PAD is common, and much research has been conducted to identify possible risk factors for PAD [15–17], evaluate appropriate diagnostic modalities for PAD , and develop effective treatments for symptomatic PAD [19, 20]. LE PAD is a common vascular condition that affects both quality of life and life expectancy, with an increased risk of cardiovascular events. Choice of endovascular or surgical intervention remains controversial in an ever-evolving field, and tissue engineering is a developing area and aims to produce grafts with similar patency . The exact incidence or prevalence of LE PAD is difficult to be evaluated due to different people, different nations, and even different states of one country. For example, a multi-centers study at 350 primary care practices of 25 cities in the United States, enrolling a total of 6979 PAD patients, showed that among them, the clinical presentation varies from no symptoms to atypical rest pain, intermittent claudication, ischemic ulcers, or gangrene. Incidence of PAD throughout the US was various from 10% to 29%, with or without symptoms . In Japanese patients with PAD, women were found to have more severe symptomatic states and uncontrolled risk factors, and the prevalence of iliac artery lesions was lower, but below the knee lesions were more severe in women . Rapid progression of PAD was found in hemodialysis Taiwanese patients, and the prevalence of ABI <0.9 increased yearly (10.4%, 22.7% and 27.9%, respectively; p < 0.001) . Another retrospective study of a Singapore hospital discharge database (2004–2009) noted that DM patients with renal disease had significantly higher rates of lower extremity amputation (7.1%) compared to DM patients without renal disease (2.5%, p < 0.001) . In the present study, gender, various age strata and co-morbidity (including diabetes, hypertension, ESRD, cardiovascular disease (CAD), hyperlipidemia and an integrated co-morbidity index) were found to have significant effects on the performance of different invasive treatment methods for hospitalized PAD cases in Taiwan.
Some epidemiological studies of asymptomatic PAD in Taiwan have been performed in specific disease groups. The ABI was similarly used to detect PAD (ABI < 0.90). For example, the records of 484 Taiwanese patients with end-stage renal disease (ESRD) were reviewed and PAD had an overall prevalence of 18.2% and was significantly more common in hemodialysis (HD) patients (21.8%) than in peritoneal dialysis (PD) patients (4.8%) . Another prospective cross-sectional study showed that the prevalence of asymptomatic PAD among COPD patients in Taiwan is lower (2.5% in the younger participants (<65 years of age, n = 118) and 10% in the elderly participants (≥65 years of age, n = 309)) than in Western countries . For the general Taiwanese population, a recent survey enrolling ambulatory participants without symptoms of PAD revealed that the overall prevalence of asymptomatic PAD was 5.4% (2.8% in the younger participants [<65 years of age, n = 1021] and 8.4% in the elderly participants [≥65 years of age, n = 894]) . The present study showed an invasive treatment incidence of LE PAD in Taiwan and the latest cumulative incidence of 7.48 per 10,000 in general population was estimated in 2011. Age and period effects had been noted. Otherwise, a gender difference was also observed, and the incidence ratio (IR) of male vs female increased from 1.34 (in 2000) to 1.57 (in 2011). A significant increase in the PAD prevalence with age has also been noted in American adults, the PAD prevalence being 12.2% (95% confidence interval (CI) = 10.9-13.5%); 7.0% (95% CI = 5.6-8.4%) for those aged 60 to 69; and 12.5% (95% CI = 10.4-14.6%) and 23.2% (95% CI = 19.8-26.7%) for those aged 70 to 79 and 80 and older .
The economic burden of PAD is high. Among the US Medicare population, Medicare program outlays totaled $3.87 billion for PAD and 88% of expenditures were for inpatient care. In total, 6.8% of the elderly Medicare population received treatment for PAD. Treatment increased with age, with rates of 4.5%, 7.5%, and 11.8% for individuals aged 65–74, 75–84, and >85 years, respectively . In the present study, the national total medical expenditure for these invasively-treated PAD cases was found to have increased quickly, from $US 15.5 million per year (in 2000) to $US 59.6 million per year (in 2011). Besides, the hospitalization incidence of PAD was found to be at least 20 times higher in the elderly (65 years or greater) than in the young (<50 years). This indicated an increased medical burden of LE PAD, and much more care for aged people should be instigated by the health policy authority in Taiwan. A study based on the REduction of Atherothrombosis for Continued Health (REACH) Registry to estimate the 2-year associated costs in US patients with established PAD showed that the mean cumulative hospitalization costs per patient were $7,445, $7,000, $10,430, and $11,693 for patients with asymptomatic PAD, a history of claudication, lower-limb amputation, and revascularization, respectively (p = 0.007) . In Taiwan, the present study showed that the total direct medical cost of one hospitalized and invasively-treated PAD case ranged from $US 4,600 to $US 5,900 on average, which is much lower than other countries.
