Anne Forhan

High Blood Glucose Concentration Is a Risk Factor for Mortality in Middle-Aged Nondiabetic Men 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study

OBJECTIVE To assess the association between high but nondiabetic blood glucose levels and the risk of death from all causes, coronary heart disease (CHD), cardiovascular disease, and neoplasms. RESEARCH DESIGN AND METHODS We studied the 20-year mortality of non-diabetic, working men, age 44–55 years, in three European cohorts known as the Whitehall Study (n = 10,025), the Paris Prospective Study (n = 6,629), and the Helsinki Policeman Study (n = 631). These men were identified by their 2-h glucose levels following an oral glucose tolerance test and by the absence of a prior diagnosis of diabetes. As the protocol for the oral glucose tolerance test and methods for measuring glucose differed between studies, mortality was analyzed according to the percentiles of the 2-h and fasting glucose distributions, using the Coxs proportional hazards model. RESULTS Men in the upper 20% of the 2-h glucose distributions and those in the upper 2.5% for fasting glucose had a significantly higher risk of all-cause mortality in comparison with men in the lower 80% of these distributions, with age-adjusted hazard ratios of 1.6 (95% CI 1.4–1.9) and 2.0 (1.6–2.6) for the upper 2.5%. For death from cardiovascular and CHD, men in the upper 2.5% of the 2-h and fasting glucose distributions were at higher risk, with age-adjusted hazard ratios for CHD of 1.8 (1.4–2.4) and 2.7 (1.7–4.4), respectively. CONCLUSIONS If early intervention aimed at lowering blood glucose concentrations can be shown to reduce mortality, it may be justified to lower the levels of both 2-h and fasting glucose, which define diabetes.

Association of KCNQ1, KCNE1, KCNH2 and SCN5A polymorphisms with QTc interval length in a healthy population

The QT interval (QT) reflects cardiac ventricular repolarization and varies according to various known factors such as heart rate, gender and age. Nevertheless, a high intrasubject stability of the QT-RR pattern also suggests that a genetic component contributes to individual QT length. To determine whether single nucleotide polymorphisms (SNPs) in genes encoding cardiac ion channels were associated with the heart-rate corrected QT (QTc) length, we analyzed two groups of 200 subjects presenting the shortest and the longest QTc from a cohort of 2008 healthy subjects. A total of 17 polymorphisms were genotyped; they were all in the Hardy–Weinberg equilibrium in both groups. Neither allele nor haplotype frequencies of the 10 KCNQ1 SNPs showed a significant difference between the two groups. In contrast, KCNH2 2690 C (K897T) and SCN5A 5457 T (D1819D) minor alleles were significantly more frequent in the group with the shortest QTc interval, whereas KCNE1 253 A (D85N), SCN5A 1673 G (H558R) and 1141-3 A minor alleles were significantly more frequent in the group with the longest QTc interval. Interestingly, an interaction was also found between the KCNH2 2690 A>C SNP and the KCNQ1 2031+932 A>G SNP suggesting that the effect of the KCNH2 2690 C allele on QTc length may occur within a particular genetic background. This suggests that genetic determinants located in KCNQ1, KCNE1, KCNH2 and SCN5A influence QTc length in healthy individuals and may represent risk factors for arrhythmias or cardiac sudden death in patients with cardiovascular diseases.

Hypertension in four African-origin populations : current 'Rule of Halves', quality of blood pressure control and attributable risk of cardiovascular disease

Objective To assess the public health burden from high blood pressure and the current status of its detection and management in four African-origin populations at emerging or high cardiovascular risk. Design Cross-site comparison using standardized measurement and techniques. Setting Rural and urban Cameroon; Jamaica; Manchester, Britain. Subjects Representative population samples in each setting. African-Caribbeans (80% of Jamaican origin) and a local European sample in Manchester. Main outcome measures Cross-site age-adjusted prevalence; population attributable risk. Results Among 1587 men and 2087 women, age-adjusted rates of blood pressure ⩾ 160 or 95 mmHg or its treatment rose from 5% in rural to 17% in urban Cameroon, despite young mean ages, to 21% in Jamaica and 29% in Caribbeans in Britain. Treatment rates reached 34% in urban Cameroon, and 69% in Jamaican- and British- Caribbean-origin women. Sub-optimal blood pressure control (> 140 and 90 mmHg) on treatment reached 88% in European women. Population attributable risks (or fractions) indicated that up to 22% of premature all-cause, and 45% of stroke mortality could be reduced by appropriate detection and treatment. Additional benefit on just strokes occurring on treatment could be up to 47% (e.g. in both urban Cameroon men and European women) from tighter blood pressure control on therapy. Cheap, effective therapy is available. Conclusion With mortality risk now higher from non-communicable than communicable diseases in sub-Saharan Africa and elsewhere, systematic measurement, detection and genuine control of hypertension once treated can go hand-in-hand with other adult health programmes in primary care. Cost implications are not great. The data from this collaborative study suggest that such efforts should be well rewarded.

