|Year : 2019 | Volume
| Issue : 9 | Page : 1201-1207
Effect of Vitamin D and parathyroid hormone levels on the coronary slow-flow phenomenon
B Kalayci1, T Karabağ1, S Kalaycı2, YT Erten1, F Köktürk3
1 Department of Cardiology, Bülent Ecevit University Hospital, Zonguldak, Turkey
2 Department of Cardiology, Zonguldak Atatürk State Hospital, Zonguldak, Turkey
3 Department of Biostatistics, Bülent Ecevit University Hospital, Zonguldak, Turkey
|Date of Acceptance||28-Apr-2019|
|Date of Web Publication||6-Sep-2019|
Dr. B Kalayci
Department of Cardiology, Bulent Ecevit University, 61600 - Zonguldak
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The presence of vitamin D, and parathyroid hormone receptors has been demonstrated in the vascular endothelium. Variations in vitamin D, and parathyroid hormone levels may affect coronary flow and cause the coronary slow-flow phenomenon (CSF). Methods: We enrolled 93 patients who had undergone coronary angiography and had near-normal coronary arteries. Blood samples were taken to determine the calcium, phosphorus, 25-hydroxy vitamin D, and parathyroid hormone levels. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D level of less than 20 ng/mL. We divided the study population into two groups according to thrombolysis in myocardial infarction frame count (TFC) levels. Results: Patients with TFC ≤27 were in the control group (n = 39), and those with TFC >27 were in the CSF group (n = 54). 25-Hydroxy vitamin D levels were similar in both groups: 17.5 [3.3-36.1] ng/ml in the CSF group and 15.2 [5.3-34] ng/ml in the control group (P = 0.129). When we analyzed TFC for each of the coronary arteries, we found a weak negative correlation between vitamin D level and TFC of the right coronary artery in the CSF group (r = −0.314, P = 0.021). Parathyroid hormone levels were similar in both groups: 48 [16-140] pg/ml in the CSF group and 52 [25-125] pg/ml in the control group (P = 0.297). Conclusion: The study failed to demonstrate a relationship between serum parathyroid hormone level and CSF. However, a weak negative correlation was found between vitamin D level and TFC of the right coronary artery.
Keywords: 25-hydroxyvitamin D, coronary artery disease, parathyroid hormone, vitamin D
|How to cite this article:|
Kalayci B, Karabağ T, Kalaycı S, Erten Y T, Köktürk F. Effect of Vitamin D and parathyroid hormone levels on the coronary slow-flow phenomenon. Niger J Clin Pract 2019;22:1201-7
|How to cite this URL:|
Kalayci B, Karabağ T, Kalaycı S, Erten Y T, Köktürk F. Effect of Vitamin D and parathyroid hormone levels on the coronary slow-flow phenomenon. Niger J Clin Pract [serial online] 2019 [cited 2019 Nov 13];22:1201-7. Available from: http://www.njcponline.com/text.asp?2019/22/9/1201/266157
| Introduction|| |
The coronary slow-flow (CSF) phenomenon was first described by Tambe et al. in 1972. It is characterized by delayed contrast passage on angiography, without significant epicardial coronary stenosis. The incidence of CSF has been reported as 1-7% of all coronary angiograms. The causes of the CSF phenomenon can be summarized as small vessel dysfunction, endothelial dysfunction, atherosclerosis, inflammation, and anatomic factors related to the coronary vessels. The CSF phenomenon has been associated with clinical manifestations, including acute myocardial ischemia, arrhythmias, and sudden cardiac death.
Vitamin D (vit D) plays a significant role in bone metabolism and calcium homeostasis. Vitamin D receptors can be seen in many tissues, including cardiac myocytes, coronary artery smooth muscle cells, and endothelial cells. In previous studies, low vit D levels were shown to be a risk factor for cardiovascular diseases such as atherosclerosis, coronary artery calcification, coronary artery disease (CAD), hypertension, and heart failure.,
Parathyroid hormone (PTH) is a peptide secreted by parathyroid cells. It plays a role in calcium and phosphorus metabolism. Previous studies have shown that serum PTH levels are closely associated with heart failure, high blood pressure, and myocardial hypertrophy.,, The cardiovascular system may also be affected by PTH levels via pro-inflammatory pathways stimulating cytokine release from inflammatory cells. Studies on the relationship between CAD and PTH levels are inconclusive. The aim of our study was to determine the correlation between CSF and vit D or PTH levels.
