Genes, fat intake, and cardiovascular disease risk factors in the Quebec Family Study

Objective: The aim of this study was to assess gene‐diet interaction effects on cardiovascular disease (CVD) risk factors (waist circumference, plasma triacylglycerol, high‐density lipoprotein‐cholesterol and fasting glucose concentrations, and diastolic and systolic blood pressure) in the Quebec Family Study cohort. Design: Sixty‐four polymorphisms from 45 candidate genes were studied in 645 subjects. Dietary fat intake was obtained from a 3‐day weighted food record. Results: We observed 18 significant interactions at a p value ≤ 0.01. Among them, the Pro12Ala polymorphism in peroxisome proliferator‐activated receptor γ, alone or in interaction with fat intake, significantly modulated waist circumference (p = 0.0005 for both effects). Additionally, the apolipoprotein E genotype in interaction with fat intake was significantly associated with diastolic and systolic blood pressure (p = 0.01 and p = 0.001, respectively). The ghrelin Leu72Met polymorphism also interacted with dietary fat in its relation to waist circumference and triacylglycerol concentrations (p = 0.0004 and p = 0.005). Discussion: These results suggest that several alleles at candidate genes interact with dietary fat intake to modulate well‐known CVD risk factors. The identification of gene‐diet interaction effects is likely to provide useful information concerning the etiology of CVD.     

Chimpanzee social intelligence: selfishness,altruism, and the mother–infant bond

To better understand the human mind from an evolutionary perspective, a great deal of research has focused on the closest living relative of humans, the chimpanzee, using various approaches, including studies of social intelligence. Here, I review recent research related to several aspects of social intelligence, including deception, understanding of perception and intention, social learning, trading, cooperation, and regard for others. Many studies have demonstrated that chimpanzees are proficient in using their social intelligence for selfish motives to benefit from their interactions with others. In contrast, it is not yet clear whether chimpanzees engage in prosocial behaviors that benefit others; however, chimpanzee mother–infant interactions indicate the possibility of such behaviors. Therefore, I propose that chimpanzees possess rudimentary traits of human mental competence not only in terms of theory of mind in a broader sense but also in terms of prosociality involving regard for others. Mother–infant interactions appear to be particularly important to understanding the manifestation of social intelligence from an evolutionary perspective.     

Genetic correlations between brain volumes and the WAIS-III dimensions of verbal comprehension, working memory, perceptual organization, and processing speed.

We recently showed that the correlation of gray and white matter volume with full scale IQ and the Working Memory dimension are completely mediated by common genetic factors (Posthuma et al., 2002). Here we examine whether the other WAIS III dimensions (Verbal Comprehension, Perceptual Organization, Processing Speed) are also related to gray and white matter volume, and whether any of the dimensions are related to cerebellar volume. Two overlapping samples provided 135 subjects from 60 extended twin families for whom both MRI scans and WAIS III data were available. All three brain volumes are related to Working Memory capacity (r = 0.27). This phenotypic correlation is completely due to a common underlying genetic factor. Processing Speed was genetically related to white matter volume (r(g) = 0.39). Perceptual Organization was both genetically (r(g) = 0.39) and environmentally (r(e) = -0.71) related to cerebellar volume. Verbal Comprehension was not related to any of the three brain volumes. It is concluded that brain volumes are genetically related to intelligence which suggests that genes that influence brain volume may also be important for intelligence. It is also noted however, that the direction of causation (i.e., do genes influence brain volume which in turn influences intelligence, or alternatively, do genes influence intelligence which in turn influences brain volume), or the presence or absence of pleiotropy has not been resolved yet.     

Plasma neuropeptide Y levels relate cigarette smoking and smoking cessation to body weight regulation

