HDL Cholesterol and Non-Cardiovascular Disease: A Narrative Review.

High density lipoprotein (HDL) cholesterol has traditionally been considered the "good cholesterol", and most of the research regarding HDL cholesterol has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within atherosclerotic cardiovascular disease. Randomized trials aiming at increasing HDL cholesterol have, however, failed and left questions to what role HDL cholesterol plays in human health and disease. Recent observational studies involving non-cardiovascular diseases have shown that high levels of HDL cholesterol are not necessarily associated with beneficial outcomes as observed for age-related macular degeneration, type II diabetes, dementia, infection, and mortality. In this narrative review, we discuss these interesting associations between HDL cholesterol and non-cardiovascular diseases, covering observational studies, human genetics, and plausible mechanisms.

Association between maternal blood lipids levels during pregnancy and risk of small-for-gestational-age infants.

Dyslipidemia in pregnancy are associated with risk of adverse outcomes. As an adverse pregnancy outcome, small-for-gestational-age has been extensively studied in Western countries. However, similar studies have rarely been conducted in Asian countries. Data were derived from 5695 pairs of non-diabetic mothers and neonates between 1 Jan 2014 and 31 Dec 2014. 5.6% neonates in our study were SGA. Serum samples were collected during second and third trimesters for evaluation on fasting lipids levels. The present study intended to explore the associations between maternal lipid profile and small-for-gestational-age neonates. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted via logistic regression analysis. After adjustments for confounders, third-trimester total cholesterol levels were associated with a decreased risk for small-for-gestational-age (aOR = 0.622, 95% CI 0.458-0.848, P = 0.002), and third-trimester high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were associated with an increased risk for small-for-gestational-age (aOR = 1.955, 95% CI 1.465-2.578, P < 0.001; aOR = 1.403, 95% CI 1.014-1.944, P = 0.041).In the highest gestational weight gain strata, especially the third-trimester, the effect of high-density lipoprotein cholesterol levels on the risk for small-for-gestational-age is larger. High high-density lipoprotein cholesterol level during third trimester could be considered as indicators of a high-risk of small-for-gestational-age, regardless of gestational weight gain.

Waist Circumference Above 80 cm Predicts Increased Systolic Blood Pressure in Healthy Young Adult Women

Abstract Background: Among anthropometric measures for assessing adiposity-related risk, waist circumference (WC) is simple and fast to perform. Cut-off values for WC proposed by the International Diabetes Federation (IDF), and the Adult Treatment Panel III of the National Cholesterol Education Program (NCEP-ATP III) are categorized by gender and are not age-specific. Objective: To analyze the association between WC and cardiometabolic risk factors in adult women. Methods: A total of 164 healthy adult women were grouped by WC according to IDF and NCEP-ATP III cutoff values. Continuous variables were described as mean ± standard deviation or median (interquartile range). The Shapiro-Wilk test was used to assess the normality of data. Variables were analyzed by unpaired Student's t-test, Mann-Whitney U and Kruskal-Wallis tests. The correlation of WC categories with systolic (SBP) and diastolic (DBP) blood pressure, fasting blood glucose, high-density lipoprotein cholesterol (HDL-c), and triglycerides were examined by Spearman's rho correlation coefficient and linear regression analysis. A p value < 0.05 was considered statistically significant. Results: Increased WC showed a significant correlation with SBP, DBP, glucose, HDL-c, and triglycerides. In bivariate linear regression, approximately 63.0 % of the variability of SBP (≥ 130 mmHg) among the age group 20-40 years was predicted by increased WC according to both criteria. Conclusion: A WC above 80 cm in women aged 20-40 years strongly predicted variability in SBP, calling attention to the importance of measuring WC for the monitoring and prevention of cardiovascular and metabolic diseases in women in this age group.

Triglyceride to HDL-cholesterol ratio and the incidence risk of type 2 diabetes in community dwelling adults: A longitudinal 12-year analysis of the Korean Genome and Epidemiology Study.

