Long-Term Exposure to AIR Pollution and COVID-19 Mortality and Morbidity in DENmark: Who Is Most Susceptible? (AIRCODEN).

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.

The association between seasonal influenza-like illness cases and foetal death: a time series analysis.

It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.

Criterion validity of the Physical Activity Scale (PAS2) in Danish adults.

BACKGROUND: The Physical Activity Scale (PAS2) was developed to measure physical activity (PA) during work, transportation and leisure time, in the Danish adult population. The objective of this study was to assess the criterion validity of PAS2 against a combined accelerometer and heart rate monitor in Danish adults and to investigate if the criterion validity differed by socio-demographic factors and body mass index. METHOD: A total of 330 Danish adults (mean age = 46.7 years, 38.5% men) participating in the Health2008 study completed the PAS2 questionnaire and wore a combined accelerometer and heart rate sensor for seven days. Average daily estimates from PAS2 were categorised into time spent in sedentary behaviour, light PA, moderate PA and vigorous PA and were compared to the objective measures. RESULTS: PAS2 accounted for 19.5 hours/day on average. Time spent in sedentary behaviour, light and moderate-intensity PA was weakly correlated with objective data (polychoric correlation coefficients (PCC): 0.18-0.20), whereas vigorous intensity PA was moderately correlated (PCC: 0.54, p = 0.04). Mean bias was -2.3 hours/day (95% limits of agreement (LoA): -9.04 to 4.34) for sedentary behaviour, 1.68 hours/day (LoA: 8.02 to -4.62) for light activity, 0.55 hours/day (LoA: 3.37 to -2.26) for moderate activity and 0.12 hours/day (LoA: 0.57 to 0.33) for vigorous activity. Criterion validity was lower in women, in participants who were above 40 years, overweight, had short education and were unemployed. CONCLUSIONS: PAS2 overestimated time spent on light, moderate and vigorous intensity PA and underestimated time spent on sedentary behaviour. Validity differed by key socio-demographic characteristics.

Educational differences in cardiovascular mortality: The role of shared family factors and cardiovascular risk factors.

AIMS: To explore the confounding effects of early family factors shared by siblings and cardiovascular risk factors in midlife on the educational differences in mortality from cardiovascular disease (CVD). METHODS: Data from national and regional health surveys in Norway (1974-2003) were linked with data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry. The study population consisted of participants with at least one full sibling among the health survey participants ( n=271,310). Data were available on CVD risk factors, including weight, height, blood pressure, total cholesterol and smoking. RESULTS: The hazards ratio (HR) of CVD mortality was 3.44 (95% confidence interval (CI) 2.98-3.96) in the lowest educational group relative to the highest. The HRs were little altered in the within-sibship analyses. Adjusted for risk factors, the HR for CVD mortality in the cohort analyses was 2.05 (CI 1.77-2.37) in the lowest educational group relative to the highest. The respective HR in the within-sibship analyses was 2.46 (CI 1.48-2.24). CONCLUSIONS: Using a sibling design, we did not find that the association between education and CVD mortality was confounded by early life factors shared by siblings, but it was explained to a large extent by CVD risk factors. These results suggest that reducing levels of CVD risk factors could have the greatest effect on mortality in less well-educated people.

Advanced paternal age and mortality of offspring under 5 years of age: a register-based cohort study.

