Carotid atherosclerosis and lipoprotein particle subclasses in familial hypercholesterolaemia and familial combined hyperlipidaemia

Background and AimsFamilial hypercholesterolaemia (FH) and familial combined hyperlipidaemia (FCH) are common atherogenic disorders with great variability in cardiovascular disease (CVD). No direct atherosclerosis burden comparisons have been performed between FH and FCH in relation to lipoprotein particle distribution.Methods and ResultsRisk factors and three measures of carotid intima-media thickness (IMT) in both sides were determined in 572 FH, 250 FCH and 200 controls. Lipoproteins were assessed by nuclear magnetic resonance (NMR) spectroscopy. Compared with controls, IMT measures were increased in FH and FCH. FCH had the highest adjusted mean–maximum IMT. FH had twice low-density lipoprotein (LDL) particles than controls, but similar LDL subclass size and distribution. FCH subjects also had increased LDL particles and the highest number of small LDL (1519 ± 731 nmol l^?1 vs. 887 ± 784 nmol l^?1 in FH and 545 ± 409 nmol l^?1 in controls). Age, gender, cholesterol/high-density lipoprotein (HDL) ratio, smoking and systolic blood pressure were independently associated with IMT in FH (r² = 0.38). The same variables, except cholesterol/HDL ratio, were associated with IMT in FCH (r² = 0.40). Among NMR lipoproteins, only VLDL and chylomicrons increased IMT prediction in FCH by 0.8%.ConclusionFH and FCH subjects show increased carotid atherosclerosis in relation to classical risk factors. Lipoprotein subclasses do not substantially contribute to IMT variability.     

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

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

Lipoprotein status among urban populations in Bangladesh

ObjectiveSerum lipoprotein is the most important predictor for microvascular diseases, and may be influenced by rapid urbanization. Currently available data are limited, particularly regarding age-specific lipoprotein status in urban Bangladeshi populations.MethodsBlood lipoprotein levels of 51,353 male and female individuals primarily residing in urban Bangladesh were analyzed. De-identified data (collected between January 2005 and December 2011) were extracted from the Clinical Biochemistry Laboratory Data Archive of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). For analyses, six age categories were created: (i) <20 years, n = 481; (ii) 20–29 years, n = 1602; (iii) 30–39 years, n = 7272; (iv) 40–49 years, n = 13,582; (v) 50–59 years, n = 15,890; and (vi) 60 years and more, n = 12,526.ResultsMean serum levels of TC, LDL, TG, LDL:HDL and TC:HDL were significantly higher among adults 30–39 years old compared to other age groups, regardless of sex. The proportion of high TC and LDL from 2005 to 2011 among individuals aged 30–39 years old varied widely (p < 0.01 for trend and all pairwise tests).Conclusion30–39 years old individuals had higher concentration of lipoprotein, which increases microvascular disease risk. Further population-based studies are needed to validate our observations in rural areas of Bangladesh.     

Advanced lipoprotein profile identifies atherosclerosis better than conventional lipids in type 1 diabetes at high cardiovascular risk

Background and aimsPeople with type 1 diabetes (T1D) present lipoprotein disturbances that could contribute to their increased cardiovascular disease (CVD) risk. We evaluated the relationship between lipoprotein alterations and atherosclerosis in patients with T1D.Methods and resultsCross-sectional study in subjects with T1D, without previous CVD, but high-risk (≥40 years, nephropathy, or ≥10 years of evolution of diabetes with another risk factor). The presence of plaque (intima-media thickness ≥1.5 mm) in the different carotid segments was determined by ultrasound. The advanced lipoprotein profile was analysed by magnetic resonance imaging (¹H NMR). We included 189 patients (42% women, 47.8 ± 10.7 years, duration of diabetes 27.3 ± 10.1 years, HbA1c 7.5% [[7], [8]]). Those with carotid plaques (35%) were older, with longer diabetes duration, had a higher prevalence of hypertension, and showed lower and smaller LDL particles (LDL-P) and HDL particles (HDL-P), but higher VLDL particles (VLDL-P). Some LDL, HDL and VLDL-related parameters were associated with atherosclerosis in sex, age and statin use adjusted models (p < 0.05), but after adjusting for multiple confounders, including conventional lipid parameters, only HDL-P (OR 0.440 [0.204–0.951]; p = 0.037), medium HDL-P (OR 0.754 [0.590–0.963]; p = 0.024), HDL-P cholesterol content (OR 0.692 [0.495–0.968]; p = 0.032), ¹H NMR LDL-P number/conventional LDL-cholesterol (OR 1.144 [1.026–1.275]; p = 0.015), and ¹H NMR non-HDL particle number/conventional non-HDL-cholesterol ratios (OR 1.178 [1.019–1.361], p = 0.026) remained associated with atherosclerosis.ConclusionsIn adults with T1D at high-risk, variables related to HDL, LDL and total atherogenic particle number are independently associated with preclinical atherosclerosis. Advanced lipoprotein profiling could be used to identify those at the highest risk of CVD.     

