http://informahealthcare.com/ceh ISSN: 1064-1963 (print), 1525-6006 (electronic) Clin Exp Hypertens, Early Online: 1–6 ! 2015 Informa Healthcare USA, Inc. DOI: 10.3109/10641963.2015.1036062
The impact of metabolic syndrome and hypertension on medical costs of patients with acute myocardial infarction at hospital Guan-Qi Fan1,2, Kai-Li Fu1,2, Ming Song1,2, Lu Han1,2, Cheng-Wei Jin1,2, Ming Zhong1,2, Yun Zhang1,2, Wei Zhang1,2, and Zhi-Hao Wang1,3 1
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, and 3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Ji’nan, P.R. China
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Abstract
Keywords
Objective: This study aimed to find out the impact of metabolic syndrome (MS) and hypertension on medical costs of patients with acute myocardial infarction (AMI) at hospital. Methods: Patients with AMI at Qilu Hospital of Shandong University during January 2011 to May 2013 were separated into four groups according to whether with MS or history of hypertension. Comparison of medical costs, complication rate and cost-effectiveness ratio were analyzed. Results: We found that total costs, each day costs, medical treatment costs, chemical examination costs and drug costs were significantly different in four groups. In variance analysis, MS led to high medical costs without significance. Hypertension was a significant factor influencing medical costs and lead to low medical costs. In multiple linear regression, we found that body mass index (BMI) and percutaneous coronary intervention (PCI) were important predictors of total costs and each day costs. With higher BMI and utilization rate of PCI, medical costs were increased. Trend of total costs in four groups is similar to that of the rate of PCI utilization. Conclusions: Metabolic syndrome has no impact on medical costs because of discordance in MS components. Hypertension will lead to lower PCI utilization rate, which results in less medical costs and bad hospital outcomes.
Acute myocardial infarction, hypertension, metabolic syndrome, medical costs
Introduction With the changes of lifestyle and eating habits, prevalence of metabolic syndrome (MS) is rapidly increasing in developing countries. This study shows that the age-standardized prevalence of MS is 9.8% in men and 17.8% in women among adults in China (1). All of the components constituting MS are risk factors of cardiovascular disease (CVD). MS is associated with an increased risk of CVD, CVD mortality and all-cause mortality (2). It is not clear that whether the risk of MS on CVD is greater than the risk conferred by the sum of individual component risk factors. A research suggests that the MS-related CVD risk is more than that of the sum of its parts in subjects with MS, with or without type 2 diabetes (3). In a large-scale, multi-ethnic, international investigation of MS, the clustering of 3 risk factors with subthreshold values is associated with an increased risk of myocardial infarction compared with having component factors with ‘‘normal’’ values (4). Among stable coronary artery disease patients in the COURAGE trial, the presence of MS identifies an increased risk for death or Correspondence: Zhi-Hao Wang, Department of Geriatric Medicine, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji’nan 250012, P.R. China. Tel: +86 531 82169339. Fax: +86 531 86169356. E-mail: [email protected]
History Received 5 January 2015 Revised 16 February 2015 Accepted 2 March 2015 Published online 15 June 2015
myocardial infarction, but MS has no independent prognostic significance after adjusting for its constituent components (5). In the COURAGE trial, the most consistent predictors of developing an adverse outcome were low high-density lipoprotein (HDL) cholesterol and hyperglycemia. However, whether MS and its components influence the medical costs of CVD patients is not studied. A survey in elderly individuals with MS shows abdominal obesity, low high-density lipoprotein (HDL) cholesterol, and hypertension but not the MS per se is important predictors of long-term costs (6). Acute myocardial infarction (AMI) is the most dangerous and emergent disease in the CVD, leading to a big economic burden. MS is associated with an increased risk of AMI (2), but whether it increases economic burden in AMI patients is not reported. It is investigated that AMI patients with MS have more stents implantation, bigger infarcted area and higher heart failure rate (7,8), which may lead to bad prognosis and increasing medical costs. It is worthwhile to study whether the increasing costs benefits AMI patients. A case-control study shows the association with myocardial infarction by the MS is similar to that of diabetes and hypertension, and significantly stronger than that of the other component risk factors (4). To study the impact of MS, with or without hypertension, we analyze medical costs, complication rate and cost-effectiveness in AMI patients at
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Qilu Hospital of Shandong University during January 2011 to May 2013.
Methods Ethics statement This research had been approved by the ethics committee of Qilu Hospital of Shandong University. Written informed consent was given by participants for their clinical records to be used in this study. All data were anonymized and de-identified prior to the analysis.
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Information of case files collection Consecutive patients with discharge diagnosis of AMI at Qilu Hospital of Shandong University during January 2011 to May 2013 were included. Patients with subacute myocardial infarction were excluded. In total, 988 patients were included. Information of case files included admission number, sex, height, weight, admitting diagnosis, discharge diagnosis, hospital stays, hospital costs, history of smoking, past medical illness, family medical history, laboratory examination, coronary arteriography, ultrasound cardiograph, complications and drug treatment. Diagnosis of AMI and hypertension According to WHO diagnostic criteria for AMI, we defined patients with AMI comply with two items of the following three components or all: typical clinical manifestation, distinctive ECG change and dynamic changes of serum cardiac markers. We defined patients with hypertension when the SBP 140 mmHg and (or) DBP 90 mmHg without antihypertensive treatment or when there is a diagnostic hypertension history with antihypertensive treatment.
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patients with hypertension and without MS (Group H, n ¼ 241), patients with MS and without hypertension (Group MS, n ¼ 79), patients with MS and hypertension (Group MS&H, n ¼ 309). Statistical analysis All analyses were conducted using SAS version 9.2 (SAS Institute Inc, Cary, NC, USA) unless otherwise stated, with p50.05 considered statistically significant. Results are expressed as means ± SD or as proportions (%). For categorical variables, the 2 test and the Fisher exact probability test were used. Variance analysis was used to study impact of the MS and hypertension on hospital stays and costs. Multiple linear regression using stepwise method was performed to examine predictors of medical costs. Cost-effectiveness analysis Calculate formula of cost-effectiveness ratio (CER): CER ¼
P C
P: rate of complication, C: mean of total costs. Calculate formula of incremental cost-effectiveness ratio (ICER): DP P1 P0 ICER ¼ ¼ DC C1 C0 P1: rate of complication in patients with percutaneous coronary intervention (PCI); C1: mean of total costs in patients with PCI; P0: rate of complication in patients without PCI; C0: mean of total costs in patients without PCI.