STUDY QUESTION: Do children born to fathers of advanced age have an increased risk of dying before the age of 5 years? SUMMARY ANSWER: Children born to fathers aged 40 years or more have an increased risk of dying in early childhood due to an excess risk of fatal congenital anomalies, malignancies and external causes. WHAT IS KNOWN ALREADY: Advanced paternal age has previously been associated with adverse reproductive outcomes and some long-term health problems in the offspring. This is possibly due to specific point mutations, a condition known to increase in the sperm with increasing paternal age. STUDY DESIGN, SIZE, DURATION: A Danish population-based register study, designed as a prospective cohort study, of 1 575 521 live born children born from 1978 to 2004. The age of the child (in days) was used as the underlying time and the children entered the cohort the day they were born and were followed until 31 December 2009. The children were censored on date of turning 5 years, date of death or date of emigration, whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from population-covering registers from Statistics Denmark including the Integrated Database for Labour Market Research, the Medical Birth Registry and the Registry of Causes of Death was linked using the unique civil registry number. Hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the risk of under-five mortality. The effect of paternal age was examined using restricted cubic splines and paternal age groups. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with children born to fathers aged 30-34 years, a statistically significant excess risk was found for children born to fathers aged 40-44 years [HR: 1.10 (95% CI: 1.00-1.21)] and children born to fathers aged 45+ years [HR: 1.16 (95% CI: 1.02-1.32)]. When only looking at 1-5 year olds, the relative risk (HR) among children born to fathers aged 40-44 years increased to 1.24 (95% CI: 1.00-1.53) and the risk in the oldest paternal age group (45+ years) rose to 1.65 (95% CI: 1.24-2.18). The results suggest that the elevated risk for children of fathers aged 40 years or more was primarily attributed to an elevated risk of dying from congenital malformations, malignancies and external causes. LIMITATIONS, REASONS FOR CAUTION: Specific causes of death might be misclassified; however, this is not likely to be dependent on paternal age. In some cases, the biological father may differ from the father registered. This misclassification is most likely non-differential. WIDER IMPLICATIONS OF THE FINDINGS: The excess risk of mortality among children born to older fathers is in accordance with the literature. The association needs further attention as it can provide valuable knowledge of the etiology of genetic diseases. Also, the association could become of greater importance in the future if the proportion of fathers aged 40+ years keeps growing. STUDY FUNDING/COMPETING INTEREST (S): None.

Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries.

OBJECTIVE: To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. DESIGN: Cross-country comparative study of linked population-based databases. SETTING: Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. POPULATION: All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995-2010). METHODS: Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). MAIN OUTCOME MEASURES: Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). RESULTS: There were 9,028,802 deliveries (3,031,399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. CONCLUSION: Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia.

Early-life environment influencing susceptibility to cytomegalovirus infection: evidence from the Leiden Longevity Study and the Longitudinal Study of Aging Danish Twins.

Human cytomegalovirus (CMV) is a common herpesvirus establishing lifelong persisting infection, which has been implicated in immunosenescence and mortality in the elderly. Little is known about how and when susceptibility to CMV infection is determined. We measured CMV seroprevalence in two genetically informative cohorts. From the Leiden Longevity Study (LLS) we selected long-lived sib-pairs (n=844) and their middle-aged offspring and the offspring's partners (n=1452). From the Longitudinal Study of Aging Danish Twins (LSADT) 604 (302 pairs) same-sex monozygotic (MZ) and dizygotic (DZ) twins aged 73-94 years were included (n=302 pairs). Offspring of the long-lived LLS participants had significantly lower seroprevalence of CMV compared to their partners (offspring: 42% vs. partners: 51%, P=0·003). Of 372 offspring living with a CMV-positive partner, only 58% were infected. The corresponding number for partners was 71% (P<0·001). In the LSADT, MZ and DZ twins had high and similar CMV-positive concordance rates (MZ: 90% vs. DZ: 88%, P=0·51) suggesting that shared family environment accounts for the similarity within twin pairs. Our findings suggest that susceptibility to CMV infection--even under continuous within-partnership exposure--appears to be more strongly influenced by early-life environment than by genetic factors and adult environment.

Inequality, Familial Aggregation, and Risk Prediction of Caries in Siblings.

INTRODUCTION: Social and family conditions are likely of great importance to dental health; however, limited evidence of familial aggregation of caries among adolescent siblings exists. Moreover, social and family-level factors have never been evaluated as isolated caries predictors at the individual level. OBJECTIVES: The objectives were to evaluate socioeconomic patterning of caries among siblings, assess sibling-specific aggregation of caries within families, and examine if such aggregation differed by parental socioeconomic position (SEP). We also evaluated the discriminant ability of sibling caries, SEP, and other social and familial factors in predicting caries in cosiblings. METHODS: This nationwide register-based study included all 15-y-olds in Denmark in 2003 (index siblings) and their biological siblings born within ±3 y (cosiblings). Clinical and sociodemographic data for each subject were compiled from Danish national dental, social, and population registers. Caries was measured by the decayed, missing, and filled tooth surfaces (DMFS) index. Predictors included SEP (parental education, income, and occupational social class), gender, birth order, immigration status, and household type. Adjusted SEP-caries associations were estimated using negative binomial regression. Familial aggregation was evaluated using adjusted pairwise odds ratios from alternating logistic regressions. Caries prediction was based on classification and regression tree (CART) analyses. RESULTS: The study included 23,847 sibling pairs (n = 47,694). Socioeconomic patterning of caries was similar among the index and cosiblings with significant graded SEP-caries associations. Significant sibling-specific aggregation of caries was observed; cosiblings of caries-affected index siblings had odds of having caries 3.9 times (95% confidence interval: 3.65-4.18) as high as that of cosiblings with caries-free index siblings. This sibling similarity was stronger in socioeconomically disadvantaged families (adjusted pairwise odds ratios: 3.08-5.47). CART revealed index sibling caries as the single most important caries predictor, with caries predicted in ≥84% of cosiblings of adolescents with ≥3 carious tooth surfaces. CONCLUSIONS: Caries in a sibling should prompt preventive family-based approaches targeting cosiblings. KNOWLEDGE TRANSFER STATEMENT: This study revealed significant socioeconomic patterning of caries in adolescent siblings. Prediction modeling indicated that the single most important caries predictor among cosiblings was index sibling caries. Information on sibling caries level should be routinely combined with clinical evaluation to identify children at risk. Moreover, information on social and family conditions should be used to target prevention and health promotion at the school or municipal level. These approaches could possibly contribute to reducing the existing caries inequalities.