Weight change and lipoprotein particle concentration and particle size: a cohort study with 6.5-year follow-up

ObjectiveObesity and overweight are related to unfavourable lipoprotein subclass profiles. Here we studied the relation between weight change and lipoprotein particle concentrations and sizes in a general population cohort in a longitudinal setting.MethodsThe cohort included 683 adults with a 6.5-year follow-up. Lipoprotein particle subclasses and mean particle sizes of VLDL, LDL, and HDL were measured by nuclear magnetic resonance spectroscopy.ResultsDuring the follow-up period, a weight loss of at least 5% was associated with decreased particle concentrations of all apoB-containing subclasses and increased concentrations of large HDL particles. Coherently, weight gain (≥5%) was associated with increases in all apoB-containing subclasses and decreases in total and medium HDL particle concentrations. The relatively largest increase occurred for large HDL particle concentration (24.1%, 95% CI 15.8–32.5) in weight loss and for large VLDL particle concentration (33.0%, 19.6–46.4) in weight gain. Weight change correlated positively with changes in apoB-containing lipoprotein particle concentrations and also with the change in average VLDL particle size. Negative correlations were found between weight change and the change in average LDL (r = ?0.10) and HDL (r = ?0.32) particle size, but not between weight change and total HDL particle concentration.ConclusionModerate weight loss is related to favourable and weight gain to unfavourable changes in lipoprotein subclass profiles. These population level findings underline the importance of weight control as a modifier of cardiovascular risk factors.     

Di-oleoyl phosphatidylcholine (PC-18:1) stimulates paraoxonase 1 (PON1) enzymatic and biological activities: in vitro and in vivo studies

ObjectiveParaoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme which possess anti-atherogenic properties. Our aim was to analyze the effect of HDL phospholipids on HDL-associated paraoxonase (PON1) catalytic and biological activities.Methods and resultsIn HDL isolated from di-oleoyl-phosphatidylcholine (PC-18:1)-enriched serum, HDL–PC-18:1 levels, as well as PON1 lactonase, arylesterase and paraoxonase activities were increased by 23%, 35%, 47% and 63%, respectively, as compared to control HDL (p < 0.01). Furthermore, PON1 contribution to HDL-mediated cholesterol efflux from J774A.1 macrophages was higher in PC-18:1-enriched HDL in comparison to control HDL.In vivo olive oil consumption by Balb C mice increased HDL phospholipids/protein (30%), and HDL–PON1 arylesterase (150%) and lactonase (94%) activities (p < 0.01). Furthermore, in the olive oil-treated mice PON1 contribution to HDL-mediated macrophage cholesterol efflux was higher by 100%, in comparison to placebo mouse HDL (p < 0.01). Similarly, olive oil consumption by healthy subjects increased HDL–PC-18:1 levels, HDL–PON1 arylesterase (88%), lactonase (52%), paraoxonase (140%) activities and PON1 stimulatory effect on HDL-mediated cholesterol efflux (53%) as compared to HDL before treatment (p < 0.01).PC-18:1 stimulatory effect on recombinant PON1 mutant (lacks 20 amino acids at the N-terminal region) paraoxonase and lactonase activities was lower by 56% and 57%, respectively, in comparison to its effect on wild type PON1 (p < 0.01).ConclusionIntervention to increase PON1 activities by HDL enrichment with PC-18:1 could be proven as a beneficial anti-atherogenic therapy.     

