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Long-term health effects of the three major diets under self-management with advice, yields high adherence and equal weight loss, but very different long-term cardiovascular health effects as measured by myocardial perfusion imaging and specific markers o
Clinical Cardiology
Abstract
Background
Obesity is caused by eating behaviours. Adherence to all diets has been extremely poor, thus, comparative data on health effects of different diets over periods of a year or more are limited. This study was designed to treat the root causes of obesity by modifying the eating behaviours and to compare the long‐term (one year) cardiovascular health affects using three major diets under isocaloric conditions.
Methods
120 obese, otherwise healthy, adults were recruited including 63 men and 57 women with a mean age and BMI of 43.7 years and 42.4 respectively. Participants agreed to follow and self‐manage diet with follow‐up at six‐week intervals to achieve 1500‐1600 calorie intake of assigned diet type: low‐to moderate‐fat, lowered‐carbohydrate, or vegan. Adherence, weight loss, changes in 14 cardiovascular lipids and coronary blood flow health risk indices were measured.
Results
One‐year body mass changes did not differ by diet (P>.999). Effect sizes (R, R2) were statistically significant for all indices. Coronary blood flow, R (CI95%) = .48 to .69, improved with low‐to‐moderate‐fat and declined with lowered carbohydrate diets. Inflammatory factor Interleukin‐6 (R = .51 to .71) increased with lowered carbohydrate and decreased with low‐to‐moderate‐fat diets.
Conclusions
One‐year lowered‐carbohydrate diet significantly increases cardiovascular risks, while a low‐to‐moderate‐fat diet significantly reduces cardiovascular risk factors. Vegan diets were intermediate. Lowered‐carbohydrate dieters were least inclined to continue dieting after conclusion of the study. Reductions in coronary blood flow reversed with appropriate dietary intervention. The major dietary effect on atherosclerotic coronary artery disease is inflammation and not weight loss.
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... The recently accepted special report [1] from the American Heart Association (AHA) and the American College of Cardiology (ACC) makes recommendations regarding the primary prevention of atherosclerotic coronary artery disease (ASCAD); recommendations, which are based upon looking at various factors which are credited with causing the inflammatory process associated with ASCAD [2,3]. The primary author recognizes his responsibility in this debate as he is the creator of the "Inflammation and Heart Disease" and "Angina" Theories [2,3] shown in Figure 1. ...
... The recently accepted special report [1] from the American Heart Association (AHA) and the American College of Cardiology (ACC) makes recommendations regarding the primary prevention of atherosclerotic coronary artery disease (ASCAD); recommendations, which are based upon looking at various factors which are credited with causing the inflammatory process associated with ASCAD [2,3]. The primary author recognizes his responsibility in this debate as he is the creator of the "Inflammation and Heart Disease" and "Angina" Theories [2,3] shown in Figure 1. It is therefore his responsibility to set the record straight. ...
... To merely measure them ignores this variability. The determination of the extent or change in the extent of disease ("Health-Spectrum") must be directly measured (quantified) and not inferred or guesstimated from these surrogate blood markers [1][2][3]. ...
Background: Scientifically published studies have demonstrated that all isotopes, including Sestamibi redistribute. Measurement of this redistribution using FMTVDM©℗ provides an accurate method for determining wash-in and washout. Methods: Using FMTVDM©℗ 1040 human coronary arteries were studied to determine their wash-in and washout redistribution measured on a pixel-by-pixel basis. From FMTVDM©℗ the percent diameter stenosis (%DS) for each artery was determined. This %DS was then used to calculate coronary flow reserve (Calculated SFR) using a proprietary quadratic equation (QCFR©, FCFR©) previously derived from quantitative coronary arteriography (QCA) measurements. These calculated CFR values were then compared with the actual measured CFR obtained directly from QCA. Results: The results of the calculated CFR from FMTVDM©℗ with that obtained by direct QCA measurement showed a regression analysis of y= (0.8758•x)+0.4291, where y=the QCFR© and x=the QCA measured CFR. The R2 value (coefficient of determination) for this demonstrated a strong relationship at 0.87582. Conclusions: The use of the FMTVDM©℗ for measurement of isotope redistribution, including Sestamibi, provides an accurate quantitative method for determining both redistribution wash-in and redistribution washout, from which %DS can be calculated on a pixel-by-pixel basis. This %DS can then be used with the proprietary equation (QCFR©, FCFR©) to calculate the CFR directly from the MPI result using FMTVDM©℗. The implementation of this power tool, will provide for additional determination of the physiological effect of CAD without requiring additional QCA equipment and expertise costs, making QCFR© possible in most if not all hospitals with nuclear medicine departments.
