New insights into the effects on blood pressure of diets low in salt and high in fruits and vegetables and low-fat dairy products

Results from the recent Dietary Approaches to Stop Hypertension (DASH)-Sodium trial provide the latest evidence concerning the effects of dietary patterns and sodium intake on blood pressure. Participants ate either the DASH diet (high in fruits, vegetables and low-fat dairy products, and reduced in saturated and total fat) or a typical US diet. Within each diet arm, participants ate higher, intermediate, and lower sodium levels, each for 30 days. The results indicated lower blood pressure with lower sodium intake for both diet groups. Although some critics would argue otherwise, these findings provide important new evidence for the value of the DASH diet and sodium reduction in controlling blood pressure

FTO Genotype and 2-Year Change in Body Composition and Fat Distribution in Response to Weight-Loss Diets: The POUNDS LOST Trial

Recent evidence suggests that the fat mass and obesity-associated gene (FTO) genotype may interact with dietary intakes in relation to adiposity. We tested the effect of FTO variant on weight loss in response to 2-year diet interventions. FTO rs1558902 was genotyped in 742 obese adults who were randomly assigned to one of four diets differing in the proportions of fat, protein, and carbohydrate. Body composition and fat distribution were measured by dual-energy x-ray absorptiometry and computed tomography. We found significant modification effects for intervention varying in dietary protein on 2-year changes in fat-free mass, whole body total percentage of fat mass, total adipose tissue mass, visceral adipose tissue mass, and superficial adipose tissue mass (for all interactions, P < 0.05). Carriers of the risk allele had a greater reduction in weight, body composition, and fat distribution in response to a high-protein diet, whereas an opposite genetic effect was observed on changes in fat distribution in response to a low-protein diet. Likewise, significant interaction patterns also were observed at 6 months. Our data suggest that a high-protein diet may be beneficial for weight loss and improvement of body composition and fat distribution in individuals with the risk allele of the FTO variant rs1558902

Apolipoprotein E in VLDL and LDL With Apolipoprotein C‐III is Associated With a Lower Risk of Coronary Heart Disease

Background: Low‐density lipoprotein (LDL) with apolipoprotein C‐III (apoC‐III) is the lipoprotein species that most strongly predicts initial and recurring coronary heart disease (CHD) events in several cohorts. Thus, a large portion of the CHD risk conferred by LDL may be attributable to LDL that contains apoC‐III. Very‐low‐density lipoprotein (VLDL) and LDL with apoC‐III have varying amounts of apoE. We hypothesized that a high content of apoE lessens the adverse influence of apoC‐III on the risk of CHD because it promotes the clearance of VLDL and LDL from plasma. Methods and Results: We studied 2 independent cohorts, the Nurses' Health Study, composed of women, and the Health Professionals Follow‐up Study, composed of men. These cohorts contributed to this study 322 women and 418 men initially free of CVD who developed a fatal or nonfatal myocardial infarction during 10 to 14 years of follow‐up and matched controls who remained free of CHD. The apoE content of LDL with apoC‐III was inversely associated with CHD after multivariable adjustment (relative risk for top versus bottom quintile 0.53, 95% CI 0.35 to 0.80). The apoE content of VLDL with apoC‐III had a similar inverse association with CHD. The highest risks were associated with a high apoB concentration and a low apoE content of LDL with apoC‐III or of VLDL+LDL with apoC‐III. The observed associations were in both male and female cohorts and independent of traditional CHD risk factors and of C‐reactive protein. Conclusions: An increased apoE content in VLDL and LDL with apoC‐III was associated with a lower risk of CHD. Strategies to enrich VLDL and LDL in apoE are worth exploring for the prevention of CHD