Targeted profiling of atherogenic phospholipids in human plasma and lipoproteins of hyperlipidemic patients using MALDI-QIT-TOF-MS/MS

ObjectivesPhospholipids (PLs) are increasingly recognized as key molecules with potential diagnostic value in acute inflammation, CVD and atherosclerosis. We introduce a pioneer mass spectrometry (MS)-based approach aiming to investigate the relationship of specific plasma PL-subsets with atherogenic blood parameters in young patients with familial hyperlipidemia representing high-CVD-risk groups.MethodsPlasma of carefully phenotyped FH and FCH patients as well as normolipidemic subjects (age 13 ± 5 years, n = 20) was used. Clinical parameters were assessed using standard laboratory techniques and lipids were subjected to a direct targeted monitoring using LC-ESI-SRM- and MALDI-QIT-TOF-MS/MS, respectively. Statistical analysis was performed to evaluate correlations between PL data and the clinical parameters.ResultsMost characteristically significant differences of SM/PC and PC/LPC ratios and positive correlations between SM vs. LDL-C (r = 0.946; p = 0.004) and LPC vs. VLDL-C (r = 0.669; p = 0.218) were observed in FH in contrast to the other study groups. OxPC levels were found in the range of ～2–20 μmol/L with predominance of short-chain aldehydic species (e.g. SOVPC). A positive correlation of OxPCs with IMT (r = 0.952; p = 0.052) and HDL-C (r = 0.893; p = 0.016) but negative correlation with OxLDL (r = ?0.910; p = 0.096) was observed.ConclusionsOur study was a first attempt to use a MALDI-QIT-TOF-MS/MS based clinical lipidomics approach to investigate atherogenic dyslipidemia in young patients with familial hyperlipidemia. This technique represents a promising platform for clinical screening of lipid biomarkers in the future.     

Increased plasma visfatin concentration is a marker of an atherogenic metabolic profile

Background and aimsVisfatin is associated with atherosclerosis-related diseases. We assessed in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis-related metabolic variables.Methods and resultsWhen study population (n = 179, age 49 ± 11 years) was divided according to visfatin tertiles, the 10-year CVD Framingham risk scores were significantly increased in the top visfatin tertile. We observed a positive association between visfatin tertiles with waist circumference and blood pressure, as well as with total cholesterol and triglyceride levels, but not with apolipoprotein C-III, fibrinogen or pre-beta1 high density lipoprotein (HDL). The percentage of large HDL subclasses was significantly lower and the percentage of small HDL subclasses over the HDL-C concentration was significantly higher in the top visfatin tertile compared with the other tertiles. The atherogenic small dense low density lipoprotein subclasses (sdLDL-C) were significantly increased in the top visfatin tertile compared with the lower tertiles. High sensitivity C-reactive protein (hsCRP) concentration was significantly increased in the top visfatin tertile compared with the lower tertiles. Although age and sex distribution did not differ between visfatin tertiles, the simultaneous adjustment for these parameters attenuated the significance of the differences observed in sdLDL-C and hsCRP levels. Similarly, after adjustment for hsCRP or waist circumference, only triglycerides and blood pressure levels, as well as the distribution of HDL subclasses, remained significantly different between visfatin tertiles.ConclusionsOur results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in increased CVD risk.     

