This cross-sectional study found quantitative, validated, left SFA pre-existent collateral function (CFI without SFA stenoses) to be directly predicted by maximal workload achieved during a physical exercise test. Accordingly, patients reporting intensive leisure time physical activity tended to have a higher SFA CFI than those without such a hobby.
Exercise and collateral function: clinical evidence
There are currently four treatment modalities reportedly reducing disability and walking distance in intermittent claudication, the most common symptom of lower limb PAD: physical exercise training, cilostazol, percutaneous intervention of pad, and surgical bypass.18 According to expert consensus,19 supervised exercise training is the primary treatment modality for patients with intermittent claudication.7 ,20 ,21 Furthermore, the efficacy of even non-supervised physical exercise training appears to be agreed upon.8 However, given the frequently employed non-specific clinical end point of walking distance, the mechanism (ischaemic preconditioning, training-induced muscle conditioning, collateral promotion) by which exercise exerts its positive effect remains elusive. In cross-sectional, as opposed to longitudinal PAD studies, the association of exercise training/performance and lower limb collateral circulation has, however, been directly addressed by using walking distance as an end point for exercise performance and not, implicitly, for the collateral circulation, which ought to be determined on its own. For example, using MRI of the SFA and collateral vessel number, McDermott et al10 found that the 6 min walking distance lost by SFA occlusion (from 1169 with patent SFA to 1031 feet) was overcompensated for by the presence of ≥8 collaterals (1246 vs 1064 feet with 0–3 collaterals). The selection of patients with total SFA occlusion in that study elegantly circumvented the pitfall of a variable influence of different SFA stenoses on collaterals. In analogy, the present study employed an artificial instead of natural SFA occlusion in the absence of SFA stenotic lesions, thus, also correcting for the diverse arteriogenic influence of varying severities of stenosis. Variable severities of stenosis instead of fixed ones (no stenosis or complete occlusion), could actually lead to opposite findings as in the just cited recent study,10 that is, a higher collateral degree associated with a reduced prevalence of asymptomatic PAD.22 In other words, the collateral circulation is both a benefactor against, and a marker for, the severity of atherosclerosis, the methodological conundrum of which has been resolved in the present study by directly measuring the SFA collateral function, and by determining two potential independent predictors, that is, GPAQ items and maximal workload achieved in an exercise test.
Most commonly used questionnaires to assess functional status and general as well as disease-specific quality of life in patients with intermittent claudication do not include GPAQ.23 To the best of our knowledge, physical activity questionnaires have not been used so far in the context of lower limb collateral function. In patients with CAD, the level of leisure time physical activity, as scored by a structured but not validated questionnaire, and coronary CFI, have been documented to be directly associated.24 In the present investigation, this result could be essentially confirmed, though the current as opposed to the past study population had much less severe stenosis in the coronary artery undergoing CFI measurement. Interestingly, coronary stenosis severity in the CFI vessel tended to be more pronounced among patients without versus with reported leisure time physical activity (see table 2); and nevertheless, coronary CFI was higher among patients engaging in leisure time physical activity. Though the coronary circulation was not in the focus of this investigation, the respective results anchor its main findings. GPAQ has been extensively validated,16 and its German version has also been employed in a recent survey on self-reported physical activity across Germany as obtained by a telephone interview.17 By comparison, the present study gained GPAQ data by telephone interview only in a minority of approximately 10% of the entire study group, that is, in those patients who did not answer the first call to fill out the questionnaire. Answering the GPAQ unassisted certainly complicated the questionnaire's part in which total physical activity durations in minutes per week had to be estimated. This is reflected by the study result that only a dichotomous GPAQ item, the grouping variable, ‘intensive leisure time physical activity’, was mirrored by maximum physical workload.
Maximal workload and quantitative SFA CFI
Maximum physical workload achieved as a continuous parameter is not dependent on an educated guess, and as such, is likely more dependable than certain GPAQ items. This appears the most probable explanation for a mere trend towards a relation between (some) GPAQ items and SFA CFI versus an actual significant and direct correlation between maximum workload and SFA CFI. However, figure 5 illustrates that approximately 92% of the SFA CFI variability was explained by parameters other than varying maximum workload. The key factor contributing to the ‘noise’ in the relation between maximum workload and SFA CFI is the time lag between the exercise test and SFA collateral function measurement. On average, the exercise test had been performed 90 days before the invasive exam with SFA CFI, and the time interval between the two events ranged from 5 years before to 1.5 years after the invasive exam. As a theoretical alternative for the scatter between the two variables, SFA CFI did not accurately reflect quantitative SFA collateral function.
Validation of quantitative SFA CFI
This hypothesis was tested in 80% of the study patients by simultaneous comparison of SFA CFI with an independent, quantitative method, transcutaneous PO2 index. It was falsified by documenting a tight and direct association between the two independent methods. Bland-Altman bias between the two methods was +0.065, and the limits of agreement −0.18 and +0.31. The trend to underestimate CFI with higher collateral function values might serve as an explanation for the flat rather than more steep relation between maximum workload and SFA CFI. Conversely, the PO2 method, though employed and validated in the past,25–27 may have technical shortcomings challenging its reference status. Notwithstanding, there was also (at least trend-wise; p=0.12) a direct association between maximum workload and transcutaneous PO2 index.