Results Baseline data
Definition of MS Chinese Diabetes Society (CDS) criterion: comply with three items of the following four components or all: (1) overweight and (or) obesity: BMI 0.25 (kg/m2); (2) hyperglycemia: FPG 6.1 mmol/L and PPG 7.8 mmol/L, and (or) the cases with diagnosed diabetes mellitus receiving treatment; (3) hypertension: SBP/DBP 140/90 mmHg, and (or) the cases with diagnosed hypertension receiving treatment; (4) lipids disorder: TG 1.7 mmol/L, and (or) HDL-C 5 0.9 mmol/L (male) or 51.0 mmol/L (female). General approaches to treatment Approaches to treatment of AMI were mainly according to 2011 and 2012 ECS guidelines for the management of AMI. Approaches to treatment of hypertension were mainly according to the Chinese Hypertension Prevention Guide (2011 revision). Approaches to treatment of MS were control of existing MS components, such as interventions of obesity, lowering serum lipids and control of serum glucose.
A total of 988 cases were included in this study. Significant differences were found between different MS–hypertension categories regarding sex, BMI, blood pressure, smoking history, serum glucose, blood lipids and renal function related biochemical indicator (Table 1). Medical costs Table 2 shows the variance analysis results of medical costs of AMI patients in the different MS–hypertension categories. We found that total costs, each day costs, medical treatment costs, chemical examination costs and drug costs were significantly different in four groups. Surprisingly, group MS had the highest total costs and each day costs; and group H had the lowest total costs and each day costs. To study which one of the two factors, MS and hypertension, significantly influenced medical costs, we performed variance analysis. Taking total costs as dependent variable, we found that hypertension was a significant factor which led to a low total cost. Taking medical treatment costs as dependent variable, the results accorded with that of total costs.
Grouping According to CDS criterion and hypertension history, all AMI patients were separated to four MS–hypertension categories: patients without MS or hypertension (control, n ¼ 359),
Major cardiovascular events Table 3 shows the rate of complications and event-free survival at hospital in different MS–hypertension categories.
Hypertension lead to lower PCI rate and less medical costs
DOI: 10.3109/10641963.2015.1036062
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Table 1. Comparison of baseline characteristics of AMI patients in different MS–hypertension categories.
Age (years) Male sex, n (%) BMI (kg/m2) SBP (mmHg) DBP (mmHg) HR (min1) Smoking history, n (%) Laboratory examination Cho (mmol/L) TG(mmol/L) HDL (mmol/L) LDL (mmol/L) NEFA (mmol/dL) PLIP (mmol/dL) Glu (mmol/L) AST (U/L) BUN (mmol/L) Cr (mmol/L) Cys-c (mg/L) UA (mmol/L) K (mmol/L) Urine protein, n (%) Treatment PCI, n (%) Twice revascularization, n (%) Beta blocker, n (%) ACEI, n (%) ARB, n (%) Statins, n (%) CCB, n (%) Diuretic, n (%)
Control (n ¼ 359)
Hypertension (n ¼ 241)
MS (n ¼ 79)
MS–hypertension (n ¼ 309)
p
62.06 ± 13.80 279 (77.7) 24.05 ± 3.70 122.93 ± 17.46 72.17 ± 10.88 75.73 ± 15.94 190 (52.9)
69.82 ± 11.64 150 (62.2) 23.34 ± 3.91 135.86 ± 21.66 76.10 ± 13.31 77.62 ± 16.15 102 (42.3)
59.11 ± 12.09 62 (78.5) 26.95 ± 2.56 130.82 ± 22.87 77.56 ± 13.87 77.75 ± 13.24 45 (57.0)
63.93 ± 12.49 199(64.4) 27.35 ± 3.07 136.15 ± 21.79 79.19 ± 13.86 78.75 ± 16.21 139(45.0)
50.001 50.001 50.001 50.001 50.001 0.102 0.017
4.45 ± 1.15 1.34 ± 1.00 1.15 ± 0.27 2.77 ± 0.96 63.54 ± 34.90 2.18 ± 0.44 5.93 ± 2.15 91.06 ± 118.17 4.99 ± 2.19 72.53 ± 18.66 1.01 ± 0.31 299.15 ± 97.79 4.06 ± 0.47 8 (2.7)
4.53 ± 1.03 1.15 ± 0.43 1.18 ± 0.22 2.81 ± 0.82 67.38 ± 28.29 2.17 ± 0.44 5.84 ± 3.14 70.50 ± 95.87 5.85 ± 4.06 84.12 ± 74.92 1.16 ± 0.65 305.36 ± 93.81 3.98 ± 0.47 17 (8.6)
4.78 ± 1.24 1.99 ± 1.01 1.00 ± 0.24 3.05 ± 0.95 71.19 ± 40.80 2.32 ± 0.69 8.46 ± 3.12 68.42 ± 95.82 5.07 ± 1.98 68.34 ± 15.01 0.93 ± 0.23 303.96 ± 84.27 4.04 ± 0.37 2 (3.1)
4.74 ± 1.20 1.97 ± 1.13 1.03 ± 0.23 2.97 ± 0.94 67.11 ± 31.94 2.30 ± 0.50 7.21 ± 2.63 75.13 ± 118.60 6.23 ± 3.84 90.82 ± 75.47 1.19 ± 0.69 328.10 ± 99.34 4.09 ± 0.58 31(12.3)
0.004 50.001 50.001 0.01 0.482 0.025 50.001 0.084 50.001 50.001 50.001 0.001 0.06 50.001
168(54.4) 21(6.8) 262(84.8)b 123(39.8) 163(52.8)a,c 290(93.8) 110(35.6)a,c 102(33.0)a
50.001 0.186 0.016 0.495 50.001 0.159 50.001 50.001
222 20 279 148 93 327 41 77
(61.8)b (5.6) (77.7) (41.2) (25.9) (99.4) (11.4) (21.4)
107 7 181 100 113 220 79 84
(44.4) (2.9) (75.1) (41.5) (46.9)a,c (91.3) (10.4)a,c (34.9)a
54 6 67 39 18 77 11 16
(68.4)b (7.6) (84.8) (49.4) (22.8) (97.5) (13.9) (20.2)
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; Cho, cholesterol; TG, triglyceride; HDL, highdensity lipoprotein; LDL, low-density lipoprotein; NEFA, non-esterified fatty acids; PLIP, phospholipids; Glu, glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Cr, creatinine; Cys-c, cysteine; UA, uric acid; PCI, percutaneous coronary intervention; ACEI, angiotensin converting enzyme inhibitor; ARB, adrenergic receptor binder; CCB, calcium channel blocker. a p50.05 compared with control; bp50.05 compared with hypertension; cp50.05 compared with MS.
