Excess coronary heart disease in Familial Combined Hyperlipidemia, in relation to genetic factors and central obesity.
OBJECTIVE
To determine the prevalence of non-fatal coronary artery disease (CAD) in kindred with Familial Combined Hyperlipidemia (FCHL) in relation to various cardiovascular risk factors and DNA variation in the apo AI-CIII-AIV gene cluster.


RESULTS
Data were collected from 18 Dutch FCHL probands, 202 living first and second degree relatives, and 175 spouses. Probands and first degree relatives showed dyslipidemia, increased plasma insulin and glucose concentrations, higher waist--hip ratio (WHR), and blood pressure, than spouses. The frequency of the minor alleles M2 and S2 was increased in probands and first degree relatives. The Odds Ratio for CAD was 5.3 in male FCHL relatives (P=0.005), and 5.1 in all FCHL relatives (P=0.001). First and second degree relatives had a markedly reduced CAD-free life-span (logrank vs. spouses: P<0.001 and P=0.03, respectively). The presence of the S2, but not M2, minor allele, showed a marked reduction in CAD-free life-span (logrank S2 present vs. S2 absent: P=0.035).


CONCLUSIONS
Men with FCHL have a severely increased risk of CAD, that appears to be mediated through genetic relation to the proband as the strongest independent risk factor for CAD, followed by increased WHR.
Voors-Pette
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Department of Medicine and Endocrinology and Cardiology Research Institute Maastricht, Academic Hospital Maastricht, PO Box 5800, 6202 AZ, Maastricht, The Netherlands.
de Bruin
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D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D001824:Body Constitution; D003327:Coronary Disease / Q000150:complications* / Q000453:epidemiology*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D009765:Obesity / Q000150:complications*; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; D001056:Apolipoproteins C; C022205:apolipoprotein A-IV