Clinical Features of Chinese Coronary Heart Disease Patients with Chronic Kidney Disease

Abstract

Objectives: To investigate the prevalence of chronic kidney disease (CKD) by stage in Chinese patients with coronary heart disease (CHD) and to identify the clinical features and examine control of cardiovascular risk factors. Methods and results: Clinical data of hospitalized patients were collected by investigators in China. CKD stages were classified according to estimated glomerular filtration rate (eGFR). A total of 2509 participants with CHD were included in the final statistical analysis. The overall prevalence of CKD stage 3 and greater (eGFR of less than 60 mL/min/1.73 m²) in the CHD patients was 32.5%. As the CKD stage increased, fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high-sensitivity C-reactive protein (HS-CRP) levels all worsened. As the CKD stage became more severe, CHD patients had comorbidities such as diabetes mellitus, periphery arterial disease, and ischemic stroke, and more CHD patients had triple vessel disease increased. Even when patients received treatment of CHD and risk factors, control of cardiovascular risk factors such as SBP, DBP, FBG, and low-density lipoprotein was worsened as CKD stage became more severe over a 6-week follow-up. Conclusions: The data suggested a high prevalence of CKD in Chinese patients with CHD. Many conventional risk factors and comorbidities were correlated with high prevalence of CKD in CHD patients. Control of cardiovascular risk factors in those patients was poor.

• coronary disease
• kidney
• risk factors

INTRODUCTION

Atherosclerotic diseases are systemic diseases, which may involve coronary heart disease (CHD), periphery arterial disease (PAD), carotid atherosclerotic disease, and atherosclerotic diseases in other arteries, and are the main causes of mortality worldwide.¹ In the past years, atherosclerotic diseases, especially CHD, had been regarded as the major cause of death in the Chinese population. CHD is often accompanied by many risk factors and comorbidities such as smoking, diabetes mellitus (DM), lipid disorders, hypertension, obesity, and renal dysfunction.^2–4

Chronic kidney disease (CKD) is also one of the important health concerns and is among the leading causes of death in industrialized world.^5,6 The increased prevalence of CKD has placed an increased burden on citizens of China.^7,8 In China, CHD has been one of the most important causes of death among dialysis patients⁷ and the prevalence of CHD increases in all stages of CKD.⁹ Many evidence indicates that CHD risk was dramatically increased in individuals with even minor renal dysfunction. CKD was strongly associated with cardiovascular end-points including total mortality.¹⁰ Patients with CHD accompanied by CKD had severe clinical conditions and had higher rate of cardiovascular events.¹¹

Thus, we carried out this multicenter study to investigate the clinical features of Chinese patients with CHD and CKD and evaluated the medical treatments in those patients. It will help to provide a scientific basis for the secondary prevention of CHD accompanied by CKD in Chinese population.

METHODS

Study Subjects

This investigation was based on a large-scale epidemiological study in China with cross-sectional and longitudinal components. Clinical data of 4000 hospitalized patients were collected by investigators from several cities in China, including Beijing, Shanghai, Changsha, and Guangdong, from July to September in 2008. Patients with any of the following conditions were excluded: acute kidney injury, New York Heart Association (NYHA) class III or IV congestive heart failure, pregnancy or currently nursing, mental disorder, serious diabetes, and resultant complications (ketoacidosis or hypertensive crisis). Patients who had already received a kidney transplant or who were receiving maintenance dialysis at admission were also excluded. This study was approved by the ethics Committee of Tongji University and informed consent was obtained prior to enrolment.

