Air pollution and trajectories of adolescent conduct problems: the roles of ethnicity and racism; evidence from the DASH longitudinal study.

PURPOSE: No known UK empirical research has investigated prospective associations between ambient air pollutants and conduct problems in adolescence. Ethnic minority children are disproportionately exposed to structural factors that could moderate any observed relationships. This prospective study examined whether exposure to PM2.5 and NO2 concentrations is associated with conduct problems in adolescence, and whether racism or ethnicity moderate such associations. METHODS: Longitudinal associations between annual mean estimated PM2.5 and NO2 concentrations at the residential address and trajectories of conduct problems, and the potential influence of racism and ethnicity were examined school-based sample of 4775 participants (2002-2003 to 2005-2006) in London, using growth curve models. RESULTS: Overall, in the fully adjusted model, exposure to lower concentrations of PM2.5 and NO2 was associated with a decrease in conduct problems during adolescence, while exposure to higher concentrations was associated with a flattened trajectory of conduct symptoms. Racism amplified the effect of PM2.5 (ß = 0.05 (95% CI 0.01 to 0.10, p < 0.01)) on adolescent trajectories of conduct problems over time. At higher concentrations of PM2.5, there was a divergence of trajectories of adolescent conduct problems between ethnic minority groups, with White British and Black Caribbean adolescents experiencing an increase in conduct problems over time. CONCLUSION: These findings suggest that the intersections between air pollution, ethnicity, and racism are important influences on the development of conduct problems in adolescence.

Longitudinal changes in vascular function parameters in pregnant women with chronic hypertension and association with adverse outcome: a cohort study.

OBJECTIVES: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity. METHODS: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10th centile) and those who delivered an infant with birth weight ≥ 10th centile and between women of black ethnicity and those of non-black ethnicity. RESULTS: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity. CONCLUSION: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Associations between air pollutants and blood pressure in an ethnically diverse cohort of adolescents in London, England.

Longitudinal evidence on the association between air pollution and blood pressure (BP) in adolescence is scarce. We explored this association in an ethnically diverse cohort of schoolchildren. Sex-stratified, linear random-effects modelling was used to examine how modelled residential exposure to annual average nitrogen dioxide (NO2), particulate matter (PM2.5, PM10) and ozone (O3), measures in µg/m3, associated with blood pressure. Estimates were based on 3,284 adolescents; 80% from ethnic minority groups, recruited from 51 schools, and followed up from 11-13 to 14-16 years old. Ethnic minorities were exposed to higher modelled annual average concentrations of pollution at residential postcode level than their White UK peers. A two-pollutant model (NO2 & PM2.5), adjusted for ethnicity, age, anthropometry, and pubertal status, highlighted associations with systolic, but not diastolic BP. A µg/m3 increase in NO2 was associated with a 0.30 mmHg (95% CI 0.18 to 0.40) decrease in systolic BP for girls and 0.19 mmHg (95% CI 0.07 to 0.31) decrease in systolic BP for boys. In contrast, a 1 µg/m3 increase in PM2.5 was associated with 1.34 mmHg (95% CI 0.85 to 1.82) increase in systolic BP for girls and 0.57 mmHg (95% CI 0.04 to 1.03) increase in systolic BP for boys. Associations did not vary by ethnicity, body size or socio-economic advantage. Associations were robust to adjustments for noise levels and lung function at 11-13 years. In summary, higher ambient levels of NO2 were associated with lower and PM2.5 with higher systolic BP across adolescence, with stronger associations for girls.

Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA): a randomized double-blind placebo-controlled trial of high- vs. low-dose atorvastatin(1).

