Sally Picciotto

Vulnerability to Heat-Related Mortality: A Multicity, Population-Based, Case-Crossover Analysis

Background: Although studies have documented increased mortality during heat waves, little information is available on the subgroups most susceptible to these effects. We evaluated the effects of summertime high temperature on daily mortality among population subgroups defined by demographic characteristics, socioeconomic status, and episodes of hospitalization for various conditions during the preceding 2 years. Methods: We studied a total of 205,019 residents of 4 Italian cities (Bologna, Milan, Rome, and Turin) age 35 or older who died during 1997–2003. The case-crossover design was applied to evaluate the association between mean apparent temperature (same and previous day) and all-cause mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) of dying at 30°C (apparent temperature) relative to 20°C were estimated accounting for time, population changes, and air pollution. Results: We found an overall OR of 1.34 (CI = 1.27–1.42) at 30°C relative to 20°C. The odds ratio increased with age and was higher among women (OR = 1.45; 1.37–1.52) and among widows and widowers (1.50; 1.33–1.69). Low area-based income modestly increased the effect. Among the preexisting medical conditions investigated, effect modification was detected for previous psychiatric disorders (1.69; 1.39–2.07), depression (1.72; 1.24–2.39), heart conduction disorders (1.77; 1.38–2.27), and circulatory disorders of the brain (1.47; 1.34–1.62). Temperature-related mortality was higher among people residing in nursing homes, and a large effect was also detected for hospitalized subjects. Conclusions: Subsets of the population that are particularly vulnerable to high summer temperatures include the elderly, women, widows and widowers, those with selected medical conditions, and those staying in nursing homes and healthcare facilities.

Ambient Air Pollution Is Associated With Increased Risk of Hospital Cardiac Readmissions of Myocardial Infarction Survivors in Five European Cities

Background— Ambient air pollution has been associated with increases in acute morbidity and mortality. The objective of this study was to evaluate the short-term effects of urban air pollution on cardiac hospital readmissions in survivors of myocardial infarction, a potentially susceptible subpopulation. Methods and Results— In this European multicenter cohort study, 22 006 survivors of a first myocardial infarction were recruited in Augsburg, Germany; Barcelona, Spain; Helsinki, Finland; Rome, Italy; and Stockholm, Sweden, from 1992 to 2000. Hospital readmissions were recorded in 1992 to 2001. Ambient nitrogen dioxide, carbon monoxide, ozone, and mass of particles <10 &mgr;m (PM10) were measured. Particle number concentrations were estimated as a proxy for ultrafine particles. Short-term effects of air pollution on hospital readmissions for myocardial infarction, angina pectoris, and cardiac causes (myocardial infarction, angina pectoris, dysrhythmia, or heart failure) were studied in city-specific Poisson regression analyses with subsequent pooling. During follow-up, 6655 cardiac readmissions were observed. Cardiac readmissions increased in association with same-day concentrations of PM10 (rate ratio [RR] 1.021, 95% CI 1.004 to 1.039) per 10 &mgr;g/m3) and estimated particle number concentrations (RR 1.026 [95% CI 1.005 to 1.048] per 10 000 particles/cm3). Effects of similar strength were observed for carbon monoxide (RR 1.014 [95% CI 1.001 to 1.026] per 200 &mgr;g/m3 [0.172 ppm]), nitrogen dioxide (RR 1.032 [95% CI 1.013 to 1.051] per 8 &mgr;g/m3 [4.16 ppb]), and ozone (RR 1.026 [95% CI 1.001 to 1.051] per 15 &mgr;g/m3 [7.5 ppb]). Pooled effect estimates for angina pectoris and myocardial infarction readmissions were comparable. Conclusions— The results suggest that ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in 5 European cities.