Table 2. Comparison of hospital costs of AMI patients in different MS–hypertension categories.
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Total costs (10 RMB) Each day costs (103RMB) Medical treatment costs (103RMB) Chemical examination costs (103RMB) Drug costs (103RMB)
Control (n ¼ 359)
Hypertension (n ¼ 241)
MS (n ¼ 79)
MS–hypertension (n ¼ 309)
p
p1
p2
p3
49.38 ± 29.41 5.08 ± 5.54 17.26 ± 24.47 1.85 ± 1.03 12.61 ± 7.85
43.76 ± 31.21 4.36 ± 4.40 13.89 ± 22.76 2.02 ± 1.22 13.28 ± 10.17
52.15 ± 31.12 5.55 ± 5.37 20.80 ± 26.03 1.85 ± 0.83 12.17 ± 7.41
47.99 ± 33.44 4.91 ± 5.02 15.50 ± 24.57 1.97 ± 1.27 13.07 ± 8.91
50.001 50.001 50.001 50.001 50.001
0.139 0.185 0.16 0.755 0.624
0.039 0.078 0.018 0.087 0.237
0.759 0.919 0.6 0.742 0.871
p: significance of corrected model; p1: significance of MS; p2: significance of hypertension; p3: significance of MS–hypertension interaction.
We found significant difference of acute heart failure and event-free incidence in different MS–hypertension categories. To be analogous with medical costs, group H had the highest acute heart failure incidence and lowest event-free incidence. Predictors of medical costs To study the main predictors of medical costs, we run multiple linear regression using stepwise method. Results showed that BMI (b ¼ 0.488, p50.001), PCI (b ¼ 0.311, p50.001), twice revascularization (b ¼ 0.132, p50.001), ventricular arrhythmia (b ¼ 0.079, p ¼ 0.003), urine protein (b ¼ 0.088, p ¼ 0.001), CCB (b ¼ 0.087, p ¼ 0.003),
glucose (b ¼ 0.153, p ¼ 0.014) and ARB (b ¼ 0.071, p ¼ 0.025) were predictors of total costs (Table 4). BMI (b ¼ 0.403, p ¼ 0.014), PCI (b ¼ 0.297, p50.001), diuretic (b ¼ 0.103, p ¼ 0.009), CCB (b ¼ 0.092, p ¼ 0.017), DBP (b ¼ 0.525, p ¼ 0.002) and age (b ¼ 0.301, p ¼ 0.020) were predictors of each day costs. We found that PCI was an important predictor of medical costs. Then whether MS and hypertension influenced the PCI usage was studied. In Table 1, group control and group MS had an obvious higher usage of PCI than group H. Also, significant differences of beta blocker, ARB, CCB and diuretic usage were found in four groups.
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Table 3. Comparison of complications rate of AMI patients at hospital in different MS–hypertension categories.
Group Control Hypertension MS MS–hypertension p
Acute heart failure N (%)
Atrial arrhythmia N (%)
Ventricular arrhythmia N (%)
Death N (%)
Event-free survival N (%)
16 (4.5) 31 (12.9)a 5 (6.3) 26 (8.4) 0.002
22 (6.1) 16 (6.6) 3 (3.8) 27 (8.7) 0.366
19 (5.3) 25 (10.4) 4 (5.1) 29 (9.4) 0.064
7 (1.9) 3 (1.2) 1 (1.3) 8 (2.6) 0.683
310 (86.4) 186 (77.2)a 67 (84.8) 243 (78.6) 0.012
a
p50.05 compared with control.
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Table 4. Multiple linear regression analysis of costs in AMI patients.
Total costs BMI PCI Twice revascularization Ventricular arrhythmia Urine protein CCB Glucose ARB Each day costs BMI PCI Diuretic CCB DBP Age
b
p
R2
0.488 0.311 0.132 0.079 0.088 0.087 0.153 0.071
50.001 50.001 50.001 0.003 0.001 0.003 0.014 0.025
0.701 0.747 0.762 0.772 0.777 0.782 0.785 0.787
0.403 0.297 0.103 0.092 0.525 0.301
0.014 50.001 0.009 0.017 0.002 0.02
0.555 0.608 0.618 0.622 0.627 0.632
BMI, body mass index; PCI, percutaneous coronary intervention; CCB, calcium channel blocker; ARB, adrenergic receptor binder; DBP, diastolic blood pressure.
Cost-effectiveness analysis In order to evaluate cost-effectiveness in different MS-hypertension categories, we calculated CER and the formula was in the method part. We found that group H and group MS&H had a higher rate of acute heart failure, atrial arrhythmia and ventricular arrhythmia at the same total costs (Figure 1). In case of death, group MS&H had the highest incidence-to-costs ratio. In case of event-free survival, group MS and group MS&H had lower incidence-to-costs ratio. In order to evaluate cost-effectiveness of PCI in patients with or without hypertension, we calculate ICER and the formula was in the method part. We found that patients with hypertension had lower ICER in aspect of acute heart failure, atrial arrhythmia, ventricular arrhythmia and death (Figure 2). And patients with hypertension had higher ICER in aspect of event-free survival. These results suggested incidence of acute heart failure, atrial arrhythmia, ventricular arrhythmia and death after PCI decreased much more in patients with hypertension and event-free incidence increased more.
