Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease.
OBJECTIVE
Leptin, an adipocyte-derived protein, regulating food intake and metabolism has been implicated in the development of coronary heart disease. We have examined the relationship between leptin and vascular risk factors including insulin resistance, metabolic, inflammatory and haemostatic risk factors.


RESULTS
The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Leptin was strongly positively correlated with waist circumference (r=0.58; p<0.0001). Leptin concentrations decreased significantly with increasing physical activity and were lowered in cigarette smokers and elevated in men with pre-existing coronary heart disease and stroke; alcohol intake showed no association with leptin concentration. After adjustment for waist circumference and these lifestyle factors, increased leptin was independently associated with significant increases in insulin resistance, triglycerides, inflammatory markers (interleukin-6, C-reactive protein, fibrinogen, plasma viscosity), coagulation factor VIII, endothelial markers von Willebrand factor, tissue plasminogen activator, and fibrin D-dimer levels; and a decrease in HDL-cholesterol. No association was seen between leptin and blood pressure, total cholesterol, glucose or white cell count after adjusting for waist circumference. Further adjustment for insulin resistance abolished the relationships between leptin and triglycerides and HDL-cholesterol, weakened the associations with the haemostatic factors although they remained significant, but made minor differences to the associations with inflammatory markers.


CONCLUSIONS
Plasma leptin is associated with insulin resistance, inflammation and disturbances in haemostasis independent of waist circumference, suggesting possible pathways by which leptin may influence risk of cardiovascular disease.
Wannamethee
S Goya
SG
Department of Primary Care and Population Sciences, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. goya@pcps.ucl.ac.uk
Tchernova
Julia
J
Whincup
Peter
P
Lowe
Gordon D O
GD
Kelly
Anne
A
Rumley
Ann
A
Wallace
A Michael
AM
Sattar
Naveed
N
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D005500:Follow-Up Studies; D006487:Hemostasis; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications*; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood*; D050356:Lipid Metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D006113:United Kingdom
D015415:Biomarkers; D020738:Leptin