Higher High-density Lipoprotein Cholesterol Concentrations Research Articles

Alcohol consumption and diabetes risk in the Diabetes Prevention Program

BackgroundModerate alcohol consumption is associated with a decreased risk of type 2 diabetes in the general population, but little is known about the effects in individuals at high risk of diabetes. ObjectivesThe objectives were to determine associations between alcohol consumption and diabetes risk factors and whether alcohol consumption was a predictor of incident diabetes in individuals enrolled in the Diabetes Prevention Program (DPP). DesignDPP participants (n = 3175) had impaired glucose tolerance (2-h glucose: 7.8–11.1 mmol/L), elevated fasting glucose (5.3–7.0 mmol/L), and a body mass index (in kg/m2) ≥24. Participants were randomly assigned to placebo, metformin, or lifestyle modification and were followed for a mean of 3.2 y. Alcohol intake was assessed at baseline and year 1 by using a semiquantitative food-frequency questionnaire. Diabetes was diagnosed by annual oral-glucose-tolerance testing and semiannual fasting plasma glucose measurement. ResultsParticipants who reported higher alcohol consumption tended to be male, older, white, and less obese and to have a higher calorie intake and a higher HDL-cholesterol concentration. Higher alcohol consumption was associated with lower insulin secretion at any level of insulin sensitivity. We found lower incidence rates of diabetes with higher alcohol consumption in the metformin (P < 0.01 for trend) and lifestyle modification (P = 0.02 for trend) groups, which remained significant after adjustment for multiple baseline covariates. No similar association was observed in the placebo group. ConclusionsDespite overall low rates of alcohol consumption, there was a reduced risk of incident diabetes in those who reported modest daily alcohol intake and were assigned to metformin or lifestyle modification. Moderate daily alcohol intake is associated with lower insulin secretion—an effect that warrants further investigation. This trial was registered at clinicaltrials.gov as NCT00038727.

Adaptation of the Framingham-Wilson Coronary Risk Equation for the Population of Navarra (RICORNA)

The Framingham equations overestimate the risk of coronary disease in populations with a low disease incidence. It is more appropriate to take the local population's characteristics into account when estimating coronary risk. Accordingly, the Framingham-Wilson equation has been adapted for the population of Navarra, Spain. This article presents 10-year overall coronary risk charts. The Framingham-Wilson equation was adapted using data on the prevalence of cardiovascular risk factors and the coronary event rate in the population of Navarra. The version of the Framingham-Wilson equation used included high-density lipoprotein cholesterol (HDL-C). The probability of an event at 10 years for different combinations of risk factors, with an HDL-C concentration of 35-59 mg/dL, are illustrated. Using the Framingham equation adapted for Navarra (i.e., the RICORNA or Riesgo Coronario Navarra), the proportion with an estimated probability of a coronary event in the next 10 years greater than 9% is approximately half that in the original Framingham population, and the proportion with a high or very high probability (i.e., 20%) is one-third. An HDL-C level <35 mg/dL increases the risk by 50% and a level > or =60 mg/dL reduces it by 50%, approximately. The average HDL-C level observed in the population was 63.9 mg/dL overall, and 70.1 mg/dL in women. The RICORNA equation can provide a more precise estimate of overall coronary risk and could be useful in primary disease prevention in Navarra. The high HDL-C concentration observed in Navarra might contribute to the associated low coronary morbidity and mortality.

Cholesterol Lowering Action and Antioxidant Status Improving Efficacy of Noodles Made from Unmarketable Oak Mushroom (Lentinus edodes) in High Cholesterol Fed Rats

The influence of noodles made from oak mushroom (Lentinus edodes) with unmarketable quality on the lipid metabolism and antioxidant system in high cholesterol fed rats was investigated. The rats were given a diet containing 1% cholesterol for 7 weeks. The control group received a highcholesterol diet only, while two other groups received high cholesterol diet supplemented with either general noodle (GN) or oak mushroom noodle (OMN) powders. At the end of the experimental period, rats fed with OMN exhibited lower plasma total cholesterol and triglycerides and higher HDL-cholesterol concentrations than that of the control and GN-fed rats. Consequently, the lowest atherogenic index was obtained in the OMN group. The hepatic antioxidant enzyme activities were highest in OMN group, with glutathione peroxidase as the most actively induced enzyme, thereby decreasing the lipid peroxidation in OMN fed rats. Results of this study indicate that consumption of unmarketable oak mushroom could be effective in lowering atherosclerosis cardiovascular disease risk.

