The main finding of our study was that high ankle %MAP acted synergistically with low ABI to improve prediction of all-cause mortality in patients with type 2 DM. Using a combination of the two indices, ABI ≤ 0.90 and %MAP > 45%, predicted an approximately two-fold mortality risk than ABI > 0.90 and %MAP ≤ 45%. These results support our previous study which showed that high %MAP was a significant predictor of all-cause mortality in subjects with normal ABI [12]. A recent study has also shown that %MAP was associated with cardiovascular mortality in patients receiving hemodialysis [16]. The strength of the present study is that we demonstrated the synergistic effect of ABI and %MAP for prediction of mortality in a large sample of more than 5000 patients with type 2 DM.
Low ABI indicates a reduced systolic blood pressure at the ankle relative to that in the brachial artery, and this suggests partial occlusion of the ankle arteries [17]. Since the systolic blood pressure will be elevated in a non-compressible artery at the ankle, a false negative PAD diagnosis may occur when ABI alone is used for screening [18, 19]. In the study by Wukich, et al., 42.7% of patients with DM and confirmed PAD had normal ABI value [20].
The %MAP represents the percentage difference between the mean and maximum amplitude of the ankle pulse volume waveform [11]. An occluded artery with a flatted waveform will result in an increased in %MAP value [10]. Therefore, the pulse volume recording at the ankle might be a sensitive indicator of an occlusive artery with a non-compressible pattern, which is frequently observed in patients with DM [21].
The prevalence of PAD is increasing worldwide, and DM is an important risk factor for PAD [22, 23]. Most patients with PAD are asymptomatic, but they have elevated risk for mortality [22–24]. In Taiwan, annual screening for foot complications is recommended in the clinical guidelines and in the P4P program for patients with DM [13, 25]. In previous studies that have used the cutoff value of ABI ≤ 0.90, the prevalence of PAD in type 2 DM was about 10.0% in patients with a mean age of 63 years in Taiwan, 10.4% in Malay patients (mean age, 63 years) who living in Singapore, and 9.5% in patients (age > 40 years) in the US [26–28]. According to the real-world database, PAD was reported in 18.7% of patients with type 2 DM (mean age, 65 years) in the UK and in 13.6% patients with type 2 DM (mean age, 66 years) in the US [29, 30]. In the present cohort, PAD prevalence was 8.4% when ABI ≤ 0.90 was the only criterion used, but increased to 17.4% when the combination of ABI ≤ 0.90 and %MAP > 45% were used. In the Taiwan National Health Insurance database, less than 2.2% patients with DM and age ≥ 65 years have a diagnosis of PAD, indicating that the condition is greatly underdiagnosed in clinical practice [31]. Thus, using ABI along with the automatically reported ankle %MAP is an effective and convenient method for PAD screening and for prediction of mortality [9, 12].
The risk factors for abnormal ABI have been well investigated, but the risk factors for high %MAP are still not specified [32, 33]. In the present study, the risk factors significantly associated with %MAP in both the different ABI groups, included age, CVD history, BMI, HbA1c, eGFR, UACR, baPWV, use of antiplatelet agents, type of oral antihyperglycemic drug, and type of hypertensive drug (Table 1). However, we did not include all cardiovascular risk factors in the present study; for example, a higher HbA1c variability has been previously reported to be associated with a higher %MAP [15]. Furthermore, this study has several limitations. First, all participants were from a single teaching hospital, and the results may not be generalizable to all population with type 2 DM. Second, this was a retrospective study and so we could not control the risk factors and treatments received during the follow-up period. Third, the cutoff value of 45% for %MAP is based on the findings of previous studies [12]; we did not assess the normal range of %MAP in the present study.
In conclusion, the use of %MAP along with ABI appears to improve prediction of all-cause mortality in patients with type 2 DM. The %MAP is automatically reported during ABI measurement and so can conveniently be used for improving prognosis prediction in clinical practice.