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Background and aims: Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia. Methods and results: Multivariable Cox analyses were made in 18,072 participants from the multicentre URRAH study stratified by sex and HDL-cholesterol category. During a median follow-up of 11.4 years there were 1307 cases of CVM. In multivariable Cox models a J-shaped association was found in the whole population, with the highest risk being present in the high HDL-cholesterol group [>80 mg/dL, adjusted hazard ratio (HR), 1.28; 95%CI, 1.02–1.61; p = 0.031)]. However, a sex-specific analysis revealed that this association was present only in women (HR, 1.34; 95%CI, 1.02–1.77; p = 0.034) but not in men. The risk of CVM related to high HDL-cholesterol was much greater in the women with high uric acid (>0.30 mmol/L, HR 1.61; 95%CI, 1.08–2.39) than in those with low uric acid (HR, 1.17; 95%CI, 0.80–1.72, p for interaction = 0.016). In women older than 70 years with hyperuricemia the risk related to high HDL-cholesterol was 1.83 (95%CI, 1.19–2.80, p < 0.005). Inclusion of BMI in the models weakened the strength of the associations. Conclusion: Our data indicate that very high HDL-cholesterol levels in women are associated with CVM in a J-shaped fashion. The risk of CVM is increased by concomitant hyperuricemia suggesting that a proinflammatory/oxidative state can enhance the detrimental cardiovascular effects associated with high HDL-cholesterol.

Telomere length (TL) is a well-known marker of age-related diseases. Oxidative stress and inflammation increase the rate of telomere shortening, triggering cellular senescence. Although lipoproteins could have anti-inflammatory and proinflammatory functional properties, the relationship between lipoprotein particles with TL and telomerase activity-related genes has not been investigated much. In this study, we assessed the associations of lipoprotein subfractions with telomere length, TERT, and WRAP53 expression in a total of 54 pre-diabetic subjects from the EPIRDEM study. We regressed TL, TERT, and WRAP53 on 12 lipoprotein subclasses, employing a Gaussian linear regression method with Lasso penalty to determine a lipoprotein profile associated with telomere-related parameters. The covariates included age, sex, body mass index (BMI), dyslipidemia, statin consumption, and physical activity leisure time. We identified a lipoprotein profile composed of four lipoprotein subfractions associated with TL (Pearson r = 0.347, p-value = 0.010), two lipoprotein subfractions associated with TERT expression (Pearson r = 0.316, p-value = 0.020), and five lipoprotein subfractions associated with WRAP53 expression (Pearson r = 0.379, p-value =0.005). After adjusting for known confounding factors, most lipoprotein profiles maintained the association with TL, TERT, and WRAP53. Overall, medium and small-sized HDL particles were associated with shorter telomeres and lower expression of TERT and WRAP53. Large HDL particles were associated with longer telomere and lower expression of WRAP53, but not with TERT. Our results suggest that the lipoprotein profiles are associated with telomere length, TERT, and WRAP53 expression and should be considered when assessing the risk of chronic diseases

[EN] Background The relationship between antidepressant response and glial, inflammatory, and metabolic markers is poorly understood in depression. This study assessed the ability of biological markers to predict antidepressant response in major depressive disorder (MDD). Methods We included 31 MDD outpatients treated with escitalopram or sertraline for 8 consecutive weeks. The Montgomery-angstrom sberg Depression Rating Scale (MADRS) was administered at baseline and at week 4 and 8 of treatment. Concomitantly, blood samples were collected for the determination of serum S100B, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL)-C levels. Treatment response was defined as >= 50% improvement in the MADRS score from baseline to either week 4 or 8. Variables associated with treatment response were included in a linear regression model as predictors of treatment response. Results Twenty-seven patients (87%) completed 8 weeks of treatment; 74% and 63% were responders at week 4 and 8, respectively. High S100B and low HDL-C levels at baseline were associated with better treatment response at both time points. Low CRP levels were correlated with better response at week 4. Multivariate analysis showed that high baseline S100B levels and low baseline HDL-C levels were good predictors of treatment response at week 4 (R(2 = )0.457, P = .001), while S100B was at week 8 (R-2 = 0.239, P = .011). Importantly, baseline S100B and HDL-C levels were not associated with depression severity and did not change over time with clinical improvement. Conclusions Serum S100B levels appear to be a useful biomarker of antidepressant response in MDD even when considering inflammatory and metabolic markers

When lean people adopt carbohydrate-restricted diets (CRDs), they may develop a lipid profile consisting of elevated LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) with low triglycerides (TGs). The magnitude of this lipid profile correlates with BMI such that those with lower BMI exhibit larger increases in both LDL-C and HDL-C. The inverse association between BMI and LDL-C and HDL-C change on CRD contributed to the discovery of a subset of individuals-termed Lean Mass Hyper-Responders (LMHR)-who, despite normal pre-diet LDL-C, as compared to non-LMHR (mean levels of 148 and 145 mg/dL, respectively), exhibited a pronounced hyperlipidemic response to a CRD, with mean LDL-C and HDL-C levels increasing to 320 and 99 mg/dL, respectively, in the context of mean TG of 47 mg/dL. In some LMHR, LDL-C levels may be in excess of 500 mg/dL, again, with relatively normal pre-diet LDL-C and absent of genetic findings indicative of familial hypercholesterolemia in those who have been tested. The Lipid Energy Model (LEM) attempts to explain this metabolic phenomenon by positing that, with carbohydrate restriction in lean persons, the increased dependence on fat as a metabolic substrate drives increased hepatic secretion and peripheral uptake of TG contained within very low-density lipoproteins (VLDL) by lipoprotein lipase, resulting in marked elevations of LDL-C and HDL-C, and low TG. Herein, we review the core features of the LEM. We review several existing lines of evidence supporting the model and suggest ways to test the model's predictions.

Polycystic ovarian syndrome can be defined as an endocrine disorder that most affects the reproductive system of women of childbearing age; its causes are not exactly known. However, the majority of the experts agree that it is a multifactorial entity with multiple factors. Genetics is becoming increasingly important. In recent years, several genes that are involved in the pathogenic processes of this syndrome have been identified. Within these, the most important ones are the ones that encode steroidogenesis enzymes and insulin receptors, as well as other hormones that are associated with the actions of insulin and gonadotropins and their receptors. The results obtained included 1) women with PCOS had significantly lower levels of adiponectin compared to controls. Adiponectin levels were significantly lower in both lean and obese women with PCOS compared to the control group. 2) PCOS women had significantly higher levels of LH, FSH, LH/FSH ratio, and total testosterone compared to controls. 3) Both lean and obese PCOS women had significantly higher levels of LH, LH/FSH ratio, and total testosterone compared to the control group, however, FSH levels were significantly increased only in obese PCOS women compared to controls. 4) PCOS women had significantly higher levels of total cholesterol, triglycerides, LDL cholesterol, VLDL cholesterol, and lower levels of HDL-cholesterol compared to controls. 5) Both lean and obese PCOS women had significantly higher levels of total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol compared to controls. Only obese PCOS women had significantly lower levels of HDL-cholesterol compared to the controls. 6) The genotype analysis of FSHR gene polymorphism showed that the heterozygote Ala/Thr genotype was significantly more frequent in PCOS patients than in controls (64.1% versus 40%).