AIMS: To compare the renal effects of low- vs. high-dose atorvastatin in patients with Type 2 diabetes mellitus and optimally managed early renal disease. METHODS: We compared the 2-year progression of nephropathy in a double-blind randomized controlled trial of atorvastatin 80 mg/day (n = 60) vs. 10 mg/day (n = 59) in patients with Type 2 diabetes with microalbuminuria or proteinuria [mean (sd): age 64 years (10 years); HbA(1c) 7.7% (1.3%), 61 mmol/mol (10 mmol/mol); blood pressure 131/73 mmHg; renin-angiotensin system blocker use > 80%; dual blockade > 67%] recruited from diabetes clinics in Greater Manchester. RESULTS: Over (mean) 2.1 years of follow-up, the Modification of Diet in Renal Disease estimated glomerular filtration rate declined by 3 ml min(-1) 1.73 m(-2) in the combined group. The mean (95% CI) between-group difference during follow-up was not significant [2.2 ml min(-1) 1.73 m(-2) (-1.1 to 5.4 ml min(-1) 1.73: m(-2) ), P = 0.20] after adjusting for baseline differences in renal function; positive difference favours 80 mg dose. Similarly, there was no significant difference in creatinine clearance by Cockcroft and Gault [2.5 ml/min (-2.4 to 7.3 ml/min), P = 0.32]; serum creatinine/24-h urine collections [4.0 ml/min (-4.8 to 12.7 ml/min), P = 0.38]; cystatin C (P = 0.69); or 24-h urine protein or albumin excretion (P = 0.92; P = 0.93). We recorded no significant between-group differences in deaths or adverse events. CONCLUSIONS: In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min(-1) 1.73 m(-2) year(-1) on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized.

Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients. METHODS: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2 x 2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril-indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA(1c) of < or = 6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of > or =2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome. RESULTS: Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n = 623) experienced incidence or progression of retinopathy compared with patients on placebo (n = 618), but the difference was not significant (OR 0.78; 95% CI 0.57-1.06; p = 0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29-0.88; p = 0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38-0.94; p = 0.025). Compared with standard glucose control (n = 611), intensive glucose control (n = 630) did not reduce (p = 0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61-1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere. CONCLUSIONS/INTERPRETATION: Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions. TRIAL REGISTRATION: ClinicalTrials.gov ID no. NCT00145925. FUNDING: Grants from Servier and the National Health and Medical Research Council of Australia.

Dietary advice for treatment of type 2 diabetes mellitus in adults.

BACKGROUND: While initial dietary management immediately after formal diagnosis is an 'accepted' cornerstone of treatment of type 2 diabetes mellitus, a formal and systematic overview of its efficacy and method of delivery is not currently available. OBJECTIVES: To assess the effects of type and frequency of different types of dietary advice for adults with type 2 diabetes. SEARCH STRATEGY: We carried out a comprehensive search of The Cochrane Library, MEDLINE, EMBASE, CINAHL, AMED, bibliographies and contacted relevant experts. SELECTION CRITERIA: All randomised controlled trials, of six months or longer, in which dietary advice was the main intervention. DATA COLLECTION AND ANALYSIS: The lead investigator performed all data extraction and quality scoring with duplication being carried out by one of the other six investigators independently with discrepancies resolved by discussion and consensus. Authors were contacted for missing data. MAIN RESULTS: Thirty-six articles reporting a total of eighteen trials following 1467 participants were included. Dietary approaches assessed in this review were low-fat/high-carbohydrate diets, high-fat/low-carbohydrate diets, low-calorie (1000 kcal per day) and very-low-calorie (500 kcal per day) diets and modified fat diets. Two trials compared the American Diabetes Association exchange diet with a standard reduced fat diet and five studies assessed low-fat diets versus moderate fat or low-carbohydrate diets. Two studies assessed the effect of a very-low-calorie diet versus a low-calorie diet. Six studies compared dietary advice with dietary advice plus exercise and three other studies assessed dietary advice versus dietary advice plus behavioural approaches. The studies all measured weight and measures of glycaemic control although not all studies reported these in the articles published. Other outcomes which were measured in these studies included mortality, blood pressure, serum cholesterol (including LDL and HDL cholesterol), serum triglycerides, maximal exercise capacity and compliance. The results suggest that adoption of regular exercise is a good way to promote better glycaemic control in type 2 diabetic patients, however all of these studies were at high risk of bias. AUTHORS' CONCLUSIONS: There are no high quality data on the efficacy of the dietary treatment of type 2 diabetes, however the data available indicate that the adoption of exercise appears to improve glycated haemoglobin at six and twelve months in people with type 2 diabetes. There is an urgent need for well-designed studies which examine a range of interventions, at various points during follow-up, although there is a promising study currently underway.

