Malattie cardiovascolari e inquinamento atmosferico

Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities
Circulation 2005;112:3073-3079 - Abstract
Air pollution and hospital admissions for ischemic and hemorrhagic stroke among medicare beneficiaries
Stroke 2005;36:2549-2553 - Abstract
Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model
Jama 2005;294:3003-3010 - Abstract

Commento:
Sono sempre più numerosi gli studi internazionali che evidenziano come la qualità dell'aria che respiriamo sia strettamente correlata ad un aumento del tasso di morbidità e di mortalità acute, soprattutto in sottogruppi di popolazione a rischio. Pazienti con broncopneumopatia cronica ostruttiva (BPCO), o insufficienza cardiaca congestizia, precedente infarto del miocardio o diabete, mostrano un rischio di morte più alto nei giorni con tassi elevati di agenti inquinanti dell'aria (PNC, PM₁₀, CO, NO₂ e O₃). Nello specifico poi i soggetti post-infartuati presentano un rischio maggiore di incorrere in eventi ischemici ricorrenti ed insufficienza cardiaca.

Lo studio di coorte multicentrico europeo HEAPSS (The Health Effects of Particles on Susceptible Subpopulation) ha stimato quanto la concentrazione di particelle inquinanti abbia influenzato il numero di nuovi ricoveri per cause cardiache, in soggetti post-infartuati (n=22.006).

I dati suggeriscono un'associazione tra inquinanti atmosferici (NO₂, CO, PNC) ed aumento del rischio di ri-ospedalizzazione per cause cardiache.

Sebbene i meccanismi biologici non siano stati ancora chiariti, alcune evidenze suggeriscono che alterazioni a carico di fattori emodinamici ed emostatici possono spiegare gli effetti cardiovascolari delle particelle inquinanti atmosferiche.
Uno studio multicentrico americano ha considerato in modo più specifico la possibile correlazione tra ictus (ischemico ed emorragico) ed inquinanti dell'aria:

Lo studio che ha coinvolto 9 città americane sparse su tutto il territorio ha evidenziato un maggior rischio di ricovero ospedaliero per ictus ischemico (ma non emorragico) associato ad un aumento delle concentrazione di PM₁₀ nell'aria.

Più precisamente il giorno del ricovero per ictus ischemico corrispondeva alla rilevazione dei livelli più alti di PM₁₀ (P_{heterogeneity}=0.71); mentre nel caso di ictus emorragico non emergeva questa correlazione (P_{heterogeneity}=0.013)

Infine uno studio condotto su un modello animale (due gruppi di topi Apolipoproteina E^-/-, a regime dietetico normale o ricco di grassi) ha evidenziato come l'esposizione cronica a basse concentrazioni di PM_2.5 altera il tono vasomotorio, induce infiammazione vascolare e favorisce il processo aterosclerotico.

Gli animali sono stati esposti per un totale di 6 mesi ad un'aria con livelli di PM2.5= 15.2 µg/mPM³, molto vicini a quelli di standard di qualità dell'aria nazionale stimati annualmente. Dai dati emerge come l'esposizione a PM_2.5 favorisca o peggiori uno stato aterosclerotico pre-esistente, in entrambe i gruppi di animali indipendentemente dal regime dietetico, anche se l'effetto maggiore si osserva tra gli animali trattati con una dieta ricca di lipidi.

In conclusione le evidenze epidemiologiche e sperimentali portano a pensare che l'inquinamento ambientale possa modificare significativamente il rischio cardiovascolare di soggetti esposti agli agenti inquinanti, specialmente al particolato, e pongono le basi per svolgere degli studi di associazione e prevenzione a livello di popolazione italiana.


Alberico L. Catapano e Alessandra Bertelli, Dipartimento di Scienze Farmacologiche, Università degli Studi di Milano

Abstract:

Ambient air pollution is associated with increased risk of hospital cardiac readmissions of myocardial infarction survivors in five European cities
von Klot S, Peters A, Aalto P, Bellander T, Berglind N, D'Ippoliti D, Elosua R, Hormann A, Kulmala M, Lanki T, Lowel H, Pekkanen J, Picciotto S, Sunyer J, Forastiere F
Circulation 2005;112:3073-9.
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 microm (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 microg/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 microg/m3 [0.172 ppm]), nitrogen dioxide (RR 1.032 [95% CI 1.013 to 1.051] per 8 microg/m3 [4.16 ppb]), and ozone (RR 1.026 [95% CI 1.001 to 1.051] per 15 microg/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.

Air pollution and hospital admissions for ischemic and hemorrhagic stroke among medicare beneficiaries
Wellenius GA, Schwartz J, Mittleman MA
Stroke 2005;36:2549-53
BACKGROUND AND PURPOSE: The association between short-term elevations in ambient air particles and increased cardiovascular morbidity and mortality is well documented. Ambient particles may similarly increase the risk of stroke. METHODS: We evaluated the association between daily levels of respirable particulate matter (aerodynamic diameter < or =10 microm, PM10) and hospital admission for ischemic and hemorrhagic stroke among Medicare recipients (age > or =65 years) in 9 US cities using a 2-stage hierarchical model. In the first stage, we applied the time-stratified case-crossover design to estimate the effect of PM10 in each city. We used a 3-day unconstrained, distributed lag model to simultaneously estimate the effect of PM10 0 to 2 days before the admission day and controlled for meteorological covariates in all of the models. In the second stage, we used random-effects metaanalytic techniques to combine the city-specific effect estimates. RESULTS: Ischemic (n=155,503) and hemorrhagic (19,314) stroke admissions were examined separately. For ischemic stroke, an interquartile range increase in PM10 was associated with a 1.03% (95% CI, 0.04% to 2.04%) increase in admissions on the same day only. Similar results were observed with CO, NO2, and SO2. For hemorrhagic stroke, no association was observed with any pollutant 0 to 2 days before admission. CONCLUSIONS: These results suggest that elevations in ambient particles may transiently increase the risk of ischemic, but not hemorrhagic, stroke. Studies with more accurate assessment of timing of stroke onset are necessary to confirm or refute these findings.

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model
Sun Q, Wang A, Jin X, Natanzon A, Duquaine D, Brook RD, Aguinaldo JG, Fayad ZA, Fuster V, Lippmann M, Chen LC, Rajagopalan S.
JAMA 2005;294:3003-10
CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<0.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = 0.15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P =0 .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = 0.03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = 0.04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<0.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.