Frequency and impact of obstetric complications prior and subsequent to unexplained secondary recurrent miscarriage.

BACKGROUND: The chance of a live birth after a diagnosis of secondary recurrent miscarriage (SRM) is reduced in patients who, prior to the miscarriages, gave birth to a boy and carry HLA class II alleles that efficiently present male-specific (H-Y) antigens to the immune system. Information about obstetric complications in births prior and subsequent to the SRM diagnosis is limited. The relations between maternal carriage of H-Y-restricting HLA, fetal sex, obstetric complications and prognosis are unknown. METHODS: Women with unexplained SRM referred to the Danish Recurrent Miscarriage Clinic between 1986 and 2006 (n = 358) were included; 213 gave birth after the diagnosis. Controls, retrieved from the Danish National Birth Registry, were all women with singleton birth of parity 0, 1982-2005 (n = 608,068) and parity 1, 1986-2008 (n = 510,264). Cross-linkage to the National Discharge Registry identified birth complication diagnoses related to the relevant births among patients and controls. RESULTS: The sex ratio was 1.49 in births prior to SRM and 0.76 in birth after SRM (P < 0.0001). For SRM patients with only late miscarriages (>10 weeks gestation), the corresponding sex ratios were 2.31 and 0.21. Compared with the control groups, obstetric complications were more frequent both before (39% versus 24% P

Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a life shortening disease, however prognosis has improved and the adult population is growing. Most adults with cystic fibrosis live independent lives and balance the demands of work and family life with a significant treatment burden. The aim of this study was to examine the relationships among treatment adherence, symptoms of depression and health-related quality of life (HRQoL) in a population of young adults with CF. METHODS: We administered three standardized questionnaires to 67 patients with CF aged 18-30 years; Morisky Medication Adherence Scale, Major Depression Inventory, and Cystic Fibrosis Questionnaire-Revised. RESULTS: There was a response rate of 77 % and a majority of the young adults (84 %) were employed or in an education program. Most participants (74 %) reported low adherence to medications. One third (32.8 %) of the participants reported symptoms of depression. HRQoL scores were especially low on Vitality and Treatment Burden, and symptoms of depression were associated with low HRQoL scores (p < 0.01) with medium to large deficits across on all HRQoL domains (Cohen's d 0.60-1.72) except for the domain treatment burden. High depression symptom scores were associated with low adherence (r = -0.412, p < 0.001). CONCLUSIONS: Despite improved physical health, many patients with CF report poor adherence, as well as impaired mental wellbeing and HRQoL. Thus, more attention to mental health issues is needed.

Erratum to: Associations between adherence, depressive symptoms and health-related quality of life in young adults with cystic fibrosis.

[This corrects the article DOI: 10.1186/s40064-016-2862-5.].

Salt-dependency of endothelin-induced, chronic hypertension in conscious rats.

