[Show abstract][Hide abstract] ABSTRACT: Adverse blood pressure (BP) is a major independent risk factor for epidemic cardiovascular diseases affecting almost one third of the US adult population. This review synthesizes results from studies published over the past few years on BP differences and prevalent hypertension between US blacks and whites and their different intakes of foods (e.g., fruits, vegetables, and dairy products) and micronutrients (e.g., vitamin D, calcium, potassium, and phosphorus). Studies have consistently reported higher prevalence of adverse BP levels and hypertension and less favorable dietary intakes in blacks than in whites, but the influence of specific dietary factors on high BP risk for blacks remains unclear.
Current Hypertension Reports 02/2015; 17(2):517. · 3.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background—Epidemiologic evidence is sparse on the effect of dietary behaviors and diet
quality on body mass index (BMI) that may be important drivers of the obesity epidemic.
Objective—This study investigated the relationships of frequency of eating and time of intake to
energy density, nutrient quality and BMI using data from the INTERnational study on MAcro/
micronutrients and blood Pressure (INTERMAP) including 2,696 men and women aged 40-59
from the United States and the United Kingdom.
Design—INTERMAP is a cross-sectional investigation with four 24-hour dietary recalls and
BMI measurements conducted between 1996 and 1999. Consumption of solid foods was
aggregated into eating occasion. Nutrient density is expressed using the Nutrient Rich Food (NRF
9.3) index. The ratio of evening/morning energy intake was calculated; mean values of four visits
Statistical analyses performed—Characteristics across eating occasion categories are
presented as adjusted mean with corresponding 95% confidence interval. Multiple linear
regression models were used to examine associations of eating occasions, ratio of evening/
morning energy intake, dietary energy density, and NRF 9.3 index with BMI.
Results—Compared to participants with < 4 eating occasions/24-hours, those with ≥ 6 eating
occasions/24-hours had lower mean: BMI: 27.3 vs. 29.0 kg/m2; total energy intake: 2,129 vs.
2,472 kcal/24-hours; dietary energy density: 1.5 vs. 2.1 kcal/g; and higher NRF 9.3 index: 34.3 vs.
28.1. In multiple regression analyses, higher evening intake relative to morning intake was directly
associated with BMI; however this did not influence the relationship between eating frequency
Conclusions—Our results suggest that a larger number of small meals may be associated with
improved diet quality and lower BMI. This may have implications for behavioral approaches to
controlling the obesity epidemic.
Journal of the American Academy of Nutrition and Dietetics 01/2015; · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.
We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24±4 kg/m2). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87%±3%; R2 = 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160%±2%; R2 = 0.92).
Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.
PLoS Medicine 12/2014; 11(12):e1001765. · 14.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Observational studies have suggested that the risks of non-communicable diseases in voluntary migrants become similar to those in the host population after one or more generations, supporting the hypothesis that these diseases have a predominantly environmental (rather than inherited) origin. However, no study has been conducted thus far to identify alterations at the molecular level that might mediate these changes in disease risk after migration.
International Journal of Epidemiology 10/2014; · 9.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The Airwave Health Monitoring Study was established to evaluate possible health risks associated with use of TETRA, a digital communication system used by police forces and other emergency services in Great Britain since 2001. The study has been broadened to investigate more generally the health of the work force.
From 2004, participants from each force who agreed to participate were enrolled either with an enrolment questionnaire or a comprehensive health screening performed locally. This includes questionnaire, 7-day food diaries, anthropometry, measurements of cardiovascular and cognitive function, blood chemistry, coagulation and haematology. Blood and urine samples are stored in vapour phase liquid nitrogen allowing long-term access for biochemical or genetic analysis. Access to the resource is via an access committee and a steering committee, including external scientific advisers as well as representatives of the police officers and staff.
By the end of 2012, the study had recruited 42,112 participants, of whom 35,199 (83.6%) had attended the health screening. Almost two thirds of participants were men and 71% of them were a TETRA user. Being in lower ranks (constable/sergeant and staff) was associated with a worse cardio-metabolic risk profile compared to higher ranks (inspector or chief inspector, superintendent and above).
The Airwave Health Monitoring Study is the only large-scale cohort study of police employees worldwide. The specificities of this sample, such as its well-defined job hierarchy, make it a particularly valuable occupational cohort. Participants have consented to the use of their data and samples for future, currently unspecified, research purposes.