Atherogenic index of plasma and its association with cardiovascular disease risk factors among postmenopausal rural women of Bangladesh

ObjectivesThere is absolute lacking of evidences on atherogenic index of plasma (AIP) and its association with cardiovascular disease (CVD) risk factors among postmenopausal women of Bangladesh. This prompted us to investigate this association between AIP and CVD risk factors among postmenopausal women in a rural setting.MethodsThis cross-sectional study recruited 265 postmenopausal women aged 40–70 years who visited a primary health-care center of Bangladesh. We used modified STEP-wise approach for the Surveillance of Noncommunicable diseases risk factors questionnaire of the World Health Organization to collect data on sociodemographic and behavioral risk factors. Physical measurements were carried out following the method described in the ‘noncommunicable disease risk factors survey Bangladesh 2010’. AIP was determined by the logarithmic transformation of triglyceride to high-density lipoprotein ratio, and association with CVD risk factors were examined by multiple linear regression analysis.ResultsOverall 35.5% respondents had a high risk level of AIP with a mean of 0.16 ± 0.25. After adjusting the confounders, CVD risk factors including duration of menopause (β = 0.606, p = 0.043), waist–hip ratio (β = 0.165, p = 0.003), 2-h plasma glucose (β = 0.118, p = 0.04), total cholesterol (β = 1.082, p < 0.001), low-density lipoprotein cholesterol (β = −1.044, p < 0.001), and metabolic equivalent of tasks (β = −0.171, p = 0.003) showed a significant association with AIP.ConclusionHigh AIP and its significant association with CVD risk factors demand proper lifestyle intervention for postmenopausal women of Bangladesh.     

Subclinical coronary atherosclerosis and resting ECG abnormalities in an unselected general population

ObjectivesExposure to cardiovascular (CV) risk factors may result in coronary atherosclerosis and myocardial disease, which is reflected in the extent of coronary artery calcification (CAC) and resting ECG abnormalities, respectively. We studied the association of CAC with ECG abnormalities in a general population without myocardial infarction or revascularization.MethodsThe total cohort of 4814 subjects (45–75 years) were randomly selected from the general population for the Heinz Nixdorf Recall Study, an ongoing study designed to assess the prognostic value of modern risk stratification methods. In addition to measuring standard risk factors, digitized resting ECGs and the EBT-based Agatston score were obtained. Subjects were separated into those without (n = 1929) and with CV disease (CVD) or treated risk factors (tRF) (n = 2558).ResultsIn both groups, a positive CAC-score was more frequent and CAC-scores were higher in men and women with ECG abnormalities as compared to those with normal ECGs (p < 0.05 each). In persons without CVD/tRF, a CAC ≥75th percentile was more frequent in those with LVH (42.4%) and QTc >440 ms (34.2%) as compared to normal ECGs (23.0%, p < 0.01 for both). In persons with CVD/tRF, a CAC-score ≥75th percentile was found in subjects with A-Fib (46.3%), borderline-LVH (39.1%), ECG signs of MI (40.5%) and major ECG abnormalities (40.3%) versus 31.2% in those with normal ECGs (p < 0.03 for all). In multivariate analysis, LVH (p = 0.025) and major ECG abnormalities (p = 0.04) remained independently associated with CAC in subjects without and with CVD/tRF, respectively.ConclusionsECG-based evidence of myocardial disease is often associated with an elevated CAC burden, suggesting a link between epicardial and myocardial manifestations of risk factor exposure. The association of CAC burden with different ECG abnormalities in different clinical groups may have implications for the interpretation of the resting ECG and CAC burden in risk stratification.     

Normal weight obese (NWO) women: an evaluation of a candidate new syndrome

Background and aimsObesity, an independent risk factor for cardiovascular disease (CVD), has been associated with the early development of coronary atherosclerosis in adolescents and young men. A subset of metabolically obese but normal weight individuals was identified, with potentially increased risks for development of the metabolic syndrome despite their normal body mass index. We determined the relationship among body fat distribution and selected CVD risk factors to distinguish normal weight obese from controls with normal metabolic profiles.Methods and resultsWe analysed anthropometric variables, body composition by DXA, RMR by indirect calorimetry and bioumoral variables of 74 clinically healthy Caucasian Italian women. Significant differences were observed in the biochemical HDL-chol values between NWO and controls and pre-obese-obese. Significant correlations were found among cardiovascular risk indexes, LEAN of the right part of the trunk and TC/HDL (R = −0.69, p < 0.001) and LDL/HDL (R = −0.72, p < 0.001), and LEAN and RMR (R = 0.44, p = 0.022) of NWO women.ConclusionsIn normal weight obese women the cardiovascular risk indexes are related to metabolic variables and to body fat mass distribution. NWO individuals showed a relationship between the decrease in LEAN of the left leg and an increase in CVD risk factors. We suggest that LEAN distribution seems to be a potential predictor of CVD.     

