Cardiovascular disease and PPARdelta: Targeting the risk factors

Metabolism, in part, is regulated by the peroxisome proliferator-activated receptors (PPARs). The PPARs act as nutritional lipid sensors and three mammalian PPAR subtypes designated PPARalpha (NR1C1), PPARgamma (NR1C3) and PPARdelta (NR1C2) have been identified. This subgroup of nuclear hormone receptors binds DNA and controls gene expression at the nexus of pathways that regulate lipid and glucose homeostasis, energy storage and expenditure in an organ-specific manner. Recent evidence has demonstrated activation of PPARdelta in the major mass peripheral tissue (ie, adipose and skeletal muscle). It enhances glucose tolerance, insulin-stimulated glucose disposal, lipid catabolism, energy expenditure, cholesterol efflux and oxygen consumption. These effects positively influence the blood-lipid profile. Furthermore, PPARdelta activation produces a predominant type I/slow twitch/oxidative muscle fiber phenotype that leads to increased endurance, insulin sensitivity and resistance to obesity. PPARdelta has rapidly emerged as a potential target in the battle against dyslipidemia, insulin insensitivity, type II diabetes and obesity, with therapeutic efficacy in the treatment of cardiovascular disease risk factors. GW-501516 is currently undergoing phase II safety and efficacy trials in human volunteers for the treatment of dyslipidemia. The outcome of these clinical trials are eagerly awaited against a background of conflicting reports about cancer risks in genetically predisposed animal models. This review focuses on the potential pharmacological utility of selective PPARdelta agonists in the context of risk factors associated with metabolic and cardiovascular disease.

Dietary enrichment by almond supplementation: effects on risk factors for cardiovascular disease

Cardiovascular disease (CVD) is the leading cause of death in Europe responsible for more than 4.3 million deaths annually. The World Health Organisation funded the Monica project (1980s-1990s) which monitored ten million subjects aged 22-6Syrs, and demonstrated that coronary heart disease (CHD) mortality declined over 10 years, was due in two thirds of cases to reduced incidence of CHD (reduced risk behaviours e.g. poor diet and smoking) and one third by improved treatments. Epidemiological evidence suggests diets rich in antioxidants decrease incidence of CVD. Regular consumption of nuts, rich in vitamin E and polyphenols reduces atherosclerosis, an important risk for heart disease. Intervention studies to date using alpha tocopherol (an active component of vitamin E) have not consistently proved beneficial. This thesis aims to investigate the effect of almond supplementation on vascular risk factors in healthy young males (18-3Syrs); mature males and female(>SOyrs); and males considered at increased risk of CVD (18-3Syrs) in a cohort of 67 subjects. The effects of almond intake were assessed after 2Sg/d for four weeks followed by SOg/d for four weeks and compared to a control group which did not consume almonds or change their diet. Cardiovascular risk was assessed by plasma lipid profiles, apolipoprotein A1, plasma nitrates/nitrates, vascular flow, BMl, blood pressure, sVCAM-1 and protein oxidation. Systolic and diastolic blood pressures were reduced in almond supplemented volunteers but not in controls. Dietary monounsaturated fatty acids, polyunsaturated fatty acid content and total dietary fats were increased by almond supplementation. Neither sVCAM-1, venous occlusion plethysmography nor plasma nitrite levels were affected by almond intake in any independent group. No significant changes in plasma lipids, and apolipoprotein A1 were observed. In conclusion almonds supplementation caused a reduction in blood pressure that may be due to increased sensitivity of the baroreceptors after increased monounsaturated fatty acid intake.

Risk factors for type 2 diabetes mellitus and cardiovascular diseases in Hispanic adolescents

This cross-sectional study evaluated risk factors (RF) for type 2 diabetes (T2DM) and cardiovascular diseases (CVD) in 100 Hispanic adolescents(50 overweight, 50 non-overweight) aged 12-16 years, and their associations with body mass index (BMI), diet, physical activity (PA), gender, and birth weight (BW). The RF studied were fasting plasma glucose (FPG), insulin sensitivity (IS), total cholesterol (TC), triacylglycerols (TG), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), acanthosis nigricans (AN), and blood pressure (BP). Dietary intakes were assessed using the Block Kids Questionnaire, fat-related intake behavior (FB) using the Fat-Related Diet Habits Questionnaire, and PA using the Modifiable Activity Questionnaire for Adolescents. Blood was collected after an overnight fast of 12 hours. All statistical analyses used SPSS 14.0. Overweight adolescents had presence of AN, higher BP, TC, TG, and LDL, and lower IS, ps < .001, as compared to non-overweight adolescents. Overweight adolescents were more likely to have 1 and 2 RF for T2DM and CVD as compared to having 0, ps < .001, and 2 RF as compared to having 1, p =.033. Adolescents with kilocalorie (Kcal) intake above requirements for age gender, and PA level were 4.6 times more likely to be overweight, p = .005. Overweight adolescents had worse FB, p = .011, and lower PA, p < .001. Adolescents with worse FB had higher BP, p = .016. Fiber below recommendations (14g/1,000 Kcal) was associated with being overweight, p = .012, and lower IS, p = .040. Adolescents with higher BW had higher FPG, p = .013. Our findings point to an association between being overweight and RF for T2DM and CVD, suggesting that overweight during adolescence may have serious health consequences for Hispanic adolescents. Also, our results indicate that Hispanic overweight adolescents eat more Kcal and less fiber than required, have worst FB, and less PA levels than their non-overweight counterparts. In addition, high BW and dietary habits of Hispanic adolescents, such as low fiber and FB, increase their risk for T2DM and CVD. We conclude that BMI can serve as a useful tool to identify Hispanic adolescents at risk for T2DM and CVD.