Presents an integrative theoretical framework to explain and to predict psychological changes achieved by different modes of treatment. This theory states that psychological procedures, whatever their form, alter the level and strength of self-efficacy. It is hypothesized that expectations of personal efficacy determine whether coping behavior will be initiated, how much effort will be expended, and how long it will be sustained in the face of obstacles and aversive experiences. Persistence in activities that are subjectively threatening but in fact relatively safe produces, through experiences of mastery, further enhancement of self-efficacy and corresponding reductions in defensive behavior. In the proposed model, expectations of personal efficacy are derived from 4 principal sources of information: performance accomplishments, vicarious experience, verbal persuasion, and physiological states. Factors influencing the cognitive processing of efficacy information arise from enactive, vicarious, exhortative, and emotive sources. The differential power of diverse therapeutic procedures is analyzed in terms of the postulated cognitive mechanism of operation. Findings are reported from microanalyses of enactive, vicarious, and emotive modes of treatment that support the hypothesized relationship between perceived self-efficacy and behavioral changes. (21/2 p ref)
Nineteen people without prior history of documented heart disease were studied for 8 months to determine the effect of treatment based on an immunologic unified theory of vascular disease. Subjects underwent myocardial perfusion imaging to quantify the extent and severity of coronary artery disease, along with assessment of wall motion abnormalities and ejection fraction by both nuclear and echocardiographic methods. These tests were repeated at the end of the study. Treatment consisted of dietary changes, treatment of cholesterol, triglycerides, homocysteine, lipoprotein (a), fibrinogen, C-reactive protein, and infection. Patients who followed the dietary recommendations demonstrated statistically reduced disease in all three major coronary arteries, whereas those individuals who followed high- protein diets demonstrated statistically greater levels of disease.
Significance
We present an unusual mechanism for the well-known association between red meat consumption and carcinoma risk involving the nonhuman sialic acid N -glycolylneuraminic acid (Neu5Gc). We first evaluate the Neu5Gc content of various foods to show that red meats are particularly rich in orally bioavailable Neu5Gc and then investigate human-like Neu5Gc-deficient mice fed this form of Neu5Gc. When such mice were challenged with anti-Neu5Gc antibodies, they developed evidence of systemic inflammation. Long-term exposure to this combination resulted in a significantly higher incidence of carcinomas (five-fold increase) and an association with Neu5Gc accumulation in the tumors. Similar mechanisms may contribute to the association of red meat consumption with other diseases, such as atherosclerosis and type 2 diabetes, which are also exacerbated by inflammation.
Patients with cancer have circulating heterophile antibodies that agglutinate animal red cells via recognition of the mammalian cell surface sialic acid N-glycolylneuraminic acid (Neu5Gc), which was long considered an oncofetal antigen in humans. However, humans are genetically deficient in Neu5Gc production and instead metabolically accumulate Neu5Gc from dietary sources, particularly red meats and milk products. Moreover, mice with a human-like defect showed no alternate pathway for Neu5Gc synthesis and even normal humans express anti-Neu5Gc antibodies. We show here that human tumors accumulate Neu5Gc that is covalently attached to multiple classes of glycans. The paradox of human tumor Neu5Gc accumulation in the face of circulating anti-Neu5Gc antibodies was hypothesized to be due to facilitation of tumor progression by the resulting low-grade chronic inflammation. Indeed, murine tumors expressing human-like levels of Neu5Gc show accelerated growth in syngeneic mice with a human-like Neu5Gc deficiency, coincident with the induction of anti-Neu5Gc antibodies and increased infiltration of inflammatory cells. Transfer of polyclonal monospecific syngeneic mouse anti-Neu5Gc serum also enhanced growth of transplanted syngeneic tumors bearing human-like levels of Neu5Gc, with tumors showing evidence for antibody deposition, enhanced angiogenesis and chronic inflammation. These effects were suppressed by a cyclooxygenase-2 inhibitor, a drug type known to reduce human carcinoma risk. Finally, affinity-purified human anti-Neu5Gc antibodies also accelerate growth of Neu5Gc-containing tumors in Neu5Gc-deficient mice. Taken together, the data suggest that the human propensity to develop diet-related carcinomas is contributed to by local chronic inflammation, resulting from interaction of metabolically-accumulated dietary Neu5Gc with circulating anti-Neu5Gc antibodies.
