Inverse Predictor Research Articles

Avancées récentes et perspectives dans le traitement des dyslipidémies athérogènes

Purpose Recent end point trials of lipid-lowering drugs have shown that patients at very high-risk for coronary disease benefit from treatments that lowers low density lipoprotein cholesterol (LDL cholesterol) plasma levels ≤ 70 mg/dl and that patients with at least 2 risk factors benefit from LDL cholesterol levels ≤ 100 mg/dl. Epidemiologic studies have shown that the concentration of high density lipoprotein cholesterol (HDL cholesterol) is a strong, independent, inverse predictor of coronary disease risk. Innovative pharmacological approaches to raise low HDL cholesterol levels are currently of considerable interest, especially for patients with type 2 diabetes or metabolic syndrome. Results Rosuvastatin has shown superior efficacy in lowering LDL cholesterol, although evidence of clinical benefit is actually lacking. Ezetimibe is a lipid-lowering drug that inhibits absorption of dietary and biliary cholesterol. Its co-administration with statin has given very interesting results. Niacin is the most effective of currently available options for raising HDL cholesterol, although tolerability can be an issue, with serious side effects such as loss of glucose control and liver toxicity. Flushing may occur in 80% of treated patients. Two CETP inhibitors have shown therapeutical efficacy to raise HDL cholesterol, but clinical benefit remains uncertain.

Cholesteryl ester transfer protein gene haplotypes, plasma high-density lipoprotein levels and the risk of coronary heart disease

High-density lipoprotein cholesterol (HDL-C) is a known inverse predictor of coronary heart disease (CHD) and is thus a potential therapeutic target. Cholesteryl ester transfer protein (CETP) is a key protein in HDL-C metabolism such that elevated CETP activity is associated with lower HDL-C. Currently available HDL-C raising drugs are relatively ineffective and evidence suggesting the role of CETP in HDL-C levels has promoted the development of CETP inhibitors as potential therapeutic agents for CHD. We investigated three SNPs in the CETP gene in two cross-sectional community-based populations (n = 1,574 and 1,109) and a population of 556 CHD patients to determine if reduced CETP activity due to genetic variations in the CETP gene would increase HDL-C levels and reduce the risk of CHD. CETP genotypes and haplotypes were tested for association with lipid levels, CETP activity and risk of CHD. Multivariate analysis showed the common AAB2 haplotype defined by the G-2708A, C-629A and TaqIB polymorphisms, was consistently associated with reduced CETP activity and increased HDL-C levels. A mean increase in HDL-C levels of 0.16-0.24 mmol/l was observed in individuals with two copies of the AAB2 haplotype relative to non AAB2 carriers across all three populations (P < 0.001). A case-control study of males indicated no association between single SNPs or haplotypes and the risk of CHD. These results suggest that raising HDL-C via CETP inhibition may not alter risk of CHD. Randomized control trials are needed to determine whether CETP inhibition will in reality reduce risk of CHD by raising HDL-C.

