The slow coronary flow (SCF) phenomenon was identified as a discrete clinical entity in 19721 in which distal opacification of the coronary artery is delayed on angiography in the absence of significant coronary artery disease. Another feature of SCF is its frequent occurrence in association with more widespread vascular abnormalities. SCF is a frequent finding in patients presenting with acute coronary syndrome, usually unstable angina.

Although some underlying etiologies such as abnormally high microvascular resistance and widespread atherosclerosis of the coronary arteries have been proposed, the exact pathophysiological mechanism of this phenomenon remains unclear. In some patients, diffuse atherosclerosis or diffuse calcifications have been identified on intravascular ultrasound.2–4 Other factors that may cause SCF are abnormalities in the coronary microcirculation, microvascular endothelial dysfunction and inflammation.5

Inflammation is controlled by various hormones and cytokines. Adipose tissue secretes a variety of adipocytokines, including leptin, adiponectin, visfatin, TNF-α, IL-6 and omentin, and it is considered an endocrine organ due to its effects on metabolism in several organs and systems.6

The inflammatory cytokine visfatin plays a key role in delayed neutrophil apoptosis in sepsis. It is highly enriched in the visceral fat of both humans and mice, and its plasma levels increase during the development of obesity,7 as well as being elevated in patients with type 2 diabetes, suggesting that measurement of plasma visfatin can be a useful tool for understanding metabolic diseases.8,9

Omentin is a recently identified adipokine that is selectively expressed in visceral adipose tissue.10,11 Recent studies have shown that omentin levels are negatively correlated with acute coronary syndrome and stable angina pectoris.12 Plasma omentin levels correlate negatively with systolic blood pressure, hemoglobin A1C, body mass index (BMI) and total cholesterol levels, and positively with HDL cholesterol.13

The relationship between plasma levels of these adipocytokines and SCF has not been investigated. We aimed to investigate the relations of visfatin and omentin plasma levels with SCF.

Forty-five consecutive patients who had undergone coronary angiography in Duzce University School of Medicine Cardiology Clinic between June 2012 and January 2013 and were found to have slow coronary flow were included in the study. Fifty-five consecutive patients with completely normal coronary arteries were recruited as the control group. The indications for coronary angiography were stable angina and positive treadmill test. Patients with a history of congestive heart failure, CAD including spasm, plaque, or ectasia, valvular heart disease, hyperthyroidism, chronic obstructive pulmonary disease and patients with acute coronary syndrome were excluded from the study. Those with a BMI of 30 or higher were considered obese. Coronary angiography was performed using the standard Judkins technique and the results were analyzed by at least two cardiologists. Slow coronary flow was defined as a corrected TIMI frame count >27 with a correction factor of 1.7 for the left anterior descending coronary artery (LAD) based upon images acquired at 30 frames/s. The study protocol was approved by the Ethics Committee of Duzce University and all subjects provided written consent.

Forty-five patients (33 men and 12 women, mean age 59.4±11.5 years) were diagnosed as having SCF. The control group was made up of 55 individuals (30 men and 25 women, mean age 57.8±9.9 years) with normal coronary vessels. The demographic and clinical characteristics of the study groups are shown in Table 1.

Rates of obesity and smoking and BMI values were significantly higher in the SCF group than in the control group (p<0.05) (Table 1). As shown in Table 2, there were no differences in laboratory variables, including white blood cell count, lipid parameters, and creatinine, between the two groups. However, hemoglobin, platelet count and mean platelet volume were higher in SCF patients than in controls (p<0.05).

Visfatin and omentin levels are summarized in Table 3. Visfatin levels were significantly higher in the SCF group (p<0.001), while omentin levels were similar between the two groups (p=0.75).

In univariate analysis, visfatin, gender, smoking, obesity, hemoglobin, platelet count and mean platelet volume were significantly correlated with SCF (Table 4). Among these, visfatin, gender and platelet counts were found to be significant predictors of SCF in multivariate logistic regression analysis (Table 5).

Adipocytokines such as leptin, resistin, visfatin and omentin are currently being investigated as potential drug targets in type 2 diabetes, lipid metabolism disorders, endothelial dysfunction and inflammatory diseases in general.

SCF is considered a variant of CAD, but its exact cause has not been fully elucidated. Several mechanisms have been proposed, including microvascular vasomotor dysfunction, diffuse atherosclerosis, small-vessel inflammation, and endothelial dysfunction.15 In this study, we aimed to investigate the relationship between coronary slow flow and the adipocytokines visfatin and omentin.

Visfatin is the most recently discovered of the family of adipocytokines and has been described as an inflammatory cytokine. Increased expression of visfatin mRNA has been observed in inflammatory conditions including atherosclerosis and inflammatory bowel disease.16 Visfatin is regarded as an inflammatory mediator, localized to foam cell macrophages within unstable atherosclerotic lesions, that potentially plays a role in plaque destabilization.17 Plasma visfatin concentrations increase in patients with overweight/obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease, and circulating visfatin level is positively associated with insulin resistance.7,9 However, the relationship between SCF and serum visfatin levels has not been investigated. Our findings show that visfatin levels is significantly higher in patients with SCF (p<0.001).

Omentin is a novel fat depot-specific adipokine that was identified in 2003 from a visceral omental adipose tissue cDNA library and has anti-inflammatory effects.18 The omentin gene is located in the 1q22-q23 chromosomal region, which has been linked to type 2 diabetes in several populations, suggesting that it may be a candidate gene for type 2 diabetes susceptibility in humans.19,20

Several clinical studies have shown that serum omentin is significantly decreased in obese patients and patients with polycystic ovary syndrome or diabetes.21,22 In addition, circulating omentin levels are negatively correlated with metabolic risk factors, including BMI, waist circumference, and insulin resistance.21,22 A negative correlation of omentin has also been shown with increased carotid intima-media thickness in patients with metabolic syndrome.23 De Souza Batista et al. showed that omentin gene expression was decreased with obesity and decreased omentin levels were associated with increasing obesity and insulin resistance.24 However, no previous studies have clarified the relationship of serum omentin with SCF.

In our study the mean plasma level of omentin was lower in the SCF group than in controls, although the difference was not statistically significant (p=0.754).

A possible limitation of the study was the small study population. The odds ratio of male gender was very large, possibly due to the small sample size. Further studies with larger study populations are required.

According to our results, the adipocytokines visfatin and omentin may play a role in the pathogenesis of slow coronary flow. In order to clarify their relationship with SCF and to investigate their potential as drug targets in endothelial dysfunction and inflammatory diseases, these molecules should be studied in larger groups.

The authors have no conflicts of interest to declare.