• antibodies
• COX-2
• Neu5Gc
• red meat
• sialic acid
Using high-pressure liquid chromatography (HPLC) and gas-liquid chromatography/mass spectrometry (GLC/MS), we have confirmed the existence of several sialic acid modifications in the adult rat and human colon. The major O-acetylated sialic acid in both species is 9-O-acetyl-N-acetylneuraminic acid; N-glycolylneuraminic acid is a major component of the adult rat colon. Both of these major modifications were found to be developmentally regulated during the perinatal period in the rat. The N-glycolyl modification is present prenatally and disappears rapidly in the postnatal period. It reappears in the preweanling period, reaching levels at weaning comparable to those found prenatally. In contrast, the 9-O-acetyl modification is very low prenatally, and undergoes a marked increase shortly after birth in both the rat and human colon. The difference in the kinetics of appearance of the two modifications suggests that they are independently regulated. Regulation of these modifications seems to be influenced by exposure to bacterial by-products or environmental stimuli. The N-glycolyl modification in the rat colon reappeared at weaning, a time of major change in enteral colonic substances. Spontaneously aborted human fetuses, including three with intrauterine infection at 27, 33, and 35 wk of gestation, showed adult levels of O-acetylation in colonic tissue. Also, although O-acetylation in freshly isolated colon tumor specimens was only somewhat lower than that in the adult normal colon, all established colon cancer cell lines studied showed minimal O-acetylation.
Recent research has demonstrated that successful simultaneous treatment of multiple risk factors including cholesterol, triglycerides, homocysteine, lipoprotein (a) [Lp(a)], fibrinogen, antioxidants, endothelial dysfunction, inflammation, infection, and dietary factors can lead to the regression of coronary artery disease and the recovery of viable myocardium. However, preliminary work revealed that a number of individuals enrolled in the original study went on popular high-protein diets in an effort to lose weight. Despite increasing numbers of individuals following high-protein diets, little or no infor mation is currently available regarding the effect of these diets on coronary artery disease and coronary blood flow.
Twenty-six people were studied for 1 year by using myocardial perfusion imaging (MPI), echocardiography (ECHO), and serial blood work to evaluate the extent of changes in regional coronary blood flow, regional wall motion abnormalities, and several independent variables known to be important in the development and progression of coronary artery disease. Treatment was based on homocysteine, Lp (a), C-reactive protein (C-RP), triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and fibrinogen levels. Each variable was independently treated as previously reported. MPI and ECHO were performed at the beginning and end of the study for each individual. The 16 people (treatment group/TG) studied modified their dietary intake as instructed. Ten additional individuals elected a different dietary regimen consisting of a "high-protein" (high protein group/HPG) diet, which they believed would "improve" their overall health.
Patients in the TG demonstrated a reduction in each of the independent variables studied with regression in both the extent and severity of coronary artery disease (CAD) as quantitatively measured by MPI. Recovery of viable myocardium was seen in 43.75% of myocardial segments in these patients, documented with both MPI and ECHO evalu ations. Individuals in the HPG showed worsening of their independent variables. Most notably, fibrinogen, Lp (a), and C-RP increased by an average of 14%, 106%, and 61% respectively. Progression of the extent and severity of CAD was documented in each of the vascular territories with an overall cumulative progression of 39.7%. The differences between progression and extension of disease in the HPG and the regression of disease in the TG were statistically (p < 0.001) significant.
Patients following recommended treatment for each of the independent variables were able to regress both the extent and severity of their coronary artery disease (CAD), as well as improve their myocardial wall motion (function) while following the prescribed medical and dietary guidelines. However, individuals receiving the same medical treatment but following a high-protein diet showed a worsening of independent risk factors, in addition to progression of CAD. These results would suggest that high-protein diets may precipitate progression of CAI) through increases in lipid deposition and inflammatory and coagulation pathways.