Selective effects of fatty acids upon cell growth and metabolic regulation

Positional isomers ofcis‐methyleneoctadecanoic acid differed greatly in their efficiency for growth of an unsaturated fatty acid auxotroph ofEscherichia coli upon glucose as a carbon source. The 8, 9, and 11 isomers were more efficient in producing cells (60–70 cells/fmole) than the others (0–7 cells/fmole), although all isomers were found esterified to a similar extent into cellular lipid. WithSaccharomyces cerevisiae mutants, all isomers between 6 and 12 supported some growth of the eukaryotic cells, and the 7 and 9 isomers were slightly more efficient than the 8‐isomer. WhenE. coli were grown with glycerol, all isomers from 5 to 14 supported growth, and those with the substituent near the center of the acyl chain had the greatest efficiency (70 cells/fmole). With the glycerol medium, the pattern of efficiencies for the variouscis‐methylene acyl chains resembled the broad selectivity reported earlier for thecis‐ethylenic isomers in glucose medium, which agreed closely with predictions based upon the physical property of their phospholipid derivatives. Thus, metabolism of glycerol appeared to allow the cyclopropane acyl chains to support cell functions to the limits expected for bulk phase chain‐chain fluidity considerations. This broad specificity was also obtained when cells were grown on glucose with cyclic AMP added to the culture. Therefore, the selective inadequacies of the 5, 6, 7, 10, 12 and 13 isomers in supporting cell growth on glucose may occur through an interaction modified by cAMP and dependent upon reduced cellular levels of cyclic AMP. The highly selective pattern of efficiency of thecis‐methylene acids forE. coli growth on glucose resembles that with the acetylenic acids, but was shifted one carbon atom toward the methyl terminus. This observed selectivity pattern seems due to interactions of the individual acyl chains with cellular protein(s) rather than to chain‐chain interactions in a bulk phase. The ability of certain positional isomers to support cell function equally well in both nutrient conditions suggests that the role of those acyl chain isomers may be independent of metabolite flux or cyclic nucleotide contents of the cell, whereas the actions of other isomeric fatty acids seem closely related to the metabolic status of the cell. A highly selective role for different fatty acids in modulating cellular function seems possible on the basis of the current evidence.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141577/1/lipd0878.pd

Plasma Pentraxin 3 Levels Do Not Predict Coronary Events but Reflect Metabolic Disorders in Patients with Coronary Artery Disease in the CARE Trial

Chronic inflammation closely associates with obesity, metabolic syndrome, diabetes mellitus, and atherosclerosis. Evidence indicates that the immunomodulator pentraxin 3 (PTX3) may serve as a biomarker of these cardiometabolic disorders, but whether PTX3 predicts cardiovascular complications is unknown. We examined the association of plasma PTX3 levels with recurrent coronary events via a prospective, nested, case-control design in the CARE trial. Among 4159 patients who had a prior myocardial infarction 3 to 20 months before enrollment and also had total cholesterol levels <240 mg/dL and LDL cholesterol levels between 115 and 175 mg/dL, we measured plasma PTX3 levels at baseline by high-sensitivity ELISA in 413 cases with recurrent myocardial infarction or coronary death during a 5-year follow-up period, and in 366 sex- and age-matched controls. Cases with recurrent coronary events and controls had similar PTX3 levels, and PTX3 did not predict recurrent coronary events — a finding that contrasts with that of C-reactive protein (CRP) and serum amyloid A (SAA) in this cohort. We then associated PTX3 levels with metabolic disorders. Low plasma PTX3 levels correlated with high body-mass index, waist circumference, and triglycerides; and with low HDL cholesterol. Overall, PTX3 levels correlated inversely with the number of metabolic syndrome components. PTX3 levels also correlated inversely with apoCIII and tissue plasminogen activator, but did not associate with CRP. Although the study further links low PTX3 levels with various features associated with metabolic syndrome, the results do not indicate that PTX3 can predict recurrent coronary events among MI survivors

Healthy Dietary Interventions and Lipoprotein (a) Plasma Levels: Results from the Omni Heart Trial

Background: Increased lipoprotein(a) [Lp(a)] levels are associated with atherosclerotic cardiovascular disease. Studies of dietary interventions on changes in Lp(a) are sparse. We aimed to compare the effects of three healthy dietary interventions differing in macronutrient content on Lp(a) concentration. Methods: Secondary analysis of a randomized, 3-period crossover feeding study including 155 (89 blacks; 66 whites) individuals. Participants were given DASH-type healthy diets rich in carbohydrates [Carb], in protein [Prot] or in unsaturated fat [Unsat Fat] for 6 weeks each. Plasma Lp(a) concentration was assessed at baseline and after each diet. Results: Compared to baseline, all interventional diets increased mean Lp(a) by 2 to 5 mg/dl. Unsat Fat increased Lp(a) less than Prot with a difference of 1.0 mg/dl (95% CI, −0.5, 2.5; p = 0.196) in whites and 3.7 mg/dl (95% CI, 2.4, 5.0; p<0.001) in blacks (p-value between races = 0.008); Unsat Fat increased Lp(a) less than Carb with a difference of −0.6 mg/dl, 95% CI, −2.1, 0.9; p = 0.441) in whites and −1.5 mg/dl (95% CI, −0.2, −2.8; p = 0.021) in blacks (p-value between races = 0.354). Prot increased Lp(a) more than Carb with a difference of 0.4 mg/dl (95% CI, −1.1, 1.9; p = 0.597) in whites and 2.2 mg/dl (95%CI, 0.9, 3.5; p = 0.001) in blacks (p-value between races = 0.082). Conclusion: Diets high in unsaturated fat increased Lp(a) levels less than diets rich in carbohydrate or protein with greater changes in blacks than whites. Our results suggest that substitutions with dietary mono- and polyunsaturated fatty acids in healthy diets may be preferable over protein or carbohydrates with regards to Lp(a). Trial Registration Clinicaltrials.gov NCT0005135

A prospective study of plasma fish oil levels and incidence of myocardial infarction in U.S. male physicians

AbstractObjectives. This study evaluated whether increased intake of fish oils (eicosapentaenoic and docosahexaenoic acids) might reduce the risk of coronary heart disease.Background.Observational and clinical studies have suggested that increased intake of fish oils, as reflected in plasma levels of fish oils, may reduce the risk of myocardial infarction.Methods.A nested case-control study was conducted among the 14,916 participants in the Physicians' Health Study with a sample of plasma before randomization. Each participant with myocardial infarction occurring during the first 5 years of follow-up was matched by smoking status and age with a randomly chosen control participant who had not developed coronary heart disease.Results.Mean levels of fish oils (with 95% confidence interval [CI] for paired differences and p values) in case and control participants, expressed as present of total fatty acids, were, for eicosapentaenoic acid, 0.26 versus 0.25 (95% CI - 0.03 to 0.05, p = 0.70) in cholesterol esters and 0.56 versus 0.54 (95% CI -0.04 to 0.09, p = 0.44) in phospholipids, and for docosahexaenoic acid, 0.23 versus 0.24 (95% CI -0.07 to 0.04, p = 0.64) in cholesterol esters and 2.22 versus 2.14 (95% CI -0.10 to 0.27, p = 0.36) in phospholipids. Results adjusted for major cardiovascular risk factors showed a very similar lack of association between fish oil levels and the incidence of myocardial infarction.Conclusions.These results indicate no beneficial effect of increased fish oil consumption on the incidence of a first myocardial infarction. However, the effect of very high levels of fish oils could not be evaluated

Racial differences between African-American and white women in insulin resistance and visceral adiposity are associated with differences in apoCIII containing apoAI and apoB lipoproteins

Background: African-Americans have higher HDL, less visceral adipose tissue (VAT) and lower triglyceride (TG) and apoCIII concentrations than whites, despite being more insulin-resistant. We studied in African-American and white women the influences of insulin resistance and VAT on the apoAI concentrations of two HDL subspecies, one that contains apoCIII that is associated with increased risk of coronary heart disease (CHD) and one that does not have apoCIII that is associated with decreased CHD; and on the apoCIII concentrations of HDL and of the apoB lipoproteins. Methods: The participants were 32 women (14 African-Americans, 18 white) of similar age (39 ± 12 vs. 42 ± 11y). Mean BMI was 34 kg/m2 in the African-Americans compared to 30 in the whites. A standard diet (33% fat, 52% carbohydrate, 15% protein) was provided for 7 days followed by a test meal (40% fat, 40% carbohydrate, 20% protein) on Day 8. Insulin sensitivity index (SI) was calculated from the minimal model. Results: After controlling for SI, African-Americans have a higher mean apoAI level in HDL with apoCIII compared with whites (12.9 ± 2.8 and 10.9 ± 2.9 mg/dL, respectively, P = 0.05). SI was associated with higher apoAI in HDL with apoCIII, whereas VAT was not associated with this HDL subspecies. This pattern of results was reversed for apoCIII concentrations in apoB lipoproteins. After adjusting for SI, African-Americans had lower apoCIII in apoB lipoproteins. SI was associated with lower apoCIII in total apoB lipoproteins, whereas VAT was associated with higher apoCIII in all the apoB lipoproteins. Additional adjustment for VAT tended to reduce the difference in apoCIII between the groups. Conclusions: African-American women have a higher HDL with apoCIII level than whites when controlled for insulin sensitivity. African-Americans have lower insulin sensitivity. Insulin sensitivity is associated with higher levels of HDL with apoCIII. ApoCIII levels in VLDL are lower in African-American women than whites, also affected by insulin sensitivity which is associated with low apoCIII in VLDL. VAT has a strong association with apoCIII in apoB lipoproteins but not with apoAI in HDL with apoCIII. Trial registration ClinicalTrials.gov Identifier: NCT0048486

