Current State of Cardiac Rehabilitation in Japan

PR O G RE S S I N C ARDI O V A S CU L A R D I S EA S E S 5 6 (2 0 1 4) 55 7–5 6 2

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Current State of Cardiac Rehabilitation in Japan Yoichi Goto⁎ Department of Cardiovascular Rehabilitation, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan

A R T I C LE I N F O

AB ST R A C T

Keywords:

In Japan, metabolic risk factors have been increasing due to the westernization and

Exercise

urbanization of lifestyle. This justifiably raises a concern that the incidence of coronary

Risk reduction

heart disease (CHD) in Japan will increase over time, and indeed, recent epidemiological

Heart disease

studies in Japan suggest the incidence of acute myocardial infarction (AMI) is increasing.

Lifestyle

Cardiac rehabilitation (CR) in Japan has been traditionally performed in the inpatient setting. To obtain reimbursement, a CR facility must fulfill certain criteria including being a medical institution with a cardiology/cardiac surgery section which has at least a cardiologist/cardiac surgeon and an experienced CR physician as full-time employees. These criteria create challenges to the availability of outpatient CR after hospital discharge. A recent analysis found outpatient CR participation rate was estimated to be between 3.8 and 7.6% in Japan. This review describes recent trends in the incidence of AMI and the current status of the use of CR in Japan. © 2014 Elsevier Inc. All rights reserved.

Cardiovascular diseases (CVD), and in particular coronary heart disease (CHD), are a major cause of death in the United States (US) and European countries. In recent decades, the incidence and mortality of both CVD and CHD have been declining in most of these countries.1,2 This decrease in CHD mortality has been attributed to improvements in medical treatments and more effective management of CHD risk factors.2 However, in Japan, metabolic risk factors have been increasing due to the westernization and urbanization of lifestyle.3 For example, in a population-based cohort study in Hisayama, the age-adjusted prevalence of hypercholesterolemia has substantially increased from 2.8% to 25.8% in men and from 6.6% to 41.6% in women from 1961 to 2002.4 This justifiably raises a concern that the incidence of CHD in Japan will increase over time. Because cardiac rehabilitation (CR) in Japan has been traditionally performed in the inpatient setting, implementation of outpatient CR after hospital

discharge remains insufficient. In this review, an overview of recent trends in the incidence of acute myocardial infarction (AMI) and the current status of the use of CR in Japan will be presented.

Incidence and mortality of CHD in Japan Trends in CVD and CHD mortality and CHD risk factors in Japan The annual report of the Organization for Economic Cooperation and Development (OECD) indicated that Japan and Korea have extraordinarily low mortality rates for CHD compared to other countries; age-adjusted mortality rates per 100,000 of the population in 2009 were 38 in Japan and 37 in Korea compared with 128 in the US, 123 in Canada and 110 in

Statement of Conflict of Interest: see page 561. ⁎ Address reprint requests to: Yoichi Goto, MD, PhD, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. E-mail address: [email protected]. 0033-0620/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pcad.2013.12.001

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Germany.5 However, according to data from AMI = acute myocardial the Japanese Ministry infarction of Health, Labor and CABG = coronary artery bypass Welfare, Japan is demgraft onstrating an increase in crude mortality CR = cardiac rehabilitation (unadjusted for age) CVD = cardiovascular disease from CVD and a decrease in stroke morCHD = coronary heart disease tality from 1950 to 2010 JCAD = Japanese coronary artery (Fig. 1). Even though disease the mortality rate from CVD in Japan reJCS = Japanese Circulation mains comparatively Society low, the increasing OECD = Organization for Ecotrend in CVD mortality nomic Co-operation and is in contrast to the Development decreasing trend in the US.1 PCI = percutaneous coronary intervention Because the Japanese society has been US = United States aging in recent decades, the true impact of CHD on premature death has to be assessed in the context of age-adjusted mortality. Indeed, the age-adjusted CHD mortality in Japan has gradually declined from approximately 50 per 100,000 in 1980 to 30 per 100,000 in 2006.6 Comparatively, while other OECD countries have also enjoyed a steady decline in CHD mortality collectively during that same time period, the rate is still higher compared to Japan; ~ 80 per 100,000 overall.6 This decreasing trend in Japan has also been shown in the national data for both men and women since

Mortality (per 100 thousands)

