B. La venta de bienes sometidos a reserva 148
2. Bienes sometidos a reserva troncal 166
Frequency, distribution and progression of cerebral small vessel disease
White matter lesions and lacunar infarcts are frequently observed on CT and MRI scans of healthy elderly people, as well as in patients with dementia and stroke (chapter 2). The frequency of these lesions varies widely among studies due to differences in meth- odology and risk factor profi les. In the Rotterdam Scan Study, almost all participants had periventricular or subcortical white matter lesions and about one-fi fth had lacunar infarcts on MRI. These numbers are in accordance with those from the Cardiovascu- lar Health Study, a methodologically comparable study in the USA.1,2 Given the high prevalence of white matter lesions, it may be more informative to describe its severity distribution, i.e. the frequencies of more severe white matter lesions (fi gure 1, chapter 2). We found that the presence and severity of white matter lesions and lacunar infarcts strongly increased with age. Silent lacunar infarcts were more common in women.3 Women also tended to have more severe white matter lesions than men,4 in line with other studies.1,2,5
Periventricular and subcortical white matter lesions showed progression in one-third of the participants within 3-years. Ten percent of all participants had marked white matter lesion progression (chapter 4.1). The Austrian Stroke Prevention Study reports any white matter lesion progression in 18% and marked progression in 8% of their par- ticipants within 3 years.6 These participants were healthier and younger compared to ours. Marked subcortical white matter progression predominantly consisted of growth and confl uence of lesions, whereas minor progression mostly consisted of new small le- sions. The extent of progression of both periventricular and subcortical white matter le- sions was, similar to the presence of lesions at baseline, strongly related to age. Women had a higher risk of marked subcortical white matter lesion progression than men. In our study, 14% of the people had one or more new infarcts on the second MRI, of which the vast majority were lacunar infarcts.7 Incidence of lacunar infarcts strongly increased with age, but was not different between men and women. In the Cardiovascular Health Study, 18% of the people without a prevalent infarct had new infarcts on MRI after 5 years follow-up.8 Over 90% of these infarcts were lacunar infarcts.
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Risk factors
Blood pressure and hypertension
Higher systolic and diastolic blood pressure levels were associated with more severe periventricular and subcortical white matter lesions (chapter 3.1). The same relation- ship was found for concurrently and previously (on average 6 years earlier) assessed blood pressure levels. Increase in blood pressure over time was strongly related with periventricular white matter lesions in particular. We did not observe large differences in these associations among nine European cohorts. Higher blood pressure was also re- lated to the progression of white matter lesions (chapter 4.1). People who were success- fully treated for hypertension had a lower risk of severe white matter lesion compared to those with uncontrolled hypertension (chapter 3.1). These data confi rm the eminent role of high blood pressure and are in line with the observation that longstanding hyperten- sion is the main risk factor in the development of white matter lesions.9
A clear decrease in diastolic blood pressure over time approximately doubled the risk of severe periventricular white matter lesions (chapter 3.1). The observation among nine pooled European cohorts that both an increase and a decrease in diastolic blood pressure is related to severe white matter lesions, confi rms earlier fi ndings in the Rot- terdam Scan Study.10 We found that in people with severe white matter lesions at base- line, higher blood pressure was no longer a risk factor for white matter lesion progres- sion (chapter 4.1). This is in agreement with an earlier fi nding that blood pressure is not related to incident silent brain infarcts in people with prevalent silent brain infarcts.7 Homocysteine
Plasma homocysteine levels are associated with silent brain infarcts and white matter lesions (chapter 3.2). The relationship between these MRI lesions and homocysteine levels was continuous. People within the top quintile of homocysteine had 3 times the risk of either silent brain infarcts or severe white matter lesions compared to those in the lowest quintile. Other studies have confi rmed these observations.11-13
Arterial oxygen saturation and chronic obstructive pulmonary disease
We found that people with COPD or lower arterial oxygen saturation had more severe periventricular white matter lesions, but not subcortical white matter lesions or lacunar infarcts (chapter 3.3). However, we did not fi nd an association with the progression of periventricular white matter lesions.
Plasma amyloid ß
Plasma Aß1-40 and Aß1-42 levels are strongly associated with white matter lesions and la- cunar brain infarcts in people who carry an APOE ε4 allele, while in non-carriers there were no or only weak associations (chapter 3.4.1).
General discussion
129 Additionally, we found that in the elderly participants of the Rotterdam Study impaired cerebral vasomotor reactivity, as measured with transcranial Doppler ultra- sonography, is related to higher plasma Aß1-40 and Aß1-42 levels measured on average 6.5 years earlier, but not to concurrent Aß levels (chapter 3.4.2). Furthermore, a decrease in plasma Aß1-40 levels over time is associated with a higher prevalence of impaired va- somotor reactivity.
Cigarette smoking
Current cigarette smoking was associated with an almost 3 times increased risk of marked white matter lesion progression compared to never smoking (chapter 4.1). Peo- ple who formally smoked cigarettes did not have a higher risk of white matter lesion progression compared to people who never smoked. As in other studies, smoking was not associated with lacunar infarcts in our population.2,14
Infl ammation
Higher CRP levels were associated with baseline severity and progression of white matter lesions, and in particular with marked lesion progression (chapter 4.2). These associations were independent of cardiovascular risk factors and carotid atherosclerosis. Higher CRP levels showed a non-signifi cant trend toward more lacunar infarcts at base- line and new lacunar infarcts during follow-up.
Diabetes
We did not observe an association between diabetes and white matter lesions (chapter 4.1). People with diabetes, who did not have an infarct at baseline had a 3 times increased
risk of an incident silent brain infarct. Other population-based studies did not observe an association between diabetes and cerebral small vessel disease either.2,6,8,15-17
Small vessel disease and the risk of lesion progression and stroke
Elderly people with silent brain infarcts or severe white matter lesions had a more than 3-fold increased risk of stroke, which could not be explained by established stroke risk factors (chapter 5). This is in line with observations from the Cardiovascular Health Study and the Atherosclerosis Risk In Community study.18,19
People with lacunar infarcts had about 6 times the risk of having marked progres- sion of periventricular or subcortical white matter lesions within 3 years, compared to those without infarcts (chapter 4.1). The strongest predictor of progression of white matter lesions was the severity of white matter lesions at baseline. Progression of white matter lesions was strongly related to new infarcts on MRI and incident stroke.20 The Cardiovascular Health Study reported that in people without infarcts on MRI, white matter lesions severity was the strongest predictor of incident lacunar infarcts.8
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