Associations of traffic related air pollutants with hospitalisation for first acute myocardial infarction: the HEAPSS study

Background: Acute myocardial infarction (AMI) is the leading cause of death attributed to cardiovascular diseases. An association between traffic related air pollution and AMI has been suggested, but the evidence is still limited. Objectives: To evaluate in a multicentre study association between hospitalisation for first AMI and daily levels of traffic related air pollution. Methods: The authors collected data on first AMI hospitalisations in five European cities. AMI registers were available in Augsburg and Barcelona; hospital discharge registers (HDRs) were used in Helsinki, Rome and Stockholm. NO2, CO, PM10 (particles <10 μm), and O3 were measured at central monitoring sites. Particle number concentration (PNC), a proxy for ultrafine particles (<0.1 μm), was measured for a year in each centre, and then modelled retrospectively for the whole study period. Generalised additive models were used for statistical analyses. Age and 28 day fatality and season were considered as potential effect modifiers in the three HDR centres. Results: Nearly 27 000 cases of first AMI were recorded. There was a suggestion of an association of the same day CO and PNC levels with AMI: RR = 1.005 (95% CI 1.000 to 1.010) per 0.2 mg/m3 and RR = 1.005 (95% CI 0.996 to 1.015) per 10000 particles/cm3, respectively. However, associations were only observed in the three cities with HDR, where power for city-specific analyses was higher. The authors observed in these cities the most consistent associations among fatal cases aged <75 years: RR at 1 day lag for CO = 1.021 (95% CI 1.000 to 1.048) per 0.2 mg/m3, for PNC = 1.058 (95% CI 1.012 to 1.107) per 10000 particles/cm3, and for NO2 = 1.032 (95% CI 0.998 to 1.066) per 8 μg/m3. Effects of air pollution were more pronounced during the warm than the cold season. Conclusions: The authors found support for the hypothesis that exposure to traffic related air pollution increases the risk of AMI. Most consistent associations were observed among fatal cases aged <75 years and in the warm season.

Air temperature and inflammatory responses in myocardial infarction survivors

Background: Temperature changes have been associated with increased cardiovascular risk, but the role of inflammatory markers in this relationship is not well understood. The objective of this study was to analyze the association between air temperature and C-reactive protein, interleukin-6 and fibrinogen in postmyocardial infarction patients. Methods: In a multicenter panel study, the 3 inflammatory blood markers were measured repeatedly. In total, 5813 blood samples in 1003 subjects were collected in 6 European cities representing different climates. Data on patient characteristics and disease history were gathered at the baseline visit. Meteorologic data were obtained from the city-specific network stations. The association was analyzed using a semiparametric model with random patient effects. Results: A 10°C decrease in the 5-day-average of air temperature before the blood withdrawal was associated with a 4% increase in C-reactive protein (4.3% [95% confidence interval = 0.2% to 8.1%]). Correspondingly, an increase of interleukin-6 was observed for the same time window (3.3% [0.1% to 6.3%]) whereas fibrinogen showed an increase of 1.3% (0.2% to 2.4%) with a lag of 3 days. Conclusion: A decrease in air temperature, particularly the average temperature of the last 5 days, was associated with an increase in both C-reactive protein and interleukin-6, whereas fibrinogen seemed to react to temperature changes after 3 days. In susceptible patients this might lead to an additional risk for cardiovascular events and suggests a biologic mechanism for the observed seasonal variation in death from ischemic heart disease and stroke in the elderly.

Traffic-related air pollution in relation to incidence and prognosis of coronary heart disease.

