American Heart Association Step Research Articles

Healthy Behavior, Risk Factor Control, and Survival in the COURAGE Trial

BackgroundIndividual risk factor control improves survival in patients with stable ischemic heart disease (SIHD). It is uncertain if multiple risk factor control further extends survival. ObjectivesThis study determined whether a greater number of risk factors at goal predicted improved survival in SIHD patients. MethodsOf 2,287 participants in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 2,102 (92%) had complete ascertainment of 6 pre-specified risk factors: systolic blood pressure, low-density lipoprotein cholesterol, smoking, physical activity, diet, and body mass index. Participants received interventions to control these risk factors. The outcome measure was mortality. ResultsDuring a mean follow-up of 6.8 years, 473 (22.5%) subjects died. In univariate analysis, the greater the number of risk factors controlled, the higher the probability of survival (unadjusted log rank: p < 0.001). In multivariate analysis, the strongest predictors at 1 year of improved survival were being a nonsmoker, regular physical activity, having a systolic blood pressure <130 mm Hg, and following the American Heart Association Step 2 diet. Baseline risk factor values and evidence-based medications did not independently predict survival once risk factor control at 1 year was included in the model. Having 4 to 6 risk factors compared with 0 to 1 risk factor at goal predicted lower mortality (hazard ratios for 4 and 6 controlled risk factors: 0.64; 95% confidence interval: 0.41 to 0.98, and 0.27; 95% confidence interval: 0.09 to 0.79, respectively). ConclusionsThe greater the number of risk factors in control, the higher the probability of survival in patients with SIHD. More effective strategies are needed to achieve comprehensive risk factor control, including healthy behaviors. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657)

Poly is more effective than monounsaturated fat for dietary management in the metabolic syndrome: The muffin study

The metabolic syndrome (MetS) is highly prevalent and associated with an increased risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle recommendations to treat MetS often include the replacement of saturated fats (SFAs) and monosaccharides with unsaturated fat. However, it is unclear whether metabolic parameters will improve more when the saturated fat in American Heart Association (AHA) diets is replaced with higher concentrations of monounsaturated or polyunsaturated fatty acids (MUFA or PUFA). To test the hypothesis that an AHA diet enriched in MUFA improves lipoprotein lipids, insulin resistance, inflammation, and endothelial function to a greater extent than a diet enriched in PUFA in middle-aged men and women with MetS. A prospective, open-label, parallel group design with randomization to a hypocaloric MUFA or PUFA-enriched diet after weight stabilization on an AHA step I diet. Participants consumed 3 MUFA-enriched or PUFA-enriched muffins daily with additional supplementation as required to ensure 25%-50% increases in dietary fat intake from these sources at the expense of SFA and the opposing unsaturated fat. Changes in MetS components were measured at baseline and after 6months of dietary intervention. Thirty-nine participants (mean age, 60.8years; 79% African-American, 60% women) with MetS completed the 6-month study. Compared to baseline, assignment to either MUFA (n=23) or PUFA (n=16) both were associated with weight loss (MUFA: -2.3±1kg, P=.06; PUFA: -4.6±2kg; P=.002), but PUFA was also associated with reductions in triglycerides (TG) (-30±18mg/dL, P=.02), systolic blood pressure (BP) (-7 ± 3mm Hg, P=.01), diastolic BP (DBP) (-4 ± 2mm Hg, P=.01) and improved flow mediated dilation (FMD) (7.1%±1.8% vs 13.6%±2%, absolute increase; P=.0001). When compared to MUFA treatment, PUFA intervention was associated with reduced TG (P=.04) and DBP (P=.07) as well as increased FMD (P=.04) even after adjustment for changes in weight. There was no effect on total cholesterol, low-density lipoprotein cholesterol, glucose, high-sensitivity C-reactive protein (hs-CRP), or other inflammatory proteins. Overall, 25% (4 of 16) assigned to PUFA and 13% (3 of 23) to MUFA converted to non-MetS status. Substitution of SFA with PUFA in patients with MetS is associated with greater reductions in TG and improvement in endothelial function than MUFA that is independent of weight loss. These preliminary findings raise the possibility that PUFA may be the unsaturated fat of choice to reduce cardiometabolic risk in patients with MetS.