Aims/hypothesis: Five clusters based on clinical characteristics have been suggested as diabetes subtypes: one autoimmune and four subtypes of type 2 diabetes. In the current study we replicate and cross-validate these type 2 diabetes clusters in three large cohorts using variables readily measured in the clinic. Methods: In three independent cohorts, in total 15,940 individuals were clustered based on age, BMI, HbA1c, random or fasting C-peptide, and HDL-cholesterol. Clusters were cross-validated against the original clusters based on HOMA measures. In addition, between cohorts, clusters were cross-validated by re-assigning people based on each cohort’s cluster centres. Finally, we compared the time to insulin requirement for each cluster. Results: Five distinct type 2 diabetes clusters were identified and mapped back to the original four All New Diabetics in Scania (ANDIS) clusters. Using C-peptide and HDL-cholesterol instead of HOMA2-B and HOMA2-IR, three of the clusters mapped with high sensitivity (80.6–90.7%) to the previously identified severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD) and mild obesity-related diabetes (MOD) clusters. The previously described ANDIS mild age-related diabetes (MARD) cluster could be mapped to the two milder groups in our study: one characterised by high HDL-cholesterol (mild diabetes with high HDL-cholesterol [MDH] cluster), and the other not having any extreme characteristic (mild diabetes [MD]). When these two milder groups were combined, they mapped well to the previously labelled MARD cluster (sensitivity 79.1%). In the cross-validation between cohorts, particularly the SIDD and MDH clusters cross-validated well, with sensitivities ranging from 73.3% to 97.1%. SIRD and MD showed a lower sensitivity, ranging from 36.1% to 92.3%, where individuals shifted from SIRD to MD and vice versa. People belonging to the SIDD cluster showed the fastest progression towards insulin requiremen

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c., Unión Europea. FP7, Ministerio de Ciencia e Innovación (MICINN)/FEDER, Instituto de Salud Carlos III (ISCIII)/FEDER, Instituto de Salud Carlos III (ISCIII)/FEDER, Instituto de Salud Carlos III (ISCIII)/FEDER, Junta de Andalucía, Generalitat Valenciana, Depto. de Medicina, Fac. de Medicina, TRUE, pub

Background: We evaluated the qualitative characteristics of high-density lipoprotein (HDL) particles in metabolically healthy and unhealthy overweight and obese subjects. Methods: The study involved 115 subject individuals classified as metabolically healthy and unhealthy, as in overweight and obese groups. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to measure oxidized HDL (OxHDL) and serum amyloid A (SAA) concentrations. Lipoprotein subfractions were separated using nondenaturing gradient gel electrophoresis. Results: An independent association was shown between increased OxHDL/HDL-cholesterol ratio and the occurrence of metabolically unhealthy phenotype in the overweight and obese groups. The OxHDL/HDL-cholesterol ratio showed excellent and acceptable diagnostic accuracy in determination of metabolic health phenotypes (overweight group, AUC = 0.881; obese group, AUC = 0.765). Accumulation of smaller HDL particles in metabolically unhealthy subjects was verified by lipoprotein subfraction analysis. SAA concentrations did not differ significantly between phenotypes. Conclusions: Increased OxHDL/HDL-cholesterol ratio may be a potential indicator of disturbed metabolic health in overweight and obese individuals.

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride (TG) levels, low HDL-cholesterol concentrations and alterations in LDL composition and concentration. A functional, non-coding −514C>T single nucleotide polymorphism (SNP) of the hepatic lipase gene (LIPC) has been related to variation in HDL-cholesterol concentrations. Objectives: To investigate the hypotheses that the LIPC −514C>T polymorphism may be associated with a deteriorated lipoprotein-lipid profile and that environmental factor, such as abdominal obesity, alters this association. Methods: A total of 235 French-Canadian men from the greater Quebec City area were assigned into three groups on the basis of their LIPC −514C>T SNP, including 149 CC homozygotes, 75 CT heterozygotes, and 11 TT homozygotes. Results: In the present study, the highest values of BMI, waist circumference, and accumulation of visceral adipose tissue (VAT) were observed among TT homozygotes (p<0.05). After adjustment for age and BMI, TT homozygotes still showed higher plasma apolipoprotein (apo) AI and HDL-TG concentrations than the two other groups (p<0.05). When the two genotype groups (CC vs CT/TT) were further divided on the basis of VAT accumulation using a cut-off point of 130 cm2 (high vs low) it appears that irrespective of the genotype subjects with low VAT had higher HDL2-cholesterol concentrations (p<0.0001). However, lean carriers of the T allele had higher plasma HDL2-cholesterol levels than lean CC homozygotes. The beneficial effect of the T allele on plasma HDL2-cholesterol levels was abolished in the presence of visceral obesity (VAT>130 cm2). Conclusion: In summary, the presence of visceral obesity attenuates the impact of the LIPC −514C>T polymorphism on plasma HDL2-cholesterol levels.

OBJECTIVE: The aim of this study was to examine the relation between the CETP-TaqIB polymorphism and reduced plasma HDL-cholesterol levels commonly observed among men characterized by abdominal obesity and features of the insulin resistance syndrome. SUBJECTS: A total of 187 sedentary men, non-smokers and free from metabolic disorders were classi®ed on the basis of their CETP-TaqIB genotype. RESULTS: Plasma HDL and HDL3-cholesterol concentrations as well as the CETP activity were signi®cantly different between the three genotypes, B1B1 men having signi®cantly lower HDL and HDL3-cholesterol levels and higher CETP activity than B2B2 homozygotes. A 23 ANOVA was used to determine the source of variation of plasma HDL and HDL2-cholesterol levels among the three genotypic groups of men divided on the basis of either a high ( 27 kg=m2) or a low (< 27 kg=m2) BMI, a high ( 130 cm2) or a low (< 130 cm2) accumulation of visceral adipose tissue assessed by computed tomography, or a low versus a high fasting plasma insulin concentration (using the median value as a cutoff point). The effect of the CETP genotype observed on plasma HDL-cholesterol concentrations was attenuated among men with features of the insulin resistance syndrome. It seems that the expected raising effect of the B2 allele on plasma HDL-cholesterol concentrations was blunted in the presence of a BMI 27 kg=m2, a high accumulation of visceral adipose tissue or hyperinsulinaemia. CONCLUSION: Our data indicate that the CETP gene TaqIB polymorphism in¯uences plasma CETP activity on one hand and plasma HDL-cholesterol concentrations on the other hand among men. The association between the TaqIB polymorphism and plasma HDL-cholesterol concentrations is altered by the presence of abdominal obesity and some features of the insulin resistance syndrome.

Evidence suggests that fibrate therapy reduces the risk of recurrent coronary heart disease among men with low levels of high density lipoprotein cholesterol (HDL-C). Indirect observations and new possible biological pathways suggest that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism might modulate the lipoprotein/lipid profile and its response to fibrate therapy. To assess the possible interaction between fibrate therapy and such variants on plasma lipid and lipoprotein levels, 65 dyslipidemic abdominally obese men were treated for 6 months with or without gemfibrozil (600 mg twice daily). No differences in baseline plasma lipid and lipoprotein levels were found between genotype groups except for the HDL(3)-C subfraction, which was higher in the DD group (p = 0.02). A two-way factorial ANOVA was used to evaluate the effect of the genotype (DD homozygotes vs I allele carriers), the treatment (placebo vs gemfibrozil), and the interaction between these two independent variables on changes observed in lipid and lipoprotein concentrations. A significant genotype-by-treatment interaction (p = 0.02) was found for the plasma HDL-C response to the intervention program. In fact, having the DD genotype and being treated with gemfibrozil had a synergical effect on HDL-C levels. The results of this study suggest that the ACE I/D polymorphism influences the effect of gemfibrozil on plasma HDL-C levels.

