Abnormal lipoprotein particles and cholesterol efflux capacity in patients with psoriasis

ObjectivesPsoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis.Methods and resultsWe prospectively enrolled a consecutive sample of patients with psoriasis (n = 122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n = 134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n = 100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dl (36–58) vs 50 (42–62), p < 0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002–1498) vs 1115 (935–1291), p = 0.02] with decrease in LDL size [20.6 (20.3–21.1) vs 21.3 (20.6–21.1), p < 0.001] beyond CV risk factors and HOMA-IR (p = 0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta ?0.14, p = 0.001).ConclusionsThese data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and 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.     

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.     

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

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

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients

Background and aimType 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients.Methods and resultsWe studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (−108C > T, 55T > A, and 192A > G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P = 0.016), OxLDL/HDL (18%; P = 0.024) and OxLDL-Ab (12%; P = 0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P < 0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (−108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P = 0.040) in patients with atherosclerosis.ConclusionOxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.     

Relationship among obesity,blood lipids and insulin resistance in Bangladeshi adults

IntroductionInsulin resistance (IR) and abnormal lipid profiles are the risk factors for cardiovascular diseases in obesity. To clarify the relationship of the changes in insulin resistance, body weight and lipid profile, the present study was performed on Bangladeshi adults, total of 1500 individuals at the time of their general health examination in the hospital.MethodsAfter exclusion of other endocrine diseases, the remaining 772 patients were classified as IR ≥ 2 and IR < 2 based on the homeostatic model assessment-estimated insulin resistance (HOMA-IR) index. The endocrine disease free subjects were further clustered based on age, gender and obesity. The anthropometric and biochemical profiles were statistically analyzed and correlated with IR ≥ 2 and IR<2 groups as well as other clusters of the subjects. Apart from some disparities, notable differences were observed in all anthropometric data.ResultsTotal cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and serum insulin levels were significantly higher in IR ≥ 2 group in comparison with IR<2 group. Obesity and dyslipidemia were associated as prevalent components of IR. Generalized linear model revealed that TC: LDL and TG: HDL had significant effect on IR. Age group II (41–60 years old) subjects had significantly higher lipid profile compared to age group I (20–40 years old) and age group III (61–80 years old).ConclusionsResults reported herein support the notion that lipoprotein ratios might be the reliable biomarkers to evaluate IR.     

Usefulness of lipoprotein ratios in assessing carotid atherosclerosis in Japanese type 2 diabetic patients

ObjectiveIt is indicated that total/HDL cholesterol and LDL/HDL cholesterol ratios have more predictive power for cardiovascular disease compared to classic lipid parameters. However, there have been few reports about the usefulness of these indices for the assessment of early stage atherosclerosis in Japanese type 2 diabetic subjects.MethodsWe examined the relation between various lipid parameters and carotid atherosclerosis in 934 type 2 diabetic subjects without apparent atherosclerotic diseases (males, 71.7%; age, 59.6 ± 10.5 years (mean ± SD)). Serum concentrations of total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride were measured. LDL cholesterol (LDL-C) level was calculated using the Friedewald formula. The presence of carotid plaque and intima-media thickness (IMT) were evaluated by ultrasonography.ResultsA stepwise multivariate regression analysis demonstrated that HDL-C (β = ?0.110, p < 0.001), TC/HDL-C (β = 0.132, p < 0.001) and LDL-C/HDL-C ratios (β = 0.132, p < 0.001) were independent determinants of IMT even after adjustment of other conventional risk factors. However, there was no significant correlation between IMT and TC, triglyceride, LDL-C, and non-HDL-C levels. TC/HDL-C and LDL-C/HDL-C ratios and non-HDL-C levels were significantly higher, but HDL-C levels were significantly lower in patients with carotid plaque than those without it (p < 0.05). There was no significant difference between the groups regarding TC, LDL-C, and triglyceride levels. Furthermore, TC/HDL-C (OR; 1.34, p < 0.001) and LDL-C/HDL-C (OR; 1.54, p < 0.001) ratios showed a positive and linear relationship with the prevalence of carotid plaque, whether covariates were adjusted or not.ConclusionsTC/HDL-C and LDL-C/HDL-C ratios are useful as a tool to assess the risk of early stage atherosclerosis in Japanese type 2 diabetic patients.     