Effects of pistachios on body weight in Chinese subjects with metabolic syndrome

BackgroundStudies have shown that pistachios can improve blood lipid profiles in subjects with moderate hypercholesterolemia which could reduce the risk of cardiovascular disease. However, there is also a widely perceived view that eating nuts can lead to body weight gain due to their high fat content.PurposeTo investigate the impact of different dosages of pistachios on body weight, blood pressure, blood lipids, blood glucose and insulin in subjects with metabolic syndrome.MethodsNinety subjects with metabolic syndrome (consistent with 2005 International Diabetes Federation metabolic syndrome standard without diabetes) were enrolled in three endocrinology outpatient clinics in Beijing. All subjects received dietary counseling according to the guidelines of the American Heart Association Step I diet. After a 4 week run-in, subjects were randomized to consume either the recommended daily serving of 42 g pistachios (RSG), a higher daily serving of 70 g pistachio (HSG) or no pistachios (DCG) for 12 weeks.ResultsSubjects in all three groups were matched at baseline for BMI: DCG 28.03 ± 4.3; RSG 28.12 ± 3.22; and HSG 28.01 ± 4.51 kg/m2. There were no significant changes in body weight or BMI in any groups during the study nor any change from baseline at any time point in any group. During the entire study, there were no significant differences in waist-to-hip ratio among the groups or any change from baseline in any group (DCG -0.00 ± 0.03, RSG -0.01 ± 0.02 and HSG 0.01 ± 0.04). There were no significant differences detected among groups in triglycerides, fasting glucose and 2 hour postprandial glucose following a 75 gram glucose challenge. Exploratory analyses demonstrated that glucose values 2 h after a 75 gm glucose challenge were significantly lower at week 12 compared with baseline values in the HSG group (-1.13 ± 2.58 mmol/L, p = 0.02), and a similar trend was noted in the RSG group (-0.77 ± 2.07 mmol/L, p = 0.06), while no significant change was seen in the DCG group (-0.15 ± 2.27 mmol/L, p = 0.530). At the end of study, serum triglyceride levels were significantly lower compared with baseline in the RSG group (-0.38 ± 0.79 mmol/L, p = 0.018), but no significant changes were observed in the HSG or DCG groups.ConclusionDespite concerns that pistachio nut consumption may promote weight gain, the daily ingestion of either 42 g or 70 g of pistachios for 12 weeks did not lead to weight gain or an increase in waist-to-hip ratio in Chinese subjects with metabolic syndrome. In addition, pistachio consumption may improve the risk factor associated with the metabolic syndrome.

P39 ASSESSMENT OF SUBCLINICAL CORONARY ATHEROSCLEROSIS IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA WITH MULTISLICE COMPUTED TOMOGRAPHY

To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin.Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown.Children with FH were randomized to placebo (n = 88) or pravastatin (n = 90) after instruction on American Heart Association step II diet. Unaffected siblings (n = 78) served as controls. The OxPL content on apolipoprotein B-100 (apoB) detected by antibody E06 (OxPL/apoB ratio), immunoglobulin (Ig)G and IgM immune complexes per apoB (IC/apoB) and on all apoB particles (total apoB-IC = IC/apoB multiplied by plasma apoB levels), autoantibodies to malondialdehyde (MDA)–low-density lipoprotein (LDL), Lp(a), and apoB levels were measured at baseline and after two years of treatment.Compared with unaffected siblings, children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies. From baseline to two-year follow-up, compared with placebo pravastatin treatment resulted in a greater mean percentage change in apoB (−18.7% vs. 0.3%; p = 0.001), total IgG apoB-IC (−31.9% vs. −12.2%; p < 0.001), and total IgM apoB-IC (−25.5% vs. 13.2%; p = 0.001). Interestingly, pravastatin also resulted in higher OxPL/apoB (48.7% vs. 29.3%; p = 0.028) and Lp(a) levels (21.9% vs. 10.7%; p = 0.044).Compared with unaffected siblings, children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies. Compared with placebo, pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a), which may represent a novel mechanism of mobilization and clearance of OxPL.

Effect of a sequential training programme on inflammatory, prothrombotic and vascular remodelling biomarkers in hypertensive overweight patients with or without metabolic syndrome

It is not known whether serum level of vascular remodelling parameters, such as matrix metalloproteinases could be modulated by physical activity and whether the eventual change could be influenced by metabolic syndrome (MS) diagnosis. Open, intervention study to evaluate the effects of a sequential physical activity training on inflammatory, prothrombotic and vascular remodelling biomarkers in overweight patients with and without MS. We enrolled 80 overweight patients (mean age: 62.9+/-8.3 years; male : female = 36 : 44) with newly diagnosed hypertension, with or without MS. After 3 months of American Heart Association step 2 diet, they followed a sequential training programme including 56 days of added three metabolic equivalent tasks/week and 56 days of six metabolic equivalent tasks/week. All patients experienced a significant decrease in body mass index, waist circumference and blood pressure after both the training phases. High-density lipoprotein-cholesterolemia, triglycerides, and glycaemia significantly improved only after the intensive training phase compared with the baseline in MS patients. Prothrombotic parameters improved irrespectively from the MS diagnosis. High-sensitivity C-reactive protein P level significantly decreased towards baseline and towards the previous phase, after exercise intensification, but only in MS patients. The plasma level of matrix metalloproteinase 2 and 9, and their activated forms improved significantly when compared with the baseline both after the first and the second training period, independently from the MS diagnosis. Diagnosis of MS is a determinant of changes in metabolic and inflammatory biomarkers, but not of the prothrombotic and vascular remodelling ones in a sample of overweight hypertensive patients.