Risk factors of type 2 diabetes and cardiovascular diseases among Jamaican adolescents

Purpose. The purpose of the study was to examine Jamaican adolescents in a school setting, for risk factors of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Methods. A descriptive epidemiological cross-sectional study of 276 Jamaican adolescents (112 males and 164 females) ages 14-19 years (15.6±1.2), randomly selected from grades 9-12 from ten high schools on the island. Thirteen risk factors were examined. Risk factors were compared with BMI levels and demographics. A sub-study validated finger prick testing of fasting blood glucose, total cholesterol, and HbA1c versus venous testing in 59 subjects. Results. Prevalence of overweight was 33.0% (n=91) with mean BMI of 23.74±7.74. Approximately 66.7% of subjects reported ≥ 3 risk factors. The number of T2DM and CVDs risk factors increased for subjects with BMI above 25. One third of the overweight subjects were classified with the metabolic syndrome. High BMI was associated with high waist circumference (r = .767, p < .01), high waist-to-hip ratio (r = .180, p < .01), presence of Acanthosis Nigricans (r = .657, p < .01), high total cholesterol (r = .158, p < .01), family history of T2DM (r = .157, p < .01), and hypertension (r = .422, p < .01). Regression analyses significantly predicted gender and physical activity (p < .001), and total number of risk factors for T2DM and CVDs (p < .001). Paired samples t-tests revealed no significant differences between methods of testing for TC and HbA1c (p < .01) but not for FBG (p > .05). Percentage bias for the methods of blood testing met the reference standards for fasting blood glucose but not for total cholesterol and HbA1c. Bland Altman tests of agreement between the two methods indicated good agreement for all three tests. Conclusion. Jamaican adolescents are at high risk for T2DM and CVDs as seen in other study populations. Effective programs to prevent T2DM and CVDs are needed. Family history of diseases, anthropometric measures, and gender identified more subjects at risk than did the biochemical measures. Comparison between finger prick and venous blood methods suggested that finger prick is an adequate method to screen for risk factors in children and adolescents.

Obesity, cardiovascular disease risk factors and weight loss in a population of adult Mexican Americans

The study of obesity has evolved into one of the most important public health issues in the United States (U.S.), particularly in Hispanic populations. Mexican Americans, the largest Hispanic ethnic subgroup in the U.S., have been significantly impacted by obesity and related cardiovascular diseases. Mexican Americans living in the Lower Rio Grande Valley (the Valley) in the Texas-Mexico border are one of the most disadvantaged and hard-to-reach minority groups. Demographic factors, socioeconomic status, acculturation, and physical activity behavior have been found to be important predictors of health, although research findings are mixed when establishing predictors of obesity in this population. Furthermore, while obesity has long been linked to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and dyslipidemia; information on the relationships between obesity and these CVD risk factors have been mostly from non-minority population groups. Overall, research has been mixed in establishing the association between obesity and related CVD risk factors in this population calling attention to the need for further research. Nevertheless, identifying predictors of success for weight loss in this population will be important if health disparities are to be addressed. The overall objective of the findings presented in this dissertation was to attain a more informed profile of obesity and CVD risk factors in this population. In particular, we examined predictors of obesity, measures of obesity and association with cardiovascular disease risk factors in a sample of 975 Mexican Americans participating in a health promotion program in the Valley region. Findings suggest acculturation factors to be one of the most important predictors of obesity in this population. Results also point to the need of identifying other possible risk factors for predicting CVD risk. Finally, initial body mass index is an important predictor of weight loss in this population group. Thus, indicating that this population is not only amenable to change, but that improvements in weight loss are feasible. This finding strengthens the relevance of prevention programs such as Beyond Sabor for Mexican populations at risk, in particular, food bank recipients.