Origins of the "black/white" difference in blood pressure: roles of birth weight, postnatal growth, early blood pressure, and adolescent body size: the Bogalusa heart study.

BACKGROUND: The determinants of differences in blood pressure that emerge in adolescence between black Americans of predominantly African descent and white Americans of predominantly European descent are unknown. One hypothesis is related to intrauterine and early childhood growth. The role of early blood pressure itself is also unclear. We tested whether differences in birth weight and in carefully standardized subsequent measures of weight, height, and blood pressure from 0 to 4 or 5 years were related to black/white differences in blood pressure in adolescence. METHODS AND RESULTS: Two Bogalusa cohorts who had complete follow-up data on birth weights and early childhood and adolescent anthropometric and blood pressure measures were pooled. One hundred eighty-five children (48 black and 47 white boys and 41 black and 49 white girls) were followed up and studied after 15 to 17 years. Birth weights were a mean 443 and 282 g lower in black boys and girls, respectively, than in whites (P<0.001). Blood pressures in adolescence were 3.4/1.9 and 1.7/0.6 mm Hg higher, respectively, and tracked from early childhood. In regression analyses, birth weight accounted for the ethnic difference in adolescent blood pressure, which was also independently predicted, in decreasing impact order, by adolescent height, adolescent body mass index, and systolic blood pressure at 4 to 5 years and inversely by growth from 0 to 4 to 5 years. CONCLUSIONS: If these results can be replicated in larger and independent samples, they suggest that efforts to improve intrauterine growth in black infants as well as lessen weight gain in adolescence might substantially reduce excess high blood pressure/hypertension in this ethnic group.

Impact of migration on coronary heart disease risk factors: comparison of Gujaratis in Britain and their contemporaries in villages of origin in India.

The causes of the excess coronary heart disease (CHD) risk in South Asian migrants from the Indian subcontinent remain unclear. Comparisons of CHD risk factors amongst South Asian migrants living in Britain with those of the general UK population provide only a partial explanation. We compared Gujaratis in Britain with similar, non-migrant Gujaratis in India, to test the hypothesis that differences in CHD risk factors associated with migration would be more informative. Randomly sampled Gujaratis aged 25-79 years living in Sandwell (n = 242) were compared with age-, gender- and caste-matched contemporaries remaining in their villages of origin in Navsari, India (n = 295). Lifestyle indices, food intake and physical activity, were assessed with standardised questionnaires and energy expenditure and metabolic parameters measured. British Gujaratis had higher, mean body mass indices by 6 (4.5-7.4) kg/m(2) mean (95% CI), and greater dietary energy intake, fat intake, blood pressure, fasting serum cholesterol, apolipoprotein B, triglycerides, non-esterified fatty acid (NEFA) and C-reative protein concentrations than Gujaratis in India. Dietary folate and serum folate and Vitamin B(12) were lower and plasma homocysteine was higher in India. Smoking was less prevalent and high-density lipoprotein cholesterol tended to be higher in Britain. Diabetes prevalence was high in both populations and impaired fasting or 2 h post-glucose challenge plasma glucose was even more prevalent in Gujarat. In India, however, where insulin secretion and NEFA were lower diabetes and impaired glucose tolerance were less frequently accompanied by excess metabolic CVD risk factors. In conclusion, exposure to increased fat intake and obesity related to migration is likely to explain the disproportionate combination of established and emerging CHD risk factors prevalent in Gujaratis in Britain. Strategies to improve nutrition and to identify and treat cardiovascular risk factors such as dyslipidaemia and hypertension are urgently required.

Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups.

Hepatic sex-hormone binding globulin (SHBG) production is down-regulated by insulin and low levels reflect insulin resistance. Because insulin resistance is closely related to the development of cardiovascular disease in different ethnic groups we examined ethnic variation in SHBG across populations with different baseline cardiovascular risk and metabolic syndrome prevalence. Participants were population-based, of European (n = 142), Pakistani (n = 130), and African-Caribbean (AfC) origin (n = 193). SHBG, fasting lipids, and glucose concentrations plus insulin sensitivity (HOMA-S) were determined. Age adjusted SHBG was significantly lower in both Pakistani men and women. Circulating SHBG levels were lower in those with impaired vs. normal glucose homeostasis. SHBG correlated positively with HOMA-S (rho = 0.28, p < 0.001), and negatively with WHR (rho = - 0.38, p < 0.001), BMI (r = - 0.30, p < 0.001), and diastolic blood pressure (rho = - 0.14, p < 0.01) across all ethnic groups. In multivariate logistic regression analysis a low SHBG increased the likelihood of the metabolic syndrome (odds ratio [OR] = 0.42 [0.21 - 0.82], p = 0.01) as did higher fasting NEFA (OR 1.47 [1.04 - 2.08], p = 0.03), low IGFBP-1 concentrations (OR 0.6 [0.44 - 0.81], p = 0.001), age (OR 1.05 [1.02 - 1.09], p = 0.003), and Pakistani ethnicity (p = 0.001) in a model which also contained gender, lnCRP, IGF-I, and IGF-II. As ethnic differences in SHBG level closely parallel differences in insulin resistance. Its measurement may be useful in identifying individuals at particular risk of the metabolic syndrome, for early intervention.

Black West Indian and matched white diabetics in Britain compared with diabetics in Jamaica: body mass, blood pressure, and vascular disease.

This study was designed to compare the prevalence of obesity, high blood pressure, diabetic vascular disease, and risk factors in Black West Indians who had emigrated to Britain (WIB) with those in Whites in England and among diabetic Jamaicans in Jamaica. Seventy-seven consecutive WIB patients were matched for age, sex, known duration of diabetes, and type of treatment of diabetes with 74 Whites from the same diabetes clinic in England. In Jamaica, a systematic random sample (95 women, 36 men) was studied. There was no difference in age at diagnosis between WIBs and Jamaicans. Effort chest pain (possible angina) was less frequent in WIBs (9%) or Jamaicans (3%) than in Whites (25%). Cigarette smoking was more common in WIBs than in Whites but still low in Jamaicans. Body mass index was greatest in WIB women (85%), significantly more than in matched White (52%) or Jamaican women (45%); 40% of White men and WIB men were obese, significantly more than Jamaicans (15% obese). Systolic blood pressure was similar, but diastolic blood pressure was significantly greater in WIBs than in matched White subjects. The prevalence of casual hypertension was high (greater than 40%) in all groups, often despite treatment. Cataracts were significantly more frequent in WIB and Jamaican groups than in Whites. Total background retinopathy after correcting for duration of diabetes did not differ between groups, and there were no significant differences in other complication rates. Levels of HbA1 were lower in Whites than in the other groups. Regression analysis showed that systolic blood pressure was most consistently related to complications, particularly retinopathy, independent of ethnic group and duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Incidence of type I diabetes in people under 30 years of age in Barbados, West Indies, 1982-1991.

