Estimation of contribution of changes in classic risk factors to trends in coronary-event rates across the WHO MONICA Project populations

Background. From the mid-1980s to mid-1990s, the WHO MONICA Project monitored coronary events and classic risk factors for coronary heart disease (CHD) in 38 populations from 21 countries. We assessed the extent to which changes in these risk factors explain the variation in the trends in coronary-event rates, across the populations. Methods. In men and women aged 35-64 years, non-fatal myocardial infarction and coronary deaths were registered continuously to assess trends in rates of coronary events. We carried out population surveys to estimate trends in risk factors. Trends in event rates were regressed on trends in risk score and in individual risk factors. Findings. Smoking rates decreased in most male populations but trends were mixed in women; mean blood pressures and cholesterol concentrations decreased, body-mass index increased, and overall risk scores and coronary-event rates decreased. The model of trends in 10-year coronary-event rates against risk scores and single risk factors showed a poor fit, but this was improved with a 4-year time lag for coronary events. The explanatory power of the analyses was limited by imprecision of the estimates and homogeneity of trends in the study populations. Interpretation. Changes in the classic risk factors seem to partly explain the variation in population trends in CHD. Residual variance is attributable to difficulties in measurement and analysis, including time lag, and to factors that were not included, such as medical interventions. The results support prevention policies based on the classic risk factors but suggest potential for prevention beyond these.

Trends in coronary risk factors in the WHO MONICA Project

Background. The World Health Organization (WHO) MONICA Project was established to determine how trends in event rates for coronary heart disease (CHD) and, optionally, stroke were related to trends in classic coronary risk factors. Risk factors were therefore monitored over ten years across 38 populations from 21 countries in four continents (overall period covered: 1979-1996). Methods. A standard protocol was applied across participating centres, in at least two, and usually three, independent surveys conducted on random samples of the study populations, well separated within the 10-year study period. Results. Smoking rates decreased in most male populations (35-64 years) but in females the majority showed increases. Systolic blood pressure showed decreasing trends in the majority of centres in both sexes. Mean levels of cholesterol generally showed downward trends, which, although the changes were small, had large effects on risk. There was a trend of increasing body mass index (BMI) with half the female populations and two-thirds of the male populations showing a significant increase. Conclusions. It is feasible to monitor the classic CHD risk factors in diverse populations through repeated surveys over a decade. In general, the risk factor trends are downwards in most populations but in particular, an increase in smoking in women in many populations and increasing BMI, especially in men, are worrying findings with significant public health implications.

Investigation of Genetic Variation in Scavenger Receptor Class B, Member 1 (SCARB1) and Association with Serum Carotenoids

Objective: To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD).
Design: A cross-sectional study of healthy adults aged 20 to 70.
Participants: We recruited 302 participants after local advertisement.
Methods: We measured MPOD by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by high-performance liquid chromatography and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and Carotenoids in Age-Related Eye Disease Study (CAREDS) cohorts.
Main Outcome Measures: Odds ratios for MPOD area, serum L and Z concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and gender.
Results: After multiple regression analysis with adjustment for age, body mass index, gender, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, smoking, and dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P = 0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P = 2×10-4), an SNP in high linkage disequilibrium with rs11057841 (r2 = 0.93). No interactions by gender were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses.
Conclusions: Our study has identified association between rs11057841 and serum L concentration (24% increase per T allele) in healthy subjects, independent of potential confounding factors. Our data supports further evaluation of the role for SCARB1 in the transport of macular pigment and the possible modulation of age-related macular degeneration risk through combating the effects of oxidative stress within the retina.
Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references. Ophthalmology 2013;120:1632–1640 © 2013 by the American Academy of Ophthalmology.

