Cardiovascular Journal of Africa: Vol 29 No 5 (September/October 2018)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018

322

AFRICA

The role of novel atherosclerosis markers in peripheral

artery disease: is there a gender difference?

Hora

iu Com

a, Dumitru Zdrenghea, Sorin Claudiu Man, Dana Pop

Abstract

Peripheral arterial disease (PAD) represents a major public

health problem due to its high and increasing prevalence,

worldwide distribution, and significant morbidity and mortal-

ity rate. Female gender is a risk factor for PAD globally and

especially in low-income countries. In this review, we summa-

rise the present knowledge regarding the role of novel athero-

sclerosis markers in the development of PAD in women. We

discuss inflammatory markers, cytokines, cellular adhesion

molecules, markers of oxidative stress and other circulating

markers, and their role in the prediction of presence, sever-

ity and complications of PAD, with particular emphasis on

gender. Although many PAD biomarkers are indicative of

PAD in both males and females, some are strongly correlated

with the disease in females. These gender differences could be

useful for the early identification and management of PAD

in women.

Keywords:

peripheral arterial disease, biomarkers, risk factors,

gender

Submitted 11/4/17, accepted 15/3/18

Published online 20/4/18

Cardiovasc J Afr

2018;

: 322–330

www.cvja.co.za

DOI: 10.5830/CVJA-2018-023

Peripheral arterial disease (PAD) represents a major public

health problem due to its high and increasing prevalence,

worldwide distribution and significant morbidity and mortality

rates.

The prevalence of PAD increases with age, especially

in individuals over 75 years of age, in males, and subjects of

African-American ethnicity.

Figures regarding prevalence of the disease and gender

distribution vary from one study to another, depending on the

criteria used to diagnose PAD and geographical variations.

However, global data on trends in PAD prevalence between 2000

and 2010, published by Fowkes and collaborators, show that in

high-income countries, PAD prevalence is reported to be higher

in men than in women, whereas in low- and middle-income

countries, rates are slightly higher in women.

This is coupled

with the fact that in developing countries the disease generally

tends to affect younger age groups.

Female gender is a risk factor for PAD globally, especially

after the age of 65 years, with apparently higher rates in low- and

middle-income countries, whereas in high-income countries, the

male gender tends to be an independent risk factor for PAD,

as data from the same analysis show.

This difference, although

unlikely to stem from an excess of conventional atherosclerotic

risk factors in females, may be related to other unidentified

factors or even a diagnostic bias due to smaller body mass index,

atypical symptoms or longer life expectancy in women.

Geo-economical differences may stem from lifestyle differences

between developing countries and the industrialised world, with

women in the former being more exposed to smoking and

uncontrolled diabetes at a younger age. We also have to take into

consideration that major differences in healthcare expenditure, and

healthcare access between high- and low/middle-income countries,

coupled with atypical symptoms and particular anthropometric

characteristics, lead to delayed diagnosis and ill-treatment of this

disease in women from less-developed countries. Unfortunately,

all these factors contribute to female patients worldwide referring

to the physician in more advanced stages of the disease, often

presenting with critical limb ischaemia.

In terms of ethno-racial distribution, several studies have

shown that the highest prevalence of PAD of all ethnic groups is

in African-American individuals, even after adjusting for other

cardiovascular risk factors.

2,4,5

Ethnic differences are therefore

unlikely to be caused by only lifestyle differences between

individuals.

During the first year after diagnosis, patients with intermittent

claudication have a mortality rate ranging from 20 to 25%, with

a five-year survival rate of less than 30%.

7,8

This is the reason

why understanding and identifying the risk factors for the

development of this disease are of utmost importance. Although

atherosclerotic disease does not become clinically apparent until

adult life, studies have shown that the onset of the atherosclerotic

process is in childhood,

even in prenatal life.

10,11

The two main risk factors for the development of PAD in

both genders are diabetes mellitus and smoking.

As is the

case for other cardiovascular conditions, female subjects have

been under-represented in PAD clinical trials. Despite this,

it was shown that women who developed PAD were older

than their male counterparts and were more frequently obese

and dyslipidaemic.

13-15

Other research has demonstrated the

involvement of endothelial dysfunction in the pathogenesis of

PAD in women. Gardner and co-workers have shown that during

physical exercise, peripheral microcirculation is more deficient

and the arterial elasticity indices are much lower in females with

PAD compared to male subjects.

Department of Internal Medicine, Faculty of Medicine,

University of Medicine and Pharmacy; and Department of

Cardiology, Rehabilitation Clinical Hospital, Cluj-Napoca,

Romania

Hora

iu Com

a, MD

Dumitru Zdrenghea, MD, PhD

Dana Pop, MD, PhD

Department of Mother and Child, Faculty of Medicine,

University of Medicine and Pharmacy, Cluj-Napoca, Romania

Sorin Claudiu Man, MD, PhD,

claudiu.man@umfcluj.ro