Definition of CHD, Risk Factors, and Comorbidities, and Medication

Possible risk factors and comorbidities were recorded including body mass index (BMI), a smoking habit, history of lipid disorders, hypertension, DM, CHD, CKD, and ischemic stroke. CHD was confirmed by coronary angiography (CAG) with a diameter stenosis greater than 50% in at least one main coronary artery, or a history of confirmed myocardial infarction, or a history of revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass graft. PAD is defined as an ankle brachial index (ABI) of ≤0.90 in either leg, or peripheral revascularization or amputation because of PAD. Ischemic stroke included atherosclerotic cerebral infarction or cerebral embolism. DM is diagnosed by demonstrating any one of the following: fasting plasma glucose level ≥7.0 mmol/L; plasma glucose ≥11.1 mmol/L 2 h after a 75 g oral glucose load as in a glucose tolerance test; symptoms of hyperglycemia and casual plasma glucose ≥11.1 mmol/L; and glycated hemoglobin (HbA1c) ≥6.5%. Patients received therapy using insulin or oral medications for diabetes. Hypertension was diagnosed when systolic blood pressure (SBP) was not less than 140 mm Hg, diastolic blood pressure (DBP) was not less than 90 mm Hg, or patients were treated by hypotensive drugs. Lipid disorders were diagnosed when total cholesterol (TC) level was not less than 5.7 mmol/L, low-density lipoprotein (LDL) level was not less than 3.6 mmol/L, high-density lipoprotein (HDL) level was 1.04 mmol/L, or receiving treatment with antihyperlipidemic agents. Smoking history was defined by using more than one piece of cigarette per day at least 1 year. The patients in this study received standard medication such as that directed at blood pressure, glucose, and lipid lowering according to their clinical conditions.

Estimated Glomerular Filtration Rate

Renal function was assessed using estimated glomerular filtration rate (eGFR). Blood samples were collected by venipuncture after an overnight fast of at least 10 h. The serum creatinine (Scr) concentration was measured by the Jaffe method. eGFR was calculated using a new equation, developed by altering the Modification of Diet in Renal Disease (MDRD) equation, based on data obtained from Chinese CKD patients.¹² eGFR (mL/min/1.73m²) = 175 × Scr (mg/dL)^−1.234 × age (year)^−0.179 (female: ×0.79). The patients were classified into three groups according to eGFR: ≥60 mL/min/1.73 m² (CKD stages 1 and 2, according to the K/DOQI estimate of the staging of CKD¹³), <30 mL/min/1.73 m² (CKD stages 4 and 5), ≥30 mL/min/1.73 m², and <60 mL/min/1.73 m² (CKD stage 3).

Statistical Analysis

Data entry and management were performed on Epidata software, version 3.1 (Epidata Association, Odense, Denmark). Data were analyzed using the SPSS 13.0 software program (SPSS Inc., Chicago, IL, USA). Continuous variables were expressed as the mean ± SD, and categorical variables were expressed as percentage. An Independent Samples t-test was used to compare continuous variables between two groups. Differences among more than three groups were analyzed by one-way analysis of variance with multiple comparisons by least significant difference (LSD) test. Chi-square test was used to compare categorical variables between two groups. Trend test was used to compare categorical variables among three groups. Multiple logistic regression analysis, which included variables identified as statistically significant in the univariate analysis, was used to assess the independence of the association with renal dysfunction (eGFR < 60 mL/min/1.73 m²) in patients with CHD. A p value of <0.05 (which is two sided) was considered statistically significant.

RESULTS

General Characteristics

A total of 1491 participants who had not records of measurement of renal function or were not diagnosed with CHD were excluded in the final statistical analysis. There were 2509 participants with CHD who were included in the final statistical analysis. CHD patients (92.5%) were diagnosed by CAG. The average age of all these participants was 65.1 ± 10.8 years. Among these 2509 participants, 882 were female whose average age was 67.2 ± 9.7 years and 1627 were male whose average age was 64.0 ± 11.2 years. Participants included 2423 Han Chinese, 45 Hui Chinese, 20 Uygur Chinese, 4 Mongolian Chinese, and 16 Chinese of other ethnic groups. General characteristics of participants are provided in Table 1.

Table 1.  Clinical features of participants with CHD in different CKD stages.