The Inuit population is often described as being protected against CVD due to their traditional dietary patterns and their unique genetic background. The objective of the present study was to examine gene–diet interaction effects on plasma lipid levels in the Inuit population. Data from the Qanuippitaa Nunavik Health Survey (n 553) were analysed via regression models which included the following: genotypes for thirty-five known polymorphisms (SNP) from twenty genes related to lipid metabolism; dietary fat intake including total fat (TotFat) and saturated fat (SatFat) estimated from a FFQ; plasma lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and TAG. The results demonstrate that allele frequencies were different in the Inuit population compared with the Caucasian population. Further, seven SNP (APOA1 − 75G/A (rs670), APOB XbAI (rs693), AGT M235T (rs699), LIPC 480C/T (rs1800588), APOA1 84T/C (rs5070), PPARG2 − 618C/G (rs10865710) and APOE 219G/T (rs405509)) in interaction with TotFat and SatFat were significantly associated with one or two plasma lipid parameters. Another four SNP (APOC3 3238C>G (rs5128), CETP I405V (rs5882), CYP1A1 A4889G (rs1048943) and ABCA1 Arg219Lys (rs2230806)) in interaction with either TotFat or SatFat intake were significantly associated with one plasma lipid variable. Further, an additive effect of these SNP in interaction with TotFat or SatFat intake was significantly associated with higher TC, LDL-C or TAG levels, as well as with lower HDL-C levels. In conclusion, the present study supports the notion that gene–diet interactions play an important role in modifying plasma lipid levels in the Inuit population.

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

Lipoproteins play a central role in the development of atherosclerosis. High and low-density lipoproteins (HDL and LDL), known as 'good' and 'bad' cholesterol, respectively, remove and/or deposit lipids into the artery wall. Hence, insight into lipid exchange processes between lipoproteins and cell membranes is of particular importance in understanding the onset and development of cardiovascular disease. In order to elucidate the impact of phospholipid tail saturation and the presence of cholesterol in cell membranes on these processes, neutron reflection was employed in the present investigation to follow lipid exchange with both HDL and LDL against model membranes. Mirroring clinical risk factors for the development of atherosclerosis, lower exchange was observed in the presence of cholesterol, as well as for an unsaturated phospholipid, compared to faster exchange when using a fully saturated phospholipid. These results highlight the importance of membrane composition on the interaction with lipoproteins, chiefly the saturation level of the lipids and presence of cholesterol, and provide novel insight into factors of importance for build-up and reversibility of atherosclerotic plaque. In addition, the correlation between the results and well-established clinical risk factors suggests that the approach taken can be employed also for understanding a broader set of risk factors including, e.g., effects of triglycerides and oxidative stress, as well as local effects of drugs on atherosclerotic plaque formation.

Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 encodes the Golgi-localized polypeptide N-acetyl-D-galactosamine-transferase 2 isoenzyme. GALNT2 is widely expressed in most cell types and directs initiation of mucin-type protein O-glycosylation. All patients showed loss of O-glycosylation of apolipoprotein C-III, a non-redundant substrate for GALNT2. Patients with GALNT2-CDG generally exhibit a syndrome characterized by global developmental delay, intellectual disability with language deficit, autistic features, behavioural abnormalities, epilepsy, chronic insomnia, white matter changes on brain MRI, dysmorphic features, decreased stature, and decreased high density lipoprotein cholesterol levels. Rodent (mouse and rat) models of GALNT2-CDG recapitulated much of the human phenotype, including poor growth and neurodevelopmental abnormalities. In behavioural studies, GALNT2-CDG mice demonstrated cerebellar motor deficits, decreased sociability, and impaired sensory integration and processing. The multisystem nature of phenotypes in patients and rodent models of GALNT2-CDG suggest that there are multiple non-redundant protein substrates of GALNT2 in various tissues, including brain, which are critical to normal growth and development.

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvención con DIeta MEDiterranea-Plus) study. The polyphenol content of foods was estimated from the Phenol-Explorer 3.6 database. The mean of total polyphenol intake was 846 ± 318 mg/day. Except for stilbenes, women had higher polyphenol intake than men. Total polyphenol intake was higher in older participants (>70 years of age) compared to their younger counterparts. Participants with body mass index (BMI) >35 kg/m2 reported lower total polyphenol, flavonoid, and stilbene intake than those with lower BMI. Total polyphenol intake was not associated with a better profile concerning MetS components, except for high-density lipoprotein cholesterol (HDL-c), although stilbenes, lignans, and other polyphenols showed an inverse association with blood pressure, fasting plasma glucose, and triglycerides. A direct association with HDL-c was found for all subclasses except lignans and phenolic acids. To conclude, in participants with MetS, higher intake of several polyphenol subclasses was associated with a better profile of MetS components, especially HDL-c.

OBJECTIVES: Non-HDL-cholesterol (non-HDL-C) has been reported to be a better marker of cardiovascular risk than LDL-cholesterol (LDL-C) especially in individuals with high triglyceride values. Further, levels of remnant cholesterol have been suggested to in part explain residual risk not captured with LDL-C. The aim of the present study was to define reference values for non-HDL-C and remnant cholesterol based on data from the Nordic Reference Interval Project (NORIP). METHODS: We analyzed the test results for total cholesterol, HDL-cholesterol and triglycerides from 1392 healthy females and 1236 healthy males. Non-HDL-C was calculated as measured total cholesterol minus measured HDL-cholesterol. Remnant cholesterol was calculated using the Friedewald equation for LDL-C: measured total cholesterol minus measured HDL-cholesterol and minus calculated LDL-cholesterol. The 2.5th and 97.5th percentiles for these markers were calculated according to the International Federation of Clinical Chemistry guidelines on the statistical treatment of reference values. RESULTS: Age (18-<30, 30-49 and ≥50 years) and sex-specific reference intervals were calculated for non-HDL-cholesterol and remnant-cholesterol. Levels of non-HDL-C and remnant cholesterol differed between sex and age strata. CONCLUSIONS: Age- and sex-specific reference intervals should be used for the triglyceride rich lipid variables non-HDL-C and remnant cholesterol. Since these markers may add information on risk burden beyond LDL-C, our hope is that these reference intervals will aid the introduction of automatic reporting of non-HDL-C by hospital laboratories.

Background: The plasma concentration ratio of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) is a simple way to estimate insulin resistance. We aimed to evaluate the TG/HDL-C ratio as a simple clinical way to identify apparently healthy individuals with insulin resistance and enhanced risk of future cardiovascular disease (CVD). Methods: One thousand seven hundred twenty men, aged 50 years, free from diabetes and CVD when evaluated at baseline in 1970-1974 were followed for 40 years regarding incident CVD (myocardial infarction and/or ischemic stroke, n=576). Results: Participants with a high TG/HDL-C ratio (highest quartile >1.8) at baseline were more insulin resistant, with a significantly more adverse cardiometabolic risk profile (P<0.001) at baseline, compared with those with a lower ratio. This group also showed an increased risk of CVD [hazard ratio, HR 1.47 (95% confidence interval 1.26-1.93) P<0.001]. Fourteen percent of subjects with metabolic syndrome, in whom insulin resistance is increased, were also at enhanced CVD risk [HR 1.75 (1.42-2.16) P<0.001]. Conclusions: Twenty-five percent of apparently healthy 50-year-old men with the highest TG/HDL-C plasma concentration ratio had a significantly more adverse cardiometabolic profile at baseline, and developed more CVD over the next 40 years, compared with those not meeting this cut point. Determining the TG/HDL-C ratio in middle-aged men provided a simple and potentially clinically useful way to identify increased risk of developing CVD in persons free of diabetes or manifest CVD.

