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Failing Heart Linked to Failing Brain - attached are both pdfs, the article & a commentary from the Jnl of the Am Heart Ass Epub
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MedPage Today
Published: August 02, 2010
"Cardiac Index Is Associated With Brain Aging The Framingham Heart Study:" our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.....Cardiac index is associated with brain volume, even in individuals without diagnosed prevalent CVD.....we propose that subtle reduc- tions in cardiac index, as well as cardiac index values in the low end of the normal range, may be implicated in accelerating age-related changes in the brain. we cannot rule out the possibility that the findings are due to some epiphenomenon. Further investigation into the mech- anisms and clinical significance of the association between cardiac index and brain aging is merited.....In this study of a community-dwelling cohort of ambulatory adults, we found that cardiac index was associated with total brain volume and lateral ventricular volume, both markers of accelerated brain aging17,42; however, when analyses excluded participants with prevalent CVD, only the association between cardiac index and total brain volume remained. The association was stronger for indi- viduals <60 years of age, which coincides with a period in the lifespan with reduced risk for abnormal brain changes, possibly allowing the influence of cardiac index on brain health to be more prominent. Individuals in the top tertile of cardiac index had a higher mean total brain volume equivalent to nearly 2 years of healthy brain aging com- pared with those participants in either the middle or bottom tertile of cardiac index. Although cardiac index as a continuous variable was unrelated to neuropsychological performances, when clinical cutoffs were applied, low cardiac index was related to information processing speed, a finding that was modestly attenuated when participants with prevalent CVD were excluded from analyses. Collectively, these results suggest that even in the absence of prevalent CVD, cardiac index is related to total brain volume, a neuroimaging marker of brain health, and low cardiac index is related to information processing speed. Prior research relating cardiac output to neuroim- aging and neuropsychological phenotypes of maladaptive brain aging in clinical cohorts has yielded significant associations"
Poor cardiac output, even at the low end of normal, may accelerate the brain volume losses that come with age, researchers said.
Cardiac index remained directly linked to total brain volume (P=0.02) after adjusting for age and other important factors and excluding those with cardiovascular disease, according to Angela L. Jefferson, PhD, of the Alzheimer's Disease Center at Boston University, and colleagues.
The threshold for risk appeared low, they reported online in Circulation: Journal of the American Heart Association.
Action Points
* Explain to patients who ask that this study suggests a relationship between cardiac output (reported as cardiac index) and brain volume, which may be related to changes in cognition associated with the aging process.
* Point out that as a cross-sectional study, it cannot make claims about causality and prospective studies with longitudinal measures would be necessary to confirm these results.
Using the normal clinical definition of low cardiac index -- 2.5 L/min/m2 -- wasn't enough.
Rather, an "average" cardiac index in the middle tertile was associated with mean brain volumes that were just as low as those in the bottom cardiac index tertile. The effect on brain volume was the equivalent of nearly two years of brain aging compared with the top tertile who had a cardiac index above 2.92 L/min/m2 (P=0.04).
The lack of a clear dose-response relationship was surprising, but this result may have wide implications, suggested Clinton B. Wright, MD, MS, and Ralph L. Sacco, MD, MS, both of the University of Miami in Miami.
"In population-based studies, we tend to think that extremes are bad and the middle is good, but in this study, it was possible to associate the brain volumes of two-thirds of a relatively healthy population with the cardiac index exposure," they wrote in an accompanying editorial.
These observational findings, which came from a brain and cardiac MRI substudy of the Framingham Heart Study, could not determine causality, the researchers cautioned.
They speculated, though, that impaired heart function might reduce perfusion to the brain, causing damage that leads to Alzheimer's disease and other forms of dementia.
While this clearly has been seen in relation to heart failure, the evidence isn't as good for subclinical cardiac dysfunction, Wright and Sacco cautioned.
Some evidence even may suggest a common "wear and tear" process from build-up of misfolded proteins in heart and brain that could account for the association rather than a direct cause-and-effect link, commented Cam Patterson, PhD, of the University of North Carolina in Chapel Hill.
Whatever the true mechanism for the link, it raises the possibility that taking better care of the heart could prevent dementia, Patterson said in an interview.
"If physicians see patients with evidence of cognitive decline, they should think about the possibility of an undiagnosed cardiac problem and, conversely, I think that we need to be aware that our patients who have some degree of cardiac dysfunction may be at increased risk of mental decline," he told MedPage Today.
One ramification may be that physicians need to ensure that their older patients with heart disease are cognitively able to handle complex medication regimens, he suggested.
It also suggests that primary care physicians and neurologists may need to be more aggressive in treating even borderline cases of heart failure, commented neurologist Liana Apostolova, MD, MSCR, of the University of California Los Angeles.
Confirmation of the results in longitudinal analyses could have a big impact on public healthcare policy as well, since a healthy lifestyle can prevent development of reduced cardiac output as a sign of heart failure, she said in an e-mail.
The researchers measured cardiac output per body surface area (cardiac index) using cardiac MRI in 1,504 individuals in the Framingham Offspring Cohort who had no history of clinical stroke, transient ischemic attack, or dementia at baseline.
All were community-dwelling and ambulatory and between the age of 34 and 84 (average 61).
After multivariable adjustment but not exclusion of those with incident cardiovascular disease, cardiac index was associated with total brain volume (P=0.03) such that each one standard deviation higher cardiac index was linked to a 0.30 increase in brain volume as a percentage of total cranial volume.
By comparison, the typical loss in total brain volume is 0.19 per year of increased age, Jefferson's group noted.
Higher cardiac index was also associated with a trend for better executive function (P=0.06) and, in a post-hoc analysis, better information processing speed (P=0.02) but lower lateral ventricular volume (P=0.048).
The link between cardiac index and brain volume appeared significant only for those under age 60, which the researchers suggested may have been because other competing causes of cognitive dysfunction become more important or mask the association in older age.
They cautioned that the study may have been limited in generalizability by the predominantly white, middle-age to elderly population and in determining directionality of the relationship because of the cross-sectional design and the acquisition of the brain MRI before the cardiac MRI.
Residual confounding was also a possibility, Jefferson's group noted, calling for further replication of their "preliminary" results.
The research was supported by the National Heart Lung Blood Institute's Framingham Heart Study, Paul B. Beeson Career Development Award in Aging Program, and the Alzheimer's Association.
The researchers reported having no conflicts of interest to disclose.
Sacco, Wright, Patterson, and Apostolova reported having no conflicts of interest to disclose.
This article was developed in collaboration with ABC News.
Primary source: Circulation: Journal of the American Heart Association
Source reference:
Jefferson AL, et al "Cardiac index is associated with brain aging: The Framingham Heart Study" Circulation 2010;
Additional source: Circulation: Journal of the American Heart Association
Source reference:
Wright CB, Sacco RL "Cardiac index as a correlate of brain volume: Separating the wheat of normal aging from the chaff of vascular cognitive disorders" Circulation 2010; DOI:10.1161/CIRCULATIONAHA.110.970301.
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