Abbreviations and Acronyms

300 280 260 240 220 200 180 160 140 120 100 80 60 40 20 0

Stroke

Heart diseases

1950

1960

1970

1980

the 1970s, and has been attributed to the corresponding decreases in systolic blood pressure and smoking rates.3 However, considering that a decrease in CHD mortality can be the result of either a decrease in incidence or an improvement in survival due to advances in treatment, the observed decline in CHD mortality does not directly indicate a decrease in CHD incidence in Japan. In fact, the smoking rate remains much higher in Japan than in the US, and serum cholesterol levels, the prevalence of diabetes/glucose intolerance and obesity have steeply increased from the 1960s to the 2000s3,4,7 (Table 1). Moreover, national data from US and Japan suggest that total cholesterol levels in the Japanese population have increased to levels similar to those in the US population; mean serum total cholesterol level in Japanese adults ≥ 30 years of age was 203 mg/dL in 2000 while that in US adults ≥ 20 years of age was 204 mg/dL in 1999–2000.1,8

Increasing trends in incidence of AMI in Japan Along with worsening CHD risk profiles, Kitamura et al9 reported that the incidence of CHD has increased in a select portion of the Japanese population, i.e., middle-aged working males (aged 40–59 years) living in an urban area (Osaka). This indicates that we need comprehensive registry data covering a community over time to accurately monitor CHD incidence in Japan. Table 2 summarizes recent reports on the trends of AMI incidence in Japanese cohorts. There are two populationbased (community-based) cohort studies7,10 and three hospital-based registry studies.11–13 Two studies7,12 compare cohorts from the 1960–70s and the 2000s, two10,11 compare cohorts from the 1990s and the 2000s, and the remaining one13 compares more recent cohorts (2004 and 2011). Although the Hisayama study7 did not show any increase in AMI incidence over 40 years, its statistical power may not be high enough to detect changes given the small number of events (15 and 34 AMIs for the two time periods, respectively). Moreover, one population-based study10 and two hospitalbased studies11,12 comparing cohorts from 1979 to 1997 and the 2000s showed consistent increases in AMI incidence in Japan. This increase in AMI incidence contrasts to the gradual decline in CHD mortality since the 1970s as reported by national statistics in Japan.3,6 The apparent discrepancy between the increasing AMI incidence and the decreasing CHD mortality may be explained by an increasing AMI incidence being offset by an improvement in medical treatment, resulting in an overall decline in mortality.

Very recent trends suggesting a decrease in incidence of AMI in Japan 1990

2000

2010

Years Fig. 1 – Cardiovascular disease mortality trends in Japan in 1947–2011. The abrupt decrease in heart disease mortality and concomitant increase in stroke mortality in 1995 was caused by the change in diagnostic criteria in death certificate in Japan. Adapted from the Japanese Ministry of Health, Labor and Welfare, 2012 (at http://www.mhlw.go.jp/ toukei/itiran/).

It is of note that the Kumamoto study13 indicated a decrease in AMI incidence in the most recent 2011 cohort compared to a 2004 cohort. Although a statistical significance was reached only in men (p = 0.029), women and the total population also had p-values close to statistical significance (p = 0.051 and 0.053, respectively). This finding is in accordance with a very recent Korean study where the incidence of AMI has decreased in 2010 compared to 2006.14 Taken together, it may be suggested that the AMI incidence in Japan has

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Table 1 – Changes in coronary risk factors over 40 years in Hisayama study.7 Men

Age (years) Hypertension (%) Antihypertensive agents (%) Hypercholesterolemia (%) Total cholesterol (mmol/L) Glucose intolerance (%) Obesity (BMI ≥ 25, %) Body mass index (BMI, kg/m2) Current smoker (%)

Women

1961 cohort (n = 1618)

2002 cohort (n = 3108)

55 ± 11 38.4 2.0 2.8 3.9 ± 0.9 11.6 7.0 21.2 ± 2.3 75.0

61 ± 12 41.3 17.5 22.2 5.1 ± 0.9 54.0 29.2 23.4 ± 2.9 47.4

recently experienced an altered trajectory from an increase to a decrease. If this observation is indeed true, it is occurring despite a worsening of metabolic risk factors (such as diabetes and obesity), possibly secondary to the widespread use of preventive medicine (statins and aspirin) in recent years. However, we have to be cautious in interpreting the data of hospital-based registry data, because AMI patients who have not been hospitalized (sudden cardiac death or silent AMI) are not included.11–13 Thus, a comprehensive population-based cohort study in which community-based and hospital-based data are integrated would be valuable.