Over 60% of Americans are overweight and a number of popular diets have been advocated, often without evidence, to alleviate this public health hazard. This study was designed to investigate the effects of several diets on weight loss, serum lipids, and other cardiovascular disease risk factors. One hundred men and women followed one of four dietary programs for 1 year: a moderate-fat (MF) program without calorie restriction (28 patients); a low-fat (LF) diet (phase I) (16) ; a MF, calorie-controlled (phase II) diet (38 patients); and a high-fat (HF) diet (18 subjects) [corrected]. Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), homocysteine (Ho), and lipoprotein(a) [Lp(a)], were measured every 4th month. The TC/HDL-C ratio was calculated and fibrinogen levels were measured at baseline and after one year. The MF diet resulted in a 2.6% (NS) decrease in weight compared with 18.4% (p=0.045) decrease in patients on phase I, 12.6% (p=0.0085) decrease in patients on phase II, and 13.7% (p=0.025) decrease in those on the HF diet. TC was reduced by 5% (NS) in the MF group, 39.1% (p=0.0005) in the phase I group, and 30.4% (p=0.0001) in the phase II group. HF group had a 4.3% (NS) increase in TC. LDL-C was reduced by 6.1% (NS) on MF, 52.0% (p=0.0001) on phase I, and 38.8% (p=0.0001) on phase II. Patients on HF had a 6.0% (NS) increase in LDL-C. There were nonsignificant reductions in HDL-C in those on MF (-1.5%) and HF (-5.8%). Patients on phase I showed an increase in HDL-C of 9.0% (NS), while those on phase II diet had a 3.6% increase (NS) in HDL-C. TC/HDL-C increased (9.8%) only in patients following the high-fat diets (NS). Patients on MF had a 5.3% (NS) reduction in TC/HDL-C, while those on LF had significant reductions on the phase I ( -45.8%; p=0.0001) diet and phase II diet (-34.7%; p=0.0001). TG levels increased on both the MF (1.0%) and HF (5.5%) diets, although neither was statistically significant. People following the phase I and II diets showed reductions of 37.3% and 36.9%, respectively. Ho levels increased by 9.7% when people followed the MF diet and by 12.4% when they followed the HF diet. Patients following the phase I and phase II diets showed reductions of 13.6% and 14.6%, respectively. Only those following phase II diets showed a tendency toward significant improvement (p=0.061). Lp(a) levels increased by 4.7% following the MF (NS) diet and by 31.0% (NS) on the HF diet. Patients following phase I showed a 7.4% (NS) reduction and a 10.8% reduction (NS) following phase II. Fibrinogen levels increased only in individuals following HF diets (11.9%), while patients following MF (-0.6%), phase I (-11.0%), and phase II (-6.3%) diets showed nonsignificant reductions in fibrinogen. Patients on MF demonstrated nonsignificant reductions in weight, LDL-C, TC, HDL-C, TC/HDL-C ratios, and fibrinogen and nonsignificant increases in TGs, Lp(a), and homocysteine. There was significant weight loss in patients on phase I and II and HF diets after 1 year. Reductions in TC, LDL-C, TGs, and TC/HDL ratios were significant only in patients either following a LF diet or a MF, calorically reduced diet. Only patients following HF diets showed a worsening of each cardiovascular disease risk factor (LDL-C, TG, TC, HDL-C, TC/HDL ratio, Ho, Lp(a), and fibrinogen), despite achieving statistically significant weight loss.
We use a regression framework and nationally representative data to compute aggregate overweight- and obesity-attributable medical spending for the United States and for select payers. Combined, such expenditures accounted for 9.1 percent of total annual U.S. medical expenditures in 1998 and may have been as high as dollar 78.5 billion (dollar 92.6 billion in 2002 dollars). Medicare and Medicaid finance approximately half of these costs.
We report here that human T cells give much stronger proliferative responses to specific activation via the T cell receptor (TCR) than those from chimpanzees, our closest evolutionary relatives. Nonspecific activation using phytohemagglutinin was robust in chimpanzee T cells, indicating that the much lower response to TCR simulation is not due to any intrinsic inability to respond to an activating stimulus. CD33-related Siglecs are inhibitory signaling molecules expressed on most immune cells and are thought to down-regulate cellular activation pathways via cytosolic immunoreceptor tyrosine-based inhibitory motifs. Among human immune cells, T lymphocytes are a striking exception, expressing little to none of these molecules. In stark contrast, we find that T lymphocytes from chimpanzees as well as the other closely related "great apes" (bonobos, gorillas, and orangutans) express several CD33-related Siglecs on their surfaces. Thus, human-specific loss of T cell Siglec expression occurred after our last common ancestor with great apes, potentially resulting in an evolutionary difference with regard to inhibitory signaling. We confirmed this by studying Siglec-5, which is prominently expressed on chimpanzee lymphocytes, including CD4 T cells. Ab-mediated clearance of Siglec-5 from chimpanzee T cells enhanced TCR-mediated activation. Conversely, primary human T cells and Jurkat cells transfected with Siglec-5 become less responsive; i.e., they behave more like chimpanzee T cells. This human-specific loss of T cell Siglec expression associated with T cell hyperactivity may help explain the strikingly disparate prevalence and severity of T cell-mediated diseases such as AIDS and chronic active hepatitis between humans and chimpanzees.
Xeno-cell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type-1 diabetes for addressing organ-shortage. However, in human, natural and elicited antibodies specific for pig xenoantigens, α(1,3)-galactose (GAL) and N-glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xeno-islet rejection. We obtained double knockout pigs (DKO) lacking GAL and Neu5Gc. As Neu5Gc-/- mice exhibit glycemic dysregulations and pancreatic β-cell dysfunctions, we evaluated islet function and glucose metabolism regulation in DKO pigs. Isolation of islets from neonate piglets yielded identical islet equivalent quantities (IEQs) to that obtained from control wild-type pigs. In contrast to wild-type islets, DKO islets did not induce anti-Neu5Gc antibody when grafted in CMAH-/- mice and exhibited in vitro normal insulin secretion stimulated by glucose and theophylline. Adult DKO pancreata showed no histological abnormalities and immunostaining of insulin and glucagon were similar to that from wild-types. Blood glucose, insulin, C-peptide, insulin:glucagon ratio and HOMA-IR in fasting adult DKO pigs, and blood glucose and C-peptide changes after I.V. glucose or insulin administration were similar to wild-types. This first evaluation of glucose homeostasis in DKO pigs for two major xenoantigens paves the way to their use in (pre)clinical studies.
