Objective: To examine the association of total cerebral blood flow (CBF) with all-cause, noncardiovascular, and cardiovascular mortality in older subjects at risk of cardiovascular disease.
Methods:We included 411 subjects with a mean age of 74.5 years from the MRI substudy of the Prospective Study of Pravastatin in the Elderly at Risk. Total CBF was measured at baseline, and occurrence of death was recorded in an average follow-up period of 11.8 years. For each participant, total CBF was standardized for brain parenchymal volume. Cox regression models were used to estimate risk of all-cause, noncardiovascular, and cardiovascular mortality in relation to CBF.Results: Mortality rates among participants in low, middle, and high thirds of total CBF were 52.1, 41.5, and 28.7 per 1,000 person-years, respectively. Compared with participants in the high third of CBF, participants in the low third had 1.88-fold (95% confidence interval [CI]: 1.30-2.72) higher risk of all-cause mortality, 1.66-fold (95% CI: 1.06-2.59) higher risk of noncardiovascular mortality, and 2.50-fold (95% CI: 1.28-4.91) higher risk of cardiovascular mortality. Likewise, compared with participants in the high third of CBF, participants in the middle third had 1.44-fold (95% CI: 0.98-2.11) higher risk of all-cause mortality, 1.29-fold (95% CI: 0.82-2.04) higher risk of noncardiovascular mortality, and 1.86-fold (95% CI: 0.93-3.74) higher risk of cardiovascular mortality. These associations were independent of prevalent vascular status and risk factors. Structural and functional integrity of the brain depends on adequate supply of nutrients and oxygen through blood flow. 1 The brain is a demanding organ and consumes approximately 20% of the oxygen inspired at rest while accounting for only 2% of the body weight. 2 This high metabolic demand renders the brain tissue vulnerable to low cerebral blood flow (CBF), as several animal studies have shown that long-standing cerebral hypoperfusion leads to neuronal loss, microvascular abnormalities, and cognitive deficit. 3,4 Decreased cerebral perfusion in patients with acute traumatic brain injury and cerebrovascular accidents has been linked to adverse clinical outcomes and shorter survival. 5,6 Likewise, clinical conditions with a state of chronic reduction in CBF, such as heart failure and carotid stenosis, have been associated with an increased risk of mortality. 7,8 Despite this evidence, the independent role of CBF in the maintenance of health and survival in old age has not been thoroughly investigated.