Variables	eGFR ≥ 60 (CKD stages 1 and 2, N = 1694)	30 ≤ eGFR < 60 (CKD stage 3, N = 738)	eGFR < 30 (CKD stages 4 and 5, N = 77)	p-Value
Age (years old)	61.66 ± 10.16	71.89 ± 7.78	75.51 ± 12.00	<0.001
Sex [male, N (%)]	1223 (72.2)	371 (50.3)	36 (46.8)	<0.001
Smoking habit [N (%)]	336 (26.1)	56 (9.4)	6 (9.4)	<0.001
FBG (mmol/L)	5.88 ± 2.27	5.96 ± 2.60	6.71 ± 3.67	0.02
HS-CRP (mg/L)	5.50 ± 10.58	8.81 ± 20.06	18.31 ± 48.40	<0.001
TC (mmol/L)	4.83 ± 1.30	4.89 ± 1.38	4.76 ± 1.30	0.51
LDL (mmol/L)	2.88 ± 0.98	2.92 ± 1.06	2.96 ± 1.34	0.64
SBP (mm Hg)	130.2 ± 18.8	132.5 ± 18.3	141.0 ± 23.6	<0.001
DBP (mm Hg)	78.6 ± 10.6	76.9 ± 10.7	80.4 ± 13.0	0.001
Ischemic stroke [N (%)]	178 (10.6)	120 (16.3)	14 (18.4)	<0.001
DM [N (%)]	380 (22.5)	191 (26.0)	26 (33.8)	<0.001
PAD [N (%)]	193 (16.7)	152 (29.2)	15 (31.3)	<0.001
Triple vessel disease [N (%)]	358 (42.3)	155 (49.5)	15 (55.6)	0.01

Prevalence of CKD in Participants with CHD

The average eGFR in all participants was 72.9 ± 25.1 mL/min/1.73 m². A total of 815 participants had an eGFR of less than 60 mL/min/1.73m². The overall prevalence of CKD stage 3 and greater in the participants with CHD was 32.5%.

Clinical Features of Participants with CHD in Different CKD Stages

Table 1 suggests that as CKD stage became more severe, fasting blood glucose (FBG) level, SBP, DBP, and high-sensitivity C-reactive protein (HS-CRP) level were higher in patients with CHD. TC and LDL levels were not significantly different in spite of different CKD stages. More patients with CHD had comorbidities such as DM, PAD, and ischemic stroke as CKD stage increased (all p < 0.001). More patients with CHD had triple vessel disease as CKD stage was more severe (p = 0.01). More CHD patients with eGFR < 30 mL/min/1.73 m² had comorbidities such as DM, PAD, ischemic stroke, and triple vessel disease than those with 30 ≤ eGFR < 60 mL/min/1.73 m² had (all p < 0.05). At the same way, More CHD patients with 30 ≤ eGFR < 60 mL/min/1.73 m² had comorbidities such as DM, PAD, ischemic stroke, and triple vessel disease than those with eGFR ≥ 60 mL/min/1.73 m² had (all p < 0.05).

Even when patients received treatment, FBG, HS-CRP, and LDL levels were higher in patients with CHD accompanied by more severe CKD stages after 6-week follow-up (all p < 0.05). SBP and DBP were also higher in patients with CHD accompanied by more severe CKD stages after 6-week follow-up (both p < 0.001, see Table 2).

Table 2.  Cardiovascular risk factors in patients with CHD after 6 weeks.

Variables	eGFR ≥ 60 (CKD stages 1 and 2, N = 1694)	30 ≤ eGFR < 60 (CKD stage 3, N = 738)	eGFR < 30 (CKD stages 4 and 5, N = 77)	p-Value
HS-CRP after 6 weeks (mmol/L)	3.70 ± 13.29	3.95 ± 4.53	46.28 ± 78.24	<0.001
FBG after 6 weeks (mmol/L)	5.64 ± 1.79	5.89 ± 2.32	6.72 ± 4.38	0.03
LDL after 6 weeks (mmol/L)	2.43 ± 0.72	2.55 ± 0.83	2.77 ± 0.82	0.03
SBP after 6 weeks (mm Hg)	126.2 ± 18.0	128.9 ± 18.1	137.1 ± 23.0	<0.001
DBP after 6 weeks (mm Hg)	73.8 ± 10.6	77.7 ± 10.7	79.3 ± 12.9	<0.001

Table 3.  Odds ratios and confidence intervals of risk factors correlated with renal dysfunction (eGFR < 60 mL/min/1.73 m²) in CHD patients.