Intra-thoracic fat, cardiometabolic risk factors, and subclinical cardiovascular disease in healthy, recently menopausal women screened for the Kronos Early Estrogen Prevention Study (KEEPS)

ObjectiveTo examine the correlations between intra-hepatic and intra-thoracic (total, epicardial, and pericardial) fat deposition with cardiovascular disease (CVD) risk factors and subclinical atherosclerosis burden in healthy, recently postmenopausal women.MethodsWomen screened for the Kronos Early Estrogen Prevention Study (mean age 52.9 years) who underwent electron beam or multidetector computed tomography (CT) imaging for the quantification of intra-hepatic fat and thoracic adipose tissue, and coronary artery calcification (CAC) were included (n = 650).ResultsHigher levels of intra-hepatic and thoracic fat were each associated with CVD risk markers. After adjustment for BMI, the associations for intra-hepatic fat with hs-CRP and insulin persisted (r = 0.21 and 0.19, respectively; P < 0.001), while those between thoracic fat indices and lipids persisted (r for total thoracic fat with HDL, LDL, and triglycerides = ?0.16, 0.11, and 0.11, respectively, P < 0.05). Total thoracic fat was associated with CAC after initial multivariable adjustment (odds ratio [OR] of 2nd, 3rd, and 4th vs. 1st quartile and [95% confidence intervals]: 0.8 [0.4–1.6], 1.5 [0.8–2.9], and 1.8 [1.0–3.4]; p for linear trend = 0.017) and was only slightly attenuated after additional adjustment for BMI. Associations between total thoracic fat and CVD risk markers and CAC appeared due slightly more to associations with epicardial than pericardial fat.ConclusionWhile hepatic fat is related to hs-CRP and insulin, cardiac fat is associated with subclinical atherosclerosis as demonstrated by CAC. Cardiac fat may represent a useful marker for increased CVD risk beyond the standard adiposity measures of BMI and WC.     

Protease inhibitor-based HAART, HDL, and CHD-risk in HIV-infected patients

ObjectiveTo study the effects of HIV-infection and protease inhibitor (PI)-based highly active anti-retroviral therapy (HAART) on the lipid and high-density lipoprotein (HDL) subpopulation profile and to relate the changes to coronary heart disease (CHD)-risk.Methods and designThe lipid and HDL subpopulation profiles of HIV-positive subjects (n = 48) were studied prospectively by comparing pre- and post-PI-HAART data as well as cross-section by comparing the profiles to HIV-negative subjects with (n = 96) and without CHD (n = 96).ResultsHIV-infected HAART-naïve subjects had lower concentrations of low-density lipoprotein cholesterol (LDL-C) and HDL-C and higher concentration of triglycerides (TG) than healthy controls. After receiving PI-based HAART, LDL-C and TG concentrations increased, while HDL-C concentrations remained unchanged. The HDL subpopulation profiles of HAART-naïve HIV-positive patients were significantly different from those of healthy controls and were similar to those with CHD. Moreover, the HDL subpopulation profile changed unfavorably after PI-based HAART, marked with increased concentrations of the small, lipid-poor pre-β-1 HDL (32% or 3.9 mg/dl; p < 0.001), and decreased concentration of the large, cholesterol-rich α-1 HDL(9% or 1 mg/dl ns).ConclusionAn already unfavorable lipid and HDL subpopulation profile of HIV-positive HAART-naïve subjects further deteriorated after receiving PI-based treatment, which may cause increased CHD-risk in these subjects.     