A Plant Stanol Yogurt Drink Alone or Combined with a Low-Dose Statin Lowers Serum Triacylglycerol and Non-HDL Cholesterol in Metabolic Syndrome Patients1–3

We evaluated the effects of 2 commonly available strategies (plant stanol ester drink and 10 mg simvastatin) on coronary heart disease (CHD) risk variables in participants with metabolic syndrome. Metabolic syndrome patients are at increased risk to develop CHD, partly due to high triacylglycerol (TAG) and low HDL cholesterol (HDL-C) concentrations and a low-grade inflammatory profile. Effects of plant stanol esters on TAG concentrations in these participants are unknown. After a 3-wk run-in period in which individuals consumed placebo yogurt drinks and placebo capsules, participants were randomly divided into 4 groups: placebo (n = 9), simvastatin + placebo drink (n = 10), placebo + stanol drink (n = 9), and simvastatin + stanol drink (n = 8). After 9 wk, we evaluated the effects on serum lipids, low-grade inflammation, and endothelial dysfunction markers. In metabolic syndrome patients, stanol esters (2.0 g/d), simvastatin, or the combination lowered non-HDL-C by 12.8% (P = 0.011), 30.7% (P < 0.001), and 35.4% (P < 0.001), respectively, compared with placebo. TAG were lowered by 27.5% (P = 0.044), 21.7% (P = 0.034), and 32.7% (P < 0.01), respectively. The total-:HDL-C ratio was significantly lowered in all 3 intervention groups. We found no treatment effects on the apolipoprotein CII:CIII ratio, cholesterol ester transfer protein mass, FFA concentrations, and markers for low-grade inflammation or endothelial dysfunction. This study shows that in metabolic syndrome patients, plant stanol esters lower not only non-HDL-C, but also TAG. Effects on TAG were also present in combination with statin treatment, illustrating an additional benefit of stanol esters in this CHD risk population.

Metabolic syndrome and serum fatty acid patterns in serum phospholipids in hypertriglyceridemic persons with human immunodeficiency virus

Background: HIV infection and its treatment are associated with abnormal lipid profiles. High triglyceride concentrations and low HDL-cholesterol concentrations are the most common health abnormalities and raise concerns about an increased risk of cardiovascular disease.Objective: We compared the fatty acid patterns of serum phospholipids between persons with HIV and non-HIV controls to determine whether there are differences that explain the elevated triglyceride concentrations, insulin resistance, and inflammation that are part of the metabolic syndrome in patients with HIV.Design: Thirty-nine persons with HIV and elevated serum triglycerides (>150 mg/dL) and/or indicators of insulin resistance were recruited to examine fatty acid profiles in serum phospholipid fractions relative to those of 2 control groups without HIV (n = 31).Results: Higher concentrations of 16:1 and 18:0 fatty acids in the phospholipid fraction indicated increased lipogenesis in the HIV patients and in the non-HIV controls at risk of the metabolic syndrome. However, the subjects with HIV had higher concentrations of both n–6 (omega-6) and n–3 fatty acids of higher elongation and desaturation levels, which indicated a greater promotion of these pathways in this population. The nanomolar percentage (%nmol) arachidonic acid was the same in all 3 groups.Conclusions: Persons with and without HIV, at risk of the metabolic syndrome, show indications of increased lipogenesis, more so in subjects with HIV taking medication. Higher proportions of distal elongation and desaturation fatty acid products were seen only in the phospholipids fatty acid fraction of the subjects with HIV.

