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Phlebology OnlineFirst, published on November 26, 2014 as doi:10.1177/0268355514560601

Original Article

Cross-sectional study on heredity and venous disorders: the end of the dominant maternal heredity dogma?

Phlebology 0(0) 1–8 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514560601 phl.sagepub.com

V Crebassa1, T Roucaute2, JJ Guex3 and FA Allaert4

Abstract Objective: To evaluate the heredity factor of the chronic venous disorders and odds ratio linked to maternal or paternal heredity. Methods: Cross-sectional epidemiological study conducted in daily practice of medical practitioners on all patients consulting them. The practitioners described the venous status of all patients consulting them and recorded the familial past history of venous disease. Results: Among 21319 patients, 60.4% have a familial history of chronic venous disorder: unilateral paternal 7.5%, unilateral maternal 40.9% and bilateral: 12.0%. Chronic venous disorder prevalence is 58.8% in the global population, 38.2% in the absence of parental history, 67.0% for unilateral paternal, 71.3% for unilateral maternal and 79.2% for bilateral (p < 0.0001). After adjustment on age and sex, results show significant (p < 0.0001) odds ratio of 3.2 for unilateral paternal, of 3.4 for unilateral maternal and of 5.6 for a history in both parents. In the context of a history in both parents, the odds ratio increased to 5.6 for women and 8.4 for men. Conclusion: This large cross-sectional study confirms the association between heredity and venous disease, but its results could call into question the maternal predominant character of the chronic venous disorder heredity.

Keywords Venous disease, heredity, gender, prevalence, odd ratio

Introduction The hereditary component of venous disease, which often appears to clinicians as self-evident, has only been documented scientifically since the early 1990s, in particular, with the work of Cornu-The´nard et al.1 Since that time, other studies have been conducted, both epidemiological2,3 and relating to the genome,4–6 but the methods of disease transmission still remain relatively poorly supported and insufficiently established. One of the problems with the investigations conducted in this area may be due to the fact that the model guiding data interpretation rests essentially on initial work1 that only related to one case-control study involving 67 patients in each group, or to epidemiological studies in which, except for a few rare cases,3 the existence of the venous disease was assessed by the patients themselves without medical control. In 2010, the Vein Consult study7 was conducted to assess the prevalence of venous disease, whether treated

or not treated, in all patients in a general medicine context, regardless of age, gender or the reason for the consultation. The study sheets included a description of the venous disease history of the parents and the results of a systematic venous clinical examination of the patients by a doctor. All of the 22,352 data items available were re-analysed from a heredity perspective in order to confirm, detail or develop previous data by drawing from significant volumes of clinically validated information.

1

Private Practice Phlebologist Montpellier, France Private Practice Geneticist Biologist, Montpellier, France 3 Private Practice Phlebologist, Nice, France 4 Chair for medical evaluation, Cenbiotech University Hospital, Dijon, France 2

Corresponding author: FA Allaert, Cen Biotech, 1 Impasse Francois Dolto, ZA Mazen, Sully, 21000 Dijon, France. Email: [email protected]

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This cross-sectional epidemiological study was conducted using a sample of 1302 French general practitioners, the representativeness of which was controlled on age and regional location. This did not involve any change in the treatment of the patients. The study took place between 07/05/2011 and 15/02/2012 and was initially conducted to determine the prevalence and the characteristics of the chronic venous disorders (CVDs) in the patients consulting their general practitioners.7 This study was approved by the French Committee on health information treatment (CCTIRS).

using patient numbers and percentages. The comparisons were conducted using variance analyses for the quantitative criteria and using chi-square tests for the qualitative criteria, or their non-parametric equivalents if the patient numbers required. The determination of odds ratios (ORs) and their 95% confidence intervals was performed as a logistic regression. The significance threshold was set at alpha ¼ 0.05. The data were recorded and analysed using the SAS statistical software package, version 9.2. In the analyses, ORs were favoured over relative risk as only ORs can be calculated in logistic regression and, as a reminder, the advantage of ORs is that they can be calculated in all types of studies, whereas relative risk cannot be calculated in case-control studies.

Patient selection

Description of the population

To observe the prevalence of CVDs, a screening questionnaire describing functional and physical signs of venous disorders was offered to all patients consulting a general practitioner over a period of 2 consecutive days of their practice, regardless of the reason for the consultation. This questionnaire was then completed by the doctor after the clinical examination of the patient. A Clinical Etiology Anatomy Physiopathology (CEAP) classification illustrated with pictures was distributed to the general practitioners in order to help them to describe the venous disorders. No exclusion criteria were involved, except if the patient was less than 18 years of age or did not wish to participate in this study.

A population of 22,352 patients consulting a general practitioner for any reason was included in the initial study, and from this population, 21,319 of the patients provided the information required for the primary endpoint of this new study. Table 1 presents the characteristics of the patients included in the study.

Methodology Nature of the study and study doctors

Data collection The study included a screening questionnaire, the first part of which was completed by the patient. The second part was completed by the doctor after assessment of the presence of any venous insufficiency and if any such insufficiency was found, assessments of its clinical stage (the ‘C’ in the CEAP classification). The ‘‘patient’’ part of the screening questionnaire described his/her social and demographic characteristics, risk factors for venous disease, family history any clinical functional and physical characteristics suggesting or indicating the existence of venous disease, and in such cases, the approach to care previously followed. The ‘‘doctor’’ part of the screening questionnaire included the clinical aspects of the CEAP classification, any treatment prescription(s) and any request(s) for specialist consultation.

Statistical analysis The quantitative variables are described using means and standard deviations and the quantitative variables

Prevalence of venous disorders and ORs according to heredity in the overall population Among these patients, 60.4% had a direct parental history of venous disorders, 7.5% unilateral paternal, 40.9% unilateral maternal and 12.0% bilateral. The prevalence of venous disorders was 58.8% among the entire population, 38.2% without direct parental history, 67.0% with unilateral paternal history, 71.3% with unilateral maternal history and 79.2% with bilateral parental history (p < 0.0001). In comparison to no family history, the OR of paternal heredity in

Table 1. Characteristics of patients included in the study (n ¼ 22352). Mean  SD Age (year) BMI (kg/m2) Sex (% female) CEAP C0: No visible or palpable signs (%) CEAP C1: Telangiectasies (%) CEAP C2: Varicose veins (%) CEAP C3: Edema(%) CEAP C4: Changes in skin (%) CEAP C5: Healed venous ulcer (%) CEAP C6: Active venous ulcer (%)

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50.8  16.7 25.4  5.0 74.4 34.5 41.9 37.4 32.9 11.1 1.5 0.5

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favour of the occurrence of venous disorders was 3.3 (2.9; 3.7) (

Cross-sectional study on heredity and venous disorders: the end of the dominant maternal heredity dogma?

To evaluate the heredity factor of the chronic venous disorders and odds ratio linked to maternal or paternal heredity...
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