Obesity and the clustering of cardiovascular disease risk factors in 14-year-old children

Although overweight and obesity in childhood are related to risk factors of cardiovascular (CVD), most studies have examined these relationships separately. Internal cut-points were used to examine the relation of overweight (>85th and ≦90th percentile) and obesity (>90th percentile) to risk factor clustering in a sample of 2731 14-year-old children from Lower Silesia, Poland, examined cross-sectionally in 1996–97. All subjects went through anthropometric and blood pressure measurements, and fasting serum levels of lipid, lipoproteins and glucose were estimated. All risk factor (>90th percentile) prevalence increased greatly at higher levels of Body Mass Index (BMI) (kg/m2). Nearly every second obese child had elevated systolic blood pressure and every third child had elevated serum levels of triglycerides. Among overweight boys 24.7% were found to have at least one risk factor, whereas among obese boys every fourth had at least one risk factor. 25% overweight girls and nearly 18% obese girls showed at least one risk factor. Standardized odds ratios for associations between overweight and obesity, and risk factor clustering, indicated that obese boys were 4.8 times more likely to have an elevated level of at least two factors; the probability increasing to 16.1 in the case of three and more factors in comparison to their lean peers. Obese girls showed more then a 7 time higher probability of having three and more risk factors in relation to their lean peers.     

Socioeconomic disparities in risk factors for cardiovascular disease.

Despite a general decline in mortality rates in recent decades, these rates are substantially higher among lower socioeconomic groups. To determine target groups for preventive health promotion programs, the prevalence of risk factors for cardiovascular disease by socioeconomic group in Canadian adults aged 20 to 69 years was examined through comparison of estimates from the 1978-79 Canada Health Survey, the 1981 Canada Fitness Survey and the labour force smoking surveys of 1975 and 1983. Level of education was used as a measure of socioeconomic status. The risk factors considered were cigarette smoking, overweight, obesity, elevated diastolic blood pressure, physical inactivity, excessive alcohol consumption, elevated serum cholesterol level, diabetes mellitus and the conjoint use of oral contraceptives and cigarettes. The prevalence of the risk factors tended to be higher among men and women with a low level of education. The results were consistent with those of recent Canadian studies showing that both men and women in lower socioeconomic groups are more likely to die from cardiovascular disease.     

Obesity and cardiovascular disease

Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low density lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features of the metabolic syndrome.     

Measures of adiposity and cardiovascular disease risk factors

Objective: To determine which of five measures of adiposity maintains the strongest association with cardiovascular disease risk factors. Research Methods and Procedures: A nationally representative sample of 12,608 adult participants of the third National Health and Nutrition Examination Survey were examined. Waist circumference, total body fat, percent body fat, BMI, and skinfold thickness were measured following a standardized protocol. Results: In multivariable adjusted models including waist circumference and BMI as independent variables, waist circumference was a significantly better predictor. The odds ratios (95% confidence intervals) for each standard deviation higher waist circumference and BMI for men were as follows: 1.88 (1.43, 2.48) and 0.99 (0.76, 1.29), respectively, for hypertension; 1.51 (0.87, 2.59) and 1.23 (0.76, 1.99), respectively, for diabetes; and 1.85 (1.48, 2.32) and 1.00 (0.80, 1.24), respectively, for low high‐density lipoprotein‐cholesterol. The analogous odds ratios (95% confidence intervals) for women were as follows: 2.28 (1.74, 3.00) and 0.91 (0.69, 1.19), respectively, for hypertension; 2.72 (1.85, 4.00) and 0.82 (0.55, 1.23), respectively, for diabetes; and 1.90 (1.47, 2.47) and 1.07 (0.83, 1.38), respectively, for low high‐density lipoprotein‐cholesterol. Results were markedly similar for waist circumference in models adjusting for total body fat, percent body fat, and skinfold thickness separately. In contrast, waist circumference was not a significantly better predictor of elevated C‐reactive protein than the other measures of adiposity. Discussion: Waist circumference maintains a stronger association with cardiovascular disease risk factors than other measures of adiposity.     

Sex differences in risk factors for cardiovascular disease: the PERU MIGRANT study

Introduction

Although men and women have similar risk factors for cardiovascular disease, many social behaviors in developing countries differ by sex. Rural-to-urban migrants have different cardiovascular risk profiles than rural or urban dwellers. The objective of this study was to evaluate the sex differences with specific cardiovascular risk factors in rural-to-urban migrants.