Environmental Research 10/2014; 134:280–285. · 3.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Dietary Approaches to Stop Hypertension-Sodium (DASH-Sodium) trial demonstrated beneficial effects on blood pressure (BP) of the DASH diet with lower sodium intake when compared with typical American diet. The subsequent Optimal Macronutrient Intake Trial for Heart Health (OMNIHEART) trial reported additional BP benefits from replacing carbohydrate in the DASH diet with either protein or monounsaturated fats. The primary aim of this study is to assess possible BP benefits of an OMNIHEART-like diet in free-living Americans using cross-sectional US population data of The International Study of Macronutrients, Micronutrients and Blood Pressure (INTERMAP) study. The INTERMAP data include four 24-hour dietary recalls, 2 timed 24-hour urine collections, 8 BP readings for 2195 individuals aged 40 to 59 years from 8 US INTERMAP population samples. Analyses are conducted using 2 approaches: (1) regression of BP on a linear OMNIHEART nutrient score calculated for each individual and (2) a Bayesian approach comparing estimated BP levels of an OMNIHEART-like nutrient profile with a typical American nutrient profile. After adjustment for potential confounders, an OMNIHEART score higher by 1 point was associated with systolic/diastolic BP differences of -1.0/-0.5 mm Hg (both P<0.001). Mean systolic/diastolic BPs were 111.3/68.4 and 115.2/70.6 mm Hg for Bayesian OMNIHEART and Control profiles, respectively, after controlling for possible confounders, with BP differences of -3.9/-2.2 mm Hg, P(difference ≤0)=0.98/0.96. Findings were comparable for men and women, for nonhypertensive participants, and with adjustment for antihypertensive treatment. Our findings from data on US population samples indicate broad generalizability of OMNIHEART results beyond the trial setting and support recommendations for an OMNIHEART-style diet for prevention/control of population-wide adverse BP levels.
[Show abstract][Hide abstract] ABSTRACT: Habitual high-salt intake raises blood pressure and risk of cardiovascular diseases. To prevent/control these risks, reduced salt diet (RSD) is recommended in many countries and some people report practicing it; however, little is known about actual achievement. This population-based study assessed level of 24-h dietary sodium intake of participants reporting RSD and others.
[Show abstract][Hide abstract] ABSTRACT: The genetic sequence variation of people from the Indian subcontinent who comprise one-quarter of the world's population, is not well described. We carried out whole genome sequencing of 168 South Asians, along with whole-exome sequencing of 147 South Asians to provide deeper characterisation of coding regions. We identify 12,962,155 autosomal sequence variants, including 2,946,861 new SNPs and 312,738 novel indels. This catalogue of SNPs and indels amongst South Asians provides the first comprehensive map of genetic variation in this major human population, and reveals evidence for selective pressures on genes involved in skin biology, metabolism, infection and immunity. Our results will accelerate the search for the genetic variants underlying susceptibility to disorders such as type-2 diabetes and cardiovascular disease which are highly prevalent amongst South Asians.
PLoS ONE 08/2014; 9(8):e102645. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fetal and postnatal growth have been associated with adult blood pressure (BP), but findings about the relative importance of growth at different stages of life on BP are inconsistent.
Journal of Epidemiology & Community Health 08/2014; · 3.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolomics is the field of "-omics" research concerned with the comprehensive characterization of the small low-molecular-weight metabolites in biological samples. In epidemiology, it represents an emerging technology and an unprecedented opportunity to measure environmental and other exposures with improved precision and far less measurement error than with standard epidemiologic methods. Advances in the application of metabolomics in large-scale epidemiologic research are now being realized through a combination of improved sample preparation and handling, automated laboratory and processing methods, and reduction in costs. The number of epidemiologic studies that use metabolic profiling is still limited, but it is fast gaining popularity in this area. In the present article, we present a roadmap for metabolomic analyses in epidemiologic studies and discuss the various challenges these data pose to large-scale studies. We discuss the steps of data preprocessing, univariate and multivariate data analysis, correction for multiplicity of comparisons with correlated data, and finally the steps of cross-validation and external validation. As data from metabolomic studies accumulate in epidemiology, there is a need for large-scale replication and synthesis of findings, increased availability of raw data, and a focus on good study design, all of which will highlight the potential clinical impact of metabolomics in this field.