Associations of Genetic Variants in ATP-Binding Cassette A1 and Cholesteryl Ester Transfer Protein and Differences in Lipoprotein Subclasses in the Multi-Ethnic Study of Atherosclerosis

ATP-binding cassette A1 (ABCA1) and cholesteryl ester transfer protein (CETP) play important roles in the reverse cholesterol transport pathway. The associations of ABCA1 and CETP polymorphisms with lipoprotein subclasses have not been extensively studied. We genotyped 2 ABCA1 and 5 CETP polymorphisms in 999 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and studied their associations with HDL and LDL subclass particle concentrations, measured by nuclear magnetic resonance spectroscopy. ABCA1 and CETP polymorphisms were associated with different and distinct changes in lipoprotein subclass concentrations. The ABCA1 1051G/A AA genotype, previously found to be associated with cardioprotective effects in this cohort, was associated with a 5.5% higher concentration of small HDL particles (P = 0.024). The CETP TaqIB B2B2, -2505C/A AA, and -629C/A AA genotypes, previously demonstrated to lack cardioprotective effects, were associated with 15.2%, 15.4%, and 11.7% higher HDL cholesterol concentrations, respectively, and 36.5%, 40.7%, and 25.4% higher large HDL particle concentrations (P < 0.0001). The minor alleles of the A373P and R451Q polymorphisms were associated with lower large HDL particle concentrations. Our study of the influence of ABCA1 and CETP genetic variants on lipoprotein subclasses demonstrates the importance of interpreting lipoprotein subclasses within the context of the biochemical processes involved in the alterations. In the case of HDL, the study of subclass particle numbers and sizes may not be sufficiently informative. Assays for HDL function may be needed to supplement quantification of HDL cholesterol and HDL particle numbers and sizes.

High-density lipoprotein cholesterol and triglycerides in the statin era: A pending issue?

MOTS CLES HDL-Cholesterol ; Triglycerides ; Statines ; Syndrome metabolique Statins are highly effective for lowering low-density lipoprotein (LDL) cholesterol and reaching LDL targets, but have a limited impact on triglycerides and high-density lipoprotein (HDL) cholesterol. In this issue of the journal, Laforest et al. demonstrate that high triglyceride and low HDL-cholesterol concentrations are frequent in patients treated with hypolipidaemic agents, mostly statins [1]. In this study, patients with high triglycerides and low HDL-cholesterol also had more additional risk factors, in particular diabetes and hypertension. These findings raise questions about the relevance of lipid disturbances with statin treatment in high-risk patients. Is there any point in paying attention to hypertriglyceridemia and low HDL-cholesterol in these patients? Studies in families with premature coronary disease have indeed shown that a low HDL level was the most common abnormality and was most often associated with Hypertriglyceridemia [2]. In recent statin trials in high-risk patients, the prevalence of an HDL-cholesterol concentration less than 43mg/dl was high, between 40% [3] and 60% [4]. Low HDL-cholesterol was predictive of major cardiovascular events. In the placebo arm of the Heart protection study (HPS), patients with HDL-cholesterol less than 35mg/dl had a 43% higher risk than those with HDL-cholesterol greater than 43mg/dl [4]. Treatment with simvastatin decreased this gap only moderately (33% higher risk for HDL-cholesterol less than 35mg/dl while on statin treatment). An excess of risk remained in patients with low HDL-cholesterol receiving a high dosage of statin and in

S447X variant of the lipoprotein lipase gene, lipids, and risk of coronary heart disease in 3 prospective cohort studies

Lipoprotein lipase (LPL) has a prominent role in the metabolism of triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C) and is a potential interesting target for the development of antiatherogenic treatment. To provide deeper insight into the role of natural variation in this gene, we investigated the association between the LPL S447X variant with lipids and risk of coronary heart disease (CHD) in 3 independent, prospective studies. The S447X variant was genotyped in case-control studies of incident CHD nested within the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Danish Diet, Cancer and Health (DCH) study, totaling 245, 258, and 962 cases, respectively. S447X carriers tended to have lower TG and higher HDL-C concentrations than noncarriers. The S447X variant was associated with a lower risk of CHD in the NHS; the association was weaker in the HPFS and not statistically significant in the DCH women and men. The pooled relative risk per minor allele was 0.74 (0.56-1.00). There was a suggestion that the associations of the S447X variant with plasma lipids and CHD risk were more pronounced in obese individuals in the NHS study, but this finding was not consistent across the studies. The LPL S447X variant tended to be associated with lower TG and higher HDL-C levels, and lower risk of CHD in all 3 cohorts. Lipoprotein lipase is an attractive target for clinical intervention, but studies are needed to clarify whether greater benefit from this variant may be conferred in some subgroups.

