Quanhe Yang

Mortality associated with Down's syndrome in the USA from 1983 to 1997: a population-based study

BACKGROUND Downs syndrome is the most frequently identified cause of mental retardation, but information about mortality and comorbidity in people with Downs syndrome is limited. METHODS We used data from US death certificates from 1983 to 1997 to calculate median age at death and standardised mortality odds ratios (SMORs) for common medical disorders in people with Downs syndrome. FINDINGS Of 17897 people reported to have Downs syndrome, median age at death increased from 25 years in 1983 to 49 years in 1997, an average increase of 1.7 years per year studied (p<0.0001). Median age at death was significantly lower in black people and people of other races than in white people with Downs syndrome. As expected, death certificates with a diagnosis of Downs syndrome were more likely to list congenital heart defects (SMOR 29.1, 95% CI 27.8-30.4), dementia (21.2, 19.6-22.7), hypothyroidism (20.3, 18.5-22.3), or leukaemia (1.6, 1.4-1.8) than were those that did not report Downs syndrome. By contrast, malignant neoplasms other than leukaemia were listed on death certificates of people with Downs syndrome less than one-tenth as often as expected (0.07, 0.06-0.08). A strikingly low SMOR for malignancy was associated with Downs syndrome at all ages, in both sexes, and for all common tumour types except leukaemia and testicular cancer. INTERPRETATION Identification of factors responsible for the racial differences recorded could facilitate further improvement in survival of people with Downs syndrome. Reduced exposure to environmental factors that contribute to cancer risk, tumour-suppressor genes on chromosome 21, or a slower rate of replication or higher likelihood of apoptosis in Downs syndrome cells, could be possible reasons for paucity of cancer in people with Downs syndrome.

Trends in Cardiovascular Health Metrics and Associations With All-Cause and CVD Mortality Among US Adults

CONTEXT Recent recommendations from the American Heart Association aim to improve cardiovascular health by encouraging the general population to meet 7 cardiovascular health metrics: not smoking; being physically active; having normal blood pressure, blood glucose and total cholesterol levels, and weight; and eating a healthy diet. OBJECTIVE To examine time trends in cardiovascular health metrics and to estimate joint associations and population-attributable fractions of these metrics in relation to all-cause and cardiovascular disease (CVD) mortality risk. DESIGN, SETTING, AND PARTICIPANTS Study of a nationally representative sample of 44,959 US adults (≥20 years), using data from the National Health and Nutrition Examination Survey (NHANES) 1988-1994, 1999-2004, and 2005-2010 and the NHANES III Linked Mortality File (through 2006). MAIN OUTCOME MEASURES All-cause, CVD, and ischemic heart disease (IHD) mortality. RESULTS Few participants met all 7 cardiovascular health metrics (2.0% [95% CI, 1.5%-2.5%] in 1988-1994, 1.2% [95% CI, 0.8%-1.9%] in 2005-2010). Among NHANES III participants, 2673 all-cause, 1085 CVD, and 576 IHD deaths occurred (median follow-up, 14.5 years). Among participants who met 1 or fewer cardiovascular health metrics, age- and sex-standardized absolute risks were 14.8 (95% CI, 13.2-16.5) deaths per 1000 person-years for all-cause mortality, 6.5 (95% CI, 5.5-7.6) for CVD mortality, and 3.7 (95% CI, 2.8-4.5) for IHD mortality. Among those who met 6 or more metrics, corresponding risks were 5.4 (95% CI, 3.6-7.3) for all-cause mortality, 1.5 (95% CI, 0.5-2.5) for CVD mortality, and 1.1 (95% CI, 0.7-2.0) for IHD mortality. Adjusted hazard ratios were 0.49 (95% CI, 0.33-0.74) for all-cause mortality, 0.24 (95% CI, 0.13-0.47) for CVD mortality, and 0.30 (95% CI, 0.13-0.68) for IHD mortality, comparing participants who met 6 or more vs 1 or fewer cardiovascular health metrics. Adjusted population-attributable fractions were 59% (95% CI, 33%-76%) for all-cause mortality, 64% (95% CI, 28%-84%) for CVD mortality, and 63% (95% CI, 5%-89%) for IHD mortality. CONCLUSION Meeting a greater number of cardiovascular health metrics was associated with a lower risk of total and CVD mortality, but the prevalence of meeting all 7 cardiovascular health metrics was low in the study population.