American Journal of Epidemiology 06/2014; · 4.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: National mortality statistics report that UK Indian Asians are at approxiamately 2 fold higher risk of cardiovascular disease mortality compared with people of European ancestry. However, previous studies in North American and European populations suggest that up to 40% of death certificates are incorrect, leading to an overestimation of cardiovascular disease mortality. The validity of routine death certification amongst Indian Asians is unknown.
[Show abstract][Hide abstract] ABSTRACT: Public concern about potential health risks associated with incineration has prompted studies to investigate the relationship between incineration and risk of cancer, and more recently, birth outcomes. We conducted a systematic review of epidemiologic studies evaluating the relationship between waste incineration and the risk of adverse birth and neonatal outcomes.
Literature searches were performed within the MEDLINE database, through PubMed and Ovid interfaces, for the search terms; incineration, birth, reproduction, neonatal, congenital anomalies and all related terms. Here we discuss and critically evaluate the findings of these studies.
A comprehensive literature search yielded fourteen studies, encompassing a range of outcomes (including congenital anomalies, birth weight, twinning, stillbirths, sex ratio and infant death), exposure assessment methods and study designs. For congenital anomalies most studies reported no association with proximity to or emissions from waste incinerators and "all anomalies", but weak associations for neural tube and heart defects and stronger associations with facial clefts and urinary tract defects. There is limited evidence for an association between incineration and twinning and no evidence of an association with birth weight, stillbirths or sex ratio, but this may reflect the sparsity of studies exploring these outcomes.
The current evidence-base is inconclusive and often limited by problems of exposure assessment, possible residual confounding, lack of statistical power with variability in study design and outcomes. However, we identified a number of higher quality studies reporting significant positive relationships with broad groups of congenital anomalies, warranting further investigation. Future studies should address the identified limitations in order to help improve our understanding of any potential adverse birth outcomes associated with incineration, particularly focussing on broad groups of anomalies, to inform risk assessment and waste policy.
Environment international 05/2014; 69C:120-132. · 6.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Evidence from animal models suggests that locomotion and blood pressure share common neurophysiological regulatory systems. As a result of this common regulation, we hypothesized that the development of locomotion in human infants would be associated with blood pressure levels in adulthood. The study sample comprised 4,347 individuals with measures of locomotive and non-locomotive neuromotor development in infancy and adult blood pressure levels within a longitudinal birth cohort study, the Northern Finland Birth Cohort 1966. Later development in all three stages of locomotive development during infancy was associated with higher systolic and diastolic blood pressure levels at age 31. For age of walking without support, 0.34 (95 % CI 0.07 to 0.60)-mm Hg higher SBP and 0.38 (95 % CI 0.15 to 0.62)-mm Hg higher DBP were estimated for each month of later achievement (P = 0.012 for SBP; P = 0.001 for DBP). No association was identified for non-locomotive neuromotor development. Conclusion: These results highlight the positive sequelae of advanced locomotive development during infancy, suggesting that the common regulatory systems between locomotion and blood pressure may influence the development of raised blood pressure over time.
European Journal of Pediatrics 05/2014; 173(10). · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Warm temperatures adversely affect disease occurrence and death, in extreme conditions as well as when the temperature changes are more modest. Therefore climate change, which is expected to affect both average temperatures and temperature variability, is likely to impact health even in temperate climates. Climate change risk assessment is enriched if there is information on vulnerability and resilience to effects of temperature. Some studies have analysed socio-demographic characteristics that make individuals vulnerable to adverse effects of temperature. Less is known about community-level vulnerability. We used geo-coded mortality and environmental data and Bayesian spatial methods to conduct a national small-area analysis of the mortality effects of warm temperature for all 376 districts in England and Wales. In the most vulnerable districts, those in London and south/southeast England, odds of dying from cardiorespiratory causes increased by more than 10% for 1 °C warmer temperature, compared with virtually no effect in the most resilient districts, which were in the far north. A 2 °C warmer summer may result in 1,552 (95% credible interval 1,307-1,762) additional deaths, about one-half of which would occur in 95 districts. The findings enable risk and adaptation analyses to incorporate local vulnerability to warm temperature and to quantify inequality in its effects.