Methods and Results

We used the rural-to-urban migrant group of the PERU MIGRANT cross-sectional study to investigate the sex differences in specific cardiovascular risk factors: obesity, hypertension, metabolic syndrome, as well as exposures of socioeconomic status, acculturation surrogates and behavioral characteristics. Logistic regression analysis was used to characterize strength of association between sex and our outcomes adjusting for potential confounders. The sample of migrants was 589 (mean age 46.5 years) and 52.4% were female. In the adjusted models, women were more likely to be obese (OR=5.97; 95%CI: 3.21–11) and have metabolic syndrome (OR=2.22; 95%CI: 1.39–3.55) than men, explaining the greatest variability for obesity and metabolic syndrome but not for hypertension.

Conclusions

Our results suggest that interventions for CVD in Peru should be sex-specific and address the unique health needs of migrant populations living in urban shantytowns since the risk factors for obesity and metabolic syndrome differ between males and females.     

Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in non- diabetic subjects: a preliminary report

Background

Osteoprotegerin is a member of the tumor necrosis factor-related family and inhibits RANK stimulation of osteoclast formation as a soluble decoy receptor. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes.

Methods

The subjects were 124 patients with type 2 diabetes mellitus, including 88 males and 36 females with a mean (± SD) age of 65.6 ± 8.2 years old. Serum levels of osteoprotegerin, osteocalcin, fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D3 and adiponectin were measured by ELISA. Vascular calcification in the cervical artery was examined by ultrasound sonography. The subjects were divided into 4 quartiles depending on serum osteoprotegerin levels.

Results

Vascular calcification was significantly higher in the 4th quartile and significantly lower in the 1st quartile of serum osteoprotegerin levels, compared to other quartiles. There were no differences in serum osteoprotegerin and vascular calcification among patients with different stages of diabetic nephropathy, but serum FGF23 levels were elevated in those with stage 4 diabetic nephropathy. Simple regression analysis showed that serum osteoprotegerin levels had significant positive correlations with age, systolic blood pressure and serum adiponectin levels, and significant negative correlations with BMI and serum 25-hydroxyvitamin D3.

Conclusions

These findings suggest that elevated serum osteoprotegerin may be involved in vascular calcification independently of progression of diabetic nephropathy in patients with type 2 diabetes.     

Glycemic index, postprandial glycemia and cardiovascular disease

PURPOSE OF REVIEW: Several lines of evidence indicate that exaggerated postprandial glycemia puts individuals without diabetes at greater risk of developing cardiovascular disease. In large, prospective observational studies, including meta-analyses, higher 120 min post-load blood glucose and glycated hemoglobin (a measure of average blood glucose level over time) independently predict cardiovascular mortality and morbidity in individuals without diabetes. These findings imply that the glycemic nature of dietary carbohydrates may also be relevant. We aim to provide a clearer perspective on how the glycemic impact of carbohydrates may modulate development of cardiovascular disease. RECENT FINDINGS: In ecological studies, average dietary glycemic index (a measure of the postprandial glycemic potential of carbohydrates) and glycemic load (average glycemic index x amount of carbohydrate) predicts coronary infarct and cardiovascular disease risk factors, including HDL cholesterol, triglycerides and C-reactive protein. In short-term intervention studies of overweight and hyperlipidemic patients, low glycemic index diets lead to improvements in cardiovascular disease risk factors, including reduced LDL cholesterol and improved insulin sensitivity, as well as greater body fat loss on energy-restricted diets. Molecular studies indicate that physiological hyperglycemia induces overproduction of superoxide by the mitochondrial electron-transport chain, resulting in inflammatory responses and endothelial dysfunction. SUMMARY: Taken together, the findings suggest that conventional high-carbohydrate diets with their high glycemic index may be suboptimal, particularly in insulin-resistant individuals. Because around one in four adults has impairments in postprandial glucose regulation, the glycemic potential of carbohydrates warrants further investigation in cardiovascular disease prevention.     

Sleep disturbance and cardiovascular risk in adolescents

Background:

Evidence suggests that inadequate or disturbed sleep is associated with increased cardiovascular risk in adults. There are limited data on sleep quality and associated cardiovascular risk in children.