The prevalence of vascular disease has increased in both the United States and Europe since the end of World War II. The pathogenesis of vascular disease has been directly linked to changes in dietary habits and lifestyle practices and the discovery of penicillin by Sir Alexander Fleming in 1928, which led to a reduction in deaths secondary to bacterial infections. Multiple theories have evolved regarding the various factors associated with an increased risk of vascular disease. It is important to realize, however, that the study of the pathogenesis and subsequent treatment of vascular disease requires a “bigger picture” approach rather than consideration of just one or two factors. In this chapter, we review the contributions made by many investigators who have looked at one or more of these issues. We discuss the relationship (Fleming’s Unified Theory of Vascular Disease1) between these factors (Figure 64.1) and their overall role in the pathogenesis of vascular disease, including coronary artery disease, carotid artery disease, and peripheral vascular disease. We also review the importance and benefit of looking at each of these contributing factors when evaluating and treating an individual with vascular disease.
Context: The scarcity of data addressing the health effects of popular diets is an important public health concern, especially since patients and physicians are interested in using popular diets as individualized eating strategies for disease prevention. Objective: To assess adherence rates and the effectiveness of 4 popular diets (Atkins, Zone, Weight Watchers, and Ornish) for weight loss and cardiac risk factor reduction. Design, Setting, and Participants: A single-center randomized trial at an academic medical center in Boston, Mass, of overweight or obese (body mass index: mean, 35; range, 27-42) adults aged 22 to 72 years with known hypertension, dyslipidemia, or fasting hyperglycemia. Participants were enrolled starting July 18, 2000, and randomized to 4 popular diet groups until January 24, 2002. Intervention: A total of 160 participants were randomly assigned to either Atkins (carbohydrate restriction, n=40). Zone (macronutrient balance, n=40), Weight Watchers (calorie restriction, n=40), or Ornish (fat restriction, n=40) diet groups. After 2 months of maximum effort, participants selected their own levels of dietary adherence. Main Outcome Measures: One-year changes in baseline weight and cardiac risk factors, and self-selected dietary adherence rates per self-report. Results: Assuming no change from baseline for participants who discontinued the study, mean (SD) weight loss at 1 year was 2.1 (4.8) kg for Atkins (21 [53 %] of 40 participants completed, P=.009), 3.2 (6.0) kg for Zone (26 [65%] of 40 completed, P=.002), 3.0 (4.9) kg for Weight Watchers (26 [65%] of 40 completed, P<.001), and 3.3 (7.3) kg for Ornish (20 [50%] of 40 completed, P=.007). Greater effects were observed in study completers. Each diet significantly reduced the low-density lipoprotein/high-density lipoprotein (HDL) cholesterol ratio by approximately 10% (all P<.05), with no significant effects on blood pressure or glucose at 1 year. Amount of weight loss was associated with self-reported dietary adherence level (r=0.60; P<.001) but not with diet type (r=0.07; P= .40). For each diet, decreasing levels of total/HDL cholesterol, C-reactive protein, and insulin were significantly associated with weight loss (mean r=0.36, 0.37, and 0.39, respectively) with no significant difference between diets (P= .48, P= .57, P= .31, respectively). Conclusions: Each popular diet modestly reduced body weight and several cardiac risk factors at 1 year. Overall dietary adherence rates were low, although increased adherence was associated with greater weight loss and cardiac risk factor reductions for each diet group.