Enhancement of a modified Mediterranean-style, low glycemic load diet with specific phytochemicals improves cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia in a randomized trial

BackgroundAs the worldwide dietary pattern becomes more westernized, the metabolic syndrome is reaching epidemic proportions. Lifestyle modifications including diet and exercise are recommended as first-line intervention for treating metabolic syndrome. Previously, we reported that a modified Mediterranean-style, low glycemic load diet with soy protein and phytosterols had a more favorable impact than the American Heart Association Step 1 diet on cardiovascular disease (CVD) risk factors. Subsequently, we screened for phytochemicals with a history of safe use that were capable of increasing insulin sensitivity through modulation of protein kinases, and identified hops rho iso-alpha acid and acacia proanthocyanidins. The objective of this study was to investigate whether enhancement of a modified Mediterranean-style, low glycemic load diet (MED) with specific phytochemicals (soy protein, phytosterols, rho iso-alpha acids and proanthocyanidins; PED) could improve cardiometabolic risk factors in subjects with metabolic syndrome and hypercholesterolemia.MethodsForty-nine subjects with metabolic syndrome and hypercholesterolemia, aged 25–80, entered a randomized, 2-arm, 12-week intervention trial; 23 randomized to the MED arm; 26 to the PED arm. Forty-four subjects completed at least 8 weeks [MED (n = 19); PED (n = 25)]. All subjects were instructed to follow the same aerobic exercise program. Three-day diet diaries and 7-day exercise diaries were assessed at each visit. Fasting blood samples were collected at baseline, 8 and 12 weeks for analysis.ResultsBoth arms experienced equal weight loss (MED: -5.7 kg; PED: -5.9 kg). However, at 12 weeks, the PED arm experienced greater reductions (P < 0.05) in cholesterol, non-HDL cholesterol, triglycerides (TG), cholesterol/HDL and TG/HDL compared with the MED arm. Only the PED arm experienced increased HDL (P < 0.05) and decreased TG/HDL (P < 0.01), and continued reduction in apo B/apo A-I from 8 to 12 weeks. Furthermore, 43% of PED subjects vs. only 22% of MED subjects had net resolution of metabolic syndrome. The Framingham 10-year CVD risk score decreased by 5.6% in the PED arm (P < 0.01) and 2.9% in the MED arm (P < 0.05).ConclusionThese results demonstrate that specific phytochemical supplementation increased the effectiveness of the modified Mediterranean-style low glycemic load dietary program on variables associated with metabolic syndrome and CVD.

Exercise Training-Induced Changes in Coagulation Factors in Older Adults

The coagulation cascade plays a critical role in the development of cardiovascular disease (CVD). Elevated plasma prothrombin fragment 1 + 2 (F1 + 2) and factor VIII antigen (FVIII:Ag) levels have been associated with a hypercoagulable state, enhancing the risk for vascular thrombotic events. Aerobic training is known to reduce CVD risk, and an improved coagulation profile may contribute to this reduction. To analyze the effect of 6 months of standardized aerobic exercise training on resting F1 + 2 and FVIII:Ag levels in men and postmenopausal women aged 50-75 while accounting for several possibly confounding factors. Sedentary men (N=16) and women (N=31) underwent supervised aerobic training 3 d x wk(-1) for 6 months while maintaining the American Heart Association step 1 diet. Baseline and final testing included measurement of F1 + 2, FVIII:Ag, plasma lipoprotein-lipid levels, body composition, and VO2max. When adjusted for baseline values and changes in diastolic blood pressure with training, F1 + 2 was found to decrease significantly with exercise training from 1.493 +/- 0.058 to 1.422 +/- 0.059 nM (P=0.014). FVIII:Ag levels were found to increase significantly with training when adjusted for baseline values, from 152.5 +/- 6.7% of standard at baseline to 156.0 +/- 6.1% of standard at final testing (P=0.005). Training-induced changes in coagulation markers were independent of changes in blood lipids, aerobic capacity, and body composition. : These results indicate that endurance training has a significant impact on the coagulation cascade, reducing coagulation activity in the common pathway and thrombin formation at rest while increasing the activation potential of the intrinsic pathway.

Oat-derived β-Glucan Significantly Improves HDLC and Diminishes LDLC and Non-HDL Cholesterol in Overweight Individuals With Mild Hypercholesterolemia