AIMS: Serum triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is known to be associated with cardiometabolic diseases. This study is aimed to evaluate the association between the TG/HDL-C ratio and incident type 2 diabetes with a large-sample, community-based Korean cohort over 12 years. METHODS: Among 10,038 participants, a total of 8655 participants aged 40 to 69 years without diabetes were selected from the Korean Genome and Epidemiology Study (KoGES). The baseline TG/HDL-C ratio was divided into quartiles. Newly developed type 2 diabetes was defined by any of the following: a fasting plasma glucose level ≥ 126 mg/dL; a glucose level ≥ 200 mg/dL 2-hours after a 75 g oral glucose tolerance test; an HbA1c ≥ 6.5%; or treatment with anti-diabetic therapy. The hazard ratios (HRs) with 95% confidence intervals (CIs) for incident type 2 diabetes were calculated using multivariate Cox proportional hazards regression models after adjusting for potentially confounding variables. RESULTS: During the 12-year follow-up period, type 2 diabetes developed in 1437 subjects (16.6%, 1437/8655), with incidence rate of 2.8-5.0 (over 2 years). Compared to the reference first quartile, the HRs (95% CIs) of incident type 2 diabetes in the second, third, and fourth quartiles increased in a dose-response manner after adjusting for potentially confounding variables. CONCLUSIONS: High TG/HDL-C ratio at baseline may be a useful surrogate indicator of future incident type 2 diabetes.

The effect of midlife cardiovascular risk factors on white matter hyperintensity volume and cognition two decades later in normal ageing women.

Cerebral White Matter Hyperintensity (WMH) lesions have been identified as markers of cerebrovascular diseases and they are associated with increased risk of cognitive impairment. In this study, we investigated the relationship between midlife cardiovascular risk factors and late life WMH volumes two decades later, and examined their association with cognitive performance. 135 participants from the Women's Healthy Ageing Project had completed midlife cardiovascular risk measurement in 1992 and late life brain MRI scan and cognitive assessment in 2012. In these community-dwelling normal aging women, we found that higher midlife Framingham Cardiovascular Risk Profile (FCRP) score was associated with greater WMH volume two decades later, and was predominantly driven by the impact of HDL cholesterol level, controlling for age, education and APOE ε4 status. Structural equation modelling demonstrated that the relationship between midlife FCRP score and late life executive function was mediated by WMH volume. These findings suggest intervention strategies that target major cardiovascular risk factors at midlife might be effective in reducing the development of WMH lesions and thus late life cognitive decline.

Cholesterol: Can't Live With It, Can't Live Without It.

Given its role in many biochemical processes essential to life, cholesterol remains a topic of intense research. Of all the plasma lipids, cholesterol is distinctive because it is a precursor to steroidogenic molecules, some of which regulate metabolism, and its blood concentration in the form of low- and high-density lipoprotein cholesterol (HDL-C) are positive and negative risk factors for atherosclerotic cardiovascular disease (ASCVD). New research, however, has challenged the widely held belief that high HDL-C levels are atheroprotective and is showing that both low and high plasma HDL-C levels confer an increased risk of ASCVD. Furthermore, it is disputing the widely cited mechanism involved in reverse cholesterol transport. This review explores the evolution of cholesterol research starting with the Gofman and Framingham studies, the development of traditional and emerging lipid-lowering therapies, and the role of reverse cholesterol transport in HDL cardioprotection.

Dieta aterogénica y alteración de los índices de riesgo cardiovascular / Atherogenic diet and alteration of cardiovascular risk indexes

