Rindert de Vries

Carotid artery intima media thickness is inversely related to serum free thyroxine in euthyroid subjects

Objective  The effect of thyroid function on cardiovascular risk may extend to the euthyroid range. In euthyroid subjects, we determined whether carotid artery intima media thickness (IMT), a measure of subclinical atherosclerosis, is related to thyroid function.

High plasma C-reactive protein (CRP) is related to low paraoxonase-I (PON-I) activity independently of high leptin and low adiponectin in type 2 diabetes mellitus.

Objectives  In type 2 diabetes mellitus, circulating C‐reactive protein (CRP) is increased, whereas the high density lipoprotein (HDL)‐associated, anti‐oxidative and anti‐inflammatory enzyme, paraoxonase‐I, is decreased. Both high CRP and low paraoxonase‐I activity may predict cardiovascular disease. It is unknown whether lower paraoxonase‐I activity contributes to higher CRP levels in diabetes. In type 2 diabetic and control subjects, we determined the relationship of CRP with paraoxonase‐I when taking account of plasma levels of pro‐ and anti‐inflammatory adipokines.

Lower plasma adiponectin is a marker of increased intima-media thickness associated with type 2 diabetes mellitus and with male gender

OBJECTIVE We tested the extent to which altered plasma adipokine levels may contribute to the increased carotid artery intima-media thickness (IMT) associated with type 2 diabetes mellitus and with male gender, independently of conventional cardiovascular risk factors, insulin resistance, and plasma C-reactive protein (CRP). DESIGN IMT (mean of three segments of both carotid arteries by ultrasonography), insulin resistance (homeostasis model assessment; HOMA(ir)), plasma CRP, lipids, adiponectin, leptin, resistin, and tumor necrosis factor-alpha (TNF-alpha) were measured in 84 type 2 diabetic patients and 85 control subjects. RESULTS In diabetic patients, IMT (P<0.001), mean arterial pressure (P<0.001), HOMA(ir) (P<0.001), plasma CRP (P=0.003), triglycerides (P=0.037), leptin (P=0.023), resistin (P=0.003), and TNF-alpha (P=0.003) levels were higher, whereas high-density lipoproteins (HDL) cholesterol (P<0.001) and adiponectin (P<0.001) levels were lower compared with control subjects. Plasma adiponectin (P<0.001) and leptin (P<0.001) were substantially lower in men than in women. IMT was positively and independently associated with age (P<0.001), diabetes (P=0.049), and male gender (P=0.002) in a multivariate regression model, not including other variables. Further analyses showed that IMT was positively related to age (P<0.001) and plasma triglycerides (P=0.038) and negatively to adiponectin (P<0.001), without independent effects of diabetes, gender, and HOMA(ir). CONCLUSIONS Increased IMT in type 2 diabetes may in part be explained by lower plasma adiponectin and higher triglycerides, but not by leptin, resistin, and TNF-alpha. The gender effect on IMT is related to lower plasma adiponectin.

Plasma Lecithin: Cholesterol Acyltransferase Activity Is Elevated in Metabolic Syndrome and Is an Independent Marker of Increased Carotid Artery Intima Media Thickness

CONTEXT Lecithin:cholesterol acyltransferase (LCAT), which esterifies free cholesterol to cholesteryl esters, is required for normal plasma lipoprotein structure and is instrumental in high density lipoprotein (HDL) remodeling, but the relationship of variation in plasma LCAT activity with subclinical atherosclerosis is unclear. OBJECTIVES The aim of the study was to determine the effect of the metabolic syndrome (MetS) on plasma LCAT activity and its relationship with carotid artery intima media thickness (IMT). SETTING The study was conducted at the vascular laboratory of a university medical center. METHODS In 74 subjects with MetS and 90 subjects without MetS (National Cholesterol Education Program Adult Treatment Panel III criteria), mean carotid artery IMT, plasma lipids, LCAT activity (exogenous substrate method), high-sensitive C-reactive protein, and homeostasis model assessment insulin resistance (HOMA(ir)) were documented. RESULTS IMT was greater (P = 0.01) and plasma LCAT activity was higher (P < 0.001) in subjects with MetS compared to subjects without MetS. Similar increases in IMT and LCAT were found in MetS subjects without type 2 diabetes mellitus. Multiple linear regression analysis demonstrated that plasma LCAT activity was independently and positively related to HOMA(ir), plasma triglycerides, non-HDL cholesterol, and HDL cholesterol (all P < 0.001). After adjustment for age and sex, IMT was positively associated with LCAT activity (P < 0.01), independently of the presence of MetS (or alternatively of plasma lipids), HOMA(ir), and high-sensitive C-reactive protein. CONCLUSIONS Plasma LCAT activity is elevated in MetS and may be a marker of subclinical atherosclerosis. Our findings do not support the contention that strategies to elevate LCAT are necessarily beneficial for cardioprotection.

Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL

Eur J Clin Invest 2012; 42 (5): 487–495

Carotid artery intima media thickness associates with skin autofluoresence in non-diabetic subjects without clinically manifest cardiovascular disease

Eur J Clin Invest 2010; 40 (9): 812–817

Fibroblast cholesterol efflux to plasma from metabolic syndrome subjects is not defective despite low high-density lipoprotein cholesterol

OBJECTIVE We tested whether in metabolic syndrome (MetS) subjects the ability of plasma to stimulate cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport pathway, is maintained despite low high-density lipoprotein (HDL) cholesterol. DESIGN In 76 subjects with and 94 subjects without MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined plasma (apo)lipoproteins, pre-beta-HDL formation, phospholipid transfer protein (PLTP) activity, cholesterol esterification (EST), cholesteryl ester transfer (CET), adiponectin, and the ability of plasma from each subject to stimulate cholesterol efflux out of cultured fibroblasts obtained from a single donor. RESULTS Apo E, PLTP activity, EST, and CET were higher (P=0.04 to <0.001), whereas adiponectin was lower in MetS subjects (P<0.01). Pre-beta-HDL and pre-beta-HDL formation were not different between subjects with and without MetS. Cellular cholesterol efflux to plasma from MetS subjects was slightly higher versus plasma from subjects without MetS (8.8+/-1.0 vs 8.5+/-0.9%, P=0.05), but the difference was not significant after age, sex, and diabetes adjustment. Cellular cholesterol efflux was positively related to pre-beta-HDL formation, EST, PLTP activity, and apo E (P<0.05 for all by multiple linear regression analysis), without an independent association with MetS and diabetes status. CONCLUSIONS The ability of plasma from MetS subjects to promote fibroblast cholesterol efflux is not defective, although HDL cholesterol is decreased. Higher cholesterol esterification, PLTP activity, and apo E levels may contribute to the maintenance of cholesterol efflux in MetS.

Carotid intima media thickness is associated with plasma lipoprotein-associated phospholipase A2 mass in nondiabetic subjects but not in patients with type 2 diabetes.

Eur J Clin Invest 2011; 41 (8): 820–827

Phospholipid transfer protein activity is determined by type 2 diabetes mellitus and metabolic syndrome, and is positively associated with serum transaminases

Background  The extent to which plasma phospholipid transfer protein (PLTP) activity is affected by type 2 diabetes mellitus (DM) and metabolic syndrome (MetS) is still unknown. PLTP is synthesized in the liver, and elevated serum transaminases are considered to predict nonalcoholic fatty liver disease (NAFLD). In this study, we examined the relationship between plasma PLTP activity and liver enzymes in subjects with and without DM and MetS.

Plasma apolipoprotein M is reduced in metabolic syndrome but does not predict intima media thickness

BACKGROUND Apolipoprotein (apo) M may exert anti-atherogenic properties in experimental studies. Its hepatic gene expression may be linked to glucose and lipid metabolism. Plasma apoM is decreased in obese mouse models. We hypothesized that plasma apoM is lower in metabolic syndrome (MetS) subjects, and determined whether intima media thickness (IMT) is associated with apoM. METHODS In 19 non-diabetic subjects with and 60 non-diabetic subjects without MetS (NCEP, ATP III criteria), the relationships of plasma apoM with obesity, glucose, insulin, lipids and adipokines, as well as with IMT were determined. RESULTS Plasma apoM was on average 15% lower in subjects with MetS compared to subjects without MetS (p=0.036). ApoM correlated inversely with body mass index and waist circumference (p<0.001), and positively with total cholesterol, LDL cholesterol and apoA-I (p<0.05). ApoM was not significantly correlated with glucose, insulin, leptin, adiponectin or resistin (p>0.20). Age- and sex adjusted IMT was lower in subjects with MetS (p<0.05), but was unrelated to apoM (p=0.68). In a multiple linear regression model that included the presence of both MetS and apoM, IMT was only related to MetS (p=0.05). CONCLUSIONS Plasma apoM is reduced in MetS. In this study, apoM did not predict subclinical atherosclerosis.