Current Status of cardiac rehabilitation delivery in Japan Cardiac rehabilitation delivery system in Japan In Japan, CR is covered by the public health insurance system for AMI, angina pectoris, and heart failure. Patients undergoing a percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery are also covered. Coverage for CR lasts five months from the time of event or surgical procedure. Health insurance covers 70% of medical fees

p <0.05 NS <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05

1961 cohort (n = 1618)

2002 cohort (n = 3108)

57 ± 12 35.9 2.1 6.6 4.2 ± 1.0 4.8 12.9 21.6 ± 2.8 16.6

62 ± 13 30.8 16.2 35.3 5.4 ± 0.9 35.1 23.8 22.9 ± 3.5 8.5

p <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05 <0.05

associated with CR in patients < 70 years of age and 90% in patients ≥ 70 years of age. For each 1-hour CR session, copayment for the patient amounts to approximately $18 for patients < 70 years of age and $6 in patients ≥ 70 years of age. To obtain health insurance reimbursement, a CR facility must fulfill the following regulatory standards: 1) The facility should be a medical institution with a cardiology/cardiac surgery section which has at least a cardiologist/cardiac surgeon and an experienced CR physician as full-time employees, 2) the facility should have 2 or more experienced CR physical therapists/nurses, and at least one of them should be engaged exclusively in CR, 3) the facility should have a training room exclusively for CR (≥ 30 m2 for a hospital, ≥20 m2 for a clinic), and 4) the facility (or a cooperating medical facility) should have an intensive care unit and emergency medical system (such as a catheterization laboratory) capable of responding to emergency situations. Of these facility criteria, the requirements of a cardiology/ cardiac surgery section and a full-time cardiologist/cardiac surgeon appear to not be necessary in providing safe and effective CR and in fact negatively impacts non-cardiology facilities ability to provide CR. Thus, these relatively strict facility standards are potentially limiting a greater dissemination of outpatient CR delivery in Japan.

Table 2 – Trends of age-adjusted incidence of acute myocardial infarction in various studies in Japan. All 10 #

Takashima (2008)

Yamagata (2010)11 § Miyagi (2010)12 § Hisayama (2013)7 # Kumamoto (2013)13 §

(1990–1992) 39.9 (1979) 7.4 (2004) 59.2

Men (1999–2001) 62.6 ⁎ (2008) 27.0 ⁎⁎ (2011) 43.1 NS

(1990–1992) 66.5 1993–1997 42.7 (1979) 18.7 (1961–1968) 193 (2004) 93.1

Women (1999–2001) 100.7 ⁎ 2003–2007 50.1 ⁎ (2008) 46.4 ⁎⁎ (2002–2009) 144 NS (2011) 70.7 ⁎

In each study, AMI incidence (/100,000persons/year) was compared between two time cohorts. ⁎ p < 0.05 compared with the baseline cohort. ⁎⁎ p < 0.001 compared with the baseline cohort. # Population-based cohort study. § Hospital-based registry study.

(1990–1992) 18.7 1993–1997 20.7 (1979) 4.2 (1961–1968) 78 (2004) 33.0

(1999–2001) 35.7 ⁎ 2003–2007 18.9 NS (2008) 9.6 NS (2002–2009) 50 NS (2011) 20.7 NS

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Current status of cardiac rehabilitation delivery in Japan In Japan, the status of CR delivery had not been investigated until 2004, when the first nation-wide survey was conducted. The 2004 nation-wide survey15 investigated the status of medical care for AMI in a total of 859 cardiology training hospitals authorized by the Japanese Circulation Society (JCS), of which 526 (61%) of the hospitals responded to the questionnaire. The results of the survey (Table 3) revealed that; 1) the cardiology training hospitals in Japan are on average moderate-sized medical institutions, 2) implementation rates of any PCI and emergency PCI are extremely high (94% and 92%, respectively), 2) the implementation rate of acute phase CR for AMI was modest (approximately 50%), 3) implementation rates of post-acute phase AMI patient care (such as patient education programs, formulated exercise prescription based on exercise testing, and cardiopulmonary exercise testing) are very low (14–23%), and most importantly, 4) the implementation rate of outpatient CR program after hospital discharge was only 9%, which was markedly lower than the implementation rate of emergency PCI in these hospitals. Five years later, a second nation-wide survey16 was conducted in 2009, collecting questionnaire replies from 597 hospitals (64%) of a total of 934 JCS-authorized cardiology training hospitals (Table 3). The results revealed that the implementation rate of PCI remained very high, and that the implementation rate of outpatient CR more than doubled

