Nutrition, Metabolism & Cardiovascular Diseases

Editorial Board

2012-01-01

Retention of atherogenic lipoproteins in the artery wall and its role in atherogenesis

P. Fogelstrand, J. Borén — 2012-01-01

Abstract: Aims: In this review, we discuss the mechanisms behind the binding of low-density lipoproteins (LDL) to the arterial wall and how this interaction might be targeted to prevent atherosclerosis.Data synthesis: An increasing body of evidence shows that accumulation of LDL in the vessel wall is a critical step in the development of atherosclerosis. The retained lipoproteins subsequently provoke an inflammatory response that ultimately leads to atherosclerosis. In the arterial wall, LDL binds ionically to proteoglycans in the extracellular matrix. In particular, proteoglycans with elongated glycosaminoglycan (GAG) chains seem to play a crucial role in this process.Conclusions: The LDL-proteoglycan interaction is a highly regulated process that might provide new therapeutic targets against cardiovascular disease.

Brachial artery diameter measurement: A tool to simplify non-invasive vascular assessment

T. Montalcini, G. Gorgone, C. Gazzaruso, S. Romeo, D. Bosco, A. Pujia — 2012-01-01

Abstract: Aim: The mechanisms of vascular remodeling have attracted great interest since it is a phenomenon related to cardiovascular diseases. We would like to examine studies that contributed to clarify the remodeling mechanisms, to explore the different faces of atherosclerosis process.Data synthesis: A number of invasive and non-invasive vascular assessment methods were developed, to detect the early sign of atherosclerosis. It became clear that the invasive tests were not applicable to large-scale studies. Consequently, a non-invasive test was developed. Studies showed that the endothelial function evaluation is a predictor of future cardiac events in individuals at cardiovascular risk and in those with established disease. However, analyzing several works, an interesting concept emerged, i.e., the inverse relation between endothelium-dependent dilation and vessel size, since large vessel tend not to dilate significantly. This notion emphasized the role of basal diameter on vascular response. In particular, as brachial artery diameter is the measure on which FMD is based, it could add more information in clinical evaluation, simplifying the assessment. Several studies showed that morphological change of brachial artery is a better indicator of the extent of coronary disease rather than FMD. Other studies showed that brachial diameter has predictive significance in the stratification of cardiovascular risk.Conclusion: Brachial diameter is a useful and simple tool. It should be incorporated into the overall assessment of cardiovascular risk but further studies are warranted to determine the final place of brachial diameter assessment in routine clinical setting.

Relation of dietary and lifestyle traits to difference in serum leptin of Japanese in Japan and Hawaii: The INTERLIPID study

2010-08-02

Abstract: Background and Aims: Previously, we found significantly higher serum leptin in Japanese-Americans in Hawaii than Japanese in Japan. We investigated whether differences in dietary and other lifestyle factors explain higher serum leptin concentrations in Japanese living a Western lifestyle in Hawaii compared with Japanese in Japan.Methods and Results: Serum leptin and nutrient intakes were examined by standardized methods in men and women ages 40–59 years from two population samples, one Japanese-American in Hawaii (88 men, 94 women), the other Japanese in central Japan (123 men, 111 women). Multiple linear regression models were used to assess role of dietary and other lifestyle traits in accounting for serum leptin difference between Hawaii and Japan. Mean leptin was significantly higher in Hawaii than Japan (7.2 ± 6.8 vs 3.7 ± 2.3 ng/ml in men, P < 0.0001; 12.8 ± 6.6 vs 8.5 ± 5.0 in women <0.0001). In men, higher BMI in Hawaii explained over 90% of the difference in serum leptin; in women, only 47%. In multiple linear regression analyses in women, further adjustment for physical activity and dietary factors – alcohol, dietary fiber, iron – produced a further reduction in the coefficient for the difference, total reduction 70.7%; P-value for the Hawaii–Japan difference became 0.126.Conclusion: The significantly higher mean leptin concentration in Hawaii than Japan may be attributable largely to differences in BMI. Differences in nutrient intake in the two samples were associated with only modest relationship to the leptin difference.