IRS1 Genotype Modulates Metabolic Syndrome Reversion in Response to 2-Year Weight-Loss Diet Intervention: The POUNDS LOST trial

OBJECTIVE Genetic variants near IRS1 are associated with features of the metabolic syndrome (MetS). We examined whether genetic variants near IRS1 might modulate the effects of diets varying in fat content on the MetS status in a 2-year weight-loss trial. RESEARCH DESIGN AND METHODS Two variants near IRS1, rs1522813 and rs2943641, were genotyped in 738 overweight/obese adults (age 60 ± 9 years; BMI 32.7 ± 3.9 kg/m2) randomly assigned to one of four weight-loss diets (a deficit of 750 kcal/day of caloric intake from baseline) varying in macronutrient contents for 2 years. We compared MetS status of high-fat (40% of caloric intake; n = 370) and low-fat (20% caloric intake; n = 368) diet groups differentiated by genotypes (rs1522813 A-allele carriers and noncarriers and rs2943641T-allele carriers and noncarriers). RESULTS Among rs1522813 A-allele carriers, the reversion rates of the MetS were higher in the high-fat diet group than those in the low-fat diet group over the 2-year intervention (P = 0.002), while no significant difference between diet groups was observed among noncarriers (P = 0.27). The genetic modulation on dietary effect was independent of weight changes. The odds ratio (OR) for the 2-year reversion of the MetS was 2.88 (95% CI 1.25–6.67) comparing the high-fat and low-fat diets among rs1522813 A-allele carriers, while the corresponding OR was 0.83 (0.36–1.92) in noncarriers. The variant rs2943641 was not observed to modulate dietary effects on the MetS status. CONCLUSIONS Our data suggest that high-fat weight-loss diets might be more effective in the management of the MetS compared with low-fat diets among individuals with the A-allele of the rs1522813 variant near IRS1

The Effects of Carbohydrate, Unsaturated Fat, and Protein Intake on Measures of Insulin Sensitivity: Results from the OmniHeart Trial

OBJECTIVE Impaired insulin sensitivity increases the risk of cardiovascular disease. Although calorie restriction and weight loss increase insulin sensitivity, the effects of modifying macronutrient composition on insulin sensitivity are uncertain. The purpose of this study is to determine the effects on insulin sensitivity of a carbohydrate-rich diet (CARB; similar to the Dietary Approaches to Stop Hypertension [DASH] diet), a protein-rich diet (PROT; protein predominantly from plant sources), and an unsaturated fat–rich diet (UNSAT; predominantly monounsaturated). RESEARCH DESIGN AND METHODS This study was a randomized, controlled, three-period, crossover feeding study. The study participants were 164 individuals with prehypertension or stage 1 hypertension without diabetes. Diets were administered for 6 weeks each, with a washout period between diets of 2–4 weeks. Weight was held constant throughout the study. For our primary outcome, we calculated the quantitative insulin sensitivity check index (QUICKI) using the end-of-period fasting serum glucose and insulin. QUICKI is a validated measure of insulin sensitivity. The primary analyses used generalized estimating equations. RESULTS At baseline, mean (SD) BMI was 30.2 (6.1) kg/m2, and mean (SD) QUICKI was 0.35 (0.04). The UNSAT diet increased QUICKI by 0.005, more than the CARB diet (P = 0.04). PROT had no significant effect compared with CARB. CONCLUSIONS A diet that partially replaces carbohydrate with unsaturated fat may improve insulin sensitivity in a population at risk for cardiovascular disease. Given the well-recognized challenges of sustaining weight loss, our results suggest an alternative approach for improving insulin sensitivity