Risk factors	Odds ratio	95% Confidence interval
Older age (>70 years old)	21.30	1.47–309.59
Sex (female)	51.08	6.76–483.14
Hypertension	1.17	0.75–1.71
DM	1.27	0.86–2.02
HS-CRP	1.05	0.74–1.76
Smoking habit	1.02	0.69–1.43
Ischemic stroke	1.15	0.72–1.62

Figure 1 shows the control rate of cardiovascular risk factors in patients with CHD at baseline and after 6-week therapy of CHD and risk factors. Blood pressure control rate including SBP and DBP (SBP < 125 mm Hg and DBP < 75 mm Hg) was poorer as CKD stage was more severe at baseline. Control rate of FBG and LDL (FBG < 6.1 mmol/L, LDL < 2.6 mmol/L) was not significantly different in patients with different CKD stages at baseline. Even when patients received treatment of CHD and risk factors, control rate of SBP and DBP was poorer as CKD stage became more severe over a 6-week follow-up period. Control rate of other cardiovascular risk factors such as FBG and LDL worsened as CKD stage was more severe over a 6-week follow-up period.

Figure 1.  Cardiovascular risk factor control rate in CHD patients at baseline and after 6-week therapy were classified into three groups according to eGFR: ≥60 mL/min/1.73 m² (CKD stage 1–2), <30 mL/min/1.73 m² (CKD stage 4–5), ≥30 mL/min/1.73 m², and <60 mL/min/1.73 m² (CKD stage 3). Control rate of SBP and DBP (SBP < 125 mm Hg, DBP < 75 mm Hg) was poorer as CKD stage was more severe at baseline (40.5% vs. 33.3% vs. 25.3%, p < 0.001; 35.7% vs. 41.0% vs. 30.7%, p = 0.02). Control rate of FBG and LDL (FBG < 6.1 mmol/L, LDL < 2.6 mmol/L) was not significantly different in patients with different CKD stages at baseline (72.6% vs. 73.3% vs. 64.8%, p = 0.31; 40.9% vs. 40.2% vs. 44.7%, p = 0.75). SBP and DBP control rate was poorer as CKD stage was more severe after 6-week therapy (43.8% vs. 36.2% vs. 30.7%, p < 0.001; 48.5% vs. 41.7% vs. 32.0%, p < 0.001). Control rate of FBG and LDL was also poorer as CKD stage was more severe after 6-week therapy (78.2% vs. 73.2% vs. 55.0%, p = 0.02; 62.0% vs. 55.8% vs. 37.5%, p = 0.03).

Multiple logistic regression analysis included variables identified as statistically significant in the univariate analysis and was used to assess the independent risk factors correlated with renal dysfunction (eGFR < 60 mL/min/1.73 m²) in CHD patients. Finally, factors including older age (>70 years old), gender (female), hypertension, DM, HS-CRP, smoking, and ischemic stroke were included in the multiple logistic regression analysis. The results indicated that older age (>70 years old) and female gender were independent risk factors correlated with renal dysfunction in CHD patients (Table 3).

DISCUSSION

Previous study suggested that CKD was a significant risk factor for all cardiovascular end points.¹⁰ Patients with CHD and CKD had severe clinical conditions and a higher rate of cardiovascular events. Since CKD has become an important public health challenge in China,⁸ a study of the clinical features of Chinese patients with CHD and CKD will help to improve the therapy in these patients in China.