Loss and disproportionate gain of body weight often seen respectively in smokers and quitters are believed to be due to disrupted energy homeostasis induced by nicotine, the major constituent of cigarette smoke. Energy homeostasis is suggested to be regulated by the coordinated actions of peripheral adipose tissue derived leptin and the brain hypothalamic orexigenic neuropeptide Y (NPY). While the studies probing the role of leptin and NPY in weight modulating effect of nicotine have so far been inconsistent and based largely on animal systems, there is a paucity of data involving human subjects. Here we measured the plasma levels of orexigenic neuropeptide Y (NPY) and leptin in 35 non-smokers and 31 cigarette smokers before and three months after smoking cessation. Compared to non-smokers, smokers were leaner and had reduced NPY and leptin levels. Smoking cessation resulted in a significant weight gain and increased waist circumference accompanied by increased leptin and NPY levels. NPY levels were significantly correlated with body weight (r=0.43, p<0.05), BMI (r=0.41, p<0.05), and waist circumference (r=0.37, p<0.05), while leptin correlated with BMI (r=0.42, p<0.05) and waist circumference (r=0.39, p<0.05). Association of leptin with smoking status, but not that of NPY, was lost after controlling for anthropometric parameters. Weight modulating effect of cigarette smoke may thus involve its direct action on NPY, independent of leptin. Altered leptin levels in smokers and quitters may merely reflect changes in body weight or precisely fat mass.     

Correlation between breakfast tryptophan content and morning-evening in Japanese infants and students aged 0-15 yrs

Tryptophan can be metabolized via 5-hydroxytryptamine=serotonin to melatonin by a series of 4 enzymes in pineal body. Lack of serotonin in body fluid in the brain during daytime can lead to several psychiatric disorders, while shortage of plasma-melatonin at night can be related to sleep disorders. The Morning-Evening (M-E) questionnaire and the original questionnaire including questions on sleep habits, mental symptoms, and contents of meals were administered to 1055 infants aged 0-6 yrs, 751 students attending an elementary school, and 473 students attending junior high school in Kochi City (33 degrees N). The index of tryptophan taken at breakfast (Trp-Index) was calculated as tryptophan amount per one meal based on the tryptophan included in each 100 g of the foods and a standard amount of food per one meal. A significant positive-correlation between M-E scores and Trp-Index was not shown by relatively older students, aged 9-15 yrs (Pearson's test, r=0.044-0.123, p=0.071-0.505), whereas a significant positive correlation was shown by infants and young elementary school students aged 0-8 yrs (r=0.180, 0.258, p<0.001). The more frequently the infants had difficulty falling asleep at bedtime and waking up in the morning, the less the Trp-Indices taken at breakfast were (Kruskall-Wallis-test, p=0.027 for difficulty falling asleep; p=0.008 for difficulty waking up). The more frequently infants became angry even by a little trigger, or depressed, the lower (more evening-typed) the M-E scores were (Kruskal-Wallis test: p相似文献   

Neural Basis of Psychological Growth following Adverse Experiences: A Resting-State Functional MRI Study

Over the past decade, research on the aftereffects of stressful or traumatic events has emphasized the negative outcomes from these experiences. However, the positive outcomes deriving from adversity are increasingly being examined, and such positive changes are described as posttraumatic growth (PTG). To investigate the relationship between basal whole-brain functional connectivity and PTG, we employed resting-state functional magnetic resonance imaging and analyzed the neural networks using independent component analysis in a sample of 33 healthy controls. Correlations were calculated between the network connectivity strength and the Posttraumatic Growth Inventory (PTGI) score. There were positive associations between the PTGI scores and brain activation in the rostral prefrontal cortex and superior parietal lobule (SPL) within the left central executive network (CEN) (respectively, r = 0.41, p < 0.001; r = 0.49, p < 0.001). Individuals with higher psychological growth following adverse experiences had stronger activation in prospective or working memory areas within the executive function network than did individuals with lower psychological growth (r = 0.40, p < 0.001). Moreover, we found that individuals with higher PTG demonstrated stronger connectivity between the SPL and supramarginal gyrus (SMG). The SMG is one of the brain regions associated with the ability to reason about the mental states of others, otherwise known as mentalizing. These findings suggest that individuals with higher psychological growth may have stronger functional connectivity between memory functions within the CEN and social functioning in the SMG, and that their better sociality may result from using more memory for mentalizing during their daily social interactions.     

On the relationship of emotional abilities and prosocial behavior

The ability to perceive and infer the meaning of facial expressions has been considered a critical component of emotional intelligence being essential for successful social functioning: Longitudinal findings suggest that the ability to recognize emotion cues is related to positive social interactions. Moreover, pronounced recognition abilities for at least some emotions facilitate prosocial behavior in everyday situations. Integrating paradigms from behavioral economics and psychometrics, we used an interdisciplinary approach to study the relationship between prosociality as trait cooperativeness and the ability to recognize emotions in others. We measured emotion recognition accuracy (ERA) using a multivariate test battery. We captured prosocial behavior in standard socio-economic games, along with spontaneous emotion expressions. Structural equation modeling revealed no significant relationship between overall ERA and prosocial behavior. However, modeling emotion-specific factors suggested that more prosocial individuals are better in recognizing fear and tend to express more spontaneous emotions during the prisoner's dilemma. In all, cooperative individuals seem to be more sensitive to the distress of others and more expressive, possibly fostering reciprocal interactions with like-minded others.     