OBJECTIVE: To determine the incidence of type I diabetes among individuals < 30 years of age on the island of Barbados in the Caribbean. The population is predominantly African in origin but exhibits a relatively westernized lifestyle. RESEARCH DESIGN AND METHODS: Cases occurring during the years 1982-1991 were drawn from records at Queen Elizabeth Hospital and from physicians treating insulin-dependent diabetes mellitus (IDDM) patients. Patients using insulin and < 30 years of age at onset were included. Ascertainment was estimated at 94%. RESULTS: The average annual incidence of type I diabetes among Barbadians was 4.1/100,000 when age-adjusted to the world's population. There were 59 incident cases during this 10-year interval. The risk for males was 4.4 and for females 4.0/100,000. Among those 0-14 years of age, the risk was 5.0/100,000. Mean age at onset (+/- SD) was 14.7 +/- 6.9 for males and 12.5 +/- 5.7 for females. Males showed marked seasonal variation in risk and a more than threefold increase in annual incidence during 1984-1985. In contrast, females exhibited a stable pattern of IDDM risk during the 10-year interval. CONCLUSIONS: The incidence rate in Barbados falls near the lower limits of rates reported for Caribbean populations. There was a marked seasonal effect among males, even though the climate varies little throughout the year. This observation, and the incidence peak during 1984-1985, provide support for the role of environmental factors in the etiology of IDDM.

Prevalence of NIDDM among populations of the African diaspora.

OBJECTIVE: Rates of non-insulin-dependent diabetes mellitus have risen sharply in recent years among blacks in the U.S. and the U.K. Increases in risk have likewise been observed in the island nations of the Caribbean and in urban West Africa. To date, however, no systematic comparison of the geographic variation of NIDDM among black populations has been undertaken. RESEARCH DESIGN AND METHODS: In the course of an international collaborative study on cardiovascular disease, we used a standardized protocol to determine the rates of NIDDM and associated risk factors in populations of the African diaspora. Representative samples were drawn from sites in Nigeria, St. Lucia, Barbados, Jamaica, the United States, and the United Kingdom. A total of 4,823 individuals aged 25-74 years were recruited, all sites combined. RESULTS: In sharp contrast to a prevalence of 2% in Nigeria, age-adjusted prevalences of self-reported NIDDM were 9% in the Caribbean and 11% in the U.S. and the U.K. Mean BMI ranged from 22 kg/m2 among men in West Africa to 31 kg/m2 in women in the U.S. Disease prevalence across sites was essentially collinear with obesity, pointing to site differences in the balance between energy intake and expenditure as the primary determinant of differential NIDDM risk among these populations. CONCLUSIONS: In ethnic groups sharing a common genetic ancestry, these comparative data demonstrate the determining influence of changes in living conditions on the population risk of NIDDM.

Standardized comparison of glucose intolerance in west African-origin populations of rural and urban Cameroon, Jamaica, and Caribbean migrants to Britain.

OBJECTIVE: To compare the prevalence of glucose intolerance in genetically similar African-origin populations within Cameroon and from Jamaica and Britain. RESEARCH DESIGN AND METHODS: Subjects studied were from rural and urban Cameroon or from Jamaica, or were Caribbean migrants, mainly Jamaican, living in Manchester, England. Sampling bases included a local census of adults aged 25-74 years in Cameroon, districts statistically representative in Jamaica, and population registers in Manchester. African-Caribbean ethnicity required three grandparents of this ethnicity. Diabetes was defined by the World Health Organization (WHO) 1985 criteria using a 75-g oral glucose tolerance test (2-h > or = 11.1 mmol/l or hypoglycemic treatment) and by the new American Diabetes Association criteria (fasting glucose > or = 7.0 mmol/l or hypoglycemic treatment). RESULTS: For men, mean BMIs were greatest in urban Cameroon and Manchester (25-27 kg/m2); in women, these were similarly high in urban Cameroon and Jamaica and highest in Manchester (27-28 kg/m2). The age-standardized diabetes prevalence using WHO criteria was 0.8% in rural Cameroon, 2.0% in urban Cameroon, 8.5% in Jamaica, and 14.6% in Manchester, with no difference between sexes (men: 1.1%, 1.0%, 6.5%, 15.3%, women: 0.5%, 2.8%, 10.6%, 14.0%), all tests for trend P < 0.001. Impaired glucose tolerance was more frequent in Jamaica. CONCLUSIONS: The transition in glucose intolerance from Cameroon to Jamaica and Britain suggests that environment determines diabetes prevalence in these populations of similar genetic origin.