Background & aims: Chocolate consumption is associated with a decreased risk for CVD. Theobromine, a compound in cocoa, may explain these effects as it favorably affected fasting serum lipids. However, long-term effects of theobromine on postprandial metabolism as well as underlying mechanisms have never been studied. The objective was to evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial lipid, lipoprotein and glucose metabolism, and duodenal gene expression.Methods: In a randomized, double-blind crossover study, 44 healthy men and women, with low baseline HDL-C concentrations consumed 500 mg theobromine or placebo daily. After 4-weeks, fasting blood was sampled and subjects participated in a 4-h postprandial test. Blood was sampled frequently for analysis of lipid and glucose metabolism. In a subgroup of 10 men, 5 h after meal consumption duodenal biopsies were taken for microarray analysis.Results: 4-weeks theobromine consumption lowered fasting LDL-C (-0.21 mmol/L; P = 0.006), and apoB100 (-0.04 g/L; P = 0.022), tended to increase HDL-C (0.03 mmol/L; P = 0.088) and increased hsCRP (1.2 mg/L; P = 0.017) concentrations. Fasting apoA-I, TAG, FFA, glucose and insulin concentrations were unchanged. In the postprandial phase, theobromine consumption increased glucose (P = 0.026), insulin (P = 0,011) and FFA (P = 0.003) concentrations, while lipids and (apo)lipoproteins were unchanged. In duodenal biopsies, microarray analysis showed no consistent changes in expression of genes, pathways or gene sets related to lipid, cholesterol or glucose metabolism.Conclusions: It is not likely that the potential beneficial effects of cocoa on CVD can be ascribed to theobromine. Although theobromine lowers serum LDL-C concentrations, it did not change fasting HDL-C, apoA-I, or postprandial lipid concentrations and duodenal gene expression, and unfavorably affected postprandial glucose and insulin responses. Thi

Background and Objective: Several studies have reported that serum antibodies against periodontal pathogens are related not only to periodontal status but also to systemic conditions, such as glycemic control and serum lipids. Therefore, this study examined the associations of serum IgG antibodies against periodontal pathogens with periodontal status and serum lipid levels in community dwellers. Materials and Methods: A community-based cross-sectional study of 409 subjects (140 men, 269 women) aged = 40 years who had at least 5 teeth was conducted in Goto, Japan in 2009 and 2010. Results: The serum IgG levels against Porphyromonas gingivalis were significantly associated with periodontal parameters and serum high-density lipoprotein cholesterol (HDL-C) in men. According to a multiple linear regression analysis adjusted for covariates, the serum IgG levels against P. gingivalis were inversely related to serum HDL-C (B = -0.1; P = 0.004). Conclusion: This study suggests that an elevated immune response to the periodontal pathogen is independently correlated with lower serum HDL-C level in community-dwelling men., Journal of Men's Health, 14(4), pp.e11-e17; 2018

Tokom normalne, nekomplikovane trudnoće dolazi do prolaznog razvoja fiziološke insulinske rezistencije, intenziviranja oksidativnog stresa, kao i do promena u parametrima lipidnog statusa majke, ali još uvek nisu poznati svi mehanizmi koji utiču na ove promene. Poslednjih godina se sve veći značaj u ovom kontekstu pridaje i tkivima koja su se tradicionalno posmatrala kao depo energije (masno tkivo), ili kao deo potpornog i lokomotornog sistema (kost), a za koje je dokazano da produkuju niz metabolički aktivnih medijatora. U prva dva trimestra trudnoće majka skladišti najveći deo nutrijenata koje unosi. Poslednji trimestar trudnoće karakteriše ubrzan rast fetusa i pojačan transfer nutrijenata kroz placentu i zbog toga kod majke dolazi do intenziviranja kataboličkih procesa, kao i do razvoja fiziološke rezistencije tkiva na insulin. Tokom trudnoće razvija se lipidni profil koji se kod negravidnih žena smatra proaterogenim. Takođe dolazi i do porasta koncentracije HDL-holesterola, koji ima ateroprotektivna, antiinflamatorna i antioksidativna svojstva. Slobodni kiseonikovi radikali nastaju u aerobnom metabolizmu i igraju značajnu ulogu kao sekundarni glasnici. S druge strane, to su visoko reaktivna jedinjenja koja reaguju sa biološkim molekulima i dovode do njihovog oštećenja. Zato postoji niz mehanizama antioksidativne zaštite u organizmu. Poremećaj njihove ravnoteže, u kome dolazi do stvaranja viška reaktivnih radikala, dovodi do oksidativnog stresa. Trudnoća je stanje koje karakteriše povećana podložnost oksidativnom stresu, a praćena je i kompenzatornim povećanjem koncentracije parametara koji spadaju u sistem antioksidativne zaštite. U trudnoći dolazi do fiziološke regulacije urođenog imunskog odgovora radi prevencije odbacivanja fetusa. Masno tkivo produkuje biološki aktivne medijatore koji se nazivaju adipocitokini od kojih su najznačajniji leptin i adiponektin. Trudnoća se smatra stanjem centralne rezistencije na leptin, koja bi mogla imati uticaj na akumulaciju, Normal uncomplicated pregnancy is characterized by a transient development of physiological insulin resistance, intensifying of oxidative stress, as well as by changes in maternal lipid status, but the mechanisms of these changes are still incompletely understood. Tissues that are traditionally seen as energy storage (adipose tissue), or as a part of the locomotor system (bones), produce a number of metabolically active mediators. They are increasingly being recognized as a part of mechanisms of aforementioned changes. During the first and second trimester, a major part of nutrients is being stored. The third trimester is characterized by an accelerated fetal growth, so the maternal catabolic processes intensify and the physiological insulin resistance develops. The changes of maternal lipid status lead towards a more atherogenic state. The HDL-cholesterol also increases, and it has atheroprotective, anti-inflammatory, and antioxidative properties. Reactive oxidative species are products of oxidative metabolism and they have an important role as second messengers. On the other hand, they are highly reactive and can lead to a damage of biomolecules. They are normally counterbalanced by different anti-oxidative mechanisms. The oxidative stress occurs when the reactive species are produced in excess. Pregnancy is a state of increased susceptibility to oxidative stress, due to an increased basal oxygen consumption. At the same time, antioxidative mechanisms increase. The innate immune response is also regulated during pregnancy, so that fetus doesn’t get rejected. Adipose tissue produces biologically active mediators- adipocytokines, among which the most important are leptin and adiponectin. Pregnancy is considered to be a state of central leptin resistance, that might influence the accumulation of energy storage and could be connected to the insulin resistance. Adiponectin is a possible mediator implicated in the regulation of the glucose metabolism in pregnancy. Pregn

The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham-REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high-risk in the PREvención con DIeta MEDiterránea (PREDIMED) study-a nutrition-intervention primary prevention trial-and the impact of adherence to the Mediterranean diet on CVD across risk categories.In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55-74 years, 57% women; 48% with type 2 diabetes mellitus). Major CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate-adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham-REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6-year follow-up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata (P>0.4 for interaction).Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non-hig

The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham-REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high-risk in the PREvención con DIeta MEDiterránea (PREDIMED) study-a nutrition-intervention primary prevention trial-and the impact of adherence to the Mediterranean diet on CVD across risk categories.In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55-74 years, 57% women; 48% with type 2 diabetes mellitus). Major CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate-adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham-REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6-year follow-up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata (P>0.4 for interaction).Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non-hig

BackgroundIn addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation.Methods and resultsWe performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1×10-4 from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5×10-8) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment.ConclusionsBased on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.

