Vector contains the intercept of , blood flow velocity, and residuals in the structural model. variables (age, sex, race, smoking, alcohol use, and systolic blood pressure) on cerebral BFV. Results Higher BMI (p=0.02) and age (p=0.004) were associated with lower mean BFV during baseline, independent of diagnosis of diabetes mellitus, hypertension or stroke, and after adjusting for all background variables and vessel diameters. Men, especially those with stroke, had a lower mean BFV than women (p = 0.01). CVR increased with BMI (p=0.001) at baseline and during head-up tilt (p=0.02), and was elevated in obese subjects (p=0.004) compared to normal weight subjects across all groups. Interpretation High BMI is associated with a reduction in cerebral BFV and increased CVR. These findings indicate that obesity can adversely affect cerebral blood flow and resistance in cerebrovascular bed, independent of diagnosis of type-2 diabetes, hypertension or stroke. Obesity may contribute to cerebromicrovascular disease, and affect clinical functional outcomes of older population. 0.05. RESULTS A total of 212 subjects were enrolled into the study. Of these, 15 subjects were excluded because of poor quality TCD examinations, poor temporal windows, or missing elements of the dataset. Data from the remaining 197 subjects (90 healthy controls, 30 diabetics, 45 hypertensives, and 32 stroke patients) were included in the analysis. MRI analysis is based Tipifarnib S enantiomer on data from 79 (40 controls, 22 diabetics, 10 hypertensives, and 7 stroke patients). Table 1 summarizes the characteristics of each of these 4 groups including demographics, risk factors, laboratory values, pulsatility index, intracranial vessels diameters and medications. Demographic factors and hematological parameters including lipids Rabbit Polyclonal to AQP12 were similar among the groups, except, as expected, for systolic blood pressure (p=0.008) and glucose (p=0.02). History of smoking, alcohol consumption was not different. MCA and ICA diameters for both sides were not different among the groups. There were Tipifarnib S enantiomer no significant differences among subjects in the diabetes, hypertension and stroke groups who were treated with angiotensin-converting enzyme inhibitors (ACE inhibitors), diuretics, -blockers, statins, or antithrombotics. We found no significant interaction between antithrombotics, ACE inhibitors, or statins and BFVs. Table 1 Characteristics of the study population. = 0.39). Higher BMI (p=0.01) and male sex (p 0.0001, = 0.57) were associated with lower HDL levels, and higher LDL levels (p=0.04, em r /em =0.37) and triglycerides (p=0.0075, em r /em =0.45). Women in our study had lower hemoglobin and hematocrit (39.32.8 vs .43.02.3%), and athrogenic index (0.260.43 vs. 0.640.54 mmol/L, p=0.004 than men, and lower hematocrit was associated with higher BFV (r=0.42, p=0.01). Hematocrit was not different in people with higher BMI. There was relative heterogeneity of stroke group in terms of stroke etiology. Stroke side, etiology and type of antihypertensive medications, however were not significant factors in our analyses. DISCUSSION Our results show that cerebral flow velocities decrease with increasing body mass and age in all groups, and that male sex is associated with lower BFV especially among stroke patients. Higher BMI is also associated with increased CVR during supine Tipifarnib S enantiomer rest and orthostatic stress. The effects of BMI on BFV and CVR are independent of those for age and sex and vessel diameter. These findings indicate that obesity may adversely affect flow velocity and resistance in cerebrovascular bed, independent of the diagnosis of type-2 diabetes, hypertension or stroke. Our findings that increased BMI, regardless of age or sex is associated with reduced cerebral BFV and increased CVR are novel and intriguing. Body mass has been recently recognized as a risk factor for cerebrovascular disease and cognitive decline in addition to age and other cardiovascular factors. [9;11] Obesity is associated with increased intima-media thickness that may affect pulsatility large arteries, and might be the consequence of metabolic dysregulation, associated dyslipidemia, inflammation, or other mechanisms [12;25]. In multivariate analysis, excess body weight and male sex were linked to progressive arterial dysfunction and impaired both endothelium mediated and independent vasodilatation [4],[14] with subsequent decrease in Tipifarnib S enantiomer arterial blood flow.[8] In addition, obesity is also associated with abnormalities in microvascular Tipifarnib S enantiomer patterns, reduced small vessel density, inflammation and impaired endothelial function and vascular reactivity [29;30] in peripheral and possibly even in central vascular beds. Our observation of increased CVR suggests that obesity may also affect the cerebral microvasculature and vasoreactivity during orthostatic stress. Few studies reported on the relationship between BMI and blood flow regulation.