Body water distribution and risk of cardiovascular morbidity and mortality in a healthy population: a prospective cohort study.
BACKGROUND
Early alterations in the cardiovascular structure and function may change normal body water distribution. The resulting fluid shifts may thus serve as an early marker for cardiovascular disease. However, studies examining this in healthy populations are absent.


OBJECTIVE
This study examined the association between the proportion of total body water that is extracellular water and subsequent development of non-fatal or fatal cardiovascular disease in a healthy population.


METHODS
Bioelectrical impedance spectroscopy is an easy-to-use, non-invasive and relatively inexpensive technique to evaluate changes in body water distribution. A random subset (n = 2120) of Danes aged 41-71 years, examined in 1993-1994 for body water distribution by bioelectrical impedance spectroscopy was included. Cox-proportional hazard models and linear splines were performed. The ratio between resistance estimates from an infinite-frequency and from no-frequency (R∞/R0) was used as a surrogate measure of ratio between extracellular water and total body water. The outcome was 13.5 years of follow-up for cardiovascular morbidity and mortality.


RESULTS
A high proportion of total body water that is extracellular water was associated with increased risk of incident cardiovascular disease. A threshold effect was evident, with greatly increased risk of cardiovascular morbidity and mortality above R∞/R0 = 0.68. Below the threshold there seemed to be no additional benefit of having a low ratio.


CONCLUSIONS
Our findings suggest that non-clinically evident oedema, measured as an increased proportion of total body water that is extracellular, above a threshold of 0.68, may be an early marker of pre-clinical cardiovascular disease. This simple, safe, cheap and easily obtainable measure of R∞/R0 from bioelectrical impedance may help the early identification of these otherwise clinically healthy individuals who are at an increased risk of future cardiovascular disease. However, more studies are needed before it can be concluded that bioelectrical impedance spectroscopy improves clinical risk prediction.
Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals as part of Copenhagen University Hospital, The Capital Region, Copenhagen, Denmark.
Nikoline Nygård
NN
Knudsen
Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals as part of Copenhagen University Hospital, The Capital Region, Copenhagen, Denmark ; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark.
Thora Majlund
TM
Kjærulff
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Leigh Cordwin
LC
Ward
Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals as part of Copenhagen University Hospital, The Capital Region, Copenhagen, Denmark.
Ditte
D
Sæbye
Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals as part of Copenhagen University Hospital, The Capital Region, Copenhagen, Denmark.
Claus
C
Holst
Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals as part of Copenhagen University Hospital, The Capital Region, Copenhagen, Denmark ; The Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, Sydney University, Sydney, Australia ; National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark ; Research Centre for Prevention and Health, Copenhagen University Hospital, Glostrup, Denmark.
Berit Lilienthal
BL
Heitmann
D000328:Adult; D000368:Aged; D001834:Body Water / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000401:mortality; D003718:Denmark / Q000453:epidemiology; D058266:Dielectric Spectroscopy / Q000379:methods; D017097:Electric Impedance; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries / Q000706:statistics & numerical data; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate