Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Blood pressure surge with alarm is reduced after exercise and diet intervention in firefighters.

BACKGROUND: Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response. PURPOSE: To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention. METHODS: SBP and DBP and BP surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured during a 12-hour workshift. Exercise and diet were self-reported. Diet was tracked with diet scores based on number of servings. RESULTS: Twenty five firefighters (43.4 ±â€…13.9 years) participated. We found changes in the magnitude of BP surge with alarm (SBP surge from16.7 ±â€…12.9 to 10.5 ±â€…11.7 mmHg, P < 0.05; DBP surge from 8.2 ±â€…10.8 to 4.9 ±â€…5.6 mmHg, P > 0.05) after intervention. We confirm that clinical (127.6 ±â€…9.1 to 120 ±â€…8.2 mmHg) and central (122.7 ±â€…11.3 to 118.2 ±â€…10.7 mmHg) SBP levels improve with exercise and diet. We report for the first time in firefighters that oxidative stress markers superoxide dismutase (9.1 ±â€…1.5 to 11.2 ±â€…2.2 U/ml) and nitric oxide (40.4 ±â€…7 to 48.9 ±â€…16.9 µmol/l) levels improve with an exercise and diet intervention. CONCLUSION: These findings have implications toward the benefit that short-term lifestyle changes make toward reducing the alarm stress response in first responders.

High pulse pressure impairs cerebral artery endothelial function in young, but not old, mice.

One of the hallmarks of vascular aging is increased pulse pressure. This elevated pulse pressure is associated with deleterious effects on cerebral vascular function; however, it is unknown if age modulates the susceptibility to high pulse pressure. To examine the effects of age on the cerebral artery response to pulse pressure, we studied isolated cerebral arteries collected from young (6.1 ± 0.2 mo) and old (26.7 ± 0.5 mo) male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure (25 mmHg), and high pulse pressure (50 mmHg). In cerebral arteries from young mice, endothelium-dependent dilation was similar between the static and low pulse pressure conditions. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young mice, mediated by less nitric oxide bioavailability and greater oxidative stress. Cerebral arteries from old mice had impaired cerebral artery endothelium-dependent dilation at static pressure compared with young cerebral arteries. However, exposure to low or high pulse pressure did not cause any further impairments to endothelium-dependent dilation in old cerebral arteries compared with static pressure. The old cerebral arteries had less distension during exposure to high pulse pressure and greater stiffness compared with young cerebral arteries. These results indicate that acute exposure to high pulse pressure impairs endothelium-dependent dilation in young, but not old, cerebral arteries. The greater stiffness of cerebral arteries from old mice potentially protects against the negative consequences of high pulse pressure.

Pyridoxamine treatment ameliorates large artery stiffening and cerebral artery endothelial dysfunction in old mice.

Age-related increases in large artery stiffness are associated with cerebrovascular dysfunction and cognitive impairment. Pyridoxamine treatment prevents large artery stiffening with advancing age, but the effects of pyridoxamine treatment on the cerebral vasculature or cognition is unknown. The purpose of this study was to investigate the effects of pyridoxamine on blood pressure, large artery stiffness, cerebral artery function, and cognitive function in old mice. Old male C57BL/6 mice consumed either pyridoxamine (2 g/L) or vehicle control in drinking water for ∼7.5 months and were compared with young male C57BL/6 mice. From pre- to post-treatment, systolic blood pressure increased in old control mice, but was maintained in pyridoxamine treated mice. Large artery stiffness decreased in pyridoxamine-treated mice but was unaffected in control mice. Pyridoxamine-treated mice had greater cerebral artery endothelium-dependent dilation compared with old control mice, and not different from young mice. Old control mice had impaired cognitive function; however, pyridoxamine only partially preserved cognitive function in old mice. In summary, pyridoxamine treatment in old mice prevented age-related increases in blood pressure, reduced large artery stiffness, preserved cerebral artery endothelial function, and partially preserved cognitive function. Taken together, these results suggest that pyridoxamine treatment may limit vascular aging.

Civilians Have Higher Adherence and More Improvements in Health With a Mediterranean Diet and Circuit Training Program Compared With Firefighters.

OBJECTIVE: To examine the relationship between diet adherence and cardiovascular disease (CVD) risk-reduction between civilians and firefighters with a 6-week Mediterranean diet and tactical training intervention. METHODS: Forty firefighters and 30 civilians participated. Blood pressure, body composition, lipid levels, vascular measures, and aerobic capacity were measured pre- and post-intervention. Diet was self-report based on number of servings consumed. Weekly diet-scores were calculated. RESULTS: Both groups had improvements in blood pressure and body composition. Civilians had improved lipid levels, higher overall adherence, a relationship between total Med-diet score and cholesterol (R = 0.68), and higher servings consumed in foods typical of Mediterranean-dietary pattern ( P < 0.05). CONCLUSION: This is the first exercise and diet intervention comparing firefighters to civilians. Adherence to a Mediterranean-dietary pattern coupled with exercise is effective at improving cardiac health. These findings substantiate the need for wellness interventions in firefighters.

Large artery stiffness and brain health: insights from animal models.

There are no effective treatments available to halt or reverse the progression of age-related cognitive decline and Alzheimer's disease. Thus, there is an urgent need to understand the underlying mechanisms of disease etiology and progression to identify novel therapeutic targets. Age-related changes to the vasculature, particularly increases in stiffness of the large elastic arteries, are now recognized as important contributors to brain aging. There is a growing body of evidence for an association between greater large artery stiffness and cognitive impairment among both healthy older adults and patients with Alzheimer's disease. However, studies in humans are limited to only correlative evidence, whereas animal models allow researchers to explore the causative mechanisms linking arterial stiffness to neurocognitive dysfunction and disease. Recently, several rodent models of direct modulation of large artery stiffness and the consequent effects on the brain have been reported. Common outcomes among these models have emerged, including evidence that greater large artery stiffness causes cerebrovascular dysfunction associated with increased oxidative stress and inflammatory signaling. The purpose of this mini-review is to highlight the recent findings associating large artery stiffness with deleterious brain outcomes, with a specific focus on causative evidence obtained from animal models. We will also discuss the gaps in knowledge that remain in our understanding of how large artery stiffness affects brain function and disease outcomes.