Discussion To our knowledge, this is the first study to examine the relationship between the MS/hypetension and medical costs among patients with AMI. The results show that hypertension, which leads to lower total costs and medical treatment costs, is an important factor of medical costs. In cost-effectiveness analysis, we find patients with hypertension or MS have a
higher mortality and lower event-free incidence when total costs are evened. Event-free incidence increases more to extra costs of PCI usage in patients with hypertension. In this study, we find MS has no impact on hospital outcomes in AMI patients, which is contrary to previous studies (8–10). At present, MS has different diagnostic criteria and studies with different criteria conclude differently. But, when total costs is evened, MS lead to less event-free survival, which suggest medical costs influence hospital outcomes in AMI patients and support a probability that MS may lead a long-term bad prognosis. We find hypertension lead to lower medical costs, which is opposite with our hypothesis. We suppose that hypertension lead to bad hospital outcomes, which is proved in our study and recent studies (11,12), and hypertension patients would need more therapies which results in higher medical costs. On the contrary, perhaps less medical costs cause bad hospital outcomes. We find that BMI is an important predictor of medical costs and medical costs increase with higher BMI. We know that both BMI and hypertension, which lead to contrary trends of medical costs, are components of MS. We can see the discordance in impact on medical costs of MS components. We also find that PCI is an important predictor of medical costs of AMI patients, which is in accordance with previous studies (13,14). We observed that medical cost varies with the rate of PCI usage. And hypertension patients have a rather low rate of PCI usage. We suppose hypertension lead to less PCI usage which leads to less medical costs and bad hospital outcomes. Percutaneous coronary intervention is the effective measure of coronary revascularization, and it can increase the benefit of AMI patients in both short term and long term (15,16). Medical costs of AMI patients were driven up as the utilization rate of PCI increases. Thus, cost-effectiveness is of vital importance to patients who are in poor circumstances. In our study, we calculate the ICER of PCI usage in different terms of hospital outcomes and find PCI is a cost-effective therapy of AMI patients and cost-effectiveness is better in patients with hypertension. However, studies of PCI cost-effectiveness are in a small amount. One related research showed that an increase in the cost was related to a decrease in mortality, but the effect was not very strong: an increase of cost per patient by E1000 will decrease one-year mortality by 0.19–0.15 percentage points (14). Our study has several limitations. Firstly, this is a retrospective study and we could not observe the impact of
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DOI: 10.3109/10641963.2015.1036062
Hypertension lead to lower PCI rate and less medical costs
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Figure 1. Comparison of cost-effectiveness ratio (CER) in different aspects in the MS–hypertension categories. CER ¼ P/C, P: rate of complication, C: mean of total costs (104RMB¥).
Conclusion Metabolic syndrome has no impact on medical costs because of discordance in MS components. PCI is an important predictor of medical costs in AMI patients. Hypertension will lead to lower PCI utilization rate, which results in less medical costs and bad hospital outcomes; and PCI is a cost-effective measure in AMI patients. Comparison of costeffectiveness of PCI and CABG needs future study.
Declaration of interest
Figure 2. Comparison of incremental cost-effectiveness ratio (ICER) of PCI in different aspects in the MS–hypertension categories. 0Þ DP ICER ¼ DC ¼ ðCP11 P C0 . P0 represents rate of complication without PCI and P1 represents rate of complication with PCI, C0 represents mean of total costs (104RMB¥) without PCI and C1 represents mean of total costs (104RMB¥) with PCI.
MS and hypertension on patients with AMI in a long term. Secondly, there are no patients with CABG and we could not compare the cost-effectiveness of PCI and CABG. Thirdly, it is a single center study and bias exists.
The authors declare no conflict of interest. This work was supported by the research grants from the National Basic Research Program of China (973 Program, Grant No.: 2013CB530700), the National Natural Science Foundation of China (81070192, 81070141, 81100605, 81270352, 81270287 and 81471036), the Natural Science Foundation of Shandong Province (BS2013YY017), the Independent Innovation Foundation of Shandong University (2012JC034), National Science and Technology Major Project (No. 2012ZX09303-016-003), and Cardiovascular Exploration Research Foundation of Chinese Medical Doctor Association (DFCMDA201320).
