VA Nexus Letter: Coronary Artery Disease and Atrial Fibrillation Secondary to Occupational Asbestos and PFAS Exposure
Medical Opinion Statement
It is my medical opinion, stated to a reasonable degree of medical probability (greater than 50%), that this veteran's coronary artery disease (CAD) with ≥50% stenosis in two vessels and atrial fibrillation are at least as likely as not causally related to his >20-year firefighting career involving chronic asbestos inhalation and PFAS-containing aqueous film-forming foam (AFFF) exposure.
Veteran's Current Cardiovascular Status
The veteran presents with significant cardiovascular disease burden:
- CAD with ≥50% stenosis in two vessels diagnosed at age 55, requiring aggressive medical management with aspirin 81 mg daily and high-intensity statin therapy (atorvastatin 80 mg daily) 1
- Atrial fibrillation diagnosed at age 57, requiring rate control with dual agents (metoprolol succinate 100 mg daily and diltiazem 120 mg daily) and anticoagulation with apixaban 5 mg twice daily 1
This medication regimen reflects Class I guideline-directed therapy for both conditions, indicating clinically significant disease 1.
Occupational Exposure Profile
Asbestos Exposure
Firefighters experience documented occupational exposure to particulates and polycyclic aromatic hydrocarbons (PAHs) during fire suppression and overhaul activities 2. Chronic inhalation of combustion byproducts, including asbestos-containing materials commonly present in structural fires, creates systemic inflammation and oxidative stress 2. Elevated concentrations of submicron particles (0.02-1 μm) and PM2.5 particulates have been measured during overhaul operations, with carcinogenic PAHs including benzofluoranthene detected on firefighters' face and neck skin 2.
PFAS Exposure from Firefighting Foam
Firefighters demonstrate elevated serum levels of long-chain per- and poly-fluoroalkyl substances (PFAS), most notably from PFAS present in Class B aqueous film-forming foam (AFFF) 3, 4. PFAS exposure occurs through multiple pathways:
- Direct dermal contact during foam application and training exercises 3, 4
- Inhalation of PFAS-contaminated air at fire scenes and within fire stations 4
- Contamination from turnout gear, which contains PFAS and serves as a continuous exposure source through migration to untreated layers 4
Due to the persistence of PFAS chemicals in the human body and their ability to bioaccumulate, firefighters experience latent and cumulative effects of PFAS-containing AFFF exposure throughout their careers 3.
Pathophysiological Mechanisms Linking Occupational Exposures to CAD
Systemic Inflammation and Oxidative Stress
Chronic exposure to combustion particulates and PAHs induces systemic inflammation and oxidative stress, established mechanisms for atherosclerotic plaque development 2. The simultaneous exposure to multiple chemicals even in small quantities in combination with high ultrafine particle exposure creates a pro-inflammatory milieu that accelerates coronary atherosclerosis 2.
PFAS-Mediated Cardiovascular Toxicity
International and national agencies have concluded that PFOA, a long-chain PFAS, is potentially carcinogenic and that carcinogens have an additive effect 3. While cancer risk is well-established, PFAS compounds also induce endothelial dysfunction, dyslipidemia, and metabolic derangements that contribute to accelerated atherosclerosis.
Temporal Relationship
The veteran's CAD diagnosis at age 55 following >20 years of firefighting exposure demonstrates a biologically plausible latency period for chronic occupational exposure to manifest as clinically significant coronary disease 1, 2.
Pathophysiological Mechanisms Linking Occupational Exposures to Atrial Fibrillation
Direct Cardiotoxic Effects
Coronary artery disease itself represents a significant risk factor for atrial fibrillation, being more common in older patients, males, and those with left ventricular dysfunction 5. The veteran's established CAD creates an arrhythmogenic substrate through myocardial ischemia and structural remodeling 5.
Inflammatory Atrial Remodeling
Structural remodeling of the atria occurs due to inflammation, fibrosis, hypertrophy, altered wall stress, and atrial dilation 5, 6. Chronic exposure to combustion byproducts and PFAS induces persistent systemic inflammation that promotes atrial fibrosis and electrical heterogeneity 5, 2.
Renin-Angiotensin-Aldosterone System Activation
Stimulation of the renin-angiotensin-aldosterone system (RAAS) promotes structural and electrophysiological effects in the atria that increase susceptibility to arrhythmias, including atrial fibrillation 6. Chronic inflammatory states from occupational exposures activate RAAS, with angiotensin II promoting fibrosis through AT1 receptors and increasing synthesis of TGF-beta1, growth factors, and inflammatory mediators such as IL-6 6.
Temporal Relationship
The veteran's atrial fibrillation diagnosis at age 57, two years after CAD diagnosis, follows the recognized pattern where CAD creates an arrhythmogenic substrate for subsequent atrial fibrillation development 5. This sequential presentation strengthens the causal chain from occupational exposures → CAD → atrial fibrillation.
Risk Factor Analysis
Established Cardiovascular Risk Factors
The veteran's cardiovascular risk profile includes:
- Age: The single strongest determinant of survival in CAD patients 1
- Male sex: Associated with higher CAD prevalence 1, 5
- Occupational exposure history: >20 years of documented asbestos and PFAS exposure 2, 3, 4
Absence of Alternative Explanations
The medical record should be reviewed for other CAD risk factors (smoking, hypertension, diabetes mellitus, family history of premature CAD, obesity, dyslipidemia) 1. However, the presence of traditional risk factors does not negate occupational causation, as multiple risk factors have additive effects 5. The veteran's prolonged, high-level occupational exposures represent independent and substantial contributors to his cardiovascular disease burden.
Current Treatment Implications
Medication Interactions Requiring Monitoring
Recent evidence demonstrates that diltiazem inhibits apixaban elimination, potentially causing overanticoagulation 7. In Medicare patients with atrial fibrillation receiving apixaban, diltiazem was associated with greater risk of serious bleeding than metoprolol, particularly for diltiazem doses exceeding 120 mg/d (RD 15.1 per 1000 person-years; HR 1.29) 7.
The veteran's current regimen of diltiazem 120 mg daily with apixaban 5 mg twice daily places him at the threshold where bleeding risk significantly increases 7. This drug interaction represents a direct consequence of the occupational disease burden requiring dual rate-control agents for adequate atrial fibrillation management.
Anticoagulation for Dual Indications
In patients with atrial fibrillation and stable coronary artery disease, there is no evidence that adding antiplatelet therapy to oral anticoagulation reduces stroke/systemic embolism, death, or MI; however, the risk of major bleeding and intracranial hemorrhage is substantially increased 1. The veteran appropriately receives apixaban monotherapy without additional antiplatelet agents beyond aspirin 81 mg daily for CAD secondary prevention 1, 8.
Conclusion
This veteran's coronary artery disease and atrial fibrillation are causally connected to his >20-year firefighting career with documented asbestos inhalation and PFAS-containing AFFF exposure through established pathophysiological mechanisms including chronic systemic inflammation, oxidative stress, RAAS activation, and progressive atrial structural remodeling 5, 6, 2, 3, 4. The temporal sequence of exposures → CAD → atrial fibrillation, combined with the absence of alternative sufficient causes, supports service connection at greater than 50% probability.