A Population-Based Study of Effects of Genetic Loci on Orofacial Clefts.

Prior genome-wide association studies for oral clefts have focused on clinic-based samples with unclear generalizability. Prior samples were also small for investigating effects by cleft type and exclusively studied isolated clefts (those occurring without other birth defects). We estimated the effects of 17 top loci on cleft types in both isolated and nonisolated cases in the largest consortium to date of European-descent population-based studies. Our analytic approach focused on a mother-child dyad case-control design, but it also allowed analyzing mother-only or child-only genotypes to maximize power. Our total sample included 1,875 cases with isolated clefts, 459 cases with nonisolated clefts, and 3,749 controls. After correcting for multiple testing, we observed significant associations between fetal single-nucleotide polymorphisms (SNPs) at IRF6, PAX7, 8q21.3, 8q24, KIAA1598-VAX1, and MAFB and isolated cleft lip only (CLO) and cleft lip and palate (CLP). Significant associations were observed between isolated CLO and fetal SNPs near TPM1 and NOG1 and between CLP and fetal SNPs at ABCA4-ARHGAP29, THADA, FOXE1, and SPRY2. Overall, effects were similar for isolated CLO and CLP, except for ABCA4-ARHGAP29. A protective effect was observed for the fetal NOG1 SNP on cleft palate only, opposite in direction to the effect on CLO. For most fetal SNPs, a dose-response allelic effect was observed. No evidence of parent-of-origin or maternal genome effects was observed. Overall, effect direction and magnitude were similar between isolated and nonisolated clefts, suggesting that several loci are modifiers of cleft risk in both isolated and nonisolated forms. Our results provide reliable estimates of the effects of top loci on risks of oral clefts in a population of European descent.

Global oral health inequalities: challenges in the prevention and management of orofacial clefts and potential solutions.

The birth prevalence of orofacial clefts, one of the most common congenital anomalies, is approximately one in 700 live births, but varies with geography, ethnicity, and socio-economic status. There is a variation in infant mortality and access to care both between and within countries, so some clefts remain unrepaired into adulthood. Quality of care also varies, and even among repaired clefts there is residual deformity and morbidity that significantly affects some children. The two major issues in attempts to address these inequalities are (a) etiology/possibilities for prevention and (b) management and quality of care. For prevention, collaborative research efforts are required in developing countries, in line with the WHO approach to implement the recommendations of the 2008 Millennium Development Goals (www.un.org/millenniumgoals). This includes the "common risk factor" approach, which analyzes biological and social determinants of health alongside other chronic health problems such as diabetes and obesity, as outlined in the Marmot Health inequalities review (2008) (www.ucl.ac.uk/gheg/marmotreview). Simultaneously, orofacial cleft research should involve clinical researchers to identify inequalities in access to treatment and identify the best interventions for minimizing mortality and residual deformity. The future research agenda also requires engagement with implementation science to get research findings into practice.

Prospective study of ready-to-eat breakfast cereal consumption and cognitive decline among elderly men and women.

OBJECTIVE: To examine associations between frequency of ready-to-eat-cereal (RTEC) consumption and cognitive function among elderly men and women of the Cache County Study on Memory Health and Aging in Utah. DESIGN: A population-based prospective cohort study established in Cache County, Utah in 1995. SETTING AND PARTICIPANTS: 3831 men and women > 65 years of age who were living in Cache County, Utah in 1995. MEASUREMENT: Diet was assessed using a 142-item food frequency questionnaire at baseline. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and three subsequent interviews over 11 years. RTEC consumption was defined as daily, weekly, or infrequent use. RESULTS: In multivariable models, more frequent RTEC consumption was not associated with a cognitive benefit. Those consuming RTEC weekly but less than daily scored higher on their baseline 3MS than did those consuming RTEC more or less frequently (91.7, 90.6, 90.6, respectively; p-value < 0.001). This association was maintained across 11 years of observation such that those consuming RTEC weekly but less than daily declined on average 3.96 points compared to an average 5.13 and 4.57 point decline for those consuming cereal more or less frequently (p-value = 0.0009). CONCLUSION: Those consuming RTEC at least daily had poorer cognitive performance at baseline and over 11 years of follow-up compared to those who consumed cereal more or less frequently. RTEC is a nutrient dense food, but should not replace the consumption of other healthy foods in the diets' of elderly people. Associations between RTEC consumption, dietary patterns, and cognitive function deserve further study.

