Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study.
OBJECTIVE
Growth-differentiation factor-15 (GDF-15) is emerging as an independent prognostic biomarker in patients with cardiovascular (CV) disease. Little is known about the pathophysiological basis for the close association of GDF-15 to future CV events. We hypothesized that GDF-15 is related to underlying CV pathologies.


RESULTS
To relate the levels of GDF-15 to indices of CV dysfunction and disease in elderly individuals, serum levels of GDF-15 were measured in 1004 subjects aged 70 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Carotid intima-media thickness and plaque burden, and left ventricular (LV) geometry and function were assessed by ultrasound. Endothelial function was evaluated in forearm resistance vessels and in the brachial artery by venous occlusion plethysmography and ultrasound imaging, respectively. Elevated levels of GDF-15 were related to several CV risk factors (male gender, current smoking, body mass index, waist circumference, diabetes, fasting glucose, triglycerides, and low HDL cholesterol). After adjustment for CV risk factors, increased levels of GDF-15 were associated with reduced endothelium-dependent vasodilation in resistance vessels, plaque burden, LV mass and concentric LV hypertrophy, reduced LV ejection fraction, and clinical manifestations of coronary artery disease and heart failure.


CONCLUSIONS
GDF-15 carries information on CV dysfunction and disease that is not captured by traditional CV risk factors in elderly individuals.
Lind
Lars
L
Department of Medicine (Cardiology and Clinical Chemistry), University of Uppsala, 75185 Uppsala, Sweden.
Wallentin
Lars
L
Kempf
Tibor
T
Tapken
Heike
H
Quint
Anja
A
Lindahl
Bertil
B
Olofsson
Sylvia
S
Venge
Per
P
Larsson
Anders
A
Hulthe
Johannes
J
Elmgren
Anders
A
Wollert
Kai C
KC
D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001916:Brachial Artery / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000503:physiopathology; D017536:Carotid Artery, Common / Q000473:pathology; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005542:Forearm / Q000098:blood supply; D055436:Growth Differentiation Factor 15 / Q000378:metabolism*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D013318:Stroke Volume / Q000502:physiology; D017540:Tunica Media / Q000473:pathology; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000503:physiopathology
D015415:Biomarkers; D055436:Growth Differentiation Factor 15