The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element. Nrf2 is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure. Nrf2 is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests that Nrf2 activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under which Nrf2 acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influence Nrf2 pathways are required before Nrf2 can be considered a therapeutic target for the treatment of cardiovascular diseases.

Highlights We carried out an umbrella review of systematic reviews with meta-analyses of observational studies on handgrip strength and all health outcomes. Three outcomes (lower all-cause mortality, lower cardiovascular mortality, and lower risk of disability) were found to have highly suggestive evidence. One outcome (chair rise performance over time) was found to have suggestive evidence. Five outcomes (walking speed, inability to balance, hospital admissions, cardiac death, and mortality in those with chronic kidney disease) were found to have weak evidence.

Background: Previous meta-analyses based on aggregate group-level data report antihypertensive effects of isometric resistance training (IRT). However, individual participant data meta-analyses provide more robust effect size estimates and permit examination of demographic and clinical variables on IRT effectiveness. Methods: We conducted a systematic search and individual participant data (IPD) analysis, using both a one-step and two-step approach, of controlled trials investigating at least 3 weeks of IRT on resting systolic, diastolic and mean arterial blood pressure. Results: Anonymized individual participant data were provided from 12 studies (14 intervention group comparisons) involving 326 participants (52.7% medicated for hypertension); 191 assigned to IRT and 135 controls, 25.2% of participants had diagnosed coronary artery disease. IRT intensity varied (8–30% MVC) and training duration ranged from 3 to 12 weeks. The IPD (one-step) meta-analysis showed a significant treatment effect for the exercise group participants experiencing a reduction in resting SBP of −6.22 mmHg (95% CI −7.75 to −4.68; P < 0.00001); DBP of −2.78 mmHg (95% CI −3.92 to −1.65; P = 0.002); and mean arterial blood pressure (MAP) of −4.12 mmHg (95% CI −5.39 to −2.85; P < 0.00001). The two-step approach yielded similar results for change in SBP −7.35 mmHg (−8.95 to −5.75; P < 0.00001), DBP MD −3.29 mmHg (95% CI −5.12 to −1.46; P = 0.0004) and MAP MD −4.63 mmHg (95% CI −6.18 to −3.09: P < 0.00001). Sub-analysis revealed that neither clinical, medication, nor demographic participant characteristics, or exercise program features, modified the IRT treatment effect. Conclusion: This individual patient analysis confirms a clinically meaningful and statistically significant effect of IRT on resting SBP, DBP and mean arterial blood pressure.

Isometric exercise training has been shown to reduce resting blood pressure, but the effect that this might have on orthostatic tolerance is poorly understood. Changes in orthostatic tolerance may also be dependent on whether the upper or lower limbs of the body are trained using isometric exercise. Twenty-seven subjects were allocated to either a training or control group. A training group first undertook 5 weeks of isometric exercise training of the legs, and after an 8 week intervening period, a second training group containing six subjects from the initial training group, undertook 5 weeks of isometric arm-training. The control group were asked to continue their normal daily activities throughout the 18 weeks of the study. In all subjects orthostatic tolerance, assessed using lower body negative pressure (LBNP), and resting blood pressure were measured before and after each of the 5 week training or control periods. Estimated lean leg volume was determined before and after leg-training. During all LBNP tests, heart rate and blood pressure were recorded each minute, and the time taken to reach the highest heart rate was derived (time to peak HR). Resting systolic blood pressure (mean & s.D.), when measured during the last week of trainiig was significantly reduced after both leg (-10 f 8.7 mmHg) and arm (-12.4 5 9.3 mmHg P < 0.05) isometric exercise training, compared to controls. This reduction disappeared when blood pressure was measured immediately before the LBNP tests, which followed training. Orthostatic tolerance only increased after leg-training (20.8 f 16.4 LTI; P < 0.05) and was accompanied by an increased time to peak HR (119.8 4 106.3 beats mir-'; P < 0.05) in this group. Blood pressure responses to LBNP did not change after arm-training, leg-training or in controls (P > 0.05). There was a small but signiticant increase in estimated lean leg volume after leg-training (0.1 f 0.1 1; P < 0.05). These results suggest that lower resting blood pressure is probably not responsible for the increased orthostatic tolerance after isometric exercise training ofthe legs. Rather, it is possible that the training altered some other aspect of cardiovascular control during orthostatic stress that was apparent in the changes in heart rate. Legtraining was accompanied by increases in estimated lean leg volume. The effects of isometric training on orthostatic tolerance appear to be specific to limbs that are directly involved in LBNP testing. Expen 'menfal Physiology (2002) 87.4, 507-5 15.

The reproducibility of tolerance to lower-body negative pressure (LBNP) has not been assessed sufficiently. Furthermore, there has been confusion concerning the most appropriate index by which LBNP tolerance can be quantified. The purpose of this study was to assess the degree of reproducibility in presyncopal-symptom-limited LBNP (LBNPtol), using an LBNP chamber. Twenty physically active subjects [median age (range) 21 (18-27) years] underwent three successive LBNPtol tests with 72-120 h between each test. LBNPtol was quantified using the LBNP tolerance index (LTI; delta mmHg.min), cumulative stress index (CSI; mmHg.min), duration of negative pressure (DNP) and maximum magnitude of negative pressure (MNP). Heart rate (fc), systolic (SBP) and diastolic (DBP) blood pressures from the three repeated tests were compared during a control period. The changes from control to maximum response (fc, SBP, DBP) during LBNP were also compared, and percentage changes in estimated blood volume were measured. There were no statistical differences between any of these comparisons (P > 0.05). LTI and CSI were greater in the third test when compared to the first two tests (P < 0.05). The values for DNP and MNP were not statistically different between tests (P > 0.05). Measures of LTI and CSI showed an acceptable level of reproducibility for the first two repeated tests. However, there was an increase in LBNPtol on the third successive exposure to LBNP. These findings have shown that it is possible to achieve reproducible measures of tolerance to LBNP when using a custom-built chamber. This only applies to a test-retest procedure. Furthermore, these data also suggest that DNP and MNP do not adequately reflect the differences shown in LBNP tolerance when using LTI and CSI as measures.