Lower HDL-cholesterol Concentrations Research Articles

Contribution of cardiorespiratory fitness, relative to traditional cardiovascular disease risk factors, to common carotid intima-media thickness.

Studies have suggested that being slightly overweight but fit is better for cardiovascular health than being somewhat leaner but unfit. Here, we sought to determine the contribution of cardiorespiratory fitness (CRF), relative to the presence of risk factors, to common carotid intima-media thickness (CIMT), a measurement of atherosclerosis and cardiovascular disease risk. Data were analysed from a cohort of 7300 German employed individuals aged 46 (±7)years who participated in a preventive health check-up at a specialized prevention centre. In addition to traditional cardiovascular disease risk factor assessment, participants performed an exercise test with spirometry to exhaustion, and common CIMT was measured. Individuals were defined as being fit or unfit based on the median age- and sex-specific relative maximum oxygen consumption. In a multivariable analysis, there was a strong inverse association between CRF and common CIMT. Individuals who were considered fit and did not have any cardiovascular disease risk factors had the lowest common CIMT values (reference group). Those who were unfit and had an increased risk factor level always had the highest common CIMT values. Good CRF partly compensated for the increased common CIMT due to a risk factor. However, unfit individuals without increased risk factor levels had a common CIMT that was not significantly different from that of the reference group, whereas fit individuals who smoked, had a high body mass index, a low HDL cholesterol concentration or a high systolic blood pressure had an increase in common CIMT. Cardiorespiratory fitness is a major determinant of common CIMT. Improved CRF does slightly, but not completely, abolish the adverse consequences of cardiovascular disease risk factors on common CIMT.

A novel ApoA-I truncation (ApoA-IMytilene) associated with decreased ApoA-I production

ObjectiveWe report a novel apolipoprotein (apo) A-I truncation (apoA-IMytilene) due to a heterozygous nonsense mutation (c.718C > T, p.Gln216*) in a 68-year-old male proband with premature coronary heart disease (CHD), corneal arcus, and very low plasma concentrations of HDL cholesterol (HDL-C) and apoA-I. Two family members also had the same mutation. Our objectives were to characterize the kindred and to examine the kinetics of apoA-I, as well as cellular cholesterol efflux capacity in the proband. MethodsWe carried out the kinetic studies using a primed constant infusion of [5,5,5-D3]L-leucine and isotopic enrichment was determined by gas chromatography mass spectrometry in the proband and seven controls with low HDL-C. To assess cellular cholesterol efflux capacity, we used a validated ex vivo system that involved incubation of J774 macrophages with apoB-depleted serum from the proband, five controls with normal HDL-C, and two controls with low HDL-C. ResultsStable isotope kinetic studies indicated that the proband had an apoA-I production rate (PR) that was 41% lower than the mean PR observed in low HDL-C controls (n = 7). The cellular cholesterol efflux capacity assessment showed normalized cholesterol efflux capacity in the proband was decreased by 36% compared to the mean normalized cholesterol efflux capacity of normal controls (n = 5). ConclusionsOur data indicate that this novel heterozygous apoA-I truncation is associated with markedly decreased levels of HDL-C, plasma apoA-I, and apoA-I in large α-1 HDL particles, as well as decreased total cellular cholesterol efflux and decreased apoA-I production.

Family-based analysis of INSR polymorphisms in Chinese PCOS

The insulin receptor (INSR), which is an indispensable component of the insulin-signalling pathway, could be a plausible candidate gene for polycystic ovary syndrome (PCOS). This study was designed to determine whether an association exists between three SNP variants (rs3786681, rs17253937 and rs2252673) of the INSR gene and PCOS in Han Chinese. A total of 224 family trios (672 participants in total) were enrolled in this family-based transmission disequilibrium test. Genotypes were obtained by sequencing. A weak association was detected in rs2252673 (P = 0.027), which indicated that INSR may confer an increased susceptibility to PCOS in Chinese. Additionally, the association between INSR gene variants and clinical and metabolic characteristics of women with PCOS was investigated. Carriers of the CG and GG genotypes in women with PCOS were slightly associated with higher cholesterol concentration (t = 2.072, P = 0.048) and lower high-density lipoprotein cholesterol concentration (t = 2.274, P = 0.026). The minor allele conferred increased odds of PCOS independently of body mass index. The present data may provide a basis for further studies of the role of the INSR in the aetiology of PCOS.