| Methods|| |
Patient population and study protocol
This was an observational, cross-sectional study including 93 patients who had undergone coronary angiography for suspected stable ischemic heart disease and were found to have normal or near-normal coronary arteries, and to have slow-flow coronary artery disease on visual assessment. Demographic characteristics, body mass index (BMI), blood pressure and the following classical cardiovascular risk factors were recorded: hypertension (blood pressure >140/90 mmHg or use of an antihypertensive drug), diabetes mellitus (fasting glucose >126 mg/dL, or use of oral hypoglycemic agents or insulin), dyslipidemia (low-density lipoprotein >130 ng/dL, total cholesterol >200 ng/dL), and smoking. Medications used by patients were recorded. Vit D deficiency was defined as a serum 25-hydroxy (25(OH)) vit D level <20 ng/mL. Patients were categorized into a vit D-deficient group and vit D non-deficient group (>20 ng/dl) for categorical analysis.
Patients with previous myocardial infarction, left ventricular ejection fraction <50%, elevated serum creatinine levels, known calcium hemostasis disorder, presence of primary and secondary hyperparathyroidism, active malignancy, and recent vit D replacement therapy were excluded. Patients who had significant epicardial coronary stenosis (more than 40%) were also excluded. All patients provided written informed consent. This study was approved by the Institutional Review Board on 14 December 2015. The approval number was 33479393/44.
The study was performed at a university hospital. Blood samples were taken shortly after coronary angiography to determine complete blood count parameters, lipid profile, blood urea nitrogen, creatinine, sodium, calcium, and phosphorus, thyroid stimulating hormone, 25(OH) vit D, and PTH levels. Serum 25(OH) vit D and PTH levels were measured using a Beckman Coulter Unicel® Dxi 600 machine. To avoid seasonal variations, all blood samples were collected during the winter months (December-February). The normal range for 25(OH) vit D is 30-100 ng/mL. Vit D deficiency was defined as a serum 25(OH) vit D level less than 20 ng/mL. The normal range for PTH is 12-88 pg/mL.
Patients were selected from among individuals with stable angina and documented coronary ischemia on exercise stress test or myocardial perfusion imaging. The patients underwent coronary angiography (Siemens Artis Zee, Nuremberg, Germany) using the standard Judkins technique, with a 6 Fr Judkins diagnostic catheter. Iohexol (Omnipaque; Nycomed Ireland Ltd, Cork, Ireland) was used as the contrast agent for all coronary angiography procedures. The coronary arteries were visualized in the left and right oblique views using cranial and caudal angulation, at a rate of 15 frames/s. The dye injection speed was the same in all study patients. Nitrates were not administered in any of the study patients, as they cause significant enlargement of the artery with consequent increase in the volume to be filled with dye, thus increasing the TFC by approximately 6 frames. We also excluded patients with pacemakers, as pacing may alter epicardial flow velocity.
All of the study patients had normal or near-normal coronary arteries, defined as stenosis of 40% or less. Patients were initially assigned to the CSF or control groups according to visual assessment by a cardiologist. All coronary angiograms were interpreted by two experienced invasive cardiologists who were blinded to the patients' details. Coronary flow velocity was evaluated by the thrombolysis in myocardial infarction frame count (TFC) method as defined by Gibson et al. The CFS phenomenon was defined as a TFC greater than 27/frame. TFC was measured for each coronary vessel, corrected TFC was measured for the left anterior descending (LAD) coronary artery, and divided by 1.7 to correct for its longer length (LAD TFC). The inter-observer variability of the TFC measurement was 2.8%.
| Results|| |
The study population consisted of 93 participants with no significant coronary stenosis on coronary angiography. First, we assigned 66 patients to the CSF group and 27 patients to the control group according to visual assessment by a cardiologist. Thereafter, we measured the TFC for each patient. We then divided the study population into two groups according to the TFC. CSF was diagnosed in 54 patients. The remaining patients (n = 39) had a normal coronary flow pattern. Thus, some patients initially diagnosed with CSF were moved to the control group.
