14 women were included. Age at onset was later in the patients with G47A mutation (33 vs 38 vs 42 yo). S52P had more weight loss (mean of 26kg vs 12-13kg) Initial symptoms were neuropathic in 66%, gastrointestinal in 18% and autonomic in 3%. Overall, men had a more severe form of the disease and worse prognosis. Specifically, men showed more GI (15 vs 11, p:0.001), GU (4 vs 13, p:0.17), and autonomic (13 vs 5, p:0.039) symptoms, had further weight loss (13±17 vs 8±4 kg, p:0.005), orthostatic SBP fall (26±15 vs 4.5±10 mmHg, p:0.01), and decreased NCV amplitudes (sensitive median 4.40 vs 7.20mV p:0.040, sural 2.5 vs 10.4mV p:0.000, motor median 2.4 vs 4.4mV p:0.014, and tibial 2.7 vs 5.8mV p:0.000 nerves). Three men (15.7%) and one woman (7.2%) died during the study period. The men died at a younger age (44±3.5 vs 62, p:0.049). Conclusions: S52P mutation showed a more aggressive course. Because the hereditary mode is autosomal dominant, no gender differences should be expected. However, 1-2% of plasma TTR circulates bound to high-density lipoprotein (HDL). The higher HDL levels associated with estrogen could explain these differences. Men should be considered for earlier liver transplant or pharmacologic treatment when available. It is possible that measures aimed to increase HDL may have some impact in the natural history of the disease. Disclosure: Dr. Gonzalez Duarte has nothing to disclose. Dr. Cardenas-Soto has nothing to disclose. Dr. Berenguer-Sanchez has nothing to disclose. Dr. Martinez-Banos has nothing to disclose. Dr. Estanol has nothing to disclose. Dr. Garcia-Ramos has nothing to disclose. Dr. Cantu-Brito has nothing to disclose.