Dietary folate, vitamin B-12, vitamin B-6 and incident Alzheimer's disease: the cache county memory, health and aging study.

OBJECTIVE: To examine associations between dietary and supplemental folate, vitamin B-12 and vitamin B-6 and incident Alzheimer's disease (AD) among elderly men and women. DESIGN, SETTING AND PARTICIPANTS: Data collected were from participants of the Cache County Memory, Health and Aging Study, a longitudinal study of 5092 men and women 65 years and older who were residents of Cache County, Utah in 1995. MEASUREMENTS: Multistage clinical assessment procedures were used to identify incident cases of AD. Dietary data were collected using a 142-item food frequency questionnaire. Cox Proportional Hazards (CPH) modeling was used to determine hazard ratios across quintiles of micronutrient intake. RESULTS: 202 participants were diagnosed with incident AD during follow-up (1995-2004). In multivariable CPH models that controlled for the effects of gender, age, education, and other covariates there were no observed differences in risk of AD or dementia by increasing quintiles of total intake of folate, vitamin B-12, or vitamin B-6. Similarly, there were no observed differences in risk of AD by regular use of either folate or B6 supplements. CONCLUSION: Dietary intake of B-vitamins from food and supplemental sources appears unrelated to incidence of dementia and AD. Further studies examining associations between dietary intakes of B-vitamins, biomarkers of B-vitamin status and cognitive endpoints are warranted.

Antioxidant intake and cognitive function of elderly men and women: the Cache County Study.

OBJECTIVE: We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah. PARTICIPANTS AND DESIGN: In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. RESULTS: Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. CONCLUSION: High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly.

Postpartum thiamine deficiency in a Karen displaced population.

BACKGROUND: Before its recognition, infantile beriberi was the leading cause of infant death in camps for displaced persons of the Karen ethnic minority on Thailand's western border. OBJECTIVE: This study aimed to document thiamine status in the peripartum period to examine the current supplementation program and the correlation between the clinical manifestations of thiamine deficiency and a biochemical measure of thiamine status. DESIGN: Women were enrolled prospectively at 30 wk of gestation and were followed up weekly until delivery and at 3 mo postpartum. Thiamine supplementation during pregnancy was based on patient symptoms. RESULTS: At 3 mo postpartum, thiamine deficiency reflected by an erythrocyte transketolase activity (ETKA) > or = 1.20% was found in 57.7% (15/26) of mothers, 26.9% (7/26) of whom had severe deficiency (ETKA > 1.25%). No significant associations between ETKA and putative maternal symptoms or use of thiamine supplements were found. CONCLUSIONS: Biochemical postpartum thiamine deficiency is still common in Karen refugee women. This situation may be improved by educating lactating women to reduce their consumption of thiaminase-containing foods and by implementing an effective thiamine supplementation program.

Comparison of a picture-sort food-frequency questionnaire with 24-hour dietary recalls in an elderly Utah population.

OBJECTIVE: To evaluate the 137-item Utah Picture-sort Food-frequency Questionnaire (FFQ) in the measurement of usual dietary intake in older adults. DESIGN: The picture-sort FFQ was administered at baseline and again one year later. Three seasonal 24-hour dietary recall interviews were collected during the year between the two FFQs. Mean nutrient intakes were compared between methods and between administrations of the FFQ. SETTING: The FFQ interviews were administered in respondents' homes or care-centres. The 24-hour diet recalls were conducted by telephone interview on random days of the week. SUBJECTS: Two-hundred-and-eight men and women aged 55-84 years were recruited by random sample of controls from a case-control study of nutrition and bone health in Utah. RESULTS: After adjustment for total energy intake, median Spearman rank correlation coefficients between the two picture-sort FFQs were 0.69 for men aged < or = 69 years, 0.66 for men aged > 69 years; and 0.68 for women aged < or = 69 years, 0.67 for women aged > 69 years. Median correlation coefficients between methods were 0.50 for men < or = 69 years old, 0.52 for men > 69 years old; 0.55 for women < or = 69 years old, 0.46 for women > 69 years old. CONCLUSIONS: We report intake correlations between methods and administrations comparable to those reported in the literature for traditional paper-and-pencil FFQs and one other picture-sort method of FFQ. This dietary assessment method may improve ease and accuracy of response in this and other populations with low literacy levels, poor memory skill, impaired hearing, or poor vision.

Candidate genes for nonsyndromic cleft lip and palate and maternal cigarette smoking and alcohol consumption: evaluation of genotype-environment interactions from a population-based case-control study of orofacial clefts.

