Abstract
Background
Several studies have reported on the circadian variation in acute coronary syndrome (ACS) onset. The influence of morning blood pressure surge, platelet aggregation and sympathetic activity is believed to cause this circadian variation. At the same time, a high frequency of ACS and sympathetic nerve hyperactivity has been reported in chronic kidney disease (CKD). Therefore, we investigated the relationship between CKD and the circadian variation in ACS.
Methods
This study included 460 consecutive patients undergoing primary percutaneous coronary intervention for ACS between 2003 and 2009. Patients undergoing hemodialysis were excluded. The subjects were divided into two groups according to the value of estimated glomerular filtration rate (eGFR): CKD group [eGFR≤60 ml/min/1.73 m 2 by Modification of Diet in Renal Disease (MDRD) equation] and No CKD group (eGFR>60 ml/min/1.73 m 2 by MDRD equation). Clinical and angiographic characteristics, as well as the time distribution of ACS, were compared between the two groups.
Results
There were no significant differences in clinical and angiographic characteristics between the two groups. A significant increase in morning coronary events was observed in the No CKD group. This increase was absent in the CKD group.
Conclusions
The existence of CKD affected the circadian variation associated with the more frequent ACS onset observed in the No CKD group patients. Probably, these data may suggest the cause of frequent cardiovascular events in CKD patients
1
Introduction
Several studies have reported on the circadian variation in acute coronary syndrome (ACS) onset . The Multicenter Investigation of Limitation of Infarct Size study investigators observed that the frequency of pain onset increased significantly between 6:00 a.m. and noon and that the incidence of myocardial infarction during this 6-h period was 1.28 times greater than that during the other three 6-h intervals of the day ( P <.01) . The reason for such circadian variation was only partially clarified .
On the other hand, mild to moderate renal dysfunction, defined as chronic kidney disease (CKD), has been reported as a risk factor for both new and recurrent cardiovascular disease for people at increased cardiovascular disease risk and also for the general population . In recent years, it was demonstrated that sympathetic nervous system hyperactivity is very common in CKD patients . This may contribute to target organ damage and adverse clinical outcomes, independent of blood pressure .
In addition, some studies have reported on decreased circadian rhythm at ACS onset among CKD patients .
The aim of this study was to investigate the relationship between CKD and the circadian variation in ACS onset.
2
Methods
2.1
Subjects
The study population comprised 552 consecutive ACS patients admitted to our institute from January 2003 to December 2009. The presence of unstable angina (uAP) was determined by chest pain within the preceding 72 h with or without ST-T wave changes and by crescendo angina of recent onset (usually within 1 month). The presence of ST-segment elevation myocardial infarction (STEMI) was determined by ≥30 min of continuous chest pain, a new ST-segment elevation ≥2 mm on at least two contiguous electrocardiographic leads. The presence of non-ST-segment elevation myocardial infarction (NSTEMI) was diagnosed by chest pain and a positive cardiac biochemical marker without new ST-segment elevation. During this period, there were 68 patients who had no coronary stenosis and were considered to have vasospastic angina pectoris after coronary angiogram. We excluded them from this study. Operation rate of percutaneous coronary intervention (PCI) was 85%. There were 12 patients with suspected ACS, but they arrived at the hospital with shock state and could not receive coronary angiogram.
Patients were divided into two groups with or without CKD, which was defined as an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m 2 and/or proteinuria. We excluded those receiving hemodialysis or having renal insufficiency as stage 5 CKD ( n =12).
Finally, the numbers of each subject were as follows: uAP, 166; STEMI, 80 and NSTEMI, 214.
Estimated GFR was calculated by the simplified, recalculated equation derived from the Modification of Diet in Renal Disease GFR . We used the modified National Kidney Foundation classification of CKD . In this study, only stage 3–4 patients were included in the CKD group.
Diabetes mellitus was defined by treatment with oral hypoglycemic agents or insulin and a fasting blood sugar level >120 mg/dl irrespective of treatment. Hypertension was defined as a history of hypertension for >1 year that required the initiation of antihypertensive therapy. Hypercholesterolemia was defined as total cholesterol ≥220 mg/dl.
Ethical review board approval from our hospital was obtained, and all subjects provided signed informed consent.
2.2
Clinical history and time of ACS onset
Physical examinations were carefully conducted by trained cardiologists at the time of arrival of the patients at our institute. Degree of congestive heart failure was classified according to the Killip classification. Cardiologists interviewed patients to determine clinical history and identified the time of initial onset of chest pain. Time onset of uAP was defined as when symptoms occurred suddenly. The hourly frequency of ACS onset was divided into four periods, each of 6-h duration (0:00–6:00, 6:00–noon, noon–18:00, 18:00–0:00).
2.3
Angiographic analysis
All patients received emergency coronary angiography. Angiographic data for patients were obtained from the cardiac catheterization laboratory records. The degree of perfusion was evaluated according to Thrombolysis In Myocardial Infarction (TIMI) criteria .Coronary artery stenosis of >50% was considered clinically significant .
2.4
Statistical analysis
Results were expressed as mean±S.D. for continuous variables. Qualitative data were presented as numbers (percentages). Continuous variables were compared using the t test, and categoric test was used for compared with Fisher’s Exact Test. Analysis of variance was used in comparing the frequency of ACS onset for each 6-h period for all patients and across each group. A P value of <.05 was considered statistically significant. To identify the independent factors associated with the frequency of ACS onset, statistical adjustment was done about baseline characteristics. All statistical studies were carried out with the SPSS program (version 15.0, SPSS, Chicago, IL, USA).
2
Methods
2.1
Subjects
The study population comprised 552 consecutive ACS patients admitted to our institute from January 2003 to December 2009. The presence of unstable angina (uAP) was determined by chest pain within the preceding 72 h with or without ST-T wave changes and by crescendo angina of recent onset (usually within 1 month). The presence of ST-segment elevation myocardial infarction (STEMI) was determined by ≥30 min of continuous chest pain, a new ST-segment elevation ≥2 mm on at least two contiguous electrocardiographic leads. The presence of non-ST-segment elevation myocardial infarction (NSTEMI) was diagnosed by chest pain and a positive cardiac biochemical marker without new ST-segment elevation. During this period, there were 68 patients who had no coronary stenosis and were considered to have vasospastic angina pectoris after coronary angiogram. We excluded them from this study. Operation rate of percutaneous coronary intervention (PCI) was 85%. There were 12 patients with suspected ACS, but they arrived at the hospital with shock state and could not receive coronary angiogram.
Patients were divided into two groups with or without CKD, which was defined as an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m 2 and/or proteinuria. We excluded those receiving hemodialysis or having renal insufficiency as stage 5 CKD ( n =12).
Finally, the numbers of each subject were as follows: uAP, 166; STEMI, 80 and NSTEMI, 214.
Estimated GFR was calculated by the simplified, recalculated equation derived from the Modification of Diet in Renal Disease GFR . We used the modified National Kidney Foundation classification of CKD . In this study, only stage 3–4 patients were included in the CKD group.
Diabetes mellitus was defined by treatment with oral hypoglycemic agents or insulin and a fasting blood sugar level >120 mg/dl irrespective of treatment. Hypertension was defined as a history of hypertension for >1 year that required the initiation of antihypertensive therapy. Hypercholesterolemia was defined as total cholesterol ≥220 mg/dl.
Ethical review board approval from our hospital was obtained, and all subjects provided signed informed consent.
2.2
Clinical history and time of ACS onset
Physical examinations were carefully conducted by trained cardiologists at the time of arrival of the patients at our institute. Degree of congestive heart failure was classified according to the Killip classification. Cardiologists interviewed patients to determine clinical history and identified the time of initial onset of chest pain. Time onset of uAP was defined as when symptoms occurred suddenly. The hourly frequency of ACS onset was divided into four periods, each of 6-h duration (0:00–6:00, 6:00–noon, noon–18:00, 18:00–0:00).
2.3
Angiographic analysis
All patients received emergency coronary angiography. Angiographic data for patients were obtained from the cardiac catheterization laboratory records. The degree of perfusion was evaluated according to Thrombolysis In Myocardial Infarction (TIMI) criteria .Coronary artery stenosis of >50% was considered clinically significant .
2.4
Statistical analysis
Results were expressed as mean±S.D. for continuous variables. Qualitative data were presented as numbers (percentages). Continuous variables were compared using the t test, and categoric test was used for compared with Fisher’s Exact Test. Analysis of variance was used in comparing the frequency of ACS onset for each 6-h period for all patients and across each group. A P value of <.05 was considered statistically significant. To identify the independent factors associated with the frequency of ACS onset, statistical adjustment was done about baseline characteristics. All statistical studies were carried out with the SPSS program (version 15.0, SPSS, Chicago, IL, USA).
3
Results
Of the 460 patients, 122 patients were assigned to the CKD group. The remaining 338 patients made up the No CKD group. The baseline characteristics of both groups are listed in Table 1 . Patients in the CKD group were more likely to be male and to be older, and more commonly had hypertension and diabetes. There was no difference in medication between both groups [aspirin, angiotensin-converting enzyme inhibitor (ACE-I), angiotensin receptor blocker (ARB), β-blocker and statin]. Table 2 lists the laboratory data of the patients. Estimated GFR and hemoglobin levels were lower in the CKD group, and peak creatine kinase levels were similar in both groups (810±468 vs. 790±480; CKD vs. No CKD; P =.38). Angiographic characteristics are depicted in Table 3 . Left ventricular ejection fraction was similar in both groups (41.2±29.5 vs. 40.6±30.3; CKD vs. No CKD; P =.46). The location of culprit lesions, number of diseased vessels, preprocedural and postprocedural TIMI flow grade, and procedural success were also similar between groups (94% vs. 92%; CKD vs. No CKD; P =.62).
| Variables | CKD group n =122 | No CKD group n =338 | P value |
|---|---|---|---|
| Age (years) | 70±9.5 | 63±10.5 | .04 |
| Men | 88(72%) | 209(62%) | .03 |
| Hypertension | 51(42) | 108(32) | .04 |
| Hypercholesterolemia | 41(34) | 108(32) | .85 |
| Diabetes mellitus | 44(36) | 95(28) | .03 |
| Current smoker | 39(32) | 115(34) | .75 |
| Killip>1 | 6(5) | 24(7) | .87 |
| Medication | |||
| Aspirin | 19(16) | 46(14) | .12 |
| ACE-I and ARB | 42(34) | 98(29) | .07 |
| β-Blocker | 15(12) | 29(9) | .23 |
| Statin | 31(25) | 76(22) | .32 |
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