Background: Frailty is a nonspecific state of vulnerability that reflects a multisystem physiological change. Recent studies suggest that impaired cerebrovascular reactivity (CVR), evaluated using the breath-holding index (BHI). is associated with a higher risk of stroke and mortality. We tested whether impaired CVR, a marker of cerebral microvascular hemodynamic dysfunction, is associated with late-life frailty among men with and without carotid large-vessel disease.
Patients and Methods: A subset of 327 men with chronic coronary heart disease (CHD) who previously participated in a clinical trial (1990 to 1997) underwent a neurovascular status evaluation by ultrasound 14.6±1.9 yrs. after baseline and were evaluated 19.9±1.0 yrs. 19.9±1 yrs. for frailty after baseline (mean age at baseline 57±6 yrs) and at the late-life evaluation 77±6.4 yrs). CVR was measured using the breath-holding index (BHI) with Transcranial Doppler and carotid large-vessel disease (bilateral plaques) using ultrasound. Frailty status was assessed using the phenotype developed by Fried which includes the following components: weight loss; self -reported exhaustion, low physical activity, slow walking speed, and low grip strength and was categorized into non-frail, pre-frail and frail. We assessed odds ratios for increasing frailty by CVR tertiles using ordered logistic regression.
Results: Among 327 patients, 112 (34.3%) were classified as non-frail, 122 (37.3%) as pre-frail and 930 (28.4%) as frail. Patients were categorized into tertiles of CVR, with cut-off points at ≤0.57, 0.58-0.94 and ≥0.95. Frailty was found among 42.4% of subjects at the bottom tertile, 30.1% at the middle tertile and 26.9% at the top tertile of CVR (p for trend=0.004). Adjusting for age, education, area of birth, BMI, systolic blood pressure, smoking (current, former, never), depressive symptoms and co morbidity score, the OR for increasing frailty for subjects at the bottom CVR tertile was 2.0 (95% confidence interval [CI], 1.2-3.5), and for those in middle tertile 1.3 (95% CI, 0.7-2.1) as compared to the top tertile. Similar associations were observed among patients with and without carotid large-vessel disease.
Conclusion: Impaired CVR was associated with a higher adjusted risk of late-life frailty among patients with pre-existing atherothrombosis. These findings emphasize the importance of cerebral hemodynamics in healthy aging.
