SLR - August 2010 - Jennifer Bell

Heritability of chronic venous disease

Reference: Fiebig, A, Krusche, P, Wolf , A, Krawczak, M, & Timm, B. (2010). Heritability of chronic venous disease. Human Genetics, doi: 10.1007/s00439-010-0812-9

Scientific Literature Review

Reviewed by: Jennifer Bell, DPM PGY-3
Residency program: OCPM/UHHS-RMC

Podiatric Relevance: 
Chronic venous disease is a common pathology and frequently manifests itself in the lower extremity.  Podiatric physicians will often treat the manifestations of chronic venous disease including varicose veins, edema, venous stasis insufficiency, venous stasis ulcers, etc. This original research article attempts to determine if there are any genetic factors or heritability of chronic venous disease.

2,701 patients with chronic venous disease (CVD) were recruited between October 2005 and July 2008 at a  vascular clinic in Germany specializing in the treatment of CVD.  A questionaire was given to each patient to obtain information including age, race, sex, date and place of birth, and parental origin.  Medical history was also obtained and included information such as  previous treatment, degree of pain, age of onsent of CVD, previous surgeries, previous deep vein thrombosis or phlebitis.  A blood sample was taken from each patient for further genetic analysis. Patients were interviewed and gave information about their first degree living  relatives which generated 4,033 families and 16, 434 individuals for analysis.  The CEAP classification was utilitzed to classify patients into appropriate categories based on their level of CVD. This classification is based on clinical severity, etiology or cause, anatomy and pathophysiology. Grades are given based on presence and severity of skin changes, ranging from grade C0 to C6. Exclusion criteria for the study were generalized debilitation of patient, acute signs of DVT and obvious congenital causes of CVD.   

After analysis of patients and their families, the combined genetic factors were found to contribute to CVD at a factor of approximately 17%.   The CEAP grades C3 through C6 affected the most patients (83.4%), with the majority having grade C3 (62.8%).  Overall mean age at CVD onset was noted to be 32.6 years.  An inverse relationship was noted in this study between disease severity and disease onset.  Patients affected by  less severe grades of CEAP classification (grades C0 to C2) were first affected by CVD at 35.8 years compared with grades C3 to C6 which were affected at 30.7 years.  A drastic increase in disease duration and disease severity was observed in the study.  No significant age difference was observed between males and females. In reference to sex itself, twice as many patients involved in the study were female (1,904).  Age of disease onset was 30.8 years in females and 36.8 years in males.  Mean BMI for study patients was 26.8.  A small, but statistically significant difference was observed between male and female BMI, 27.5 and 26.6, accordingly. BMI was noted to be 26.5 for grade C3, 28.3 for C4, and 29.6 for C5 and C6

The main risk factors identifiable with CVD to date have been female sex, age and family history.  This is the first study to include age at disease onset and disease duration. Results from this sutdy confirm previouslyl proposed hypotheses.  For example,  it has been previously reported that there is a larger number of female patients with CVD.  This gender predilection can be explained by numerous reasons including the fact that women are more likely to seek medical attention and undergo treatment than men. Also, as observed by this study, disease onset was approximately 6 years earlier in females.  The inverse relationhip observed between severity could be explained by the fact that CVD is a progressive disease which can cause those with longer disease duration to demonstrate the worst phenotype. BMI was noted to be statistically significant between males and females in this study,  Previous chronic venous disease studies have reported that BMI is more important in females than males.  However, the current study also discovered that obesity can play a larger role in the development of more severe forms of CVD. 

It can be concluded from this study that there is a true genetic compontent to CVD. Additional studies could determine if the results of this study correspond with CVD in the international population.  It may be possible for specific genes affecting vascular supply to the lower extremity can be identified with futher genetic analysis.

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