Pollutants in the Atherosclerotic Plaque and Cardiovascular Events

NCT05900947 | Completed

• 1 other identifier: 2704.2023
• Study Type: observational
• Target: 312
• Locations: 1 country
• Sites: 1

Brief Summary

Air pollution, microplastics and climate change pose serious public health risks. In recent years, air pollution has been associated with an increased risk of morbidity, all-cause mortality, cardio-respiratory-related mortality, and cancer. A growing body of evidence has recently confirmed a direct association between particulate matter with an aerodynamic diameter less than or equal to 2.5 mm (PM2.5), Ozone (O3) and aromatic polycyclic hydrocarbons with all-cause mortality irrespective of social context and geographic or economic disparities, suggesting a causal relationship between the two factors. The effects of air and environmental pollutants on public health have been observed also for short-term exposure to rapid increases in particulate matter. High PM 2.5 values have also been associated with a higher rate of atherosclerosis and coronary artery disease expressed by high calcium score values, with the elderly, male and diabetic patients being at greater risk. To date, however, the pathophysiological basis of the relationship between air pollutants, and long-term events remains speculative, and there is no evidence that can correlate the concentration of environmental pollutants directly with anatomical-pathological and/or biomolecular alterations. In this study the investigators will assess the presence and the burden of pollutants within the carotid plaques from patients undergoing carotid endarterectomy with pyrolysis-gas chromatography-mass spectrometry and electronic microscopy. Plaque stability will be explored trough molecular markers. Participants will be followed up for a composite of myocardial infarction, stroke, and all-cause mortality to evaluate whether the presence and the abundance of pollutants are associated with the development of the outcome through adjusted Cox regressions.

Conditions

Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Incidence of a composite of myocardial infarction, stroke, and all-cause mortality in patients with polluted vs non-polluted plaques

  Patients will be categorized (post-hoc) as having polluted plaques (having detectable levels of at least one microplastics) or non-polluted plaques. Cox regression analysis will be used to examine the association between the presence of pollutants (yes/no) and the incidence of the composite outcome, adjusted for age, sex, BMI, systolic and diastolic blood pressure, the prevalence of diabetes, dyslipidaemia, and smoking.

  24 months

Secondary Outcomes (1)

• Incidence of a composite of myocardial infarction, stroke, and all-cause mortality according to terciles of pollutants burden

  24 months

Other Outcomes (2)

• Comparison of plaque stability markers between polluted and non-polluted plaques

  12 months

• Comparison of inflammatory markers between polluted and non-polluted plaques

  12 months

Interventions

analysis of carotid atherosclerotic plaque OTHER

To assess the presence of air pollutants (benzene, toluene, xylene, and ethylbenzene) or of microplastics within tissues from atherosclerotic plaques by Chromatographic analyses.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include the patients with carotid stenosis (according to North American Symptomatic Carotid Endarterectomy Trial classification) enlisted to undergo carotid endarterectomy for extracranial high-grade (\>70%) internal carotid artery stenosis. The patients will be male and female subjects, with age \> 18 and \< 75 years. We will select patients with asymptomatic carotid disease. All patients will have a baseline clinical examination, and receive computed tomography or MRI to assess cerebral lesions, and previous health records will be evaluated. Clinical variables will be measured with standard procedures after overnight fasting. Patients with diabetes will be categorized according to the ADA criteria.

You may qualify if:

• patients with carotid stenosis (according to North American Symptomatic Carotid Endarterectomy Trial classification) enlisted to undergo carotid endarterectomy for extracranial high-grade (\>70%) internal carotid artery stenosis.

You may not qualify if:

• All patients with clinical or laboratory evidence of heart failure, valvular defects, malignant neoplasms, or secondary causes of hypertension will be excluded from the study.

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead
• Cardarelli Hospital: collaborator
• IRCCS Multimedica: collaborator

Study Sites (1)

Celestino Sardu

Naples, 80138, Italy

Location

Related Publications (5)

• Perera F, Nadeau K. Climate Change, Fossil-Fuel Pollution, and Children's Health. N Engl J Med. 2022 Jun 16;386(24):2303-2314. doi: 10.1056/NEJMra2117706. No abstract available.