Trends in the prevalence of obesity in the French adult population between 1980 and 1991

OBJECTIVE: To determine changes in the prevalences of overweight and obesity between 1980 and 1991 in French adults.DESIGN: Two cross-sectional studies were performed in 1980 and 1991 by the French National Institute of Statistics and Economics Studies in representative samples of the non-institutionalized French population using a similar random sampling of households from the last available national population census. Overweight and obesity were defined, based on reported height and weight, by a body mass index (BMI)≥;25 kg/m2 and≥;30 kg/m2, respectively. As age and socio-economic class (SEC) distributions changed between 1980 and 1991, results were compared before and after a direct age class and SEC standardization of the 1991 data, according to the 1980 population distribution.SUBJECTS: 6792 men and 7150 women in 1980, 7250 men and 7856 women in 1991, aged at least 20 y, about 1\2500th of the French non-institutionalized adult population.RESULTS: In women, between 1980 and 1991, there were slight increases in the prevalences of obesity (from 6.3% to 7.0%, P<0.08) and of overweight (26.8% and 27.5%, not statistically significant NS). These increases were most pronounced in women aged 20–29 y (obesity: 1.4–2.1%, P<0.15; overweight: 8.0–11.5%, P<0.01). In men, the corresponding prevalences were 6.4% and 6.5%, (NS), and 39.4% and 40.8% (NS). After standardization, the increases in the prevalences of obesity and overweight were even higher between 1980 and 1991 in women (the standardized prevalences in 1991 were respectively: 7.8% and 28.9%), but were unchanged in men.CONCLUSIONS: There were slight overall increases in the prevalences of overweight and obesity between 1980 and 1991 in both genders, which were most pronounced among young women. Changes in the age and SEC distribution in the French population have limited the increase in the prevalences of overweight and obesity in women. These results, based on reported data, may underestimate the prevalences of overweight and obesity and their increase. Nevertheless, the prevalences of reported obesity are similar to those of other European countries, such as Sweden and The Netherlands, and lower than in the UK, USA and Canada.

Maternal Personal Exposure to Airborne Benzene and Intrauterine Growth

Background Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight. Objective Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth. Methods We recruited pregnant women in two French maternity hospitals in 2005–2006 as part of the EDEN mother–child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth. Results Median benzene exposure was 1.8 μg/m3 (5th, 95th percentiles, 0.5, 7.5 μg/m3). Log-transformed benzene exposure was associated with a gestational age–adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), −135 to −1 g] and of 1.9 mm in mean head circumference at birth (95% CI, −3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, −4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, −3.1 to 0 mm). Conclusions Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.

Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The 'EDEN mother-child' cohort (study of pre- and early postnatal determinants of the child's development and health)

Recent studies suggest a benefit of seafood and n-3 fatty acid intake on fetal growth and infant development. The objective was to study the association between fatty acid intake and fetal growth in pregnant French women. Pregnant women included in the EDEN mother-child cohort study completed FFQ on their usual diet: (1) in the year before pregnancy and (2) during the last 3 months of pregnancy (n 1439). Conversion into nutrient intakes was performed using data on portion size and a French food composition table. Associations between maternal fatty acid intakes and several neonatal anthropometric measurements were studied using linear regressions adjusted for centre, mothers age, smoking habits, height, parity, gestational age and newborns sex. Due to significant interaction, analyses were stratified according to maternal pre-pregnancy overweight status. Neither total lipid nor SFA, MUFA or PUFA intake was significantly associated with newborn size. In overweight women only (n 366), a high pre-pregnancy n-3 fatty acid intake (% PUFA) was positively associated with the newborns birth weight (P=0.01), head, arm and wrist circumferences and sum of skinfolds (P<0.04). A substitution of 1% of n-3 fatty acids per d before pregnancy by other PUFA was related to an average decrease in birth weight of 60 g (P=0.01). Relationships with n-3 fatty acid intake at the end of pregnancy were weaker and not significant. We concluded that a high pre-pregnancy n-3 fatty acid:PUFA ratio may sustain fetal growth in overweight women. Follow-up of the children may help determine whether this has beneficial consequences for the childs health and development.