To investigate the effect of bread formulated with 6 g of beta-glucan (oat soluble fiber) on serum lipids in overweight normotensive subjects with mild to moderate hypercholesterolemia. Thirty-eight male subjects [mean age 59.8 +/- 0.6 yr, mean body mass index (BMI) 28.3 +/- 0.6 kg/m(2)] who were eligible for the study ate an isocaloric diet for a 1-week period. They were then divided into 2 groups: group A (n = 19), who were maintained on American Heart Association (AHA) Step II diet, including whole wheat bread, and group B (n = 19), who were maintained on AHA Step II diet containing high levels of monounsaturated fatty acids plus bread containing 6 g of beta-glucan (Nutrim-OB) for 8 weeks. Plasma lipids and glucose were measured at baseline and after weeks 8 in all subjects. All subjects were advised to walk for 60 minutes every day. There was a significant increase (upward arrow 27.8%) in plasma high density lipoprotein (HDL) cholesterol in the beta-glucan group (group A) from 39.4 +/- 2.0 to 49.5 +/- 2.1 mg/dL (P < 0.001), but there was no change in group B. There was a significant reduction in total cholesterol in the 2 groups to approximately the same extent: group A, from 232.8 +/- 2.7 mg/dL to 202.7 +/- 6.7 mg/dL; P < 0.001; and group B, from 231.8 +/- 4.3 mg/dL to 194.2 +/- 4.3 mg dL; P < 0.001. Plasma low density lipoprotein (LDL) cholesterol also decreased significantly in the two groups: group A, from 160.3 +/- 2.8 mg/dL to 133.2 +/- 5.4 mg/dL; P < 0.001; group B, from 167.9 +/- 4.3 mg/dL to 120.9 +/- 4.3 mg/dL; P < 0.001; however, the beta-glucan fortified diet was significantly more effective (downward arrow 27.3% vs. downward arrow 16.8%; P < 0.04). There was a small and insignificant reduction in plasma very LDL (VLDL) cholesterol and triglycerides in the two groups. Similarly, non-HDL cholesterol levels were also decreased, with beta-glucan diet producing significantly higher effect (downward arrow 24.5% vs. downward arrow 16.1%; P < 0.04). The beta-glucan diet also produced higher reduction in total cholesterol/HDL cholesterol ratio (downward arrow 33.3% vs. downward arrow 8.4%; P < 0.003) and LDL cholesterol/HDL cholesterol ratio (downward arrow 42.1% vs. downward arrow 13.3%; P < 0.001) than the diet without beta-glucan. The beta-glucan diet also decreased fasting plasma glucose (P < 0.4), whereas the other diet had no effect. Interestingly, both diets reduced body weight and BMI significantly, with beta-glucan diet having a greater effect. Six grams of beta-glucan from oats added to the AHA Step II diet and moderate physical activity improved lipid profile and caused a decrease in weight and, thus, reduced the risk of cardiovascular events in overweight male individuals with mild to moderate hypercholesterolemia. The diet with added beta-glucan was well accepted and tolerated.

Ciprofibrate Treatment Decreases Non-high Density Lipoprotein Cholesterol and Triglycerides and Increases High Density Lipoprotein Cholesterol in Patients With Frederickson Type IV Dyslipidemia Phenotype

The combination of hypertriglyceridemia and low high density lipoprotein (HDL) cholesterol is one of the most common lipid abnormalities. Thus, the aim of this study was to determine the effects of ciprofibrate on lipid profile in patients with Frederickson's type IV dyslipidemia phenotype. Seventy-five patients with type IV dyslipidemia were assigned at random to 1 of 2 therapeutic options: group A (control), American Heart Association (AHA) Step II diet and physical activity; and group B, AHA diet, physical activity, and ciprofibrate 100 mg daily for 8 weeks. The lipid profile of all patients was determined at baseline and after therapeutic intervention. Patients in group B (treated with ciprofibrate) compared with group A (control) had significantly higher reductions in total cholesterol (downward arrow 14.2% vs. downward arrow 4.8%; P < 0.02), triglycerides (downward arrow 38.0% vs. downward arrow 21.6%; P < 0.007), very low density lipoprotein cholesterol (downward arrow 38.0% vs. downward arrow 21.6%; P < 0.007), non-HDL cholesterol (downward arrow 20.5% vs. downward arrow 7.1%; P < 0.007), and total cholesterol/high density cholesterol ratio (downward arrow 25.6% vs. downward arrow 9.4%; P < 0.01). The ciprofibrate group had a significantly higher increase in HDL cholesterol levels compared with the other group (upward arrow 25.0% vs. upward arrow 9.6%, P < 0.02). Ciprofibrate treatment effectively reduced triglyceride-rich particles and non-HDL cholesterol, and significantly increased HDL cholesterol, proving its effectiveness in patients with low HDL cholesterol and type IV Frederickson's hyperlipidemia.

Suppression of Rage as a Basis of Simvastatin-Dependent Plaque Stabilization in Type 2 Diabetes