Coronary artery disease, cerebral non-fatal ischemic stroke in retinal vein occlusion: An 8-yr follow-up

2010-08-02

Abstract: Forty-five consecutive subjects (26M, 19F; mean age 54 ± 14 yrs) with a diagnosed retinal vein occlusion (RVO), were followed-up for 8 yrs. As many as 145 sex-age- and blood pressure-matched individuals (78M, 67F; mean age 54.4 ± 13.5 yrs), that did not experience any vascular event, served as controls. At the time of the RVO, controls and subjects did not differ as to hypercholesterolemia, hypertrigliceridemia, diabetes mellitus, smoking habits, inherited/acquired thrombophilia. At the follow-up completion, they differed as to statin consumption (p = 0.016). During the 8-yrs follow-up, in the control population, 11 out of 145 (7.6%) subjects had experienced a major vascular event (8 coronary artery disease; 3 cerebral non-fatal ischemic stroke). In contrast, of the 45 subjects with a history of RVO, as many as 10 (22.2%) had experienced a major vascular event: 4 coronary artery disease; 4 cerebral non-fatal ischemic stroke; 2 cardiovascular + cerebrovascular event (p = 0.012). A prolonged antiplatelet treatment, prior to the major vascular event, was found in 5/45 cases (11.1%) vs 23/145 (15.9%) controls (p = 0.63). In contrast, a long-lasting administration of anti-hypertensive drugs, to achieve a control of blood pressure, was found in 83.4% of controls and only in 46.7% of cases (p < 0.0001). In conclusion, in a 8-yr follow-up, coronary artery disease and/or non-fatal ischemic stroke were more common in subjects with a history of RVO than in a large setting of subjects comparable for cardiovascular risk factors. These data also argue for RVO as a vascular disease in which aggressive anti-hypertensive therapy to prevent stroke and/or myocardial infarction is needed.

Glycaemic index and body fat distribution in children: The results of the ARCA project

2010-08-02

Abstract: Background and aims: Various dietary factors may play a critical role in body weight regulation. Among them, the role of glycaemic index (GI) remains a subject of debate. The present study aimed at evaluating the association between dietary GI, body mass index (BMI) and body fat distribution in school children.Methods and results: 3734 Italian children (M/F = 1883/1851; age range 6–11 years) were cross-sectionally screened for anthropometry (BMI, waist circumference), lifestyle and clinical history (questionnaire) and dietary habits (1-year food frequency questionnaire). Energy and macronutrients intake, dietary GI and glycaemic load (GL) were calculated.GI was directly associated with age, waist and BMI z-scores, energy, fibre and carbohydrate intake (r: from 0.080 to 0.238, P < 0.001), and negatively with fat intake (r: −0.060, P < 0.0001). BMI, waist circumference, energy intake, carbohydrate, protein and fibre intake and GL significantly increased, whilst fat intake decreased, going up across quartiles of residuals of dietary GI. At linear regression analysis, GI was associated with BMI and waist z-scores independently of age, sex, parental overweight/obesity, parental education, and energy intake, protein, fat, carbohydrate, fibre and GL residuals. In particular, GI was the sole nutritional factor among those under investigation, significantly associated with waist circumference.Controlling for covariates, the risk of overweight/obesity or of central fat distribution was almost two-folds higher in the upper quartile in comparison to the lowest quartile of dietary GI.Conclusion: Dietary GI is an independent determinant of body fat distribution in children as well as of total adiposity

Short term dietary sodium restriction decreases HDL cholesterol, apolipoprotein A-I and high molecular weight adiponectin in healthy young men: Relationships with renal hemodynamics and RAAS activation

J.A. Krikken, G.M. Dallinga-Thie, G. Navis, R.P.F. Dullaart — 2010-08-02

Abstract: Background and aims: We aimed to determine the effect of short-term dietary sodium restriction on plasma total cholesterol, LDL-C, HDL-C, triglycerides, apolipoprotein (apo) A-I, apo B and high molecular weight (HMW) adiponectin in non-obese, normotensive young men. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), plasma renin activity (PRA) and aldosterone were also measured.Methods and results: Sixty-five men, aged 23 ± 7 years, were randomly studied on a high sodium intake (HS, 228 ± 77 mmol Na+/24 h) and a low sodium intake (LS, 36 ± 27 mmol Na+/24 h), each period lasting 1 week. LS decreased GFR and ERPF and increased PRA and aldosterone (p < 0.0001 for all). LS also induced a decrease in HDL-C (3.8 ± 10.8%), apo A-I (3.7 ± 6.5%) and HMW-adiponectin (13.6 ± 40.5%) (p < 0.05 for all), but plasma total cholesterol, LDL-C, triglycerides and apo B did not significantly change. The changes in HDL-C and apo A-I were correlated negatively to the changes in effective renal plasma flow (p < 0.05), whereas the changes in HMW adiponectin were correlated negatively to the changes in PRA and aldosterone (p < 0.05 for both).Conclusion: Short term sodium restriction modestly decreases HDL-C, apo A-I and HMW-adiponectin in healthy men. Changes in GFR and ERPF and in the renin-angiotensin-aldosterone system as induced by LS may be involved in these responses.

