Annette Peters

Particulate Matter Air Pollution and Cardiovascular Disease An Update to the Scientific Statement From the American Heart Association

In 2004, the first American Heart Association scientific statement on “Air Pollution and Cardiovascular Disease” concluded that exposure to particulate matter (PM) air pollution contributes to cardiovascular morbidity and mortality. In the interim, numerous studies have expanded our understanding of this association and further elucidated the physiological and molecular mechanisms involved. The main objective of this updated American Heart Association scientific statement is to provide a comprehensive review of the new evidence linking PM exposure with cardiovascular disease, with a specific focus on highlighting the clinical implications for researchers and healthcare providers. The writing group also sought to provide expert consensus opinions on many aspects of the current state of science and updated suggestions for areas of future research. On the basis of the findings of this review, several new conclusions were reached, including the following: Exposure to PM <2.5 &mgr;m in diameter (PM2.5) over a few hours to weeks can trigger cardiovascular disease–related mortality and nonfatal events; longer-term exposure (eg, a few years) increases the risk for cardiovascular mortality to an even greater extent than exposures over a few days and reduces life expectancy within more highly exposed segments of the population by several months to a few years; reductions in PM levels are associated with decreases in cardiovascular mortality within a time frame as short as a few years; and many credible pathological mechanisms have been elucidated that lend biological plausibility to these findings. It is the opinion of the writing group that the overall evidence is consistent with a causal relationship between PM2.5 exposure and cardiovascular morbidity and mortality. This body of evidence has grown and been strengthened substantially since the first American Heart Association scientific statement was published. Finally, PM2.5 exposure is deemed a modifiable factor that contributes to cardiovascular morbidity and mortality.

A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease.

To identify rare causal variants in late-onset Parkinson disease (PD), we investigated an Austrian family with 16 affected individuals by exome sequencing. We found a missense mutation, c.1858G>A (p.Asp620Asn), in the VPS35 gene in all seven affected family members who are alive. By screening additional PD cases, we saw the same variant cosegregating with the disease in an autosomal-dominant mode with high but incomplete penetrance in two further families with five and ten affected members, respectively. The mean age of onset in the affected individuals was 53 years. Genotyping showed that the shared haplotype extends across 65 kilobases around VPS35. Screening the entire VPS35 coding sequence in an additional 860 cases and 1014 controls revealed six further nonsynonymous missense variants. Three were only present in cases, two were only present in controls, and one was present in cases and controls. The familial mutation p.Asp620Asn and a further variant, c.1570C>T (p.Arg524Trp), detected in a sporadic PD case were predicted to be damaging by sequence-based and molecular-dynamics analyses. VPS35 is a component of the retromer complex and mediates retrograde transport between endosomes and the trans-Golgi network, and it has recently been found to be involved in Alzheimer disease.

New susceptibility locus for coronary artery disease on chromosome 3q22.3

We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in ∼25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 × 10−13; OR = 1.15, 95% CI = 1.11–1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 × 10−7; OR = 1.08, 95% CI = 1.05–1.11).

Translocation and potential neurological effects of fine and ultrafine particles a critical update

Particulate air pollution has been associated with respiratory and cardiovascular disease. Evidence for cardiovascular and neurodegenerative effects of ambient particles was reviewed as part of a workshop. The purpose of this critical update is to summarize the evidence presented for the mechanisms involved in the translocation of particles from the lung to other organs and to highlight the potential of particles to cause neurodegenerative effects.Fine and ultrafine particles, after deposition on the surfactant film at the air-liquid interface, are displaced by surface forces exerted on them by surfactant film and may then interact with primary target cells upon this displacement. Ultrafine and fine particles can then penetrate through the different tissue compartments of the lungs and eventually reach the capillaries and circulating cells or constituents, e.g. erythrocytes. These particles are then translocated by the circulation to other organs including the liver, the spleen, the kidneys, the heart and the brain, where they may be deposited. It remains to be shown by which mechanisms ultrafine particles penetrate through pulmonary tissue and enter capillaries. In addition to translocation of ultrafine particles through the tissue, fine and coarse particles may be phagocytized by macrophages and dendritic cells which may carry the particles to lymph nodes in the lung or to those closely associated with the lungs. There is the potential for neurodegenerative consequence of particle entry to the brain. Histological evidence of neurodegeneration has been reported in both canine and human brains exposed to high ambient PM levels, suggesting the potential for neurotoxic consequences of PM-CNS entry. PM mediated damage may be caused by the oxidative stress pathway. Thus, oxidative stress due to nutrition, age, genetics among others may increase the susceptibility for neurodegenerative diseases. The relationship between PM exposure and CNS degeneration can also be detected under controlled experimental conditions. Transgenic mice (Apo E -/-), known to have high base line levels of oxidative stress, were exposed by inhalation to well characterized, concentrated ambient air pollution. Morphometric analysis of the CNS indicated unequivocally that the brain is a critical target for PM exposure and implicated oxidative stress as a predisposing factor that links PM exposure and susceptibility to neurodegeneration.Together, these data present evidence for potential translocation of ambient particles on organs distant from the lung and the neurodegenerative consequences of exposure to air pollutants.