Differential Influence of Diet and Physical Activity on Components of Metabolic Syndrome in a Multiethnic Sample of Children

Background Treatment of the metabolic syndrome in adults is generally approached with diet and physical activity. The influence of diet and physical activity on cardiometabolic outcomes in children has not been clearly established. Objective The main objective of this study was to test the hypothesis that the distribution of energy from fat and carbohydrate in addition to limited time spent engaging in physical activity would contribute to the prevalence of the metabolic syndrome and its components in a multiethnic pediatric population. Design Observational, cross-sectional study. Diet was assessed by two 24-hour recalls, physical activity by accelerometry, body composition by dual-energy absorptiometry, and glucose and lipid levels using fasting sera. Main outcome measures Presence of metabolic syndrome and its components. Subjects 202 African-American (n=79), white (n=68), or Hispanic (n=55) healthy children aged 7 to 12 years. Statistical analysis The contribution of diet and physical activity to the metabolic syndrome and its components were assessed by logistic regression and multiple linear regression analyses. Results Prevalence of the metabolic syndrome in the total sample was 8.4%, with Hispanics more likely than whites and African Americans to meet the criteria. A greater intake of energy from carbohydrate was related to a greater waist circumference and higher concentrations of triglyceride and glucose particularly apparent within the African-American sample ( P<0.05). Fat intake was associated with a lower waist circumference ( P<0.05) and with lower concentrations of triglyceride ( P<0.05) and glucose ( P<0.001) in the total sample. Greater moderate/hard physical activity was associated with higher high-density lipoprotein cholesterol concentrations in whites ( P<0.05). Increased sedentary behavior was related to greater glucose concentration in whites and Hispanics ( P<0.05 for both). Conclusions Diet composition was more closely related to the components of the metabolic syndrome than was physical activity, with carbohydrate intake being adversely related to waist circumference, triglyceride levels, and glucose levels. Furthermore, relationships among diet and metabolic syndrome outcomes were stronger among African-American children, suggesting that nutrition interventions in this group may be particularly beneficial.

Relationships between common polymorphisms of adenosine triphosphate–binding cassette transporter A1 and high-density lipoprotein cholesterol and coronary heart disease in a population with type 2 diabetes mellitus

Patients with type 2 diabetes mellitus (T2D) have a high coronary risk partly because of low levels of high-density lipoprotein-cholesterol (HDL-C). The adenosine triphosphate–binding cassette transporter A1 (ABCA1) plays a key role in HDL metabolism. We studied the association of common single nucleotide polymorphisms (SNPs) in the ABCA1 gene with HDL-C levels and coronary risk in a cohort of subjects with T2D. We studied 5 SNPs: +69C>T, +378G>C, R219K, I883M, and R1587K. The C allele of +378G>C was significantly associated with lower HDL-C concentrations ( P = .04); and the M allele of I883M, with higher HDL-C concentrations ( P = .03). No significant association was found between these SNPs and the incidence of new coronary events. Nevertheless, cross-sectional data on entry showed that the frequency of K219 was lower in patients with previous coronary heart disease (angina pectoris and/or myocardial infarction) (odds ratio, OR [95% confidence interval, CI] = 0.80 [0.65-0.98], P = .03, after adjustment for multiple risk factors other than HDL-C). The frequency of K1587 was higher in patients with angina pectoris (OR [95% CI] = 1.27 [1.01-1.58], P = .04, after multiple adjustment). The TT genotype of the C69T SNP was less frequent in subjects with prior myocardial infarction (OR [95% CI] = 0.28 [0.13-0.61], P = .001, after multiple adjustment). These associations persisted after further adjustment for HDL-C levels. In conclusion, common genetic variations of ABCA1 had a moderate influence on HDL-C levels and/or coronary heart disease in patients with T2D. These 2 effects were independent.