Mortality associated with congenital heart defects in the United States : Trends and racial disparities, 1979-1997

Background—Surgical series and some population-based studies have documented a decrease in mortality from heart defects. Recent population-based data for the United States are lacking, however. We examined population-based data for patterns, time trends, and racial differences of mortality from heart defects for the United States from 1979 through 1997. Methods and Results—We examined the multiple-cause mortality files compiled by the National Center for Health Statistics of the CDC from all death certificates filed in the United States. From these data, we derived death rates (deaths per 100 000 population) by the decedent’s age, race, year of death, and heart defect type. We also analyzed age at death as an indirect indicator of survival. From 1979 through 1997, mortality from heart defects (all ages) declined 39%, from 2.5 to 1.5 per 100 000 population; among infants, the decline was 39%, or 2.7% per year. In 1995 to 1997, heart defects contributed to 5822 deaths per year. Of these deaths, 51% were among infants and 7% among children 1 to 4 years old. Mortality was on average 19% higher among blacks than among whites; this gap does not appear to be closing. Age at death increased for most heart defects, although less among blacks than among whites. Conclusions—Mortality from heart defects is declining in the United States, although it remains a major cause of death in infancy and childhood. Age at death is increasing, suggesting that more affected persons are living to adolescence and adulthood. The racial discrepancies should be investigated to identify opportunities for prevention.

Improvement in Stroke Mortality in Canada and the United States, 1990 to 2002

Background— In the United States and Canada, folic acid fortification of enriched grain products was fully implemented by 1998. The resulting population-wide reduction in blood homocysteine concentrations might be expected to reduce stroke mortality if high homocysteine levels are an independent risk factor for stroke. Methods and Results— In this population-based cohort study with quasi-experimental intervention, we used segmented log-linear regression to evaluate trends in stroke-related mortality before and after folic acid fortification in the United States and Canada and, as a comparison, during the same period in England and Wales, where fortification is not required. Average blood folate concentrations increased and homocysteine concentrations decreased in the United States after fortification. The ongoing decline in stroke mortality observed in the United States between 1990 and 1997 accelerated in 1998 to 2002 in nearly all population strata, with an overall change from −0.3% (95% CI, −0.7 to 0.08) to −2.9 (95% CI, −3.5 to −2.3) per year (P=0.0005). Sensitivity analyses indicate that changes in other major recognized risk factors are unlikely to account for the reduced number of stroke-related deaths in the United States. The fall in stroke mortality in Canada averaged −1.0% (95% CI, −1.4 to −0.6) per year from 1990 to 1997 and accelerated to −5.4% (95% CI, −6.0 to −4.7) per year in 1998 to 2002 (P≤0.0001). In contrast, the decline in stroke mortality in England and Wales did not change significantly between 1990 and 2002. Conclusions— The improvement in stroke mortality observed after folic acid fortification in the United States and Canada but not in England and Wales is consistent with the hypothesis that folic acid fortification helps to reduce deaths from stroke.

Mortality in neurofibromatosis 1: an analysis using U.S. death certificates.

Although neurofibromatosis 1 (NF1) is a relatively common autosomal dominant condition, information about its effect on mortality is limited. We used Multiple-Cause Mortality Files, compiled from U.S. death certificates by the National Center for Health Statistics, for 1983 through 1997. We identified 3,770 cases of presumed NF1 among 32,722,122 deaths in the United States, a frequency of 1/8,700, which is one-third to one-half the estimated prevalence. Mean and median ages at death for persons with NF1 were 54.4 and 59 years, respectively, compared with 70.1 and 74 years in the general population. Results of proportionate mortality ratio (PMR) analyses showed that persons with NF1 were 34 times more likely (PMR=34.3, 95% confidence interval [CI] 30.8-38.0) to have a malignant connective or other soft-tissue neoplasm listed on their death certificates than were persons without NF1. Overall, persons with NF1 were 1.2 times more likely than expected (PMR=1.21, 95% CI 1.14-1.28) to have a malignant neoplasm listed on their death certificates, but the PMR was 6.07 (95% CI 4.88-7.45) for persons who died at 10-19 years of age and was 4.93 (95% CI 4.14-5.82) for those who died at 20-29 years of age. Similarly, vascular disease was recorded more often than expected on death certificates of persons with NF1 who died at <30 years of age (PMR=3.26, 95% CI 1.31-6.71 at age <10 years; PMR=2.68, 95% CI 1.38-4.68 at age 10-19 years; and PMR=2.25, 95% CI 1.46-3.32 at 20-29 years) but not in older persons. This study supports previous findings of decreased life expectancy for persons with NF1 and, within the limitations of death certificates, provides population-based data about NF1 morbidity and mortality that are useful to clinicians caring for patients with NF1.

