Etiologic factors in renovascular fibromuscular dysplasia. A case-control study.

Abstract

The role of several factors that have been suggested as being of etiologic importance in renovascular fibromuscular dysplasia was examined in a case-control study of 33 patients with angiographically demonstrated fibromuscular dysplasia and 61 renal transplant donor control subjects with normal renal arteries. The factors studied included use of oral contraceptive agents or markers of sex hormone dysfunction, mechanical stress to the renal artery wall, human lymphocytic antigen (HLA) type, cigarette smoking, history of hypertension for more than 5 years, and family history of cardiovascular disease. The risk of fibromuscular dysplasia was significantly (/»=0.003) increased (odds ratio=4.1, 95% confidence interval=1.5-10.9) among cigarette smokers. A significant (/xO.001) dose-response relation was noted between cigarette use and the risk of fibromuscular dysplasia developing (odds ratio=8.6 for those who had smoked more than 10 pack-years). Personal history of hypertension more than 5 years was also associated (odds ratio=5.0,95% confidence interval^ 1.1-22.8) with a significantly (p=0.036) increased risk for the development of fibromuscular dysplasia. HLA-DRw6 antigen was more common in the 33 fibromuscular dysplasia patients than in the 61 renal transplant donor control subjects (odds ratio=3.00, /?=0.067) or a second group of 934 ambulatory control subjects (odds ratio=2.51, p=0.03l). Adjustment for cigarette smoking increased the odds ratio to 5.0 (95% confidence interval=1.3-19.6). There was a positive though not statistically significant (odds ratio=1. Received November 15, 1988; accepted in revised form June 30, 1989. has yet to be determined. The most commonly mentioned putative etiologic factors include exposure to exogenous estrogens, mechanical stress to the renal arteries, and genetic predisposition. However, these suggestions have primarily been derived from patterns noted in single case reports and case series. A better understanding of the factors responsible for the etiology of FMD would provide a rational basis for planning strategies to prevent FMD. With this in mind, we conducted a casecontrol study of etiologic factors in FMD. Our study was primarily designed to examine the etiologic roles of: 1) oral contraceptive administration and markers of sex hormone function, 2) mechanical stress to the renal arterial wall resulting from excessive mobility of the kidneys, 3) genetic predisposition, 4) cigarette smoking, and 5) history of cardiovascular disease in patients or their families.

Increased severity of multifocal renal arterial fibromuscular dysplasia in smokers

“…This study found a lower prevalence of smoking in FMD patients than previous studies (approx 50% vs 70-80% in other studies [4][5][6] ), possibly as a result of effective anti-smoking campaigns by the National Heart Foundation of Australia. The fact that over half the patients with multifocal lesions had never smoked proves conclusively that a personal history of smoking is not essential for the development of FMD.…”

“…Nicholson et al 5 found a significantly higher percentage of smokers in female FMD patients (71% of 21) than in female controls (41% of 158, P Ͻ 0.0005). Sang et al, 6 in a case-control study of 33 FMD patients (15 with beaded lesions) and 61 renal transplant donor controls, found not only a significantly higher percentage of smokers in the FMD group (79% vs 53%, P = 0.003) but also a positive relationship between pack years of smoking and the presence of FMD (P Ͻ 0.001).…”

“…[4][5][6] As a result, the question of smoking contributing to, and possibly causing FMD was raised. [4][5][6] Mackay et al 4 found 13 (72%) of 18 FMD patients to be current smokers, a rate significantly higher than in randomly-drawn sex-and age-matched hypertensive outpatient controls (39% of 18, P Ͻ 0.05). Nicholson et al 5 found a significantly higher percentage of smokers in female FMD patients (71% of 21) than in female controls (41% of 158, P Ͻ 0.0005).…”

“…1,[3][4][5][6]10 Since the age distribution at diagnosis was unimodal in non-smokers, but bimodal in smokers, smoking may affect a subset of patients with FMD who are 'susceptible', the remainder presenting at a similar age to non-smokers.…”

“…Several studies have suggested that smoking is also a risk factor for renal arterial FMD. [4][5][6] Tobacco constituents have been shown to stimulate vascular smooth muscle cell (VSMC) proliferation and synthetic activity, [7][8][9] which may contribute to the development of FMD.…”