Association of the cholesteryl ester transfer protein Taq1 B2B2 genotype with higher high-density lipoprotein cholesterol concentrations and lower risk of coronary artery disease in a Tunisian population

The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is undergoing debate. In this prospective study, we sought to explore the role of the CETP Taq1B variant in coronary artery disease risk, and its association with plasma lipid and apolipoprotein concentrations. DNA was extracted from 316 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured by enzymatic and nephelometric assays. In our study population, the B2 allele frequency was 0.29. B2 allele carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype (1.041+/-0.294 versus 0.995+/-0.277; p=0.039). After adjusting for age, sex, smoking status, diabetes, hypertension and dyslipidaemia, the odds ratio (OR) for significant stenosis associated with the B2 allele was 0.82 (95% confidence interval (CI) 0.60-0.97; p=0.039), suggesting that the B2 allele is associated with an 18% lower risk of significant stenosis. This protective effect seemed to be more significant in male nonsmokers (38% lower risk; OR 0.62, 95% CI 0.29-0.92; p=0.029). No significant protective effects were observed in women or male smokers. Our data suggest that the B2 allele is associated with higher concentrations of HDL-C, which confer a protective effect with regard to coronary atherosclerosis. This effect seems to be more significant in men than in women and in nonsmokers than in smokers.

The lack of effect of isoflavones on high-density lipoprotein cholesterol concentrations in adolescent boys: a 6-week randomised trial

A substantial fall in high-density lipoprotein cholesterol (HDL-C) during puberty in boys, but not girls, has been reported in Western populations. The fall in boys is believed to be due to hormonal changes--androgens have been shown to be associated with lower HDL-C, whereas oestrogens are associated with higher HDL-C. The fall in HDL-C during puberty was not observed, however, in a study of Moslem boys in Israel, nor in a group of Japanese boys. A diet high in phyto-oestrogens may account for the lack of a fall in HDL-C in these populations. To examine the effect of dietary supplementation with phyto-oestrogens on the HDL-C concentration of adolescent boys from a Western population. We hypothesised that dietary supplementation of 50 mg of the isoflavones daidzein and genistein would produce a 12% higher HDL-C concentration than in controls at the end of a 6-week intervention period. A randomised controlled trial. Hellyer College in Burnie (Tasmania, Australia). Adolescent boys (aged 16-18 years) were recruited through a letter sent to parents. A total of 132 eligible participants enrolled and five subjects withdrew from the trial. No significant increase in HDL-C was observed in the treatment group (-0.02 mmol l(-1), standard error (SE)=0.03, P = 0.53) or the placebo group (0.05 mmol l(-1), SE = 0.03, P = 0.11). Factors other than isolated dietary isoflavones may be responsible for the lack of fall in HDL-C during puberty in Japanese and Moslem boys.

Association of polymorphisms at restriction enzyme recognition sites of apolipoprotein B and E gene with dyslipidemia in children undergoing primary nephrotic syndrome

