Cecily Kelleher

A common genetic polymorphism associated with lower coagulation factor VII levels in healthy individuals.

We have identified a genetic polymorphism of factor VII that is strongly associated with plasma factor VII coagulant activity (factor VIIc) in healthy individuals from the United Kingdom. This polymorphism was detected after Msp I digestion of polymerase chain reaction-amplified genomic DNA. In a sample of 284 men, the frequency of the M2 allele (loss of cutting site) is 0.1, and individuals with the M1M2 genotype have factor VIIc levels 22% below the sample mean (p less than 0.0001). Msp I genotype was found to be the strongest predictor of factor VIIc, accounting for 20.2% of the variance, with cholesterol accounting for an additional 3.5%. The base change that gives rise to the Msp I polymorphism is a G-to-A substitution in the codon for amino acid 353, leading to replacement of arginine (Arg) with glutamine (Gln) in the protein product of the M2 allele (designated Gln 353). Three individuals homozygous for the M2 allele have both low factor VIIc and low factor VII protein concentrations. The conformation of the Gln 353 molecule may be different from that of the Arg 353 protein, affecting its intracellular processing, secretion, turnover in plasma, or activity. In view of its association with lower factor VIIc levels, possession of the M2 allele may confer protection against thrombosis and myocardial infarction.

Serum uric acid is an independent predictor for all major forms of cardiovascular death in 28,613 elderly women: a prospective 21-year follow-up study.

BACKGROUND The role of serum uric acid (SUA) as a risk factor for cardiovascular disease (CVD) remains controversial. Little is known about its predictive value for mortality from congestive heart failure (CHF) and stroke, particularly in elderly, post-menopausal women. METHODS The relation of SUA to risk of death from total CVD, CHF, stroke and coronary heart disease (CHD) was examined prospectively in a large cohort of 28613 elderly Austrian women (mean age 62.3 years), followed-up for a median of 15.2 years. Adjusted Cox proportional hazards models were calculated to evaluate SUA as an independent predictor for fatal CVD events. RESULTS SUA in the highest quartile (>or=5.41 mg/dL) was significantly associated with mortality from total CVD (p<0.0001), showing a clear dose-response relationship; the adjusted hazard ratio (95%CI) in comparison to the lowest SUA quartile was 1.35 (1.20-1.52). In subgroup analyses SUA was independently predictive for deaths from acute and subacute (p<0.0001) and chronic forms (p=0.035) of CHD, yielding adjusted hazard ratios for the highest versus lowest SUA quartile of 1.58 (1.19-2.10) and 1.25 (1.01-1.56), respectively. SUA was further significantly related to fatal CHF (p<0.0001) and stroke (p=0.018); the adjusted hazard ratios for the highest versus lowest SUA quartile were 1.50 (1.04-2.17) and 1.37 (1.09-1.74), respectively. CONCLUSIONS These findings, for the first time, demonstrate that SUA is an independent predictor for all major forms of death from CVD including acute, subacute and chronic forms of CHD, CHF and stroke in elderly, post-menopausal women.

Fibrinogen, factor VII clotting activity and coronary artery disease severity

To asses the relationship between fibrinogen, factor VII coagulant (VIIc) activity and extent of coronary artery disease, we studied 43 white males shown to have greater than 50% stenosis of at least one major coronary artery. Thirty six had a definite history of myocardial infarction at least 3 months earlier and were classified as having 1, 2 or 3 vessel disease while 7 had 2 or 3 vessel disease, but no prior infarction. Groups were similar with regard to age, body mass index and blood pressure. In those with documented prior infarction, there was a significant relationship between the extent of atheroma and coagulation variables factor VIIc and fibrinogen. However, given a similar degree of atheroma, patients with prior infarction had significantly higher levels of factor VIIc activity compared with patients without such a history. These results corroborate those from prospective studies confirming a significant role for the coagulation system in the clinical manifestation of coronary artery disease.