Validity of self-reported abdominal obesity in Thai adults: A comparison of waist circumference, waist-to-hip ratio and waist-to-stature ratio

L.L.-Y. Lim, Sam-ang Seubsman, A. Sleigh, C. Bain — 2010-08-02

Abstract: Background and aims: Waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-stature ratio (WSR), being common proxy measures of abdominal obesity, are useful tools in epidemiologic studies, but little is known about their validity when the indices are derived from self-reported measurements. We determine and compare the validity of self-reported WC, WHR and WSR in order to identify the optimal index for use in epidemiologic surveys.Methods and Results: Technician- and self-reported measurements of height, waist and hip circumference were obtained from 613 Thai adults (mean age 35 years). Regarding technician-reported measurements as reference, diagnostic test properties were derived and performances of the indices compared using receiver-operator-characteristic curves and the area-under-the-curve (AUC) analyses. There was good agreement between technician- and self-reported measurements for WC and WSR (concordance correlation coefficients ranged from 0.84 to 0.90) but not for WHR (0.50 in men, 0.45 in women). The sensitivity and specificity of self-reported WC and self-reported WSR as measures of abdominal obesity were superior to those of self-reported WHR in both sexes. AUCs for WC and WSR were comparable (0.93 and 0.92, respectively, in men; 0.88 and 0.87 in women) and significantly higher than for WHR (0.80 in men; 0.76 in women; p<0.0001).Conclusion: WC and WSR derived from self-reported waist and height measurements are valid methods for determining abdominal obesity. Self-reported measurements should not be used to derive the WHR. In Asian populations, WSR may be the optimal index of abdominal obesity when measurements are derived from self-reports in epidemiologic surveys.

Food selection based on high total antioxidant capacity improves endothelial function in a low cardiovascular risk population

2010-08-02

Abstract: Background and aims: Oxidative stress has been advocated as a major cause for cardiovascular disease (CVD), and low plasma antioxidant concentrations are associated with endothelial dysfunction, the first step towards atherosclerosis. However, although the antioxidant content in fruits and vegetables may explain at least in part their protective effect against CVD, supplementation with antioxidant vitamins fails to improve endothelial function and reduce CVD risk. The aim of this study was to investigate the impact of a diet rich in antioxidants on endothelial function measured by flow-mediated dilatation (FMD) in volunteers at low cardiovascular risk.Methods and results: In a crossover trial, 24 subjects (13 women, mean age 61 ± 3 years), received, in a randomised order, a 14-day high (HT) and a 14-day low (LT) antioxidant diets, with a 2-week wash-out (WO) in between. Both diets were comparable in daily portions of fruits and vegetables, and in alcohol, fibre and macronutrient intake, but differed in their total antioxidant capacity. Before and after each diet, anthropometrics, blood pressure, fasting plasma glucose, lipid profile, hepatic enzymes, circulating antioxidant concentrations, high sensitivity C-reactive protein (hs-CRP) and FMD were assessed.FMD increased significantly during the HT diet compared to the LT (p < 0.000). FMD values were 2.3% higher after HT compared with LT (p < 0.001) after adjustment for age, gender and diet order. α-tocopherol increased significantly (p < 0.05) and hs-CRP and of γ-glutamyltranspeptidase decreased significantly (p < 0.05 and p < 0.01, respectively) during the HT diet, compared with the LT diet.Conclusions: A short-term HT diet improves endothelial function in volunteers at low cardiovascular risk, which may further reduce their risk of CVD.

Effects of chronic elevation of atrial natriuretic peptide and free fatty acid levels in the induction of type 2 diabetes mellitus and insulin resistance in patients with mitral valve disease

2010-08-16

Summary: Background and aims: The relationship between atrial natriuretic peptide (ANP), increased free fatty acid (FFA) and insulin resistance in patients with mitral valve disease (MVD), a group characterised by elevated atrial pressure and increased ANP levels, is not defined. The present study was performed to evaluate, in MVD patients, the relationship between increased ANP and FFA levels and insulin resistance and the role of mitral valve replacement/repair in ameliorating these metabolic alterations. Conversely, coronary heart disease (CHD) patients were evaluated before and after coronary artery bypass grafting (CABG), since they are known to be insulin resistant in the presence of chronic FFA increase.Methods and results: Fifty MVD patients and 55 CHD patients were studied before and 2 months after surgery and compared with 166 normal subjects. Before surgery, 56% of MVD patients had impaired glucose tolerance or newly diagnosed type 2 diabetes after a standard oral glucose load and this percentage decreased to 46% after surgery. In CHD, impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetic patients were 67% of patients before and after CABG. In MVD, left atrial (LA) volume, ANP, FFA incremental area and insulin levels were higher and Insulin Sensitivity (IS) index significantly reduced while after surgery, LA volume, ANP and FFA significantly decreased and IS index significantly improved. In CHD, insulin resistance and hyperinsulinaemia were present both before and after surgery with increased tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels.Conclusion: In MVD, a higher degree of abnormal glucose tolerance and insulin resistance are associated to increased levels of ANP and FFA, while these metabolic alterations are improved by mitral valve replacement/repair surgery.Clinical Trial.gov registration number NCT 00520962.

