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REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
8
VOLUME 12 NUMBER 1 • JULY 2015
Novel cardiovascular risk markers in women with ischaemic
heart disease
DANA POP, ALEXANDRA D
Ă
DÂRLAT, D ZDRENGHEA
Correspondence to: Alexandra D
ă
dârlat
Dana Pop, D Zdrenghea
University of Medicine and Pharmacy Iuliu Ha
ţ
ieganu, Cluj-Napoca, Romania
e-mail:
ale_dadarlat@yahoo.comPreviously published in
Cardiovasc J Afr
2014;
25
(3): 137–141
S Afr J Diabetes Vasc Dis
2015;
12
: 8–11
Abstract
The incidence of coronary heart disease in premenopausal
women is lower than in men because of their hormonal
protection. Angina pectoris occurs in women about 10 years
later than in men. However, mortality from ischaemic heart
disease remains higher in women than in men. Current studies
are focusing on novel cardiovascular risk biomarkers because
it seems that traditional cardiovascular risk factors and their
assessment scores underestimate the risk in females. Increased
plasma levels of these newly established biomarkers of risk
have been found to worsen endothelial dysfunction and
inflammation, both of which play a key role in the pathogenesis
ofmicrovascular angina,which is very common inwomen. These
novel cardiovascular risk markers can be classified into three
categories: inflammatory markers, markers of haemostasis, and
other biomarkers.
Keywords:
ischaemic heart disease, women, new cardiovascular
risk factors
Cardiovascular disease (CVD) represents the leading cause of death
among women in Europe. About 53% of female deaths are due to
CVD, particularly coronary heart disease and stroke.
1-9
The incidence
of coronary heart disease is significantly lower in premenopausal
women, due to their hormonal protection, but there are reportedly
more complex mechanisms involved. Angina pectoris and heart
attack occur in women about 10 and 20 years, respectively, later
than in men.
5
There are significant gender-related differences concerning
coronary heart disease. The particularities regarding women are:
higher prevalence in women over 75 years, the first coronary event
is 10 years later than in men, atypical symptoms, high incidence of
non-Q-wave myocardial infarction, and the prevalence of coronary
arteries without angiographic findings is twice as common as in
men.
6
Since 2004, guidelines have been emphasising the importance
of recognising cardiovascular risk factors in women and also to
classify women at high, intermediate or ‘ideal’ cardiovascular risk.
2-4
A high-risk status is given not only by the presence of coronary
artery disease, cerebrovascular disease, chronic arterial occlusive
disease, aortic aneurysm or a Framingham score over 10%, but
also by the presence of chronic kidney disease or diabetes.
2
Women who face the threat of cardiovascular disease
present with one or more risk factors including: smoking, pro-
atherogenic diet, obesity (especially central obesity), family
history of cardiovascular disease at a young age, hypertension
and dyslipidaemia. Furthermore, it seems that subclinical vascular
disease (such as coronary calcification), the metabolic syndrome,
a low effort capacity or an abnormal heart rate recovery after
the exercise stress test creates a prominent cardiovascular risk
among women.
2
Latest studies show that women diagnosed with
collagen disease (auto-immune disease), a history of pre-eclampsia,
gestational diabetes or pregnancy-induced hypertension require
strict medical management due to their high predictive ability for
the development of cardiovascular disease.
2
Ideal cardiovascular health status is gained by women with
blood pressure below 120/80 mmHg, total cholesterol level below
200 mg/dl, fasting plasma glucose below 100 mg/dl (without
specific treatment), body mass index (BMI) below 25 kg/m
2
and,
undoubtedly, by those who practice intense physical exercise at
least 150 minutes per week, or moderate exercise for 75 minutes
per week, and by non-smoking women.
2
Review of the evidence reveals that compilation of traditional
risk factors and cardiovascular risk scores underestimates the risk
in women. Therefore, ongoing areas of research are focusing on
novel markers of cardiovascular risk. These novel cardiovascular
risk biomarkers have been selected because their increased plasma
levels worsen endothelial dysfunction and inflammation, both being
key players in the pathogenesis of microvascular angina, which is a
common phenomenon in women.
1
The Women’s Health Initiative hormone trials showed that at
least 18 new biomarkers are useful in estimating cardiovascular risk
in postmenopausal women. These are lipoprotein (a), homocysteine,
insulin, C-reactive protein (CRP), E-selectin, interleukin-6, matrix
metalloproteinase-9, fibrin D-dimer, factor VIII, plasminogen
activator inhibitor-1 antigen, prothrombin fragment 1.2, plasmin–
antiplasmin complex, thrombin-activatable fibrinolysis inhibitor, von
Willebrand factor, fibrinogen, haematocrit, leukocyte and platelet
counts.
10
These novel biomarkers of cardiovascular risk are classified
into three categories: inflammatory markers, haemostasis markers,
and other biomarkers.
Inflammatory markers
High-sensitivity C-reactive protein (hs-CRP)
The latest European guidelines on CVD prevention in clinical practice
(2012) recommend the determination of high-sensitivity CRP levels
as part of the refined risk assessment in patients with an unusual or
moderate CVD risk profile (class IIB, level B).
11
Normal values for this
inflammatory factor are below 2 mg/dl.
CRP levels in women are higher than in men, especially during
puberty.
2
The JUPITER trial reported that an hs-CRP value over
2mg/dl in associationwith a low-density lipoprotein (LDL) cholesterol
value below 130 mg/dl in women without cardiovascular pathology
increases the risk of cardiovascular events.
12
Moreover, high levels
of CRP in women without cardiovascular disease are important
predictors for the development of fatal heart attack and stroke.
13