Prenatal stressful life events predict child cognitive outcomes

Introduction: There is growing evidence that prenatal maternal stress is associated with poorer behavioural [1] and cognitive [2] development in the child. What has not been established is whether this is because antenatal stress has a direct effect on the fetus. Animal models indicate that prenatal stress can have a long-term effect on the neuroendocrine stress response in the offspring, specifically the HPA axis [3], although other possible mechanisms include genetic predisposition or postnatal effects mediated by parenting. What is also unclear is the nature of the antenatal stress that is most harmful for child outcomes. We are conducting a study aiming to examine the association between maternal antenatal and postnatal stress and infant cognitive and behavioural development, and to explore possible mediating hormonal mechanisms. Here we present infant outcomes in relation to maternal stress during pregnancy and in the postnatal period. Methods: Women were originally recruited from an amniocentesis clinic, after obtaining written consent. Mothers completed a 26-item questionnaire relating to antenatal and postnatal stressful life events [4]. A trained developmental researcher administered the Bayley Scales of Infant Development (Second Edition) assessing mental (MDI) and motor (PDI) development. The study was approved by the local research ethics committee and is funded by the March of Dimes. Results: Seventy women returned for assessments when their child was about 18 months old ([mean±S.D.] 17.4± 1.1 months). English was the first language in the family and the children (32 girls and 36 boys) were all born at full term (>37 weeks; [mean±S.D.] 39.49±1.26 weeks) and had no clinical problems. Two mothers and babies were excluded because of insufficient English. There was a significant correlation between the total number of stressful life events in the antenatal period and infant MDI [Spearman's correlation (rs)=−0.43, p<0.0001]; the association with PDI was in the same direction but weaker and non-significant (rs =−0.19, n=68). A bivariate analysis showed that the mean±S.D. MDI scores of the children whose mother had experienced three or more life events during pregnancy was 85.8±8.2 (n=15), compared with 98.7±9.0 (n=53) for those children whose mother had experienced under 3 (p<0.0001). In contrast, the association between the total number of postnatal life events and MDI and PDI were non-significant (rs=−.12 and −.02, respectively). In a multivariate analysis including both antenatal and postnatal stressful life event scores, maternal education, antenatal maternal smoking, alcohol and street drug consumption, parity, infant gestational age at birth, infant sex, and infant birthweight for gestational age, the association between antenatal life events and child MDI remained significant (B=−3.19; S.E.= 0.71; β=−0.55; p<0.0001), although birthweight for gestational age also emerged as a significant inverse predictor (B=−2.51; S.E.=2.27; β=−0.12; p=0.05). However, while antenatal life events alone explained 22% of the observed variance in child MDI scores, birthweight for gestational age explained only 6% of the variance. Stressful life events indicative of a strained relationship between the mother and her partner (“you were separated/ divorced”, “you had a serious argument with your partner” and “your partner was emotionally cruel to you”) accounted for 40% of the variance in infant MDI due to life events. Discussion: This study adds evidence to support the hypothesis that stressful life events during pregnancy have a lasting and clinically relevant effect on the cognitive outcome for the child. It supports the concept that intrauterine influences affect behavioural and mental development, independent of postnatal factors. Although birthweight for gestational age emerged as a significant predictor of child MDI scores, the relationship is weak. The data presented here represents half of the final cohort, and future analyses with a fuller cohort will help to clarify this finding. The mediators responsible for the effect of antenatal events are as yet unknown.

Relationship between the concentration and antiatherogenic activity of high-density lipoproteins

The relationship between the concentration of high-density lipoprotein cholesterol and their protective function is addressed. Strong epidemiologic evidence indicates that the concentration of high-density lipoproteins is a powerful inverse predictor of cardiovascular risk. This is consistent with the fact that high levels of high-density lipoprotein are generally associated with an increased concentration of large high-density lipoprotein particles that are now known to be the preferred acceptors of cholesterol released from macrophages via the adenosine triphosphate-binding cassette A1 pathway. Some of the protective activity, however, of high-density lipoproteins may reflect functions of specific subpopulations or variations in the 'quality' of high-density lipoprotein particles and may be unrelated to the concentration of the total high-density lipoprotein fraction. This review summarizes the cardiovascular protective role of high-density lipoproteins and addresses how the concentration and antiatherogenic activity of high-density lipoproteins are related. Some of the protective functions of high-density lipoprotein are closely related to the simple concentration of high-density lipoproteins; others may not be related. Given the current high level of interest in therapies that raise the concentration of high-density lipoprotein, it is essential to conduct further research to identify precisely how high-density lipoproteins protect.

How Does Maternal and Child Feeding Behavior Relate to Weight Gain and Failure to Thrive? Data From a Prospective Birth Cohort