Dyslipidemia, a common complication, is very prevalent in children with primary nephrotic syndrome (PNS). Recent studies have shown that genetic basis may be involved in the onset of HLP secondary to PNS. ApoB and E have been identified as the important candidate genes for lipid abnormalities. To investigate the association of apolipoprotein B (apoB) and E (apoE) genetic polymorphisms (Xba I, EcoR I, Msp I, and Hha I) with parameters describing the serum lipid profiles in children undergoing PNS. Genomic DNA was extracted from 250 children diagnosed with PNS and 200 healthy controls with neither allergic nor renal disease. ApoB (Xba I, EcoR I, and Msp I) and apoE (Hha I) genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. The fasting serum lipoprotein (a) [Lp(a)], total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), apoB, and total protein from a 24-h urine sample were measured. No significant differences in genotypes and alleles frequencies were observed for the apoB Xba I, EcoR I, Msp I and the apoE Hha I restriction sites in PNS patients as compared to controls (P > 0.05). Patients and controls with X + allele exhibited significantly higher serum levels of Lp(a), TC, nonHDL-C, LDL-C, LDL-C/HDL-C ratio, and apoB than that with X- allele (P < 0.05), whereas for apoA1/B ratio the opposite was found (P < 0.01). E-/E- carriers had significantly higher Lp(a), TC, HDL-C, and apoA1 concentrations than did E+/E- or E+/E+ carriers in control group (P < 0.05). Healthy children carrying the rare EcoR I allele had higher mean Lp(a), TC, and HDL-C levels than homozygotes for E+ (P < 0.05). Higher Lp(a) serum concentrations were observed in patients with E- allele (P < 0.05). No significant differences in lipid parameters were determined for the apoB Msp I and apoE Hha I the polymorphisms study (P > 0.05). When genetic variations were compared with urinary protein excretion, the Xba I X- allele was more frequent in patients with elevated proteinuria (P < 0.01). Presence of Xba I X+ allele and/or EcoR I E- at the apoB gene may be risk factors for lipid abnormalities secondary to childhood PNS.

Plasma Polyunsaturated Fatty Acids and the Decline of Renal Function

Recent studies suggest an association between polyunsaturated fatty acids (PUFAs) and the development of chronic kidney disease. The aim of this study was to examine the relationship between PUFAs and renal function in older adults. We performed a cross-sectional and prospective analysis of 931 adults, > or = 65 years old, enrolled in the InCHIANTI study, a population-based cohort in Tuscany, Italy. Plasma PUFAs were measured at enrollment, and creatinine clearance was estimated by the Cockcroft-Gault equation at baseline and after 3-year follow-up. At enrollment, participants with higher creatinine clearance had higher concentrations of HDL cholesterol, total plasma PUFAs, plasma n-3 fatty acid (FA), and plasma n-6 FA and lower triglycerides. From enrollment to the 3-year follow-up visit, creatinine clearance declined by 7.8 (12.2) mL/min (P <0.0001). Baseline total plasma PUFAs, n-3 FA, n-6 FA, and linoleic, linolenic, and arachidonic acids were strong independent predictors of less steep decline in creatinine clearance from baseline to follow-up (P <0.0001, after adjusting for baseline creatinine clearance). After adjusting for baseline creatinine, baseline total plasma PUFAs, n-3 FA, and linoleic, linolenic, and arachidonic acids were negatively associated with creatinine at 3-year follow-up. Participants with higher plasma PUFAs at enrollment had a lower risk of developing renal insufficiency, defined by a creatinine clearance <60 mL/min, during 3-year follow-up. High PUFA concentrations, both n-3 FA and n-6 FA, may attenuate the age-associated decline in renal function among older community-dwelling women and men.

Dietary patterns and the insulin resistance phenotypes among non‐diabetic adults

Background: Information on the relation between dietary patterns derived by cluster analysis and insulin resistance is scarce.Objective: To compare insulin resistance phenotypes, including waist circumference, body mass index, fasting and 2‐hour post‐challenge insulin, insulin sensitivity index (ISI 0,120), HDL cholesterol, and triacylglycerol across the dietary patterns identified by cluster analysis.Design: Dietary patterns and insulin resistance phenotypes were assessed in a cross‐sectional study of 2,875 non‐diabetic subjects participating in the Framingham Offspring Study at the fifth examination cycle.Results: Four dietary patterns were identified (Healthy, Sweet, Alcohol, and Soda). After adjusting for multiple comparisons and potential confounders, in comparison to the Healthy pattern, fasting insulin was significantly higher in the Soda pattern (29.3 vs. 27.1μU/mL). Compared to the Healthy pattern, the Alcohol pattern had significantly lower 2‐hour post‐challenge insulin (65.6 vs. 75.8μU/mL), higher ISI 0,120 (28.1 vs. 26.6) and higher HDL cholesterol concentrations (55.5 vs. 48.5 mg/dL).Conclusions: Compared to the healthy dietary pattern, individuals in the soda pattern had higher fasting insulin, while those in the Alcohol pattern had better insulin sensitivity. Further studies are needed to examine the effects of beverage consumption on insulin sensitivity.