Receptor for advanced glycation end products (AGEs) (RAGE) plays a central role in the process of plaque rupture in diabetic patients. Recently, it has been reported that RAGE may be downregulated by improving glycemic control. In contrast, despite being well known that RAGE may be induced in human vessels in a glucose-independent fashion, also by myeloperoxidase (MPO)-dependent AGE generation, no data exist regarding the possibility of a pharmacological modulation of glucose-independent RAGE generation. Thus, the aim of this study was to characterize the effect of simvastatin on the expression of RAGE and RAGE-dependent plaque-destabilizing genes in human atherosclerotic plaques. Seventy type 2 diabetic patients with asymptomatic carotid artery stenosis (>70%) were randomized to American Heart Association (AHA) step 1 diet plus simvastatin (40 mg/d) or AHA step 1 diet alone for 4 months before endarterectomy. Plaque expression of MPO, AGEs, RAGE, NF-kappaB, COX-2, mPGES-1, matrix metalloproteinase (MMP)-2 and MMP-9, lipid and oxidized LDL (oxLDL) content, procollagen 1, and interstitial collagen was analyzed by immunohistochemistry and Western blot; zymography was used to detect MMP activity. Plaques from the simvastatin group had less (P<0.0001) immunoreactivity for MPO, AGEs, RAGE, p65, COX-2, mPGES-1, MMP-2, and MMP-9, lipids and oxLDL; reduced (P<0.0001) gelatinolytic activity; increased (P<0.0001) procollagen 1 and collagen content; and fewer (P<0.0001) macrophages, T-lymphocytes, and HLA-DR+ cells. Of interest, RAGE inhibition by simvastatin, observed not only in plaque sections but also in plaque-derived macrophages, was reverted by addition of AGEs in vitro. This study supports the hypothesis that simvastatin inhibits plaque RAGE expression by decreasing MPO-dependent AGE generation. This effect in turn might contribute to plaque stabilization by inhibiting the biosynthesis of PGE2-dependent MMPs, responsible for plaque rupture.

Tacrolimus as Intervention in the Treatment of Hyperlipidemia after Liver Transplant

To measure the effect on serum lipids and other risk factors for cardiovascular disease, we converted the primary immunosuppression of dyslipidemic stable liver transplant recipients from cyclosporine A to tacrolimus. Patients underwent a four-month dietary stabilization period (American Heart Association Step II diet) and serum lipid samples were collected for analysis at a central laboratory. After conversion, dietary counseling and lipid analyses were performed over a six-month postconversion observation period. Enrollment was terminated prematurely due to low patient recruitment rates. Thirteen patients were enrolled and provided postconversion data showing surprisingly strong results. At six months postconversion, total cholesterol (C) was reduced by a mean of 0.61 mmol/L (P=0.017), high density lipoprotein cholesterol (HDL-C) remained unchanged; the mean total C:HDL-C ratio was reduced by 0.87 (P=0.001). Low density lipoprotein cholesterol (LDL-C) reductions were not statistically significant, but we observed a significant and persistent decrease in apolipoprotein B (-0.15 g/L six months postconversion, P=0.031). No changes in homocysteine or in vitamins B6 and B12 were discerned, but although red cell folate remained stable, serum folate increased after conversion. We observed no rejection episodes or any other clinically notable events following conversion. In this study, conversion from cyclosporine to tacrolimus provided a safe and well-tolerated alternative that reduced hyperlipidemia and other recognized cardiovascular risk factors.

Oxidized Low-Density Lipoprotein in Children With Familial Hypercholesterolemia and Unaffected Siblings: Effect of Pravastatin

To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The significance of OxPL markers in children is unknown. Children with FH were randomized to placebo (n = 88) or pravastatin (n = 90) after instruction on American Heart Association step II diet. Unaffected siblings (n = 78) served as controls. The OxPL content on apolipoprotein B-100 (apoB) detected by antibody E06 (OxPL/apoB ratio), immunoglobulin (Ig)G and IgM immune complexes per apoB (IC/apoB) and on all apoB particles (total apoB-IC = IC/apoB multiplied by plasma apoB levels), autoantibodies to malondialdehyde (MDA)-low-density lipoprotein (LDL), Lp(a), and apoB levels were measured at baseline and after two years of treatment. Compared with unaffected siblings, children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies. From baseline to two-year follow-up, compared with placebo pravastatin treatment resulted in a greater mean percentage change in apoB (-18.7% vs. 0.3%; p = 0.001), total IgG apoB-IC (-31.9% vs. -12.2%; p < 0.001), and total IgM apoB-IC (-25.5% vs. 13.2%; p = 0.001). Interestingly, pravastatin also resulted in higher OxPL/apoB (48.7% vs. 29.3%; p = 0.028) and Lp(a) levels (21.9% vs. 10.7%; p = 0.044). Compared with unaffected siblings, children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies. Compared with placebo, pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a), which may represent a novel mechanism of mobilization and clearance of OxPL.

Effects of Short-Term Fenofibrate Treatment on Circulating Markers of Inflammation and Hemostasis in Patients with Impaired Glucose Tolerance