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2. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol 2010;56:1113–32. 3. Athyros VG, Mikhailidis DP, Papageorgiou AA, et al. Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study. Curr Med Res Opin 2004;20: 1691–701. 4. Mente A, Yusuf S, Islam S, et al. Metabolic syndrome and risk of acute myocardial infarction a case-control study of 26,903 subjects from 52 countries. J Am Coll Cardiol 2010;55: 2390–8. 5. Maron DJ, Boden WE, Spertus JA, et al. Impact of metabolic syndrome and diabetes on prognosis and outcomes with early percutaneous coronary intervention in the courage (clinical outcomes utilizing revascularization and aggressive drug evaluation) trial. J Am Coll Cardiol 2011;58:131–7. 6. Curtis LH, Hammill BG, Bethel MA, et al. Costs of the metabolic syndrome in elderly individuals: findings from the cardiovascular health study. Diabetes Care 2007;30:2553-8. 7. Kranjcec D, Altabas V. Metabolic syndrome influencing infarct size and heart failure in patients with acute coronary syndrome: does gender matter? Endocrine J 2012;59:1065–76. 8. Islam MS, Bari MA, Paul GK, et al. Impact of metabolic syndrome in acute myocardial infarction at hospital. MMJ 2013; 22:261–6. 9. Clavijo LC, Pinto TL, Kuchulakanti PK, et al. Metabolic syndrome in patients with acute myocardial infarction is associated with
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increased infarct size and in-hospital complications. Cardiovasc Revasc Med 2006;7:7–11. Zeller M, Steg PG, Ravisy J, et al.; Observatoire des Infarctus de Cote-d’Or Survey Working Group. Prevalence and impact of metabolic syndrome on hospital outcomes in acute myocardial infarction. Adv Intern Med 2005;165:1192–8. Cho JY, Jeong MH, Ahn Y, et al.; Korea Acute Myocardial Infarction Registry I. Impact of high admission blood pressure without history of hypertension on clinical outcomes of patients with acute myocardial infarction: from Korea Acute Myocardial Infarction Registry. Int J Cardiol 2014;172:e54–8. Lee D, Goodman SG, Fox KA, et al. Prognostic significance of presenting blood pressure in non-ST-segment elevation acute coronary syndrome in relation to prior history of hypertension. Am Heart J 2013;166:716–22. Etemad LR, McCollam PL. Predictors of high-cost managed care patients with acute coronary syndrome. Curr Med Res Opin 2005; 21:1977–84. Hakkinen U, Hartikainen J, Juntunen M, et al. Analysing current trends in care of acute myocardial infarction using perfect data. Ann Med 2011;43:S14–21. Brodie BR, Grines CL, Ivanhoe R, et al. Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction. Final results from the primary angioplasty registry. Circulation 1994;90:156–62. Krumholz HM, Chen J, Murillo JE, et al. Clinical correlates of in-hospital costs for acute myocardial infarction in patients 65 years of age and older. Am Heart J 1998;135:523–31.
The impact of metabolic syndrome and hypertension on medical costs of patients with acute myocardial infarction at hospital Guan-Qi Fan1,2, Kai-Li Fu1,2, Ming Song1,2, Lu Han1,2, Cheng-Wei Jin1,2, Ming Zhong1,2, Yun Zhang1,2, Wei Zhang1,2, and Zhi-Hao Wang1,3 1
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, and 3Department of Geriatric Medicine, Qilu Hospital of Shandong University, Ji’nan, P.R. China
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Abstract
Keywords
Objective: This study aimed to find out the impact of metabolic syndrome (MS) and hypertension on medical costs of patients with acute myocardial infarction (AMI) at hospital. Methods: Patients with AMI at Qilu Hospital of Shandong University during January 2011 to May 2013 were separated into four groups according to whether with MS or history of hypertension. Comparison of medical costs, complication rate and cost-effectiveness ratio were analyzed. Results: We found that total costs, each day costs, medical treatment costs, chemical examination costs and drug costs were significantly different in four groups. In variance analysis, MS led to high medical costs without significance. Hypertension was a significant factor influencing medical costs and lead to low medical costs. In multiple linear regression, we found that body mass index (BMI) and percutaneous coronary intervention (PCI) were important predictors of total costs and each day costs. With higher BMI and utilization rate of PCI, medical costs were increased. Trend of total costs in four groups is similar to that of the rate of PCI utilization. Conclusions: Metabolic syndrome has no impact on medical costs because of discordance in MS components. Hypertension will lead to lower PCI utilization rate, which results in less medical costs and bad hospital outcomes.
Acute myocardial infarction, hypertension, metabolic syndrome, medical costs
Introduction With the changes of lifestyle and eating habits, prevalence of metabolic syndrome (MS) is rapidly increasing in developing countries. This study shows that the age-standardized prevalence of MS is 9.8% in men and 17.8% in women among adults in China (1). All of the components constituting MS are risk factors of cardiovascular disease (CVD). MS is associated with an increased risk of CVD, CVD mortality and all-cause mortality (2). It is not clear that whether the risk of MS on CVD is greater than the risk conferred by the sum of individual component risk factors. A research suggests that the MS-related CVD risk is more than that of the sum of its parts in subjects with MS, with or without type 2 diabetes (3). In a large-scale, multi-ethnic, international investigation of MS, the clustering of 3 risk factors with subthreshold values is associated with an increased risk of myocardial infarction compared with having component factors with ‘‘normal’’ values (4). Among stable coronary artery disease patients in the COURAGE trial, the presence of MS identifies an increased risk for death or Correspondence: Zhi-Hao Wang, Department of Geriatric Medicine, Qilu Hospital of Shandong University, No. 107, Wen Hua Xi Road, Ji’nan 250012, P.R. China. Tel: +86 531 82169339. Fax: +86 531 86169356. E-mail: [email protected]
History Received 5 January 2015 Revised 16 February 2015 Accepted 2 March 2015 Published online 15 June 2015
myocardial infarction, but MS has no independent prognostic significance after adjusting for its constituent components (5). In the COURAGE trial, the most consistent predictors of developing an adverse outcome were low high-density lipoprotein (HDL) cholesterol and hyperglycemia. However, whether MS and its components influence the medical costs of CVD patients is not studied. A survey in elderly individuals with MS shows abdominal obesity, low high-density lipoprotein (HDL) cholesterol, and hypertension but not the MS per se is important predictors of long-term costs (6). Acute myocardial infarction (AMI) is the most dangerous and emergent disease in the CVD, leading to a big economic burden. MS is associated with an increased risk of AMI (2), but whether it increases economic burden in AMI patients is not reported. It is investigated that AMI patients with MS have more stents implantation, bigger infarcted area and higher heart failure rate (7,8), which may lead to bad prognosis and increasing medical costs. It is worthwhile to study whether the increasing costs benefits AMI patients. A case-control study shows the association with myocardial infarction by the MS is similar to that of diabetes and hypertension, and significantly stronger than that of the other component risk factors (4). To study the impact of MS, with or without hypertension, we analyze medical costs, complication rate and cost-effectiveness in AMI patients at
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Qilu Hospital of Shandong University during January 2011 to May 2013.
Methods Ethics statement This research had been approved by the ethics committee of Qilu Hospital of Shandong University. Written informed consent was given by participants for their clinical records to be used in this study. All data were anonymized and de-identified prior to the analysis.