Expression of 11β-hydroxysteroid dehydrogenase type 1 in visceral and subcutaneous adipose tissues of patients with polycystic ovary syndrome is associated with adiposity

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR) and central obesity. The impact of adipose tissue cortisol reactivation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on markers of obesity and IR was assessed in PCOS patients. Eighty-five PCOS patients and 43 controls were enrolled for subcutaneous adipose tissue biopsy; 25/85 patients and 29/43 controls underwent also visceral adipose tissue biopsy. HSD11B1 gene expression and expression of lipid metabolism genes were measured in subcutaneous and visceral adipose tissues. Anthropometric and biochemical markers of IR and PCOS were also assessed. HSD11B1 expression in visceral and subcutaneous adipose tissue was increased in PCOS patients compared to controls (p<0.05). After BMI adjustment, the difference was no longer significant. In PCOS patients, visceral HSD11B1 expression correlated positively with waist circumference (p=0.001), BMI (p=0.002), plasma insulin (p<0.05), systolic blood pressure (p=0.003), and lipoprotein lipase (LPL), hormone-sensitive lipase (LIPE) and peroxisome-proliferator activated receptor γ gene expression. Subcutaneous HSD11B1 expression correlated positively with BMI, waist circumference (p<0.001 for both) and HOMA-IR (p=0.003), and negatively with LPL, LIPE, adiponectin and glucose transporter GLUT4 gene expression. HSD11B1 expression in both depots showed a negative correlation with plasma HDL-cholesterol (p<0.03) and a positive one with C-reactive protein (p<0.001). In multiple regression analysis, HSD11B1 expression in visceral adipose tissue was most prominently associated with waist circumference, and that in subcutaneous adipose tissue with BMI (p<0.001 for both). Our results show that PCOS is not associated with increased HSD11B1 expression once adiposity is controlled for. Increased expression of this gene correlates with markers of adiposity and predicts IR and an unfavorable metabolic profile, independently of PCOS.     

Glycogen in the brain of Drosophila melanogaster: diurnal rhythm and the effect of rest deprivation

One function of sleep is thought to be the restoration of energy stores in the brain depleted during wakefulness. One such energy store found in mammalian brains is glycogen. Many of the genes involved in glycogen regulation in mammals have also been found in Drosophila melanogaster and rest behavior in Drosophila has recently been shown to have the characteristics of sleep. We therefore examined, in the fly, variation in the glycogen contents of the brain, the whole head and the body throughout the rest/activity cycle and after rest deprivation. Glycogen in the brain varies significantly throughout the day (p=0.001) and is highest during rest and lowest while flies are active. Glycogen levels in the whole head and body do not show diurnal variation. Brain glycogen drops significantly when flies are rest deprived for 3 h (p=0.034) but no significant differences are observed after 6 h of rest deprivation. In contrast, glycogen is significantly depleted in the body after both 3 and 6 h of rest deprivation (p<0.0001 and p<0.0001, respectively). Glycogen in the fly brain changes in relationship to rest and activity and demonstrates a biphasic response to rest deprivation similar to that observed in mammalian astrocytes in culture.     

The evolution of brain size and intelligence in man

The brain size of hominids has increased approximately threefold during the evolution of the hominids fromAustralopithecus toHomo sapiens. It is proposed that the principal reason for this increase is that larger brains conferred greater intelligence, and greater intelligence conferred a selection advantage. A number of anthropologists have difficulty accepting this thesis because they believe that brain size is not associated with intelligence in man. Evidence is reviewed, and new evidence from two studies is presented, to show that brain size as measured by head size is positively correlated with intelligence as measured by intelligence tests. On two recent samples statistically significant correlations of .21 and .30 were obtained between estimates of brain size and IQ. It is considered that brain size is positively associated with intelligence in man and that this is the major reason for the increase in brain size of the hominids during the last 3.2 million years.     