Background: Long-term air pollution exposure is associated with increased mortality, but the association with incidence of fatal and nonfatal coronary heart disease is less certain. Moreover, it is unknown how chronic exposure to air pollution affects prognosis among survivors of a first coronary event. This study evaluated the association between long-term traffic-related air pollution exposure and incidence of nonfatal and fatal coronary events, as well as subsequent hospital readmission and mortality among myocardial infarction survivors. Methods: The study population comprised all residents of Rome aged 35–84 years during the period 1998–2000. Residential nitrogen dioxide (NO2) exposure as a marker of traffic pollution was assessed by a land-use regression model in 1995–1996 (R2 = 0.69). A total of 11,167 incident coronary events were observed (4654 fatal, including 3598 out-of-hospital coronary deaths, and 6513 nonfatal). The cohort of 6513 survivors was followed 4.0–7.5 years for readmission or mortality, starting 28 days from the date of first event. Relative risks per 10 &mgr;g/m3 of NO2 exposure, adjusted for age, sex, and socioeconomic status, were calculated by Poisson regression (population-based incidence) and Cox regression (cohort analysis). Results: The relative risk for incidence in coronary events per 10 &mgr;g/m3 of NO2 was 1.03 (95% confidence interval = 1.00–1.07). Stronger associations were found for fatal cases (1.07; 1.02–1.12) and out-of-hospital deaths (1.08; 1.02–1.13). Using NO2 exposure at the time of the first event, there was no association of air pollution exposure with either subsequent hospital readmission or mortality among survivors of the first coronary event. Conclusions: Long-term air pollution exposure increases the risk of coronary heart disease, particularly fatal events. Hospital readmission or subsequent mortality among survivors was not associated with traffic air pollution.

Air Pollution and Inflammatory Response in Myocardial Infarction Survivors: Gene–Environment Interactions in a High-Risk Group

Ambient air pollution has been associated with an increased risk of hospital admission and mortality in potentially susceptible subpopulations, including myocardial infarction (MI) survivors. The multicenter epidemiological study described in this report was set up to study the role of air pollution in eliciting inflammation in MI survivors in six European cities, Helsinki, Stockholm, Augsburg, Rome, Barcelona, and Athens. Outcomes of interest are plasma concentrations of the proinflammatory cytokine interleukin 6 (IL-6) and the acute-phase proteins C-reactive protein (CRP) and fibrinogen. In addition, the study was designed to assess the role of candidate gene polymorphisms hypothesized to lead to a modification of the short-term effects of ambient air pollution. In total, 1003 MI survivors were recruited and assessed with at least 2 repeated clinic visits without any signs of infections. In total, 5813 blood samples were collected, equivalent to an average of 5.8 repeated clinic visits per subject (97% of the scheduled 6 repeated visits). Subjects across the six cities varied with respect to risk factor profiles. Most of the subjects were nonsmokers, but light smokers were included in Rome, Barcelona, and Athens. Substantial inter- and intraindividual variability was observed for IL-6 and CRP. The study will permit assessing the role of cardiovascular disease risk factors, including ambient air pollution and genetic polymorphisms in candidate genes, in determining the inter- and the intraindividual variability in plasma IL-6, CRP, and fibrinogen concentrations in MI survivors.

Associations of area based deprivation status and individual educational attainment with incidence, treatment, and prognosis of first coronary event in Rome, Italy.

Background: Socioeconomic gradients in the occurrence of myocardial infarction are well known, but few studies have examined socioeconomic disparities in post-infarction outcomes. The objective of this study was to explore relations of socioeconomic status with the incidence, treatment, and outcome of first coronary event in Rome, Italy, during the period 1998–2000, examining effect modification by gender. Methods: Subjects were Rome residents aged 35–84 years who died from first acute coronary event before reaching the hospital (n = 3470) or were hospitalised for first acute myocardial infarction (n = 8467). Area based deprivation status and patients’ educational attainment were the exposure variables. The outcomes were: incidence of coronary event; recanalisation at the index hospitalisation and fatality within 28 days of hospitalisation; cardiac readmissions and fatality between 28 days and one year of index hospitalisation. Results: Incidence rates increased as area based deprivation status increased; the effect was stronger among women than among men (men RR = 1.40, 95%CI:1.30, 1.50, women RR = 1.78, 95%CI:1.60, 1.98, most compared with least deprived). Rates of recanalisation were significantly lower in the most deprived patients than in the least deprived (OR = 0.77, 95%CI:0.59, 0.99) and in the less educated than in the highly educated (OR = 0.73, 95%CI:0.58, 0.90). Associations of short term fatality with area based deprivation status and educational attainment were weak and inconsistent. However, neither deprivation status nor education was associated with one year outcomes. Conclusions: Area based deprivation status is strongly related to incidence of coronary events, and more so among women than among men. Deprivation status and educational attainment are weakly and inconsistently associated with short term fatality but seem not to influence one year prognosis of acute myocardial infarction. Deprived and less educated patients experience limited access to recanalisation procedures.

