High CAC Scores Associated With Increased Dementia, Mortality Risk in 'Oldest Old'

Deborah Brauser

March 02, 2016

PITTSBURGH, PA — Measures of subclinical CVD may help predict risk of cardiac events, mortality, and dementia in the "very elderly," new research suggests[1].

Analysis of more than 500 patients older than 80 years from the Cardiovascular Health Study–Cognition Study showed that a high coronary artery calcium (CAC) score was significantly associated with adjusted mortality, CHD, and MI rates.

In addition, there was a significantly decreased incidence of dementia in the white female participants with low CAC scores.

Lead investigator Dr Lewis H Kuller (University of Pittsburgh, PA) told heartwire from Medscape he was surprised to find increased longevity and "a fairly substantial reduction" in dementia risk in the white women who had low levels of coronary atherosclerosis and that "this seems to be independent of some of the other variables."

"I felt this was unusual and fairly important because we have the ability to reduce the extent of vascular disease. And if vascular disease is a major cause of dementia, we have a potential approach to reducing dementia in older people," said Kuller.

The findings were published in the March 8, 2016 issue of the Journal of the American College of Cardiology.

In an accompanying editorial[2], Drs Walter Swardfager and Sandra E Black (University of Toronto, ON) note that "accurate, well-understood predictive biomarkers and precisely targeted interventions" are needed to optimize outcomes in aging individuals.

"This new study provided some new evidence of the impact of subclinical heart disease on the brain," said Swardfager to heartwire . "We don't currently know the best way to reduce this effect, but it's critically important that we learn how to protect the brain from it."

Number of Elderly "Increasing Dramatically"

Kuller noted the investigators previously published a study showing that approximately 60% of their participants between 80 and 85 had developed dementia. "It's a huge problem. And with the improving life expectancy in the US, the number of older people is increasing dramatically—especially in the oldest old," he said.

"So we wanted to ask whether you're protected against coronary disease by having a low risk of atherosclerosis—and would that reduce risk of dementia in an older cohort we were studying?" asked Kuller.

"We basically wanted to see if you were heart healthy you might also potentially be brain healthy."

In this analysis, the researchers assessed 532 individuals older than 80 years who participated in the cognitive portion of the CV Health Study between 1998–1999 and 2012–2013 and were located in Pittsburgh. All underwent brain MRIs at baseline, as well as second MRIs and/or detailed cognitive evaluations.

In the 433 participants who had CAC measurements, 311 (72%) were free of clinical CAD at baseline. This included 157 white women, 77 white men, 45 black women, 29 black men, and three participants who were classified as "other." Other measures included ankle-brachial index (ABI) and stenosis.

CAC scores higher than 400 were found in 36% of the study participants. The lowest CAC scores were found in women vs men and in blacks vs whites.

"CAC score and number of coronary calcifications were directly related to age-adjusted total mortality," report the investigators. The hazard ratio for mortality was 1.73 (95% CI 1.18–2.54) for those with CAC scores greater than 400 vs scores lower than 10. In addition, CAC score was significantly associated with mortality in white men and in black women.

CAC score was also significantly linked to CHD incidence and MIs in white and black women and in white men. And more calcifications were associated with CHD in the white participants (P=0.03).

Dementia Risks

Dementia incidence rates were higher than CHD rates for women in all age groups and for the older men. Although dementia rates did not differ significantly between all of the men vs all of the women, white women with a CAC score of zero had lower dementia incidence than white women with a score greater than 400 (age-adjusted rates per 1000 person-years, 102 vs 31, respectively; P=0.04).

CAC score was not significantly linked to dementia risk for the white men or for the black men or women. However, "the analysis was limited by the small number of participants, especially for subjects with low CAC scores," note the researchers.

Increased dementia risk was also significantly associated with lower vs higher ABI in white women (P=0.02) and with maximal percent stenosis in white men (P<0.05).

An assessment of all deaths that occurred during the study period found that 25% were caused by CHD vs 16% caused by dementia. Still, "approximately 64% of those who died had a prior diagnosis of dementia."

The investigators point out that it's still unknown whether interventions that reduce atherosclerosis risk could also decrease incidence of dementia.

"The alternative could be an unfortunate outcome: that successful control of risk factors and treatment of CHD results in an increasing epidemic of dementia among older people," they write.

On the other hand, Kuller noted that if their findings bear out in "good, aggressive studies," there could be a profound effect on healthy longevity in this patient population as dementia risk is decreased. "There's no question in my mind that this could potentially be a very big payoff for the older populations in the United States," he said.

"For now, I think the key is to work aggressively to prevent atherosclerosis complications in people as they age."

Intervention Studies Needed

In the editorial, Swardfager and Black agree, noting "the importance of pharmacological and nonpharmacological management of vascular risk factors in midlife." Their list of modifiable risk factors include hypertension, diabetes, obesity, sedentary behavior, and smoking.

"I think it's a little premature to suggest that doing all of those things will prevent what the authors found. But it certainly makes a case for understanding how these risk factors may affect the brain," Swardfager said to heartwire.

He noted that one of the most interesting study findings was that "the presence of calcification in the coronary artery, even in those who hadn't had a heart attack up to the age of 80, still predicted dementia onset."

And he stressed the need for more studies to deal with these issues. "We have a lot of observational evidence that fitness is beneficial to preserve brain function later in life. But, unfortunately, we don't know what the most effective training regimens are." For example, nobody knows whether resistance training or aerobic training is better, or what intensity or amount is required. "Or is it just sedentary behavior we need to avoid?" he speculated.

"So, designing interventions to prevent calcification and thereby prevent its effect on the brain will have to take into account a lot of variables," said Swardfager.

In addition, "specialists are going to need to start working together more in order to prevent dementia in later life. This includes cardiologists and neurologists, as well as family physicians, who will be the first to recognize some of these symptoms."

The study was funded by grants from the National Heart, Lung, and Blood Institute and by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging. The study authors report no relevant financial relationships. Swardfager reports being supported by Sunnybrook Health Sciences Center, Sunnybrook Research Institute, and the Canadian Partnership for Stroke Recovery. Black reports being supported by the Sunnybrook Health Sciences Center and Sunnybrook Research Institute and the Toronto Dementia Research Alliance; she has received institutional grants from Pfizer, GE Healthcare, Eli Lilly, Transition Therapeutics, Novartis, Roche, Cognoptix, and Biogen Idec and personal honoraria from Boehringer Ingelheim, Novartis, and Merck.

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