Author + information
- S0735109716006045-470729725bd5f6f73e68aa6095baf719Sarah O’Connor, MD,
- S0735109716006045-3b104f5f3df6054d5960b8ac31d75eccHeather L. Gornik, MD, MHS,
- S0735109716006045-512364fda545e1e3ab5a4b00dd72e09fJames B. Froehlich, MD, MPH,
- S0735109716006045-8ec5f5d98349407ed59f4a9fa28bba18Xiaokui Gu, MA,
- S0735109716006045-06e0f31e36e0057bb0fb000820829fa5Bruce H. Gray, DO,
- S0735109716006045-3f9d0cda135512f4558d38bd6787d2fdPamela D. Mace, RN,
- S0735109716006045-537ccd7fbb0dc3cf0b5926ea9bfbe1c9Aditya Sharma, MD,
- S0735109716006045-d16d6dfacb1dc41d127babb70e4d4ec4Jeffrey W. Olin, DO and
- S0735109716006045-a17ab2d36a93c6796f4ac61b71043283Esther S.H. Kim, MD, MPH∗ ()
- ↵∗Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-5, Cleveland, Ohio 44195
The pathophysiology of fibromuscular dysplasia (FMD) is unknown; however, smoking has been implicated as a potential contributing factor (1,2). Prior studies have shown a higher prevalence of smoking among those with renal FMD compared with matched hypertensive control subjects (3). The association between smoking and cerebrovascular FMD and the impact of smoking on the development of major vascular complications is undefined. We investigated the association of smoking with symptoms and clinical outcomes among patients with FMD.
Demographics, medical history, presenting signs and symptoms, procedures, and vascular events were queried from the United States Registry for Fibromuscular Dysplasia and stratified according to smoking status. Registry methodology has been detailed previously (4). Major vascular events were defined as subarachnoid hemorrhage, transient ischemic attack, stroke, mesenteric ischemia, renal infarction, myocardial infarction, or coronary revascularization.
Differences in presenting features and clinical outcomes by smoking status were examined using Student t tests and Fisher exact tests, and summary statistics are presented as mean ± SD and percentages. Because no significant differences among clinical outcomes stratified by current versus former smoking existed, the groups were combined. The effect of smoking on major vascular events was further explored with logistic regression analysis controlling for patient characteristics. All statistics were analyzed by the coordinating center statistician (X.G.) using SAS (SAS Institute Inc., Cary, North Carolina).
At the time of data query, 949 of 1,003 patients (94.6%) had smoking status recorded and were included; 91.6% were women, and the mean age at diagnosis was 52.8 ± 13.4 years. The renal and extracranial carotid arteries were the most commonly involved, in 69.9% and 72.1%, respectively. As described previously (4), vascular imaging was performed on the basis of symptoms or at the discretion of the site investigator. More than 60% of patients (574 of 949) had intracranial imaging and >90% had ≥2 vascular beds imaged. Smoking histories were reported in 327 patients (34.5%), and of those, 113 (11.9%) were current smokers. Clinical manifestations by smoking are shown in Table 1. Smokers were older at diagnosis, 54.1 years versus 52.1 years (p = 0.025), but there was no significant difference in age at symptom onset, 49.2 versus 48.1 years (p = 0.25), or arterial involvement. Aneurysms were present in 21% of patients, with a higher prevalence in smokers (24.8% vs. 18.9%, p = 0.047). Aortic aneurysms (4.8% vs. 1.5%, p < 0.01) and intracerebral aneurysms (4.8% vs. 1.7%, p < 0.01) were more common in smokers. Smokers experienced more symptoms of claudication (p < 0.001) and underwent more therapeutic vascular procedures (p = 0.006). No difference in dissections was observed, although there was a trend toward increased composite major vascular events among smokers.
Smoking has a significant impact on patients with FMD. Diagnosis of FMD may have been delayed in patients who had ever smoked, because symptoms could have been attributed to smoking-related disease. Smokers with FMD had significantly higher rates of claudication, aneurysm, and need for therapeutic intervention. Of note, therapeutic interventions for non-FMD indications were excluded from analysis, and the arteries on which therapeutic interventions were performed were consistent with the arterial beds with FMD involvement. Thus, atherosclerosis is not the driver of therapeutic interventions in smokers with FMD. Smokers also tended to have an increase in the prevalence of major vascular events (42.8% vs 36.8%, p = 0.077). A multivariate logistic regression adjusting for age at diagnosis, sex, and other characteristics also did not show statistical significance (odds ratio: 1.16; 95% confidence interval: 0.86 to 1.57; p = 0.34). Lack of statistical significance could reflect the lack of power to detect this association in a cohort of 949 patients with FMD.
The high prevalence of aneurysms is concerning. Although it is well known that smoking is associated with aneurysms, smoking also appears to increase the risk for aneurysms in patients with FMD, a population in which the risk for aneurysmal disease is already significant (4). Screening for intracranial aneurysms in all patients with FMD is recommended (5); however, the method of screening for aneurysm in other vascular beds is yet undefined. The recently published scientific statement on FMD (5) lists the creation of a vascular screening approach for patients with FMD as a top research priority. The present study emphasizes the importance of screening, particularly for aneurysm, and particularly in patients with histories of smoking.
Please note: This work was supported by the Fibromuscular Dysplasia Study of America, a nonprofit organization. Dr. Gornik is an unpaid member of the medical advisory board of the FMD Society of America, a nonprofit organization. Dr. Froehlich is a consultant for Pfizer, Janssen Pharmaceuticals, Merck, Boehringer-Ingelheim, and Novartis. Dr. Gray has consultant agreements without financial benefit with Abbott Vascular and Trivascular; and research agreements without financial benefit with SilkRoad, Medtronic, Abbott, and Gore. Ms. Mace is an employee of the FMD Society of America. Dr. Olin is an unpaid member of the medical advisory board of the FMD Society of America. Dr. Kim is a consultant for Philips Ultrasound. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Robert Rordorf, MD, served as Guest Editor for this paper.
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