Decreased HDL-cholesterol Levels Research Articles

VNN1 Gene Expression Levels and the G-137T Polymorphism Are Associated with HDL-C Levels in Mexican Prepubertal Children

Background VNN1 gene expression levels and the G-137T polymorphism have been associated with high density lipoprotein cholesterol (HDL-C) levels in Mexican American adults. We aim to evaluate the contribution of VNN1 gene expression and the G-137T variant to HDL-C levels and other metabolic traits in Mexican prepubertal children.Methodology/Principal Findings VNN1 mRNA expression levels were quantified in peripheral blood leukocytes from 224 unrelated Mexican-Mestizo children aged 6–8 years (107 boys and 117 girls) and were genotyped for the G-137T variant (rs4897612). To account for population stratification, a panel of 10 ancestry informative markers was analyzed. After adjustment for admixture, the TT genotype was significantly associated with lower VNN1 mRNA expression levels (P = 2.9 × 10−5), decreased HDL-C levels (β = −6.19, P = 0.028) and with higher body mass index (BMI) z-score (β = 0.48, P = 0.024) in the total sample. In addition, VNN1 expression showed a positive correlation with HDL-C levels (r = 0.220; P = 0.017) and a negative correlation with BMI z-score (r = −0.225; P = 0.015) only in girls.Conclusion/SignificanceOur data suggest that VNN1 gene expression and the G-137T variant are associated with HDL-C levels in Mexican children, particularly in prepubertal girls.

Association of resistin gene polymorphisms with insulin resistance in Egyptian obese patients

BackgroundObesity associated insulin resistance is a major risk factor for type 2 diabetes mellitus. Resistin is recently reported to provide a link between obesity, insulin resistance and type 2 diabetes mellitus. We aimed to investigate the possible associations of resistin gene (RETN) polymorphisms with obesity, and to detect whether these polymorphisms are associated with glucose intolerance and type 2 diabetes mellitus in obese patients. MethodsOne hundred and forty-five Egyptian obese patients with or without glucose intolerance and 155 unrelated healthy controls were enrolled in this study. Polymorphisms of RETN +299G>A and RETN –420 C>G gene were detected by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP). Serum resistin was measured by ELISA. ResultsRETN +299 AA and RETN −420 GG genotypes were significantly associated with obesity in Egyptian population. Moreover, the mutant alleles or genotypes of both examined polymorphisms were associated with impaired glucose tolerance and diabetes mellitus compared to normal glucose tolerant obese patients. Furthermore, our results revealed elevated waist/hip ratio, BMI, blood pressure, fasting blood glucose level, HOMA-IR, triglycerides, total cholesterol, resistin level, and decreased HDL cholesterol level in homozygote mutant genotypes carriers of both RETN polymorphisms among obese patients. ConclusionResistin gene polymorphisms may play an important role in pathogenesis and susceptibility to obesity, impaired glucose tolerance, and type 2 diabetes mellitus in Egyptian population.

Endothelial Lipase Activity Predicts High-Density Lipoprotein Catabolism in Hemodialysis