Comparative analysis of biochemical parameters in diabetic and non-diabetic acute myocardial infarction patients

BackgroundDiabetes is a metabolic disorder characterized by enhanced production of free radicals hence oxidative stress. The aim of this study was to evaluate the activity of cardiac and antioxidant enzymes in diabetic and non-diabetic acute myocardial infarction (AMI) patients.MethodsThis case–control study was conducted on 450 subjects (70–85 years). Subjects were divided into three groups (Normal, N; Non-diabetic AMI, N-AMI; and Diabetic AMI, D-AMI). Each individual was subjected to a detailed history, clinical examination, and cardiovascular parameters analysis (fasting blood sugar, HbA1c, systolic and diasystolic blood pressure, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), TC/HDL and LDL/HDL ratios). Cardiac markers (Troponin-I, creatine phosphokinase (CPK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP) and aspartate aminotransferase (AST)) and oxidative stress markers (superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT)) were also assessed. All these parameters were compared between diabetic and non-diabetic AMI patients.ResultsD-AMI individuals had high level of TC, TG, LDL, and low level of HDL in comparison to N-AMI individuals. Study suggests that cardiac markers such as Troponin I, CPK, CK-MB, AST, LDH, and CRP levels were significantly increased in patients suffering from myocardial infarction with diabetes mellitus (DM) compared to patients of myocardial infarction without DM. The activity levels of antioxidant SOD and GSH were lower in D-AMI patients than in N-AMI. However, levels of MDA and CAT were higher in D-AMI than in N-AMI controls.ConclusionStudy suggests elevated cardiac markers and reduced antioxidants in D-AMI patients compared to N-AMI patients.     

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.     

Carbohydrate restriction favorably alters lipoprotein metabolism in Emirati subjects classified with the metabolic syndrome

Background and aimsCarbohydrate restriction (CR) has been shown to improve dyslipidemias associated with metabolic syndrome (MetS). We evaluated the effects of CR on lipoprotein subfractions and apolipoproteins in Emirati adults classified with the MetS.Methods and results39 subjects (15 men/24 women) were randomly allocated to a CR diet [20–25% energy from carbohydrate (CHO)] for 12 wk (CRD group) or a combination treatment consisting of CRD for 6 wk followed by the American Heart Association diet (50–55% CHO, AHA group) for an additional 6 wk. All subjects reduced body weight, LDL cholesterol and triglycerides (P < 0.01). At baseline all subjects had low concentrations of medium VLDL and total HDL particles associated with the very low plasma triglycerides and HDL cholesterol in this population. After 12 wk, the large VLDL subfraction was decreased over time for subjects in the CRD group (P < 0.01) while these changes were not observed in those subjects who changed to the AHA diet. The number of medium and small LDL particles decreased for all subjects rendering a less atherogenic lipoprotein profile. In agreement with these results, a significant decrease in apolipoprotein (apo) B was observed (P < 0.01). The medium HDL subfraction and apo A-II, which can be considered pro-atherogenic, were also decreased over time in the CRD group only.ConclusionsThese results suggest that weight loss favorably affects lipoprotein metabolism and that the CRD had a better effect on atherogenic VLDL and HDL than the low fat diet recommended by AHA.     

Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA)

ObjectiveTo assess the relationship of lipoprotein subfractions to coronary heart disease (CHD).MethodsProspective 29.1-year follow-up of 1905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Vital status was determined for 97.2% of the cohort. Blinded physician medical record and death certificate review confirmed 179 CHD deaths. Follow-up questionnaires identified 182 nonfatal myocardial infarctions and 93 revascularization procedures from 1346 (98.3%) of the surviving cohort and from the next-of-kin of 153 men who died.ResultsWhen adjusted for age, total incident CHD was inversely related to HDL2-mass (P = 0.0001) and HDL3-mass (P = 0.02), and concordantly related to LDL-mass (P < 10^?11), IDL-mass (P < 10^?7), and small (P < 10^?7) and large VLDL-mass concentrations (P = 0.003). The hazard reduction per mg/dl of HDL was greater for HDL2-mass than HDL3-mass (P = 0.04). The lowest quartiles of both HDL2-mass (P = 0.007) and HDL3-mass (P = 0.001) independently predicted total incident CHD when adjusted for traditional risk factors. Risk for premature CHD (≤65 years old) was significantly greater in men within the lowest HDL2 (P = 0.03) and HDL3 quartiles (P = 0.04) and having higher LDL-mass concentrations (P = 0.001). Serum cholesterol's relationship to incident CHD (P < 10^?8) was accounted for by adjustment for LDL-mass concentrations (adjusted P = 0.90).ConclusionsLipoprotein subfractions differ in their relationship to CHD.     

Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia

ObjectiveDetermine the effects of treatment with a selective PPAR-δ agonist ± statin on plasma lipoprotein subfractions in dyslipidemic individuals.MethodsIon mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-δ agonist MBX-8025 (50 and 100 mg/d) ± atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial.ResultsMBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in ～90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL–IDL–LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (?24.5 ± 5.3% vs. ?47.8 ± 4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL.ConclusionPPAR-δ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia.     