Risk factors of type 2 diabetes and cardiovascular diseases among Jamaican adolescents

Purpose: The purpose of the study was to examine Jamaican adolescents in a school setting, for risk factors of type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Methods: A descriptive epidemiological cross-sectional study of 276 Jamaican adolescents (112 males and 164 females) ages 14-19 years (15.6±1.2), randomly selected from grades 9-12 from ten high schools on the island. Thirteen risk factors were examined. Risk factors were compared with BMI levels and demographics. A sub-study validated finger prick testing of fasting blood glucose, total cholesterol, and HbAlc versus venous testing in 59 subjects. Results: Prevalence of overweight was 33.0% (n=91) with mean BMI of 23.74±7.74. Approximately 66.7% of subjects reported > 3 risk factors. The number of T2DM and CVDs risk factors increased for subjects with BMI above 25. One third of the overweight subjects were classified with the metabolic syndrome. High BMI was associated with high waist circumference (r =.767, p (r = .180, p.05). Percentage bias for the methods of blood testing met the reference standards for fasting blood glucose but not for total cholesterol and HbAlc. Bland Altman tests of agreement between the two methods indicated good agreement for all three tests. Conclusion: Jamaican adolescents are at high risk for T2DM and CVDs as seen in other study populations. Effective programs to prevent T2DM and CVDs are needed. Family history of diseases, anthropometric measures, and gender identified more subjects at risk than did the biochemical measures. Comparison between finger prick and venous blood methods suggested that finger prick is an adequate method to screen for risk factors in children and adolescents.

Comparison of Cardiovascular Disease Risk Factors between Single and Partnered Mothers: Data from the 2006 Health Survey of Adults and Children in Bermuda

Women are a high-risk population for cardiovascular diseases (CVD); however relationships between CVD and subpopulations of mothers are sparse. A secondary data analysis of the 2006 Health Survey of Adults and Children in Bermuda was conducted to compare the prevalence of CVD risk factors in single (n=77) and partnered (n=241) mothers. A higher percentage of single mothers were Black (p25 kg/m2 (p=0.01) and reported high blood pressure (p=0.004) and high cholesterol (0.017). Single mothers were nearly three times (OR=2.66) more likely to experience high blood pressure and two times (OR= 2.22) more likely to have high cholesterol. Single mothers may benefit from nutrition education programs related to lowering CVD risk.

Sustainability of a multimodal intervention to promote lifestyle factors associated with the prevention of cardiovascular disease in midlife Australian women : a 5-year follow-up

We evaluated sustainability of an intervention to reduce women’s cardiovascular risk factors, determined the influence of self-efficacy, and described women’s current health. We used a mixed method approach that utilized forced choice and open-ended questionnaire items about health status, habits, and self-efficacy. Sixty women, average age 61, returned questionnaires. Women in the original intervention group continued health behaviors intended to reduce cardiovascular disease (CVD) at a higher rate than the control group, supporting the feasibility of a targeted intervention built around women’s individual goals. The role of self-efficacy in behavior change is unclear. The original intervention group reported higher self-reported health.

Assessing Cardiovascular Risk in Regional Areas: The Healthy Hearts – Beyond City Limits Program

Background: Cardiovascular disease (CVD) is more prevalent in regional and remote Australia compared to metropolitan areas. The aim of Healthy Hearts was to determine age and sex specific CVD risk factor levels and the potential value of national risk clinics. Methods: Healthy Hearts was an observational research study conducted in four purposefully selected higher risk communities in regional Victoria, Australia. The main outcome measures were the proportion of participants with CVD risk factors with group comparisons to determine the adjusted likelihood of elevated risk factor levels. Trained personnel used a standardized protocol over four weeks per community to measure CVD risk factor levels, estimate absolute CVD risk and provide feedback and advice. Results: A total of 2125 self-selected participants were assessed (mean age 58 ± 15 years, 57% women). Overall, CVD risk factors were highly prevalent. More men than women had ≥ 2 modifiable CVD risk factors (76% vs. 68%, p < .001), pre-existing CVD (20 vs. 15%, p < .01) and a major ECG abnormality requiring follow-up (15% vs. 7%, p < .001) . Less men reported depressive symptoms compared to women (28% vs. 22%, p < .01). A higher proportion of women were obese (adjusted OR 1.36, 95% CI 1.13 to 1.63), and physically inactive (adjusted OR 1.32, 95% CI 1.07 to 1.63). Conclusions: High CVD risk factor levels were confirmed for regional Victoria. Close engagement with individuals and communities provides scope for the application of regional risk management clinics to reduce the burden of CVD risk in regional Australia.