Vasculopathy in Turner syndrome: arterial dilatation and intimal thickening without endothelial dysfunction

CONTEXT: Women with Turner syndrome (TS) have an increased cardiovascular mortality rate from both structural and ischemic heart disease, especially aortic dissection. OBJECTIVE: We hypothesized that TS women have a fundamental arterial wall defect that may be due to genetic factors or estrogen deficiency. DESIGN, SETTING, AND PATIENTS: TS women (n = 93) were compared with normal controls (n = 25) and women with 46,XX primary amenorrhea (PA) (n = 11) with a similar history of estrogen deficiency. Clinical parameters, aortic root diameter, extraaortic arterial structure [common carotid (CD), brachial artery diameter, and carotid intima-media thickness (IMT)], arterial stiffness (pulse-wave velocity, augmentation index), and endothelial function (flow-mediated dilatation) were assessed. MAIN OUTCOME MEASURES: These included arterial diameters and vascular physiology parameters. RESULTS: Differences in arterial structure were observed among TS, normal controls, and 46,XX PA women: IMT (0.61 +/- 0.07 vs. 0.55 +/- 0.06 vs. 0.60 +/- 0.05 mm, respectively; P < 0.001), CD (5.71 +/- 0.64 vs. 5.27 +/- 0.34 vs. 5.22 +/- 0.38 mm; P < 0.001), and brachial artery diameter (3.29 +/- 0.44 vs. 3.06 +/- 0.36 vs. 2.97 +/- 0.30 mm; P = 0.006). Aortic root diameter was greater in TS than normal control women. TS status, height, weight, and IMT were independently associated with increased CD after multivariate adjustment (P < 0.05). TS status, age, diastolic blood pressure, and CD remained independently associated with increased IMT after multivariate adjustment (P < 0.05). Pulse-wave velocity and flow-mediated dilatation were similar among the three groups. CONCLUSION: Women with TS have greater IMT and conduit artery diameters than normal controls. Similarly, increased IMT in TS and 46,XX PA women suggests that estrogen deficiency contributes to intimal thickening. Interventional studies are required to determine the extent to which blood pressure and estrogen deficiency may be appropriate therapeutic targets to reduce cardiovascular risk in TS