Previous studies suggest that the relationship between genes and nonsyndromic cleft lip +/- cleft palate (CLP) or cleft palate only (CP) may be modified by the environment. Using data from a population-based case-control study, we examined allelic variants for three genes, i.e., transforming growth factor alpha (TGFA), transforming growth factor beta 3 (TGFB3), and Msh (Drosophila) homeobox homolog 1 (MSX1), and their interactions with two exposures during pregnancy (maternal cigarette smoking and alcohol consumption) as risk factors for CLP and CP. For each cleft phenotype, risk estimates associated with most allelic variants tended to be near unity. Risk estimates for maternal smoking (> or = 10 cigarettes/day) were significantly elevated for CP and were most elevated among infants with allelic variants at the TGFB3 or MSX1 sites. By comparison, risk estimates for maternal alcohol consumption (> or = 4 drinks/month) were significantly elevated for CLP and were most elevated among infants with allelic variants at the MSX1 site. Our results suggest that development of CLP and CP may be influenced independently by maternal exposures but more significantly by interaction of such exposures and specific allelic variants.

Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women.

BACKGROUND: The role of dietary protein intake in osteoporosis remains controversial. Protein is an important structural component of bone and protein supplementation improves the medical outcome of hip fracture patients, but it is unknown whether protein intake can reduce the incidence risk of hip fracture. OBJECTIVE: The relation between intake of protein and other nutrients and subsequent incidence of hip fracture was evaluated. DESIGN: Nutrient intake was assessed with a food-frequency questionnaire in a cohort of Iowa women aged 55-69 y at baseline in 1986. Incident hip fractures were ascertained through follow-up questionnaires mailed to participants in 1987 and 1989 and verified by physician reports. RESULTS: Forty-four cases of incident hip fractures were included in the analyses of 104338 person-years (the number of subjects studied times the number of years of follow-up) of follow-up data. The risk of hip fracture was not related to intake of calcium or vitamin D, but was negatively associated with total protein intake. Animal rather than vegetable sources of protein appeared to account for this association. In a multivariate model with inclusion of age, body size, parity, smoking, alcohol intake, estrogen use, and physical activity, the relative risks of hip fracture decreased across increasing quartiles of intake of animal protein as follows: 1.00 (reference), 0.59 (95% CI: 0.26, 1.34), 0.63 (0.28, 1.42), and 0.31 (0.10, 0.93); P for trend = 0.037. CONCLUSION: Intake of dietary protein, especially from animal sources, may be associated with a reduced incidence of hip fractures in postmenopausal women.

Bangungut in Manila: sudden and unexplained death in sleep of adult Filipinos.

BACKGROUND: Sudden and unexplained death in sleep (SUDS) is a leading cause of death of young men in several Asian populations, but the history and epidemiology of SUDS are not well known. METHODS: Autopsy records were reviewed in Manila in a study of the classification of SUDS. Death certificates filed in Manila during 1948-1982 were then reviewed in a study of SUDS incidence. A nested case-control study of death certificates examined birthplace as an indicator of SUDS risk. RESULTS: The classification of SUDS cases in Manila during 1948-1982 (N = 722) evolved from the folk term, bangungut ('to rise and moan during sleep'), to various descriptions of post-mortem artefacts. The characteristics of victims in each of the groups were similar: 96% male, mean age 33 years, and modal time of death 3:00 a.m. The deaths were seasonal, peaking in December-January. SUDS victims were more likely than deceased controls to have been born outside of the Manila region (relative odds = 2.11; 95% CI: 1.59-2.78). The SUDS rate for men aged 25-44 years increased from 10.8 to 26.3 per 100000 person-years from 1948 to 1982. CONCLUSION: The death certificate classification of SUDS in Manila has changed considerably, obscuring an increase in incidence. SUDS appears to be a regional phenomenon in Southeast Asia and environmental causes are likely because the deaths are seasonal, increased over the timespan studied, and are more common among migrants to Manila than among those born there.

The effect of follow-up on limiting non-participation bias in genetic epidemiologic investigations.