Low energy and carbohydrate intake associated with higher total antioxidant capacity in apparently healthy adults

ObjectivesThe aim of this study was to investigate the associations between plasma total antioxidant capacity (TAC) and anthropometric, biochemical, clinical, and dietary measurements in young and apparently healthy individuals. MethodsWe evaluated 156 individuals (91 women and 65 men; ages 23.1 ± 3.5 y; body mass index 22 ± 2.9 kg/m2) for anthropometrics, biochemical markers, clinical, dietary, and some components of the antioxidant defense system, including the plasma TAC. Statistical analyses were performed to detect differences between individuals with TAC higher and lower than the mean value and to screen the associations between TAC and variables of interest. A linear regression model was fitted to identify TAC predictors. ResultsDaily caloric intake and macronutrient consumption were lower in individuals who exhibited the highest TAC values (P < 0.05). Linear regression analysis showed that daily calories and carbohydrate intake was a possible negative TAC predictor (P < 0.05). Nevertheless, there was no difference in the values of oxidized low-density lipoprotein in the individuals separated by means of TAC. In contrast, individuals whose plasma TAC values were above the mean showed higher low-density lipoprotein cholesterol concentrations, total cholesterol/high-density lipoprotein cholesterol values, and selenium in nails (P < 0.05). ConclusionsIn physiological conditions, the caloric intake level seems to be an important factor to act in the modulation of plasma TAC, before establishing anthropometric impairments of body or metabolic composition, or both. Additionally, the plasma TAC increase may be able to act as a compensatory mechanism.

Subclinical hypothyroidism in patients with polycystic ovary syndrome: Distribution and its association with lipid profiles

ObjectiveThe aim of this study was to examine the distribution of subclinical hypothyroidism (SCH) in patients with polycystic ovary syndrome (PCOS). We also aimed to investigate the associations between thyroid stimulating hormone (TSH) and lipid profiles and to determine the values at which TSH levels affected dyslipidemia risk in this population. Study designWomen with PCOS (n=428) from a Chinese Han population were recruited and stratified into five groups based on TSH levels. Multiple linear regression analysis was performed to investigate the associations between serum TSH and lipid profiles. Receiver operating characteristic (ROC) analysis was used to find the optimal TSH cut-off point for dyslipidemia risk. ResultsThe SCH distribution was observed similarly in PCOS patients with different phenotypes (Chi-squares=2.184, P=0.535). There was a significant positive correlation between TSH and low density lipoprotein cholesterol (LDLc) (P=0.001), even after adjustment for age, body mass index, waist to hip ratio, fasting plasma glucose, homeostatic model assessment-insulin resistance and free androgen index (P<0.001). The optimal TSH cut-off point to indicate elevated LDLc risk was 4.07mIU/L by ROC analysis. ConclusionOur data indicate that TSH is strongly associated with higher LDLc concentrations in PCOS patients. The optimal TSH cut-off point for elevated LDLc risk in this cohort was 4.07mIU/L. These findings demonstrate that more attention might be paid to PCOS paients prior to overt clinical presentation.

Relative lymphocyte count as a marker of progression of chronic kidney disease

Although low relative lymphocyte count (RLC) is associated with poor outcomes in patients with chronic kidney disease (CKD), the relationship between low RLC and progression of CKD is poorly defined. The aim of this study was to determine the association between low RLC and the progression of CKD. Between January 2003 and December 2009, 288 CKD patients were analyzed. RLC was calculated as the ratio between lymphocyte and total white blood cell counts. The median RLC was 29.1% [interquartile range (IQR) 24.1-34.1]. When the patients were compared according to a level below or above the median value for RLC, the rate of CKD progression to end-stage renal disease (ESRD) was greater in patients with low RLC count than in patients with high RLC (48 vs. 25%, p < 0.001) during the median follow-up of 5.5 years (IQR 3.5-7.6). The variables found to be predictive of progression to the ESRD included younger age, smoking, diabetes, higher systolic blood pressure, no use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lower hemoglobin and serum albumin levels, higher low-density lipoprotein cholesterol concentration, presence of proteinuria, and low RLC in the univariate Cox proportional hazards regression analysis. However, after adjustment, younger age, male, higher systolic blood pressure, no use of ACEIs or ARBs, lower hemoglobin and serum albumin concentrations, higher proteinuria, and lower RLC were significantly associated with progression to ESRD in multivariate analysis. Low RLC is independently associated with increased rate of progression in patients with CKD.