The aim of this study was to study the influences of child and maternal feeding behavior on weight gain and failure to thrive in the first year of life. The Millennium Infant Study recruited a population birth cohort in Northeast England shortly after birth and studied them prospectively to the age of 13 months. Parents completed questionnaires at 6 weeks and 4, 8, and 12 months. Appetite was rated on a 5-point scale at each age, and a core group of questions was used to generate scores of oromotor dysfunction, avoidant eating behavior, maternal feeding anxiety, and response to food refusal. Routinely collected weights were used to assess weight gain using the thrive index (TI); weight faltering was defined as TI below the 5th percentile from birth to age 6 weeks or 4, 8, or 12 months. Of 923 eligible infants, 75% of the mothers returned at least 1 questionnaire and > or =2 weights. Weight gain to 6 weeks was independently related to appetite and oromotor dysfunction rated at 6 weeks. Appetite rated at 6 weeks and 12 months both independently predicted weight gain to 12 months. Some avoidant eating behavior was seen in most children by 12 months old, but there was no relationship with weight gain or faltering after adjustment for appetite. However, the extent to which caregivers responded to food refusal was a significant inverse predictor of weight gain, even after adjustment for appetite. Inherent child appetite characteristics seem to be an important risk factor for weight faltering and failure to thrive, but high maternal promotion of feeding may also have an adverse influence.

Urotensin II is an inverse predictor of incident cardiovascular events in end-stage renal disease

Urotensin II (UTN) is a vasoactive substance that may induce vasoconstriction or vasodilatation. Although this peptide is seen as a vasculotoxic substance, to date there is no prospective study examining the relationship between UTN and hard end points like cardiovascular (CV) events. UTN is much increased in end-stage renal disease (ESRD) and this disease may represent a useful natural model to explore the relationship between UTN and CV outcomes. In this study, we analysed the relationship between plasma UTN and incident CV events (fatal and non-fatal) in a cohort of 191 haemodialysis patients followed up for an average time of 3.6 years (range 0.07-5.8 years). Plasma UTN in haemodialysis patients (median: 6.5 ng/ml) was twice higher than in healthy subjects (median: 3.3 ng/ml). During the follow-up period, 94 patients died and 88 had incident fatal and non-fatal CV events. UTN was significantly lower in patients with incident CV events (median: 5.3 ng/ml) than in events-free patients (median: 7.1 ng/ml), and in a Kaplan-Meier analysis, high UTN was strongly and inversely associated with incident CV events (P<0.001). Multivariate Cox's regression analysis fully confirmed plasma UTN as an inverse predictor of adverse CV outcomes, and in this analysis, UTN resulted to be the third factor in rank, after age and diabetes, explaining the incidence of CV events. UTN is an inverse predictor of CV outcomes in ESRD. Our data suggest that UTN should not be necessarily seen as a vasculotoxic peptide in haemodialysis patients.

Impact of Body Mass Index on Cardiac Mortality in Patients With Known or Suspected Coronary Artery Disease Undergoing Myocardial Perfusion Single-Photon Emission Computed Tomography

The purpose of this study was to assess the relationship between body mass index (BMI) and the prognostic value of myocardial perfusion single-photon emission computed tomography (MPS). The prognostic value of MPS in the obese has not been evaluated. We studied 4,720 patients with and 10,019 patients without known coronary artery disease (CAD) who underwent rest Tl-201/stress Tc-99m sestamibi MPS, including 5,233 gated MPS studies and followed up (mean 2.7 to 3.2 years). Patients were categorized as normal weight (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), or obese (BMI > or =30.0 kg/m2). Unadjusted annual rates of cardiac death (CD) rose versus stress MPS abnormalities in all weight groups (p < 0.001). Obese or overweight patients with or without known CAD who had normal MPS were at low CD risk (<1%/year), similar to normal weight patients. In CAD, obese and overweight patients with abnormal MPS had lower rates of CD compared with normal weight patients (p < 0.01). In patients with low ejection fraction (EF) by gated MPS, those with normal weight had highest CD rate (p = 0.001). Multivariable models revealed that BMI was not a predictor of CD in suspected CAD patients (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.95 to 1.02) but was an independent inverse predictor of CD in known CAD patients (HR 0.95; 95% CI 0.92 to 0.98), especially in women, adenosine stress, low EF, or abnormal perfusion. Normal MPS was associated with low risk of CD in patients of all weight categories. In patients with known CAD undergoing MPS, obese and overweight patients were at lower risk of CD over three years than normal weight patients.