Research on association between variants and haplotypes of TRPV1 and TRPA1 genes with growth traits in three cattle breeds

The objective of this study was to examine the association of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) genes polymorphisms with growth traits in three Chinese cattle breeds (Jiaxian red cattle, Qinchuan cattle and Luxi cattle). Through experiments we identified three single nucleotide polymorphisms (SNPs) in these three cattle breeds TRPV1 and TRPA1 genes using PCR-SSCP, (forced) PCR-RFLP methods. Three of these polymorphisms are all synonymous mutation which includes (NW_003104493.1: 30327 C?>?T), (NW_003104493.1: 33394 A?>?G) and (NW_003104493.1: 38471?G?>?A) are in exons. The other three polymorphisms are located at 3'UTR. Furthermore, we evaluated the haplotype frequency and the statistical analyses indicated that these SNPs of TRPV1 and TRPA1 genes were associated with bovine body height, body length, waist angle width, hucklebone width, cross ministry height, chest qingwidth (p?<?0.05) and recommendation height, cannon circumference (p?<?0.01) of Qingchuan cattle; body length, waist angle width (p?<?0.05) of Jiaxian red cattle; body weight, Body length, cannon circumference, chest circumference (p?<?0.05) and body height (p?<?0.01) of Luxi cattle. Our result confirms the polymorphisms in the TRPV1 and TRPA1 genes are associated with growth traits that may be used for marker-assisted selection (MAS) in three beef breeds programs.     

Relationships between Head Circumference,Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.     

Serum urate, metabolic syndrome, and cardiovascular risk factors. A population-based study

We studied the associations between serum urate levels (determined in 503 subjects from a population of 1,344 subjects living in northern Madrid) and both the metabolic syndrome (MS) (defined by the Adult Treatment Panel III criteria) and C-reactive protein (CRP, determined in 382 subjects). MS was diagnosed in 25% (95%CI, 21-28%) and was associated with hyperuricemia (p<0.001). There was a graded increase in serum urate levels with increasing number of MS components. Urate concentrations significantly correlated with waist circumference (r=0,455, p<0.01). Serum urate was not independently associated with CRP levels. This study shows that serum urate levels are associated with the presence of MS and each of its features.     

Effects of growth hormone treatment on cognitive function and head circumference in children born small for gestational age

Short stature is not the only problem faced by children born small for gestational age (SGA). Being born SGA has also been associated with lowered intelligence, poor academic performance, low social competence and behavioural problems. This paper summarizes the results of a randomized, double-blind, growth hormone (GH) dose-response study (1 or 2 mg/m2/day [ approximately 0.035 or 0.07 mg/kg/day]) on growth, intelligence quotient (IQ) and psychosocial functioning in 79 children born SGA at the start, and after 2 and 8 years of GH therapy, and addresses the associations with head circumference. Mean age at start of therapy was 7.4 years; mean duration of GH treatment was 8.0 years. In 2001, 91% of children born SGA had reached a normal height (> -2.0 standard deviation score [SDS]). Block-design s-score (Performal IQ) and Total IQ score increased (p < 0.001 for both indices) from scores significantly lower than those of Dutch peers at the start of therapy (p < 0.001) to scores that were comparable to those of Dutch peers in 2001. Vocabulary s-score (Verbal IQ) was normal at the start of therapy and remained so over time. Externalizing Problem Behaviour SDS and Total Problem Behaviour SDS improved during GH therapy (p < 0.01-0.05) to scores comparable to those of Dutch peers. Internalizing Problem Behaviour SDS was comparable to that of Dutch peers at the start of therapy and remained so, whereas Self-Perception improved from the start of GH therapy until 2001 (p < 0.001), when it reached normal scores. Head circumference SDS at the start of GH therapy and head growth during GH therapy were positively related to all IQ scores (p < 0.01), whereas neither were related to height SDS at the start of, or to its improvement during, GH therapy. A significant improvement in height and head circumference in children born SGA was seen after only 3 years of GH therapy, in contrast to randomized SGA controls. In conclusion, most children born SGA showed a normalization of height during GH therapy and, in parallel to this, a significant improvement in Performal IQ and Total IQ. In addition, problem behaviour and self-perception improved significantly. Interestingly, Performal, Verbal and Total IQ scores were positively related to head circumference, both at the start of, and during, GH therapy; head circumference increased in GH-treated children born SGA, but not in untreated SGA controls. These results are encouraging but also warrant confirmational studies and further investigations into the effects of GH on the central nervous system.     