Hyperhomocysteinemia, lipid and lipoprotein disturbances in patients with primary hypertension

PurposesThe main aim of the study was to answer two questions: what are the concentrations of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I (apolipoprotein A-I), apo B (apolipoprotein B) and Lp(a) (lipoprotein(a)) in serum of patients with primary hypertension and with hyperhomocysteinemia? Is there any correlation between the concentration of homocysteine in blood serum and investigated lipid and lipoprotein parameters in patients with primary hypertension? Material/methodsWe investigated 42 patients with primary hypertension, aged 22–57. The control group consisted of 20 healthy volunteers. The concentration of homocysteine in serum was evaluated using immunochemical method (FPIA – Fluorescence Polarization Immunoassay). The concentration of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides in blood serum were estimated using enzymatic method. Apo A-I, apo B and lipoprotein(a) were assessed using nephelometric method. ResultsThe analysis of the results revealed statistically significant lower concentrations of HDL-cholesterol and apo A-I in blood serum of patients with primary hypertension and hyperhomocysteinemia than in the population with hypertension and normohomocysteinemia. Negative correlation between homocysteine and HDL-cholesterol as well as apo A-I has been revealed. ConclusionQuantitative analysis of the concentration of lipids and lipoproteins in blood serum in patients with primary hypertension and hyperhomocysteinemia may suggest that this type of human population might be more susceptible to atherosclerosis than those with primary hypertension and normal values of homocysteine.

Metabolic Syndrome and Cardiometabolic Risk Factors

The metabolic syndrome (MetS) is a cluster of metabolic conditions associated to abdominal obesity, such as elevated blood pressure, impaired glucose tolerance, insulin resistance, elevated triglycerides, and low high-density lipoprotein cholesterol concentrations. Each of the associated conditions has an independent effect, but clustering together they become synergistic, making the risk of developing cardiovascular disease (CVD) greater. There is a big debate as to whether the MetS alone or its associated health conditions are more important for CVD incidence and mortality or whether prevention and/or treatment of the MetS will reduce CVD incidence and mortality. This article reviews the evidence that demonstrates that individuals with the MetS are at increased risk for CVD incidence and mortality and discusses these debated issues.

Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects

BackgroundWe have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects.MethodsWe have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-1HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption.ResultsIn the high-HDL-C group, we found lower plasma concentrations of triglycerides, alanine aminotransferase, insulin, HOMA-IR index, activities of LCAT and HL compared with the low HDL-C group; additionally, we found higher activity of LPL and pre-beta-1HDL concentration in the high-HDL-C group. There were no differences in the plasma CETP and PLTP activities.ConclusionsThese findings indicate that in healthy hyperalphalipoproteinemia subjects, several parameters that control the metabolism of plasma cholesterol and lipoproteins are related to a higher degree of insulin sensitivity.

Morbid Obesity Resulting from Inactivation of the Ciliary Protein CEP19 in Humans and Mice

Obesity is a major public health concern, and complementary research strategies have been directed toward the identification of the underlying causative gene mutations that affect the normal pathways and networks that regulate energy balance. Here, we describe an autosomal-recessive morbid-obesity syndrome and identify the disease-causing gene defect. The average body mass index of affected family members was 48.7 (range = 36.7-61.0), and all had features of the metabolic syndrome. Homozygosity mapping localized the disease locus to a region in 3q29; we designated this region the morbid obesity 1 (MO1) locus. Sequence analysis identified a homozygous nonsense mutation in CEP19, the gene encoding the ciliary protein CEP19, in all affected family members. CEP19 is highly conserved in vertebrates and invertebrates, is expressed in multiple tissues, and localizes to the centrosome and primary cilia. Homozygous Cep19-knockout mice were morbidly obese, hyperphagic, glucose intolerant, and insulin resistant. Thus, loss of the ciliary protein CEP19 in humans and mice causes morbid obesity and defines a target for investigating the molecular pathogenesis of this disease and potential treatments for obesity and malnutrition.

Abnormal Lipid levels as a risk factor of eclampsia, study conducted in tertiary care Hospitals of Khyber Pakhtunkhwa Province - Pakistan

To evaluate abnormal lipid metabolism as a risk factor of eclampsia in pregnant women. This cross sectional study was conducted in three tertiary care hospitals of Peshawar. Serum total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), triglyceride (TG), apolipoprotein A1 (APO-A1), APO-B100, lipoprotein-a (Lpa) were measured in 110 women with eclampsia and compared with 90 healthy pregnant women. Mean lipid levels in cases and controls were compared using student's t test". Mean systolic/diastolic blood pressure, TC, TG, VLDL-C and Lpa levels were significantly higher (p<0.001) in patients compared to control women. Similarly TC: HDL-C, LDL-C: HDL-C and TG: HDL-C ratio in the patients group were significantly higher (p<0.001) and HDL-C: VLDL-C ratio was significantly lower (p<0.001) in the patients as compared to control group. Undesirable cholesterol were noted in 35.8% patients, HDL-C in 50.5%, borderline high concentration of LDL-C in 23.6%, high triglycerides levels in 73.2%, undesirable cholesterol ratio in 52.3% and undesirable LDL-C ratio were noted in 82.1% patients of eclampsia. Serum lipids were found significantly higher thus early assessment may be helpful in prevention of complications in the eclampsia patients.