Apart from lowering lipid levels, peroxisome proliferator-activated receptor (PPAR) alpha activators (fibrates) produce many other favorable effects that may contribute to their clinical effectiveness in dyslipidemic and diabetic patients. The objective of this study was to compare the impact of a short-term treatment with fenofibrate and the American Heart Association (AHA) step 1 diet on systemic inflammation, hemostasis, and monocyte secretory function in relationship with their metabolic actions. This was a prospective, randomized, placebo-controlled trial involving the group of 91 ambulatory patients with impaired glucose tolerance (IGT) (diagnosed on the basis of the American Diabetes Association criteria), randomly divided into three groups, simultaneously treated for 30 d with the AHA step 1 diet (n = 30), micronized fenofibrate (267 mg/d, n = 31), or placebo (n = 30). The control group included 34 age-, sex-, and weight-matched subjects with normal glucose tolerance. Eighty-six (95%) patients and all control subjects completed the study. Plasma markers of inflammation and hemostasis and monocyte release of proinflammatory cytokines were measured. Compared with subjects with normal glucose tolerance, IGT patients exhibited higher plasma levels/activities of fibrinogen, factor VII, plasminogen activator inhibitor-1, high-sensitivity C-reactive protein, and oxidized low-density lipoproteins. Lipopolysaccharide-activated monocytes from IGT patients released significantly more TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 in comparison with monocytes from control subjects. Thirty-day treatment with fenofibrate but not with the AHA step 1 diet: 1) improved lipid/lipoprotein profile and glucose metabolism, and 2) reversed or alleviated all the above-mentioned abnormalities. The favorable effects of fenofibrate on plasma high-sensitivity C-reactive protein and on monocyte release of TNF-alpha, IL-1beta, IL-6, and monocyte chemoattractant protein-1 did not correlate with its action on plasma lipids but was related to the improvement in insulin sensitivity and weakly to free fatty acid-lowering action. Our study is the first to show that relatively small disturbances in glucose metabolism are associated with marked and multidirectional abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Moreover, fenofibrate may exhibit early pleiotropic effects in patients with IGT.

Effect of a low glycemic index diet with soy protein and phytosterols on CVD risk factors in postmenopausal women

Objectives Cardiovascular disease (CVD) is the leading cause of death in women. Hyperlipidemia is a major risk factor for CVD, but research suggests that metabolic syndrome and type 2 diabetes are also key factors in CVD in postmenopausal women. Most dietary programs, however, focus only on hyperlipidemia and not on insulin resistance associated with diabetes and metabolic syndrome. This 12-wk trial compared the effects of a dietary program combining a low glycemic index diet with a functional food delivering 30 g of soy protein and 4 g of phytosterols per day (LGID) with a standard dietary program (American Heart Association Step 1 diet; AHAD) in postmenopausal women. Methods Fifty-nine postmenopausal women (average age 54.6 y, range 44–65 y) with a body mass index of 27 to 39 kg/m 2 were randomly assigned to the LGID or the AHAD program for 12 wk. Total caloric intake and exercise were matched in each arm. Results Twenty-seven women completed the LGID program, and 26 completed the AHAD program. The participants on the LGID program showed statistically significant decreases in total cholesterol (15.8%, P = 0.0036 between-group comparison), low-density lipoprotein cholesterol (14.8%, P = 0.004 between-group comparison), and triacylglycerol (44.8%, P = 0.006 between-group comparison). In addition, significant improvements were observed in ratios of total to high-density lipoprotein cholesterol and of triacylglycerol to high-density lipoprotein cholesterol, blood pressure, and Framingham risk assessment for coronary heart disease compared with the AHAD program. Conclusions A significantly greater improvement was observed in CVD risk factors in postmenopausal women on the LGID program (incorporating 30 g of soy protein and 4 g of phytosterols per day) than with a standard therapy.

Effects of Exercise and Nutrition on Memory in Japanese Americans With Impaired Glucose Tolerance

Type 2 diabetes, impaired glucose tolerance (IGT), and associated hyperinsulinemia increase the risk for impaired verbal memory (1–3). In rodents, insulin resistance adversely affects brain structures that support memory (4). In humans, pharmacologic management of diabetes improves cognitive functioning (5,6). Weight loss and exercise decrease the incidence of diabetes (7,8). This study examined whether endurance exercise and dietary fat restriction would improve cognition in Japanese American adults who have a high risk for IGT and type 2 diabetes (9). Adults with IGT were recruited from the Japanese American Community Diabetes Study. Screening and diagnostic procedures have been described previously (10). Participants (15 active and 13 control) completed cognitive testing at baseline and at 6 and 12 months. Treatment was randomly assigned, and groups were equivalent with respect to baseline age ([mean ± SD] active 58.0 ± 9.7 and control 60.6 ± 9.0 years), BMI (active 24.7 ± 3.2 and control 26.7 ± 4.3 kg/m2), V o2max (active 29.5 ± 7.1 and control 27.4 ± 5.6 ml · kg−1 · min−1), and 2-h oral glucose tolerance test (OGTT) glucose levels (active 9.4 ± 1.1 and control 9.4 ± 0.9 mmol/l). Active participants followed an American Heart Association step 2 eucaloric diet (total calories <30% fat, <7% saturated fat, 55% carbohydrate, and 15% protein). An exercise physiologist supervised walking or jogging on a treadmill three times weekly for 1 h. …

A Reduced-Fat Diet and Aerobic Exercise in Japanese Americans With Impaired Glucose Tolerance Decreases Intra-Abdominal Fat and Improves Insulin Sensitivity but not β-Cell Function