The effect of salt intake on the hypertensive response to long-term infusion of endothelin-1 was investigated. Chronically instrumented male Sprague-Dawley rats (325-375 g) were used in a 15-day protocol that included 3 control days followed by 7 days of endothelin-1 infusion at 5.0 pmol.kg-1.min-1 and 5 days of recovery. Rats were maintained on either a normal sodium chloride intake (2.0 meq Na+ per day; normal sodium) or a high sodium chloride intake (6.0 meq Na+ per day; high sodium) throughout the protocol. Control rats received normal or high sodium intakes but not endothelin-1. In high-sodium rats, endothelin-1 produced a significant increase in mean arterial pressure and total peripheral resistance; a significant bradycardia was observed only on the first day after the start of the endothelin-1 infusion. Cardiac output, stroke volume, water balance, and urinary sodium and potassium excretion remained unchanged. Termination of endothelin-1 infusion resulted in rapid normalization of both arterial pressure and peripheral resistance. In contrast, normal sodium rats exhibited no alteration in mean arterial pressure, heart rate, total peripheral resistance, stroke volume, water balance, or urinary sodium and potassium excretion throughout the endothelin-1 infusion protocol. The hypertension produced by endothelin-1 infusion cannot be explained by alterations in salt or water balance since endothelin-1 infusion in high sodium animals produced significant increases in mean arterial pressure with no observable changes in water or electrolyte balance. These results indicate that endothelin-induced hypertension in conscious rats is a salt-dependent model of hypertension.

Captopril prevents chronic hypertension produced by infusion of endothelin-1 in rats.

Endothelin-1 (ET-1), a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, has been previously shown to produce a sustained, salt-sensitive elevation in mean arterial pressure when chronically infused over a 7-day period into male Sprague-Dawley rats. In addition to other physiological actions, ET-1 has been shown to have potent effects on various renal functions, including renin production. Activation of the renin-angiotensin system, therefore, may contribute to the pressor response induced by ET-1. In this investigation, captopril ([2S]-1-[3-mercapto-2-methylpropionyl]-L-proline), a sulfhydryl-containing angiotensin I converting enzyme inhibitor, was chronically administered to endothelin-infused rats to elucidate the role of the renin-angiotensin system in this animal model of hypertension. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6.0 meq.day-1 sodium intake throughout the experiment, with daily measurements taken of mean arterial pressure, heart rate, water intake, urine output, and urinary sodium and potassium excretions. Infusion of ET-1 alone at a rate of 5.0 pmol.kg-1.min-1 for 7 days was associated with a significant and sustained increase in mean arterial pressure; concomitant chronic administration of captopril in another group of rats at a rate of 1.0 mg.kg-1.hr-1 prevented the ET-1-induced hypertension. In an additional study, however, increases in plasma angiotensin II concentration were not observed in rats administered ET-1 alone at 5.0 pmol.kg-1.min-1. These results indicate that endothelin-induced hypertension may involve stimulation of the renin-angiotensin system but not an increase in circulating angiotensin II concentration.

Effects of lateral parabrachial nucleus lesions in chronic renal hypertensive rats.

Neuroanatomic studies describing forebrain projections to the lateral parabrachial nucleus suggest a central integrative role in cardiovascular regulation. We performed this study to examine the role of this pontine nucleus in the maintenance of one-kidney, figure-8 renal-wrap hypertension. Bilateral ibotenic acid ablation of the lateral parabrachial nucleus was performed 4 weeks after induction of hypertension or sham operation. In hypertensive rats, ablation produced a significant reduction in mean arterial pressure from 160 +/- 4 to 118 +/- 2 mm Hg and a transient but significant increase in heart rate from 381 +/- 5 to 408 +/- 8 beats per minute on the first day after ablation; arterial pressure returned to preablation values by day 5 after ablation. In sham-operated, normotensive animals, arterial pressure was not altered by ablation, and a transient but significant increase in heart rate from 384 +/- 8 to 419 +/- 7 beats per minute was again observed. Before ablation, trimethaphan administration produced a significantly greater drop in arterial pressure in hypertensive (delta-72.8 +/- 4.6 mm Hg) versus normotensive (delta-55.7 +/- 4.1 mm Hg) animals. This effect was eliminated on day 1 after ablation yet returned on day 4 after ablation. In blood samples obtained before ablation and on days 1 and 4 after ablation, circulating plasma catecholamine concentrations in both groups remained unchanged. These observations suggest that, because of possible alternate neural compensatory mechanisms, lateral parabrachial nucleus ablation produces a significant yet transient reversal of renal-wrap hypertension. Thus, the lateral parabrachial nucleus may contribute to the increased sympathetic nervous system function associated with this model.

Obese Zucker rats are normotensive on normal and increased sodium intake.