Effects of simvastatin on carotenoid status in plasma

M. Rydén, P. Leanderson, K.-O. Kastbom, L. Jonasson — 2010-08-02

Abstract: Background and aims: Carotenoids are potent antioxidants mainly transported in the low density lipoprotein (LDL) fraction. They may also influence the immune response and inverse associations with inflammatory markers have been reported. We investigated whether simvastatin, by exerting both lipid-lowering and anti-inflammatory effects, altered the carotenoid status in plasma.Methods and results: A randomized, double-blind, placebo-controlled study design was applied. Eighty volunteers with mild to moderate hypercholesterolemia received either simvastatin 40 mg or placebo for 6 weeks. Lipids, oxidized LDL (ox-LDL), C-reactive protein (CRP), interleukin (IL)-6, oxygenated carotenoids (lutein, zeaxanthin, β-cryptoxanthin) and hydrocarbon carotenoids (α-carotene, β-carotene, lycopene) were measured in plasma. Simvastatin use was associated with significant reductions in total cholesterol, LDL, ox-LDL and CRP. Simvastatin therapy also resulted in reduced plasma levels of both oxygenated and hydrocarbon carotenoids. However, when adjusted for lipids, all carotenoids except β-cryptoxanthin showed significant increases after simvastatin therapy. Both crude and lipid-adjusted carotenoids were inversely correlated with CRP and IL-6 in plasma but the change in carotenoid status during simvastatin therapy was not specifically related to any changes in inflammatory markers.Conclusions: To summarize, the change in carotenoid status during simvastatin therapy was mainly attributed to the lowering of cholesterol and not to the suppression of inflammatory activity. After adjustment for lipids, the levels of lutein, lycopene, α-carotene and β-carotene were significantly increased by simvastatin suggesting an increased ratio of carotenoids per particle.

Bilberry anthocyanin-rich extract alters expression of genes related to atherosclerosis development in aorta of apo E-deficient mice

A. Mauray, C. Felgines, C. Morand, A. Mazur, A. Scalbert, D. Milenkovic — 2010-08-02

Abstract: Intake of anthocyanin-rich foods has been associated with a reduced risk of cardiovascular diseases. We recently reported that a nutritional supplementation with a bilberry anthocyanin-rich extract (BE) attenuates atherosclerotic lesion development in apolipoprotein E-deficient (apoE−/−) mice. However, the mechanism(s) of their preventive action are not completely understood. Anthocyanins may alter mRNA levels of genes related to atherosclerosis in cultured macrophages and endothelial cells, but in vivo studies remain scarce. The aim of the present study was to explore the in vivo mechanisms of action of the same bilberry extract, administered by supplementation at a nutritional level, in the aorta of apo E−/− mice using a global transcriptomic approach. This study focused on the early stage of atherosclerosis development for better assessment of BE action on initiation mechanisms of this pathology. After a two week period, plasma lipid and antioxidant capacity were evaluated and the global genomic analysis was carried out using pangenomic microarrays. BE supplementation significantly improved hypercholesterolemia whereas the plasmatic antioxidant status remained unchanged. Nutrigenomic analysis identified 1261 genes which expression was modulated by BE in the aorta. Bioinformatic analysis revealed that these genes are implicated in different cellular processes such as oxidative stress, inflammation, transendothelial migration and angiogenesis, processes associated with atherosclerosis development/protection. Some of the most significantly down-regulated genes included genes coding for AOX1, CYP2E1 or TXNIP implicated in the regulation of oxidative stress, JAM-A coding for adhesion molecules or VEGFR2 implicate in regulation of angiogenesis. Other genes were up-regulated, such as CRB3, CLDN14 or CDH4 potentially associated with increased cell–cell adhesion and decreased paracellular permeability. These results provide a global integrated view of the mechanisms involved in the preventive action of bilberry anthocyanin-rich extract against atherosclerosis.