Lifestyle modification reduces the risk of developing type 2 diabetes and may have its effect through improving insulin sensitivity, beta-cell function, or both. To determine whether diet and exercise improve insulin sensitivity and/or beta-cell function and to evaluate these effects over time, we quantified insulin sensitivity and the acute insulin response to glucose (AIRg) in 62 Japanese Americans (age 56.5 +/- 1.3 years; mean +/- SE) with impaired glucose tolerance (IGT) who were randomized to the American Heart Association (AHA) Step 2 diet plus endurance exercise (n = 30) versus the AHA Step 1 diet plus stretching (n = 32) for 24 months. beta-Cell function (disposition index [DI]) was calculated as S(i) x AIRg, where S(i) is the insulin sensitivity index. The incremental area under the curve for glucose (incAUCg) was calculated from a 75-g oral glucose tolerance test. Intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas were measured by computed tomography. At 24 months, the Step 2/endurance group had lower weight (63.1 +/- 2.4 vs. 71.3 +/- 2.9 kg; P = 0.004) and IAF (75.0 +/- 7.9 vs. 112.7 +/- 10.4 cm(2); P = 0.03) and SCF (196.5 +/- 18.0 vs. 227.7 +/- 19.9 cm(2); P < 0.001) areas, greater S(i) (4.7 +/- 0.5 vs. 3.3 +/- 0.3 x 10(-5) min . pmol(-1) . l(-1); P = 0.01), and a trend toward lower AIRg (294.9 +/- 50.0 vs. 305.4 +/- 30.0 pmol/l; P = 0.06) and incAUCg (8,217.3 +/- 350.7 vs. 8,902.0 +/- 367.2 mg . dl(-1) . 2 h(-1); P = 0.08) compared with the Step 1/stretching group after adjusting for baseline values. There was no difference in the DI (P = 0.7) between the groups. S(i) was associated with changes in weight (r = -0.426, P = 0.001) and IAF (r = -0.395, P = 0.003) and SCF (r = -0.341, P = 0.01) areas. Thus, the lifestyle modifications decreased weight and central adiposity and improved insulin sensitivity in Japanese Americans with IGT. However, such changes did not improve beta-cell function, suggesting that this degree of lifestyle modifications may be limited in preventing type 2 diabetes over the long term.

Diets containing barley significantly reduce lipids in mildly hypercholesterolemic men and women

Barley has high amounts of soluble fiber but is not extensively consumed in the US diet. This study investigated whether consumption of barley would reduce cardiovascular disease risk factors comparably with that of other sources of soluble fiber. Mildly hypercholesterolemic subjects (9 postmenopausal women, 9 premenopausal women, and 7 men) consumed controlled American Heart Association Step 1 diets for 17 wk. After a 2-wk adaptation period, whole-grain foods containing 0, 3, or 6 g beta-glucan/d from barley were included in the Step 1 diet menus. Diets were consumed for 5 wk each and were fed in a Latin-square design. Fasting blood samples were collected twice weekly. Total cholesterol was significantly lower when the diet contained 3 or 6 g beta-glucan/d from barley than when it contained no beta-glucan; the greatest change occurred in the men and postmenopausal women. HDL and triacylglycerol concentrations did not differ with the 3 amounts of dietary beta-glucan. Large LDL and small VLDL fractions and mean LDL particle size significantly decreased when whole grains were incorporated into the 3 diets. Large LDL and large and intermediate HDL fractions were significantly higher, mean LDL particle size was significantly greater, and intermediate VLDL fractions were significantly lower in the postmenopausal women than in the other 2 groups. A group-by-diet interaction effect was observed on LDL fractions and small LDL particle size. The addition of barley to a healthy diet may be effective in lowering total and LDL cholesterol in both men and women.

Vascular effects of diet and statin in hypercholesterolemic patients

Objective: We investigated whether statin improves nitric oxide (NO) bioactivity and reduces serological markers of oxidant stress and inflammation and whether statin-induced reduction in markers of oxidant stress and inflammation is mediated by improvement in NO bioactivity or lipoprotein changes, compared with American Heart Association Step I Diet (Diet). Methods: We administered diet+placebo and diet+simvastatin 20 mg daily during 14 weeks with randomized order to 31 and 32 patients with coronary artery disease, respectively, with a randomized design. Results: Compared with diet alone, simvastatin significantly improved the percent flow-mediated dilator response to hyperemia and lowered plasma levels of tumor necrosis factor (TNF)-α, intercellular adhesion molecule type-1 (ICAM-1), serum levels of CRP, and fibrinogen ( P<0.001, P<0.001, P=0.035, P<0.001 and P=0.014, respectively). Compared with diet alone, simvastatin lowered but statistically insignificant plasma levels of nitrate and malondialdehyde (MDA) ( P=0.164 and P=0.150, respectively). Further, we observed that patients with the highest pretreatment TNF-α, ICAM-1, and CRP levels showed the greatest extent of reductions on simvastatin. There were significant inverse correlation between low-density lipoprotein (LDL) cholesterol or the ratio of LDL to HDL cholesterol levels and flow-mediated dilation percent ( r=−0.342, P=0.009 and r=−0.356, P=0.006, respectively). Of interest, there were significant inverse correlations between flow-mediated dilation percent and TNF-α levels ( r=−0.329, P=0.010). However, no significant correlations between lipoprotein levels and levels of inflammation markers were determined. Despite the significant changes of lipoproteins, diet alone did not decrease the markers of inflammation. Conclusions: Compared with diet alone, simvastatin significantly reduced markers of inflammation more. These effects were independent of lipoprotein changes.