Genetic and environmental determinants of factor VII coagulant activity in ethnic groups at differing risk of coronary heart disease.

It has been shown previously that individuals possessing the Gln353 allele of factor VII have significantly lower factor VIIc levels. In this population based study of Europeans, Afro-Caribbeans and Gujarati Indians, the Gln353 allele was associated with lower factor VIIc in all groups, carriers having factor VIIc levels 20-25% below the group mean. Although the Afro-Caribbeans had the lowest factor VIIc levels, the frequency of the Gln353 allele was not different from the European sample. However, in the Gujaratis, the frequency of the Gln353 allele was significantly higher than in the Europeans (0.25 compared to 0.09, P less than 0.001). Factor VIIc is known to be positively correlated with plasma triglyceride levels, although the Gujaratis, having the highest mean triglyceride levels, did not have the highest mean factor VIIc levels. On examination of the relationship between triglycerides and factor VIIc in the Gujaratis there was a correlation (r = 0.23, P = 0.13) in individuals homozygous for the factor VII Arg353 allele, but no correlation (r = 0.001, P = 0.5) among Gln353 carriers. This striking difference suggests that the effect of triglycerides on factor VIIc is genotype specific and thus provides an example of gene-environment interaction. The high frequency of the Gln353 allele, with its associated lack of relationship between triglyceride and factor VIIc levels, may explain the lower than expected factor VIIc levels in the Gujaratis.

Factor VII coagulant activity is strongly associated with the plasma concentration of large lipoprotein particles in middle-aged men.

A community survey of factor VII coagulant activity (VIIc) and the lipoprotein profile in non-fasting plasma of middle-aged men in NW London was undertaken to search for the determinants of VIIc in the general community. The data demonstrates that associations between VIIc and the plasma concentrations of cholesterol and of triglycerides previously shown in the general population can be explained by the strong and positive associations between VIIc and the large lipoprotein particles, chylomicrons, VLDL and IDL. Consistent with the possibility that the concentration of large lipoproteins determines the in vivo reactivity of factor VII, the association between VIIc and the ratio of lipid in the d greater than 1.019 fraction to the total plasma lipid was also highly significant but negative. The observed correlations between VIIc and lipoproteins smaller than VLDL may be the product of the interrelations that exist between the lipoprotein fractions in plasma. However, the associations between VIIc and the chylomicron lipid concentrations are especially strong when allowance is made for the considerable bias towards zero in the observed correlation, due to large within-person variance in chylomicron concentration.

Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition.

Nine adults took two 7-day diets of standardised energy and total fat content, but with a dietary polyunsaturated/saturated fat ratio of less than 0.3 and greater than 3.0 respectively, while adhering to their daily routine. Blood was drawn on 6 occasions between 09.00 and 22.45 h on the final day of each dietary period for factor VII activity (VIIc), factor VII antigen (VIIag) and lipoprotein lipid concentrations. Diurnal variation was described for each variable in terms of its deviation from the individual's daily mean value at each time point across the day. Plasma triglyceride remained low until after the midday meal, whereafter a marked rise was sustained into the later evening. Plasma VIIc declined until early afternoon, but showed a marked rise in the late afternoon. Plasma VIIag showed no significant diurnal variation. Changes in plasma triglyceride concentration during the day were related positively to changes in VIIc about 160 min later, but not to VIIc at other time points. This effect of postprandial triglyceridaemia on VIIc persisted after allowance for the effect of VIIag on VIIc. Dietary fat composition did not influence VIIc or VIIag. The results suggested an acute but evanescent effect of triglyceride-rich lipoproteins on the reactivity of factor VII, irrespective of their lipid core composition.