[Show abstract][Hide abstract] ABSTRACT: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
[Show abstract][Hide abstract] ABSTRACT: Background: Epidemiological evidence is limited and inconclusive on the
separate contributions of soluble, insoluble fiber and dietary sugars to blood
pressure (BP). This population based study examines relations to systolic and
diastolic BP (SBP/DBP) of total dietary fiber and sugar and their individual
Methods: Cross-sectional data were analysed from the population-based
INTERMAP study, including 2,195 participants ages 40 to 59 from the United
States. During 4 visits, eight BP readings were recorded and dietary intake was
assessed by four in-depth 24-hour dietary recalls. Intakes of fiber and sugars
(g/1000 kcal) were averaged over 4 days. In successive models, BP regression
coefficients per 2 SD higher intake were estimated using isocaloric,
multivariable linear regression with adjustment for multiple possible
confounders (non-dietary and dietary), including each of the other individual
dietary fiber or sugars.
Results: Average intake (SD; g/1000 kcal) of total fiber was 8.8(3.3); soluble
fiber 2.8(1.0); insoluble fiber 5.3(2.2). Average intake (SD; %kcal) of total sugar
was 26.7(7.9) and of sucrose, the largest component, 10.8 (5.1). Partial Pearson
correlation coefficients were low between total fiber and total sugar (r=0.02),
and high between soluble and insoluble fiber (r=0.80). Correlations between
fructose and other individual sugars were high only for glucose (r=0.93), low
(r<0.15) for other sugars.Total dietary fiber intake higher by 7 g/1000 kcal was
associated with SBP lower by 1.7 mm Hg (P=0.01) in an isocaloric model
adjusted for lifestyle factors in addition to total sugar (%); this was attenuated
with further adjustment for urinary potassium excretion. This association was
accounted for by the observed inverse association of insoluble fiber with SBP (-
2.0 mm Hg, P=0.04), additionally adjusted for soluble fiber. Inverse
associations with SBP were found for dietary galactose (-1.5 mm Hg; P=0.04)
and lactose (-2.1 mm Hg;P=0.0006). Intakes of total sugar, fructose, glucose,
maltose, and sucrose were not associated with BP in isocaloric models adjusted
for lifestyle factors and each of the other individual dietary sugars.
Conclusions: Higher intakes of dietary fiber, especially insoluble fiber, may
contribute to lower BP, possibly driven by potassium present in high fiber
foods. Total sugar intake was not associated with blood pressure; however,
intakes of galactose and lactose may favorably influence blood pressure.
[Show abstract][Hide abstract] ABSTRACT: The results of cohort studies relating sodium (Na) intake to blood pressure-related cardiovascular disease (CVD) are inconsistent. To understand whether methodological issues account for the inconsistency, we reviewed the quality of these studies.
We reviewed cohort studies that examined the association between Na and CVD. We then identified methodological issues with greatest potential to alter the direction of association (reverse causality, systematic error in Na assessment), some potential to alter the direction of association (residual confounding, inadequate follow-up), and the potential to yield false null results (random error in Na assessment, insufficient power). We included 26 studies with 31 independent analyses. Of these, 13 found direct associations between Na and CVD, 8 found inverse associations, 2 found J-shaped associations, and 8 found null associations only. On average there were 3 to 4 methodological issues per study. Issues with greater potential to alter the direction of association were present in all but 1 of the 26 studies (systematic error, 22; reverse causality, 16). Issues with lesser potential to alter the direction of association were present in 18 studies, whereas those with potential to yield false null results were present in 23.
Methodological issues may account for the inconsistent findings in currently available observational studies relating Na to CVD. Until well-designed cohort studies in the general population are available, it remains appropriate to base Na guidelines on the robust body of evidence linking Na with elevated blood pressure and the few existing general population trials of the effects of Na reduction on CVD.