High-density lipoprotein-cholesterol, its subfractions, and responses to exercise training are dependent on endothelial lipase genotype

Plasma high-density lipoprotein cholesterol (HDL-C) levels are an important independent risk factor for cardiovascular disease (CVD) that can be modified through exercise training. However, levels of HDL-C and its subfractions and their response to standardized exercise training are highly variable among individuals. Such variability suggests that levels of HDL-C, its subfractions, and their response to exercise training may be influenced by genetic variation and the interaction of that genetic variation with physical activity. The endothelial lipase gene (LIPG) may influence HDL-C metabolism and has several recently identified genetic variants. We hypothesized that the LIPG Thr111Ile polymorphism would be associated with variation in HDL-C levels and its subfractions and their response to exercise training. Eighty-three sedentary, healthy 50- to 75-year-old subjects were weight-maintained on an American Heart Association Step 1 Diet and then studied before and after aerobic exercise training. Sample size varied according to outcome measure as complete data was not available for all subjects. Initial age, body composition, and maximum oxygen consumption (Vo2max) did not differ between LIPG genotype groups (CC, n = 41 to 44; CT/TT, n = 37 to 39). Initial total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels were not significantly different between groups. The CT/TT group had lower initial HDL2NMR-C (12 ± 1.0 v 17 ± 1.1 mg/dL; P = .002) and integrated HDL1,2NMR-C (13 ± 1.0 v18 ± 1.1 mg/dL; P = .002) levels and somewhat higher initial levels of integrated HDL3,4,5-C (31 ± 2.2 v 25 ± 2.3 mg/dL; P = .06). With exercise training, Vo2max increased, and body weight, total body fat, and visceral adipose tissue decreased similarly in both groups. With training, HDL-C levels increased twice as much (4.4 ± 0.8 v 1.9 ± 0.9 mg/dL; P = .04), HDL3-C levels increased almost 2-fold greater (3.8 ± 0.7 v 2.2 ± 0.6 mg/dL; P = .07), and HDL5NMR-C levels increased more than 4 times as much (2.2 ± 0.8 v 0.5 ± 0.6 mg/dL; P = .08) in the CC compared to the CT/TT group. We conclude that the LIPG genotype is associated with interindividual variability in HDL-C and its subfractions and their response to exercise training.

Validation of the MEDFICTS dietary questionnaire: a clinical tool to assess adherence to American Heart Association dietary fat intake guidelines.

BackgroundDietary assessment tools are often too long, difficult to quantify, expensive to process, and largely used for research purposes. A rapid and accurate assessment of dietary fat intake is critically important in clinical decision-making regarding dietary advice for coronary risk reduction. We assessed the validity of the MEDFICTS (MF) questionnaire, a brief instrument developed to assess fat intake according to the American Heart Association (AHA) dietary "steps".MethodsWe surveyed 164 active-duty US Army personnel without known coronary artery disease at their intake interview for a primary prevention cardiac intervention trial using the Block food frequency (FFQ) and MF questionnaires. Both surveys were completed on the same intake visit and independently scored. Correlations between each tools' assessment of fat intake, the agreement in AHA step categorization of dietary quality with each tool, and the test characteristics of the MF using the FFQ as the gold standard were assessed.ResultsSubjects consumed a mean of 36.0 ± 13.0% of their total calories as fat, which included saturated fat consumption of 13.0 ± 0.4%. The majority of subjects (125/164; 76.2%) had a high fat (worse than AHA Step 1) diet. There were significant correlations between the MF and the FFQ for the intake of total fat (r = 0.52, P < 0.0001) and saturated fat (r = 0.52, P < 0.0001). Despite these modest correlations, the currently recommended MF cutpoints correctly identified only 29 of 125 (23.3%) high fat (worse than AHA Step 1) diets. Overall agreement for the AHA diet step between the FFQ and MF (using the previously proposed MF score cutoffs of 0–39 [AHA Step 2], 40–70 [Step 1], and >70 [high fat diet]) was negligible (kappa statistic = 0.036). The MF was accurate at the extremes of fat intake, but could not reliably identify the 3 AHA dietary classifications. Alternative MF cutpoints of <30 (Step 2), 30–50 (Step 1), and >50 (high fat diet) were highly sensitive (96%), but had low specificity (46%) for a high fat diet. ROC curve analysis identified that a MF score cutoff of 38 provided optimal sensitivity 75% and specificity 72%, and had modest agreement (kappa = 0.39, P < 0.001) with the FFQ for the identification of subjects with a high fat diet.ConclusionsThe MEDFICTS questionnaire is most suitable as a tool to identify high fat diets, rather than discriminate AHA Step 1 and Step 2 diets. Currently recommended MEDFICTS cutpoints are too high, leading to overestimation of dietary quality. A cutpoint of 38 appears to be providing optimal identification of patients who do not meet AHA dietary guidelines for fat intake.