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Information of case files collection Consecutive patients with discharge diagnosis of AMI at Qilu Hospital of Shandong University during January 2011 to May 2013 were included. Patients with subacute myocardial infarction were excluded. In total, 988 patients were included. Information of case files included admission number, sex, height, weight, admitting diagnosis, discharge diagnosis, hospital stays, hospital costs, history of smoking, past medical illness, family medical history, laboratory examination, coronary arteriography, ultrasound cardiograph, complications and drug treatment. Diagnosis of AMI and hypertension According to WHO diagnostic criteria for AMI, we defined patients with AMI comply with two items of the following three components or all: typical clinical manifestation, distinctive ECG change and dynamic changes of serum cardiac markers. We defined patients with hypertension when the SBP 140 mmHg and (or) DBP 90 mmHg without antihypertensive treatment or when there is a diagnostic hypertension history with antihypertensive treatment.
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patients with hypertension and without MS (Group H, n ¼ 241), patients with MS and without hypertension (Group MS, n ¼ 79), patients with MS and hypertension (Group MS&H, n ¼ 309). Statistical analysis All analyses were conducted using SAS version 9.2 (SAS Institute Inc, Cary, NC, USA) unless otherwise stated, with p50.05 considered statistically significant. Results are expressed as means ± SD or as proportions (%). For categorical variables, the 2 test and the Fisher exact probability test were used. Variance analysis was used to study impact of the MS and hypertension on hospital stays and costs. Multiple linear regression using stepwise method was performed to examine predictors of medical costs. Cost-effectiveness analysis Calculate formula of cost-effectiveness ratio (CER): CER ¼
P C
P: rate of complication, C: mean of total costs. Calculate formula of incremental cost-effectiveness ratio (ICER): DP P1 P0 ICER ¼ ¼ DC C1 C0 P1: rate of complication in patients with percutaneous coronary intervention (PCI); C1: mean of total costs in patients with PCI; P0: rate of complication in patients without PCI; C0: mean of total costs in patients without PCI.
Results Baseline data
Definition of MS Chinese Diabetes Society (CDS) criterion: comply with three items of the following four components or all: (1) overweight and (or) obesity: BMI 0.25 (kg/m2); (2) hyperglycemia: FPG 6.1 mmol/L and PPG 7.8 mmol/L, and (or) the cases with diagnosed diabetes mellitus receiving treatment; (3) hypertension: SBP/DBP 140/90 mmHg, and (or) the cases with diagnosed hypertension receiving treatment; (4) lipids disorder: TG 1.7 mmol/L, and (or) HDL-C 5 0.9 mmol/L (male) or 51.0 mmol/L (female). General approaches to treatment Approaches to treatment of AMI were mainly according to 2011 and 2012 ECS guidelines for the management of AMI. Approaches to treatment of hypertension were mainly according to the Chinese Hypertension Prevention Guide (2011 revision). Approaches to treatment of MS were control of existing MS components, such as interventions of obesity, lowering serum lipids and control of serum glucose.
A total of 988 cases were included in this study. Significant differences were found between different MS–hypertension categories regarding sex, BMI, blood pressure, smoking history, serum glucose, blood lipids and renal function related biochemical indicator (Table 1). Medical costs Table 2 shows the variance analysis results of medical costs of AMI patients in the different MS–hypertension categories. We found that total costs, each day costs, medical treatment costs, chemical examination costs and drug costs were significantly different in four groups. Surprisingly, group MS had the highest total costs and each day costs; and group H had the lowest total costs and each day costs. To study which one of the two factors, MS and hypertension, significantly influenced medical costs, we performed variance analysis. Taking total costs as dependent variable, we found that hypertension was a significant factor which led to a low total cost. Taking medical treatment costs as dependent variable, the results accorded with that of total costs.
Grouping According to CDS criterion and hypertension history, all AMI patients were separated to four MS–hypertension categories: patients without MS or hypertension (control, n ¼ 359),
Major cardiovascular events Table 3 shows the rate of complications and event-free survival at hospital in different MS–hypertension categories.
Hypertension lead to lower PCI rate and less medical costs
DOI: 10.3109/10641963.2015.1036062
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Table 1. Comparison of baseline characteristics of AMI patients in different MS–hypertension categories.
Age (years) Male sex, n (%) BMI (kg/m2) SBP (mmHg) DBP (mmHg) HR (min1) Smoking history, n (%) Laboratory examination Cho (mmol/L) TG(mmol/L) HDL (mmol/L) LDL (mmol/L) NEFA (mmol/dL) PLIP (mmol/dL) Glu (mmol/L) AST (U/L) BUN (mmol/L) Cr (mmol/L) Cys-c (mg/L) UA (mmol/L) K (mmol/L) Urine protein, n (%) Treatment PCI, n (%) Twice revascularization, n (%) Beta blocker, n (%) ACEI, n (%) ARB, n (%) Statins, n (%) CCB, n (%) Diuretic, n (%)