Dyslipidemia in Pediatric Systemic Lupus Erythematosus: The Relationship with Disease Activity and Plasma Homocysteine and Cysteine Concentrations

Objective: To evaluate the presence of dyslipidemia and plasma concentrations of homocysteine (Hcy) and cysteine (Cys) in adolescents with juvenile systemic lupus erythematosus (SLE) and relate these findings to disease activity (Systemic Lupus Erythematosus Disease Activity Index, SLEDAI) and cardiovascular risk factors. Methods: A cross-sectional controlled study including 26 female adolescents with SLE and 26 healthy controls was conducted. We evaluated SLEDAI, medications, anthropometric data, dietary intake, lipid profile, proteinuria, Hcy, Cys, folic acid, vitamin B₁₂, and high-sensitivity C-reactive protein levels. Results: Dyslipidemia was observed in 46.2% of the patients and in 19.2% of the controls. The SLE group had a higher Cys concentration and a lower high-density lipoprotein cholesterol concentration compared with the controls. In the multivariate analysis only Hcy was significantly and independently associated with the presence of dyslipidemia in the juvenile SLE group; an increase of 1 μmol/l in the Hcy concentration doubled the chance of dyslipidemia (OR: 2.1; 95% CI: 1.1-4.9; p = 0.030). The Cys concentration was correlated with Hcy, total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations. Conclusion: We observed the presence of cardiovascular risk factors in adolescents with juvenile SLE. The early identification of biochemical alterations allows the development of intervention strategies that may lower the risk of cardiovascular disease.

Serum Lipid Levels Are Associated with the Severity of Acute Pancreatitis

Background/Aims: Serum lipid concentrations react during acute disease. We sought to measure changes in the serum lipid profile during acute pancreatitis and ascertain whether these changes were associated with the severity of the disease. Methods: A total of 233 patients (71% male, median age 48 years) hospitalized for acute pancreatitis were included in the study. The most common etiology for acute pancreatitis was alcohol (n = 131, 56%), followed by biliary (n = 48, 21%) and idiopathic pancreatitis (n = 36, 16%). Serum lipid levels were measured enzymatically. We analyzed samples obtained during the first days of hospitalization and later follow-up samples to measure changes during the course of the disease. Results: We report profound changes in the serum lipid concentrations during acute pancreatitis. Serum total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol concentrations measured within 2 days of admission (n = 203) were significantly lower in patients who developed severe pancreatitis (3.20 vs. 3.80 mmol/l, p = 0.001; 0.72 vs. 1.05 mmol/l, p < 0.000, and 1.60 vs. 2.14 mmol/l, p < 0.000, respectively). Low serum total cholesterol, HDL cholesterol and LDL cholesterol concentrations were moreover associated with in-hospital mortalities and longer hospitalization (p < 0.05). In the subgroup analysis, the findings remained statistically significant in patients with alcohol-induced acute pancreatitis. Conclusion: Levels of serum total cholesterol, HDL cholesterol and LDL cholesterol are significantly lower in patients with severe acute pancreatitis and are associated with longer hospitalization.

Metabolic disregulation in obese adolescents with sleep‐disordered breathing before and after weight loss

Sleep-disordered breathing (SDB) is prevalent in obesity. Weight loss is one of the most effective treatment options. The aim was to assess the association of SDB and metabolic disruption before and after weight loss. Obese adolescents were included when entering an in-patient weight loss program. Fasting blood analysis was performed at baseline and after 4-6 months. Sleep screening was done at baseline and at follow-up in case of baseline SDB. 224 obese adolescents were included. Median age was 15.5 years (10.1-18.0) and mean BMI z-score was 2.74 ± 0.42. About 30% had SDB at baseline (N = 68). High-density lipoprotein (HDL)-cholesterol was associated with mean nocturnal oxygen saturation (<SaO2>) (partial r = 0.21; P = 0.002). Aspartate aminotransferase (ASAT) and alanine aminotransferase were related with oxygen desaturation index (partial r = -0.15; P = 0.03 and partial r = -0.15; P = 0.02), but this became insignificant after correction for sex. After weight loss, 24% had residual SDB. Linear regression showed an association between ASAT and <SaO2> (partial r = -0.34; P = 0.002). There were no significant correlations between improvements in laboratory measurements and sleep parameters. HDL-cholesterol improved in relation with the decrease in BMI z-score. SDB at baseline was associated with higher levels of liver enzymes and lower HDL-cholesterol concentration. Improvements in sleep parameters were not associated with improvements in laboratory measurements.