[Table 1] lists the baseline characteristics of the study population stratified by TFC. There was no statistically significant difference in hypertension, gender, BMI, waist circumference, systolic blood pressure, or diastolic blood pressure between the groups. The mean age was significantly higher in the CSF group compared to the control group (54 ± 9.5 years versus 50 ± 9.8 years; P = 0.019). The presence of diabetes mellitus, hyperlipidemia, smoking, and metabolic syndrome was significantly higher in the CSF group. Antiplatelet drugs, beta-blockers and statin usage was also more common in patients with CSF.
|Table 1: Basal and clinical characteristics of study patients accordig to coronary slow-flow phenomenon|
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Comparative analysis of laboratory parameters of all the patients in the CSF and control groups are shown in [Table 2]. The mean 25(OH) vit D level was 15.2 (5.3-34) ng/ml in the CSF group and 17.5 (3.3-36.1) ng/ml in the control group. There was no statistically significant difference between the two groups (P = 0.129). Box plot presentation comparison of the serum 25(OH) vit D level and TFC groups (CSF and control group) is shown in [Figure 1]. There was also no significant difference in vit D deficiency between the groups (P = 0.227). Mean PTH level was 52 (25-125) pg/ml in the CSF group and 48 (16-140) pg/ml in the control group (P = 0.297; [Figure 2]). There was no difference in serum calcium and phosphorus levels between the two groups; P = 0.991, P = 0.435, respectively. When we analyzed the basal and clinical characteristics according to 25(OH) vit D deficiency, we found no differences between the groups [Table 3].
|Table 2: Comparative analysis of laboratory parameters between two groups|
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|Figure 1: Box plot presentation comparison of the serum 25(OH) vitamin D level and thrombolysis in myocardial infarction frame count (TFC) groups|
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|Figure 2: Box plot presentation comparison of the Parathyroid hormone level and thrombolysis in myocardial infarction frame count (TFC) groups|
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|Table 3: Basal and clinical characteristics of study patients according to 25(OH) vitamin D deficiency|
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There was no statistically significant difference in the TFC of the LAD coronary artery, circumflex coronary artery, and right coronary artery (RCA) and the mean TFC in the vit D-deficient and vit D non-deficient groups [Table 4]. However, when we reanalyzed according to vit D levels the results were different.
|Table 4: Thrombolysis in myocardial infarction frame count of each coronary artery and vitamin D deficiency|
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Correlation analysis was performed between the value of TFC of each coronary artery, and PTH, and vit D levels in all patients in the CSF and control groups. There was no significant difference between vit D levels and the value of TFC or mean TFC of each coronary artery, except in the RCA. There was a weak and negative correlation between vit D levels and the value of TFC of the RCA in the CSF group (r = −0.314, P = 0.021). However, there was no significant difference between PTH levels and TFC of the other coronary arteries (r = −0.05, P = 0.576).
| Discussion|| |
We had thought that there might be an association between the CSF phenomenon and the serum 25(OH) vit D and PTH levels. However, in the present study we did not find a strong association between the CSF phenomenon and 25(OH) vit D and PTH levels. We did, however, demonstrate a weak and negative correlation between the vit D level and TFC of the RCA. The RCA is the most frequently involved vessel for coronary slow-flow. This may be related to the coronary artery anatomy and vascular curvature. In this study, we found a significant difference only for the RCA.
Vit D deficiency is a common health problem worldwide. To our knowledge, previous studies of the association between vit D deficiency, and the CSF phenomenon are inconclusive. The mechanisms of the cardioprotective effects of vit D are not known well. Vit D receptors have been shown in cardiomyocytes, vascular smooth muscle cells and endothelium. The association between vit D and vit D receptor stimulation-related cardiovascular disease development may be explained by its inducing the proliferation of vascular smooth muscle cells, expression of vascular endothelial growth factor, and inhibiting the proliferation of cardiomyocytes. Described mechanisms for vit D deficiency-related cardiovascular disorders include endothelial dysfunction, increased inflammation, renin-angiotensin-aldosterone system activation, and arterial calcification and stiffness. In light of these findings, we postulate that vit D deficiency may affect coronary arteries and myocardium. The association between the renin-angiotensin-aldosterone system and vit D has been shown in previous studies. Vit D directly suppresses renin gene expression, with a resultant increase in renin level in vit D deficiency. Increased renin level activates the renin-angiotensin-aldosterone system and affects blood pressure regulation. The relationship between vit D level and hypertension has previously been demonstrated. However, in this study, the presence of hypertension was similar in the CSF and control groups.