Darwinian evolution of humans from our common ancestors with nonhuman primates involved many gene-environment interactions at the population level, and the resulting human-specific genetic changes must contribute to the "Human Condition." Recent data indicate that the biology of sialic acids (which directly involves less than 60 genes) shows more than 10 uniquely human genetic changes in comparison with our closest evolutionary relatives. Known outcomes are tissue-specific changes in abundant cell-surface glycans, changes in specificity and/or expression of multiple proteins that recognize these glycans, and novel pathogen regimes. Specific events include Alu-mediated inactivation of the CMAH gene, resulting in loss of synthesis of the Sia N-glycolylneuraminic acid (Neu5Gc) and increase in expression of the precursor N-acetylneuraminic acid (Neu5Ac); increased expression of alpha2-6-linked Sias (likely because of changed expression of ST6GALI); and multiple changes in SIGLEC genes encoding Sia-recognizing Ig-like lectins (Siglecs). The last includes binding specificity changes (in Siglecs -5, -7, -9, -11, and -12); expression pattern changes (in Siglecs -1, -5, -6, and -11); gene conversion (SIGLEC11); and deletion or pseudogenization (SIGLEC13, SIGLEC14, and SIGLEC16). A nongenetic outcome of the CMAH mutation is human metabolic incorporation of foreign dietary Neu5Gc, in the face of circulating anti-Neu5Gc antibodies, generating a novel "xeno-auto-antigen" situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative "hot spot" of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.
Although humans and chimpanzees share >99% identity in alignable protein sequences, they differ surprisingly in the incidence and severity of some common diseases. In general, humans infected with various viruses, such as HIV and hepatitis C virus, appear to develop stronger reactions and long-term complications. Humans also appear to suffer more from other diseases associated with over-reactivity of the adaptive immune system, such as asthma, psoriasis, and rheumatoid arthritis. In this study, we show that human T cells are more reactive than chimpanzee T cells to a wide variety of stimuli, including anti-TCR Abs of multiple isotypes, l-phytohemagglutin, Staphylococcus aureus superantigen, a superagonist anti-CD28 Ab, and in MLRs. We also extend this observation to B cells, again showing a human propensity to react more strongly to stimuli. Finally, we show a relative increase in activation markers and cytokine production in human lymphocytes in response to uridine-rich (viral-like) ssRNA. Thus, humans manifest a generalized lymphocyte over-reactivity relative to chimpanzees, a finding that is correlated with decreased levels of inhibitory sialic acid-recognizing Ig-superfamily lectins (Siglecs; particularly Siglec-5) on human T and B cells. Furthermore, Siglec-5 levels are upregulated by activation in chimpanzee but not human lymphocytes, and human T cell reactivity can be downmodulated by forced expression of Siglec-5. Thus, a key difference in the immune reactivity of chimp and human lymphocytes appears to be related to the differential expression of Siglec-5. Taken together, these data may help explain human propensities for diseases associated with excessive activation of the adaptive immune system.
In part 1 of a three-part study, 14 novice readers and 6 experienced cardiologists interpreted phantom images of known stenosis severity. No difference between the interpretations of experienced and novice readers was detectable. Visual estimates of "moderately" severe stenosis were 30% higher than actual percent diameter stenosis. In part 2 of the study, visual interpretation of percent diameter stenosis from 212 stenoses on 241 arteriograms was compared with quantitative coronary arteriographic assessment. The visual analysis overestimated disease severity in arteries with greater than or equal to 50% diameter stenosis (except for right coronary lesions) and underestimated severity in all arteries with less than 50% diameter stenosis. Of the 241 arteriograms, 40 had quantitative and visual analysis of all three coronary arteries for assessment of significant disease. In only 62% of the cases did visual and quantitative methods agree on the presence of severe disease; visual estimates diagnosed significantly (p less than 0.05) more three-vessel disease. In part 3 of the study, comparison of percent diameter stenosis by visual estimate with quantitative coronary arteriographic assessment before and after balloon angioplasty of 38 stenoses showed that visual interpretation significantly (p less than 0.001) overestimated initial lesion severity and underestimated stenosis severity after angioplasty.
Determination of the effects of dietary modification and hyperlipidemic medications in the elderly (> sixty-five years of age) patient has not been significantly investigated to date despite knowledge that elevated cholesterol (TC) and triglyceride (TG) levels increase the risk of coronary artery disease (CAD).
Twenty-seven individuals were placed into one of three treatment groups and longitudinally followed up to examine the effects of diet and hyperlipidemic medications on TC and TG levels. Group 1 (n = 14) received neither dietary nor drug therapy. Group 2 (n = 9) received dietary counseling without concomitant hyperlipidemic medications. Subjects in group 3 (n = 4) underwent dietary instruction for six months and hyperlipidemic medication(s) for eighteen months.
Subjects in group 1 demonstrated a statistical increase in TC (P < or = 0.001) during the study. Patients in groups 2 (P < or = 0.001) and 3 (P < or = 0.05) demonstrated statistical improvement in TC reduction during dietary counseling. The effect on TC was blunted in group 3 after dietary counseling was discontinued. Reductions in TG levels were significant (P < or = 0.001) only for patients in group 2.
Elderly individuals were able to significantly reduce both TC and TG levels by dietary modification alone. Minimal improvement was seen with the addition of hyperlipidemic medications.