[Show abstract][Hide abstract] ABSTRACT: The Indian Asian population accounts for a fifth of all global deaths from coronary heart disease (CHD). CHD deaths on the Indian subcontinent have doubled since 1990, and are predicted to rise a further 50% by 2030. Reasons underlying the increased CHD mortality among Indian Asians remain unknown. Although conventional cardiovascular risk factors contribute to CHD in Indian Asians as in other populations, these do not account for their increased risk. Type-2 diabetes, insulin resistance and related metabolic disturbances are more prevalent amongst Indian Asians than Europeans, and have been proposed as major determinants of higher CHD risk among Indian Asians. However, this view is not supported by prospective data. Genome-wide association studies have not identified differences in allele frequencies or effect sizes in known loci to explain the increased CHD risk in Indian Asians. Limited knowledge of mechanisms underlying higher CHD risk amongst Indian Asians presents a major obstacle to reducing the burden of CHD in this population. Systems biology approaches such as genomics, epigenomics, metabolomics and transcriptomics, provide a non-biased approach for discovery of novel biomarkers and disease pathways underlying CHD. Incorporation of these 'omic' approaches in prospective Indian Asian cohorts such as the London Life Sciences Population Study (LOLIPOP) provide an exciting opportunity for the identification of new risk factors underlying CHD in this high risk population.
Global cardiology science & practice. 01/2014; 2014(1):13-23.
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[Show abstract][Hide abstract] ABSTRACT: Abstract
High sodium intake increases blood pressure, a risk factor for cardiovascular disease, but the effects of sodium intake on global cardiovascular mortality are uncertain.
We collected data from surveys on sodium intake as determined by urinary excretion and diet in persons from 66 countries (accounting for 74.1% of adults throughout the world), and we used these data to quantify the global consumption of sodium according to age, sex, and country. The effects of sodium on blood pressure, according to age, race, and the presence or absence of hypertension, were calculated from data in a new meta-analysis of 107 randomized interventions, and the effects of blood pressure on cardiovascular mortality, according to age, were calculated from a meta-analysis of cohorts. Cause-specific mortality was derived from the Global Burden of Disease Study 2010. Using comparative risk assessment, we estimated the cardiovascular effects of current sodium intake, as compared with a reference intake of 2.0 g of sodium per day, according to age, sex, and country.
In 2010, the estimated mean level of global sodium consumption was 3.95 g per day, and regional mean levels ranged from 2.18 to 5.51 g per day. Globally, 1.65 million annual deaths from cardiovascular causes (95% uncertainty interval [confidence interval], 1.10 million to 2.22 million) were attributed to sodium intake above the reference level; 61.9% of these deaths occurred in men and 38.1% occurred in women. These deaths accounted for nearly 1 of every 10 deaths from cardiovascular causes (9.5%). Four of every 5 deaths (84.3%) occurred in low- and middle-income countries, and 2 of every 5 deaths (40.4%) were premature (before 70 years of age). The rate of death from cardiovascular causes associated with sodium intake above the reference level was highest in the country of Georgia and lowest in Kenya.
In this modeling study, 1.65 million deaths from cardiovascular causes that occurred in 2010 were attributed to sodium consumption above a reference level of 2.0 g per day. (Funded by the Bill and Melinda Gates Foundation.).
[Show abstract][Hide abstract] ABSTRACT: Genome-wide association studies (GWAS) have identified >500 common variants associated with quantitative metabolic traits, but in aggregate such variants explain at most 20-30% of the heritable component of population variation in these traits. To further investigate the impact of genotypic variation on metabolic traits, we conducted re-sequencing studies in >6,000 members of a Finnish population cohort (The Northern Finland Birth Cohort of 1966 [NFBC]) and a type 2 diabetes case-control sample (The Finland-United States Investigation of NIDDM Genetics [FUSION] study). By sequencing the coding sequence and 5' and 3' untranslated regions of 78 genes at 17 GWAS loci associated with one or more of six metabolic traits (serum levels of fasting HDL-C, LDL-C, total cholesterol, triglycerides, plasma glucose, and insulin), and conducting both single-variant and gene-level association tests, we obtained a more complete understanding of phenotype-genotype associations at eight of these loci. At all eight of these loci, the identification of new associations provides significant evidence for multiple genetic signals to one or more phenotypes, and at two loci, in the genes ABCA1 and CETP, we found significant gene-level evidence of association to non-synonymous variants with MAF<1%. Additionally, two potentially deleterious variants that demonstrated significant associations (rs138726309, a missense variant in G6PC2, and rs28933094, a missense variant in LIPC) were considerably more common in these Finnish samples than in European reference populations, supporting our prior hypothesis that deleterious variants could attain high frequencies in this isolated population, likely due to the effects of population bottlenecks. Our results highlight the value of large, well-phenotyped samples for rare-variant association analysis, and the challenge of evaluating the phenotypic impact of such variants.