Methods:

We obtained data on adolescents from the 2009/10 cycle of the Healthy Heart Schools’ Program, a population-based cross-sectional study in the Niagara region of Ontario. Participants underwent measurements of cardiometabolic risk factors, including body mass index (BMI), lipid profile and blood pressure, and they completed questionnaires measuring sleeping habits and nutritional status. We assessed sleep disturbance using the sleep disturbance score derived from the Pittsburgh Sleep Quality Index. We explored associations between sleeping habits and cardiovascular risk factors.

Results:

Among 4104 adolescents (51% male), the mean hours of sleep per night (± standard deviation) were 7.9 ± 1.1 on weeknights and 9.4 ± 1.6 on weekends. In total, 19% of participants reported their sleep quality as fairly bad or very bad on weeknights and 10% reported it as fairly bad or very bad on weekends. In the multivariable regression models, a higher sleep disturbance score was associated with increased odds of being at high cardiovascular risk (highest v. lowest tertile odds ratio [OR] 1.43 [95% confidence interval (CI) 1.16–1.77], p < 0.001), increased odds of hypertension (highest v. lowest tertile OR 1.44 [95% CI 1.02–2.05], p = 0.05) and increased odds of elevated non-high density lipoprotein cholesterol (highest v. lowest tertile OR 1.28 [95% CI 1.00–1.64], p = 0.05). The mean duration of sleep was not associated with these outcomes.

Interpretation:

In healthy adolescents, sleep disturbance is associated with cardiovascular risk factor abnormalities. Intervention strategies to optimize sleep hygiene early in life may be important for the prevention of cardiovascular disease.There is emerging evidence in experimental and epidemiologic studies that sleep parameters, specifically sleep duration and quality, are associated with cardiovascular outcomes, including hypertension,¹ as well as diabetes,² hypercholesterolemia³ and obesity.⁴ A recent meta-analysis involving 400 000 adults concluded that short sleep duration was associated with a greater risk of developing or dying from coronary heart disease.⁵ On average, adolescents sleep less than 8 hours per night,⁶ less than the recommended 9 hours,⁷ and about 20% of adolescents have significant sleep problems.⁶ Despite this knowledge, there is a paucity of epidemiologic research on the cardiovascular consequences of short sleep duration and impaired sleep quality in adolescents.In this study, we investigated the association between sleep disturbance and duration and measures of cardiovascular disease risk, including cholesterol, hypertension, body mass index (BMI) and dietary factors in adolescents.     

Obesity and its relation to cardiovascular disease risk factors in Canadian adults. Canadian Heart Health Surveys Research Group.

OBJECTIVE: To describe the distribution of weight and abdominal obesity among Canadian adults and to determine the association of obesity with other risk factors for cardiovascular disease. DESIGN: Population-based cross-sectional surveys. Survey nurses administered a standard questionnaire and recorded two blood pressure measurements during a home visit. At a subsequent visit to a survey clinic two further blood pressure readings were made, anthropometric measurements recorded and a blood specimen taken for plasma lipid determination. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registration files of each province. Anthropometry was performed on 17,858 subjects. OUTCOME MEASURES: Body mass index (BMI), ratio of waist to hip circumference (WHR), mean plasma lipid levels, prevalence of high blood pressure (diastolic greater than or equal to 90 mm Hg or patient on treatment) and self-reported diabetes mellitus. MAIN RESULTS: The prevalence of obesity (BMI greater than or equal to 27) increased with age and was greater in men (35%) than in women (27%). Abdominal obesity was likewise higher in men and increased with both age and BMI. The prevalence of high blood pressure was greater in those with higher BMI, especially in those with a high WHR. Although total plasma cholesterol levels increased only modestly with BMI, levels of low density lipoprotein (LDL) cholesterol and triglycerides and the ratio of total cholesterol to high density lipoprotein (HDL) cholesterol increased steadily, while HDL-cholesterol decreased consistently with increasing BMI. High total cholesterol levels (greater than or equal to 5.2 mmol/L) were more prevalent among people with high BMI, especially those with a high WHR. The prevalence of diabetes increased with BMI among those 35 years or older, especially those with abdominal obesity. About half of men and two-thirds of women who were obese were trying to lose weight. CONCLUSION: Obesity remains common among Canadian adults. There is a need for broad-based programs that facilitate healthy eating and activity patterns for all age groups. Health professionals should incorporate measurement of BMI and WHR into their routine examinations of patients to enhance their evaluation of health risk.     