The purpose of this study was to determine whether genetically obese Zucker rats have higher arterial pressures than lean littermates on normal and high sodium intakes. Mean arterial pressure was directly measured in chronically instrumented Zucker rats (six lean [weight, 345.8 +/- 8.0 g] and five obese [529.0 +/- 6.2 g]) for 2 weeks on both a normal (2 meq sodium/day) and high (6 meq sodium/day) sodium intake (7 days each). In addition, daily heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, and weekly fasting plasma insulin levels were measured. Obese rats exhibited significantly lower heart rate and greater water intake and urine output compared with lean rats whether maintained on control or high sodium intakes. Urinary sodium excretion, however, was identical in lean and obese rats throughout the experiment. Fasting plasma insulin levels in obese rats were seven times greater than those in lean rats. When the rats were maintained on a 2 meq/day sodium intake, mean arterial pressures obtained from the two groups were similar: 103 +/- 1 versus 106 +/- 1 mm Hg (lean versus obese). An increase in sodium intake did not significantly affect mean arterial pressure in either group: 101 +/- 1 versus 105 +/- 1 mm Hg (lean versus obese). These results indicate that at 12-14 weeks of age, male obese Zucker rats do not exhibit higher resting arterial pressures than lean littermates when maintained on normal or high sodium intake.

Chronic hypertension produced by infusion of endothelin in rats.

Endothelin, a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, was chronically infused into male Sprague-Dawley rats to determine whether a long-term increase in circulating endothelin levels would cause a sustained elevation in mean arterial pressure. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6 meq/day sodium intake throughout the experiment with daily measurements including mean arterial pressure, heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, cardiac output, total peripheral resistance, and stroke volume. Infusion of endothelin-1 (ET-1) at rates of 3, 5, or 7.5 pmol/kg/min for 7 days was associated with significant, sustained, and dose-dependent increases in mean arterial pressure and smaller less consistent elevations in total peripheral resistance. Other parameters were unaffected. Similar results were observed in rats receiving endothelin-3 (ET-3), except that a higher dose of ET-3 was required. These results indicate that elevated blood levels of endothelin could produce a maintained hypertension without sodium or water retention and that the hemodynamic basis for the increased mean arterial pressure is similar to that seen in most other forms of experimental and clinical hypertension.

Time is on whose side? Time trends in the association between maternal social disadvantage and offspring fetal growth. A study of 1 409 339 births in Denmark, 1981-2004.

BACKGROUND: Fetal growth is highly socially patterned and is related to health across the life course, but how the social patterns of fetal growth change over time remains understudied. The time trends in maternal social disadvantage in relation to fetal growth were examined in the context of a universal welfare state under changing macroeconomic conditions over a 24-year period. METHODS: All births in Denmark from 1981 to 2004 were included, and the association between maternal social disadvantage and birthweight was examined for gestational age z-scores over time using linear regression. RESULTS: All measures of social disadvantage were associated with decreased fetal growth (p<0.001), but with considerable differences in the magnitude of the associations. The association was strongest for non-Western ethnicity (-0.28 z-score), low education (-0.19), teenage motherhood (-0.14), single motherhood (-0.13) and poverty (-0.12) and weakest for unemployment (-0.04). The deficit in fetal growth increased over time for all associations except for unemployment. Also, the measures of social adversity increasingly clustered within individuals over time. CONCLUSION: Maternal social disadvantage is associated with decreased fetal growth in a welfare state. Social disadvantage is increasingly clustered so that fewer pregnancies are exposed, but those exposed suffer a greater disadvantage in fetal growth. The economic upturn in the last decade did not appear to weaken the association between maternal social disadvantage and decreased fetal growth.

Ethnic disparity in stillbirth and infant mortality in Denmark 1981-2003.