Cholesteryl ester transfer protein genetic polymorphisms, HDL cholesterol, and subclinical cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis

The cholesteryl ester transfer protein (CETP) plays a key role in high-density lipoprotein (HDL) metabolism. Genetic variants that alter CETP activity and concentration may cause significant alterations in HDL-cholesterol (HDL-C) concentration; however, controversies remain about whether these genetic variants are associated with atherosclerosis. We genotyped the CETP R451Q, A373P, −629C/A, Taq1B, and −2505C/A polymorphisms in a cohort of Caucasian, Chinese, African-American, and Hispanic individuals within the Multi-Ethnic Study of Atherosclerosis. Genotypes were examined in relationship to HDL-C, CETP activity, CETP concentration, and three measures of subclinical cardiovascular disease (CVD): coronary artery calcium (CAC) measured by fast CT scanning, carotid intimal-medial thickness (IMT), and carotid artery plaque measured by ultrasonography. Carriers of the 451Q and 373P alleles have a significantly higher CETP concentration (22.4% and 19.5%, respectively; p < 0.001) and activity (13.1% and 9.4%, respectively; p < 0.01) and lower HDL-C (5.6% and 6.0%, respectively; p < 0.05). The minor alleles of the R451Q and A373P polymorphisms are associated with the presence of CAC, even after adjusting for CVD risk factors and HDL-C ( p = 0.006 and p = 0.01, respectively). The R451Q polymorphism is also associated with presence of carotid artery plaque ( p = 0.036). Polymorphism is associated with neither common nor internal carotid IMT. We confirmed that the −629A, Taq1B B2, and −2505A alleles are significantly associated with lower CETP concentration (20.8%, 25.0%, and 23.7%, respectively; p < 0.001) and activity (14.8%, 19.8%, and 18.4%, respectively; p < 0.001) and higher HDL-C concentration (9.7%, 11.5%, and 10.4%, respectively; p < 0.01). However, we did not find any associations between these non-coding polymorphisms and subclinical CVD.

Detection of small dense LDL-cholesterol: is it necessary to determine particle size?

Evaluation of: Julius U, Dittrich M, Pietzsch J: Factors influencing the formation of small dense low-density lipoprotein particles in dependence on the presence of the metabolic syndrome and on the degree of glucose intolerance. Int. J. Clin. Pract. 61(11), 1798–1804 (2007). Samples from the Familial Metabolic Syndrome Study in Saxony were used to assess the determinants of small dense LDL levels. After correction for degree of hyperglycemia, hyperinsulinemia, age, gender and BMI the strongest correlates of particle size were the levels of VLDL triglyceride (r = -0.598) or plasma triglycerides (r = -0.623). The study reviewed has highlighted the great utility of triglycerides as a simple practical surrogate for the detection of small dense LDL particles, but has also suggested that significant quantities of small dense LDL may occur at far higher HDL-cholesterol concentrations than previously suspected, suggesting that formal measurement of levels of small dense particles may be necessary. However it sti...

USF1 gene variants contribute to metabolic traits in men in a longitudinal 32-year follow-up study

