Fat Gain and Cardiovascular Disease Mechanisms
Condition: Hypertension; Sleep Apnea Syndromes; Obesity
MeSH terms: Sleep Apnea Syndromes; Cardiovascular Diseases
Study type: Interventional
Phase: Phase 3

Summary: 
      Understanding the mechanisms of obesity-induced hypertension is important both for prevention
      and therapy. Studies of patients with established obesity have provided valuable information
      on pathophysiologic links between obesity and both blood pressure and cardiovascular risk.
      However, these studies are necessarily limited by the heterogeneity of obesity-associated
      disease so that the relative contribution of obesity or hypertension or other co-existing
      diseases to specific regulatory abnormalities is often not clear. Clarification of whether
      any abnormalities associated with increased cardiovascular risk were present before or after
      the development of obesity has also been problematic.

      We therefore propose a series of novel studies directed at establishing the effects of
      increased body fat in otherwise healthy individuals. We will determine the distribution
      patterns of increased body fat and how both increased body fat and fat distribution relate to
      changes in blood pressure, and in neural, endothelial and inflammatory mechanisms which have
      been implicated in the development and progression of cardiac and vascular disease.

      We will study non-obese subjects with and without a family history of hypertension. These
      subjects will undergo an eight-week program of overfeeding with the objective of inducing a 4
      kg fat gain. We will determine the nature of fat distribution in these individuals after the
      fat gain program and subsequently after an eight-week period of weight loss and restoration
      of normal body weight. Measurements will be compared to those obtained in a matched control
      group with and without a family history of hypertension, who will continue their normal
      diets. We will test the following hypotheses:

        -  Individuals with a family history of hypertension will gain more visceral fat and upper
           body subcutaneous fat and will have greater blood pressure increases with overfeeding-
           compared with those without such a family history.

        -  For all overfed subjects, increases in blood pressure and insulin resistance with fat
           gain will be most marked in those individuals with a predominantly upper body and
           visceral fat accumulation.

        -  Upper body and visceral fat gain will also be associated with greater impairment in
           cardiovascular function, higher nocturnal blood pressures and an increased likelihood of
           sleep disordered breathing.
    


Intervention name(s): 1000 extra calories
Intervention type(s): Dietary Supplement
Intervention description(s): Each subject received 1000 kcal/d in addition to weight maintenance requirements. The diet composition throughout the study was 40% carbohydrate, 40% fat, and 20% protein.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Prevention