A novel phospholipase assay was used to measure for the first time the behavior of endothelial and hepatic phospholipase activities in postheparin human plasma of hemodialyzed patients and its relationship with atherogenic and antiatherogenic lipoprotein levels. Endothelial and hepatic phospholipase activity was assessed in a total SN1-specific phospholipase assay, using (1-decanoylthio-1-deoxy-2-decanoyl-sn-glycero-3-phosphoryl) ethylene glycol as the substrate. Hemodialyzed patients presented lower values of total and hepatic phospholipase activity than controls: 4.4 (1.9-9.0) versus 7.5 (3.6-18.0) and 2.6 (0.7-6.2) versus 6.6 (1.3-15.2) μmol of fatty acid released per milliliter of postheparin plasma per hour, respectively (P<0.001); however, endothelial lipase (EL) phospholipase activity was increased in patients: 1.7 (0.8-3.0) versus 1.1 (0.1-2.7) μmol of fatty acid released per milliliter of postheparin plasma per hour (P=0.008). EL was negatively associated with high-density lipoprotein (HDL)-cholesterol (r=-0.427; P=0.001), and apolipoprotein A-I levels, total phospholipase, and hepatic lipase activity were directly associated with low-density lipoprotein-cholesterol and apolipoprotein B. The association of EL and HDL-cholesterol remained significant when adjusting for waist circumference (β=-0.26; P=0.05), and the effect of hepatic lipase on low-density lipoprotein-cholesterol continued after adjusting for age (β=0.46; P= 0.001). Our results support the hypothesis that EL is the predominant enzyme responsible for lipolytic catabolism of HDLs in hemodialyzed patients and resolve the apparent paradox observed between low hepatic lipase activity and decreased HDL-cholesterol levels observed in these patients. In addition, the ability to assess total hepatic lipase and EL phospholipase activity in plasma will increase our knowledge of the mechanisms involved in controlling HDL levels and cardiovascular risk in hemodialyzed patients, as well as other populations with low levels of HDL-cholesterol.

Diet‐Induced Weight Loss in Overweight or Obese Women and Changes in High‐Density Lipoprotein Levels and Function

Diet-induced weight loss in women may be associated with decreases not only in plasma levels of low-density lipoprotein cholesterol (LDL-C), but also in high-density lipoprotein cholesterol (HDL-C). Whether a decrease in HDL-C is associated with altered HDL function is unknown. One hundred overweight or obese women (age 46 ± 11 years, 60 black; 12 diabetic) were enrolled in the 6-month program of reduced fat and total energy diet and low-intensity exercise. Serum cholesterol efflux capacity was measured in 3H-cholesterol-labeled BHK cells expressing ABCA1, ABCG1, or SR-B1 transporters and incubated with 1% apolipoprotein B (apoB)-depleted serum. Antioxidant properties of HDL were estimated by paraoxonase-1 (PON1) activity and oxygen radical absorbance capacity (ORAC). Endothelial nitric oxide synthase (eNOS) activation was measured by conversion of L-arginine to L-citrulline in endothelial cells incubated with HDL from 49 subjects. Participants achieved an average weight loss of 2.2 ± 3.9 kg (P < 0.001), associated with reductions in both LDL-C (−6 ± 21 mg/dl, P = 0.004) and HDL-C (−3 ± 9 mg/dl, P = 0.016). Cholesterol efflux capacity by the ABCA1 transporter decreased by 10% (P = 0.006); efflux capacities by the ABCG1 and SR-B1 transporters were not significantly altered. ORAC decreased by 15% (P = 0.018); neither PON1 activity nor eNOS activation was significantly altered by reduction in HDL-C. Findings were similar for diabetic and nondiabetic subjects. Diet-induced weight loss in overweight or obese women is associated with a decrease in HDL-C levels, but overall HDL function is relatively spared, suggesting that decrease in HDL-C in this setting is not deleterious to cardiovascular risk.

Effect of age on atherogenicity of LDL and inflammatory markers in healthy women

Background and aimSince using LDL level alone is insufficient as a method to identify individuals with incident coronary artery disease (CAD), other factors may be implicated in the pathogenesis of CAD. Additionally, controversy still remains regarding whether there is an age-related increase in circulating cytokines in healthy individuals. We investigated the influence of age on atherogenicity of LDL and inflammatory markers in healthy women. Methods and resultsTwo thousand nine hundred forty four healthy women form 30–79 years old (23.3 ± 0.05 kg/m2) were categorized into 5 age groups: 30–39, 40–49, 50–59, 60–69 and 70–79 years. BMI, smoking, drinking, and metabolic syndrome prevalence adjusted mean values of total-cholesterol progressively increased from the group age 30–39 years to the group age 40–49 and 50–59 years and thereafter decreased in the group age 60–69 and 70–79 years. Serum concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were higher in women aged 60–79 years than women aged 30–59 years. Plasma ox-LDL levels increased in the group age 50–59 years compared with the group age 30–39 and 40–49 years and further increased in the group age 60–69 and 70–79 years. Mean values of LDL particle size were smaller in women aged 60–79 years than those in women aged 30–59 years. After adjustment for BMI, smoking, drinking, and metabolic syndrome status, age was positively correlated with LDL-cholesterol (r = 0.095, P < 0.001), oxidized LDL (r = 0.305, P < 0.001), hs-CRP (r = 0.150, P < 0.001), TNF-α (r = 0.171, P < 0.001) and IL-6 (r = 0.294, P < 0.001) and negatively with LDL particle size (r = −0.239, P < 0.001). ConclusionOur results indicate that LDL atherogenicity and inflammatory mediators can be better markers of CAD risk than known risk factors such as elevated concentrations of total- and LDL-cholesterol, decreased HDL-cholesterol levels and smoking in old healthy women.

Angiographically-assessed coronary artery disease associates with HDL particle size in women

It has been suggested that a reduced HDL particle size could be another feature of the atherogenic dyslipidemia found among viscerally obese subjects. ObjectiveTo investigate, in women, the relationship between HDL particle size and coronary artery disease (CAD). MethodsAverage HDL particle size was measured in a sample of 239 women on whom CAD was assessed by angiography. ResultsOverall, women who had CAD were characterized by a deteriorated fasting metabolic risk profile, which was accompanied by smaller HDL particles compared to women without CAD (80.4 ± 2.2 Å vs. 81.5 ± 2.7 Å, p < 0.01). In addition, a reduced HDL particle size was a significant correlate of several features of the atherogenic metabolic profile of abdominal obesity such as increased triglyceride and apolipoprotein B concentrations, decreased HDL cholesterol levels, an elevated cholesterol/HDL cholesterol ratio and hyperinsulinemia and was also associated with an increased waist circumference (0.13≤|r|≤0.21, p < 0.05). Odds ratio of being affected by CAD was increased by 2.5-fold (95% CI: 1.4–4.5; p < 0.01) among women with smaller HDL particles compared to women with larger HDL particles. Finally, women characterized by the presence of the NCEP-ATP III clinical criteria or by hypertriglyceridemic waist were characterized by smaller HDL particles compared to women without these clinical phenotypes (p < 0.05). ConclusionHDL particle size appears to be another relevant feature of a dysmetabolic state which is related to CAD risk in women.

The lipid profiles in Japanese patients with schizophrenia treated with antipsychotic agents

ObjectiveAntipsychotic-treated schizophrenia patients are susceptible to dyslipidemia. However, the results of previous studies of North American and UK populations including various races have been contradictory with regard to which lipid measure was the most affected in patients with schizophrenia taking antipsychotic agents. The aim of this study was to investigate the effect of schizophrenia patients receiving antipsychotic agents on each lipid measure in a Japanese population. MethodsThe samples included 136 control individuals and 157 patients with schizophrenia treated with antipsychotic agents. Age, gender distribution and body mass index (BMI) of the controls were matched with the patients. ResultsThe high-density lipoprotein cholesterol (HDL-cholesterol) levels were significantly lower in patients than in the control subjects (P<.001). However, there were no significant differences in either the low-density lipoprotein cholesterol (LDL-cholesterol) or triglyceride levels between the patient and control groups. We performed a multiple linear regression analysis, and schizophrenia receiving antipsychotics was an independent predictor of decreased HDL-cholesterol. An increased BMI, male gender and cigarette smoking were also major predictors of a decreased HDL-cholesterol level (r2=0.42, P<.001). ConclusionAt least in Japanese with schizophrenia receiving antipsychotic agents, the HDL-cholesterol levels should be closely monitored in all patients, even those who are not obese or do not smoke, to decrease their risk of cardiovascular disease.

ApoE promotes hepatic selective uptake but not RCT due to increased ABCA1-mediated cholesterol efflux to plasma

ApoE plays an important role in lipoprotein metabolism. This study investigated the effects of adenovirus-mediated human apoE overexpression (AdhApoE3) on sterol metabolism and in vivo reverse cholesterol transport (RCT). In wild-type mice, AdhApoE3 resulted in decreased HDL cholesterol levels and a shift toward larger HDL in plasma, whereas hepatic cholesterol content increased (P < 0.05). These effects were dependent on scavenger receptor class B type I (SR-BI) as confirmed using SR-BI-deficient mice. Kinetic studies demonstrated increased plasma HDL cholesteryl ester catabolic rates (P < 0.05) and higher hepatic selective uptake of HDL cholesteryl esters in AdhApoE3-injected wild-type mice (P < 0.01). However, biliary and fecal sterol output as well as in vivo macrophage-to-feces RCT studied with (3)H-cholesterol-loaded mouse macrophage foam cells remained unchanged upon human apoE overexpression. Similar results were obtained using hApoE3 overexpression in human CETP transgenic mice. However, blocking ABCA1-mediated cholesterol efflux from hepatocytes in AdhApoE3-injected mice using probucol increased biliary cholesterol secretion (P < 0.05), fecal neutral sterol excretion (P < 0.05), and in vivo RCT (P < 0.01), specifically within neutral sterols. These combined data demonstrate that systemic apoE overexpression increases i) SR-BI-mediated selective uptake into the liver and ii) ABCA1-mediated efflux of RCT-relevant cholesterol from hepatocytes back to the plasma compartment, thereby resulting in unchanged fecal mass sterol excretion and overall in vivo RCT.

The relation of serum paraoxonase-1 activity with isolated coronary artery ectasia: an observational study

Coronary artery ectasia (CAE) is a congenital or acquired anomaly characterized with localized or diffuse dilatations of coronary arteries. Paraoxonase (PON-1) is a high-density lipoprotein-cholesterol (HDLC) associated antioxidant enzyme that prevents atherosclerosis. The aim of this study was to investigate serum paraoxonase-1 enzyme activity (SPA) in patients with CAE in comparison patients with coronary artery disease (CAD) and normal coronary arteries. We have evaluated 44 patients with isolated IKAE, 40 cases with normal coronary arteries (NCA), 40 cases with critical CAD (CAD) and 40 cases with minimal CAD (MCAD) in this cross-sectional observational study. Demographic and biochemical data of patients were collected. SPA was determined spectrophotometrically. Among-group comparisons, ANOVA, Kruskal-Wallis and Chi-square tests were used; Bonferroni test was used for post-hoc analysis, Pearson's correlation analysis to determine the parameters associated with the SPA. There were no differences among groups with regard to age, sex, presence of diabetes, hypertension and smoking (p>0.05 for all). The highest HDLC was detected in patients with NCA and lowest HDLC was detected in patients with CAD (respectively 52±15 mg/dL; 41±16 mg/d L, p=0.021). CAD and CAE groups were similar with respect to HDLC levels (p>0.05). The highest SPA level was detected in patients with NKA and the lowest SPA level was detected in patients with CAD (respectively 250.78±59.37U/L; 163.39±49.28 U/L, p=0.005). CAD and CAE groups were similar with respect to SPA levels (p>0.05). Both decreased SPA and decreased HDLC levels are closely related to the development of the CAE similar to CAD.

Genetic variation in cholesterol ester transfer protein, serum CETP activity, and coronary artery disease risk in Asian Indian diabetic cohort

The role of cholesteryl ester transfer protein (CETP) in the metabolism of high-density lipoprotein cholesterol (HDL-C) is well studied but still controversial. More recently, genome-wide association studies and meta-analyses reported the association of a promoter variant (rs3764261) with HDL-C in Caucasians and other ethnic groups. In this study, we have examined the role of genetic variation in the promoter region of CETP with HDL-C, CETP activity, coronary artery disease (CAD), CAD risk factors, and the interaction of genetic factors with environment in a unique diabetic cohort of Asian Indian Sikhs. We genotyped four variants; three tagging single nucleotide polymorphisms from promoter (rs3764261, rs12447924, rs4783961) and one intronic variant (rs708272 Taq1B) on 2431 individuals from the Sikh Diabetes study. Two variants (rs3764261 and rs708272) exhibited a strong association with HDL-C in both normoglycemic controls (β=0.12; P=9.35×10 for rs3764261; β=0.10, P=0.002 for rs708272) and diabetic cases (β=0.07, P=0.016 for rs3764261; β=0.08, P=0.005 for rs708272) with increased levels among minor homozygous 'AA' carriers. In addition, the same 'A' allele carriers in rs3764261 showed a significant decrease in systolic blood pressure (β=-0.08, P=0.002) in normoglycemic controls. Haplotype analysis of rs3764261, rs12447924, rs4783961, and rs708272 further revealed a significant association of 'ATAA' haplotype with an increased HDL-C (β=2.71, P=6.38×10) and 'CTAG' haplotype with decreased HDL-C levels (β=-1.78, P=2.5×10). Although there was no direct association of CETP activity and CETP polymorphisms, low CETP activity was associated with an increased risk to CAD (age, BMI, and sex-adjusted odds ratio=2.2; 95% confidence interval: 1.4-3.4; P=0.001) in this study. Our data revealed a strong interaction of rs3764261 and rs708272 for affecting the association between CETP activity and HDL-C levels (P=2.2×10 and P=4.4×10, respectively). Our results, in conjunction with earlier reports confirm low CETP activity to be associated with higher CAD risk. Although there was no direct association of CETP activity with CETP polymorphisms, our findings revealed a significant interaction between CETP variants and CETP activity for affecting HDL-C levels. These results urge a deeper evaluation of the individual genetic variation in the CETP before implementing pharmaceutical intervention of blocking CETP for preventing CAD events.

Effects of the lipoprotein lipase activator NO-1886 as a suppressor agent of atherosclerosis in aorta of mild diabetic rabbits.

The synthetic compound NO-1886 ([4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase activator which decreases plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C) levels. However, the effects of NO-1886 on plasma glucose level and atherosclerosis in diabetes are not clear. The aim of this study was to ascertain whether the compound lowers plasma glucose and suppresses atherosclerosis in New Zealand White rabbits with high fat/high sucrose-induced mild diabetes. High fat/high sucrose feeding increased plasma total cholesterol, triglyceride and glucose levels and decreased HDL-C levels resulting in atherosclerosis in the aorta. Administration of NO-1886 to the rabbits resulted in decreased plasma total cholesterol, triglyceride and glucose levels and increased HDL-C levels after 20 weeks of treatment. Furthermore, NO-1886 provided protection against the development of atherosclerosis in the aorta. These data indicate that NO-1886 not only ameliorates the lipid disorder, but also lowers plasma glucose levels and suppresses atherosclerosis in the aorta of diabetic rabbits.

LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear. We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants in the Copenhagen General Population Study (CGPS), of which 991 and 1,693 participants, respectively, had developed myocardial infarction (MI) by August 2010. Participants in the CCHS were genotyped for all six variants identified by resequencing lecithin-cholesterol acyltransferase in 380 individuals. One variant, S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis. Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies combined was 0.49 (0.11-2.16), whereas the hazard ratio for MI for a 50% reduction in plasma HDL cholesterol in the CCHS was 2.11 (1.70-2.62) (P(comparison) = 0.03). Low plasma HDL cholesterol levels robustly associated with increased risk of MI but genetically decreased HDL cholesterol did not. This may suggest that low HDL cholesterol levels per se do not cause MI.

Microcirculation and atherothrombotic parameters in prolactinoma patients: a pilot study

Atherothrombosis is a multifactorial process, governed by an interaction between the vessel wall, hemodynamic factors and systemic atherothrombotic risk factors. Recent in vitro, human ex vivo and animal studies have implicated the hormone prolactin as an atherothrombotic mediator. To address this issue, we evaluated the anatomy and function of various microvascular beds as well as plasma atherothrombosis markers in patients with elevated prolactin levels. In this pilot study, involving 10 prolactinoma patients and 10 control subjects, sidestream dark field (SDF) imaging revealed a marked perturbation of the sublingual microcirculation in prolactinoma patients compared to control subjects, as attested to by significant changes in microvascular flow index (2.74 ± 0.12 vs. 2.91 ± 0.05, respectively; P = 0.0006), in heterogeneity index (0.28 [IQR 0.18–0.31] vs. 0.09 [IQR 0.08–0.17], respectively; P = 0.002) and lower proportion of perfused vessels (90 ± 4.0% vs. 95 ± 3.0%, respectively; P = 0.016). In the retina, fluorescein angiography (FAG) confirmed these data, since prolactinoma patients more often have dilatated perifoveal capillaries. In plasma, prolactinoma patients displayed several pro-atherogenic disturbances, including a higher endogenous thrombin potential and prothrombin levels as well as decreased HDL-cholesterol levels. Prolactinoma patients are characterized by microvascular dysfunction as well as plasma markers indicating a pro-atherothrombotic state. Further studies are required to assess if prolactin is causally involved in atherothrombotic disease.

Association of the Apolipoprotein A5 Gene -1131T>C Polymorphism with Serum Lipids in Korean Subjects: Impact of Sasang Constitution.

Apolipoprotein A5 (APOA5) was identified as a strong modulator of serum lipids. Moreover, an APOA5 gene −1131T>C polymorphism has been associated with serum lipids, but the results are inconsistent according to ethnic and racial groups. We have genotyped and analyzed 1,619 outpatients of Korean oriental medicine hospitals who were classified into three Sasang constitution groups (SCGs), So-Yang (SY), So-Eum (SE), and Tae-Eum (TE). There were no significant difference in the distribution of the APOA5 −1131T>C genotype among the three SCGs. Subjects with the C allele in SY and TE showed significantly lower serum high-density lipoprotein cholesterol (HDL-C) and higher triglyceride (TG) levels than noncarriers of the C allele. These results show the differences in the prevalence of decreasing serum HDL-C and elevating serum TG levels along with APOA5 −1131T>C polymorphism according to SCG and suggest that SCG may act as a significant risk factor for hypo-HDL-C-emia and hypertriglyceridemia susceptibility.

The prevalence of metabolic syndrome in Korean patients with schizophrenia receiving a monotherapy with aripiprazole, olanzapine or risperidone

Second-generation antipsychotics (SGAs) increase the risk of metabolic syndrome (MetS). Although ethnicity also contributes to MetS risk, the majority of the studies on the relationship of SGAs to this syndrome come from Western countries, whereas few reports have come from Asian countries, especially regarding patients taking a single SGA. We reviewed the electronic medical records of patients with schizophrenia who received aripiprazole, olanzapine or risperidone monotherapies for at least three months. We evaluated the prevalence of MetS in our sample as well as the indirect standardized prevalence ratio (ISPR) using data from the 4th Korean National Health and Nutrition Examination Survey (KNHNES, 2007). The prevalence of MetS in our sample (n=145) was 31.7%, and the ISPR was 2.09. Male patients had a higher prevalence of MetS than female patients (odds ratio [OR]=4.18, 95% CI=1.93-9.03). The ISPR of male patients was 2.67 and statistically significant, whereas the ISPR of female patients was not significant. In our sample, the frequency of abnormal MetS subcomponents occurred in descending order: increased waist circumference, increased triglyceride levels, decreased HDL-cholesterol levels, elevated blood pressure and elevated fasting blood glucose levels. Patients who received aripiprazole were significantly less likely to have MetS. However, a logistic regression showed that age and sex, but not the type of antipsychotic, its dose or the use of antidepressants, were significantly related to the presence of MetS. There were no statistically significant differences among SGAs in terms of MetS subcomponent abnormalities of after adjusting for age and sex. In conclusion, only male Korean patients with schizophrenia who received a monotherapy of aripiprazole, olanzapine or risperidone for more than three months were more likely to have MetS than the general population.

Increased cortisol level

Vasomotor symptoms may increase the risk for cardiovascular diseases through still elusive mechanisms. Increased cortisol release may favor atherosclerosis. In this study, we tested whether vasomotor and psychological symptoms are associated with an increase in cortisol levels. A cross-sectional investigation on women in early menopause enrolled consecutively between January and June 2009 was conducted. This study was set at a menopause outpatient service at University Hospital. Participants included 85 healthy women who were 6 months to 5 years postmenopause. The 24-hour urinary cortisol level and Greene Climacteric Scale scores were evaluated. Anthropometric parameters and fasting blood samples for the determination of high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, glucose, and insulin levels were measured. Body mass index, waist-to-hip ratio, and homeostatic model assessment of insulin resistance were calculated. The relation between Greene Climacteric Scale scores and 24-hour urinary cortisol level and between 24-hour urinary cortisol level and lipid levels or insulin resistance was determined. The Greene Climacteric Scale score for climacteric symptoms (coefficient of regression [CR], 1.343; 95% CI, 0.441-2.246) and body mass index (CR, 4.469; 95% CI, 1.259-7.678) explained 32.5% and 10.3%, respectively, of the variance in 24-hour urinary cortisol level (r = 0.428; P = 0.0003). Twenty-four-hour urinary cortisol level was inversely related to HDL-cholesterol level (CR, -0.065; 95% CI, -0.114 to -0.017; r = 0.283; P = 0.009) and was related to waist girth (CR, 0.685; 95% CI, 0.306-1.063) and homeostatic model assessment of insulin resistance (CR, 0.097; 95% CI, 0.032-0.162; r = 0.510; P = 0.0001). In early postmenopausal women, the Greene Climacteric Scale score is associated with increased 24-hour urinary cortisol level. Increased cortisol level is associated with known risk factors for cardiovascular disease, such as insulin resistance and decreased HDL-cholesterol level.

Total cholesterol, high density lipoprotein and triglyceride for cardiovascular disease in elderly patients treated with metformin

Metformin reduces total cholesterol level, low density lipoprotein cholesterol (LDL-C) level, blood glucose level and increases high density lipoprotein cholesterol (HDL-C) level associated with cardiovascular disease. We evaluated effect of metformin on lipid profile in Korean patients with type 2 diabetes aged 64 years or older. We retrospectively examined 307 outpatients treated with metformin in a hospital setting with a follow-up period of 4.7 years. Metformin was not associated with the improvement in total cholesterol level (adjusted mean difference; 30.6 mg/dl, 95% CI: 24.9 to 36.4) and HDL-C level (adjusted mean difference; 2.6 mg/dl, 95% CI: 0.09 to 4.64) but may be associated with improvement in triglyceride level (adjusted mean difference; 41.5 mg/dl, 95% CI: 24.7 to 58.3). In comparison to the placebo groups (Kooy et al., 2009), there was a 1.5-fold decrease in triglyceride level and a 2-fold decrease in HDL-C level in our study. The frequency of Scr level that increased above the defined level [Scr ≥ 1.5 mg/dl for male, ≥1.4 mg/dl for female] was 6.7% [mean difference of elevated Scr: -0.9 mg/dl, 95% CI: -0.41 to -1.44, p < 0.002]. To confirm the efficacy of metformin use on triglyceride level and HDL-C level associated with the risk of cardiovascular disease in patient with diabetes, further placebo-controlled investigations are required.

