Abdominal obesity, measured by waist-to-hip ratio (WHR) or waist circumference, has been associated with an increased risk of type 2 diabetes, metabolic syndrome, myocardial infarction, hypertension and stroke. Simultaneous measurements of waist circumference and fasting triglycerides (TGs) have been proposed as inexpensive screening tools to identify men at elevated risk of CAD who are characterized by the atherogenic metabolic triad: hyperinsulinemia, elevated apo B, and small low-density lipoprotein.
Familial combined hyperlipidemia (FCHL) is the most frequent genetic lipid abnormality in humans, characterized by hyperlipidemia. FCHL subjects have a 5- to 10-fold increased risk of early myocardial infarction, mediated by genetic factors measured as the genetic relation to the proband, but also by abdominal obesity measured as WHR. To evaluate further the association of abdominal obesity with hyperlipidemia in relatives from well-defined FCHL families, a recent study from the Netherlands assessed the odds ratios (ORs) for the expression of hyperlipidemia in different categories of BMI, waist circumference and WHR in both FCHL relatives and spouses.
Fifty-two unrelated white FCHL index patients (probands) were discovered at the Lipid Clinic of the Utrecht Academic Hospital or the Maastricht Academic Hospital. Relatives and spouses of the probands visited the clinics, where they answered a standardized questionnaire and underwent a physical examination, which included lab work. Weight, height, and waist circumference were measured and BMI and WHR were subsequently calculated.
In total, 618 FCHL relatives and 297 spouses, representing a total of 52 families, were included in the study. In FCHL relatives, a graded, continuous effect of WHR on the prevalence of hyperlipidemia was found, ranging from 16% in the lowest WHR category to 57.6% in the highest category. In FCHL relatives, categories of BMI or waist circumference showed the same trend as found with WHR in FCHL, that is, a significant positive contribution to the prevalence of hyperlipidemia among FCHL relatives. In the whole study population, frequency of hypertriglyceridemia showed a significant interaction only between WHR categories and FCHL but predominant expression of hypertriglyceridemia was observed with higher categories of WHR in FCHL relatives but not in spouses.
The results clearly suggest that the genetic susceptibility to hyperlipidemia in FCHL has an interaction with abdominal obesity. It appears that WHR was the most informative and specific obesity marker associated with hyperlipidemia in FCHL. This knowledge is of value in genetic studies, where incomplete penetrance is an issue in the selection strategy and in medical treatment of FCHL subjects, where abdominal overweight should be addressed by weight loss strategies.
Carla J.H. van der Kallen, Christine Voors-Pette, and Tjerk W.A. de Bruin, Abdominal Obesity and Expression of Familial Combined Hyperlipidemia, Obesity Research 12(12): 2054-2060 (December 2004) [Address correspondence to Carla J.H. van der Kallen, Lab of Molecular Metabolism and Endocrinology, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: c.vanderkallen@inumed.unimaas.nl]
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