Effect of lifestyle intervention plus rosiglitazone or placebo therapy on left ventricular mass assessed with cardiovascular magnetic resonance in the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>To evaluate the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on left ventricular (LV) mass, using cardiovascular magnetic resonance (CMR) in the metabolic syndrome.</p> <p>Methods</p> <p>The present study was a pre-specified substudy of a double-blind randomized controlled trial evaluating the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on carotid artery atherosclerosis in the metabolic syndrome. From this original study population, 10 subjects from the placebo group and 10 from the rosiglitazone group were randomly selected. At baseline and follow-up (52 weeks), clinical and laboratory measurements were assessed and a CMR-examination was performed to evaluate LV mass indexed for body surface area (LV mass-I). Subsequently, the effect of therapy (rosiglitazone vs. placebo) and clinical and laboratory variables on LV mass-I was evaluated.</p> <p>Results</p> <p>In both groups, body mass index, waist circumference, systolic and diastolic blood pressure significantly decreased during follow-up. Interestingly, LV mass-I significantly decreased in the placebo group (48.9 ± 5.3 g/m²vs. 44.3 ± 5.6 g/m², p < 0.001) indicating reverse remodeling, whereas LV mass-I remained unchanged in the rosiglitazone group (54.7 ± 9.9 g/m²vs. 53.7 ± 9.2 g/m², p = 0.3). After correction for systolic and diastolic blood pressure and triglyceride, the kind of therapy (rosiglitazone vs. placebo) remained the only significant predictor of LV mass-I reduction.</p> <p>Conclusions</p> <p>Lifestyle intervention resulted in a reduction of LV mass-I in the metabolic syndrome, indicating reverse remodeling. However, rosiglitazone therapy may have inhibited this positive reverse remodeling.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN54951661">ISRCTN54951661</a>.</p

Angptl4 Protects against Severe Proinflammatory Effects of Saturated Fat by Inhibiting Fatty Acid Uptake into Mesenteric Lymph Node Macrophages

SummaryDietary saturated fat is linked to numerous chronic diseases, including cardiovascular disease. Here we study the role of the lipoprotein lipase inhibitor Angptl4 in the response to dietary saturated fat. Strikingly, in mice lacking Angptl4, saturated fat induces a severe and lethal phenotype characterized by fibrinopurulent peritonitis, ascites, intestinal fibrosis, and cachexia. These abnormalities are preceded by a massive acute phase response induced by saturated but not unsaturated fat or medium-chain fat, originating in mesenteric lymph nodes (MLNs). MLNs undergo dramatic expansion and contain numerous lipid-laden macrophages. In peritoneal macrophages incubated with chyle, Angptl4 dramatically reduced foam cell formation, inflammatory gene expression, and chyle-induced activation of ER stress. Induction of macrophage Angptl4 by fatty acids is part of a mechanism that serves to reduce postprandial lipid uptake from chyle into MLN-resident macrophages by inhibiting triglyceride hydrolysis, thereby preventing macrophage activation and foam cell formation and protecting against progressive, uncontrolled saturated fat-induced inflammation

Pioglitazone Decreases Plasma Cholesteryl Ester Transfer Protein Mass, Associated With a Decrease in Hepatic Triglyceride Content, in Patients With Type 2 Diabetes

Thiazolidinediones reduce hepatic steatosis and increase HDL cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is associated with a decrease in plasma cholesteryl ester transfer protein (CETP) mass and an increase in HDL levels. Therefore, the aim of the present study was to assess the effects of pioglitazone on CETP mass in patients with type 2 diabetes. We included 78 men with type 2 diabetes (aged 56.5 +/- 0.6 years; HbA1c 7.1 +/- 0.1%) who were randomly assigned to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL cholesterol levels and CETP mass were measured, and hepatic triglyceride content was assessed by proton magnetic resonance spectroscopy. RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6-17.4] versus 4.1 [1.9-12.3]%, P <0.05), decreased plasma CETP mass (2.33 +/- 0.10 vs. 2.06 +/- 0.10 microg/ml, P <0.05), and increased plasma HDL cholesterol level (1.22 +/- 0.05 vs. 1.34 +/- 0.05 mmol/l, P <0.05). Metformin did not significantly change any of these parameters. A decrease in hepatic triglyceride content by pioglitazone is accompanied by a decrease in plasma CETP mass and associated with an increase in HDL cholesterol levels. These results in patients with type 2 diabetes fully confirm recent findings in mic