© 2016 Idoia Ibero-Baraibar et al. Background: Cardiometabolic profile is usually altered in obesity. Interestingly, the consumption of flavanolrich foods might be protective against those metabolic alterations. Objective: To evaluate the postprandial cardiometabolic effects after the acute consumption of cocoa extract before and after 4 weeks of its daily intake. Furthermore, the bioavailability of cocoa extract was investigated. Design: Twenty-four overweight/obese middle-aged subjects participated in a 4-week intervention study. Half of the volunteers consumed a test meal enriched with 1.4 g of cocoa extract (415 mg flavanols), while the rest of the volunteers consumed the same meal without the cocoa extract (control group). Glucose and lipid profile, as well as blood pressure and cocoa metabolites in plasma, were assessed before and at 60, 120, and 180 min post-consumption, at the beginning of the study (Postprandial 1) and after following a 4-week 15% energy-restricted diet including meals containing or not containing the cocoa extract (Postprandial 2). Results: In the Postprandial 1 test, the area under the curve (AUC) of systolic blood pressure (SBP) was significantly higher in the cocoa group compared with the control group (p0.007), showing significant differences after 120 min of intake. However, no differences between groups were observed at Postprandial 2. Interestingly, the reduction of postprandial AUC of SBP (AUC-Postprandial 2-AUC-Postprandial 1) was higher in the cocoa group (p0.016). Furthermore, cocoa-derived metabolites were detected in plasma of the cocoa group, while the absence or significantly lower amounts of metabolites were found in the control group. Conclusions: The daily consumption of cocoa extract within an energy-restricted diet for 4 we

Aims: To relate the consumption of dietary fiber and saturated fat to biochemical markers in individuals with metabolic syndrome. Methods: The database of this cross-sectional study consisted of both male and female adults diagnosed with metabolic syndrome, according to the National Cholesterol Education Program's Adult Treatment Panel III, who participated in a study at the Pontifical Catholic University of Rio Grande do Sul. Data on all individuals registered at baseline who had complete information about their food intake were used. Consumption of dietary fiber and saturated fat was calculated based on the information provided by a 24-hour recall survey and a two-day food record. We evaluated the subjects in general and stratified by gender. The data were analyzed using descriptive statistics and the Student’s t test. The correlation between fiber and saturated fat intake and biochemical markers was measured by Pearson’s correlation coefficient. The significance level was set at 5%. Results: There were 79 individuals whose records contained complete information and who were eventually included in the study. A significant positive correlation was observed between saturated fat intake and serum triglyceride levels (r=0.30; p=0.008) and between saturated fat intake and insulin (r=0.26; p=0.021). Also, a significant inverse correlation was observed between fiber intake and serum levels of HDL cholesterol (r=-0.28; p=0.011). When stratified by gender, the positive correlation between consumption of saturated fat and triglycerides remained significant only among men (r=0.44; p=0.034). Conclusions: In this population diagnosed with metabolic syndrome, lower levels of HDL cholesterol were found in individuals who referred higher intake of dietary fiber, while individuals who reported elevated consumption of saturated fat had higher levels of insulin and triglycerides. In the gender-stratified analysis, positive correlation was found only between saturated fat consumption

Les dernières recommandations américaines concernant la prise en charge des dyslipidémies en prévention cardiovasculaire ont soulevé de nombreuses questions par leurs différences avec nos approches habituelles. Entre autres, elles ont éradiqué la nécessité de « cible » de LDL-C à atteindre en fonction du niveau de risque cardiovasculaire et ont proposé plutôt une stratégie basée sur l’intensité de la réduction relative du LDL-C. L’examen critique et la comparaison des recommandations européennes et américaines font apparaitre, toutefois, plus de similitudes que de différences, tout en encourageant à repenser certains aspects de notre pratique et à raviver notre motivation pour le plus grand bien des patients., [What are the provisions in the new American recommendations regarding the management of dyslipidemia in cardiovascular prevention? Comparison with the European and Belgian recommendations] The latest American recommendations on dyslipidemia management in cardiovascular prevention have raised several questions, due to inherent differences with our standard approaches. Among others, these new recommendations have eradicated the need for a LDL-choiesterol 'target' depending on the level of cardiovascular risk. Instead, they have proposed a strategy based on the extent of the relative reduction in LDL-choiesterol. Critical review of European and American recommendations reveals, however, more similarities than differences. Comparing these recommendations Invites us to rethink several aspects of our clinical practice while enhancing our motivation to the greatest benefit of our patients.

The latest American recommendations on dyslipidemia management in cardiovascular prevention have raised several questions, due to inherent differences with our standard approaches. Among others, these new recommendations have eradicated the need for a LDL-choiesterol 'target' depending on the level of cardiovascular risk. Instead, they have proposed a strategy based on the extent of the relative reduction in LDL-choiesterol. Critical review of European and American recommendations reveals, however, more similarities than differences. Comparing these recommendations Invites us to rethink several aspects of our clinical practice while enhancing our motivation to the greatest benefit of our patients., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Etravirine (ETR) was approved for patients with virological failure and antiretroviral resistance mutations. It has also shown antiviral efficacy in antiretroviral-naive patients. However, data on the switching from protease inhibitors (PI) to ETR are lacking.; Methods: HIV-1-infected patients with suppressed viral load (VL) during a PI-containing regimen (>12 months) and no previous virological failure were randomized to switch from the PI to ETR (400 mg/day, dissolved in water) (ETR group, n = 22) or to continue with the same regimen (control group, n = 21). Percentage of patients with VL <= 50 copies/mL were assessed at week 48, as well as changes in CD4 T-cell counts and metabolic profile.; Results: We included 43 patients [72.9% male, 46.3 (42.2; 50.6) years]. Two patients receiving ETR (grade-1 diarrhea and voluntary discontinuation) and another in the control group (simplification) discontinued therapy early. No patients presented virological failure (two consecutive VL>50 copies/mL); treatment was successful in 95.2% of the control group and 90.9% of the ETR group (intention-to-treat analysis, missing = failure) (p = 0.58). CD4+ T-cell counts did not significantly vary [+49 cells/mu L in the ETR group (p = 0.25) and -4 cells/mu L in the control group (p = 0.71)]. The ETR group showed significant reductions in cholesterol (p<0.001), triglycerides (p=<0.001), and glycemia (p = 0.03) and higher satisfaction (0-10 scale) (p = 0.04). Trough plasma concentrations of ETR were similar to observed in studies using ETR twice daily.; Conclusion: Switch from a PI-based regimen to a once-daily combination based on ETR maintained undetectable VL during 48 weeks in virologically suppressed HIV-infected patients while lipid profile and patient satisfaction improved significantly., Peer Reviewed, Postprint (published version)

The Inuit population is often described as being protected against CVD due to their traditional dietary patterns and their unique genetic background. The objective of the present study was to examine gene–diet interaction effects on plasma lipid levels in the Inuit population. Data from the Qanuippitaa Nunavik Health Survey (n 553) were analysed via regression models which included the following: genotypes for thirty-five known polymorphisms (SNP) from twenty genes related to lipid metabolism; dietary fat intake including total fat (TotFat) and saturated fat (SatFat) estimated from a FFQ; plasma lipid levels, namely total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and TAG. The results demonstrate that allele frequencies were different in the Inuit population compared with the Caucasian population. Further, seven SNP (APOA1 − 75G/A (rs670), APOB XbAI (rs693), AGT M235T (rs699), LIPC 480C/T (rs1800588), APOA1 84T/C (rs5070), PPARG2 − 618C/G (rs10865710) and APOE 219G/T (rs405509)) in interaction with TotFat and SatFat were significantly associated with one or two plasma lipid parameters. Another four SNP (APOC3 3238C>G (rs5128), CETP I405V (rs5882), CYP1A1 A4889G (rs1048943) and ABCA1 Arg219Lys (rs2230806)) in interaction with either TotFat or SatFat intake were significantly associated with one plasma lipid variable. Further, an additive effect of these SNP in interaction with TotFat or SatFat intake was significantly associated with higher TC, LDL-C or TAG levels, as well as with lower HDL-C levels. In conclusion, the present study supports the notion that gene–diet interactions play an important role in modifying plasma lipid levels in the Inuit population.

Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%, p

Coronary heart disease (CHD), a manifestation of atherosclerosis, is the leading single cause of death in Finland. CHD is affected by numerous genetic and environmental factors, their combined effects and interactions between them. Low HDL-cholesterol (HDL-C) is an independent risk factor for atherosclerosis and the most common dyslipidemia associated with early onset CHD, but the mechanisms regulating HDL-C levels and protecting from atherosclerosis are still not completely understood. Adiponectin is a hormone that is secreted by adipose tissue and has several anti-atherosclerotic effects. There is multiple evidence suggesting that adiponectin could protect against CHD via positive effects on HDL metabolism. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor that has a potentially conflicting role in atherosclerosis; it may have protecting or predisposing effects. The objective of this thesis was to study the genetic background of HDL-C regulation and atherosclerosis. Three studies were executed using extended families with CHD or case-control setting, with samples collected from Northern Finland. In the first study, seven chromosomal regions showing suggestive evidence of linkage were identified for HDL-C regulation, using genome-wide linkage approach. In the second study, we found a strong correlation between HDL-C and adiponectin, but failed to show evidence of a shared genetic background. However, a genetic correlation between adiponectin and low-density lipoprotein-cholesterol was revealed. We also studied the genetic regulation of adiponectin, and for the first time its most active form, high-molecular weight adiponectin, and found suggestive evidence of linkage to three chromosomal regions. In the third study, it was discovered that the studied VEGF gene polymorphisms did not have a major effect on atherosclerosis quantified as carotid intima-media thickness or the risk of acute myocardial infarction (AMI). This thesis pr, Tiivistelmä Sepelvaltimotauti, eräs valtimonkovettumataudin ilmentymä, on yleisin yksittäinen kuolinsyy maassamme. Taudin syntyyn vaikuttavat lukuisat geneettiset ja ympäristötekijät sekä niiden väliset yhteis- ja vuorovaikutukset. Pieni HDL-kolesterolipitoisuus on valtimonkovettumataudin itsenäinen riskitekijä ja yleisin kolesterolipoikkeavuus, joka liittyy varhain ilmenevään sepelvaltimotautiin. HDL-kolesterolin vaihtelun syitä ja tämän ”hyvän kolesterolin” sepelvaltimotaudilta suojaavia vaikutusmekanismeja ei kuitenkaan pystytä täysin selittämään. Adiponektiini on rasvakudoksen tuottama hormoni, jonka sepelvaltimotaudilta suojaavan ominaisuuden on ehdotettu johtuvan siitä, että se vaikuttaisi HDL-kolesterolin aineenvaihduntaan. VEGF (vascular endothelial growth factor) on verisuonten sisäseinämissä vaikuttava kasvutekijä, jolla saattaa olla joko sepelvaltimotaudilta suojaavia tai sille altistavia vaikutuksia. Väitöskirjatyön tavoitteena oli tutkia HDL-kolesterolin ja valtimonkovettumataudin geneettistä taustaa. Kolmessa osatyössä tutkittiin suuria pohjoissuomalaisia sepelvaltimotautisukuja; lisäksi käytettiin väestö- ja potilasaineistoja. Ensimmäisessä tutkimuksessa löydettiin koko genomin kytkentäkartoitusmenetelmällä seitsemän kromosomialuetta, jotka saattavat vaikuttaa HDL-kolesterolin säätelyyn. Toisessa tutkimuksessa selvitettiin adiponektiinin, ja ensimmäistä kertaa myös sen aktiivisimman muodon, HMW-adiponektiinin geneettistä taustaa. Kytkentäanalyysissä saatiin viitteitä kolmesta adiponektiineja mahdollisesti säätelevästä kromosomialueesta. Havaittiin myös, että HDL-kolesterolin ja adiponektiinin pitoisuudet korreloivat vahvasti keskenään, mutta yhteistä geneettistä säätelytekijää ei pystytty osoittamaan. LDL-kolesterolin ja adiponektiinin välillä kuitenkin havaittiin geneettinen korrelaatio. Kolmannessa tutkimuksessa todettiin, ettei tutkituilla VEGF-geenin nukleotidimuutoksilla todennäköisesti ole merkittävää syy-yhteyttä valtimonkovettumatautiin kaulav

Purpose: The relationship between plasma lipid levels and neoplastic diseases is still unclear The aim of this study was to analyse the lipid profile of individuals with non-Hodgkin lymphoma (NHL) or prostate carcinoma (CaP) and to follow serum lipid levels changes in NHL patients according to their response to chemotherapy. Patients and methods: Forty-seven patients with NHL, 57 patients with CaP two control groups composed of 29 and 43 age- and sex-matched healthy adults, related to NHL and CaP patients, respectively, were included in the study. Follow-up studies of NHL patients were carried out after the 3rd and 6th cycle of chemotherapy. Results: Initial plasma cholesterol (Chol), HDL-cholesterol (HDL-Chol) and phospholipids (PL) values were signficantly lower in patients with NHL or CaP than in controls. Following chemotherapy we noticed a progressive increase in lipid levels in NHL patients with complete remission (CR) and stable disease (SD), and further decrease in patients with the disease progression. Conclusion: Decreased plasma Chol, HDL-Chol and PL levels of patients with NHL or CaP can be considered as nonspecific prognostic parameters in patients with these malignancies.

Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human CETP transgene, niacin dose-dependently decreased plasma triglycerides (up to -77%, P<0.001) and total cholesterol (up to -66%, P<0.001). Concomitantly, niacin dose-dependently increased HDL-cholesterol (up to +87%, P<0.001), plasma apoAI (up to +72%, P<0.001), as well as the HDL particle size. In contrast, in APOE*3Leiden mice, not expressing CETP, niacin also decreased total cholesterol and triglycerides but did not increase HDL-cholesterol. In fact, in APOE*3Leiden.CETP mice, niacin dose-dependently decreased the hepatic expression of CETP (up to -88%; P<0.01) as well as plasma CETP mass (up to -45%, P<0.001) and CETP activity (up to -52%, P<0.001). Additionally, niacin dose-dependently decreased the clearance of apoAI from plasma and reduced the uptake of apoAI by the kidneys (up to -90%, P<0.01). Conclusion - Niacin markedly increases HDL-cholesterol in APOE*3Leiden. CETP mice by reducing CETP activity, as related to lower hepatic CETP expression and a reduced plasma (V)LDL pool, and increases HDL-apoAI by decreasing the clearance of apoAI from plasma. © 2008 American Heart Association, Inc.

Det övergripande syftet var att undersöka mat- och måltidsrelaterade faktorer som bidragande orsak till övervikt och hjärt-kärlsjukdom. I en sensorisk studie jämfördes individer som insjuknat i hjärtinfarkt med en frisk kontroll-grupp med avseende på preferens för mat med hög respektive låg fetthalt, smakkänslighet för grundsmakerna (surt, beskt, salt, sött, umami och metalliskt) samt det beska ämnet 6-n-propylthiouracil (PROP). Undersökningsgruppen hade mer ogynnsam metabolisk profil, vilket kan indikera högre intag av fet, energirik mat och mindre intag av frukt och grönsaker, jämfört med kontrollgruppen. Det påvisades emellertid ingen signifikant skillnad i smakkänslighet mel-lan grupperna. När grupperna slogs samman konstaterades däremot att känslighet för surt var relaterat till lågt body mass index (BMI), och känslighet för beska var relaterat till lågt HDL-kolesterol samt högt BMI och bukfetma. Det indikerar ett samband mellan riskprofil, smak-känslighet och matvanor. Upplevd beska kan vara en bidragande orsak till låg konsumtion av frukt och grönsaker. Båda grupperna föredrog generellt mat med hög fetthalt, varför preferens för hög fetthalt i sig inte kan anses vara en bidragande riskfaktor för insjuknande i hjärtinfarkt. För hälften av rätterna påvisades emellertid ingen signifikant skillnad i preferens för hög- respek-tive låg fetthalt. För att undersöka hur sensoriska egenskaper förändras vid olika fetthalter stu-derades två såser med varierande smörmängd. Totalt sett minskade smakegenskaperna (tomat, vitlök, timjan, kyckling, syrlighet) när mer smör tillsattes, medan smörsmaken och såsernas vis-kositet ökade. Stor skillnad i smörmängd (energiinnehåll) frambringar däremot endast små smakförändringar. I en enkätstudie påvisades att matvanor och inställning till mat och hälsa skilde sig mellan män och kvinnor samt beroende av BMI. En klusteranalys resulterade i tre grupper, varav en grupp med jämn könsfördelning som i genomsnitt hade högre BMI och sämre mat, The overall aim was to study risk factors for obesity and coronary heart disease (CHD), in relation to food and meals. A case-control study of people diagnosed with CHD was used to evaluate preferences for full-fat versus low-fat versions of a range of foods, along with basic taste sensitivity and sensitivity to the bitter substance PROP. No significant differences in taste perception were obtained between the groups. However, in the pooled sample, a heightened sensitivity to sour taste was correlated with low BMI, while a heightened sensitiv-ity to bitter taste was correlated with low HDL-cholesterol, and high BMI and abdominal fat. This indicates a relationship between risk profile, taste sensitivity and food intake. Heightened sensitivity to bitter taste might result in lower consumption of fruit and vegeta-bles including those with a bitter tone. Preference related to total fat content per se was not confirmed as a risk factor for CHD. However, a less favourable metabolic profile were seen in the CHD group, indicating a higher intake of fat-rich and energy-rich food. The sensory effects of fat content were also evaluated, using two sauces as the vehicle. Overall, increased butter content resulted in decreased perception of all flavours except butter flavour, which increased, as did viscosity. However, a high fat content could not always be justified in terms of taste; large increases in energy content produced only small sensory differences. Data were also collected through a survey on eating habits and attitudes to health and food consumption. A cluster analysis revealed the existence of a gender-mixed overweight group, with less healthy eating habits. This group seems to consist of women less interested in health and men more interested in getting pleasure from food than general, demonstrating different reasons for unhealthy eating between genders. The essence of a good meal was found to include a number of demands on both food (a restaurant-type meal, a prope