The contribution of occupational factors to social inequalities in health: Findings from the national French SUMER survey

Social inequalities in health have long been demonstrated, but the understanding of these inequalities remains unclear. Work and its related occupational factors may contribute to these inequalities. The objective of this study was to study the contribution of work factors using an integrated approach (including all types of exposures) to social inequalities in three health outcomes: poor self-reported health, long sickness absence, and work injury. Respondents were 14,241 men and 10,245 women drawn from a survey of the national French working population (response rate: 96.5%). Work factors included job characteristics, and occupational exposures of the physical, ergonomic, biological, chemical, and psychosocial work environment. All work factors were measured through expert evaluation by occupational physicians, except psychosocial work factors, which were self-reported. Strong social gradients were found for all work factors, except for psychological demands, workplace bullying, and aggression from the public. Marked social gradients were also observed for the health outcomes studied, blue collar workers being more likely to report poor self-reported health, long sickness absence, and work injury. The social differences in health were reduced strongly after adjustment for work factors (psychological demands excluded) by 24-58% according to sex and health outcomes. The strongest impacts were found for decision latitude, ergonomic, physical, and chemical exposures, as well as for work schedules. A detailed analysis allowed us to identify more precisely the contributing occupational factors. It suggests that concerted prevention of occupational risk factors would be useful not only to improve health at work, but also to reduce social inequalities in health.

Long-term tracking of cardiovascular risk factors among men and women in a large population-based health system: the Vorarlberg Health Monitoring & Promotion Programme.

AIMS To document tracking patterns, if any, over time, of classical cardiovascular risk factors in men and women participants in the Vorarlberg Health Monitoring and Promotion Programme (VHM&PP) METHODS AND RESULTS: 67,413 men and 82,237 women underwent a total of 45,4448 standardised examinations in the 15 year period 1985-1999. Measures included were systolic and diastolic blood pressure, height, weight and fasting sample for total cholesterol, triglycerides, gamma-gt and blood glucose. Tracking coefficients were calculated by multivariable regression models using the GEE estimation method. All variables showed evidence of significant tracking over time, whether estimated in 10-year age bands or among individuals categorized as being at high risk using cut-points proposed by international guidelines. Effects were most marked for body mass index (0.87, SE0.005 in men and 0.89, SE0.003 in women), and were also associated with increasing age. Women who died during follow-up showed stronger tracking patterns for triglycerides and gamma-gt and weaker effects for blood pressure, but there was no effect on patterns according to survival in men. Tracking coefficients were weaker among initially high-risk individuals. CONCLUSIONS This is the largest study yet of adults to demonstrate significant tracking effects of cardiovascular risk factors over time. The strength of this effect should be considered in assessing effectiveness of risk factor modification programmes. The study is novel too in highlighting more fully differences according to gender and social circumstances and in taking account of the impact on long-term survival.

Pregnancy and Birth Cohort Resources in Europe: a Large Opportunity for Aetiological Child Health Research

BACKGROUND During the past 25 years, many pregnancy and birth cohorts have been established. Each cohort provides unique opportunities for examining associations of early-life exposures with child development and health. However, to fully exploit the large amount of available resources and to facilitate cross-cohort collaboration, it is necessary to have accessible information on each cohort and its individual characteristics. The aim of this work was to provide an overview of European pregnancy and birth cohorts registered in a freely accessible database located at http://www.birthcohorts.net. METHODS European pregnancy and birth cohorts initiated in 1980 or later with at least 300 mother-child pairs enrolled during pregnancy or at birth, and with postnatal data, were eligible for inclusion. Eligible cohorts were invited to provide information on the data and biological samples collected, as well as the timing of data collection. RESULTS In total, 70 cohorts were identified. Of these, 56 fulfilled the inclusion criteria encompassing a total of more than 500,000 live-born European children. The cohorts represented 19 countries with the majority of cohorts located in Northern and Western Europe. Some cohorts were general with multiple aims, whilst others focused on specific health or exposure-related research questions. CONCLUSION This work demonstrates a great potential for cross-cohort collaboration addressing important aspects of child health. The web site, http://www.birthcohorts.net, proved to be a useful tool for accessing information on European pregnancy and birth cohorts and their characteristics.

Socio-demographic predictors of self-rated health in the Republic of Ireland: findings from the National Survey on Lifestyle, Attitudes and Nutrition, SLAN.

