Does an acute inflammatory response temporarily attenuate parasympathetic reactivation?

PURPOSE: Although observational studies suggest that inflammatory markers are associated with autonomic nervous system function, the causal relationship of this is not clear. We tested the hypothesis that acute inflammation will temporarily attenuate vagal reactivation as measured by heart rate recovery after exercise. METHODS: In this double-blind randomized study, 24 healthy subjects were assigned to receive either an influenza vaccine (n = 15) as a model to generate a systemic inflammatory response or a sham vaccine (n = 9). Heart rate recovery after exercise testing was used as an index of parasympathetic nervous function and was calculated as the difference between maximal heart rate during the test and heart rate 1 and 2 min after cessation of exercise. Both blood analysis and treadmill exercise stress tests were conducted before and 48 h after each vaccination. RESULTS: Inflammatory marker, log C-reactive protein (1.9 +/- 1.2 to 2.8 +/- 1.4, p < 0.05) was significantly increased after the influenza vaccine. Heart rate recovery 1 was significantly attenuated 48 h after the influenza vaccination (23.4 +/- 6.4 to 20.5 +/- 4.9, p < 0.05) but not sham vaccination. CONCLUSIONS: These findings show that acute inflammation is associated with a temporary deterioration in cardiac autonomic nervous system function in healthy subjects.

Association between heart rate recovery after exercise testing and plasminogen activator inhibitor 1, tissue plasminogen activator, and fibrinogen in apparently healthy men.

OBJECTIVE: Delayed heart rate recovery (HRR) following exercise testing, an indicator of decreased autonomic nervous system activity, is associated with an increased risk of cardiovascular events. Because autonomic nervous system function may be associated with fibrinolytic factors, we tested the hypothesis that delayed HRR is associated with elevated fibrinolytic factors. METHODS: In 547 (mean age 49.4+/-6.9 years) healthy men who underwent exercise treadmill testing and fasting blood analysis for fibrinolytic factors, we calculated HRR as the difference between maximum heart rate during the test and heart rate 1 min after cessation of exercise. RESULTS: HRR was inversely correlated with plasminogen activator inhibitor 1 (PAI-1) activity (r=-0.23, p<0.001), tissue plasminogen activator (t-PA) antigen (r=-0.19, p<0.001), and fibrinogen (r=-0.11, p<0.05). Men in the lowest quartile of HRR had significantly higher PAI-1, t-PA, and fibrinogen than men in the highest quartile of HRR (all p trend <0.001). HRR was independently associated with PAI-1 (beta=-0.12, p<0.01) and fibrinogen (beta=-0.09, p=0.04) but not t-PA (beta=-0.06, p=0.29) in a multiple regression analysis. CONCLUSIONS: These results suggest that delayed HRR after exercise testing is associated with elevated fibrinolytic factors in cross-section. The presence of other CHD risk factors does not explain this association, but further research is needed to identify the direction of the association.

Relation of heart rate recovery after exercise to C-reactive protein and white blood cell count.

This study was conducted to test the hypothesis that slow and abnormal heart rate recovery (HRR), an indicator of decreased autonomic nervous system activity, after exercise is associated with inflammatory markers. Subjects who underwent exercise treadmill testing (n = 5,527, mean age 50.4 +/- 8.5 years) were studied in a cross-sectional design. HRR was calculated as the difference between maximum heart rate during the test and heart rate 1 minute after the cessation of exercise. Abnormal HRR was defined as < or =12 beats/min. Subjects with abnormal HRR had higher levels of log C-reactive protein (CRP; 1.38 +/- 0.6 vs 1.11 +/- 0.4 mg/dl, p <0.001) and higher white blood cell counts (6.9 +/- 2.1 vs 6.2 +/- 1.7 x 10(9) cells/L, p <0.001) than those with normal HRR. HRR was associated with CRP (r = -0.21, p <0.001) and white blood cell count (r = -0.19, p <0.001). HRR was independently associated with CRP (beta = -0.13, p = 0.001) in a stepwise multiple regression. In a logistic multivariate model, the group within the highest quartile of CRP (odds ratio 1.54, 95% confidence interval 1.05 to 2.27) was more likely to have abnormal HRR than those within the lowest quartile. In conclusion, slow and abnormal HRR after exercise testing is associated with inflammatory markers, which could contribute to the high incidence of cardiovascular disease in these subjects.

Exaggerated blood pressure response to exercise is associated with carotid atherosclerosis in apparently healthy men.

OBJECTIVE: Although an exaggerated systolic blood pressure (SBP) response to exercise is a predictor of future hypertension and cardiovascular mortality, the underlying mechanisms are not fully understood. We tested the hypothesis that an exaggerated SBP response is associated with carotid atherosclerosis in a cross-sectional study of 9073 healthy men (aged 47.8 +/- 8.8 years). METHODS: Exaggerated SBP response was defined as an SBP of 210 mmHg or greater during a maximal treadmill test. Carotid atherosclerosis was defined as stenosis greater than 25% or intima-media thickness greater than 1.2 mm using B-mode ultrasonography. RESULTS: An exaggerated SBP response was present in 375 men (4.1%). The proportion of individuals with carotid atherosclerosis in the group with an exaggerated SBP response to exercise was higher than in the group with a normal SBP response (14.4 versus 5.3%, P < 0.001). In a multivariable logistic regression model, individuals with an exaggerated SBP (>or= 210 mmHg) response to exercise had a 2.02 times [95% confidence interval (CI) 1.33-3.05] increased risk of carotid atherosclerosis compared with individuals with an SBP response of less than 210 mmHg. The highest quartile (> 61 mmHg) group of relative exercise-induced increases in SBP showed a 1.57 (95% CI 1.18-2.08) greater risk of carotid atherosclerosis compared with individuals in the lowest quartile (< 38 mmHg) in the adjusted model. CONCLUSIONS: These results suggest that an exaggerated SBP response to exercise is strongly associated with carotid atherosclerosis, independent of established risk factors in healthy men. It may be an important factor in evaluating hypertension related to target-organ damage.