We previously evaluated the responses to dietary cholesterol in children and young adults. In this study, the effects of dietary cholesterol on plasma lipids and LDL atherogenicity were evaluated in 42 elderly subjects (29 postmenopausal women and 13 men > 60 y old). Our exclusion criteria were diabetes, heart disease, and the use of reductase inhibitors. The study followed a randomized crossover design in which subjects were assigned to consume the equivalent of 3 large eggs (EGG) daily or the same amount of a cholesterol-free, fat-free egg substitute (SUB) for a 1-mo period. After a 3-wk washout period, subjects were assigned to the alternate treatment. The concentration of plasma cholesterol after the EGG period varied among subjects. When all subjects were evaluated, there were significant increases in LDL cholesterol (LDL-C) (P < 0.05) and HDL-C (P < 0.001) for both men and women during the EGG period, resulting in no alterations in the LDL-C:HDL-C or the total cholesterol:HDL-C ratios. In addition, the LDL peak diameter was increased during the EGG period for all subjects. In contrast, the measured parameters of LDL oxidation, conjugated diene formation, and LDL lag time did not differ between the EGG and the SUB periods. We conclude from this study that dietary cholesterol provided by eggs does not increase the risk for heart disease in a healthy elderly population.

An increased risk for coronary heart disease among shift workers is earlier shown in the epidemiological literature. The aim of this thesis has been to penetrate metabolic disturbances and obesity among shift workers compared to day workers, and to compare if there are differences in total mortality or cause specific mortality of coronary heart disease (CHD), diabetes or ischaemic stroke in between the two groups. In an intervention study on female nurses (N=11), on night schedules in Umeå hospital, the highest peak value of glucose and insulin after meal ingestion was seen in the late evening (23:30). The post-prandial area under curve (AUC) of glucose and insulin was correspondingly largest after meal ingestion the same clock hour compared to meal ingestion other clock times. In two different cross-sectional studies Västerbotten Inventory Study (VIP) (N= 27,485) and in a subset of Work, Lipids and Fibrinogen Study (WOLF) (N= 1,324) metabolic differences in between shift and day workers has been evaluated. In both studies have obesity, high triglycerides and low HDL-cholesterol been more prevalent among the shift-working group compared to the day-working group. After adjustments for age and socio-economic factors in the VIP-study obesity and high triglycerides remained as risk factors in shift workers in both men and women. After directly age standardisation, a clustering effect, simultaneously, of two or more metabolic risk factors (obesity, hypertension, and high triglycerides) was seen in both genders among the shift workers compared to the day workers. Correspondingly, in the Wolf study low HDL-cholesterol and high triglycerides remained as significant risk factors after adjustments of confounders as age, socio-economic group, physical activity, current smoking, low social support and high job strain. In a cohort study from one company (MoDo) with two plants in the pulp and paper industry 2,354 male shift workers and 3,088 male day workers were followed from Ja

The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride (TG) levels, low HDL-cholesterol concentrations and alterations in LDL composition and concentration. A functional, non-coding −514C>T single nucleotide polymorphism (SNP) of the hepatic lipase gene (LIPC) has been related to variation in HDL-cholesterol concentrations. Objectives: To investigate the hypotheses that the LIPC −514C>T polymorphism may be associated with a deteriorated lipoprotein-lipid profile and that environmental factor, such as abdominal obesity, alters this association. Methods: A total of 235 French-Canadian men from the greater Quebec City area were assigned into three groups on the basis of their LIPC −514C>T SNP, including 149 CC homozygotes, 75 CT heterozygotes, and 11 TT homozygotes. Results: In the present study, the highest values of BMI, waist circumference, and accumulation of visceral adipose tissue (VAT) were observed among TT homozygotes (p < 0:05). After adjustment for age and BMI, TT homozygotes still showed higher plasma apolipoprotein (apo) AI and HDL-TG concentrations than the two other groups (p < 0:05). When the two genotype groups (CC vs CT/TT) were further divided on the basis of VAT accumulation using a cut-off point of 130 cm2 (high vs low) it appears that irrespective of the genotype subjects with low VAT had higher HDL2-cholesterol concentrations (p < 0:0001). However, lean carriers of the T allele had higher plasma HDL2-cholesterol levels than lean CC homozygotes. The beneficial effect of the T allele on plasma HDL2-cholesterol levels was abolished in the presence of visceral obesity (VAT > 130 cm2). Conclusion: In summary, the presence of visceral obesity attenuates the impact of the LIPC −514C>T polymorphism on plasma HDL2-cholesterol levels.

The purpose of this study was to examine the effect of prolonged exercise oil plasma lipid and lipoprotein concentrations and to identify caloric time-points where changes occurred. Eleven active male Subjects ran oil a treadmill at 70%,, of maximal fitness (VO2max) and expended 6 278.7 kilojoules (Kj) energy (1500 kcal). Blood samples were obtained at the 4185.8 Kj (1000 kcal) time-point during exercise and at each additional 418.6 Kj (100 kcal) expenditure until 6278.7 Kj was expended. After correcting for plasma volume changes, decreases in low-density lipoprotein cholesterol (LDL-C) were observed during exercise at time-points corresponding to 4604.4 and 5441.5 Kj (1100 and 1300 kcal) of energy expenditure, and immediately after exercise. Total cholesterol concentrations decreased significantly at exercise kilojoule expenditures of 4604.4, 5441.5 and 5860.1 (1100, 1300 and 1400 kcal). There were also exercise induced increases in high-density lipoprotein cholesterol (HDL-C) and HDL2-C concentrations immediately after exercise. Although acute lipid and lipoprotein changes are typically reported in the days following exercise, the Current data indicate that some lipoprotein concentrations change during acute exercise. Our data suggest that a threshold of exercise may be necessary to change lipoproteins during exercise. Future work Should identify potential mechanisms (lipoprotein lipase, cholesterol ester transport protein, LDL uptake) that alter lipoprotein concentrations during prolonged exercise.