  PMID: 35704482 BACKGROUND

• Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H, Amann M, Anderson HR, Andrews KG, Aryee M, Atkinson C, Bacchus LJ, Bahalim AN, Balakrishnan K, Balmes J, Barker-Collo S, Baxter A, Bell ML, Blore JD, Blyth F, Bonner C, Borges G, Bourne R, Boussinesq M, Brauer M, Brooks P, Bruce NG, Brunekreef B, Bryan-Hancock C, Bucello C, Buchbinder R, Bull F, Burnett RT, Byers TE, Calabria B, Carapetis J, Carnahan E, Chafe Z, Charlson F, Chen H, Chen JS, Cheng AT, Child JC, Cohen A, Colson KE, Cowie BC, Darby S, Darling S, Davis A, Degenhardt L, Dentener F, Des Jarlais DC, Devries K, Dherani M, Ding EL, Dorsey ER, Driscoll T, Edmond K, Ali SE, Engell RE, Erwin PJ, Fahimi S, Falder G, Farzadfar F, Ferrari A, Finucane MM, Flaxman S, Fowkes FG, Freedman G, Freeman MK, Gakidou E, Ghosh S, Giovannucci E, Gmel G, Graham K, Grainger R, Grant B, Gunnell D, Gutierrez HR, Hall W, Hoek HW, Hogan A, Hosgood HD 3rd, Hoy D, Hu H, Hubbell BJ, Hutchings SJ, Ibeanusi SE, Jacklyn GL, Jasrasaria R, Jonas JB, Kan H, Kanis JA, Kassebaum N, Kawakami N, Khang YH, Khatibzadeh S, Khoo JP, Kok C, Laden F, Lalloo R, Lan Q, Lathlean T, Leasher JL, Leigh J, Li Y, Lin JK, Lipshultz SE, London S, Lozano R, Lu Y, Mak J, Malekzadeh R, Mallinger L, Marcenes W, March L, Marks R, Martin R, McGale P, McGrath J, Mehta S, Mensah GA, Merriman TR, Micha R, Michaud C, Mishra V, Mohd Hanafiah K, Mokdad AA, Morawska L, Mozaffarian D, Murphy T, Naghavi M, Neal B, Nelson PK, Nolla JM, Norman R, Olives C, Omer SB, Orchard J, Osborne R, Ostro B, Page A, Pandey KD, Parry CD, Passmore E, Patra J, Pearce N, Pelizzari PM, Petzold M, Phillips MR, Pope D, Pope CA 3rd, Powles J, Rao M, Razavi H, Rehfuess EA, Rehm JT, Ritz B, Rivara FP, Roberts T, Robinson C, Rodriguez-Portales JA, Romieu I, Room R, Rosenfeld LC, Roy A, Rushton L, Salomon JA, Sampson U, Sanchez-Riera L, Sanman E, Sapkota A, Seedat S, Shi P, Shield K, Shivakoti R, Singh GM, Sleet DA, Smith E, Smith KR, Stapelberg NJ, Steenland K, Stockl H, Stovner LJ, Straif K, Straney L, Thurston GD, Tran JH, Van Dingenen R, van Donkelaar A, Veerman JL, Vijayakumar L, Weintraub R, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams W, Wilson N, Woolf AD, Yip P, Zielinski JM, Lopez AD, Murray CJ, Ezzati M, AlMazroa MA, Memish ZA. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2224-60. doi: 10.1016/S0140-6736(12)61766-8.

  PMID: 23245609 BACKGROUND

• Di Q, Wang Y, Zanobetti A, Wang Y, Koutrakis P, Choirat C, Dominici F, Schwartz JD. Air Pollution and Mortality in the Medicare Population. N Engl J Med. 2017 Jun 29;376(26):2513-2522. doi: 10.1056/NEJMoa1702747.

  PMID: 28657878 BACKGROUND

• Bevan GH, Al-Kindi SG, Brook RD, Munzel T, Rajagopalan S. Ambient Air Pollution and Atherosclerosis: Insights Into Dose, Time, and Mechanisms. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):628-637. doi: 10.1161/ATVBAHA.120.315219. Epub 2020 Dec 17.

  PMID: 33327745 BACKGROUND

• Marfella R, Prattichizzo F, Sardu C, Fulgenzi G, Graciotti L, Spadoni T, D'Onofrio N, Scisciola L, La Grotta R, Frige C, Pellegrini V, Municino M, Siniscalchi M, Spinetti F, Vigliotti G, Vecchione C, Carrizzo A, Accarino G, Squillante A, Spaziano G, Mirra D, Esposito R, Altieri S, Falco G, Fenti A, Galoppo S, Canzano S, Sasso FC, Matacchione G, Olivieri F, Ferraraccio F, Panarese I, Paolisso P, Barbato E, Lubritto C, Balestrieri ML, Mauro C, Caballero AE, Rajagopalan S, Ceriello A, D'Agostino B, Iovino P, Paolisso G. Microplastics and Nanoplastics in Atheromas and Cardiovascular Events. N Engl J Med. 2024 Mar 7;390(10):900-910. doi: 10.1056/NEJMoa2309822.

  PMID: 38446676 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Carotid plaques

MeSH Terms

Conditions

Atherosclerosis

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Raffaele Marfella, MD,PhD

  Università della Campania Vanvitelli

  PRINCIPAL INVESTIGATOR

• Celestino Sardu, MD

  Università degli Studi della Campania

  STUDY CHAIR

• Francesco Prattichizzo, PhD

  IRCCS Multimedica

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: full professor

Study Record Dates

• First Submitted: April 28, 2023
• First Posted: June 13, 2023
• Study Start: September 1, 2019
• Primary Completion: July 30, 2023
• Study Completion: August 1, 2023
• Last Updated: October 12, 2023

Record last verified: 2023-10

Locations

IT (1)