Genetic variants of upstream transcription factor 1 (USF1) have previously been associated with dyslipidaemias in family studies. Our aim was to further address the role of USF1 in metabolic syndrome and cardiovascular traits at the population level in a large Swedish male cohort (n=2,322) with multiple measurements for risk factors during 32 years of follow-up. Participants, born in 1920-1924, were examined at 50, 60, 70 and 77 years of age. The follow-up period for cardiovascular events was 1970-2002. We genotyped three haplotype tagging polymorphisms capturing the major allelic variants of USF1. SNP rs2774279 was associated with the metabolic syndrome. The minor allele of rs2774279 was less common among individuals with metabolic syndrome than among healthy controls [p=0.0029 when metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III; p=0.0073 when defined according to the International Diabetes Federation (IDF)]. The minor allele of rs2774279 was also associated with lower BMI, lower fasting glucose values and higher HDL-cholesterol concentrations in longitudinal analyses. With SNP rs2073658, a borderline association with metabolic syndrome was observed (p=0.036, IDF), the minor allele being the risk-increasing allele. The minor allele of rs2073658 also associated with higher total and LDL-cholesterol, apolipoprotein B-100 and lipoprotein(a) concentrations in longitudinal analyses. Importantly, these trends with respect to the allelic variants prevailed throughout the follow-up time of three decades. Our results suggest that USF1 variants associate with the metabolic syndrome at population level and influence the cardiovascular risk factors throughout adulthood in a consistent, longitudinal manner.

Associations between HDL-cholesterol and polymorphisms in hepatic lipase and lipoprotein lipase genes are modified by dietary fat intake in African American and White adults

Polymorphisms in genes involved in HDL-cholesterol (HDL-C) metabolism influence plasma HDL-C concentrations. We examined whether dietary fat intake modified relations between HDL-C and polymorphisms in hepatic lipase ( LIPC-514C → T), cholesteryl ester transfer protein ( CETP TaqIB), and lipoprotein lipase ( LPL S447X) genes. Diet (food frequency questionnaire), plasma lipids, and LIPC, CETP, and LPL genotypes were assessed in ∼12,000 White and African American adults. In both races and all genotypes studied, minor allele homozygotes had highest HDL-C concentrations compared to the other genotypes ( P < 0.001). However, main effects were modified by usual dietary fat intake. In African Americans – women somewhat more strongly than men – LIPC TT homozygotes with fat intake ≥33.2% of energy had ∼3–4 mg/dL higher HDL-C concentrations than CC and CT genotypes. In contrast, when fat intake was <33.2% of energy, TT homozygotes had HDL-C concentrations ∼3.5 mg/dL greater than those with the CC genotype but not different from those with the CT genotype ( P interaction = 0.013). In Whites, LPL GG homozygotes had greatest HDL-C at lower total, saturated, and monounsaturated fat intakes but lowest HDL-C at higher intakes of these fats ( P interaction ≤ 0.002). Dietary fat did not modify associations between CETP and HDL-C. In conclusion, these data show that plasma HDL-C differs according to LIPC, LPL, and CETP genotypes. In the case of LIPC and LPL, data suggest dietary fat modifies these relations.

The long‐term effects of rosiglitazone on serum lipid concentrations and body weight

Although rosiglitazone, an insulin sensitizer, is known to have beneficial effects on high density lipoprotein cholesterol (HDL-C) concentrations and low density lipoprotein (LDL) particle size, it has unwanted effects on total cholesterol (TC) and LDL cholesterol (LDL-C) concentrations and body weight in some short-term studies. The aim of this study was to evaluate the long-term effects of rosiglitazone on serum lipid levels and body weight. Open labelled clinical study. We prospectively evaluated fasting serum glucose, haemoglobin A(1c) (HbA(1c)), lipid profiles and body weight at baseline and every 3 months after the use of rosiglitazone (4 mg/day) for 18 months in 202 type 2 diabetic patients. TC levels increased maximally at 3 months and decreased thereafter. However, overall, TC levels remained significantly higher at 18 months than those at baseline. LDL-C levels from the 3-month to the 12-month timepoint were significantly higher than those at baseline. However, after 15 months, LDL-C concentrations were not significantly different from basal LDL-C concentrations. HDL-C levels increased after the first 3 months and these levels were maintained. The increment of change in HDL-C was more prominent in patients with low basal HDL-C concentrations than in patients with high basal HDL-C concentrations. Body weight increased after the first 3 months and these levels were maintained. HDL-C and body weight increased and remained elevated for the duration of the study. There was an initial increase in LDL-C but this attenuated and by the end of the study was not significantly elevated above baseline levels.