25(OH) vit D may be categorized as deficient (<20 ng/mL), insufficient (20 to 30 ng/mL) or sufficient (≥30 ng/mL). Previous studies identified vit D deficiency as a significant risk factor for atherosclerosis. Vit D deficiency was associated with an increased prevalence of CAD, heart failure, and peripheral vascular disease; endothelial dysfunction and subclinical atherosclerosis; and coronary artery ectasia. Results from the Third National Health and Nutrition Examination Survey demonstrated a strong and independent relationship between vit D deficiency and cardiovascular disease. However, the Framingham Offspring Study showed no relationship between a low vit D level and the composite endpoint of myocardial infarction, coronary insufficiency, and heart failure in normotensive patients. Furthermore, there was no correlation between vit D deficiency and severity of CAD on angiography. However, a large meta-analysis revealed a favorable effect of vit D supplementation on endothelial dysfunction. In another study, a large single dose of vit D (10,000 IU) improved endothelial function and decreased blood pressure in diabetic patients. Furthermore, several studies revealed that vit D supplementation reduced plasma renin activity, blood pressure, and myocardial hypertrophy.
The relationship between CSF and vit D level has only been investigated in one study. Oz et al. found that the incidence of CSF was significantly higher in the vit D insufficient group (vit D < 30 ng/ml) than the vit D sufficient group (≥30 ng/ml). In this study, the mean vit D level was higher than in our study (31.8 ng/ml vs 17.2 ng/ml). These results have not been confirmed by another study. In our study, we failed to demonstrate a strong association between vit D deficiency and CSF. The reason for the differing results may be related to the season. We collected all the blood samples in winter from one center in the Black Sea region, where the weather is often cloudy, and vit D deficiency is a common problem. The median vit D level was low in both groups in our study, but there was no statistically significant difference between the two groups (17.5 ng/ml, 15.2 ng/ml, P = 0.129). Oz et al. compared to the vit D sufficient and insufficient groups. A vit D level >30 ng/ml was accepted as vit D sufficient in the study of Oz et al. However, when we compared the patients with vit D deficiency and the non-deficient group, the cut-off limits were different. This may explain the different results in the two studies.
PTH receptors were shown in various locations, such as the vascular smooth muscle cells, endothelium, and myocardium. This may explain the effect of PTH on the cardiovascular system. PTH regulates blood calcium and phosphorus levels; elevated calcium may cause coronary calcification and atherosclerosis. PTH overexpression may have an effect on cardiovascular and peripheral artery disease. A previous study showed that elevated serum PTH levels may play a role in the development of CAD with normal calcium levels. However, Gronhoj et al. found no association between coronary artery calcification and serum vit D and PTH levels in both sexes. Given the current literature, we can state that the association between PTH and CAD is unclear. To our knowledge, there is no previous study describing the association between serum PTH level and coronary slow-flow. Our study showed no relationship between serum PTH levels and the CSF phenomenon.
We didn't mentioned about the type of coronary atherosclerosis in study population, single or multiple coronary artery disease. Presence of multi-vessel coronary artery disease may be affected of vit D or PTH level. It was a limitation of our study.
| Conclusion|| |
There are several limitations to this study. First, our sample size was relatively small. Second, the vit D and PTH levels were measured only once. Third, the study was conducted in a single center in one region, West Black Sea. These limitations may have affected the results. The cross-sectional and observational nature of our study does not allow us to study the longitudinal effects of vit D and PTH on coronary endothelial function. Future studies will be necessary to assess this.
In conclusion, our study does not show a strong association between CSF and vit D and the PTH levels. However, a weak and negative correlation was found between the vit D level, and TFC of the RCA in the CSF group. With the available data, it is difficult to argue that vit D and PTH have no effect on epicardial coronary flow velocity. We need to conduct further studies to evaluate the effect of PTH and vit D on epicardial coronary flow velocity.
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Conflicts of interest
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]