The use of a comprehensive follow-up strategy to limit non-participation bias was evaluated in a population-based case-control study of orofacial clefts. Birth parents were requested to provide exposure data, and index children and parents were asked to provide blood specimens. Follow-up included telephone or postal reminders every two weeks for up to three months. Consent to participate was received from 281 (76.6%) case mothers and 246 (72.4%) case fathers. The corresponding totals for controls were 279 (54.7%) and 245 (49.8%). Evaluation of participation rates by intensity of follow-up showed that 23% of case and 18% of control families consented without reminders (first stage); 81% of cases and 83% of controls agreed following one or two reminders (second stage); and the remainder of participants consented following three or more reminders (final stage). Cumulative distributions of sociodemographic characteristics differed little between second and final stage participants. Odds ratios for maternal multivitamin use were similar between second and final stage participants, whereas those for maternal and paternal smoking tended to decline. Although follow-up measures were necessary to enroll most families, use of more than two reminders did not appear to increase the representativeness of the sample; however, termination of recruitment after only two reminders would have led to different conclusions. Future studies require data collection protocols that encourage participation from all population subgroups, and one alternative is presented.

Maternal alcohol use and risk of orofacial cleft birth defects.

Maternal alcohol use during pregnancy is a known cause of birth defects associated with the fetal alcohol syndrome, but its role in more common, isolated, craniofacial birth defects is not well understood. A population-based, case-control study of orofacial clefts was conducted in Iowa using births during 1987-1991. Cases were identified by the Iowa Birth Defects Registry and classified as having a cleft lip with or without cleft palate (CLP) or cleft palate only (CP) and whether the cleft was isolated or occurred with other birth defects. Controls were selected from normal Iowa births. Maternal alcohol use during pregnancy was classified according to self-reported drinks consumed per month. Results are based on 302 controls and the following numbers in each case group: 118 isolated CLP, 56 isolated CP, 51 CLP with multiple defects, and 62 CP with multiple defects. Compared to women who did not drink alcohol during pregnancy, the relative odds of isolated CLP rose with increasing level of maternal drinking as follows: 1-3 drinks per months, 1.5; 4-10 drinks per month, 3.1; more than 10 drinks per month, 4.7 (chi-square test for trend, P = 0.003). Adjustment for maternal smoking, vitamin use, education, and household income did not substantially alter these results. No significant association was found between alcohol use and isolated cleft palate or clefts in children with multiple birth defects. Alcohol use during pregnancy may be a cause of isolated cleft lip with or without cleft palate.

Association of transforming growth-factor alpha gene polymorphisms with nonsyndromic cleft palate only (CPO).

Genetic analysis and tissue-specific expression studies support a role for transforming growth-factor alpha (TGFA) in craniofacial development. Previous studies have confirmed an association of alleles for TGFA with nonsyndromic cleft lip with or without cleft palate (CL/P) in humans. We carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO). The PCR products from 12 overlapping sets of primers to the TGFA cDNA were examined by using single-strand conformational polymorphism analysis. Four DNA polymorphic sites for TGFA were identified in the 3' untranslated region of the TGFA gene. These variants, as well as previously identified RFLPs for TGFA, were characterized in case and control populations for CPO by using chi 2 analysis. A significant association between alleles of TGFA and CPO was identified which further supports a role for this gene as one of the genetic determinants of craniofacial development. Sequence analysis of the variants disclosed a cluster of three variable sites within 30 bp of each other in the 3' untranslated region previously associated with an antisense transcript. These studies extend the role for TGFA in craniofacial morphogenesis and support an interrelated mechanism underlying nonsyndromic forms of CL/P.

Transfusion history and cancer risk in older women.

OBJECTIVE: To test the hypothesis that history of blood transfusion is associated with an increased incidence of cancer in older women. DESIGN: Prospective cohort study. SETTING: General community in the state of Iowa. PARTICIPANTS: Random sample of 37,337 cancer-free Iowa women ages 55 to 69 years. MEASUREMENTS: Transfusion history was assessed with a mailed questionnaire completed in January 1986. Cancer incidence in 5 years was ascertained by a population-based cancer registry. RESULTS: Women who had ever received a blood transfusion were at an increased risk for non-Hodgkin lymphoma (relative risk (RR) = 2.20; 95% CI, 1.35 to 3.58) and kidney cancer (RR = 2.53; CI, 1.34 to 4.78). The relative risks for these cancers were greater with decreasing time from first transfusion. No increased risk occurred for cancers of the breast, lung, uterine corpus, ovary, pancreas, colon, rectum, skin (melanoma), or for all cancers considered together. CONCLUSION: These findings suggest that previous blood transfusion may be a risk factor for non-Hodgkin lymphoma and kidney cancer but is not associated with the most common neoplasms.

Sudden and unexplained deaths in sleep (Laitai) of young men in rural northeastern Thailand.