Introducción: una alimentación muy selectiva y poco variada durante la primera infancia, puede modificar seriamente los índices de riesgo cardiovascular, ante lo cual, la detección de la alteración lipídica es de suma importancia para promover e implementar el cambio de hábitos. Caso clínico: se presenta una niña de 6 años con una dieta a base de alimentos industriales, a quien se le realizó un perfil lipídico, por considerar que la alimentación tan limitada que consumía era un factor de riesgo aterogénico. Esto permitió diagnosticar una marcada disminución del HDL-colesterol, hipertrigliceridemia y franca alteración de los índices de riesgo. Discusión: existe una relación directa entre la hipertrigliceridemia y el consumo de azúcares simples, presentes en las golosinas, postres o gaseosas. Además, las grasas saturadas e industriales (trans) son responsables de la disminución del colesterol HDL. Llamó la atención la contundencia que ejerció la alteración del laboratorio, sobre el accionar de los padres. Luego de 6 meses de poner en práctica las indicaciones, los valores y los índices de riesgo se normalizaron. Conclusiones: se destaca la importancia de realizar un perfil lipídico en niños mayores de 2 años cuando se detecta el consumo de una dieta aterogénica, dado que el descenso de colesterol HDL tiene relación directa con la alimentación y el estilo de vida. Un valor inferior a 45 mg/dL es un factor de riesgo que puede ser modificado(AU)

Introduction: a very selective and little varied diet during early childhood can seriously modify the cardiovascular risk indexes, and because of that the detection of lipid alteration is very important to promote and implement the change of habits. Clinical case: a 6-year-old girl was presented with a diet based on industrial foods. A lipid profile was made considering that the very limited diet she consumed was an atherogenic risk factor. This allowed diagnosing a marked decrease in HDL-cholesterol, hypertriglyceridemia and real alteration in the risk indexes. Discussion: there is a direct relation among hypertriglyceridemia and the consumption of simple sugars, which are present in sweets, desserts or sodas. In addition, saturated and industrial (trans) fats are responsible for lowering HDL cholesterol. It was significant the impact of the alteration in the laboratory results in the actions taken by the parents. After 6 months of putting the indications into practice, the values and risk indexes were normalized. Conclusions: it is highlighted the importance of performing a lipid profile in children older than 2 years when the consumption of an atherogenic diet is detected, since the decrease in HDL cholesterol is directly related to diet and lifestyle. A value below 45 mg/dL is a risk factor that can be modified(AU)

Dieta aterogénica y alteración de los índices de riesgo cardiovascular / Atherogenic diet and alteration of cardiovascular risk indexes

Introducción: una alimentación muy selectiva y poco variada durante la primera infancia, puede modificar seriamente los índices de riesgo cardiovascular, ante lo cual, la detección de la alteración lipídica es de suma importancia para promover e implementar el cambio de hábitos. Caso clínico: se presenta una niña de 6 años con una dieta a base de alimentos industriales, a quien se le realizó un perfil lipídico, por considerar que la alimentación tan limitada que consumía era un factor de riesgo aterogénico. Esto permitió diagnosticar una marcada disminución del HDL-colesterol, hipertrigliceridemia y franca alteración de los índices de riesgo. Discusión: existe una relación directa entre la hipertrigliceridemia y el consumo de azúcares simples, presentes en las golosinas, postres o gaseosas. Además, las grasas saturadas e industriales (trans) son responsables de la disminución del colesterol HDL. Llamó la atención la contundencia que ejerció la alteración del laboratorio, sobre el accionar de los padres. Luego de 6 meses de poner en práctica las indicaciones, los valores y los índices de riesgo se normalizaron. Conclusiones: se destaca la importancia de realizar un perfil lipídico en niños mayores de 2 años cuando se detecta el consumo de una dieta aterogénica, dado que el descenso de colesterol HDL tiene relación directa con la alimentación y el estilo de vida. Un valor inferior a 45 mg/dL es un factor de riesgo que puede ser modificado(AU)

Introduction: a very selective and little varied diet during early childhood can seriously modify the cardiovascular risk indexes, and because of that the detection of lipid alteration is very important to promote and implement the change of habits. Clinical case: a 6-year-old girl was presented with a diet based on industrial foods. A lipid profile was made considering that the very limited diet she consumed was an atherogenic risk factor. This allowed diagnosing a marked decrease in HDL-cholesterol, hypertriglyceridemia and real alteration in the risk indexes. Discussion: there is a direct relation among hypertriglyceridemia and the consumption of simple sugars, which are present in sweets, desserts or sodas. In addition, saturated and industrial (trans) fats are responsible for lowering HDL cholesterol. It was significant the impact of the alteration in the laboratory results in the actions taken by the parents. After 6 months of putting the indications into practice, the values and risk indexes were normalized. Conclusions: it is highlighted the importance of performing a lipid profile in children older than 2 years when the consumption of an atherogenic diet is detected, since the decrease in HDL cholesterol is directly related to diet and lifestyle. A value below 45 mg/dL is a risk factor that can be modified(AU)

Decreased serum HDL at initial diagnosis correlates with worse outcomes for triple-negative breast cancer but not non-TNBCs.

