Prolonged Peripheral Hypoperfusion Promotes Neuroprotection in Ischemic Stroke.

Objectives Sublethal, transient occlusion of peripheral vessels, called remote ischemic preconditioning (RIPC), induces a neuroprotective state against brain infarction. Recent studies suggest chronic hypoperfusion in patients with peripheral vascular disease (PVD) has analogous effects. We hypothesized a positive correlation between the severity of chronic hypoperfusion and the extent of neuroprotection. To determine if this correlation exists, we compared stroke volumes and clinical measures of modified ranking scale (mRS) and National Institute of Health Stroke Scale (NIHSS) between cases with and without PVD, subgrouping PVD cases by ankle-brachial-index (ABI) values. Patients and methods Cases of ischemic stroke with and without PVD were sampled retrospectively from a local institutional data base. Charts were manually reviewed for demographics (age, sex, ethnicity), comorbidities (diabetes, hypertension, hyperlipidemia, coronary artery disease, smoking, and stroke history), clinical measures (admission NIHSS, prior mRS, three-month mRS, and survival) and stroke volumes in each case. Those diagnosed with PVD and ABI indicating active disease were grouped as PVD cases; those not diagnosed with PVD or having ABI indicating absence of disease were used as controls. PVD cases were subgrouped by disease severity per ABI values: mild (ABI 0.8-0.9), moderate (ABI 0.5-0.9) and severe (ABI < 0.5). Data were analyzed in R using adjusted logarithmic-multivariate models. Adjusted cox proportional hazards models were used to estimate associations between survival and PVD. Results A total of 105 patients, 50 PVD cases and 55 controls, were collected. Mean age was 72.54 years, 51.4% were males and 48.6% females, and 94% were Caucasian. There were 17 mild, 22 moderate, and 11 severe cases of PVD. A higher incidence of comorbidities was present in PVD cases. The mean admission NIHSS was 4.44 and did not differ significantly between groups. Stroke volumes were significantly lower (p = .021) in PVD cases (4.39 ± 8.97 ml) compared to controls (19.33 ± 44.31 ml). There was also a significant difference (p = .04) between volumes of mild (3.86 ± 5.47 ml) and severe (0.63 ± 0.76 ml) PVD cases. There were significant differences (p = .012) in the incidence of good outcomes in moderate to severe PVD cases (100%) compared to controls (83.3%). There was no difference in survival between groups (p = .538). Conclusion Increasing degrees of hypoperfusion related to PVD have a potential neuroprotective effect in acute ischemic stroke quantified by lower stroke volumes and better clinical outcomes at three months as seen in other preclinical models of RIPC.