The multi-faceted outcomes of conjunct diabetes and cardiovascular familial history in type 2 diabetes

BackgroundFamilial history of early-onset CHD (EOCHD) is a major risk factor for CHD. Familial diabetes history (FDH) impacts β-cell function. Some transmissible, accretional gradient of CHD risk may exist when diabetes and EOCHD familial histories combine. We investigated whether the impact of such combination is neutral, additive, or potentiating in T2DM descendants, as regards cardiometabolic phenotype, glucose homeostasis and micro-/macroangiopathies.MethodsCross-sectional retrospective cohort study of 796 T2DM divided according to presence (Diab[+]) or absence (Diab[?]) of 1st-degree diabetes familial history and/or EOCHD (CVD(+) and (?)). Four subgroups: (i) [Diab(?)CVD(?)] (n = 355); (ii) [Diab(+)CVD(?)] (n = 338); (iii) [Diab(?)CVD(+)] (n = 47); and (iv) [Diab(+)CVD(+)] (n = 56).ResultsNo interaction on subgroup distribution between presence of both familial histories, the combination of which translated into additive detrimental outcomes and higher rates of fat mass, sarcopenia, _hsCRP and retinopathy. FDH(+) had lower insulinemia, insulin secretion, hyperbolic product, and accelerated hyperbolic product loss. An EOCHD family history affected neither insulin secretion nor sensitivity. There were significant differences regarding macroangiopathy/CAD, more prevalent in [Diab(?)CVD(+)] and [Diab(+)CVD(+)]. Among CVD(+), the highest macroangiopathy prevalence was observed in [Diab(?)CVD(+)], who had 66% macroangiopathy, and 57% CAD, rates higher (absolute-relative) by 23%–53% (overall) and 21%–58% (CAD) than [Diab(+)CVD(+)], who inherited the direst cardiometabolic familial history (p 0.0288 and 0.0310).ConclusionsA parental history for diabetes markedly affects residual insulin secretion and secretory loss rate in T2DM offspring without worsening insulin resistance. It paradoxically translated into lower macroangiopathy with concurrent familial EOCHD. Conjunct diabetes and CV familial histories generate multi-faceted vascular outcomes in offspring, including lesser macroangiopathy/CAD.     

Reduced growth hormone secretion in obesity is associated with smaller LDL and HDL particle size

Objective Reduced growth hormone (GH) secretion is observed in obesity and may contribute to increases in cardiovascular disease (CVD) risk. Lipoprotein characteristics including increased small dense low‐density lipoprotein (LDL) particles are known independent risk factors for CVD. We hypothesized that reduced GH secretion in obesity would be associated with a more atherogenic lipid profile including increased small dense LDL particles. Design To evaluate this hypothesis, we studied 102 normal weight and obese men and women using standard GH stimulation testing to assess GH secretory capacity and performed comprehensive lipoprotein analyses including determination of lipoprotein particle size and subclass concentrations using proton NMR spectroscopy. Results Obese subjects were stratified into reduced or sufficient GH secretion based on the median peak‐stimulated GH (≤6·25 μg/l). Obese subjects with reduced GH secretion (n = 35) demonstrated a smaller mean LDL and HDL particle size in comparison to normal weight subjects (n = 33) or obese subjects with sufficient GH (n = 34) by anova (P < 0·0001). Univariate analyses demonstrated peak‐stimulated GH was positively associated with LDL (r = 0·50; P < 0·0001) and HDL (r = 0·57; P < 0·0001), but not VLDL (P = 0·06) particle size. Multivariate regression analysis controlling for age, gender, race, ethnicity, tobacco, use of lipid‐lowering medication, BMI and HOMA demonstrated peak‐stimulated GH remained significantly associated with LDL particle size (β = 0·01; P = 0·01; R² = 0·42; P < 0·0001 for overall model) and HDL particle size (β = 0·008; P = 0·001; R² = 0·44; P < 0·0001 for overall model). Conclusions These results suggest reduced peak‐stimulated GH in obesity is independently associated with a more atherogenic lipoprotein profile defined in terms of particle size.     