PURPOSE: This study aimed to evaluate the associations between metabolic syndrome (MS) and its components at initial diagnosis and outcomes of breast cancer including triple-negative breast cancer (TNBC) and non-TNBC. METHODS: A cohort of 1,391 patients was reviewed between January 2004 and July 2008 (including 394 TNBC and 855 non-TNBC cases). MS and its components including body mass index (BMI), serum high-density lipoprotein (HDL) and triglycerides (TG) and their relationships with clinical outcomes were analyzed and then compared between groups. RESULTS: The incidences of MS and its components including BMI, the levels of HDL and TG were not differently distributed between the 2 groups (all p's >0.05). However, more TNBC than non-TNBC patients presented with hypertension and elevated serum glucose (20.3% vs. 14.9% and 16.0% vs. 10.8%, p = 0.018 and p = 0.012, respectively). TNBC patients had poorer 5-year relapse-free survival (RFS) than non-TNBC patients (72.8% vs. 84.2%, p<0.0001). Only in the TNBC group, patients with low high-density lipoprotein (HDL) demonstrated worse RFS and overall survival (OS; p<0.0001). Multivariate analysis identified that low HDL was an independent worse prognostic factor for both RFS (hazard ratio [HR] = 3.266, 95% confidence interval [95%CI], 2.087-5.112, p<0.0001) and OS (HR = 3.071, 95%CI, 1.732-5.445, p<0.0001) in TNBC patients. CONCLUSIONS: Decreased level of HDL may predict worse outcomes both in terms of RFS and OS for TNBC patients but not for non-TNBC patients. Further investigations are warranted to detect the underlying mechanisms.

Pharmacist-led group medical appointments for the management of type 2 diabetes with comorbid depression in older adults.

BACKGROUND: Depression is associated with poor glycemic control, increased number of microvascular and macrovascular complications, functional impairment, mortality, and 4.5 times higher total health care costs in patients with diabetes. Shared medical appointments (SMAs) may be an effective method to attain national guideline recommendations for glycemic control in diabetes for patients with depression through peer support, counseling, problem solving, and improved access to care. OBJECTIVE: To test the efficacy as assessed by attainment of a hemoglobin A(1c) (A1C) <7% of pharmacist-led group SMA visits, Veterans Affairs Multidisciplinary Education in Diabetes and Intervention for Cardiac Risk Reduction in Depression (VA-MEDIC-D), in patients with type 2 diabetes mellitus. METHODS: This was a randomized controlled trial of VA-MEDIC-D added to standard care versus standard care alone in depressed patients with diabetes with A1C >6.5%. VA-MEDIC-D consisted of 4 once-weekly, 2-hour sessions followed by 5 monthly 90-minute group sessions. Each SMA session consisted of multidisciplinary education and pharmacist-led behavioral and pharmacologic interventions for diabetes, lipids, smoking, and blood pressure. No pharmacologic interventions for depression were provided. The change in the proportion of participants who achieved an A1C <7% at 6 months was compared. RESULTS: Compared to standard care (n = 44), a lower proportion of patients in VA-MEDIC-D (n = 44) had systolic blood pressure (SBP) <130 mm Hg at baseline, but were similar in other cardiovascular risk factors and psychiatric comorbidity. The change in the proportion of participants achieving an A1C <7% was greater in the VA-MEDIC-D arm than in the standard care arm (29.6% vs 11.9%), with odds ratio 3.6 (95% CI 1.1 to 12.3). VA-MEDIC-D participants also achieved significant reductions in SBP, low-density lipoprotein cholesterol, and non-high-density lipoprotein (HDL) cholesterol from baseline, whereas significant reductions were attained only in non-HDL cholesterol with standard care. There was no significant change in depressive symptoms for either arm. CONCLUSIONS: Pharmacist-led group SMA visits are efficacious in attainment of glycemic control in patients with diabetes and depression without change in depression symptoms.