Sudden and unexplained death in sleep (SUDS) is a significant cause of death of young adults in several Asian populations, but its distribution and incidence are not well known. We conducted a survey by mail of SUDS (known as 'laitai' in the local dialect) that occurred in adults during 1988-1989 in 3867 villages in northeastern Thailand with a total population of 5.42 million. Headmen of 2651 villages (68.6%) returned the questionnaire and sudden deaths of adults 20-49 years old were reported in 396 of these villages. The validity of reports was assessed by interviewing next of kin and witnesses in a sample of 92 villages reporting sudden deaths; 60 of 127 reports of SUDS from these villages were verified (47.2%). Officials and villagers in seven villages that did not respond to the questionnaire were also interviewed and no cases of sudden death were found. The verified SUDS victims were all men wth a mean age of 35.9 years (SD 7.8). A family history of SUDS was reported in 40.3% of index cases and 18.3% had brothers who had died similarly; no such deaths were reported among sisters. The estimated annual rate of death from SUDS among men 20-49 years was 25.9 per 100,000 person years (95% confidence interval (CI): 21.0-30.7). The sudden deaths were seasonal with 38% occurring during March-May and 10% during September-October (chi 2 = 9.45, P = 0.02). Sudden death in sleep is a leading cause of death of young men in rural northeastern Thailand and the characteristics of Thai victims are similar to those of other Asian victims of this unexplained syndrome.

Dietary fat and postmenopausal breast cancer.

BACKGROUND: Although the results of animal studies and cross-cultural comparisons generally support a role for dietary fat in the etiology of breast cancer, results of analytic epidemiology studies are equivocal. PURPOSE: The association between dietary fat and subsequent breast cancer was examined in a cohort of 34,388 postmenopausal women from Iowa. METHODS: Dietary habits were assessed by a food-frequency questionnaire mailed in January 1986. Through December 31, 1989, 459 incident cases of breast cancer occurred in this cohort. Proportional hazards regression was used to examine the dietary fat-breast cancer association while adjusting for potential confounders. The effects on this association of four analytic approaches to adjustment for energy intake were also considered. RESULTS: After adjustment for known determinants of breast cancer, a modest positive association of total fat intake with risk of breast cancer was seen. Polyunsaturated fat intake was also positively associated with breast cancer (relative risk from lowest to highest intake, 1.0, 1.25, 1.31, and 1.49; P for trend = .052). Different approaches to adjustment for energy intake, however, provided different impressions of the dietary fat-breast cancer association. One method, involving categorization of crude fat intake and inclusion of total energy intake in regression analysis, gave relative risk estimates from low to high fat intake of 1.0, 1.17, 1.25, and 1.38 (P for trend = .18). Another method, based on categorization of fat intake residuals in which the variation in fat due to total energy intake was removed, gave corresponding estimates of 1.0, 1.24, 1.30, and 1.16 (P for trend = .29). The former suggests increasing breast cancer risk with increasing fat intake; the latter suggests no association. CONCLUSIONS: These results are consistent with other cohort studies that have shown a weak association or no association between dietary fat and breast cancer. They are also consistent with studies suggesting that fat intake is a determinant of breast cancer, particularly after accounting for inaccuracies in dietary assessment. The effects of different energy-adjustment methods may account in part for the varying interpretations of four previous cohort studies of dietary fat and breast cancer. IMPLICATIONS: Further work is needed to clarify not only the nature of the dietary fat-breast cancer association, but also the impact of different analytic methods used in the investigation of diet-disease associations.

Dietary assessment of older Iowa women with a food frequency questionnaire: nutrient intake, reproducibility, and comparison with 24-hour dietary recall interviews.

The authors report the results of a dietary survey of 38,121 Iowa women, 55-69 years of age in 1986, based on a semiquantitative food frequency questionnaire previously tested among Boston-area women aged 34-59 years. The Iowa women, compared with the younger Boston-area women, consumed a similar amount of calories (1,767 vs. 1,844 kcal) and a similar amount of total calories from fat (35 vs. 37%) but had markedly greater intake of the following micronutrients after including supplement use: iron (+18%), calcium (+33%), vitamin A (+43%), riboflavin (+46%), thiamine (+50%), and pyridoxine (+122%). The reproducibility of the questionnaire was examined in two more administrations to 44 of the Iowa women in January and June of 1988. Reproducibility was highest for alcohol (Pearson's r = 0.99), caffeine (r = 0.95), and vitamin E (r = 0.90) and lowest for sucrose (r = 0.53), polyunsaturated fat (r = 0.56), and iron (r = 0.59). Micronutrient intakes were generally more reproducible than macronutrient intakes. The agreement between the June 1988 questionnaire and the average of five 24-hour dietary recalls was also assessed in the 44 subjects. The median correlations of energy-adjusted intake were as follows: for macronutrients, r = 0.45; for micronutrients without supplements, r = 0.33; and for micronutrients with supplements, r = 0.64. This food frequency questionnaire appears to be reasonably reproducible and accurate, so that its use may be extended to epidemiologic studies of older women with a broad range of socioeconomic backgrounds.