Table 3 – Comparison of performance of cardiology training hospitals between the 2004 and 2009 nationwide surveys in Japan. 2004 Survey 2009 Survey (n = 526) (n = 597) Number of hospital beds Number of cardiology beds Approved for ICU facility standards (%) Number of cardiologists (full-time) Implementing CAG (%) Number of CAG (procedures/year) Implementing PCI (%) Number of PCI (procedures/year) Number of patients with AMI (patients/year) AMI length of hospital stay (days) Implementing in-hospital CR (%) Implementing outpatient CR (%)

p

469 ± 258 40 ± 19 45

456 ± 241 42 ± 25 55

NS NS <0.01

6.4 ± 6.7

7.4 ± 7.5

<0.05

96 655 +/-717

98 640 ± 611

<0.05 NS

94 200 ± 214

96 231 ± 209

NS <0.05

60 ± 50

65 ± 52

NS

19 ± 9

15 ± 6

<0.001

55

64

<0.01

9

21

<0.001

The 2004 Survey was adapted from Goto et al15 and Nakanishi et al16. ICU, Intensive care unit; CAG, coronary arteriography; PCI, percutaneous coronary intervention; AMI, acute myocardial infarction; CR, cardiac rehabilitation.

from 9% in 2004 to 21% in 2009, but remained disproportionately lower than that of PCI. Nakanishi et al examined the relationship between annual volumes of AMI and CR in 708 hospitals treating AMI in Japan.16 Although there was a weak correlation between the annual volumes of AMI and CR, it was readily apparent that there are many (>50%) hospitals not providing CR despite relatively large numbers of AMI. It should be noted that, although the length of hospital stay of AMI patients has shortened significantly from 19 ± 9 days in 2004 to 15 ± 6 days in 2009 (p < 0.001) (Table 3), it remains much longer than that in the US (on average 5.3 days).17 However, this difference is not attributable to disease severity but rather to the difference in healthcare systems between Japan and the US.18 Partly because of this long hospital stay, CR in Japan has been traditionally performed in the inpatient setting rather than the outpatient setting. According to data from the Japanese Ministry of Health, Labor and Welfare, the number of registered medical institutions for CR has been steadily increasing; from 186 institutions in the year of 2005, to 330 in 2007, 495 in 2010, and 608 in 2011.19 However, according to the Japanese Association of CR, the number of the medical institutions which are providing outpatient CR is only 325 in 2013. This number is in sharp contrast to the number of medical institutions performing PCI being 1,240 in Japan,20 and also to the number of CR programs in the US (mostly in the outpatient setting) being 2,621.21 Clearly, this small number of outpatient CR programs is a major obstacle for CR availability to eligible patients in Japan.

Patient participation rate in cardiac rehabilitation in Japan As described above, because CR in Japan has been delivered almost exclusively by cardiology hospitals, hospitalized AMI patients start in-hospital CR and are automatically transferred to the outpatient CR program of the same hospital if the hospital is providing outpatient CR services. There is virtually no referral system for CR in Japan, i.e., if the initial cardiology hospital to which a patient was hospitalized has no outpatient CR program, the patient would not participate in any CR after hospital discharge. Therefore, the CR participation rate in each institution rather than a referral rate, in addition to the institutional CR implementation rate, determines the nationwide CR participation rate in Japan. According to a small survey, 22 the CR participation rate was estimated to be 5–12% among hospitalized AMI patients in Japan from 1996 to 1998. However, this study, which included data from more than 10 years ago, was a small survey in only 46 cardiology hospitals. From the data of the 2004 nationwide survey, the participation rate in CR after AMI in Japan was estimated.15 Assuming that the AMI acute phase mortality rate is 10% and that 50–100% of acute phase survivor patients received care in hospitals providing an outpatient CR program would participate in outpatient CR after hospital discharge, the nationwide CR participation rate was estimated to be between 3.8 and 7.6%. Fig. 2 depicts CR participation rates according to patient background and country based on the data in previous