The MDRD equation was recommended for estimating GFR in adults. However, ethnicity effects occurred when using this equation.^13,14 A new equation for estimating GFR was developed by modifying the MDRD equation based on data from Chinese CKD patients, offering significant advantages categorizing different CKD stages when applied to the Chinese population.¹⁵

A study in the Chinese population suggested that prevalence of 34.1% of CKD stage 3 and greater in 3423 patients who were at least 50 years old and had a history of CHD, stroke, PAD, or with two or more cardiovascular risk factors.¹⁶ Another study indicated that 2310 Chinese patients with metabolic syndrome and at least 40 years old had a higher prevalence of CKD (15.4%; CKD was defined as albuminuria and of an eGFR 60 mL/min/1.73 m²).¹⁷ In a multicenter study carried out in outpatient clinics belonging to cardiology, internal medicine, and endocrinology departments, Cases Amenós A and his colleagues¹⁸ found that prevalence of CKD (an eGFR 60 mL/min/1.73 m²) in 2608 patients with or at a high risk of cardiovascular disease was 37.4%. In this study, the overall prevalence of CKD stage 3 and greater in the patients with CHD was 32.5%, which was very high perhaps because more patients with CHD had hypertension or DM which can lead to kidney injury. High prevalence of CKD in CHD patients should be cared by cardiologists because lots of contrast agents are used in CHD patients these years due to CAG and PCI which may cause or aggravate renal impairment.

Research over the past decade had led to the current understanding of atherosclerosis as an inflammatory disease that occurs in response to endothelial dysfunction.^19,20 C-reactive protein (CRP), an acute-phase reactant synthesized in the liver in response to the cytokine interleukin-6, is also a factor in the development of atherosclerotic plaque and plays an active role in atherogenesis.²¹ Many studies suggested that CRP levels were a marker of atheromatous plaque vulnerability and CHD activity and could predict future cardiovascular events.^22,23 This study indicated that patients with CHD and CKD had higher HS-CRP levels which may manifest severe atheromatous plaque vulnerability and CHD activity and further would predict more future cardiovascular events. More patients with CHD and CKD also had comorbidities such as PAD and ischemic stroke and had triple vessel disease which means more extensive systemic atherosclerosis and severe coronary occlusion. The above-mentioned data suggested that patients with CHD and CKD may have worse clinical conditions and poorer prognosis than CHD patients without CKD.

Multiple logistic regression analysis suggested that older age and female gender were correlated with the high prevalence of CKD in Chinese patients with CHD. Many other studies suggested that GFR decreased with increasing age. High blood pressure and DM might cause renal function damage,²⁴ but was not included as the independent factors associated with CHD and CKD in this Chinese population. This discrepancy could be because patients included in this study received medications.

Many risk factors had been confirmed as major independent predictors of CHD, with their modification reducing cardiovascular risk. High risk-factor levels and a low level of intervention on those risk factors lead to higher mortality rate in patients with CHD. The most important modifiable cardiovascular risk factors are dyslipidemia (particularly low HDL cholesterol), smoking, hypertension, DM, and central obesity, which should be addressed to prevent adverse cardiovascular events.²⁵ Our study indicated that risk factor control such as blood pressure levels, blood sugar, and LDL was very poor in Chinese patients with CHD with severe stage CKD in this Chinese population even when they received treatment. It is then reasonable to speculate that Chinese patients with CHD and CKD will suffer from higher risk for adverse cardiovascular events. Many studies suggested that CRP levels could predict cardiovascular events. In patients with eGFR < 30 mL/min/1.73 m², there was substantial increase in CRP levels after 6 weeks. It might mean that patients with CHD and severe CKD would have worse prognoses even when they received treatment.

China and other economically developing countries have experienced a cardiovascular epidemic in recent decades, with cardiovascular morbidity and mortality predicted to increase yet further in China.²⁶ CKD aggravates the prognosis of patients with CHD and the therapy provided these were inadequate. The findings of our study point to the urgent necessity for more comprehensive measures to diagnose, and control disease in these patients which will help to ease the financial burden of chronic disease on China’s limited health care.

ACKNOWLEDGMENTS

The authors are grateful to subjects participated in the study and to physicians for their assistance with subject recruitment.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.