Prolonged QT interval and risk of sudden death in South-East Asian men.

Sudden death in sleep occurs in substantial numbers among young men in South-East Asia. The frequencies of electrocardiographic abnormalities were measured in groups with varying risks of such sudden death. The mean heart-rate-corrected QT interval (QTc) was significantly (p less than 0.05) greater among 123 Laotian refugees in Thailand at high risk (405 [95% confidence interval 397-413] ms) than in 77 Laotian refugees in the United States at lower risk (364 [359-369] ms) and 199 non-Asian US residents at negligible risk (358 [354-362] ms). Among refugees in Thailand, prolonged QTc interval was associated with poor thiamine status and a history of seizure-like episodes in sleep. Thiamine deficiency may be a cause of prolonged QT interval and sudden death in this region.

Elevated blood pressure among Southeast Asian refugee children in Minnesota.

The blood pressures and body sizes of children aged 10-15 years in the Minneapolis and St. Paul, Minnesota, public schools were measured during 1986 and 1987. The sample consisted of 1,680 Southeast Asian refugees--including 219 Cambodians, 1,086 Hmong, 149 Lao, and 226 Vietnamese--and 3,424 blacks and 11,336 whites. Mean systolic blood pressure in Hmong boys was higher than that in black boys and white boys. Mean systolic blood pressures of Hmong, Lao, and Vietnamese girls were lower than those of black girls and white girls. The mean diastolic blood pressures of Hmong boys and of Cambodian and Hmong girls were greater than those of blacks and whites of the same sexes. Southeast Asian children were shorter and weighed less than black children and white children. Body size may confound associations between ethnic groups and blood pressures and may obscure the problem of hypertension among the smaller Southeast Asian children. Southeast Asian boys had greater mean systolic blood pressures than did black and white boys across all weight strata; a similar contrast among girls did not reveal this difference. The risk of hypertension, defined by US National Heart, Lung, and Blood Institute guidelines, was assessed in multiple logistic regression analyses that controlled for differences in weight, height, age, and pulse rate. The odds ratios for hypertension, relative to blacks and whites of the same sexes, were 2.69 (95% confidence interval (CI) 1.85-3.65) in Hmong boys, 2.89 (95% CI 1.35-6.21) in Lao boys, 2.10 (95% CI 1.03-4.28) in Cambodian girls, and 1.49 (95% CI 1.00-2.20) in Hmong girls. Hypertension and subsequent cardiovascular disease may emerge as a significant problem among Southeast Asian refugees in the United States.

Hemostatic variables in Japanese and Caucasian men. Tissue plasminogen activator, antithrombin III, and protein C and their relations to coronary risk factors.

Mortality rates of coronary heart disease are much lower in Japan than in the United States. The authors' previous report on coagulation factors showed that population levels of plasma fibrinogen and factor VII activity parallel this mortality difference. To investigate other hemostatic variables, the authors assessed indicators of fibrinolytic activity (tissue plasminogen activator antigen) and coagulation inhibition (antithrombin III activity and protein C) in 136 men aged 34-55 years in four different samples: rural Japanese, urban Japanese, Japanese Americans, and Caucasian Americans. Mean tissue plasminogen activator antigen was higher in Caucasians and Japanese Americans than in rural and urban Japanese (p less than 0.01), while a contrasting trend in mean antithrombin III activity was suggested (p = 0.10). No significant differences were observed in mean levels of protein C. After controlling for known coronary risk factors, mean levels of tissue plasminogen activator antigen remained significantly different across the four samples (p less than 0.01); mean antithrombin III activity was not different (p = 0.23). Population differences in tissue plasminogen activator antigen parallel the coronary heart disease mortality difference between Japan and the United States. Although no definite evidence is available showing that tissue plasminogen activator antigen is a risk factor for coronary heart disease, the present study suggests a positive ecologic association between this hemostatic factor and coronary heart disease mortality.