Association of high-density lipoprotein cholesterol with coronary heart disease risk across categories of low-density lipoprotein cholesterol: the atherosclerosis risk in communities study

IntroductionNational cholesterol treatment guidelines include a low level of high-density lipoprotein (HDL) cholesterol (< 40 mg/dL) as a major risk factor for coronary heart disease (CHD) that should be considered when making decisions on treatment of low- density lipoprotein (LDL) cholesterol.MethodsWe investigated the association of HDL and LDL-cholesterol with incident CHD events (fatal or nonfatal CHD) over 14 years of follow-up among 13,615 adults aged 45 to 64 years in the Atherosclerosis Risk in Communities study.ResultsA total of 966 (7.1%) participants had a CHD event during follow-up. After adjustment for age, race, sex, diabetes, smoking, alcohol consumption, systolic blood pressure, waist circumference, chronic kidney disease and physical activity, a graded association was present between progressively lower levels of HDL-cholesterol and higher CHD risk, overall (P < 0.001) and within each level of LDL-cholesterol (< 100, 100–129, 130–159, 160–189 and ≥ 190 mg/ dL) investigated (all P < 0.05). In addition, after multivariable adjustment including LDL-cholesterol, each standard deviation higher HDL- cholesterol (18 mg/dL) was associated with a hazard ratio of incident CHD of 0.70 (95% Cl: 0.63–0.77).ConclusionsThese data suggest a graded association exists between lower levels of HDL-cholesterol and CHD across the full range of LDL-cholesterol levels. As interventions targeting HDL levels are developed, the combinatorial effects of lower HDL levels with various levels of LDL-cholesterol should be examined.     

Impact of electronegative low-density lipoprotein on angiographic coronary atherosclerotic burden

ObjectiveLow density lipoproteins (LDL) with an electronegative charge [LDL(?)] may cause endothelial injury. We assessed the association between serum LDL(?) levels and coronary artery disease (CAD) severity.MethodsWe prospectively enrolled patients with CAD angiographic evidence [stable angina (SA) or non-ST-elevation-acute coronary syndrome (NSTE-ACS)], or with normal coronary arteries (NCA). Baseline LDL(?) serum levels were measured in all patients. Angiographic CAD extent was assessed by using the Bogaty extent index, while CAD severity by evaluating the presence of multi-vessel disease.ResultsForty-seven patients (age 61 ± 9 years, male sex 60%) were enrolled (17 SA, 15 NSTE-ACS and 15 NCA patients). LDL(?) levels were significantly higher in SA [21% (18–34) p = 0.0001] and NSTE-ACS [22% (18–28), p = 0.0001] as compared to NCA [6% (5–8)], without significant differences between SA and NSTE-ACS (p = 0.92). Multi-vessel disease patients had higher LDL(?) levels as compared to single-vessel disease patients (p = 0.002) but similar total LDL levels (p = 0.66). LDL(?) significantly correlated with extent index (r = 0.38, p = 0.03), while total LDL did not (p = 0.24).ConclusionLDL(?) serum levels are associated with CAD angiographic severity and extent. This exploratory analysis should prime further larger studies in order to assess LDL(?) proatherogenic role.     

ApoB/apoA-I ratio is related to femoral artery plaques in 64-year-old women also in cases with low LDL cholesterol

IntroductionThe apolipoproteinB (apoB)/apolipoproteinA-I (apoA-I) ratio mirrors the number of pro-atherogenic and anti-atherogenic lipoprotein particles. This ratio may carry more information on risk for atherosclerosis than LDL in cohorts with impaired glucose tolerance. The aim was to examine the association between the apoB/apoA-I ratio and ultrasound-assessed atherosclerosis in the carotid and femoral arteries in women with varying degrees of glucose tolerance.MethodsPlaque occurrence, and intima-media thickness in the carotid and femoral arteries were examined by B-mode ultrasound in a random sample of 64-year-old women (n = 646) living in Gothenburg, Sweden, representing different degrees of glucose intolerance (diabetes (n = 234), impaired (n = 212) and normal glucose tolerance (n = 200)). Traditional risk factors and serum concentrations of apolipoproteins were analysed.ResultsFor subjects in the lowest LDL tertile, the risk of having a plaque in the femoral artery was three times greater for subjects in the highest apoB/apoA-I tertile compared to subjects in the lowest tertile (OR: 3.0, 95% CI: 1.2–7.5). A clear increase in the occurrence of femoral plaque was observed already at a cut-off value of 0.63 (OR: 1.8, 95% CI: 1.2–2.6). ApoB/apoA-I was also related to femoral plaque occurrence in women with low HbA1c. ApoB/A-I ratio was associated with carotid and femoral IMT but not carotid plaques.ConclusionThe apoB/apoA-I ratio improved the identification of cases with femoral artery atherosclerosis in a cohort of women with varying degrees of glucose tolerance. Such cases could also be identified in women with normal LDL and HbA1c levels. The results indicate that an apoB/apoA-I ratio above 0.63 should be used as a marker of increased risk.     

