Plasma leptin levels and incidence of heart failure, cardiovascular disease, and total mortality in elderly individuals.
OBJECTIVE
Obesity predisposes individuals to congestive heart failure (CHF) and cardiovascular disease (CVD). Leptin regulates energy homeostasis, is elevated in obesity, and influences ventricular and vascular remodeling. We tested the hypothesis that leptin levels are associated with greater risk of CHF, CVD, and mortality in elderly individuals.


METHODS
We evaluated 818 elderly (mean age 79 years, 62% women) Framingham Study participants attending a routine examination at which plasma leptin was assayed.


RESULTS
Leptin levels were higher in women and strongly correlated with BMI (P < 0.0001). On follow-up (mean 8.0 years), 129 (of 775 free of CHF) participants developed CHF, 187 (of 532 free of CVD) experienced a first CVD event, and 391 individuals died. In multivariable Cox regression models adjusting for established risk factors, log-leptin was positively associated with incidence of CHF and CVD (hazard ratio [HR] per SD increment 1.26 [95% CI 1.03-1.55] and 1.28 [1.09-1.50], respectively). Additional adjustment for BMI nullified the association with CHF (0.97 [0.75-1.24]) but only modestly attenuated the relation to CVD incidence (1.23 [1.00-1.51], P = 0.052). We observed a nonlinear, U-shaped relation between log-leptin and mortality (P = 0.005 for quadratic term) with greater risk of death evident at both low and high leptin levels.


CONCLUSIONS
In our moderate-sized community-based elderly sample, higher circulating leptin levels were associated with a greater risk of CHF and CVD, but leptin did not provide incremental prognostic information beyond BMI. Additional investigations are warranted to elucidate the U-shaped relation of leptin to mortality.
Lieb
Wolfgang
W
Framingham Heart Study, Framingham, Massachusetts, USA.
Sullivan
Lisa M
LM
Harris
Tamara B
TB
Roubenoff
Ronenn
R
Benjamin
Emelia J
EJ
Levy
Daniel
D
Fox
Caroline S
CS
Wang
Thomas J
TJ
Wilson
Peter W
PW
Kannel
William B
WB
Vasan
Ramachandran S
RS
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology* / Q000401:mortality; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000453:epidemiology* / Q000401:mortality; D006801:Humans; D015994:Incidence; D020738:Leptin / Q000097:blood*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D009765:Obesity / Q000150:complications; D012044:Regression Analysis; D012307:Risk Factors
D008076:Cholesterol, HDL; D020738:Leptin