A comparison of standard methods with g-estimation of accelerated failure-time models to address the healthy-worker survivor effect: application in a cohort of autoworkers exposed to metalworking fluids.

Background: Studies of autoworkers exposed to straight metalworking fluids report excess risks of several cancers. These studies, however, have not addressed the healthy-worker survivor effect. Most methods proposed to address this bias do not consider that it may be caused by time-varying confounders affected by prior exposure. G-estimation of accelerated failure-time models was developed to handle this issue but has never been applied to account for the healthy-worker survivor effect. Methods: We compare results from Cox models and g-estimation in 38,747 autoworkers exposed to straight metalworking fluids. Exposure was defined based on job records and air samples. We examine relationships between duration of exposure and mortality from all causes, cancers, ischemic heart disease, and chronic obstructive pulmonary disease (COPD). Results: In standard models, hazard ratios were elevated for cancers of the larynx, prostate, and rectum, but below or approximately equal to 1.0 for all other outcomes considered. Adjustment for the healthy-worker survivor effect using time off work, employment status, time since hire, and restriction to inactive workers after 15 years of follow-up did not substantially change the hazard ratios. However, g-estimation yielded higher hazard ratios than standard Cox models for most outcomes. Exposure was related to increased risks of mortality from all causes combined, heart disease, COPD, and all cancers, as well as lung and prostate cancers. Conclusions: G-estimation may provide a better control for the healthy-worker survivor effect than standard methods.

Relation between three classes of structural models for the effect of a time-varying exposure on survival

Standard methods for estimating the effect of a time-varying exposure on survival may be biased in the presence of time-dependent confounders themselves affected by prior exposure. This problem can be overcome by inverse probability weighted estimation of Marginal Structural Cox Models (Cox MSM), g-estimation of Structural Nested Accelerated Failure Time Models (SNAFTM) and g-estimation of Structural Nested Cumulative Failure Time Models (SNCFTM). In this paper, we describe a data generation mechanism that approximately satisfies a Cox MSM, an SNAFTM and an SNCFTM. Besides providing a procedure for data simulation, our formal description of a data generation mechanism that satisfies all three models allows one to assess the relative advantages and disadvantages of each modeling approach. A simulation study is also presented to compare effect estimates across the three models.

Ambient air pollution and daily mortality among survivors of myocardial infarction

Background: Certain subgroups in the general population, such as persons with existing cardiovascular or respiratory disease, may be more likely to experience adverse health effects from air pollution. Methods: In this European multicenter study, 25,006 myocardial infarction (MI) survivors in 5 cities were recruited from 1992 to 2002 via registers, and daily mortality was followed for 6 to 12 years in relation to ambient particulate and gaseous air pollution exposure. Daily air pollution levels were obtained from central monitor sites, and particle number concentrations were measured in 2001 and estimated retrospectively based on measured pollutants and meteorology. City-specific effect estimates from time-series analyses with Poisson regression were pooled over all 5 cities. Results: Particle number concentrations and PM10 averaged over 2 days (lag 0–1) were associated with increased total nontrauma mortality for patients of age 35 to 74 (5.6% [95% confidence interval, 2.8%–8.5%] per 10,000/cm3 and 5.1% [1.6%–9.3%] per 10 &mgr;g/m3, respectively). For longer averaging times (5 and 15 days), carbon monoxide and nitrogen dioxide were also associated with mortality. There were no clear associations with ozone or sulfur dioxide. Conclusion: Exposure to traffic-related air pollution was associated with daily mortality in MI survivors. Point estimates suggest a stronger effect of air pollution in MI survivors than among the general population.