An antioxidant probiotic reduces postprandial lipemia and oxidative stress

Reducing postprandial oxidative stress (OxS), decreasing postprandial blood triglyceride level (TG) and improving lipoprotein status is likely to have a preventive impact on the development of cardiovascular disease (CVD). Previously we have shown that the antioxidant probiotic Lactobacillus fermentum ME-3 (DSM14241) is characterized by antiatherogenic effects. This randomized double-blind placebo-controlled study evaluated the influence of kefir enriched with an antioxidative probiotic L. fermentum ME-3 (LfKef) on postprandial OxS, blood TG response and lipoprotein status. 100 clinically healthy subjects were recruited into the study. Blood parameters of postprandial OxS, TG and lipoprotein status were determined by oxidized LDL, baseline diene conjugation in LDL (BDC-LDL), oxidized LDL complex with beta-2 glycoprotein (Beta2-GPI-oxLDL), paraoxonase (PON) activity, LDL-Chol, HDL-Chol and TG. To evaluate general body postprandial OxS-load we measured 8-isoprostanes (8-EPI) in the urine. Consumption of LfKef significantly reduced the postprandial level of oxidized LDL, BDC-LDL, Beta2-GPI-oxLDL, urinary 8-isoprostanes and postprandial TG and caused a significant increase in HDL-Chol and PON activity. This is the first evidence that kefir enriched with an antioxidant probiotic may have a positive effect on both postprandial OxS and TG response as well as on lipoprotein status.     

Familial genetic risk factors in premature cardiovascular disease: a family study

Cardiovascular disease (CVD) is closely associated with familial predisposition. The aim of the present study was to investigate predisposing risk factors in the family of a young patient who underwent coronary artery bypass graft surgery due to CVD. The father and uncle of the patient died at an early age due to myocardial infarction. Various stages of CVD were identified in both of the patient’s brothers (28 and 32 years of age). Biochemical tests (fasting blood glucose, lipid profile, urea, creatinine and liver enzymes) and a complete blood count (haemoglobin, haematocrit, white blood cell count, and platelet count) were performed. Physiological coagulation inhibitory factors (protein C, protein S, and antithrombin III), prothrombotic genetic risk factors (factor V Leiden, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase A1C and C6T, angiotensin-converting enzyme, β-fibrinogen, glycoprotein IIIa and factor XIII) and homocysteine levels were evaluated in all cases. Defects were observed in many genetic factors and in the systems regulated by these factors. The results were compatible with those reported in the literature. In conclusion, it is possible to determine a specific family history in young adults with CVD. From this perspective, the emergence of more serious CVD may be prevented by providing disease-related information to the other family members and implementing preventive measures.     

Docosahexaenoic acid (DHA) and cardiovascular disease risk factors

Numerous epidemiological and controlled interventional trials have supported the health benefits of long-chain omega-3 fatty acids in the form of docosahexaenoic acid (DHA, 22:6n-3) plus eicosapentaenoic acid (EPA, 20:5n-3) from fish and fish oils as well as from algal sources. The beneficial effects on cardiovascular disease and related mortality including various risk factors for cardiovascular disease (particularly lowering circulating triglyceride levels and the triglyceride:HDL-cholesterol ratio) have been observed in the absence of any concomitant blood cholesterol lowering. With appropriate dosages, consistent reductions in both fasting and postprandial triglyceride levels and moderate increases in fasting HDL-cholesterol levels have been observed with algal DHA in the majority of trials. These results are similar to findings for fish oils containing DHA and EPA. Related to greater fish intake, higher levels of DHA in circulating blood biomarkers (such as serum phospholipid) have been associated with reduced risks for the progression of coronary atherosclerosis and lowered risk from sudden cardiac death. Controlled clinical trials have also indicated the potential for algal DHA supplementation to have moderate beneficial effects on other cardiovascular disease risk factors including blood pressures and resting heart rates. Recommended intakes of DHA+EPA from numerous international groups for the prevention and management of cardiovascular disease have been forthcoming, although most have not offered specific recommendations for the optimal individual intake of DHA and EPA.     