Testing metabolic scaling theory using intraspecific allometries in Antarctic microarthropods

Quantitative scaling relationships among body mass, temperature and metabolic rate of organisms are still controversial, while resolution may be further complicated through the use of different and possibly inappropriate approaches to statistical analysis. We propose the application of a modelling strategy based on the theoretical approach of Akaike's information criteria and non-linear model fitting (nlm). Accordingly, we collated and modelled available data at intraspecific level on the individual standard metabolic rate of Antarctic microarthropods as a function of body mass (M), temperature (T), species identity (S) and high rank taxa to which species belong (G) and tested predictions from metabolic scaling theory (mass-metabolism allometric exponent b = 0.75, activation energy range 0.2-1.2 eV). We also performed allometric analysis based on logarithmic transformations (lm). Conclusions from lm and nlm approaches were different. Best-supported models from lm incorporated T, M and S. The estimates of the allometric scaling exponent linking body mass and metabolic rate resulted in a value of 0.696 +/- 0.105 (mean +/- 95% CI). In contrast, the four best-supported nlm models suggested that both the scaling exponent and activation energy significantly vary across the high rank taxa (Collembola, Cryptostigmata, Mesostigmata and Prostigmata) to which species belong, with mean values of b ranging from about 0.6 to 0.8. We therefore reached two conclusions: 1, published analyses of arthropod metabolism based on logarithmic data may be biased by data transformation; 2, non-linear models applied to Antarctic microarthropod metabolic rate suggest that intraspecific scaling of standard metabolic rate in Antarctic microarthropods is highly variable and can be characterised by scaling exponents that greatly vary within taxa, which may have biased previous interspecific comparisons that neglected intraspecific variability.

Maternal Vitamin D Status in Type 1 Diabetic Pregnancy: Impact on Neonatal Vitamin D Status and Association with Maternal Glycaemic Control

Objective: The first aim of this study was to assess 25-hydroxy vitamin D (25OHD) concentrations in women with type 1 diabetes (T1DM) during pregnancy, post-delivery and also foetal (cord blood) 25OHD concentrations and to examine relationships between these. The second aim of the study was to investigate potential interactions between maternal body mass index (BMI) and foetal vitamin D status. A further study aim was to examine potential relationships between maternal 25OHD and glycosylated haemoglobin (HbA_1c) throughout pregnancy.

Research Design and Methods: This was an observational study of 52 pregnant controls without diabetes and 65 pregnant women with T1DM in a university teaching hospital. Maternal serum 25OHD was measured serially throughout the pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS).

Results: Vitamin D deficiency (25OHD <25 nmol/L) was apparent in both the T1DM subjects and controls at all 3 pregnancy trimesters. Vitamin D levels in all cord blood were <50 nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3 trimesters in the T1DM group (p= 0.02; p<0.001; p<0.001). 25OHD levels within cord blood were significantly lower for women with diabetes classified as obese vs. normal weight at booking [normal weight BMI <25 kg/m² vs. obese BMI >30 kg/m² (nmol/L±SD); 19.93±11.15 vs. 13.73±4.74, p= 0.026]. In the T1DM group, HbA_1c at booking was significantly negatively correlated with maternal 25OHD at all 3 trimesters (p= 0.004; p = 0.001; p= 0.05).

Conclusion: In T1DM pregnancy, low vitamin D levels persist throughout gestation and post-delivery. Cord blood vitamin D levels correlate with those of the mother, and are significantly lower in obese women than in their normal weight counterparts. Maternal vitamin D levels exhibit a significant negative relationship with HbA_1c levels, supporting a potential role for this vitamin in maintaining glycaemic control. 

Plasma Lipoproteins and Preeclampsia in Women with Type 1 Diabetes: A Prospective Study

Context: In nondiabetic pregnancy, cross-sectional studies have shown associations between maternal dyslipidemia and preeclampsia (PE). In type 1 diabetes mellitus (T1DM), the prevalence of PE is increased 4-fold, but prospective associations with plasma lipoproteins are unknown.

Objectives: The aim of this study was to define lipoprotein-related markers and potential mechanisms for PE in T1DM.

Design and Settings: We conducted a multicenter prospective study in T1DM pregnancy.

Patients: We studied 118 T1DM women (26 developed PE, 92 remained normotensive). Subjects were studied at three visits before PE onset [12.2 1.9, 21.6 1.5, and 31.5 1.7 wk gestation (means SD)] and at term (37.6 2.0 wk). Nondiabetic normotensive pregnant women (n 21) were included for reference.