Angiogenic Factors in Women Ten Years after Severe Very Early Onset Preeclampsia

Background: Women with a history of mainly severe and early onset preeclampsia have an increased risk of future cardiovascular disease. During these complicated pregnancies increased levels of anti-angiogenic factors can be found. We hypothesize that women with a history of severe very early onset preeclampsia still have increased levels of these biomarkers years after this pregnancy, resulting in increased risk for cardiovascular disease. Methods: Twenty women with severe early onset preeclampsia before 24 weeks' gestation, who delivered between 1993-2003 in a tertiary referral centre and twenty matched controls with uncomplicated pregnancies and healthy term infants, were addressed for participation in the study. Venous plasma samples were analyzed for basic fibroblast growth factor (bFGF), placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), E- and P-selectin, soluble intercellular adhesion molecule-3 (sICAM-3) and thrombomodulin by ELISA. Results: Sixteen case subjects and 18 control subjects consented participation. The median time interval index pregnancy to study was 9.4 and 9.7 years for cases and controls, respectively. Median levels for cases-controls (p-value) were not different; bFGF: 17.43-11.11 pg/mL (0.33), sFlt-1: 102.98-101.92 pg/ml (0.84), PLGF: 3.57-4.20 pg/mL (0.38), VEGF: 64.05-45.72 pg/mL (0.73), E-selectin: 5.11-4.68 ng/mL (0.20), P-selectin: 85.35-71.69 ng/mL (0.69), sICAM-3: 0.42-0.63 ng/mL (0.41) and Thrombomodulin: 0.92-0.93 ng/mL (0.59). Conclusion: There were no differences in angiogenic biomarkers between women with a history of severe early onset preeclampsia versus uncomplicated pregnancy almost 10 years later, suggesting that these angiogenic factors will not contribute to the early detection of women at risk for future cardiovascular disease

10-Year cardiovascular event risks for women who experienced hypertensive disorders in late pregnancy: the HyRAS study

ABSTRACT: BACKGROUND: Cardiovascular disease is the cause of death in 32% of women in the Netherlands. Prediction of an individual's risk for cardiovascular disease is difficult, in particular in younger women due to low sensitive and specific tests for these women. 10% to 15% of all pregnancies are complicated by hypertensive disorders, the vast majority of which develop only after 36 weeks of gestation. Preeclampsia and cardiovascular disease in later life show both features of "the metabolic syndrome" and atherosclerosis. Hypertensive disorders in pregnancy and cardiovascular disease may develop by common pathophysiologic pathways initiated by similar vascular risk factors. Vascular damage occurring during preeclampsia or gestational hypertension may contribute to the development of future cardiovascular disease, or is already present before pregnancy. At present clinicians do not systematically aim at the possible cardiovascular consequences in later life after a hypertensive pregnancy disorder at term. However, screening for risk factors after preeclampsia or gestational hypertension at term may give insight into an individual's cardiovascular risk profile. METHODS: Women with a history of preeclampsia or gestational hypertension will be invited to participate in a cohort study 2,5 years after delivery. Participants will be screened for established modifiable cardiovascular risk indicators. The primary outcome is the 10-year cardiovascular event risk. Secondary outcomes include differences in cardiovascular parameters, SNP's in glucose metabolism, and neonatal outcome. DISCUSSION: This study will provide evidence on the potential health gains of a modifiable cardiovascular risk factor screening program for women whose pregnancy was complicated by hypertension or preeclampsia. The calculation of individual 10-year cardiovascular event risks will allow identification of those women who will benefit from primary prevention by tailored interventions, at a relatively young age. Trail registration The HYPITAT trial is registered in the clinical trial register as ISRCTN08132825

Elevated CRP levels are associated with increased carotid atherosclerosis independent of visceral obesity

Visceral obesity (VO) is associated with an increased risk of cardiovascular disease. Elevated C-reactive protein (CRP) levels are associated with VO and cardiovascular disease. After exploring the relation between CRP and VO, we aimed to evaluate the VO independent relation between CRP and carotid atherosclerosis. The prevalence of inflammation was evaluated in 439 male subjects with VO without type 2 diabetes and manifest cardiovascular disease. Waist circumference significantly correlated with CRP (r: 0.20, p 118 cm had low CRP levels. From the 439 subjects, 40 subjects were prospectively selected for MRI assessment of carotid atherosclerosis and visceral and subcutaneous adipose tissue distribution in a case-control setting matching for age and waist circumference. Twenty male subjects with age >50 years with CRP levels >2.5mg/L (CRP+) were compared to 20 controls with CRP levels <1.8 mg/L (CRP-). Maximum vessel wall thickness in CRP+ was significantly higher both in the common carotid artery (15%, p <0.01) and the bulb region (18%, p <0.01). The distribution of fat in visceral and subcutaneous deposits was not significantly different between CRP+ and CRP-. Elevated CRP levels are associated with significantly increased maximum vessel wall thickness independent of VO and of MRI measured adipose tissue distribution, both in the common carotid artery and the carotid bul