Age-specific sex-differences in cerebral blood flow velocity in relation to haemoglobin levels.

INTRODUCTION

Cerebral blood flow (CBF) declines with age and abnormalities in CBF are associated with age-related cerebrovascular disease and neurodegeneration. Women have higher CBF than men, although this sex-difference diminishes to some extent with age in healthy subjects. The physiological drivers of these age/sex differences are uncertain, but might be secondary to age and sex-differences in haemoglobin (Hb) level. Hb levels are inversely correlated with CBF, are lower in women, and decline with age in men, but the interrelations between these factors have not been explored systematically either in healthy subjects or across the full age-range in patients with vascular risk factors. We aimed to determine the age-specific interrelations between sex, Hb, and CBF velocity in a large cohort of patients with cerebrovascular disease.

PATIENTS AND METHODS

In patients with a recent transient ischaemic attack or minor stroke (Oxford Vascular Study) and no ipsilateral or contralateral stenosis of the carotid or intracranial arteries, we related peak-systolic velocity (PSV) and other parameters on transcranial Doppler ultrasound (TCD) of the middle cerebral artery to sex, age, Hb and vascular risk factors.

RESULTS

Of 958 eligible subjects (mean age/SD = 68.04/14.26, 53.2% male), younger women (age < 55 years) had higher CBF velocities than men (mean sex difference in PSV at age < 55 years = 16.31 cm/s;  < 0.001), but this difference declined with age (interaction  < 0.001), such that it was no longer significant at age 75-84 (∆PSV = 3.26 cm/s;  = 0.12) and was reversed at age ⩾ 85 (∆PSV = -7.42 cm/s;  = 0.05). These changes mirrored trends in levels of Hb, which were higher in men at age < 55 (∆Hb = 1.92 g/dL;  < 0.001), but steadily decreased with age in men but not in women (interaction  < 0.001), with no residual sex-difference at age ⩾ 85 (∆Hb = 0.12 g/dL;  = 0.70). There was an inverse correlation between Hb and PSV in both women and men (both  ⩽ 0.01), and the sex-difference in PSV at age < 55 was substantially diminished after adjustment for Hb (∆PSV = 6.92;  = 0.036; ∆PSV = 5.92,  = 0.13 with further adjustment for end-tidal CO). In contrast, the sex difference in PSV was unaffected by adjustment for systolic and diastolic blood pressure, heart rate, and vascular risk factors (history of hypertension, diabetes, hyperlipidaemia and smoking).

DISCUSSION

CBF velocity is strongly correlated with Hb level at all ages, and sex-differences in CBF velocity appear to be explained in major part by age-related sex-differences in Hb.