| Part 1 Correlation of the location and extent of ischemic white matter lesions with blood pressure variability in patients with hypertensionPurpose:The process of ischemic white matter lesions (WML) causing brain damage is significantly heterogeneous with variable clinical manifestations. The process is associated with multiple risk factors, involving multiple possibilities of pathogenesis, while the specific pathogenesis and related risk factors are not yet fully understood. Analyzing the risk factors associated with the location and extent of the lesions will help to define the pathogenesis of WML and facilitate individualized prevention and treatment protocols. The study analyzed vascular risk factors associated with the location and extent of WML, in particular, the correlation of the location and extent of ischemic white matter lesions with ambulatory blood pressure in patients with hypertension, since hypertension features ambulatory blood pressure, to explore the possible pathophysiological mechanisms for WML.Methods:Middle-aged and elderly outpatients and inpatients with hypertension who took part in cerebrovascular disease screening studies in Wei Fang Traditional Chinese Hospital from September 2013 to December 2014 were selected as subjects of the study. After clinical data collection and the completion of head magnetic resonance imaging (MRI) and 24h ambulatory blood pressure monitoring (ABPM), a total of 192 cases of complete data were collected, which, according to brain MRI performance, were divided into the group with white matter lesions (WML group, n=119) and the group without white matter lesions (WML-free group, n=73). According to Fazekas ratings, the patients with WML were divided into those with periventricular lesions (PVL) and those with deep white matter lesions (DWML), respectively, and the extent of the lesions at both locations were evaluated. All patients were simultaneously subject to 24h ambulatory blood pressure monitoring, during which the mean blood pressures (systolic blood pressure, SBP, and diastolic blood pressure, DBP) of the 24 hours, the day and the night as well as the corresponding coefficient of variability (CV) of blood pressure during each of the above periods of time were recorded, and the peak and valley values of 24hSBP and 24hDBP were determined. Single-factor and Multi-factor Logistic regression analysis and relevant analysis methods were used for the statistical analysis on the correlation of traditional vascular risk factors and ambulatory blood pressure with the location and extent of ischemic white matter lesions and, in particular, the influence of ambulatory blood pressure parameters on the location and extent of white matter lesions.Results:1. Comparison of clinic data between WML and WML group:compared with WML-free group, patients in WML group were older (P<0.05), with longer course of hypertension (P<0.05) and higher level of homocysteine (Hcy) (P<0.05); comparison of ambulatory blood pressure parameters between the two groups:24hSBP,24hDBP, dSBP, nSBP,24hSBP-CV, dSBP-CV, the valley and peak values of 24hSBP of WML group were all higher than those of WML-free group (p< 0.05).2. Analysis of PVL risk factors:as shown by single-factor analysis,9 factors including age, course of hypertension, Hcy,24hSBP, dSBP, nSBP,24hSBP-CV, dSBP-CV, valley and peak values of 24hSBP were statistically significant (P<0.05) when put into the regression equation, and therefore were possible PVL risk factors; Multi-factor Logistic regression analysis showed that OR values of age (OR= 1.804), Hcy (OR=1.115), dSBP-CV (OR= 4.102), valley and peak values of 24hSBP (OR= 1.122) were all greater than 1, and therefore were PVL risk factors. Among them dSBP-CV was the most dangerous factor.3. DWML risk factors:single-factor Logistic regression analysis showed:11 factors including age, course of hypertension, drinking, Hcy,24hSBP,24hDBP, dSBP, nSBP, 24hSBP-CV, dSBP-CV, valley and peak values of 24hSBP were statistically significant (P <0.05) when put into the regression equation, and therefore were risk factor of DWML; Multi-factor Logistic regression analysis showed that the main factors after variable selection were drinking (OR= 3.221),24hDBP (OR= 1.109), valley and peak values of 24hSBP (OR= 1.143), dSBP-CV (OR= 6.061), the OR values of which were all greater than 1. These factors were therefore risk factors of DWML group. Among them dSBP-CV was the most dangerous factors.4. Analysis of factors related the extent of PVL:analysis of PVL risk factors and PVL ratings showed that PVL-1 was associated with valley and peak values of 24hSBP; both PVL-2 and PVL-3 were associated with age, dSBP-CV, Hcy, valley and peak values of 24hSBP.5. Analysis of factors related the severity of DWML:analysis of DWML risk factors and DWML ratings showed that DWML-1 was associated with peak and valley values of 24hSBP; DWML-2 was associated with dSBP-CV, valley and peak values of 24hSBP; DWML-3 was associated with dSBP-CV,24hDBP and valley and peak values of 24hSBP.Conclusion:1. Risk factors for WML at different locations and extent were not entirely consistent;2. Overlapping and difference existed in ambulatory blood pressure parameters related to PVL and DWML;3. Ambulatory blood pressure parameters had different impact on PVL and DWML at different extent, and there were more parameters associated with the severity of PVL and DWML.Part 2 Diffusion tensor imaging study on MRI of white matter damage associated with ambulitory blood pressurePurpose:Ischemic white matter lesions are irreversible brain damage, and currently the evolution of the disease is not clear. For the early determination of white matter damage characteristics to prevent and control the progress of the disease by controlling associated risk factors, diffusion tensor imaging (DTI) was used for quantitative study of the impact of blood pressure variability on the white matter of hypertensive patients with normal MRI results, to observe the