Main Outcome Measures: Conventional lipid profiles, lipoprotein subclasses [defined by size (nuclear magnetic resonance) and by apolipoprotein content], serum apolipoproteins (ApoAI, ApoB, and ApoCIII), and lipolysis (ApoCIII ratio) were measured in T1DM women with and without subsequent PE.

Results: In women with vs. without subsequent PE, at the first and/or second study visits: lowdensity lipoprotein (LDL)-cholesterol, particle concentrations of total LDL and large (but not small) LDL, serum ApoB, and ApoB:ApoAI ratio were all increased (P 0.05); peripheral lipoprotein lipolysis was decreased (P0.01). These early differences remained significant in covariate analysis (glycated hemoglobin, actual prandial status, gravidity, body mass index, and diabetes duration) but were not present at the third study visit. High-density lipoprotein and very low-density lipoprotein subclasses did not differ between groups before PE onset.

Conclusions: Early in pregnancy, increased cholesterol-rich lipoproteins and an index suggesting decreased peripheral lipolysis were associated with subsequent PE in T1DM women. Background maternal lipoprotein characteristics, perhaps masked by effects of late pregnancy, may influence PE risk.

Low clusterin levels in high-density lipoprotein associate with insulin resistance, obesity, and dyslipoproteinemia

To determine whether obesity and insulin resistance associate with changes in the protein content of high-density lipoprotein (HDL) in 2 different groups of men by using targeted proteomics.

Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome

Strawberries have been reported to be potent antioxidants and reduce cardiovascular risk factors, such as elevated blood pressure, hyperglycemia, dyslipidemia, and inflammation in limited studies. We hypothesized that freeze-dried strawberry supplementation will improve blood pressure, impaired glucose, dyslipidemia, or circulating adhesion molecules in obese subjects with metabolic syndrome, thereby lowering cardiovascular risk factors in these subjects. Twenty-seven subjects with metabolic syndrome (2 males and 25 females; body mass index, 37.5 +/- 2.15 kg/m(2); age, 47.0 +/- 3.0 years [means +/- SE]) consumed 4 cups of freeze-dried strawberry beverage (50 g freeze-dried strawberries approximately 3 cups fresh strawberries) or equivalent amounts of fluids (controls, 4 cups of water) daily for 8 weeks in a randomized controlled trial. Anthropometrics and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screen and 8 weeks of the study. Strawberry supplementation significantly decreased total and low-density lipoprotein cholesterol (5.8 +/- 0.2 to 5.2 +/- 0.2 mmol/L and 3.5 +/- 0.2 to 3.1 +/- 0.1 mmol/L, respectively [means +/- SE], P <.05) and small low-density lipoprotein particles using nuclear magnetic resonance-determined lipoprotein subclass profile vs controls at 8 weeks (794.6 +/- 94.0 to 681.8 +/- 86.0 nmol/L [means +/- SE], P <.05). Strawberry supplementation further decreased circulating levels of vascular cell adhesion molecule-1 vs controls at 8 weeks (272.7 +/- 17.4 to 223.0 +/- 14.0 ng/mL [means +/- SE], P <.05). Serum glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure, and waist circumference were not affected. Thus, short-term freeze-dried strawberry supplementation improved selected atherosclerotic risk factors, including dyslipidemia and circulating adhesion molecules in subjects with metabolic syndrome, and these results need confirmation in future trials.

Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes

To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress.

