Background: Definition of pregnancy risk in women with Marfan syndrome (MFS) has been confounded by ascertainment bias, lack of imaging data, small sample size, and inclusion of women without a known MFS diagnosis before a pregnancy complication. To lessen these limitations, we analyzed MFS women participating in the large GenTAC Registry. Results: Among 184 women in whom pregnancy information was available, 94 women (51%) had a total of 227 pregnancies (average 2.5, range 1-6). Compared to MFS women who never became pregnant, those with pregnancies were older at time of MFS diagnosis (27 vs. 13 years, p<0.0001) and at time of GenTAC enrollment (47 vs. 37 years, p<0.0001). When comparing ever-pregnant to never-pregnant women with MFS at the time of registry entry, higher historical rates of aortic dissection and prophylactic proximal aortic surgery were observed (24/94 [25.5%] vs. 13/90 [14.4%], p=0.068 and 15/94 [16.0%] vs. 4/90 [4.4%], p=0.014; respectively). Among the 94 MFS women with pregnancies, 10 (10.6%) experienced a pregnancy-related aortic complication (4 Type A and 3 Type B dissections, one coronary artery dissection, and 2 with significant [≥3 mm] aortic growth, 1 of whom required post-partum prophylactic surgery). Four of the aortic dissections, including all 3 Type B, and the coronary dissection occurred in the post-partum period. Only 3 of 7 women (43%) with an aortic dissection related to pregnancy were aware of their MFS diagnosis before pregnancy. Women with and without pregnancy-associated aortic complications did not differ in phenotypic features. The rate of aortic dissection was higher during pregnancy + post-partum period (3.5 per 100 person-years vs. 0.8 per 100 person-years, odds ratio 4.6 [95% confidence interval 2.1-10.1], p=0.0002). Conclusions: Pregnancy in MFS is associated with an increased risk of aortic dissection, both Types A and B, particularly in the immediate post-partum period, and more frequent prophylactic surgery. Lack of knowledge of underlying MFS diagnosis before aortic dissection is a major contributing factor. These findings underscore the need for early diagnosis, pre-pregnancy risk counselling, and multi-disciplinary peri-partum management.
Unless otherwise noted, data are presented as the mean Ϯ SD.HDL ϭ high-density lipoprotein; NS ϭ not significant.† To convert to mol/L, multiply by 88.402.‡ To convert to mmol/L, multiply by 0.0259.§ To convert to mmol/L, multiply by 0.0555.
Systemic lupus erythematosus (SLE) is independently associated with accelerated atherosclerosis and premature arterial stiffening. Asymmetric dimethylarginine (ADMA) and homocysteine are mechanistically interrelated mediators of endothelial dysfunction and correlates of atherosclerosis in the general population. The aim of this study was to assess the relationship of ADMA and homocysteine to subclinical vascular disease in patients with SLE.One hundred twenty-five patients with SLE who were participating in a study of cardiovascular disease underwent clinical and laboratory assessment, carotid artery ultrasonography to detect atherosclerosis, and radial artery applanation tonometry to measure arterial stiffness.Neither ADMA nor homocysteine correlated with the presence or extent of carotid atherosclerosis. In contrast, ADMA was significantly related to the arterial stiffness index. Independent correlates of arterial stiffening included the ADMA concentration, the presence of diabetes mellitus, older age at the time of diagnosis, longer disease duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary multivariable analysis substituting homocysteine for ADMA demonstrated comparable relationships with arterial stiffness (r(2) = 0.616 for homocysteine and r(2) = 0.595 for ADMA).ADMA and homocysteine are biomarkers for and may be mediators of premature arterial stiffening in patients with SLE. Because arterial stiffness has independent prognostic value for cardiovascular morbidity and mortality, its predictors may identify patients who are at increased risk of cardiovascular disease.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
