CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 1, February 2012
AFRICA
23
Interaction between dyslipidaemia, oxidative stress and
inflammatory response in patients with angiographically
proven coronary artery disease
D TAYAL, B GOSWAMI, S TYAGI, M CHAUDHARY, V MALLIKA
Abstract
Introduction:
Coronary artery disease (CAD) is emerging as
the biggest killer of the 21st century. A number of theories
have been postulated to explain the aetiology of atherosclero-
sis. The present study attempts to elucidate the interaction, if
any, between inflammation, oxidative stress and dyslipidae-
mia in CAD.
Methods:
A total of 753 patients undergoing angiography
were evaluated and 476 were included in the study. The
parameters studied included complete lipid profile, and
apolipoprotein B, ferritin and nitric oxide (NO) levels.
Statistical analysis was carried out to determine the inter-
relationship between these parameters and the best predic-
tor of CAD risk. Cut-off points were determined from the
receiver operating characteristics curves, and the specificity,
sensitivity, positive predictive value, negative predictive value,
odds ratio and confidence intervals were calculated.
Results:
The levels of the parameters studied increased with
the stenotic state and a positive correlation was observed
between ferritin, NO and apolipoprotein B. NO emerged as
the most reliable predictor of CAD, with an area under the
curve of 0.992 and sensitivity and specificity of 97 and 98%,
respectively.
Conclusion:
Environmental and genetic risk factors for CAD
interact in a highly complex manner to initiate the athero-
sclerotic process. These risk factors should be considered
mutually inclusive, not exclusive when devising pharmaco-
logical interventions, as multi-factorial risk management is
the cornerstone of CAD management
Keywords:
nitric oxide, ferritin, apolipoprotein B, coronary
artery disease
Submitted 9/3/10, accepted 26/11/10
Cardiovasc J Afr
2012;
23
: 23–27
DOI: 10.5830/CVJA-2010-092
Coronary artery disease (CAD) is the leading cause of death in
India. Moreover, about 50% of coronary heart disease-related
deaths in India occur in people younger than 70 years of age,
compared with only 22% in the West.
1
The WHO estimated that,
over the next 10 years, India would lose 237 billion US dollars
due to heart disease, stroke and diabetes mellitus.
Factors presumed to be responsible for the higher prevalence
of CAD in India include increased central obesity, insulin resist-
ance, higher prevalence of diabetes mellitus and atherogenic
dyslipidaemia, characterised by low high-density lipid (HDL)
concentrations, increased triglycerides (TG), small dense low-
density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp
(a)] concentrations.
2
The established risk factors of CAD, such
as age, gender, cholesterol, smoking, hypertension and impaired
glucose tolerance do not account for its overall risk.
Coronary artery disease, a major cause of morbidity and
mortality, has a multi-factorial aetiology and long pre-clinical
phase that further complicates the timely identification of a
population at risk and the elucidation of molecular mechanisms
that lead to the pathogenesis of this condition. Whereas most
clinicians previously regarded an atheroma as a bland lesion,
the current notion that inflammation and immune response
contribute to atherogenesis has garnered increased interest.
3
A
picture emerges of a chronic disease that from its origin to its
ultimate complications involves inflammatory cells (T cells,
monocytes, macrophages), inflammatory proteins [cytokines,
chemokines, ferritin, C-reactive protein (CRP), etc] and inflam-
matory responses from vascular cells.
4
The present understand-
ing of atherosclerosis is that of a complex phenomenon that
encompasses the intricate interplay of dyslipidaemia, oxidative
stress and inflammation.
Serum ferritin level has been evaluated as a marker of inflam-
mation in our study. Many studies suggest the ‘iron hypothesis’
is a link between iron storage and the development of coronary
artery disease.
5-7
According to these studies, ferritin may act as a
pro-oxidant. Iron donates an electron to promote the formation
of reactive oxygen species via the Fenton reaction and this causes
oxidation of LDL, a trigger for the development of atheroscle-
rotic CAD.
6,7
Inflammation is associated with an abnormality in
the redox state in the vasculature. Oxidants, as reactive oxygen
species, release iron from ferritin either directly or through
haeme oxygenase.
8
This accelerates atherosclerosis via the
stimulation of LDL oxidation.
Nitric oxide (NO) is universally accepted as an important
regulator of vascular tone, capillary permeability and platelet
adhesion and is involved in other cellular functions. Most of the
cytotoxicity attributed to NO is due to peroxynitrite, produced
from the diffusion-controlled reaction between NO and another
free radical, the superoxide anion (ROS).
9
Under pathophysi-
ological conditions, ROS and NO react readily and therefore
the half-life of bioactive NO is reduced and reactive nitrogen
species, particularly dinitrogen trioxide and peroxy nitrite are
generated, causing significant damage to cellular components
Department of Biochemistry, GB Pant Hospital, New Delhi,
India
D TAYAL, MBBS, MD
B GOSWAMI, MBBS, MD, DNB,
M CHAUDHARY, MBBS
V MALLIKA, MBBS, MD
Department of Cardiology, GB Pant Hospital, New Delhi,
India
S TYAGI, MBBS, MD, DM