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.     

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.     

Relationship of plasma apolipoprotein M with proprotein convertase subtilisin-kexin type 9 levels in non-diabetic subjects

PurposeApolipoprotein M (apoM) retards atherosclerosis development in murine models, and may be regulated by pathways involved in LDL metabolism. Proprotein convertase subtilisin–kexin type 9 (PCSK9) plays a key role in LDL receptor processing. We determined the extent to which plasma apoM is related to PCSK9 levels in subjects with varying degrees of obesity.MethodsWe sought correlations between plasma apoM and PCSK9, measured using recently developed ELISAs, in 79 non-diabetic subjects.ResultsApoM and PCSK9 levels were both correlated positively with total cholesterol, non-HDL cholesterol, LDL cholesterol and apoB (P < 0.05 to P < 0.001). ApoM correlated positively with PCSK9 in lean individuals (n = 37, r = 0.337, P = 0.041), but not in overweight subjects (n = 32, r = 0.125, P = 0.50) and in obese subjects (n = 10, r = ?0.055, P = 0.88).ConclusionsThe PCSK9 pathway may contribute to plasma apoM regulation in humans. The influence of PCSK9 on circulating apoM appears to be modified by adiposity.     

Glycated apolipoprotein B and myocardial infarction

AimsTo evaluate the association of serum concentrations of glycated apolipoprotein B (ApoBg) with the incidence of myocardial infarction (MI) in subjects with and without diabetes.MethodsThe design is a nested case-control study. The cohort included 5632 subjects over 50 years of age attending the clinical laboratories of a small geographic area in southern Italy. After five years, 4563 subjects were traced and 103 had developed MI. We sampled from the cohort two controls for each incident case of MI, frequency matched for sex and diabetes. ApoBg was measured using a monoclonal antibody. Logistic regression was used for statistical analysis of the data.ResultsApoBg at baseline was higher in subjects who developed myocardial infarction than in controls in both non-diabetic and diabetic subjects (t test, P = 0.009 and P = 0.05 respectively). MI odds ratio in the third tertile of ApoBg was 2.01 (95 % CI 0.93–4.33) in non-diabetic and 2.88 (0.85–9.68) in diabetic subjects (chi-square test for trend; non-diabetics P = 0.03, diabetics P = 0.06). Serum triglycerides, cholesterol, HDL and LDL cholesterol, glucose and insulin were not associated with MI (P > 0.10).ConclusionApoBg at baseline is directly associated with the development of MI in the following five years in both diabetic and non-diabetic individuals.     

LDL and HDL subclasses in acute ischemic stroke: Prediction of risk and short-term mortality

ObjectiveSmall, dense low-density lipoprotein (sdLDL) and small-sized high-density lipoprotein (HDL) particles are established risk factors for ischemic heart disease. However, their clinical significance for acute ischemic stroke (AIS) is uncertain. This study evaluates associations of LDL and HDL particle sizes and subclasses with AIS risk and short-term mortality after AIS.MethodsTwo hundred AIS patients hospitalised for first-in-a-lifetime stroke and 162 apparently healthy controls were included in the study. LDL and HDL particles were separated by gradient gel electrophoresis and serum lipid parameters were measured by standard laboratory methods. Baseline characteristics of LDL and HDL particles were evaluated for the prediction of AIS and short-term mortality after AIS.ResultsAIS patients had significantly more LDL III and IVb, but less LDL I and II particles. They also had significantly smaller HDL size, more HDL 3a, 3b and 3c and less HDL 2b subclasses. The relative content of both sdLDL and small-sized HDL particles was significantly increased in patients (P < 0.001 and P < 0.001, respectively). In addition, sdLDL was significantly higher in AIS fatalities (n = 25) compared with survivors (n = 175, P < 0.05). Increased sdLDL was a significant predictor of AIS (OR = 4.31; P < 0.001) and in-hospital mortality after AIS (OR = 5.50; P < 0.05). The observed relationships persisted after adjustment for conventional risk factors.ConclusionsAIS is associated with adverse distributions of LDL and HDL subclasses. In addition, short-term mortality after AIS is associated with increased sdLDL particles. Our results indicate that sdLDL is an independent predictor of both AIS onset and consecutive short-term mortality.