Prevalence and risk factors of elevated blood pressure, overweight, and dyslipidemia in adolescent and young adults in rural Nepal.

Chronic disease begins early in life, yet population data are sparse on potential causal factors in children and young adults in South Asia. We assessed risk factors for chronic disease in two population cohorts, aged 9-23 years, in rural Nepal. Assessed variables included short height (less than -2 z), high body mass index (BMI) (z>0.42), waist circumference (WC) >90 cm (male) or 80 cm (female) or age-adjusted child cutoff], high blood pressure (>120/80 mmHg), fasting glucose (≥100 mg/dL), glycosylated hemoglobin (HbA1c) (>7%), blood lipids [triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol], diet, smoking, alcohol, and socioeconomic status (SES) factors. The population was stunted (46%) and few were overweight (∼2%-4% with high BMI or WC). Twelve percent had high blood pressure. Plasma hypertriglyceridemia (≥150 mg/dL) affected ∼8.5%, and 78% had low HDL-C concentrations <40 mg/dL (male) or <50 mg/dL (female)], while few (≤3%) had elevated total cholesterol (≥180 mg/dL), glucose, and HbA1c. Females were at higher risk than males for high blood pressure [odds ratio (OR) 1.9; 95% confidence interval (CI) 1.6-2.3] and overweight (4.2; 3.0-5.8), but had lower risk of dyslipidemia (0.7; 0.6-0.9). Ethnic plains Madheshi were less likely to be overweight (0.3; 0.2-0.4), but had greater risk of dyslipidemia (1.4; 1.1-1.7) versus those of Hill origin. Some dietary factors were significantly associated with high blood pressure or dyslipidemia, but not overweight. Dyslipidemia and high blood pressure are emerging health concerns among young adults in rural Nepal.

Association between ABCA1 R230C polymorphism, dietary intake, anthropometric measurements and biochemical parameters in subjects with and without metabolic syndrome

Approximately, 20% of the adult Mexican population shows a polymorphism (SNP) in the ABCA1 gene (R230C) associated with low HDL‐cholesterol (HDL‐C) concentration, obesity and diabetes. On the other hand, 40–50% of the adults have metabolic syndrome (MetS). Thus, the aim of this study was to evaluate the association between the presence of the ABCA1 polymorphism and food intake on blood lipids, anthropometric measurements, physical activity and energy expenditure in 298 Mexican subjects with and without MetS (71 men, 227 women). The frequency of the non‐common allele (T) was 11%. The frequency of homozygous for the non‐common allele (C230C) and heterozygous (R230C) was 19.3%. The frequency of R230C and C230C of ABCA1 gene was similar in patients with and without MetS. However, the subjects with and without MetS with R230C and C230C SNP, as the energy intake increased the serum HDL‐C increased. However, HDL‐C remained constant as the energy intake increased in women with MetS and R230C and C230C SNP. Grant CONACYT 181685 (to MGC).Grant Funding Source: CONACYT

Association between C-reactive protein, pro-oxidant-antioxidant balance and traditional cardiovascular risk factors in an Iranian population

Inflammatory states are known to cause an imbalance in the redox status. We aimed to study the possible associations between pro-oxidant-antioxidant balance (PAB) and serum high-sensitive C-reactive protein (hs-CRP) concentrations and traditional cardiovascular disease (CVD) risk factors in an unselected Iranian population and in groups of individuals with specific disease. The study was conducted among an unselected population of 758 male subjects. Biochemical markers, including hs-CRP and PAB values, were measured. Serum hs-CRP concentrations were positively associated with serum PAB values (r = 0.260, P ≤ 0.001). Univariate analysis showed that PAB values were statistically higher in individuals who were obese or smokers compared with non-obese and non-smokers individuals (P < 0.01). While serum hs-CRP concentrations were significantly higher in older subjects, subjects with obesity, diabetes mellitus, metabolic syndrome, central obesity, hypertriglyceridaemia, higher low-density lipoprotein cholesterol concentrations, positive history of CVD and lower physical activity than subjects without these risk factors (P < 0.05). Comparing hs-CRP and PAB values in different CVD risk score subgroups showed a significant incremental rise in both parameters as CVD risk score increased (P < 0.05). Using multiple linear regression analysis we found a strong association between PAB values and hs-CRP concentrations. This study showed that among Iranian subjects, the inflammatory marker, hs-CRP, was strongly and positively associated with a marker of oxidative stress and also with several traditional risk factors of CVD. Moreover, the impact of traditional cardiovascular risk factors on hs-CRP concentrations and PAB values differed.

