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D-dimer in Marfan syndrome: effect of obstructive sleep apnea induced blood pressure surges
Mudiaga Sowho1, Hartmut Schneider2, Jonathan Jun1
1Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland.
Abstract:
Aortic dissection and rupture are the major causes of premature death in persons with Marfan syndrome (MFS), a rare genetic disorder featuring cardiovascular, skeletal, and ocular impairments. We and others have found that obstructive sleep apnea (OSA) confers significant vascular stress in this population and may accelerate aortic disease progression. We hypothesized that D-dimer, a diagnostic biomarker for several types of vascular injury that is also elevated in persons with MFS with aortic enlargement, may be sensitive to cardiovascular stresses caused by OSA. To test this concept, we recruited 16 persons with MFS without aortic dissection and randomized them to two nights of polysomnography, without (baseline) and with OSA treatment: continuous positive airway pressure (CPAP). In addition to scoring OSA by the apnea-hypopnea index (AHI), beat-by-beat systolic BP (SBP) and pulse-pressure (PP) fluctuations were quantified. Morning blood samples were also assayed for D-dimer levels. In this cohort (male:female, 10:6; age, 36 ± 13 yr; aortic diameter, 4 ± 1 cm), CPAP eliminated OSA (AHI: 20 ± 17 vs. 3 ± 2 events/h, P = 0.001) and decreased fluctuations in SBP (13 ± 4 vs. 9 ± 3 mmHg, P = 0.011) and PP (7 ± 2 vs. 5 ± 2 mmHg, P = 0.013). CPAP also reduced D-dimer levels from 1,108 ± 656 to 882 ± 532 ng/mL (P = 0.023). Linear regression revealed a positive association between the maximum PP during OSA and D-dimer in both the unadjusted (r = 0.523, P = 0.038) and a model adjusted for contemporaneous aortic root diameter (r = 0.733, P = 0.028). Our study revealed that overnight CPAP reduces D-dimer levels commensurate with the elimination of OSA and concomitant hemodynamic fluctuations. Morning D-dimer measurements together with OSA screening might serve as predictors of vascular injury in MFS.NEW & NOTEWORTHY What is New? Surges in blood pressure caused by obstructive sleep apnea during sleep increase vascular stress and D-dimer levels in Marfan syndrome. Elevations in D-dimer can be lowered with CPAP. What is Noteworthy? D-dimer levels might serve as a marker for determining the significance of obstructive sleep apnea in persons with Marfan syndrome. D-dimer or obstructive sleep apnea screening is a potential method to identify persons with Marfan syndrome at risk for adverse cardiovascular events.
Insights
Obstructive sleep apnea (OSA) increases vascular stress and D-dimer levels in Marfan syndrome (MFS). Continuous positive airway pressure (CPAP) treatment for OSA reduces these levels, suggesting D-dimer may predict vascular injury risk in MFS patients.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Sleep Medicine
Background:
- Marfan syndrome (MFS) is a genetic disorder associated with significant cardiovascular risks, including aortic dissection and rupture.
- Obstructive sleep apnea (OSA) is increasingly recognized as a contributor to vascular stress in MFS patients, potentially accelerating aortic disease.
- D-dimer, a biomarker for vascular injury, is elevated in MFS patients with aortic enlargement and may reflect OSA-induced stress.
Purpose of the Study:
- To investigate whether D-dimer levels in Marfan syndrome patients are sensitive to the cardiovascular stresses imposed by obstructive sleep apnea.
- To determine if continuous positive airway pressure (CPAP) treatment for OSA can reduce D-dimer levels and associated hemodynamic fluctuations in MFS.
Main Methods:
- Sixteen MFS patients without aortic dissection were enrolled and underwent two nights of polysomnography: one without OSA treatment (baseline) and one with CPAP.
- Apnea-hypopnea index (AHI) was measured to quantify OSA severity.
- Beat-by-beat systolic blood pressure (SBP) and pulse pressure (PP) fluctuations were recorded, and morning blood samples were analyzed for D-dimer levels.
Main Results:
- CPAP treatment effectively eliminated OSA (AHI reduced from 20±17 to 3±2 events/h, P=0.001) and significantly decreased SBP (13±4 to 9±3 mmHg, P=0.011) and PP (7±2 to 5±2 mmHg, P=0.013) fluctuations.
- D-dimer levels were significantly reduced following CPAP treatment, decreasing from 1,108±656 to 882±532 ng/mL (P=0.023).
- A positive association was found between maximum PP during OSA and D-dimer levels, even after adjusting for aortic root diameter (r=0.733, P=0.028).
Conclusions:
- Overnight CPAP treatment reduces D-dimer levels in MFS patients, correlating with the elimination of OSA and associated hemodynamic instability.
- Morning D-dimer levels, in conjunction with OSA screening, may serve as valuable predictors of vascular injury in individuals with Marfan syndrome.
- These findings highlight the potential of D-dimer and OSA screening as methods to identify MFS patients at higher risk for adverse cardiovascular events.
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