Control (n ¼ 359)
Hypertension (n ¼ 241)
MS (n ¼ 79)
MS–hypertension (n ¼ 309)
p
62.06 ± 13.80 279 (77.7) 24.05 ± 3.70 122.93 ± 17.46 72.17 ± 10.88 75.73 ± 15.94 190 (52.9)
69.82 ± 11.64 150 (62.2) 23.34 ± 3.91 135.86 ± 21.66 76.10 ± 13.31 77.62 ± 16.15 102 (42.3)
59.11 ± 12.09 62 (78.5) 26.95 ± 2.56 130.82 ± 22.87 77.56 ± 13.87 77.75 ± 13.24 45 (57.0)
63.93 ± 12.49 199(64.4) 27.35 ± 3.07 136.15 ± 21.79 79.19 ± 13.86 78.75 ± 16.21 139(45.0)
50.001 50.001 50.001 50.001 50.001 0.102 0.017
4.45 ± 1.15 1.34 ± 1.00 1.15 ± 0.27 2.77 ± 0.96 63.54 ± 34.90 2.18 ± 0.44 5.93 ± 2.15 91.06 ± 118.17 4.99 ± 2.19 72.53 ± 18.66 1.01 ± 0.31 299.15 ± 97.79 4.06 ± 0.47 8 (2.7)
4.53 ± 1.03 1.15 ± 0.43 1.18 ± 0.22 2.81 ± 0.82 67.38 ± 28.29 2.17 ± 0.44 5.84 ± 3.14 70.50 ± 95.87 5.85 ± 4.06 84.12 ± 74.92 1.16 ± 0.65 305.36 ± 93.81 3.98 ± 0.47 17 (8.6)
4.78 ± 1.24 1.99 ± 1.01 1.00 ± 0.24 3.05 ± 0.95 71.19 ± 40.80 2.32 ± 0.69 8.46 ± 3.12 68.42 ± 95.82 5.07 ± 1.98 68.34 ± 15.01 0.93 ± 0.23 303.96 ± 84.27 4.04 ± 0.37 2 (3.1)
4.74 ± 1.20 1.97 ± 1.13 1.03 ± 0.23 2.97 ± 0.94 67.11 ± 31.94 2.30 ± 0.50 7.21 ± 2.63 75.13 ± 118.60 6.23 ± 3.84 90.82 ± 75.47 1.19 ± 0.69 328.10 ± 99.34 4.09 ± 0.58 31(12.3)
0.004 50.001 50.001 0.01 0.482 0.025 50.001 0.084 50.001 50.001 50.001 0.001 0.06 50.001
168(54.4) 21(6.8) 262(84.8)b 123(39.8) 163(52.8)a,c 290(93.8) 110(35.6)a,c 102(33.0)a
50.001 0.186 0.016 0.495 50.001 0.159 50.001 50.001
222 20 279 148 93 327 41 77
(61.8)b (5.6) (77.7) (41.2) (25.9) (99.4) (11.4) (21.4)
107 7 181 100 113 220 79 84
(44.4) (2.9) (75.1) (41.5) (46.9)a,c (91.3) (10.4)a,c (34.9)a
54 6 67 39 18 77 11 16
(68.4)b (7.6) (84.8) (49.4) (22.8) (97.5) (13.9) (20.2)
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; Cho, cholesterol; TG, triglyceride; HDL, highdensity lipoprotein; LDL, low-density lipoprotein; NEFA, non-esterified fatty acids; PLIP, phospholipids; Glu, glucose; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; Cr, creatinine; Cys-c, cysteine; UA, uric acid; PCI, percutaneous coronary intervention; ACEI, angiotensin converting enzyme inhibitor; ARB, adrenergic receptor binder; CCB, calcium channel blocker. a p50.05 compared with control; bp50.05 compared with hypertension; cp50.05 compared with MS.
Table 2. Comparison of hospital costs of AMI patients in different MS–hypertension categories.
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Total costs (10 RMB) Each day costs (103RMB) Medical treatment costs (103RMB) Chemical examination costs (103RMB) Drug costs (103RMB)
Control (n ¼ 359)
Hypertension (n ¼ 241)
MS (n ¼ 79)
MS–hypertension (n ¼ 309)
p
p1
p2
p3
49.38 ± 29.41 5.08 ± 5.54 17.26 ± 24.47 1.85 ± 1.03 12.61 ± 7.85
43.76 ± 31.21 4.36 ± 4.40 13.89 ± 22.76 2.02 ± 1.22 13.28 ± 10.17
52.15 ± 31.12 5.55 ± 5.37 20.80 ± 26.03 1.85 ± 0.83 12.17 ± 7.41
47.99 ± 33.44 4.91 ± 5.02 15.50 ± 24.57 1.97 ± 1.27 13.07 ± 8.91
50.001 50.001 50.001 50.001 50.001
0.139 0.185 0.16 0.755 0.624
0.039 0.078 0.018 0.087 0.237
0.759 0.919 0.6 0.742 0.871
p: significance of corrected model; p1: significance of MS; p2: significance of hypertension; p3: significance of MS–hypertension interaction.
We found significant difference of acute heart failure and event-free incidence in different MS–hypertension categories. To be analogous with medical costs, group H had the highest acute heart failure incidence and lowest event-free incidence. Predictors of medical costs To study the main predictors of medical costs, we run multiple linear regression using stepwise method. Results showed that BMI (b ¼ 0.488, p50.001), PCI (b ¼ 0.311, p50.001), twice revascularization (b ¼ 0.132, p50.001), ventricular arrhythmia (b ¼ 0.079, p ¼ 0.003), urine protein (b ¼ 0.088, p ¼ 0.001), CCB (b ¼ 0.087, p ¼ 0.003),
glucose (b ¼ 0.153, p ¼ 0.014) and ARB (b ¼ 0.071, p ¼ 0.025) were predictors of total costs (Table 4). BMI (b ¼ 0.403, p ¼ 0.014), PCI (b ¼ 0.297, p50.001), diuretic (b ¼ 0.103, p ¼ 0.009), CCB (b ¼ 0.092, p ¼ 0.017), DBP (b ¼ 0.525, p ¼ 0.002) and age (b ¼ 0.301, p ¼ 0.020) were predictors of each day costs. We found that PCI was an important predictor of medical costs. Then whether MS and hypertension influenced the PCI usage was studied. In Table 1, group control and group MS had an obvious higher usage of PCI than group H. Also, significant differences of beta blocker, ARB, CCB and diuretic usage were found in four groups.
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Table 3. Comparison of complications rate of AMI patients at hospital in different MS–hypertension categories.
Group Control Hypertension MS MS–hypertension p
Acute heart failure N (%)
Atrial arrhythmia N (%)
Ventricular arrhythmia N (%)
Death N (%)
Event-free survival N (%)
16 (4.5) 31 (12.9)a 5 (6.3) 26 (8.4) 0.002
22 (6.1) 16 (6.6) 3 (3.8) 27 (8.7) 0.366
19 (5.3) 25 (10.4) 4 (5.1) 29 (9.4) 0.064
7 (1.9) 3 (1.2) 1 (1.3) 8 (2.6) 0.683
310 (86.4) 186 (77.2)a 67 (84.8) 243 (78.6) 0.012
a
p50.05 compared with control.