What intervention trials don't tell us: the residual risk in primary prevention.

A number of epidemiological studies and intervention clinical trials demonstrated that the in spite of the achievement of recommended targets of low-density lipoprotein (LDL)-cholesterol in subjects not yet affected by cardiovascular diseases, a substantial percentage of them still remain at risk of acute events. Beyond LDL-c, additional abnormalities of lipid profile, consisting of low high-density lipoprotein (HDL)-cholesterol and high levels of triglycerides or the combination of the two, may play a role in determining the cardiovascular prognosis. The mentioned lipid abnormalities, together with elevated apolipoprotein B and non-HDL cholesterol, do represent the burden of the so-called residual cardiovascular risk of lipid nature. Although it is plausible that there is benefit in normalizing lipid abnormalities other than LDL-C in primary prevention, it is still controversial that this actually reduces clinical events. Recent attempts to further reduce the risk of patients already given statin therapy with drugs raising HDL-c or lowering triglycerides levels failed to demonstrate a favorable impact on secondary prevention. Of importance, evidence is completely lacking for people at lower risk such as those requiring primary prevention. New and more safe/effective drugs are currently under investigation in this field. Until further information is available on the efficacy and safety of interventions aimed at restoring normal levels of triglycerides and HDL, we have to continue to implement safe and effective methods we already have to blunt the cardiovascular risk, consisting mainly of lifestyle changes and statin therapy.

Estado nutricional de trabajadores bajo turnos rotativos o permanentes / Nutritional state of workers under steady or rotating shifts

Restrictions of sleep predispose to experience, in the long-term, excess malnutrition and non-transmissible chronic diseases. The objective of this research has to study the influence of working shifts on nutritional status lipid profile and fasting blood glucose (FBG). Study of a series of cases considered a total of47 recruited workers from which 31 of them had a rotating shift (day and night) and 16 a steady shift (day). The nutritional assessment involved: BMI (Body Mass index), waist and hip circumference, tricipital, bicipital, sub scapular and supra iliac skin folds. Sleep hours were studied with a weekly record, food intake was studied by means of 24-hours dietary recall. It was determined: total cholesterol, c-HDL, c-LDL, blood triglycerides and fasting blood glucose (FBG). The sample was composed by 87 percent women and 13 percent men, average age of 38,7years [19,0] v/s 44,7[25¿2] (p=0,420) in rotating and steady shifts respectively. The rotating shift did not show any significant differences compared to the steady shift in terms of anthropometric parameters except for sub scapular skin fold that was significantly higher (p=0,032) in relation to the macronutrients intake. Lipid profile and glycerin did not show important differences (p=>0,05). The prevalence of the nutritional status was: rotating shift 35,4 percent normal, 45,1 percent overweight and 19,5 percent obese. On the other hand, the steady shift showed: 43,7 percent normal and 56¿ percent overweight. Seniority only in the rotating shift showed a positive correlation of BMI (r=0,436 p<0,005) body fat (r=0,454 p<0,005) total cholesterol (r= 0,¿94 p<0,005) LDL (r=0,484 p<0,005) and glycerin (r=0,405 p<0,005). We concluded that workers of the rotating and steady shift did not show significant differences among variables studied except for the sub scapular skin fold that was significantly higher in the rotating shift, that can be associated to predominantly central fat distribution.