characteristics of early ultrastructural damage of white matter in hypertensive patients.Methods:From the outpatients and inpatients with primary hypertension who took part in cerebrovascular disease screening studies in Wei Fang Traditional Chinese Hospital from September 2013 to December 2014,26 cases of patients who had no clinical symptoms and showed no high signal in white matter on T2WI were selected as the hypertension group; during the same period,19 cases of healthy subjects at similar ages who had no history of hypertension and showed no high signal in white matter on T2WI were selected as the control group. Both groups underwent ambulatory blood pressure monitoring, MRI, DTI and clinical data checks. Fractional anisotropy (FA) and mean diffusivity (MD) in regions of interest at different locations were analyzed, and the correlation of FA, MD values with the blood pressure variability parameters at locations of white matter where difference in the DTI parameter was found were analyzed.Results:1. Comparison of the ambulatory blood pressure parameters between the two groups:24hSBP, dSBP and nSBP levels of the hypertension group were significantly higher, with statistically significant difference (P<0.05); statistically significant difference was found between the two groups in 24hSBP-CV, dSBP-CV, valley and peak values of 24hSBP. But no statistically significant difference was found between the two groups in diastolic blood pressure and diastolic blood pressure variations in any period (P> 0.05); difference was found between the two groups in the constituent ratio of circadian rhythm, with non-dipper blood pressure rhythm of the hypertension group up to 38.45%, significantly higher than that of the control group.2. Comparison of the DTI parameters in ROI area at the same locations between the two groups:FA, MD values were statistically different (P<0.05) between the two groups in the anterior and posterior horns of the lateral ventricle and the centrum semiovale. In the comparison of DTI parameters in the ROI region of subcortex white matter of frontal lobe and the body of lateral ventricle, only the FD value was significantly different between the two groups (P<0.05), while FA, MD values in subcortex white matter of the temporal lobe, parietal lobe, occipital lobe showed no significant differences between the two groups (P> 0.05).3. Correlation of FA, MD values with the blood pressure variability parameters at relevant locations:FA of white matter in anterior horn of lateral ventricle was in significant negative correlation with 24hSBP, dSBP, nSBP,24hSBP-CV, dSBP-CV and the peak and valley values of 24hSBP; FA of white matter in posterior horn of lateral ventricle was in negative correlation with 24hSBP-CV, dSBP-CV and the peak and valley values of 24hSBP; FA of the body of lateral ventricle was in negative correlation with 24hSBP,24hDBP, dSBP, dDBP, nSBP, nDBP,24hSBP-CV, dSBP-CV and the peak and valley values of 24hSBP; FA of the centrum semiovale was in significant negative correlation with dSBP,24hSBP-CV, nSBP-CV and the peak and valley values of 24hSBP and 24hDBP; FA of the inferior frontal white matter areas was in significant negative correlation with nSBP, nDBP and nDBP-CV. Furthermore, MD values of the anterior horn of lateral ventricle and s centrum semiovale were both in significant positive correlation with 24hSBP, dSBP, nSBP,24hSBP-CV, dSBP-CV and the peak and valley values of 24hSBP; MD value of the posterior horn of lateral ventricles was in significant positive correlation with 24hSBP-CV, dSBP-CV and 24hDBP.4. Difference in DTI parameters between different circadian rhythm in patients of the hypertension group:The control group, dipper hypertension group, non-dipper hypertension group showed a decreasing trend of FA value and an increasing trend of MD value in the anterior horn, posterior horn and body of lateral ventricle, and the centrum semiovale. Inter-group comparison of FA values in the ROI area of these four locations showed statistical significance between the non-dipper hypertension group and both the other two groups; the dipper hypertension group and the control group were only statistically different in the anterior horn and posterior horn of lateral ventricle, and the centrum semiovale. Inter-group comparison of MD values showed statistical significance between the dipper hypertension group or the non-dipper hypertension group and the control groups in the anterior horn and posterior horn of lateral ventricle, and the centrum semiovale; the non-dipper hypertension group and the dipper hypertension group were only statistically different in the anterior horn and the centrum semiovale. These results suggested that although it was the dipper hypertension that caused early damage to the common areas subject to white matter damage, damage caused by non-dipper hypertension was more obvious. Comparison of FA and MD values among the three groups in the subcortex white matter areas of frontal lobe, parietal lobe, temporal lobe and occipital lobe showed no significant difference (P> 0.05).Conclusion:1. Early damage caused by hypertension to white matter was mainly found in the anterior horn, posterior horn of lateral ventricle, and the centrum semiovale. Certain extent of damage was also found in the subcortex white matter area of the frontal lobe and the body of lateral ventricle, while early damage in the subcortex white matter area of the temporal lobe, parietal lobe, and occipital lobe was not obvious.2.Elevated blood pressure, blood pressure variability and circadian rhythm abnormalities were all factors that may cause white matter damage, and the effects of the blood pressure parameters on different locations of the white matter were inhomogeneous.3. Even in the same location, the blood pressure parameters associated with MD and FA values at the same ROI area would not completely overlap, but would be different to some extent. |
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