We divided all patients into quartiles based on ABI and IASBPD to analyze the risk of clinical outcomes. Table 3 shows the Cox proportional hazard analyses for the associations of ABI and IASBPD in quartiles with composite events and all-cause mortality. Only patients in the lowest quartile of ABI had a significant risk of composite events (HR, 3.27; 95% CI, 1.64–6.49, P < .01) and all-cause mortality (HR, 13.26; 95% CI, 1.72–102.71, P = .01). However, this association was not found when patients were divided based on IASBPD.
In the present study, ABI < 0.9 rather than IASBPD > 10 mm Hg exhibited a significant association with composite events and all-cause mortality in patients with T2DM. The tremendous increment of risk in cardiovascular outcomes was found in the lowest quartile group of ABI. The risk of cardiovascular events increased along with increment in IASBPD; however, the HR of the highest quartile group with IASBPD majorly >10 mm Hg did not reach statistical significance. Neither ABI < 0.9 plus IASBPD ≥ 10 mm Hg (data not shown) nor IASBPD associated with all-cause mortality demonstrated that the non-HDL-c was less important factor to be influenced on the risk of composite events and all-cause mortality in this analysis comparing ABI.
Furthermore, ABI plays a complementary role in risk stratification of cardiovascular disease. The Framingham risk score is a well-known validated tool to assess cardiovascular risk factors and identify high-risk individuals among individuals without diabetes. Additional parameters are needed together with the Framingham risk score to assess cardiovascular risk, particularly for asymptomatic individuals with diabetes. ABI was considered as a parameter to improve the accuracy of cardiovascular risk prediction beyond the Framingham risk score. A device can obtain IASBPD and ABI simultaneously, preventing the bias of measurement resulting from discrepancy of different devices or timing of data collection; therefore, direct comparison between ABI and IASBPD was reasonable in the present study. Increased differences in blood pressure between limbs are recognized as the consequence of PAD.[25,26] IASBPD was indicated to be associated with pulse-wave velocity[27,28] and carotid intima medial thickness. However, the IASBPD was not associated with primary or secondary outcomes in our cohort of patients with T2DM. The IASBPD was associated with some parameters, which were associated with cardiovascular outcomes, but the association of IASBPD with cardiovascular outcomes cannot be found because the actual mechanisms of differences of blood pressure between limbs are not completely understood in patients with diabetes. Furthermore, the normal range threshold seems to be changed in different populations, except for elusive mechanisms of IASBPD. Several reports described IASBPD > 10 mm Hg to be associated with elevated cardiovascular event rates, but 15 mm Hg seems to be a more appropriate threshold for diabetes.[30–32] We did not find an association between IASBPD and cardiovascular outcomes in the present study, and even the highest quartile group of IASBPD included patients with IASBPD > 9 mm Hg. In addition, IASBPD was also not associated with all-cause mortality in the previous cohort study. Another possible explanation for neutral effects on outcomes of IASBPD was the influence of medications. Our patients were being treated with several medications including angiotensin converting enzyme inhibitor, angiotensin II receptor blockade, statin, beta-blocker, or antiplatelet drugs. The use of these medications might influence the association between IASBPD and all-cause mortality, but there was no imbalance in the use of specific medications in our study. Further studies to assess the impact of medication on cardiovascular outcomes in diabetes with or without PAD should be conducted in the future.
This study has some limitations. First, this is a retrospective study conducted in a single center in Taiwan; therefore, the selection bias is inevitable, and whether the results can be applied to other ethnicities should be verified by further research. Second, the numbers of patients with diabetes with ABI < 0.9 were relatively too small compared with the general population; however, the prevalence rate is consistent with the present study. Furthermore, multicenter prospective studies are warranted to confirm the conclusion of our study. Finally, the medical histories and cardiovascular events based on medical records might have led to bias in this analysis.
The authors thank the Medical Sciences and Technology Building of Taipei Veterans General Hospital for providing them with an experimental space and facilities.
Analysis data: LYL, CHC, LHC.
Cases contributor: CMH, JGSW, LYL.
Study design and data collection: LYL, CMH, LHC.
Writing the manuscript: LYL, CHC, LHC.
Li-Hsin Chang orcid: 0000-0002-6969-5432.
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