High-density lipoproteins as therapeutic targets

The concentration of cholesterol in HDL is an inverse predictor of future cardiovascular disease, with evidence mounting that therapies that increase HDL concentration are antiatherogenic. The best known antiatherogenic function of HDL particles relates to their ability to promote the efflux of cholesterol from cells. However, they also have antioxidant, antiinflammatory and antithrombotic properties. The past year has seen the publication of several papers that highlight a potential major protective role of HDL in states of acute inflammation. Papers showing extremely promising results using novel inhibitors of cholesteryl ester transfer protein as HDL-raising agents have also appeared. Finally, the discovery that ATP-binding cassette transporter G1 (ABCG1) transports cell cholesterol to large HDL particles in the extracellular space has largely reconciled apparent inconsistencies between basic research indicating that small, pre-beta-migrating HDL particles are the antiatherogenic components of HDL and epidemiological research that implicates larger HDL particles as the protective fraction. The finding that ABCG1 promotes the efflux of cholesterol from cells to large HDL particles also provides powerful circumstantial evidence that cholesteryl ester transfer protein inhibition (which increases HDL size) may enhance, rather than reduce, cholesterol efflux, and thus inhibit the development of atherosclerosis.

The effects of socioeconomic development on worldwide hepatitis A virus seroprevalence patterns

Hepatitis A virus (HAV) infection confers long-term immunity, so mathematical analysis of age-specific seroprevalence in populations can reveal changes in the infection rate over time. HAV transmission is related to access to clean drinking water, personal hygiene and public sanitation. We used an SIR (susceptible-infectious-recovered) compartmental model with age structure to fit a time-dependent logistic function for HAV force of infection for 157 published age-seroprevalence data sets. We then fit linear regression models for socioeconomic variables and infection rate. The proportion of the population with access to clean drinking water, the value of the human development index (HDI), and per capita gross domestic product (GDP) are all inverse predictors of HAV infection rates. Declining infection rates were observed in 65.6% of the surveys. Discussion This work demonstrates the utility of HAV seroprevalence studies to reveal patterns of change in force of infection and to assess the association between socioeconomic risk factors and transmission rates.

Behavioral and self-reported aggression as a function of domain-specific self-esteem

On the basis of a domain-specific theory of self-esteem, it was hypothesized that functionally distinct domains of self-esteem would predict aggression differentially. Participants completed self-report measures of self-perceived superiority, mate value, social inclusion, and global self-esteem, as well as of aggression. Self-assessed mate value emerged as a reliable, positive predictor, and social inclusion as a reliable inverse predictor, of self-reported hostility and aggression. In a subsequent laboratory experiment, in which participants had an opportunity to aggress against the source of positive or negative feedback about a personal essay that they had written, mate value again predicted increased aggression, whereas global self-esteem predicted decreased aggression. These main effects were moderated by the feedback manipulation, such that their respective simple effects were only present among participants that received negative feedback. Aggr. Behav. 00:1–11, 2005. © 2005 Wiley-Liss, Inc.

Inflammatory proteins as predictors of cardiovascular disease in patients with end-stage renal disease.

Patients with end-stage renal disease (ESRD) are at high risk from potentially devastating cardiovascular sequelae due to the unique clustering of risk factors in these patients. Inflammation is believed to play a key role in the pathogenesis of these cardiovascular lesions. Both pro- and anti-inflammatory cytokines produced from monocytes, and also from adipocytes, have been studied in this regard. Pro-inflammatory cytokines, although cytoprotective acutely, correlate with increased risk of cardiovascular disease (CVD) in chronic situations. Conversely, elevated levels of anti-inflammatory mediators are associated with increased patient survival times. Statistical modelling, calculation of relative risk and cost considerations indicate that determination of serum C-reactive protein levels may be a useful predictor of CVD in ESRD patients. Adipocytes are a rich source of many of the same cytokines produced by monocytes, including interleukin-6, tumour necrosis factor-alpha, as well as adipocyte-specific proteins, leptin and adiponectin (ADPN). ADPN, which is produced in much greater quantities than leptin, is inversely related to body mass index and to insulin resistance, suggesting a possible role in type 2 diabetes. Additionally, ADPN has been shown to modulate the endothelial inflammatory response in vitro. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with ESRD. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.