Particulate Air Pollution and Risk of ST-Segment Depression During Repeated Submaximal Exercise Tests Among Subjects With Coronary Heart Disease The Exposure and Risk Assessment for Fine and Ultrafine Particles in Ambient Air (ULTRA) Study

Background—Daily variations in ambient particulate air pollution have been associated with cardiovascular mortality and morbidity. We therefore assessed the associations between levels of the 3 main modes of urban aerosol distribution and the occurrence of ST-segment depressions during repeated exercise tests. Methods and Results—Repeated biweekly submaximal exercise tests were performed during 6 months among adult subjects with stable coronary heart disease in Helsinki, Finland. Seventy-two exercise-induced ST-segment depressions >0.1 mV occurred during 342 exercise tests among 45 subjects. Simultaneously, particle mass <2.5 &mgr;m (PM2.5) and the number concentrations of ultrafine particles (particle diameter 10 to 100 nm [NC0.01–0.1]) and accumulation mode particles (100 to 1000 nm [NC0.1–1]) were monitored at a central site. Levels of particulate air pollution 2 days before the clinic visit were significantly associated with increased risk of ST-segment depression during exercise test. The association was most consistent for measures of particles reflecting accumulation mode particles (odds ratio 3.29; 95% CI, 1.57 to 6.92 for NC0.1–1 and 2.84; 95% CI, 1.42 to 5.66 for PM2.5), but ultrafine particles also had an effect (odds ratio 3.14; 95% CI, 1.56 to 6.32), which was independent of PM2.5. Also, gaseous pollutants NO2 and CO were associated with an increased risk for ST-segment depressions. No consistent association was observed for coarse particles. The associations tended to be stronger among subjects who did not use &bgr;-blockers. Conclusions—The present results suggest that the effect of particulate air pollution on cardiovascular morbidity is at least partly mediated through increased susceptibility to myocardial ischemia.

Novel biomarkers for pre-diabetes identified by metabolomics

Type 2 diabetes (T2D) can be prevented in pre‐diabetic individuals with impaired glucose tolerance (IGT). Here, we have used a metabolomics approach to identify candidate biomarkers of pre‐diabetes. We quantified 140 metabolites for 4297 fasting serum samples in the population‐based Cooperative Health Research in the Region of Augsburg (KORA) cohort. Our study revealed significant metabolic variation in pre‐diabetic individuals that are distinct from known diabetes risk indicators, such as glycosylated hemoglobin levels, fasting glucose and insulin. We identified three metabolites (glycine, lysophosphatidylcholine (LPC) (18:2) and acetylcarnitine) that had significantly altered levels in IGT individuals as compared to those with normal glucose tolerance, with P‐values ranging from 2.4 × 10−4 to 2.1 × 10−13. Lower levels of glycine and LPC were found to be predictors not only for IGT but also for T2D, and were independently confirmed in the European Prospective Investigation into Cancer and Nutrition (EPIC)‐Potsdam cohort. Using metabolite–protein network analysis, we identified seven T2D‐related genes that are associated with these three IGT‐specific metabolites by multiple interactions with four enzymes. The expression levels of these enzymes correlate with changes in the metabolite concentrations linked to diabetes. Our results may help developing novel strategies to prevent T2D.

Health effects of particulate air pollution: A review of epidemiological evidence

Health effects of air pollution Everyone is exposed to ambient air pollution every day, some to a more and some to a lesser extent. When the first scientist examined the effect of air pollution on health after the Meuse Valley fog in 1930 (Firket, 1936) or the London smog in 1952 (Ministry of health, 1954), no one could have known what an extended field of research they started. Today, a lot of research is done on various aspects of air pollution. As shown in Figure 1, human health can be affected in all stages of life—from conception to old age. This review seeks to give an overview on the variety of health risks air pollution poses with a focus on epidemiological studies. Due to the vastness of the field, this review cannot go into too much detail in each section. However, it will give the reader a comprehensive impression on the large number of health effects of air pollution. Where available, the authors refer to existing reviews that might offer more depth in a certain field for the interested reader. The first six sections deal with different health outcomes in respect to ambient air pollution. Section 7 explains potential mechanisms that may lead from the inhalation of particles to adverse health outcomes. The last section finally gives an overview on research gaps that exist in the field and possible directions that research might take.

Epidemiological Evidence on Health Effects of Ultrafine Particles

Evidence from epidemiologic studies linking ambient concentrations of particulate matter to morbidity and mortality influenced the guidelines for air quality standards worldwide. With the improvement of measurement techniques, clearer effects were observed with smaller particle sizes. Based on these effects and results from animal studies on the potential toxicity of ultrafine particles, recent epidemiologic studies focus on the health effects of particles which are less than 100nm in diameter. However, most of the studies are ongoing and only few results have been available so far. Six panel studies with patients suffering from chronic pulmonary diseases have been performed in Germany, Finland and the United Kingdom. Overall, a decrease of peak expiratory flow (PEF) and an increase of daily symptoms and medication use was found for elevated daily particle concentrations. Effects were seen with both fine and ultrafine particles. One large study on daily mortality from Germany showed comparable effects of fine and ultrafine particles in all size classes considered. However, fine particles showed more immediate effects while ultrafine particles showed more delayed effects on mortality. The limited number of epidemiological studies suggest that there are health effects of fine and ultrafine particles which might be independent of each other. If these effects are confirmed by ongoing research, monitoring and regulation of particulate air pollution may need to be revised.

Association of Early Repolarization Pattern on ECG with Risk of Cardiac and All-Cause Mortality: A Population-Based Prospective Cohort Study (MONICA/KORA)

In a population-based cohort study of middle-aged people in Central Europe, Stefan Kääb and colleagues find an association between electrocardiographic early repolarization pattern and mortality risk.

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.