Objective: Prader-Willi syndrome (PWS) is a genetic obesity syndrome characterized by hyperphagia, behavioural disturbance and intellectual disability. PWS appears to be associated with a high incidence of sudden death, suspected to be cardiopulmonary in origin. We therefore sought to provide an assessment of cardiac and vascular structure and function in patients with PWS.
Patients: Nine patients with genetically confirmed PWS, mean age 28 years, body mass index (BMI) 42 kg/m2, were compared with nine age- and gender-matched lean controls.
Measurements: Lipid parameters, high-sensitivity C-reactive protein (hs-CRP) and fasting glucose and insulin were measured. To assess cardiac structure and function, a resting electrocardiogram (ECG), exercise stress test, 24-h continuous ECG monitoring, and echocardiogram were obtained. Patients and control subjects also underwent comprehensive noninvasive vascular assessment, including venous-occlusion forearm plethysmography, brachial artery flow-mediated dilatation (FMD), radial artery tonometry and carotid intima-media thickness (IMT) measurements.
Results: All patients with PWS had significantly elevated hs-CRP (> 3.0 mg/l) (mean 11.5 mg/l, median 11.47, interquartile range: 4.48-15.8 mg/l), compared with controls (P < 0.001). Five of nine patients with PWS had subnormal exercise capacity (< 4 mets on exercise stress testing). Twenty-four-hour ECG monitoring revealed prolonged sinus pauses in one patient, up to 4.8 s, requiring pacemaker insertion. Microvascular function as assessed by peak hyperaemic flow response was decreased in PWS (6.1 +/- 1.0 times baseline flow vs. controls 13.5 +/- 1.6 times baseline flow, P = 0.01). Other measures were similar between PWS and controls.
Conclusions: This group of PWS patients had significantly raised levels of the inflammatory marker hs-CRP and evidence of microcirculatory dysfunction, both of which are associated with coronary artery disease and early sudden death. The sinus node dysfunction may in itself be a risk factor for sudden cardiac death.