Cardiovascular Journal of Africa: Vol 28 No 1 (January/February 2016)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 1, January/February 2017

AFRICA

Despite this abundance of parameters for diagnosing

EPACS, a million patients annually seek care in emergency,

cardiology and cardiovascular surgery departments with chest

pain or other symptoms suggesting an ACS, although only

around 10% are subsequently confirmed to have EPACS.

Therefore, emergency, cardiology and cardiovascular surgery

doctors need novel advance, accurate, fast, easily accessible

and cost-effective cardiac markers for better patient outcomes

and fewer complications.

Adropin is a peptide hormone secreted from pancreatic,

liver, brain and kidney tissues and from the endocardium,

myocardium and epicardium of the heart.

10-12

It circulates in

the blood to activate the release of nitric oxide and regulate

apoptosis and energy homeostasis,

13,14

and could be a novel

predictor of heart failure. Adropin secretion is controlled

by many factors including glucose levels and myocardial

infarction.

Decreased adropin level is an independent risk factor for

endothelial dysfunction, a key early event in atherogenesis, and

is integral to the onset of coronary artery disease (CAD) and

ACS.

It is also an independent predictor of clinically relevant

coronary atherosclerosis.

Adropin levels are significantly

lower in patients with cardiac syndrome X than in healthy

subjects, so low serum adropin level could be an independent

risk factor for this condition.

It is also closely related to

type 2 diabetes mellitus and gestational diabetes mellitus.

16,17

In addition, a recent study revealed that adropin levels were

decreased in patients with late saphenous vein graft occlusion

and it could have been causally related.

On the basis of these findings, it was hypothesised that the

adropin synthesised in the endocardium, myocardium and

epicardium

could serve as a novel biological marker for the

diagnosis and prognosis of myocardial ischaemia, because

ischaemic injury to heart muscle cells is likely to release

adropin into the bloodstream. However, there have been

contradictory reports from animal studies that examined the

association between adropin expression and isoproterenol-

induced myocardial infarction, which indicated that the

gradual increase in serum adropin levels could serve as an

alternative to troponin I measurement for diagnosing EPACS,

and human studies, showing that single-timing serum adropin

levels were lower in EPACS patients than in stable angina

pectoris (SAP) patients or controls.

This conflict needs to be resolved. Therefore, the purposes

of this study were: (1) to determine the changes in adropin

and troponin I concentrations in sera from EPACS patients;

(2) to determine whether this hormone is produced by

the three major salivary glands, parotid, sublingual and

submandibular; and (3) to determine whether saliva contains

adropin, because obtaining saliva samples is non-invasive,

making it advantageous over blood sampling.

Methods

All protocols for the human studies in this work accorded

with the principles set out (date 6/3/2014; issue no: 03) by the

Institutional Human Ethics Committee (FUIHC) and with the

ethical principles in the most recent version of the Declaration

of Helsinki. Written informed consent to participate in the study

was individually obtained.

A total of 46 subjects (22 EPACS patients and 24 controls)

were admitted to the Emergency Department at Elazig Education

and Research Hospital due to chest pain or other symptoms

(within 30–40 minutes of onset). Our hospital is conveniently

located in downtown Elazig so it can be reached from any part

of the city within 15 minutes of the first symptoms. The heart

team (cardiologists and cardiovascular surgeons) evaluated the

patients admitted, as described previously.

A diagnosis of EPACS was made by integrating the history

of the presenting illness, an increase in serum troponin I

concentration (1

upper limit of the hospital normal range),

and associated symptoms of ischaemia, chest pain and/or

characteristic ECG signs (ST-segment–T-wave changes or

development of pathological Q waves).

6-8

All patients (

22)

were screened for EPACS by coronary angiography. Healthy

volunteers (

24) having routine annual check ups (08.00–

09.00) served as controls.

The patients were treated as explained elsewhere.

Briefly,

their EPACS was treated as primary PCI (first loading dose 600

mg clopidogrel

300 mg acetylsalicylic acid/day, and maintained

on 75 mg clopidogrel

300 mg acetylsalicylic acid/day;

5), thrombolytic therapy was given (10 U reteplase

75 mg

clopidogrel

300 mg acetylsalicylic acid/day;

9), and routine

anti-anginal therapy was provided (first loading dose 600 mg

clopidogrel

300 mg acetylsalicylic acid/day, and maintained on

75 mg clopidogrel

300 mg acetylsalicylic acid/day;

8).

Exclusion criteria were: over 75 or under 50 years old,

surgery or trauma within two months of the study, known

cardiomyopathy, and family history of cardiovascular disease

(CVD) (having a father who developed CVD before 55 years of

age, a mother before 65 years, or a sibling at any age).

We defined CVD as coronary heart disease, hypertension

(hypertension was defined as resting systolic blood pressure (SBP)

≥

140 mmHg and/or diastolic blood pressure (DBP)

≥

90 mmHg

according toWHO–ISH criteria),

or on current antihypertensive

treatment, rheumatic heart disease, known malignant diseases,

febrile conditions, acute or chronic inflammatory disease, gastro-

intestinal diseases, suspected myocarditis or pericarditis, diabetes

mellitus of any type, severe heart failure, advanced renal or

hepatic disease, alcohol consumption of more than one unit per

day, no regular intense exercise (

15 min of aerobics three times

per week), and use of tobacco products (former and current).

All the study participants, including the control subjects,

underwent a standard clinical examination. Other details relevant

to the EPACS studies were described previously.

8,21

The first saliva and venous blood samples were collected

when patients were admitted to the Emergency Department

(within 30–40 minutes of onset) and before angiography. Other

samples (two, four, six, 12, 24, 48 and 72 hours) were drawn

from the antecubital veins of all participants into plain sterile

tubes for serum, and into sterile urine cups for whole resting

saliva at 08.00 hours in the Department of Cardiology. Saliva

and serum were collected simultaneously at each sampling time

after thorough rinsing of the mouth with water, as previously

described.

21,23,24

Circadian variation in the onset of EPACS has been

documented. To avoid this influence, only EPACS patients

admitted in the morning were included in this study.

Blood samples were divided into two aliquots, one for classical

biochemical parameters and the other for measuring adropin