Assessment of coronary artery disease by quantitative coronary arteriography (QCA), while highly accurate, is more expensive than visual estimates of disease and involves the measurement of numerous variables requiring specialized equipment and personnel, thereby reducing its clinical applicability. In part 1 of this paper, the independent variables that influence flow of 1040 coronary artery segments were analyzed.
Using the information previously reported in part 1 of this paper, we set out to determine the importance of each of the independent variables (percent diameter and area stenosis, length, absolute diameter, entry and exit angles) in the prediction of stenosis flow reserve (SFR). Analysis of variance (ANOVA) was used to determine the importance of each of these variables, as well as their interactions, on the determination of SFR. Only percent diameter stenosis (%DS) demonstrated statistical significance (P < 0.001) in determining stenosis flow reserve. When the results of SFR were plotted against %DS, a quadratic relationship was demonstrated with an R2 value of 0.903 (r = 0.95). To verify the quadratic equation, the %DS of 100 different arterial stenoses was measured and used to calculate an SFR by the quadratic formula. The QCA and quadratic (calculated) determined SFRs compared favorably, with a correlation of 0.97.
The ability to calculate SFR directly from measured %DS allows the incorporation of calculated SFR into the clinical setting, where cardiologists can interpret lesion severity both anatomically and hemodynamically. This incorporation can be done without additional cost to the physician, hospital, patient, or third-party payers.
Determination of changes in total cholesterol (TC) and triglyceride (TG) levels has focused primarily on hypolipidemic drug effects. Changes resulting from dietary effect alone versus diet and drug effect have not yet been fully established.
Seventy subjects were enrolled into four treatment groups to determine the impact of diet and drug effect upon TC and TG. Group 1 (n = 28) served as the control group and received no dietary counseling or drug therapy. Group 2 (n = 22) received dietary coun seling. Group 3 (n = 7) underwent dietary counseling for six months and drug therapy for eighteen months. Subjects in groups 1-3 were monitored for eighteen months. Patients in group 4 (n = 13) were followed up for thirty-six months. No intervention occurred during the first eighteen months, and hypolipidemic medications were used during the second eighteen-month period.
Subjects in groups 1 and 4 received no specific dietary counseling and demonstrated no significant improvement over the course of the study. Patients in groups 2 and 3 showed significant reductions in both TC and TG. The improvement in TC seen for patients in group 3 was reduced after dietary counseling ceased.
Dietary intervention is necessary if patients are to statistically significantly reduce TC and TG levels. Drug therapy demonstrated the expected reductions in both TC and TG but did not statistically significantly lower lipid levels without concomitant dietary coun seling. When dietary counseling and hypolipidemic medications are used together, reduc tions in TC and TG values are even greater than those seen with dietary effect alone. Diet control alone appears to significantly reduce TC and TG levels, resulting in reduced need for antianginal medications.
To determine the effect of a 6-month very low carbohydrate diet program on body weight and other metabolic parameters.Fifty-one overweight or obese healthy volunteers who wanted to lose weight were placed on a very low carbohydrate diet (<25 g/d), with no limit on caloric intake. They also received nutritional supplementation and recommendations about exercise, and attended group meetings at a research clinic. The outcomes were body weight, body mass index, percentage of body fat (estimated by skinfold thickness), serum chemistry and lipid values, 24-hour urine measurements, and subjective adverse effects.Forty-one (80%) of the 51 subjects attended visits through 6 months. In these subjects, the mean (+/- SD) body weight decreased 10.3% +/- 5.9% (P <0.001) from baseline to 6 months (body weight reduction of 9.0 +/- 5.3 kg and body mass index reduction of 3.2 +/- 1.9 kg/m(2)). The mean percentage of body weight that was fat decreased 2.9% +/- 3.2% from baseline to 6 months (P <0.001). The mean serum bicarbonate level decreased 2 +/- 2.4 mmol/L (P <0.001) and blood urea nitrogen level increased 2 +/- 4 mg/dL (P <0.001). Serum total cholesterol level decreased 11 +/- 26 mg/dL (P = 0.006), low-density lipoprotein cholesterol level decreased 10 +/- 25 mg/dL (P = 0.01), triglyceride level decreased 56 +/- 45 mg/dL (P <0.001), high-density lipoprotein (HDL) cholesterol level increased 10 +/- 8 mg/dL (P <0.001), and the cholesterol/HDL cholesterol ratio decreased 0.9 +/- 0.6 units (P <0.001). There were no serious adverse effects, but the possibility of adverse effects in the 10 subjects who did not adhere to the program cannot be eliminated.A very low carbohydrate diet program led to sustained weight loss during a 6-month period. Further controlled research is warranted.
