title: Cardiovascular abnormalities in Klinefelter syndrome.
abstract: BACKGROUND
  Several epidemiological studies have demonstrated an increased mortality from cardiovascular causes in patients with Klinefelter Syndrome (KS). Little information is available about the nature of the underlying cardiovascular abnormalities. Aim of the study was to investigate exercise performance, left ventricular architecture and function, vascular reactivity, and carotid intima-media thickness in a group of patients with KS.
  
  
  METHODS
  Sixty-nine patients with KS and 48 age-matched controls participated in our population-controlled study. Forty-eight Klinefelter subjects were on testosterone treatment at the time of the investigation while 21 were naive and underwent a complete Doppler echocardiographic examination, a cardiopulmonary exercise test as well as a vascular study including measures of carotid intima-media thickness and endothelial function with flow-mediated dilation of the brachial artery. Patients with KS on testosterone therapy (n=48) were also matched against a population of men with treated secondary hypogonadism (n=21).
  
  
  RESULTS
  Patients with KS exhibited a wide array of cardiovascular abnormalities including left ventricular diastolic dysfunction, reduced maximal oxygen consumption (p<0.01), increased intima-media thickness (p<0.05) (-34% and +42% vs. controls, respectively) and a high prevalence of chronotropic incompetence (55% of patients, p<0.01). No significant difference was found between treated and untreated KS in variance with men treated for secondary hypogonadism.
  
  
  CONCLUSIONS
  Left ventricular diastolic dysfunction, impaired cardiopulmonary performance, chronotropic incompetence, and increased intima-media thickness suggest that cardiovascular abnormalities are a common finding in KS that is not reversed by testosterone replacement therapy and may represent the pathophysiological underpinnings of the increased risk of dying from heart disease.
authors.affiliation: Department of Cardiothoracic and Respiratory Science, Endocrinology Unit, Second University of Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pasquali
authors.forename: Michele
authors.initials: M
authors.lastname: Arcopinto
authors.forename: Andrea
authors.initials: A
authors.lastname: Renzullo
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Accardo
authors.forename: Andrea
authors.initials: A
authors.lastname: Salzano
authors.forename: Daniela
authors.initials: D
authors.lastname: Esposito
authors.forename: Lavinia
authors.initials: L
authors.lastname: Saldamarco
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Isidori
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Marra
authors.forename: Antonio
authors.initials: A
authors.lastname: Ruvolo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Napoli
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bossone
authors.forename: Andrea
authors.initials: A
authors.lastname: Lenzi
authors.forename: Ragavendra R
authors.initials: RR
authors.lastname: Baliga
authors.forename: Luigi
authors.initials: L
authors.lastname: Saccà
authors.forename: Antonio
authors.initials: A
authors.lastname: Cittadini
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000502:physiology*; D001916:Brachial Artery / Q000502:physiology; D018376:Cardiovascular Abnormalities / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D015150:Echocardiography, Doppler / Q000379:methods; D005080:Exercise Test / Q000379:methods; D006801:Humans; D007713:Klinefelter Syndrome / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D011159:Population Surveillance / Q000379:methods; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology
keywords: 12-lead scalar Electrocardiogram; BMI; BP; Blood Pressure; Body Mass Index; CI; CPET; Carbon Dioxide Production; Cardio-pulmonary Exercise Test; Cardiovascular abnormalities; Chronotropic Incompetence; Chronotropic incompetence; ECG; FMD; Flow-mediated Dilation; HOMA; HR; HRR; Heart; Heart Rate; Heart Recovery Rate; Homeostasis Model Assessment; IMT; IRT; Intima-Media Thickness; Isovolumic Relaxation Time; KS; Klinefelter; Klinefelter Syndrome; LV; Left Ventricle; Oxygen Uptake; TDI; Tissue Doppler Imaging; VCO(2); VE; VO(2); Ventilation per Minute