Cohort Profile: The EDEN mother-child cohort on the prenatal and early postnatal determinants of child health and development

The overall objective of the EDEN study was to examine the relations and potential interactions between maternal exposures and health status during pregnancy, fetal development, health status of the infant at birth and the childs health and development.

Association between maternal blood cadmium during pregnancy and birth weight and the risk of fetal growth restriction: The EDEN mother–child cohort study

The objective of this study is to investigate the potential effect of maternal environmental cadmium (Cd) exposure on birth weight and fetal growth restriction (FGR). A total of 901 pregnant women from the EDEN cohort study were enrolled from two maternity units. Blood Cd was measured at mid-pregnancy and associations with birth weight and FGR were analyzed. Maternal Cd levels were associated with reduced birth weight in the offspring of women who smoked during pregnancy (b=-113.7; p=0.001). Smoking during pregnancy and maternal blood Cd concentrations had comparable effects on FGR incidence (OR 1.89; 95% CI: 1.00-3.58 and OR=1.41; 95% CI: 1.00-1.99, respectively). This study highlights the effect of Cd toxicity on fetal growth through the probable accumulation and transmission of this metal through the placenta. The close relationship between blood Cd levels and smoking habits indicates that Cd may be a relevant biomarker for smoking toxicity on fetal development.

Determinants of early ponderal and statural growth in full-term infants in the EDEN mother-child cohort study

BACKGROUND Growth velocity in the first months of postnatal life has been associated with later overweight and obesity. OBJECTIVE We analyzed prenatal and postnatal factors in association with weight, length, and growth velocities in the first 3 mo of life. DESIGN We estimated weight, length, and instantaneous weight- and length-growth velocities (in g/d and mm/d) in 1418 term infants at 1 and 3 mo of age and evaluated the following potential determinants: maternal prepregnancy body mass index (BMI), 1-h plasma glucose concentrations during pregnancy, smoking, socioeconomic status, parity, paternal BMI, parental heights, and infant feeding, gestational age, and sex. RESULTS Maternal obesity and plasma glucose concentrations were associated with the weights and lengths of offspring at birth but not at 1 and 3 mo after birth. In contrast, there was no association between paternal BMI and anthropometric measures of offspring at birth, but by 3 mo of age infants of obese fathers had significantly higher weights and weight-growth velocities than did infants of fathers with a normal BMI. Maternal weight gain was a significant predictor of weight at birth and 3 mo of age. Exclusively breastfed infants had a slower weight-growth velocity as early as 1 mo of age compared with exclusively formula-fed infants. CONCLUSIONS In the first 3 mo of life, the positive associations between maternal obesity, plasma glucose concentrations, and infant anthropometric measures at birth seem to progressively fade away, whereas the emerging association with paternal BMI may indicate an early postnatal influence of paternal genetics. Among the determinants we evaluated, some are potentially modifiable, such as maternal gestational weight gain and infant feeding. The identification of optimal patterns of growth remains crucial before providing any clinical recommendations.

Maternal Blood Lead Levels and the Risk of Pregnancy-Induced Hypertension: The EDEN Cohort Study

Background Prior studies revealed associations of environmental lead exposure with risks of hypertension and elevated blood pressure. Objective We examined the effect of blood lead levels on blood pressure and the incidence of pregnancy-induced hypertension (PIH) in the second and third trimesters of pregnancy. Methods One thousand seventeen pregnant women were enrolled in two French municipalities between 2003 and 2005 for the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l′ Enfant) cohort study. Blood lead concentrations were measured by atomic absorption spectrometry in mothers between 24 and 28 weeks of gestation. Results PIH was diagnosed in 106 subjects (10.9%). Age, parity, weight gain, alcohol, smoking habits, and calcium supplementation were comparable between hypertensive and nonhypertensive women. Lead levels were significantly higher in PIH cases (mean ± SD, 2.2 ± 1.4 μg/dL) than in normotensive patients (1.9 ± 1.2 μg/dL; p = 0.02). Adjustment for potential confounder effects slightly attenuated but did not eliminate the significant association between blood lead levels and the risk of PIH (adjusted odds ratio of PIH = 3.3; 95% confidence interval, 1.1–9.7). We also observed geographic differences in lead exposure and in the incidence of PIH and found significant correlations between blood lead levels and unadjusted as well as adjusted systolic and diastolic blood pressures after 24 weeks of gestation. Conclusions These findings confirm the relationship between blood lead levels at mid-pregnancy and blood pressure and suggest that environmental lead exposure may play an etiologic role in PIH.