Causal Relevance of Blood Lipid Fractions in the Development of Carotid Atherosclerosis

Background— Carotid intima–media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with risk of coronary heart disease events. Statins reduce progression of CIMT and coronary heart disease risk in proportion to the reduction in low-density lipoprotein cholesterol. However, interventions targeting triglycerides (TGs) or high-density lipoprotein cholesterol (HDL-C) have produced inconsistent effects on CIMT and coronary heart disease risk, making it uncertain whether such agents are ineffective for coronary heart disease prevention or whether CIMT is an inadequate marker of HDL-C or TG-mediated effects. We aimed to determine the causal association among the 3 major blood lipid fractions and common CIMT using mendelian randomization analysis. Methods and Results— Genetic scores specific for low-density lipoprotein cholesterol, HDL-C, and TGs were derived based on single nucleotide polymorphisms from a gene-centric array in ≈5000 individuals (Cardiochip scores) and from a genome-wide association meta-analysis in &gt;100 000 individuals (Global Lipids Genetic Consortium scores). These were used as instruments in a mendelian randomization analysis in 2 prospective cohort studies. A genetically predicted 1 mmol/L higher low-density lipoprotein cholesterol concentration was associated with a higher common CIMT by 0.03 mm (95% confidence interval, 0.01–0.04) and 0.04 mm (95% confidence interval, 0.02–0.06) based on the Cardiochip and Global Lipids Genetic Consortium scores, respectively. HDL-C and TGs were not causally associated with CIMT. Conclusions— Our findings confirm a causal relationship between low-density lipoprotein cholesterol and CIMT but not with HDL-C and TGs. At present, the suitability of CIMT as a surrogate marker in trials of cardiovascular therapies targeting HDL-C and TGs is questionable and requires further study.

Determinants of Serum Concentrations of Lipopolysaccharide-Binding Protein (LBP) in the Adult Population: The Role of Obesity

Background and AimAssessment of serum concentration of lipopolysaccharide (LPS)-binding protein (LBP) has been suggested as a useful biomarker to indicate activation of innate immune responses to microbial products. We investigated LBP concentrations and associations with demographics, lifestyle factors, and common metabolic abnormalities in adults. We also examined if LBP concentrations were associated with common polymorphisms in genes coding for LBP (rs2232618), CD14 (rs2569190), and TLR4 (rs4986790), the molecules responsible for the innate immune response to LPS, or serum levels of soluble CD14 (sCD14) and proinflammatory cytokines.MethodsSerum LBP was measured with a commercial immunoassay in a random sample of the adult population (n = 420, 45% males, age 18–92 years) from a single municipality.ResultsSerum LBP concentrations increased with age (P<0.001) and were higher in individuals who were overweight or obese than in normal-weight individuals (P<0.001). Similarly, LBP concentrations were higher in individuals with metabolic syndrome than in individuals without it (P<0.001). Among metabolic syndrome components, LBP concentrations were independently associated with abdominal obesity (P = 0.002) and low concentrations of HDL-cholesterol (P<0.001). Serum LBP concentrations tended to be independently associated with smoking (P = 0.05), but not with alcohol consumption. Likewise, there was not significant association between LBP concentrations and gene polymorphisms. Concentrations of LBP significantly correlated with serum levels of proinflammatory cytokines (IL-6 and IL-8), sCD14, and with liver enzymes.ConclusionsSerum LBP concentrations increased with age. Overweight, obesity, and having metabolic syndrome (particularly, low HDL cholesterol levels) were associated with higher LBP concentrations. These findings are consistent with microbial exposure playing a role in these inflammatory, metabolic abnormalities.

Implication of Low HDL-c Levels in Patients with Average LDL-c Levels: A Focus on Oxidized LDL, Large HDL Subpopulation, and Adiponectin

To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF-α, adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.