Apolipoprotein C-III protein concentrations and gene polymorphisms in type 1 diabetes:associations with lipoprotein subclasses

Serum apolipoprotein C-III (apoCIII) concentration and apoCIII gene polymorphisms have been shown to be a risk factor for cardiovascular disease; however, the underlying mechanisms remain unclear. In addition, no studies have been performed that address these issues in type 1 diabetes. The current study investigated apoCIII protein and apoCIII gene variation in a normotriglyceridemic (82 +/- 57 mg/dL) population of patients with type 1 diabetes, the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort. Blood samples were obtained in 409 patients after an overnight fast. Serum apoCIII concentration was highly correlated with multiple changes in lipids and lipoproteins that resulted in an adverse cardiovascular disease risk profile. Higher apoCIII concentrations were associated (P <.0001) with increased triglycerides (r = 0.78), total (r = 0.61) and low-density lipoprotein (LDL) (r = 0.40) cholesterol, apoA-I (r = 0.26), and apoB (r = 0.50), and these relationships persisted after controlling for age, gender, body mass index (BMI), and hemoglobin A1c (HbA1c). Nuclear magnetic resonance (NMR) lipoprotein subclass analyses demonstrated that apoCIII was correlated with an increase in very-low-density lipoprotein (VLDL) subclasses (P = .0001). There also was a highly significant positive relationship between serum apoCIII concentration and the LDL particle concentration in both men (r = 0.49, P = .001) and women (r = 0.40, P = .001), and a highly significant negative relationship between serum apoCIII levels and average LDL particle size in both men (r = -0.37, P = .001) and women (r = -0.22, P = .001) due primarily to an augmentation in the small L1 subclass (r = 0.42, P = .0001). Neither the T(-455) --> C polymorphism affecting an insulin response element in the apoCIII gene promoter nor a SacI polymorphism in the 3'UTR were associated with any alterations in circulating apoCIII concentrations, serum lipids, apolipoprotein concentrations, lipoprotein composition, or parameters measured by NMR lipoprotein subclass analyses. In summary, elevated apoCIII concentration was associated with risk factors for cardiovascular disease in normolipidemic type 1 diabetic patients through associated changes in lipoprotein subfraction distributions, which were independent of apoCIII genotype.

Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients

Serum PEDF levels (mean (S.D.)) were increased in 96 Type 2 diabetic vs. 54 non-diabetic subjects; 5.3 (2.8) vs. 3.2 (2.0)mug/ml, p

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study:preeclampsia

Objective: The purpose of this study was to examine associations of fasting C-peptide, body mass index (BMI), and maternal glucose with the risk of preeclampsia in a multicenter multinational study. Study Design: We conducted a secondary analysis of a blinded observational cohort study. Subjects underwent a 75-g oral glucose tolerance test at 24-32 weeks' gestation. Associations of preeclampsia with fasting C-peptide, BMI, and maternal glucose were assessed with the use of multiple logistic regression analyses and adjustment for potential confounders. Results: Of 21,364 women who were included in the analyses, 5.2% had preeclampsia. Adjusted odds ratios for preeclampsia for 1 SD higher fasting C-peptide (0.87 ug/L), BMI (5.1 kg/m), and fasting (6.9 mg/dL), 1-hour (30.9 mg/dL), and 2-hour plasma glucose (23.5 mg/dL) were 1.28 (95% confidence interval [CI], 1.20-1.36), 1.60 (95% CI, 1.60-1.71), 1.08 (95% CI, 1.00-1.16), 1.19 (95% CI, 1.11-1.28), and 1.21 (95% CI,1.13-1.30), respectively. Conclusion: Results indicate strong, independent associations of fasting C-peptide and BMI with preeclampsia. Maternal glucose levels (below diabetes mellitus) had weaker associations with preeclampsia, particularly after adjustment for fasting C-peptide and BMI. © 2010 Mosby, Inc. All rights reserved.

Pioglitazone protects HDL(2&3) against oxidation in overweight and obese men

The worldwide epidemic of obesity is a major public health concern and is persuasively linked to the rising prevalence of diabetes and cardiovascular disease. Obesity is often associated with an abnormal lipoprotein profile, which may be partly negated by pioglitazone intervention, as this can influence the composition and oxidation characteristics of low-density lipoprotein (LDL). However, as pioglitazone's impact on these parameters within high-density lipoprotein (HDL), specifically HDL(2&3), is absent from the literature, this study was performed to address this shortcoming.

A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study

Objective: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.

Design: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort.

Results: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric
cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m2). Mutual adjustment of WHR and BMI attenuated
both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.

Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI

Common variant at 16p11.2 conferring risk of psychosis

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).