Restricciones del sueño predisponen a padecer, a largo plazo, malnutrición por exceso y enfermedades crónicas no transmisibles. El objetivo fue estudiar la influencia del turno laboral sobre estado nutricional, perfil lipídico y glicemia en ayuno. Estudio exploratorio del tipo de serie de casos, 47 reclutados; 31 turnos rotativos (día y noche), y 16 turno permanente (día). La evaluación nutricional se efectuó mediante el IMC, la circunferencia cintura-cadera y los pliegues tricipital, bícipital, subescapular y suprailiaco. Se estudió las horas sueño mediante un registro semanal, la ingesta dietética por encuesta de recordatorio de 24 horas. Se determinó el colesterol total, c-HDL, c-LDL, triglicéri-dos séricos y glicemia. La muestra estuvo representada en un 87 por ciento mujeres y 13 por ciento por hombres, cuya mediana de edad fue de 38,7 años [19,0] y 44,7[25,2] (p=0,420) en turno rotativo y permanente, respectivamente. El turno rotativo no mostró diferencias significativas respecto al turno permanente en los parámetros antropométricos a excepción, del pliegue subescapular que fue significativamente superior (p=0,032), respecto a ingesta de macronutrientes, perfil lipídico y glicemia tampoco mostró diferencias significativas (p=> 0,05). La prevalencia del estado nutricional en el turno rotativo fue en 35,4 por ciento normal, en 45,1 por ciento sobrepeso y en 19,5 por ciento obesidad, y turno permanente: 43,7 por ciento normal y 56,3 por ciento sobrepeso. La antigüedad laboral sólo en el turno rotativo se correlacionó positivamente con IMC (r=0,436 p<0,005), grasa corporal (r=0,454 p<0,005), el colesterol total (r= 0,394 p<0,005) el LDL (r=0,484 p<0,005) y la glicemia (r=0,405 p<0,005). En conclusión, los funcionarios del turno rotativo y permanente no mostraron diferencias significativas entre las variables estudiadas, a excepción del pliegue subescapular que fue significativamente mayor en el turno rotativo, lo que podría asociarse a la distribución de la...

Dyslipidaemia in diabetic patients: time for a rethink.

Patients with type 2 diabetes have a marked increase in the risk of premature coronary heart disease (CHD). One of the underlying reasons for this increased risk is atherogenic dyslipidaemia, which is common in this patient group and characterized by low plasma levels of high-density lipoprotein cholesterol (HDL-C), increased levels of serum triglycerides, specifically very low-density lipoprotein triglycerides, and an increase in small, dense low-density lipoprotein (LDL) particles. Current management strategies focus on the initial use of statin or fibrate therapy (the latter approach indicated in patients with pronounced hypertriglyceridaemia). Recent treatment guidelines also emphasize the need for reduction in LDL-cholesterol (LDL-C) below 100 mg/dl (2.6 mmol/l) in diabetic patients, as this patient group has a clustering of cardiovascular risk factors that collectively lead to an excess risk of premature mortality. Multidrug lipid-modifying therapy has been proposed to further reduce CHD risk in diabetic patients. Adding nicotinic acid to primary statin therapy would be a logical approach based on the complementary therapeutic benefits of these treatments. Nicotinic acid is the most potent agent currently available for raising HDL-C and is also effective in reducing triglycerides and LDL-C. Moreover, clinical trial data have shown that nicotinic acid can be safely used in diabetic patients. Data from the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER 2) study in patients with established CHD and low HDL-C (27% of whom had type 2 diabetes) show the atheroprotective effects of nicotinic acid/statin combination therapy. The clinical benefits of this combination therapy are indicated by subgroup analyses from the HDL-Atherosclerosis Treatment Study, which showed 40% reduction in coronary event frequency in patients with impaired glucose tolerance. Together, these data support the proposed strategy of aggressive multidrug treatment of diabetic dyslipidaemia to improve patient outcome.

The beneficial effects of high-density lipoprotein on adipocytes may relate to its anti-atherogenic properties.

High-density lipoprotein (HDL) has significant anti-atherogenic properties, whereas the underlying mechanisms are complex and have not been completely elucidated. Adipocytes produce a variety of adipokines with cardiovascular effects. The dysregulated secretion of adipokines by adipocytes may contribute to the increased risk of atherosclerosis associated with obesity. Clinical evidences indicate that higher plasma HDL-C levels are associated with a favourable adipokines secretion profile, suggesting that HDL might improve the dysregulated adipokines secretion. HDL may diminish lipid accumulation in adipocytes through phosphorylation of PPARgamma and inhibition of aP2 expression, which possibly account for the favourable effects of HDL on adipokines secretion. Therefore, we hypothesize that HDL might exert several beneficial effects on adipocytes, which may relate to its anti-atherogenic properties.