Pancreatic β-cell function relates positively to HDL functionality in well-controlled type 2 diabetes mellitus

BackgroundHigh density lipoproteins (HDLs) have been implicated in glucose homeostasis. Among subjects with normal fasting glucose (NFG), impaired fasting glucose (IFG) and Type 2 diabetes mellitus (T2DM) we tested whether pancreatic β-cell function relates to HDL functionality, as determined by HDL anti-oxidative capacity and cellular cholesterol efflux to plasma.Subjects and methodsHDL anti-oxidative capacity (inhibition of LDL oxidation in vitro), cellular cholesterol efflux (the ability of plasma to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single human donor), glucose and insulin were determined in fasting plasma samples from 37 subjects with NFG, 36 with IFG and 22 with T2DM (no glucose lowering drug or insulin treatment; HbA1c 6.0 ± 1.0%). Homeostasis model assessment was used to estimate pancreatic β-cell function (HOMA-β) and insulin resistance (HOMAir).ResultsHOMA-β was lowest, whereas HOMAir was highest in T2DM (P < 0.01 and P < 0.001 vs. NFG). HDL anti-oxidative capacity and cellular cholesterol efflux did not differ significantly according to glucose tolerance category. In univariate analysis and after controlling for HOMAir both HDL anti-oxidative capacity (P < 0.05) and cellular cholesterol efflux (P < 0.01) were positively correlated with HOMA-β in T2DM, but not in NFG and IFG. In age-, sex- and HOMAir-adjusted analyses, T2DM status interacted positively with HDL anti-oxidative capacity (P = 0.001) and cellular cholesterol efflux (P = 0.042) on HOMA-β. HbA1c interacted similarly with HDL functionality measures on HOMA-β.ConclusionsPancreatic β-cell function relates to pathophysiologically relevant measures of HDL function in T2DM, but not in NFG and IFG. Better HDL functionality may contribute to maintenance of β-cell function in subjects with well-controlled T2DM.     

Adiponectin G276T gene polymorphism is associated with cardiovascular disease in Japanese patients with type 2 diabetes

ObjectiveAdiponectin has anti-atherogenic properties and reduced serum adiponectin levels are associated with cardiovascular disease (CVD). In this study, we examined the relationship between CVD and adiponectin (ADIPOQ) gene G276T polymorphism that is associated with serum adiponectin level in a large cohort of type 2 diabetic patients.Research design and methodsWe enrolled 2637 Japanese type 2 diabetic subjects (males, 61.1%; age, 54.9 ± 7.9 years old), determined their genotypes regarding ADIPOQ G276T polymorphisms, and evaluated the association between this polymorphism and the prevalence of CVD (myocardial infarction and/or cerebral infarction).ResultsThe prevalence of CVD tended to be higher as the number of G alleles increased [GG (9.5%), GT (6.8%), TT (5.6%), p value for trend = 0.0059] and was significantly higher in the subjects with GG genotype compared to those with GT or TT genotype (9.5% vs. 6.6%, p = 0.0060). Multiple logistic regression analyses revealed that the number of G alleles (Odds ratio (OR) = 1.49 with 95%CI 1.09–2.05, p = 0.0125) and GG genotype (OR = 1.66 with 95%CI 1.13–2.43, p = 0.0098) were significantly associated with CVD even after adjustment for conventional risk factors. Interestingly, the presence of obesity further and significantly increased the risk of CVD in the subjects with GG genotype (OR = 1.67 with 95%CI 1.14–2.44, p = 0.0090) but not in the subjects with TT or GT genotype (OR = 1.17 with 95%CI 0.73–1.89, NS).ConclusionsIt is likely that the G allele of the ADIPOQ G276T polymorphism is a susceptibility allele for CVD in Japanese type 2 diabetic patients, especially when they accompany obesity.     

Postprandial modulation of serum paraoxonase activity and concentration in diabetic and non-diabetic subjects