A decline in ejection fraction at stress compared with rest images has been associated with increased severity of coronary artery disease (CAD) and suggests a poorer prognosis. Myocardial perfusion imaging (MPI) using high-dose dipyridamole (HDD) has been shown to more accurately detect CAD than either standard dose dipyridamole (SDD) or exercise-induced stress (EST), but has not been looked at to determine its usefulness in detecting changes in stress and rest ejection fractions. To determine the relationship between changes in left ventricular ejection fraction (LVEF) and the severity of CAD, 36 Individuals underwent gated single photon emission computed tomography (SPECT) MPI using HDD. In each case resting and stress LVEFs were determined along with MPI results. Subjects with single-vessel CAD demonstrated an increase in LVEF from 77.8% (sd +/-8.8%) to 85.6% (sd +/-8.4%) resulting in a statistically significant increase in LVEF of 7.8% (p = 0.009). Patients with two-vessel disease showed a smaller increase from 73.2% (sd + 8.3%) to 79.8% (sd + 9.8%) following HDD stress. This increase was statistically (p = 0.008) significant. Patients with triple-vessel CAD showed a reduction in LVEF from 67.4% (sd +/-14.07) to 65.1% (sd +/-16.5%) which represented a decrease in LVEF of 2.7% and approached (p = 0.25) but did not reach statistical significance. Both the resting and stress LVEFs were statistically lower (p<0.05) in patients with triple-vessel CAD. Changes in resting LVEF (REF) and HDD pharmacologically induced stress LVEF (SEF) provide a valuable diagnostic marker as to the number of significantly diseased coronary arteries and can be acquired from gated SPECT sestamibi images.
The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed.
We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet.
Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [+/-SD], -5.8+/-8.6 kg vs. -1.9+/-4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, -20+/-43 percent vs. -4+/-31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6+/-9 percent vs. -3+/-8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity.
Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.
Insulin resistance is more common in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease. Given the current epidemic of obesity and the fact that lifestyle interventions, such as weight loss and exercise, decrease insulin resistance, a relatively simple means to identify overweight individuals who are insulin resistant would be clinically useful.
To evaluate the ability of metabolic markers associated with insulin resistance and increased risk for cardiovascular disease to identify the subset of overweight individuals who are insulin resistant.
Cross-sectional study.
General clinical research center.
258 nondiabetic, overweight volunteers.
Body mass index; fasting glucose, insulin, lipid and lipoprotein concentrations; and insulin-mediated glucose disposal as quantified by the steady-state plasma glucose concentration during the insulin suppression test. Overweight was defined as body mass index of 25 kg/m2 or greater, and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations. Receiver-operating characteristic curve analysis was used to identify the best markers of insulin resistance; optimal cut-points were identified and analyzed for predictive power.
Plasma triglyceride concentration, ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were the most useful metabolic markers in identifying insulin-resistant individuals. The optimal cut-points were 1.47 mmol/L (130 mg/dL) for triglyceride, 1.8 in SI units (3.0 in traditional units) for the triglyceride-high-density lipoprotein cholesterol ratio, and 109 pmol/L for insulin. Respective sensitivity and specificity for these cut-points were 67%, 64%, and 57% and 71%, 68%, and 85%. Their ability to identify insulin-resistant individuals was similar to the ability of the criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%).
Three relatively simple metabolic markers can help identify overweight individuals who are sufficiently insulin resistant to be at increased risk for various adverse outcomes. In the absence of a standardized insulin assay, we suggest that the most practical approach to identify overweight individuals who are insulin resistant is to use the cut-points for either triglyceride concentration or the triglyceride-high-density lipoprotein cholesterol concentration ratio.
What's good for your waistline may not be good for your food company stocks
- Krtb News
News KRTB. What's good for your waistline may not be good for your food company
stocks. Saint Paul Pioneer Press 2004 Feb 1, 2004.
Angina and coronary ischemia are the result of coronary regional blood flow differences
- R Fleming
Fleming R. Angina and coronary ischemia are the result of coronary regional blood flow
differences. J Am Coll Angiol 2003;1:127-142.
The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons©℗
- R M Fleming
- M R Fleming
- A Mckusick
- T Chaudhuri
Fleming RM, Fleming MR, McKusick A, Chaudhuri T. The Fleming Method for Tissue
and Vascular Differentiation and Metabolism (FMTVDM) using same state single or
sequential quantification comparisons©℗. An EVOLUNTIONARY Quantum Leap
Forward for Nuclear Cardiology & Nuclear Medicine. JVasc Dz & Treat 2018.
The Man Who Touched His Own Heart. Chapter 16
- R Dunn
Dunn R. The Man Who Touched His Own Heart. Chapter 16. Sugarcoating Heart
Disease. New York, Little Brown and Company, 2015.