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Table 4. Multiple linear regression analysis of costs in AMI patients.
Total costs BMI PCI Twice revascularization Ventricular arrhythmia Urine protein CCB Glucose ARB Each day costs BMI PCI Diuretic CCB DBP Age
b
p
R2
0.488 0.311 0.132 0.079 0.088 0.087 0.153 0.071
50.001 50.001 50.001 0.003 0.001 0.003 0.014 0.025
0.701 0.747 0.762 0.772 0.777 0.782 0.785 0.787
0.403 0.297 0.103 0.092 0.525 0.301
0.014 50.001 0.009 0.017 0.002 0.02
0.555 0.608 0.618 0.622 0.627 0.632
BMI, body mass index; PCI, percutaneous coronary intervention; CCB, calcium channel blocker; ARB, adrenergic receptor binder; DBP, diastolic blood pressure.
Cost-effectiveness analysis In order to evaluate cost-effectiveness in different MS-hypertension categories, we calculated CER and the formula was in the method part. We found that group H and group MS&H had a higher rate of acute heart failure, atrial arrhythmia and ventricular arrhythmia at the same total costs (Figure 1). In case of death, group MS&H had the highest incidence-to-costs ratio. In case of event-free survival, group MS and group MS&H had lower incidence-to-costs ratio. In order to evaluate cost-effectiveness of PCI in patients with or without hypertension, we calculate ICER and the formula was in the method part. We found that patients with hypertension had lower ICER in aspect of acute heart failure, atrial arrhythmia, ventricular arrhythmia and death (Figure 2). And patients with hypertension had higher ICER in aspect of event-free survival. These results suggested incidence of acute heart failure, atrial arrhythmia, ventricular arrhythmia and death after PCI decreased much more in patients with hypertension and event-free incidence increased more.
Discussion To our knowledge, this is the first study to examine the relationship between the MS/hypetension and medical costs among patients with AMI. The results show that hypertension, which leads to lower total costs and medical treatment costs, is an important factor of medical costs. In cost-effectiveness analysis, we find patients with hypertension or MS have a
higher mortality and lower event-free incidence when total costs are evened. Event-free incidence increases more to extra costs of PCI usage in patients with hypertension. In this study, we find MS has no impact on hospital outcomes in AMI patients, which is contrary to previous studies (8–10). At present, MS has different diagnostic criteria and studies with different criteria conclude differently. But, when total costs is evened, MS lead to less event-free survival, which suggest medical costs influence hospital outcomes in AMI patients and support a probability that MS may lead a long-term bad prognosis. We find hypertension lead to lower medical costs, which is opposite with our hypothesis. We suppose that hypertension lead to bad hospital outcomes, which is proved in our study and recent studies (11,12), and hypertension patients would need more therapies which results in higher medical costs. On the contrary, perhaps less medical costs cause bad hospital outcomes. We find that BMI is an important predictor of medical costs and medical costs increase with higher BMI. We know that both BMI and hypertension, which lead to contrary trends of medical costs, are components of MS. We can see the discordance in impact on medical costs of MS components. We also find that PCI is an important predictor of medical costs of AMI patients, which is in accordance with previous studies (13,14). We observed that medical cost varies with the rate of PCI usage. And hypertension patients have a rather low rate of PCI usage. We suppose hypertension lead to less PCI usage which leads to less medical costs and bad hospital outcomes. Percutaneous coronary intervention is the effective measure of coronary revascularization, and it can increase the benefit of AMI patients in both short term and long term (15,16). Medical costs of AMI patients were driven up as the utilization rate of PCI increases. Thus, cost-effectiveness is of vital importance to patients who are in poor circumstances. In our study, we calculate the ICER of PCI usage in different terms of hospital outcomes and find PCI is a cost-effective therapy of AMI patients and cost-effectiveness is better in patients with hypertension. However, studies of PCI cost-effectiveness are in a small amount. One related research showed that an increase in the cost was related to a decrease in mortality, but the effect was not very strong: an increase of cost per patient by E1000 will decrease one-year mortality by 0.19–0.15 percentage points (14). Our study has several limitations. Firstly, this is a retrospective study and we could not observe the impact of
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DOI: 10.3109/10641963.2015.1036062
Hypertension lead to lower PCI rate and less medical costs
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Figure 1. Comparison of cost-effectiveness ratio (CER) in different aspects in the MS–hypertension categories. CER ¼ P/C, P: rate of complication, C: mean of total costs (104RMB¥).
Conclusion Metabolic syndrome has no impact on medical costs because of discordance in MS components. PCI is an important predictor of medical costs in AMI patients. Hypertension will lead to lower PCI utilization rate, which results in less medical costs and bad hospital outcomes; and PCI is a cost-effective measure in AMI patients. Comparison of costeffectiveness of PCI and CABG needs future study.
Declaration of interest
Figure 2. Comparison of incremental cost-effectiveness ratio (ICER) of PCI in different aspects in the MS–hypertension categories. 0Þ DP ICER ¼ DC ¼ ðCP11 P C0 . P0 represents rate of complication without PCI and P1 represents rate of complication with PCI, C0 represents mean of total costs (104RMB¥) without PCI and C1 represents mean of total costs (104RMB¥) with PCI.
MS and hypertension on patients with AMI in a long term. Secondly, there are no patients with CABG and we could not compare the cost-effectiveness of PCI and CABG. Thirdly, it is a single center study and bias exists.
The authors declare no conflict of interest. This work was supported by the research grants from the National Basic Research Program of China (973 Program, Grant No.: 2013CB530700), the National Natural Science Foundation of China (81070192, 81070141, 81100605, 81270352, 81270287 and 81471036), the Natural Science Foundation of Shandong Province (BS2013YY017), the Independent Innovation Foundation of Shandong University (2012JC034), National Science and Technology Major Project (No. 2012ZX09303-016-003), and Cardiovascular Exploration Research Foundation of Chinese Medical Doctor Association (DFCMDA201320).
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