OBJECTIVE: Ethnic minorities constitute a growing part of the Danish population but little is known about ethnic disparity in early life mortality in this population. The aim of this study was to investigate ethnic disparities in stillbirth risk and infant mortality in Denmark from 1981 to 2003. METHODS: From population-covering registries, all live and stillbirths of women from the five largest ethnic minority groups and of women from the (Danish) majority population (N = 1,333,452) were identified. The liveborn were followed up for vital status to the age of 1 year. Log-binomial regression was used to estimate relative risks according to ethnic group. The main outcome measure was stillbirth and infant death. RESULTS: Compared with the majority population, the relative risks of stillbirth were 1.28 (95% CI: 1.07 to 1.53) for Turkish, 1.62 (1.25 to 2.09) for Pakistani and 2.11 (1.60 to 2.77) for Somali women. The relative risks of infant mortality were 1.41 (1.22 to 1.63), 1.88 (1.53 to 2.30) and 1.39 (1.03 to 1.89) for children born to Turkish, Pakistani and Somali mothers respectively. The fetal and infant mortality in offspring of Lebanese and Former Yugoslavian women was not different from the mortality in the Danish group. The differences found were, in general, not attributable to ethnic differences in socioeconomic position. Turkish, Pakistani and Somali children had an excess relative risk of infant death due to congenital malformations and the risk of death from perinatal causes was increased among the Pakistani offspring. CONCLUSION: Among the five largest ethnic minorities, the Turkish. Pakistani and Somali population had substantially higher fetal and infant mortality compared with the Danish majority population, while the Lebanese and Former Yugoslavian minorities were at the same level as the majority population. The excess risk was not attributable to socioeconomic conditions.

Pre-morbid intelligence, the metabolic syndrome and mortality: the Vietnam Experience Study.

AIMS/HYPOTHESIS: We examined the relationship between pre-morbid intelligence quotient (IQ) and the metabolic syndrome, and assessed the role of the metabolic syndrome as a mediating factor in the association of IQ with total and cardiovascular disease (CVD) mortality. METHODS: In this cohort study, 4,157 men with IQ test results from late adolescence or early adulthood [mean age (range) 20.4 (16-30) years] attended a clinical examination in middle-age [38.3 (31-46) years] at which the components of the metabolic syndrome were measured. They were then followed for 15 years to assess mortality. RESULTS: In age-adjusted analyses, IQ was significantly inversely related to four of the five individual components comprising the metabolic syndrome: hypertension, high BMI, high triglycerides and high blood glucose, but not low HDL-cholesterol. After controlling for a range of covariates that included socioeconomic position, higher IQ scores were associated with a reduced prevalence of the metabolic syndrome itself (odds ratio(1 SD increase in IQ) 0.87, 95% CI 0.78-0.98). Structural equation modelling revealed that education was not a mediator of the relationship between IQ and the metabolic syndrome. The metabolic syndrome partially mediated the relationship between IQ and CVD but not that between IQ and total mortality. CONCLUSIONS/INTERPRETATION: In this cohort, higher scores on a pre-morbid IQ test were associated with a lower prevalence of the metabolic syndrome and most of its components. The metabolic syndrome was a mediating variable in the IQ-CVD relationship.

Does IQ predict total and cardiovascular disease mortality as strongly as other risk factors? Comparison of effect estimates using the Vietnam Experience Study.

OBJECTIVE: To compare the strength of the relation of two measurements of IQ and 11 established risk factors with total and cardiovascular disease (CVD) mortality. METHODS: Cohort study of 4166 US male former army personnel with data on IQ test scores (in early adulthood and middle age), a range of established risk factors and 15-year mortality surveillance. RESULTS: When CVD mortality (n = 61) was the outcome of interest, the relative index of inequality (RII: hazard ratio; 95% CI) for the most disadvantaged relative to the advantaged (in descending order of magnitude of the first six based on age-adjusted analyses) was: 6.58 (2.54 to 17.1) for family income; 5.55 (2.16 to 14.2) for total cholesterol; 5.12 (2.01 to 13.0) for body mass index; 4.70 (1.89 to 11.7) for IQ in middle age; 4.29 (1.70 to 10.8) for blood glucose and 4.08 (1.63 to 10.2) for high-density lipoprotein cholesterol (the RII for IQ in early adulthood was ranked tenth: 2.88; 1.19 to 6.97). In analyses featuring all deaths (n = 233), the RII for risk factors most strongly related to this outcome was 7.46 (4.54 to 12.3) for family income; 4.41 (2.77 to 7.03) for IQ in middle age; 4.02 (2.37 to 6.83) for smoking; 3.81 (2.35 to 6.17) for educational attainment; 3.40 (2.14 to 5.41) for pulse rate and 3.26 (2.06 to 5.15) for IQ in early adulthood. Multivariable adjustment led to marked attenuation of these relations, particularly those for IQ. CONCLUSIONS: Lower scores on measures of IQ at two time points were associated with CVD and, particularly, total mortality, at a level of magnitude greater than several other established risk factors.