Added Sugar Intake and Cardiovascular Diseases Mortality Among US Adults

IMPORTANCE Epidemiologic studies have suggested that higher intake of added sugar is associated with cardiovascular disease (CVD) risk factors. Few prospective studies have examined the association of added sugar intake with CVD mortality. OBJECTIVE To examine time trends of added sugar consumption as percentage of daily calories in the United States and investigate the association of this consumption with CVD mortality. DESIGN, SETTING, AND PARTICIPANTS National Health and Nutrition Examination Survey (NHANES, 1988-1994 [III], 1999-2004, and 2005-2010 [n = 31,147]) for the time trend analysis and NHANES III Linked Mortality cohort (1988-2006 [n = 11 733]), a prospective cohort of a nationally representative sample of US adults for the association study. MAIN OUTCOMES AND MEASURES Cardiovascular disease mortality. RESULTS Among US adults, the adjusted mean percentage of daily calories from added sugar increased from 15.7% (95% CI, 15.0%-16.4%) in 1988-1994 to 16.8% (16.0%-17.7%; P = .02) in 1999-2004 and decreased to 14.9% (14.2%-15.5%; P < .001) in 2005-2010. Most adults consumed 10% or more of calories from added sugar (71.4%) and approximately 10% consumed 25% or more in 2005-2010. During a median follow-up period of 14.6 years, we documented 831 CVD deaths during 163,039 person-years. Age-, sex-, and race/ethnicity-adjusted hazard ratios (HRs) of CVD mortality across quintiles of the percentage of daily calories consumed from added sugar were 1.00 (reference), 1.09 (95% CI, 1.05-1.13), 1.23 (1.12-1.34), 1.49 (1.24-1.78), and 2.43 (1.63-3.62; P < .001), respectively. After additional adjustment for sociodemographic, behavioral, and clinical characteristics, HRs were 1.00 (reference), 1.07 (1.02-1.12), 1.18 (1.06-1.31), 1.38 (1.11-1.70), and 2.03 (1.26-3.27; P = .004), respectively. Adjusted HRs were 1.30 (95% CI, 1.09-1.55) and 2.75 (1.40-5.42; P = .004), respectively, comparing participants who consumed 10.0% to 24.9% or 25.0% or more calories from added sugar with those who consumed less than 10.0% of calories from added sugar. These findings were largely consistent across age group, sex, race/ethnicity (except among non-Hispanic blacks), educational attainment, physical activity, health eating index, and body mass index. CONCLUSIONS AND RELEVANCE Most US adults consume more added sugar than is recommended for a healthy diet. We observed a significant relationship between added sugar consumption and increased risk for CVD mortality.

Accounting for Unmeasured Population Substructure in Case-Control Studies of Genetic Association Using a Novel Latent-Class Model

We propose a novel latent-class approach to detect and account for population stratification in a case-control study of association between a candidate gene and a disease. In our approach, population substructure is detected and accounted for using data on additional loci that are in linkage equilibrium within subpopulations but have alleles that vary in frequency between subpopulations. We have tested our approach using simulated data based on allele frequencies in 12 short tandem repeat (STR) loci in four populations in Argentina.