Age-related changes in the glutathione redox system

The effect of aging on the glutathione redox system was evaluated in this study. For this purpose, we determined reduced glutathione (GSH) and oxidized glutathione (GSSG) in whole blood, glutathione peroxidase (GPx) and glutathione reductase (GSSGR) in erythrocytes and selenium (Se) in plasma in 176 healthy individuals. We also calculated GSH/GSSG molar ratios. These subjects were divided into five groups: group 1 (n=25; 0.2-1 years old); group 2 (n=28; 2-11 years old); group 3 (n=23; 12-24 years old); group 4 (n=40; 25-40 years old); group 5 (n=60; 41-69 years old). GSH levels in groups 1 and 5 were significantly lower than the other groups (p<0.001). Conversely, GSSG levels were significantly high in these periods (p<0.001). The GSH/GSSG molar ratio was found to be low both in the first year of life and in the oldest group (p<0.001, respectively). GPx activity in group 5 was increased as compared to the other groups (p<0.001). GSSGR activity was significantly lower in the oldest groups than in the other groups (p<0.001). Se levels were found to be low in the oldest group (p<0.001). Selenium levels of women in group 5 were significantly high as compared to the men (p<0.01). We found negative correlations between age and GSH levels (r=0.402; p<0.001), selenium levels (r=0.454; p<0.001), GSH/GSSG molar ratio (r=0.557; p<0.001) and GSSGR activity (r=0.556; p<0.001). There were positive correlations between age and GPx (r=0.538; p<0.001) and GSSG level (r=0.551; p<0.001). In conclusion, our findings show that the glutathione redox system is affected by age. Oxidative stress increases during the aging process. There is no effect of aging on the glutathione redox system according to sex except for the Se level.     

Associations between XRCC1 and ERCC2 polymorphisms and DNA damage in peripheral blood lymphocyte among coke oven workers.

A wide variety of base damages and single-strand breaks formed by reactive oxygen species during metabolic activation of polycyclic aromatic hydrocarbons (PAHs) have been recognized to be involved in PAH carcinogenesis. In this study, alkaline comet assay was used to detect the DNA damage in peripheral blood lymphocytes among 143 coke-oven workers and 50 non-coke-oven workers, and the effects of genetic polymorphisms of XRCC1 and ERCC2 genes on DNA damage were evaluated. The olive tail moment was significantly higher in coke-oven workers than in non-coke-oven workers (2.6, 95% CI=2.1-3.3 versus 1.0, 95% CI=0.8-1.2, p<0.01), and significant correlation between ln-transformed urinary 1-OHP and ln-transformed olive tail moment was found in total population (n=193, Pearson's r=0.393, p<0.001) and in coke-oven workers (n=143, Pearson's r=0.224, p=0.007). The olive tail moment was significantly higher in coke-oven workers with GA genotype of G27466A polymorphism of XRCC1 than those with GG genotype (4.6, 95% CI=2.5-8.7 versus 2.4, 95% CI=1.9-2.9, p<0.01 with adjustment for covariates). No significant associations between C26304T, G28152A and G36189A polymorphisms of XRCC1 and G23591A and A35931C polymorphisms of ERCC2 and olive tail moment were found in both groups. The study showed that the alkaline comet assay is a suitable biomarker in the detection of DNA damage among coke-oven workers and it suggested that the A allele of G27466A polymorphism of XRCC1 may be associated with decreased DNA repair capacity toward PAH-induced base damage and strand breaks.     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

Insights into the change in brain natriuretic peptide after ST-elevation myocardial infarction (STEMI): why should it be better than baseline?