Dietary Patterns Predict Mortality in a National Cohort: The National Health Interview Surveys, 1987 and 1992

We examined the association of mortality and dietary patterns using data from the National Health Interview Surveys of 1987 and 1992 (n = 10,084), aged >/=45 y at baseline (with 2287 deaths due to all causes over 5.9 median years of follow-up). The approximately 60-item FFQ administered at baseline was examined for mentions of foods and dietary behaviors recommended in current dietary guidance (fruits, vegetables, lean poultry and alternates, low-fat dairy, and whole grains), and the resulting patterns were expressed as follows: 1) a Recommended Foods and Behavior Score (RFBS), 2) factor scores from factor analysis, and 3) clusters from cluster analysis. The multivariate-adjusted relative risk (RR) of mortality for each of the 3 types of dietary patterns was examined using Cox proportional hazards regression analysis. In men, RR of all-cause mortality was 0.72 (95% CI: 0.56, 0.92, P for trend < 0.001) for RFBS, and 0.74 (95% CI: 0.57, 0.95, P for trend = 0.002) for the fruit-vegetable-whole grain factor score when comparing extreme quartiles. Membership in 1 of the 4 clusters also was associated with lower risk in men (RR = 0.82, 95% CI: 0.66, 1.01). For women, the RFBS was a modest inverse predictor of mortality after multivariate adjustment (RR = 0.80, 95% CI: 0.61, 1.04, P for trend = 0.04), but estimates for factor and cluster patterns were attenuated. The population-attributable fraction due to diet was 0.16 in men and 0.09 in women. Dietary patterns characterized by compliance with prevailing food-based dietary guidance were associated with a lower risk of all-cause mortality.

Genetic determinants of low high-density lipoprotein cholesterol.

High-density lipoprotein cholesterol (HDL-C) has been well established as an inverse predictor of coronary heart disease (CHD), and in recent years, investigations have focused on the genetic regulation of high-density lipoprotein. Although numerous candidate genes contribute to the low HDL-C phenotype, their impact on CHD is heterogeneous, reflecting diverse gene-gene interactions and gene-environmental relationships. This review summarizes recent data involving HDL regulatory genes and their role in atherothrombosis. The primary genetic determinants associated with relative HDL-C deficiency states are the ATP binding cassette protein, ABCA1; apolipoprotein (APO) A1; and lecithin cholesteryl acyl transferase. Other potentially important candidates invoked in low HDL-C syndromes in humans include APOC3, lipoprotein lipase, sphingomyelin phosphodiesterase 1, and glucocerebrosidase. Molecular variation in ABCAI and APOAI and, in selected cases, lecithin cholesteryl acyl transferase deficiency have been associated with increased CHD, whereas two notable variants, APOAIMilano and APOAIParis, are associated with reduced risk. Low HDL-C syndromes have generally been correlated with an increased risk of CHD. However, single-gene abnormalities responsible for HDL-C deficiency states may have variable effects on atherothrombotic risk.

Association of serum carotenoids and tocopherols with gamma-glutamyltransferase: the Cardiovascular Risk Development in Young Adults (CARDIA) Study.

Our previous studies suggest that serum gamma-glutamyltransferase (GGT) activity may be related to oxidative stress, supporting findings of experimental studies. To further examine the role of GGT in relation to oxidative stress, we investigated the association between serum carotenoids and tocopherols, which have antioxidant properties, and serum GGT. Study participants were 3128 black and white men and women 17-35 years of age in 1985-1986. Serum carotenoids and tocopherols were measured at years 0 and 7, and serum GGT was measured at years 0 and 10. Circulating concentrations of alpha-carotene, beta-carotene, and beta-cryptoxanthin inversely predicted the serum GGT concentration measured 10 years later in a dose-response manner (P for trend <0.01). Year 0 zeaxanthin/lutein was weakly inversely associated with year 10 GGT (P for trend = 0.08), and year 0 lycopene was unrelated to year 10 GGT. Adjusted geometric means of serum GGT at year 10 according to quintile of the sum of four carotenoids at year 0 (alpha-carotene, beta-carotene, beta-cryptoxanthin, and zeaxanthin/lutein) were 19.9, 19.4, 18.9, 17.8, and 17.3 U/L (P for trend <0.01). Year 0 alpha-tocopherol was also a significant inverse predictor of year 10 serum GGT concentration (P for trend = 0.03), whereas gamma-tocopherol showed an inconsistent or possibly U-shaped association. However, year 0 serum GGT did not predict serum antioxidants measured 7 years later. Our present findings support the contention that serum GGT concentration is a marker related with oxidative stress.