Genetic variants in lipid metabolism are independently associated with multiple features of the metabolic syndrome

BackgroundOur objective was to find single nucleotide polymorphisms (SNPs), within transcriptional pathways of glucose and lipid metabolism, which are related to multiple features of the metabolic syndrome (MetS).Methods373 SNPs were measured in 3575 subjects of the Doetinchem cohort. Prevalence of MetS features, i.e. hyperglycemia, abdominal obesity, decreased HDL-cholesterol levels and hypertension, were measured twice in 6 years. Associations between the SNPs and the individual MetS features were analyzed by log-linear models. For SNPs related to multiple MetS features (P < 0.01), we investigated whether these associations were independent of each other.ResultsTwo SNPs, CETP Ile405Val and APOE Cys112Arg, were associated with both the prevalence of low HDL-cholesterol level (Ile405Val P = < .0001; Cys112Arg P = 0.001) and with the prevalence of abdominal obesity (Ile405Val P = 0.007; Cys112Arg P = 0.007). For both SNPs, the association with HDL-cholesterol was partly independent of the association with abdominal obesity and vice versa.ConclusionTwo SNPs, mainly known for their role in lipid metabolism, were associated with two MetS features i.e., low HDL-cholesterol concentration, as well as, independent of this association, abdominal obesity. These SNPs may help to explain why low HDL-cholesterol levels and abdominal obesity frequently co-occur.

Mutations in APOA-I and ABCA1 in Norwegians with low levels of HDL cholesterol

Background Epidemiological studies have shown that low levels of plasma high density lipoprotein (HDL) cholesterol are associated with increased risk of ischemic heart disease (IHD), but it appears that genetic forms of low HDL cholesterol levels, as opposed to lifestyle-induced low levels of HDL cholesterol, do not result in increased risk of IHD. Therefore, the etiology of reduced levels of plasma HDL cholesterol may represent a factor that should be considered in risk stratification with respect to primary prevention. Genes encoding proteins involved in HDL metabolism, such as the ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes for harboring mutations that lead to low HDL cholesterol levels. Methods The ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol level of 0.53 (± 0.15) mmol/l, were subjected to DNA sequencing. Results Several mutations were identified in the ABCA1 gene, and two mutations were identified in the apoA-I gene. A total of 18 patients (32%) were carriers of mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45 (± 0.15) mmol/l compared to 0.57 (± 0.14) mmol/l in noncarriers (p < 0.005). Conclusion Mutations in the genes encoding ABCA1 and apoA-I are common in Norwegians, with a markedly decreased HDL cholesterol level.

CAMP Responsive Element Binding Protein 1

Life scientists, especially those of us from a previous generation (or two), were trained to focus our efforts on generating large mean differences between groups or large changes with interventions while minimizing variability. The goal was to maximize effect size, thereby optimizing the chance of generating a statistically significant difference or change that, in turn, increased the odds that the data would be publishable. And, yes, even “way” back then, publications were still the “coin of the realm.” Article see p 294 However, investigators from more recent generations, and even some from previous generations, have finally begun to realize that the variability among individuals or their responses to interventions are also important. This realization was quite pointedly brought to my attention in an initial discussion with a geneticist about a possible collaboration. He asked, “How does blood pressure change with exercise training?” I responded, “Our previous reviews indicate that the average change in systolic and diastolic blood pressure with exercise training is …,” at which point he stopped me and asked, “No, what was the variability in the responses?” Not surprisingly, given my training in the previous generations as a life scientist, I did not have an answer. Thus began my path to recognizing the importance of the interindividual variability in responses to exercise training. This variability took on even more importance at that time in light of the relatively recently initiated Human Genome Project and its potential to produce a new era of personalized medicine. That thought-provoking question spurred me to revisit some of my previous data but now with a focus on the interindividual variability for the exercise training-induced responses of the cardiovascular (CV) disease risk factors that I studied throughout my career. Sure enough, interindividual variability in these responses is substantial! Most of us missed this potentially …