The prevalence and clinical impact of obesity in adults with Marfan syndrome

Abstract

Despite improvement in survival noted throughout the past few decades (1), patients with Marfan syndrome remain at risk for premature death secondary to the cardiovascular complications of aortic dilation and dissection (2). Risk factors for such complications remain poorly defined, thereby impeding attempts at risk stratification for the individual patient. Family history of aortic dissection (3) and spontaneous genetic mutations (4) have been identified as risk factors but, currently, no potentially modifiable risk factors have been elucidated.The underlying biomechanical abnormalities in Marfan syndrome have been well described. Patients with Marfan syndrome have reduced aortic distensibility, which becomes progressively more abnormal with increasing age (5). These biomechanical abnormalities precede the vascular complication of aortic dilation and dissection, and may reflect both endothelial and vascular smooth muscle cell abnormalities of the aortic wall (6-8).The current obesity epidemic has been the subject of much lay and scientific attention. Obesity, hyperlipidemia, smoking and hypertension have been established as clear risk factors for atherosclerotic arterial disease (9). These risk factors predispose to impaired vascular endothelial function, thereby increasing the risk of vascular complications including coronary arterial obstructive disease and stroke (10). Marfan syndrome is characteristically associated with an asthenic body habitus; as a result, these patients have been considered to be exempt from the current obesity epidemic.We sought to determine the prevalence of obesity and overweight in an adult cohort of patients with Marfan syndrome, to assess the prevalence of other cardiovascular risk factors among this patient group -namely smoking, hyperlipidemia, diabetes and hypertensionand to determine what, if any, clinical impact such risk factors had on outcome in this patient cohort. BACKGROUND:Patients with Marfan syndrome characteristically have an asthenic body habitus and are considered to be exempt from the obesity epidemic. OBJECTIVE: To examine the prevalence and clinical impact of obesity in a cohort of adults with Marfan syndrome. METHODS: Fifty outpatients (30 female) with a mean (± SD) age of 38±13 years were studied. Demographic variables including previously identified risk factors for aortic dissection were recorded. Body mass index (BMI) was determined and patients were classified as normal (BMI less than 25 kg/m 2 ), overweight (BMI 25 kg/m 2 to 29.9 kg/m 2 ) or obese (BMI 30 kg/m 2 or greater). Other cardiovascular risk factors were examined. An adverse clinical outcome was defined as either the attainment of surgical criteria for aortic root replacement or the presence of aortic dissection. RESULTS: A family history of aortic dissection was present in 13 (26%) patients. In 23 (46%) patients, there was no known family history of Marfan syndrome. Mean BMI was 25.4±7.4 kg/m 2 , with 18 (36%) patients having an elevated BMI. Positive smoking status was present in 15 (30%), hyp...

The Immediate and Long-Term Impact of Pregnancy on Aortic Growth Rate and Mortality in Women With Marfan Syndrome

“…While MFS is associated with diverse clinical manifestations in multiple organ systems, it is the cardiovascular complications of aortic dilation and dissection that account for the morbidity and mortality associated with the disease (2). Risk factors for adverse aortic outcomes, namely the need for aortic surgery, aortic insufficiency, and aortic dissection, have been identified and include greater aortic size (2), obesity (3), family history of aortic dissection (2), and older age (2). The impact of gender on risk remains controversial with some studies noting female gender, and others, male gender, as a risk factor for aortic dissection.…”

Management of cardiovascular disease in Turner syndrome

“…As is the case in the other aortopathies, obesity, even in the absence of hypertension, is associated with an increased incidence of aortic complications [39]. This phenomenon may be mediated by increased release of adopokines resulting in an increased angiotensin II effect [37,39].…”

“…Hypertension in the general population is known to further impair aortic distensibility through increased quenching of nitric oxide, leading to increased MMP production with aortic diameters bearing close correlation with plasma MMP levels [38]. As is the case in the other aortopathies, obesity, even in the absence of hypertension, is associated with an increased incidence of aortic complications [39]. This phenomenon may be mediated by increased release of adopokines resulting in an increased angiotensin II effect [37,39].…”

“…The distinctly altered body composition probably plays a role in the increased incidence of abnormal glucose metabolism, as well as coronary artery disease. In addition, increased body fat has been shown to be associated with an increased incidence of aortic complications in other populations with aortopathy [37,39]. It has been theorized that metabolically active adopokines may play a role through the release of angiotensin II and other vasoconstrictors [37,39].…”

Features of Marfan syndrome not listed in the Ghent nosology – the dark side of the disease

“…The frequency of atherosclerotic coronary artery disease in Marfan syndrome is unknown. Risk factors for atherosclerosis, including obesity, smoking, hyperlipidemia, and hypertension do not differ from the general population [104]. In addition, carotid intimal thickness, a surrogate measure for coronary artery disease, has been shown not to differ between Marfan syndrome and the general population [105].…”