ObjectivesTo analyse the HDL associated anti-oxidant enzyme paraoxonase-1, during postprandial hyperlipaemia.Methods and resultsType 2 diabetic patients (n = 72), glucose intolerant patients (n = 10) and controls (n = 38) consumed a high fat:high carbohydrate meal. Blood samples were collected up to 4 h and analysed for lipids and paraoxonase-1. In vitro studies examined HDL function with respect to the enzyme. There were significant postprandial increases in serum triglycerides. Paraoxonase-1 activity decreased significantly throughout the postprandial phase. Concentrations of the enzyme initially decreased significantly, but returned to fasting concentrations at 4 h. Specific activities were significantly lower at 4 h, compared to fasting. The decrease in specific activity was linked to the dynamic phase of postprandial lipoprotein metabolism. Apo AI limited loss of paraoxonase-1. HDL isolated after being subjected to postprandial conditions in vitro had reduced capacity to associate with and stabilise PON1.ConclusionsPostprandial hyperlipaemia was associated with changes to serum paraoxonase-1, consistent with a reduced anti-oxidant potential of HDL. No differences were observed between diabetic and non-diabetic patients, suggesting that the effect was linked to postprandial hyperlipaemia. Modifications to paraoxonase-1 could contribute to increased risk of vascular disease associated with postprandial lipaemia, particularly in diabetic patients, who are already deficient in serum paraoxonase-1.     

Obesity markers and estimated 10-year fatal cardiovascular risk in Switzerland

Background and aimThere is an ongoing debate on which obesity marker better predicts cardiovascular disease (CVD). In this study, the relationships between obesity markers and high (>5%) 10-year risk of fatal CVD were assessed.Methods and resultsA cross-sectional study was conducted including 3047 women and 2689 men aged 35–75 years. Body fat percentage was assessed by tetrapolar bioimpedance. CVD risk was assessed using the SCORE risk function and gender- and age-specific cut points for body fat were derived. The diagnostic accuracy of each obesity marker was evaluated through receiver operating characteristics (ROC) analysis.In men, body fat presented a higher correlation (r = 0.31) with 10-year CVD risk than waist/hip ratio (WHR, r = 0.22), waist (r = 0.22) or BMI (r = 0.19); the corresponding values in women were 0.18, 0.15, 0.11 and 0.05, respectively (all p < 0.05). In both genders, body fat showed the highest area under the ROC curve (AUC): in men, the AUC (95% confidence interval) were 76.0 (73.8–78.2), 67.3 (64.6–69.9), 65.8 (63.1–68.5) and 60.6 (57.9–63.5) for body fat, WHR, waist and BMI, respectively. In women, the corresponding values were 72.3 (69.2–75.3), 66.6 (63.1–70.2), 64.1 (60.6–67.6) and 58.8 (55.2–62.4). The use of the body fat percentage criterion enabled the capture of three times more subjects with high CVD risk than the BMI criterion, and almost twice as much as the WHR criterion.ConclusionObesity defined by body fat percentage is more related with 10-year risk of fatal CVD than obesity markers based on WHR, waist or BMI.     

Intima-media thickness predicts stroke risk in the Heinz Nixdorf Recall study in association with vascular risk factors, age and gender

Background and purposeIndividual risk stratification requires reliable information on preexisting vascular disease. The intima-media thickness of the common carotid artery (CIMT) is a non-invasively accessible marker of atherosclerosis, which can be used for risk evaluation.MethodsIn a sample of 3669 initially stroke-free subjects aged 45–75 years belonging to the population-based Heinz Nixdorf Recall cohort, the predictive value of CIMT for incident stroke was evaluated over 85.3 ± 17.4 months in addition to established risk factors.ResultsIn a multivariable Cox regression analysis with traditional cardiovascular risk factors including age, gender, systolic blood pressure, LDL and HDL, diabetes, body mass index, smoking and CIMT, CIMT was a moderate stroke predictor (hazard ratio = 1.20 per 0.1 mm, 95% confidence interval = 1.01–1.44; p = 0.043), additional to e.g. age (1.46 per 5 years, 1.21–1.75; p < 0.001), systolic blood pressure (1.16 per 10 mm Hg, 1.04–1.30; p = 0.008) and current smoking (1.93, 1.12–3.31; p = 0.014). CIMT was associated with stroke risk in subjects above but not below 65 years. CIMT predicted stroke events in men, but not women. CIMT discriminated stroke incidence specifically in subjects belonging to the highest Framingham risk score tercile.ConclusionsCIMT is a moderate independent stroke predictor, which discriminates stroke incidence in subjects at high vascular risk.