There is now a trend towards endovascular revascularization for most PAD patients. A study using the US Nationwide Inpatient Sample (NIS) database (1999–2007), identifying patients who had an identifiable ICD-9 diagnosis code of atherosclerotic disease (claudication [440.21] or limb threat [440.22-440.24]), showed that the number of patients per year undergoing PTA increased threefold . Much more dramatically in Taiwan, the present study revealed that the number of PTA procedures remarkably increased by 15 times from 2000 to 2011, which perhaps was partially contributed to by the doubled numbers of hospitals with the ability to perform PTA skills from 2000 to 2011. Data of US Medicare beneficiaries analyzed between 1996 and 2006 revealed that bypass surgery decreased by 42% (219 to 126 per 100,000; RR = 0.58; 95% CI: 0.5-0.7) . In Taiwan, the incidence of bypass surgery for PAD cases among residents aged 30 years or more was estimated as 8.4 per 100,000 and reduced to 6.4 per 100,000 from 2000 to 2011 in the present study, which showed a similar decreasing trend but was much lower than the study mentioned above. The deployment of medical resources for vascular surgeries in Taiwan may be further evaluated by the health policy authority.
Traditionally, amputation represents end-stage failure for those with LE PAD. Using data from the US Centers for Medicare & Medicaid Services (CMS) from 2000 to 2008, among 2,730,742 older patients (aged 65 years or more) with identified PAD, the overall rate of LE amputation decreased from 7,258 per 100,000 patients with PAD to 5,790 per 100,000 (p < 0.001 for trend) . In the present study, the number of limb amputations varied annually, and ranged between 4,100 and 5,100 per year (equal to 34 to 40 per 100,000) for the general population. Compared to the above study in the US, the amputation rate for LE PAD patients in Taiwan was lower. Another study using the US Nationwide Inpatient Sample (NIS) database (1999–2007) revealed that in-hospital amputation rates were significantly higher for patients who had PTA (7%) than a peripheral bypass graft (BPG) (3.9%, odds ratio [OR], 1.67 [1.49-1.85]; p < 0.01) or patients who underwent aorto-femoral bypass (ABF) (3.0%; OR, 2.32 [1.79, 3.03]; p < 0.01) . In our present study, we calculated the 2-year failure rate of PTAs, and found these to be 22.13%, 11.91% and 10.61% (including 14.86%, 8.16% and 8.51% referred for amputation) among the first (2000–2001), second (2004–2005) and third (2008–2009) cohorts, respectively. Otherwise, aging, the female gender and higher co-morbidities were found to be associated with the above 2-year PTA failure rates.
Socioeconomic disparities could persist in the amputation rates of LE PAD. Data from the US Nationwide Inpatient Sample (NIS) from 1998 to 2002 showed that multivariate analysis indicated significantly higher odds of amputation associated with the following variables: nonwhites (1.91, 95% confidence interval [CI], 1.65, 2.20), low-income bracket (1.41, 95% CI, 1.18, 1.60), and Medicare & Medicaid patients (1.81, 95% CI, 1.66, 1.97) . Another study of NIS data comparing two periods (2001–2003 and 2004–2007) found that annually, the total number of interventions increased by 15% and the average annual number of endovascular interventions increased by 78% (p < 0.001). After adjusting for age and co-morbidities, African Americans were found to have a 2.4 times greater odds of amputation as compared with Caucasians, whereas those under Medicare or Medicaid had a 1.5 times greater odds . These economically disadvantaged patients were thought to have had a delayed diagnosis of peripheral vascular disease, probably due to lack of adequate primary care or access to vascular interventions, or both. In Taiwan, the policy of listing NHI-defined catastrophic illnesses exempts some vulnerable populations from the co-payment economic burden and protects their human rights with regards to access to necessary medical care. A recent study revealed that the prevalence of certificated catastrophic illness in Taiwan’s elderly population utilizing ambulatory medical services was 10.16%. On average, 61.62 emergency department (ED) visits/1,000 persons (95% CI: 59.22–64.01) per month was estimated for elderly Taiwanese with a catastrophic illness, which was significantly greater than that for the elderly without a catastrophic illness (mean 33.53, 95% CI: 32.34–34.71). A significantly greater total medical expenditure for emergency care was observed in the catastrophic illness subgroup ($US 145.6 ± 193.5) as compared with the non-catastrophic illness group ($US 108.7 ± 338.0) (p < 0.001) . In the present study, these disadvantaged populations, including low-income people and catastrophic illness certificated patients, were evaluated. Among 51.3% of all the enrolled PAD cases treated with limb amputations, low-income people had a tendency to undergo amputation due to their condition (OR: 1.41, 95% CI: 1.30-1.53); 37.6% of those treated with PTAs with CIR had a greater opportunity to receive a PTA procedure (OR: 1.81, 95% CI: 1.76-1.87). Perhaps there was a higher opportunity to receive amputation for those on a low income, and a negative effect of low-income status on the failure of original PTAs could be observed.