While baseline N-terminal brain natriuretic peptide (NT-proBNP) is useful in the prognosis of acute ST-elevation myocardial infarction (STEMI), it is unclear whether a relationship exists between serial NT-proBNP, reperfusion success, and prognosis. We prospectively defined a NT-proBNP analysis in the WEST (Which Early ST-elevation myocardial infarction Therapy) trial that enrolled 304 acute STEMI patients. NT-proBNP (pg/mL) was measured at baseline prior to treatment (n=258) and 72 to 96 h (n=247) and 30 days (n=221) after treatment (Delta NT-proBNP=72 h value - the baseline NT-proBNP). Reperfusion success was measured by ST-segment resolution at 180 min, infarct size by peak creatine kinase (CK) during the first 24 h, and QRS score at discharge (QRSd). The primary endpoint was a 30 day clinical composite. The ability of either baseline NT-proBNP or Delta NT-proBNP to predict the primary endpoint was compared using single-variable logistic regression and the c-statistic. Median (interquartile range) NT-proBNP in pg/mL was 87 (39-316) at baseline, 864 (338-1857) at 72 h, and 585 (264-1212) at 30 days. ST resolution was inversely correlated with Delta NT-proBNP (r=-0.23, p=0.002) and 30 day NT-proBNP (30 day NT-proBNP 1016, 828, and 397 for <30%, 30%-70%, >or=70% STR, respectively, p<0.001). Infarct size was correlated with Delta NT-proBNP by CK (r=0.41, p<0.001) and QRSd (r=0.31, p<0.001); the 30 day NT-proBNP relationship was similar for CK (r=0.48, p<0.001) and QRSd (p=0.003). The baseline NT-proBNP was associated with an increased 30-day composite endpoint (Q1, 19%; Q2, 20%; Q3, 15%; Q4, 38%; p=0.03 for trend) as was Delta NT-proBNP (Q1, 16%; Q2, 18%; Q3, 19%; Q4, 37%; p=0.009 for trend). The c-statistic for baseline, 72 to 96 h, and Delta NT-proBNP was 0.59, 0.61, and 0.62 for the 30-day composite and 0.64, 0.62, and 0.62 for the 90-day composite, respectively. Delta NT-proBNP clearly predicts short-term adverse cardiac events and is superior to baseline NT-proBNP, but similar to the 72 to 96 h NT-proBNP in predicting clinical events after STEMI. This likely reflects the variability in NT-proBNP at presentation and the ability to integrate subsequent important physiologic sequelae of STEMI such as reperfusion and infarct size.     

Relationship of Serum Adiponectin and Leptin Concentrations with Body Fat Distribution in Humans

Objective: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin. Research Methods and Procedures: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist‐to‐hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of the lower leg as assessed by magnetic resonance imaging. Results: After adjusting for sex and percentage of body fat, adiponectin was negatively (r = ?0.17, p < 0.001) and leptin was positively (r = 0.22, p < 0.001) correlated with waist‐to‐hip ratio. Leptin, but not adiponectin, correlated with both waist (r = 0.49, p < 0.001) and hip circumference (r = 0.46, p < 0.001). Furthermore, leptin, but not adiponectin, correlated with the proportion of subcutaneous fat of the lower leg cross‐sectional area (r = 0.37, p < 0.001). Discussion: These data suggest that both adipocytokines are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment.     

Which Obesity Index Best Explains Prevalence Differences in Type 2 Diabetes Mellitus?

Objective: Obesity drives the diabetes epidemic. However, it is not known which obesity index best explains variations in type 2 diabetes mellitus prevalence across populations. Research Methods and Procedures: We analyzed three cross‐sectional studies from San Antonio, TX, (Mexican‐Americans and non‐Hispanic whites, n = 2839), Mexico City (n = 2233), and Spain (n = 2161) (age range, 35 to 64 years). We used the area under the receiver operating characteristic curve (AUC) to assess performance for identifying diabetic subjects and logistic regression analysis to examine differences in diabetes prevalence. Results: AUCs for waist circumference and BMI were similar in white subjects, but the AUC for waist circumference was greater in Mexican‐origin subjects (Mexican men, 0.594 vs. 0.549, p = 0.008; and women, 0.605 vs. 0.557, p = 0.002; Mexican‐American men, 0.648 vs. 0.600, p < 0.001; and women, 0.744 vs. 0.693, p < 0.001). The AUC for waist‐to‐height ratio tended to be greater than that for waist circumference, but statistical significance was demonstrated only in Mexican women (0.628 vs. 0.613, p = 0.044), Mexican‐American women (0.774 vs. 0.758, p < 0.001), and Spanish women (0.734 vs. 0.715, p = 0.039). No obesity index was consistently superior to the others for explaining differences in diabetes prevalence among populations. Conclusions: In white and Mexican‐origin men, waist circumference may be the preferred marker for identifying diabetic subjects on account of its simplicity; in women, waist‐to‐height ratio may be better. Differences in diabetes prevalence among these populations cannot be attributed to a single measure of obesity.