Temporal profiles of blood pressure, circulating nitric oxide, and adrenomedullin as predictors of clinical outcome in acute ischemic stroke patients

Abstract

Stroke remains an important health and social challenge. The present study investigated whether blood pressure (BP) parameters and circulating levels of nitric oxide metabolites (NOx) and adrenomedullin (AM) may predict clinical outcomes of stroke. Patients (n=76) diagnosed with acute ischemic stroke were admitted to the stroke unit and clinical history data and monitored parameters were recorded. Blood plasma was collected at days 1, 2, and 7 to measure NOx and AM levels. Infarct volume, neurological severity [on the National Institutes of Health Stroke Scale (NIHSS)], and functional prognosis (on the Rankin scale) were measured as clinical outcomes. Patients with higher BP had more severe symptoms (NIHSS >3; P<0.01) and BP variability predicted neurological severity and growth of infarct volume. NOx values were significantly lower in stroke patients than in healthy controls (P<0.01). An increase in NOx levels from day 1 to day 2 was beneficial for the patients as measured by NIHSS at 7 days and 3 months, and by Rankin at 3 months [odds ratio (OR), 0.91] whereas a steep increase from day 2 to day 7 was detrimental and associated with an increase in infarct volume (OR, 35.3). AM levels were significantly higher in patients at day 1 and 2 than in healthy individuals (P<0.01) and these levels returned to normal at day 7. Patients with high AM levels at day 2 had significantly higher NIHSS scores measured at day 1 (P<0.05) and 7 (P<0.01). A receiving operating characteristic curve analysis identified that AM levels at day 2 of >522.13 pg/ml predicted increased neurological severity at day 7 (area under the curve=0.721). Multivariate logistic regression indicated that AM levels at day 2 predicted increased neurological severity at 7 days and at 3 months. BP parameters and changing levels for NOx and AM predicted long‑term clinical outcomes as measured by infarct volume, neurological severity scale, and functional prognosis.

Figure 1

Evolution of BP parameters during the stay at the stroke unit and association with the NIHSS. SAP and DAP were measured at the ER and during the next 3 days. (A) Women had significantly higher SAP than men. ^*P<0.05 and ^**P<0.01 vs. the data from male patients. (B) At admission and at day 1 and 2, SAP was higher in patients with a history of hypertension. (C) SAP and DAP were reduced over time due to the stroke unit care. (D) There was a direct association between higher SAP and higher neurological severity measured at 24 h. Bars represent the mean ± standard deviation. ^*P<0.05; ^**P<0.01; ^***P<0.001. BP, blood pressure; NIHSS, National Institutes of Health Stroke Scale; SAP, systolic arterial pressure; DAP, diastolic arterial pressure; ER, emergency room; D1, day 1; D2, day 2; D3, day 3.

Figure 2

Evolution of NOx levels and their association with NIHSS and blood pressure. (A) The amount of circulating NOx was measured in healthy controls and stroke patients at days 1, 2, and 7. (B) Patients with higher NOx levels measured at day 2 had a lower NIHSS score at day 1. (C) When NOx data were divided in tertiles, patients in the third (highest) tertile had lower DAP at day 2 and 3. (D) Also, patients with higher SAP (third tertile) at admission had the lowest levels of circulating NOx. Bars represent the mean ± standard deviation for DAP and the median ± interquartile range for NO. ^*P<0.05; ^**P<0.01; ^***P<0.001. NIHSS, National Institutes of Health Stroke Scale; NO, nitric oxide; NOx, nitrate/nitrite and S-nitroso compounds; DAP, diastolic arterial pressure; SAP, systolic arterial pressure; C, control; T1, tertile 1; T2, tertile 2; T3, tertile 3.

Figure 3

Evolution of AM levels and their association with NIHSS. (A) The amount of circulating AM was measured in healthy controls and stroke patients at days 1, 2, and 7. Patients with higher AM levels had a higher NIHSS score measured either at (B) 24 h or at (C) 7 days. (D) A receiving operating characteristic analysis for AM predicted NIHSS at 7 days with an area under the curve of 0.721, a sensitivity of 70%, and a specificity of 60%. Bars represent the median ± interquartile range. ^*P<0.05; ^**P<0.01; ^***P<0.001. AM, adrenomedullin; NIHSS, National Institutes of Health Stroke Scale.