Diurnal changes in nitric oxide emissions from conventional tillage and pasture sites in the Amazon Basin: influence of soil temperature

We have investigated a subset of restoration practices applied to a degraded pasture at Fazenda Nova Vida, a 22000 ha cattle ranch in Rond^onia, Brazil. Nitric oxide (NO) and carbon dioxide (CO2) emissions from soils were measured in conventional tillage and current pasture sites to assess N and C losses. Mean daily NO emissions from tilled plots were at least twice those from the pasture. Nitric oxide emissions from the tilled sites showed a strong diurnal pattern, while those from the pasture sites did not. Mean daytime NO emissions from the tilled sites were 9.7 μg NO-N m−2 h−1, while mean nighttime emissions were 29.7 μg NO-N m−2 h−1. In the pasture sites, NO emissions were 7.6 μg NO-N m−2 h−1 during the day, and 7.7 μg NO-N m−2 h−1 at night. Surface soil temperature was a good inverse predictor (r2=0.75) of NO emissions from the tilled sites. Carbon dioxide emissions from the tilled sites were generally larger than CO2 emissions from the pasture sites. The mean CO2 emission rate from the tilled sites was 179 mg C m−2 h−1, while it was 123 mg C m−2 h−1 from the pasture sites. There was no distinct diurnal pattern for CO2 emissions. We found that the very high temperatures measured at the soil surface in the tillage plots, in the range of 40–45°C, reduced the rate of NO emission. The reduction in NO emissions may be because of the sensitivity of autotrophic nitrifiers to high temperatures. This study provides insights on how land-use change may alter regional NO fluxes by exposing certain microbial communities to extreme environmental conditions. Future studies of NO emissions in tropical agricultural systems where soils are bare for extend periods need to make diurnal measurements or the daily fluxes will be substantially underestimated.

The prevalence and predictors of psychological distress in men with prostate cancer who are seeking support.

The incidence of prostate cancer has risen sharply in the last decade, yet knowledge about the psychological health of men with this disease is still limited. A study was therefore undertaken to identify (1) the prevalence of psychological distress in these males, and (2) factors predicting psychological distress. Retrospective cross-sectional survey design by means of a self-administered questionnaire. A sample of 94 men with various stages of prostate cancer completed the Functional Assessment of Cancer Therapy-Prostate Instrument (FACT-P), the Hospital Anxiety Depression Scale (HADS) and items measuring satisfaction with medical care. We detected a prevalence rate of 38% of participants reporting psychological distress corresponding to a HADS cut-off score at or above 15. A standard multivariate regression analysis revealed social/family well-being, physical well-being and functional well-being as significant inverse predictors of psychological distress. Health professionals should be aware of the potential for psychological distress in patients exhibiting poor physical functioning and those with apparent deficits in social or family support in this under-studied group of patients. Strategies for psychosocial intervention are implied.

Adipose tissue as a source of inflammatory cytokines in health and disease: Focus on end-stage renal disease

Adipose tissue is a necessary survival characteristic of species that do not have constant access to food. TNF-alpha is a very fundamental "internal regulator" (intra-system) of adipose tissue metabolism, and IL-6 and IL-1 beta are relevant control factors, as well. Leptin and IL-6, but not TNF-alpha, appear to be the major signals linking adipose tissue to the systemic immunologic response. In ESRD, it has been coherently observed that acute-phase reactants like CRP and serum amyloid A are independently associated to atherosclerosis, death, and cardiovascular complications. Leptin is inversely related with plasma creatinine, suggesting that reduced renal clearance is a primary factor responsible for hyperleptinemia in ESRD. On the other hand, this adipose tissue hormone behaves as an inverse acute-phase reactant (i.e., it decreases during spontaneous episodes of the acute-phase response). Dialysis patients with hyperleptinemia have more severe degrees of insulin resistance but further studies are required to see whether leptin plays a role in insulin resistance in these patients. The most abundant protein synthesized in the adipose tissue, adiponectin, is inversely related to metabolic risk factors like glucose, triglycerides, insulin, and HDL cholesterol in uremic patients, suggesting that this cytokine is a protective factor for the cardiovascular system. Accordingly, plasma adiponectin is an independent, inverse predictor of incident cardiovascular events in dialysis patients.