Though Ireland continues to have a poor health profile compared with other European Union countries, previous research on social variations has been limited. For the first time in the Republic of Ireland, the influence on self-rated health of various socio-demographic indicators was assessed in a multi-variate logistic regression model, separately for men and women. Data were from the first National Survey of Lifestyles, Attitudes and Nutrition, SLAN, conducted by post in a multi-stage, cluster random sample across 26 counties. There were 6539 respondents (45.4% males). Mean self-rated health differed significantly according to age, marital status, tenure, educational status, social class, household size and eligibility for general medical services (GMS), but not according to gender or rurality. There were also differences if residing in a district with low level of affluence, or according to social cluster groupings. There were numerous significant correlations between the nine socio-demographic measures, but the most consistent pattern was between GMS eligibility and the various indicators, for both men and women. In the case of men, whether social class was included in the multi-variate model or not, education status remained predictive in the final model, (OR 2.36 CI 1.35-4.12) as did smoking status (OR 2.11 CI 1.47-3.02). Odds ratio for GMS eligibility was 3.33 (CI 2.61-4.26) attenuated to 1.70 (CI 1.12-2.56) in the final model. For women the pattern was somewhat different. Only GMS status (OR 2.64 CI 1.74-3.99) and level of education (2.25 CI 1.19-4.24) were predictive in the final model. A multi-level analysis showed that area level of affluence was not significantly predictive of self-rated health when individual level factors were taken into account.

Longitudinal change in serum gamma-glutamyltransferase and cardiovascular disease mortality: a prospective population-based study in 76,113 Austrian adults.

Objective—The purpose of this study was to investigate the association of longitudinal change in serum γ-glutamyltransferase (GGT) with mortality from cardiovascular disease (CVD). Methods and Results—A population-based cohort of 76 113 Austrian men and women with 455 331 serial GGT measurements was prospectively followed-up for a median of 10.2 years after assessment of longitudinal GGT change during an average period of 6.9 years. Cox proportional hazards regression with time-varying covariates was used to evaluate GGT change as an independent predictor for CVD death. Independently of baseline GGT and other classical CVD risk factors, a pronounced increase in GGT (7-year change >9.2 U/L) was significantly associated with increased total CVD mortality in men (P=0.005); the adjusted hazard ratio (95% confidence interval) in comparison to stable GGT (7-year change −0.7 to 1.3 U/L) was 1.40 (1.09 to 1.81). Similarly, total CVD risk was elevated for increasing GGT in women, although effects were less pronounced and statistically significant only in subanalyses regarding coronary heart disease. Age of participants significantly modified the relation between GGT change and CVD mortality, with markedly stronger associations to be observable for younger individuals. Conclusion—Our study is the first to demonstrate that a longitudinal increase in GGT, independently of baseline GGT and even within its normal range, significantly increases risk of fatal CVD.

Social diversity of Irish adults nutritional intake.

Objective: The first health and lifestyle survey of Irish adults was carried out in 1998 and aimed to describe the health-related lifestyle behaviours of a cross-section of various population strata residing in the Republic of Ireland. This paper reports on the social variation in nutrient intake.Design: A self-administered postal questionnaire, including a 149 food item semiquantitative food frequency section, from which nutrient intakes were estimated based on McCance and Widdowson food composition tables.Setting: Community-based adults aged 18 years and over residing in the Republic of Ireland on the Register of Electors.Subjects: A stratified sample of adults on the Register of Electors received the questionnaire, of which 6539 (62%) were returned.Results: The contribution of fat to total energy intake increased with decreasing socioeconomic grouping, a finding reflective of the higher consumption levels of foods high in fat by respondents from socially disadvantaged groups. Energy from carbohydrates was greatest among those from socially advantaged groups, and was close to the recommended 50% of the total energy intake. Conversely, energy from protein decreased with increasing social status group. The mean intake of vitamins and minerals was generally close to or above the recommended values. Significant variation was observed among females across the different levels of education, whereas living with someone appeared to influence the micronutrient intake of males. The reported diets of males and females over the age of 65 years were lacking in vitamin D. Mean calcium levels among males were borderline and females over the age of 65 years had mean dietary iron levels below the recommended intake.Conclusions: For the first time, quantification of nutrient intake in the different social groups in Ireland has been undertaken. A healthy balance of energy derived from fat, protein and carbohydrate is best achieved among respondents from higher social positions. The positive relation observed with healthy food intake and increasing education level was also present in macronutrient intake and a clear gender and social support interplay was seen in the nutrient intake levels.

Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder.

Patients with major depressive disorder (MDD) who attempt or complete suicide have elevated inflammation compared to nonsuicidal patients with MDD. However, greater severity of depression and the medical lethality of suicide attempts could account for such elevated inflammation in suicide attempters and suicide completers.