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561

Participation Rate (%)

50

Future directions for CR research and clinical practice in Japan

41%

40

35% 31%

30

29%

23% 20

14%

12%

10 0

4 AMI

AMI Elder

CAD CABG CABG Elder Elder Canada

AMI UK

8%

AMI AMI France Japan

USA Fig. 2 – Comparisons of patient participation rates in cardiac rehabilitation according to clinical background and country. Participation rate is relatively high in post-CABG patients, low in elderly patients, and, when comparing countries, lowest in Japan (drawn from data in Suaya et al23 and Goto et al15.

studies,15,23 indicating that the CR participation rate is relatively high in post-CABG patients, low in elderly patients, and, when comparing countries, lowest in Japan.

Evidence-based review supporting CR in Japan Because of the marked underutilization of CR in Japan, the evidence supporting CR is scarce in Japan. In a small randomized study, Seki et al24 demonstrated that participation in a 6-month outpatient CR improved both SF-36 subscales and anxiety scores in elderly CHD patients. Soga et al25 demonstrated that early exercise training starting one day following elective PCI, with a training intensity based on the Borg 6-20 scale (training target = 13), did not increase the incidence of stent thrombosis or CVD events at 30 days. The same authors also reported in a prospective observational study in 3,672 patients that exercise training after PCI did not increase the incidence of stent thrombosis while decreasing unscheduled hospital visits for angina.26 In the Japanese Coronary Artery Disease (JCAD) 3-year follow-up study in a large cohort of 11,893 hospitalized Japanese CHD patients, Suzuki et al27 reported that 4,237 (36%) patients who underwent an exercise intervention had a significantly lower all-cause mortality (hazard ratio 0.73 [95% CI 0.55–0.96] after adjustment for clinical variables) compared to those who did not receive the exercise intervention. Finally, Kamakura et al28 demonstrated that AMI patients at prognostically low risk (young patients with successful reperfusion and preserved ejection fraction, without heart failure) have a higher prevalence of multiple (≥3) CHD risk factors than higher risk patients (49% versus 39%, p < 0.05) and that even in these low risk patients, active participation in CR affords significant improvements in exercise capacity and CHD risk profile. Although these data support CR/exercise training in the modern era in Japan, more supporting evidence is needed.

Numerous research questions remain to be answered and practical issues need to be solved in the field of CR in Japan. Many of these research-related issues regarding CR in Japan are consistent with concerns in other countries (e.g. low referral rates, long-term compliance, and program availability). After reviewing the current status of CHD and CR in Japan, I would propose the following future tasks in CR research and practice: 1) As for CR research, the first thing to be done is to construct new evidence supporting CR specific to Japan, because lifestyle, CHD risk factors, and social background are all greatly different in Japan compared to western countries, where most evidence supporting CR has been conducted to this point, 2) though not necessarily specific to Japan, there is a need to explore the optimal/best exercise training mode for CVD patients. For example, it is necessary to evaluate outcomes amongst high-intensity interval training, moderate-intensity endurance training, and low-level resistance training programs for CHD patients and 3) there is a need to establish optimal/standard exercise training programs for elderly patients in general and heart failure patients in particular. As for CR clinical practice, there are three issues requiring solutions in Japan: 1) To promote CR use nationwide, 2) to construct a CR plan for patients of advanced age (octogenarians), given the long life-expectancy enjoyed by the Japanese population, and 3) to establish a mechanism to improve patient adherence to the CR program and to maintain lifelong adherence to a healthy lifestyle. For the first goal of nationwide CR promotion, I would propose the following: 1) substantially increase CR institutions by relaxing Japanese CR facility standards requiring a cardiology/cardiac surgery section and a full-time cardiologist/cardiac surgeon, 2) maximally utilize the currently limited number of CR institutions by constructing a “regional CR referral critical path” or “CR community cooperation network” among multiple medical institutions, and 3) greatly enhance social visibility of CR by announcing/advertising the benefits of CR to the public.

Conclusion In conclusion, in contrast to the decreasing trends in CHD incidence in the US and Europe, CHD (or AMI) incidence has been increasing in Japan, along with worsening of metabolic risk factors. Although CR is a promising intervention to improve exercise capacity, quality of life, risk factors and prognosis, additional research and a rethinking of current policies are needed in Japan.

Statement of Conflict of Interest All authors declare that there are no conflicts of interest.

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