Evidence suggests that fibrate therapy reduces the risk of recurrent coronary heart disease among men with low levels of high density lipoprotein cholesterol (HDL-C). Indirect observations and new possible biological pathways suggest that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism might modulate the lipoprotein/lipid profile and its response to fibrate therapy. To assess the possible interaction between fibrate therapy and such variants on plasma lipid and lipoprotein levels, 65 dyslipidemic abdominally obese men were treated for 6 months with or without gemfibrozil (600 mg twice daily). No differences in baseline plasma lipid and lipoprotein levels were found between genotype groups except for the HDL(3)-C subfraction, which was higher in the DD group (p = 0.02). A two-way factorial ANOVA was used to evaluate the effect of the genotype (DD homozygotes vs I allele carriers), the treatment (placebo vs gemfibrozil), and the interaction between these two independent variables on changes observed in lipid and lipoprotein concentrations. A significant genotype-by-treatment interaction (p = 0.02) was found for the plasma HDL-C response to the intervention program. In fact, having the DD genotype and being treated with gemfibrozil had a synergical effect on HDL-C levels. The results of this study suggest that the ACE I/D polymorphism influences the effect of gemfibrozil on plasma HDL-C levels.

OBJECTIVE: The aim of this study was to examine the relation between the CETP-TaqIB polymorphism and reduced plasma HDL-cholesterol levels commonly observed among men characterized by abdominal obesity and features of the insulin resistance syndrome. SUBJECTS: A total of 187 sedentary men, non-smokers and free from metabolic disorders were classi®ed on the basis of their CETP-TaqIB genotype. RESULTS: Plasma HDL and HDL3-cholesterol concentrations as well as the CETP activity were signi®cantly different between the three genotypes, B1B1 men having signi®cantly lower HDL and HDL3-cholesterol levels and higher CETP activity than B2B2 homozygotes. A 23 ANOVA was used to determine the source of variation of plasma HDL and HDL2-cholesterol levels among the three genotypic groups of men divided on the basis of either a high ( 27 kg=m2 ) or a low (< 27 kg=m2 ) BMI, a high ( 130 cm2 ) or a low (< 130 cm2 ) accumulation of visceral adipose tissue assessed by computed tomography, or a low versus a high fasting plasma insulin concentration (using the median value as a cutoff point). The effect of the CETP genotype observed on plasma HDL-cholesterol concentrations was attenuated among men with features of the insulin resistance syndrome. It seems that the expected raising effect of the B2 allele on plasma HDL-cholesterol concentrations was blunted in the presence of a BMI 27 kg=m2 , a high accumulation of visceral adipose tissue or hyperinsulinaemia. CONCLUSION: Our data indicate that the CETP gene TaqIB polymorphism in¯uences plasma CETP activity on one hand and plasma HDL-cholesterol concentrations on the other hand among men. The association between the TaqIB polymorphism and plasma HDL-cholesterol concentrations is altered by the presence of abdominal obesity and some features of the insulin resistance syndrome.

BACKGROUND: the lipid factor is currently considered to be the main agent responsible for cardiovascular risk in young individuals. This is already present during infancy in proportions that give rise to concern, and is growing, as has would seem to have been shown by several national studies. This study analyses the prevalence of hyperlipidemia in children within the province of Caceres according to several different criteria, and describes changes according to age groups and sex, comparing the overall results with those of other national studies. METHODS: a cross - sectional descriptive study of a representative and proportional sample of 2,150 children aged 2 to 6 years old in the province of Caceres (N = 91,083). The following were determined: total cholesterol, fractions, apolipoproteins and risk coefficients (enzymatic technique). RESULTS: 27.9% of children presented total cholesterol values of >200 mg/dl; 7.5% of females and 4.7% of males had figures of more than 230 mg/dl. Levels of C-LDL > 130 mg/dl appear in 26.4%, Apo-B >75 mg/dl in 65.5% and C-NO-HDL > 165 in 8.4%. C-HDL- <35 mg/dl was found in 3.3% of individuals, while Apo-A < 100 mg/dl was only found in 0.3%. The ratios between CT/HDL > 3.5 and LDL/HDL > 2.2 were found to be 36..1% and 39.8%, respectively. The prevalence of hyperlipidemia is higher in females and pre-puberty stages. CONCLUSIONS: overall, and independently of the criteria used, the proportion of cases of hyperlipidemia is high, and is above the levels cited in other Spanish studies. The prevalence of hyperlipidemia is highest in females before puberty, who display the most discriminatory risk coefficients, and best identify the change in the lipid profile at puberty., FUNDAMENTO: Actualmente se considera al factor lipídico como el principal responsable del riesgo cardiovascular del individuo joven, factor ya presente en la infancia en proporciones preocupantes y crecientes como parecen mostrar diversos estudios nacionales. En el presente trabajo se analiza la prevalencia de hiperlipidemia en niños de la provincia de Cáceres según diversos criterios, describiendo los cambios según grupos de edad y sexo, y comparando los resultados globales con otros estudios autóctonos. MÉTODO: Estudio descriptivo transversal de una muestra representativa y proporcional de 2.150 niños (2 a 16 años) de la provincia de Cáceres (N=91.083). Se determina: colesterol total, fracciones, apolipoproteinas y cocientes de riesgo (técnica enzimática). RESULTADOS: El 27.9% de los niños presenta valores de colesterol total >200 mg/dl.; 7.5% de las mujeres y 4.7% de los varones muestran cifras superiores a 230 mg/dl. Niveles de C-LDL>130 mg/dl. aparecen en un 26.4%, de Apo-B>75 mg/dl en el 65.5% y de C-NO-HDL>165 en el 8.4%. Un C-HDL<35 mg/dl. se encontró en 3.3% de los individuos mientras que la Apo-A<100 mg/dl. sólo apareció en el 0.3%. Las relaciones CT/HDL>3.5 y LDL/HDL>2.2 se mostraron en el 36.1% y en el 39.8% respectivamente. La prevalencia de hiperlipidemia es superior en mujeres y etapas prepuberales. CONCLUSIONES: De forma global, e independientemente del criterio utilizado, la proporción de casos de hiperlipidemia es elevada y superior a la referida en otros estudios españoles. La prevalencia de hiperlipidemia es mayor en mujeres prepuberales, mostrándose los cocientes de riesgo mas discriminativos e identificando mejor el cambio del perfil lipídico puberal.

Background. Hypercholesterolemia, diabetes and obesity are risk factors of cardiovascular diseases (CVDs), and most agencies advise a prudent low fat diet for treatment. Plant health products are rich sources of fiber and flavonoids which are known to inhibit athero-thrombosis due to hypolipidemic, hypoglycemic and insulin sensitivity activating effects. In the present trial, we examine the effects of fenugreek seeds on risk of CVDs. Design and setting. Randomized, double blind, placebocontrolled trial in a hospital. Subjects and Methods. All subjects (n = 61) with hyperlipidemia (<7.76 nmol/l) were assigned to American Heart Association step 1 diet for a period of 12 weeks and then randomized to two different intervention agents in identical sachets for another 12 weeks. The test agents were fenugreek seed powder (60.0g/day) and cellulose placebo (3.g/day). Results: Of 61 subjects with serum cholesterol between 5.17 and 7.76 nmol/1, 59 successfully completed 12 weeks of AHA step I diet and then augmented the diet with one of the fiber or fenugreek supplement for 12 additional weeks. Incremental differences from placebo for low-density lipoprotein (LDL) cholesterol were: -15.1% (P < 0.001) for fenugreek; for total cholesterol -13.4% (P < 0.001) for fenugreek. The incremental differences in triglycerides (significant) for fenugreek were -9.2% (P < 0.001) with a 4.4% (P < 0.05) increase in HDL cholesterol. LDL/HDL cholesterol ratio showed a statistically significant decline from the reference concentrations in the fenugreek group, but no such changes in the control group; the incremental difference was 11.4% (P < 0.001). The incremental differences in fasting and postprandial blood glucose, which showed statistically significant declines in the fenugreek group compared to the control group, were 9.8% (P < 0.05) and 19.4% (P < 0.001), respectively. Compliances to treatment varied between 92% and 99% and only mild gastrointestinal side effects were observed. Conclusions