Effect of high-density lipoprotein associated cyclosporine on hepatic metabolism and renal function.

Cyclosporine (CSA), in both humans and animals, is associated with plasma lipoproteins. It has been demonstrated that CSA-lipoprotein association is partly responsible for the distribution and toxicity related to CSA use. Altered plasma lipoprotein profiles are often seen in transplantation recipients undergoing CSA treatment. In the present study, daily 0.1 mg/kg intravenous injections of either high-density lipoprotein-associated CSA (HDL-CSA), plasma-associated CSA (Plasma-CSA), or CSA in Cremophor (CSA) were administered to adult male rats for 14 days. Vehicle controls included daily administrations of 0.5 ml/kg of Cremophor or saline. Serum creatinine levels, a marker of renal function, increased in rats administered Plasma-CSA as compared with control rats treated with CSA. CYP3A and CYP2C11 protein expression was suppressed by 27% and 39%, respectively, in the HDL-CSA treatment group and by 38% and 40% in the Plasma-CSA treated group as compared with CSA controls. In addition, 6beta-hydroxytestosterone, a marker of CYP3A activity, was reduced by 33% and 34% in the HDL-CSA and the Plasma-CSA treatment groups, respectively, as compared with the CSA control group. CYP2C11 activity was measured by the in vitro formation of 2alpha-hydroxytestosterone. Activity levels in rats treated with HDL-CSA and Plasma-CSA were slightly induced as compared to CSA controls, however these differences were not found to be statistically significant. In summary, Plasma-CSA treatment resulted in renal dysfunction and suppressed CYP3A and CPY2C11 protein expression. These results demonstratethat intravenous lipoprotein-associated CSA alters the metabolism of CSA in the rat differently than CSA alone.

Advances in the understanding and management of dyslipidemia: using niacin-based therapies.

The use of niacin, alone and in combination, for the treatment of dyslipidemia in patients with or at risk for coronary heart disease (CHD), is discussed. Cardiovascular risk is independently predicted not only by high levels of low-density lipoprotein cholesterol (LDL-C), but also low levels of high-density lipoprotein cholesterol (HDL-C) and elevated triglycerides. Moreover, we now understand that LDL particle size and number are associated with differing levels of atherogenicity. Metabolic syndrome, increasingly being recognized as a marker for elevated cardiovascular risk, is associated with atherogenic dyslipidemia characterized by low HDL-C, high triglycerides, and small, dense LDL particles. Controlled clinical studies have shown that niacin therapy effectively increases HDL-C and lowers triglyceride and LDL-C levels while causing a shift toward larger, less atherogenic LDL particles. Niacin, alone or in combination, prevents progression and promotes regression of coronary atherogenic lesions and significantly reduces CHD-related morbidity and mortality. Statin monotherapy causes modest increases in HDL-C and decreases triglycerides, while more potently reducing LDL-C. Combinations of lipid-modifying agents may better address the full spectrum of lipoprotein abnormalities in some patients. Investigations have shown that combining statin therapy with niacin results in additive improvement in the major lipids and lipoproteins and improves clinical outcome. With recently broadened treatment recommendations, it seems likely that combination therapy will be increasingly deemed the appropriate choice for addressing a range of lipid abnormalities.

Correction of the P-value after multiple coding of an explanatory variable in logistic regression.

We propose a method and a program to determine a significance level for a series of codings of an explanatory variable in logistic regression. Dichotomous and Box-Cox transformations are considered. Three methods of correcting the significance level are studied: the Bonferroni method; Efron's method, which uses the correlation between successive tests, and the exact calculation by numerical integration using all correlations. A simulation study has led to a strategy for the choice and number of the different codings of the variable. This method is illustrated using the data of a study of the relation between cholesterol and dementia.