HIGH DENSITY LIPOPROTEIN: GUARDIAN OF THE VASCULAR SYSTEM?

SUMMARYThe role of low‐density lipoprotein in the development of coronary heart disease (CHD) is well recognised. There is also growing evidence that high‐density lipoprotein cholesterol (HDL‐C) is a powerful inverse predictor for premature CHD and that maintaining a high HDL‐C level may guard against atherosclerosis. Patients with low HDL‐C levels often also have central obesity, insulin resistance and other features of the metabolic syndrome. This syndrome is both increasingly common and strongly implicated in the growing worldwide epidemic of type 2 diabetes. HDL‐C may be increased by lifestyle changes, e.g. weight loss, physical activity and smoking cessation. Pharmacological agents such as fibrates, niacin and statins have also been shown significantly to elevate HDL‐C. Although current guidelines are beginning to recognise the protective role of HDL‐C level in preventing coronary events, HDL‐C should be adopted soon as a target for intervention in its own right.

Two Dimensions of Attachment to God and Their Relation to Affect, Religiosity, and Personality Constructs

In this study we sought to address several limitations of previous research on attachment theory and religion by (1) developing a dimensional attachment to God scale, and (2) demonstrating that dimensions of attachment to God are predictive of measures of affect and personality after controlling for social desirability and other related dimensions of religiosity. Questionnaire measures of these constructs were completed by a sample of university students and community adults (total n= 374). Consistent with prior research on adult romantic attachment, two dimensions of attachment to God were identified: avoidance and anxiety. After statistically controlling for social desirability, intrinsic religiousness, doctrinal orthodoxy, and loving God image, anxious attachment to God remained a significant predictor of neuroticism, negative affect, and (inversely) positive affect; avoidant attachment to God remained a significant inverse predictor of religious symbolic immortality and agreeableness. These findings are evidence that correlations between attachment to God and measures of personality and affect are not merely byproducts of confounding effects of socially desirable responding or other dimensions of religiosity.

Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease.

Adiponectin (ADPN), which is a secretory protein of adipose tissue, attenuates endothelial inflammatory responses in vitro. Among human subjects, plasma ADPN concentrations are reduced among patients with atherosclerotic complications but are substantially increased among patients with advanced renal failure. The clinical and biochemical correlates of plasma ADPN levels were investigated and the predictive power of ADPN levels with respect to survival rates and cardiovascular events was prospectively tested in a cohort of 227 hemodialysis patients, who were monitored for 31 +/- 13 mo. Plasma ADPN levels were 2.5 times higher (P < 0.0001) among dialysis patients (15.0 +/- 7.7 microg/ml) than among healthy subjects (6.3 +/- 2.0 microg/ml), were independent of age, and were higher (P = 0.03) among women (15.2 +/- 7.9 microg/ml) than among men (14.0 +/- 7.4 microg/ml). For both genders, plasma ADPN levels were inversely related to body mass index values, plasma leptin levels, insulin levels, serum triglyceride levels, and homeostatic model assessment index values. Furthermore, plasma ADPN levels were directly related to HDL cholesterol levels and inversely related to von Willebrand factor levels. Plasma ADPN levels were lower (P < 0.05) among patients who experienced new cardiovascular events (13.7 +/- 7.3 microg/ml) than among event-free patients (15.8 +/- 7.8 microg/ml). There was a 3% risk reduction for each 1 microg/ml increase in plasma ADPN levels, and the relative risk of adverse cardiovascular events was 1.56 times (95% confidence interval, 1.12 to 1.99 times) higher among patients in the first ADPN tertile, compared with those in the third tertile. Plasma ADPN levels are an inverse predictor of cardiovascular outcomes among patients with end-stage renal disease. Furthermore, ADPN is related to several metabolic risk factors in a manner consistent with the hypothesis that this protein acts as a protective factor for the cardiovascular system.