Correlation between body composition and risk factors for cardiovascular disease and metabolic syndrome

Body mass index (BMI) is an important diagnostic tool for determining obesity; however, while BMI reflects the influence of body height over body weight, it does not reveal body fat percentage (BF%). We explored whether BF% correlated with risk factors for cardiovascular disease and metabolic syndrome and whether metabolically obese, normal weight people were at risk for these diseases. A total of 2,867 healthy volunteers participated in this study. Blood pressure, height, weight, waist circumference, BMI, BF%, lipid profile, fasting glucose, uric acid, and lifestyle factors were collected from healthy subjects during their annual health examinations. In both males and females, BF% correlated positively with BMI and waist circumference. Participants were divided into three groups according to BF% and data were compared between groups. The results suggest that BF% correlates with risk factors for cardiovascular disease and metabolic syndrome for both men and women, and that BF% may be a useful predictor of risk, particularly in metabolically obese, normal weight individuals. ? 2012 International Union of Biochemistry and Molecular Biology, Inc.     

Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease

Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.     

Isoprostanes and isofurans as non-traditional risk factors for cardiovascular disease among Canadian Inuit

Abstract Objectives: The aim of the present study was to investigate the potential importance of oxidative stress, measured by isoprostanes-related compounds, as non-traditional risk factor for cardiovascular disease. We planned to examine the relationship between concentrations of plasma F(2)-isoprostanes (F(2)-IsoPs), isofurans (IsoFs), measures of obesity and various cardiometabolic risk factors. Materials and methods: Cross-sectional study using a sub-sample from the population of a survey conducted in the summer and fall 2007 and 2008 by Canadian Coastguard Ship Amundsen in 36 Canadian Arctic Inuit communities. Subjects included a subset (n =?233) of a total study population (n =?2595) with a mean age 42.56 ± 15.39 years and body mass index 27.78 ± 5.65 kg/m(2). Plasma levels of F(2)-IsoPs and IsoFs was determined by gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method; and their relationships to waist circumference (WC), blood pressure C reactive proteins (CRP), blood lipids and fasting glucose were assessed by multivariate analyses. Results: Plasma F(2)-IsoPs correlated positively with CRP (r =.132, P =.048) and systolic blood pressure (SBP) (r =.157, P =.024) after adjustment for age, sex and body mass index. IsoFs correlated with WC (r =.190, P =.005) and SBP (r =.137, P =.048). F2-IsoPs were not found elevated in smokers (P =.034), whereas IsoFs were decreased in smokers (P =.001). WC, SBP and sex were found to be major correlates of oxidative stress in Canadian Inuit. Conclusions: Plasma measures of F(2)-IsoPs and IsoFs increase with increased obesity and associated cardiometabolic risk factors, including CRP and blood pressure. Simultaneous measurement of IsoFs provides an advantageous mechanistic insight into oxidative stress not captured by F(2)-IsoPs alone.     

Isoprostanes and isofurans as non-traditional risk factors for cardiovascular disease among Canadian Inuit

Abstract

Objectives: The aim of the present study was to investigate the potential importance of oxidative stress, measured by isoprostanes-related compounds, as non-traditional risk factor for cardiovascular disease. We planned to examine the relationship between concentrations of plasma F₂-isoprostanes (F₂-IsoPs), isofurans (IsoFs), measures of obesity and various cardiometabolic risk factors. Materials and methods: Cross-sectional study using a sub-sample from the population of a survey conducted in the summer and fall 2007 and 2008 by Canadian Coastguard Ship Amundsen in 36 Canadian Arctic Inuit communities. Subjects included a subset (n =?233) of a total study population (n =?2595) with a mean age 42.56 ± 15.39 years and body mass index 27.78 ± 5.65 kg/m². Plasma levels of F₂-IsoPs and IsoFs was determined by gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method; and their relationships to waist circumference (WC), blood pressure C reactive proteins (CRP), blood lipids and fasting glucose were assessed by multivariate analyses. Results: Plasma F₂-IsoPs correlated positively with CRP (r =.132, P =.048) and systolic blood pressure (SBP) (r =.157, P =.024) after adjustment for age, sex and body mass index. IsoFs correlated with WC (r =.190, P =.005) and SBP (r =.137, P =.048). F2-IsoPs were not found elevated in smokers (P =.034), whereas IsoFs were decreased in smokers (P =.001). WC, SBP and sex were found to be major correlates of oxidative stress in Canadian Inuit. Conclusions: Plasma measures of F₂-IsoPs and IsoFs increase with increased obesity and associated cardiometabolic risk factors, including CRP and blood pressure. Simultaneous measurement of IsoFs provides an advantageous mechanistic insight into oxidative stress not captured by F₂-IsoPs alone.