Sodium and Potassium Intake and Mortality Among US Adults: Prospective Data From the Third National Health and Nutrition Examination Survey

BACKGROUND Several epidemiologic studies suggested that higher sodium and lower potassium intakes were associated with increased risk of cardiovascular diseases (CVD). Few studies have examined joint effects of dietary sodium and potassium intake on risk of mortality. METHODS To investigate estimated usual intakes of sodium and potassium as well as their ratio in relation to risk of all-cause and CVD mortality, the Third National Health and Nutrition Examination Survey Linked Mortality File (1988-2006), a prospective cohort study of a nationally representative sample of 12,267 US adults, studied all-cause, cardiovascular, and ischemic heart (IHD) diseases mortality. RESULTS During a mean follow-up period of 14.8 years, we documented a total of 2270 deaths, including 825 CVD deaths and 443 IHD deaths. After multivariable adjustment, higher sodium intake was associated with increased all-cause mortality (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.03-1.41 per 1000 mg/d), whereas higher potassium intake was associated with lower mortality risk (HR, 0.80; 95% CI, 0.67-0.94 per 1000 mg/d). For sodium-potassium ratio, the adjusted HRs comparing the highest quartile with the lowest quartile were HR, 1.46 (95% CI, 1.27-1.67) for all-cause mortality; HR, 1.46 (95% CI, 1.11-1.92) for CVD mortality; and HR, 2.15 (95% CI, 1.48-3.12) for IHD mortality. These findings did not differ significantly by sex, race/ethnicity, body mass index, hypertension status, education levels, or physical activity. CONCLUSION Our findings suggest that a higher sodium-potassium ratio is associated with significantly increased risk of CVD and all-cause mortality, and higher sodium intake is associated with increased total mortality in the general US population.

Trends in the postfortification prevalence of spina bifida and anencephaly in the United States

BACKGROUND The prevalence of NTDs in the US declined significantly after mandatory folic acid fortification; however, it is not known if the prevalence of NTDs has continued to decrease in recent years relative to the period immediately following the fortification mandate. METHODS Population-based data from 21 birth defects surveillance systems were used to examine trends in the birth prevalence of spina bifida and anencephaly during 1999-2000, 2001-2002, and 2003-2004. Prevalence data were stratified by non-Hispanic White, non-Hispanic Black, and Hispanic race or ethnicity. Prevalence ratios were calculated by dividing the birth prevalences during the later time periods (2001-2002 and 2003-2004) by the birth prevalences during 1999-2000. RESULTS During 1999-2004, 3,311 cases of spina bifida and 2,116 cases of anencephaly were reported. Hispanic infants had the highest prevalences of NTDs for all years. For all infants, the combined birth prevalences of spina bifida and anencephaly decreased 10% from the 1999-2000 period to the 2003-2004 period. The decline in spina bifida (3%) was not significant; however the decline in anencephaly (20%) was statistically significant. CONCLUSIONS While the prevalences of spina bifida and anencephaly in the United States have declined since folic acid fortification in the food supply began, these data suggest that reductions in the prevalence of anencephaly continued during 2001-2004 and that racial and ethnic and other disparities remain.

Sodium and potassium intakes among US adults: NHANES 2003–2008

BACKGROUND The American Heart Association (AHA), Institute of Medicine (IOM), and US Departments of Health and Human Services and Agriculture (USDA) Dietary Guidelines for Americans all recommend that Americans limit sodium intake and choose foods that contain potassium to decrease the risk of hypertension and other adverse health outcomes. OBJECTIVE We estimated the distributions of usual daily sodium and potassium intakes by sociodemographic and health characteristics relative to current recommendations. DESIGN We used 24-h dietary recalls and other data from 12,581 adults aged ≥20 y who participated in NHANES in 2003-2008. Estimates of sodium and potassium intakes were adjusted for within-individual day-to-day variation by using measurement error models. SEs and 95% CIs were assessed by using jackknife replicate weights. RESULTS Overall, 99.4% (95% CI: 99.3%, 99.5%) of US adults consumed more sodium daily than recommended by the AHA (<1500 mg), and 90.7% (89.6%, 91.8%) consumed more than the IOM Tolerable Upper Intake Level (2300 mg). In US adults who are recommended by the Dietary Guidelines to further reduce sodium intake to 1500 mg/d (ie, African Americans aged ≥51 y or persons with hypertension, diabetes, or chronic kidney disease), 98.8% (98.4%, 99.2%) overall consumed >1500 mg/d, and 60.4% consumed >3000 mg/d-more than double the recommendation. Overall, <2% of US adults and ~5% of US men consumed ≥4700 mg K/d (ie, met recommendations for potassium). CONCLUSION Regardless of recommendations or sociodemographic or health characteristics, the vast majority of US adults consume too much sodium and too little potassium.